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What is the abbreviation of Alliance for Risk Assessment?

kqbn0226

kqbn0226_p13, kqbn0226_p14, kqbn0226_p15

ARA

NAS (2014) & IRIS Process "Finding: IRIS-specific guidelines for consistent, coherent, and transparent assessment and communication of uncertainty remain incompletely developed. The inconsistent treatment of uncertainties remains a source of confusion and causes difficulty in characterizing and communicating uncertainty. Recommendation: Uncertainty analysis should be conducted systematically and coherently in IRIS assessments. To that end, EPA should develop IRIS-specific guidelines to frame uncertainty analysis and uncertainty communication. Moreover, uncertainty analysis should become an integral component of the IRIS process." [emphasis added] 12 Source: https://www.industrydocuments.ucsf.edu/docs/kqbn0226 Problem Response: Alliance for Risk Assessment (ARA) ARA TCE Workgroup formed in the Fall of 2012 Open invitation: over 300 scientists from multiple international organizations, including government, industry, academia and NGOs, on 6 conference calls and one webinar. Trichloroethylene (TCE) Risk Assessment Guidance for Contaminated Sites (April 2013) Webcast: Practical Guidance for Contaminated Sites:TCE Risk Assessment Case Study (November 4, 2013) 13 Source: ttps://www.industrydocuments.ucsf.edu/docs/kqbn0226 Problem Response: Alliance for Risk Assessment (ARA) Guidance for Contaminated Sites:Trichloroethylene Case Study. Gadagbui, et al., SOT, 53rd Annual Meeting & ToxExpo,23-27 March 2014, Phoenix,AZ. Development of a Non-cancer Hazard Range for Effective Risk Assessment and Risk Management of Contaminated Sites:A Case Study with TCE and Other Chemicals, Beyond Science & Decisions: Problem Formulation to Dose- Response Assessment,Workshop VIII, 21-22 May 2014, Austin, TX. 14 Source: ittps://www.industrydocuments.ucsf.edu/docs/kqbn0226

What does Figure 2 represents?

mxcn0226

mxcn0226_p0, mxcn0226_p1, mxcn0226_p2, mxcn0226_p3, mxcn0226_p4, mxcn0226_p5, mxcn0226_p6, mxcn0226_p7, mxcn0226_p8, mxcn0226_p9, mxcn0226_p10, mxcn0226_p11, mxcn0226_p12, mxcn0226_p13, mxcn0226_p14, mxcn0226_p15

Ah Receptor Activation - HIPS with and without FR

202 From: Erraguntla, Neeraja To: White. Kimberly; Admon. Smadar: Anderson Steven; Batoon Audrey; Bradley, Kevin: de Lacy Catharine; Elkan, Han; Goodman. Bryan; Hochschwender. Lane Jacobi Svlvia. B: Kannah. Kasturirangan; Levan, Steve: Levchik, Sergei; Little, Barbara; Manor. Orit: Prero. Judab; Rothenbacher. Klaus; Saunders Eric L.; Scherrer, Steve: Simon. Robert; Tavior. Jennifer: Tenney, Joel; Thorn, Amelia: West Jay; Hayes, A. Wallace; Rein. Guillermo; [email protected] Troitzsch, Jurgen; Blais, Matthew; Dourson. Michael (doursomi); Kacew Sam; Osimitz, Thomas Cc: Erraguntia. Neeraia Subject: RE: Clarification -Updated Smoke Toxicity Proposal -SAC May 2017 - Meeting Materials Date: Tuesday, May 16, 2017 11:11:42 AM Attachments: Update - Smoke Toxicity Project - April 2017 to NAFRA. pdf Re-sending the proposal to follow Tom's discussion on Smoke toxicity right now at the SAC mtg on May 16. Kind regards, Neera Neeraja Erraguntia, Ph.D., DABT| American Chemistry Council Director, Chemical Products & Technology Division Neeraja [email protected] 700 2nd Street NE Washington, DC | 20002 O: (202) 249-6712 C (202) 779-0524 www.americanchemistry.com From: Erraguntla, Neeraja Sent: Tuesday, May 16, 2017 9:08 AM To: White, Kimberly; Admon, Smadar; Anderson, Steven; Batoon, Audrey; Bradley, Kevin; de Lacy, Catharine; Elkan, Ilan; Goodman, Bryan; Hochschwender, Lane; Jacobi, Sylvia R.; Kannah, Kasturirangan; LeVan, Steve; Levchik, Sergei; Little, Barbara; Manor, Orit; Prero, Judah; Rothenbacher, Klaus; Saunders, Eric L.; Scherrer, Steve; Simon, Robert; Taylor, Jennifer; Tenney, Joel; Thorn, Amelia; West, Jay; Hayes, A. Wallace; Rein, Guillermo; [email protected]; Troitzsch, Jurgen; Blais, Matthew; Michael Dourson ([email protected]); Kacew, Sam; Osimitz, Thomas Cc: Erraguntla, Neeraja Subject: RE: Clarification - -Updated Smoke Toxicity Proposal - -SAC May 2017 - Meeting Materials Dear All, Tom provided additional clarification on the updated smoke toxicity proposal. Kind regards, Neera Neeraja Erraguntia, Ph.D., DABT American Chemistry Council Director, Chemical Products & Technology Division Neeraja [email protected] 700 2nd Street NE I Washington, DC I 20002 O: (202) 249-6712 C: (202)779-0524 www.americanchemistry.com Source: https://www.industrydocuments.ucsf.edu/docs/mxcn0226 203 From: Erraguntla, Neeraja Sent: Sunday, May 14, 2017 4:38 PM To: White, Kimberly; Admon, Smadar; Anderson, Steven; Batoon, Audrey; Bradley, Kevin; de Lacy, Catharine; Elkan, Ilan; Goodman, Bryan; Hochschwender, Lane; Jacobi, Sylvia R.; Kannah, Kasturirangan; LeVan, Steve; Levchik, Sergei; Little, Barbara; Manor, Orit; Prero, Judah; Rothenbacher, Klaus; Saunders, Eric L.; Scherrer, Steve; Simon, Robert; Taylor, Jennifer; Tenney, Joel; Thorn, Amelia; West, Jay; Hayes, A. Wallace; Rein, Guillermo; [email protected] Troitzsch, Jurgen; Blais, Matthew; Michael Dourson ([email protected]); Kacew, Sam; Osimitz, Thomas Subject: RE: Updated Smoke Toxicity Proposal -SAC May 2017 - Meeting Materials Dear All, Please see the attached Updated Smoke Toxicity Proposal from Tom for consideration and action at the SAC meeting this week. Kind regards, Neera Neeraja Erraguntia, Ph.D., DABT American Chemistry Council Director, Chemical Products & Technology Division Neeraja [email protected] 700 2nd Street NE Washington DO I 20002 O: (202) 249-6712 C: (202) 779-0524 www.americanchemistry.cor From: White, Kimberly Sent: Tuesday, May 9, 2017 5:28 PM To: Admon, Smadar; Anderson, Steven; Batoon, Audrey; Bradley, Kevin; de Lacy, Catharine; Elkan, Ilan; Erraguntla, Neeraja; Goodman, Bryan; Hochschwender, Lane; Jacobi, Sylvia R.; Kannah, Kasturirangan; LeVan, Steve; Levchik, Sergei; Little, Barbara; Manor, Orit; Prero, Judah; Rothenbacher, Klaus; Saunders, Eric L.; Scherrer, Steve; Simon, Robert; Taylor, Jennifer; Tenney, Joel; Thorn, Amelia; West, Jay; White, Kimberly; Hayes, A. Wallace; Rein, Guillermo; [email protected]; Troitzsch, Jurgen; Blais, Matthew; Michael Dourson ([email protected]); Kacew, Sam; Osimitz, Thomas Subject: SAC May 2017 - Meeting Materials Dear NAFRA, BSEF and SAC members: In preparation for the May 16th-17th SAC meeting, attached are associated meeting materials. Hard copies will also be available onsite. In addition to the attached materials, we also anticipate additional information on the dermal exposure project, the smoke toxicity project and the baby monitor combustion project to be disseminated in the coming days. Below are general meeting logistics. General Logistics Meeting Dates/Times: May 16, 2017 (Meeting from 9:00 a.m. -5:00 p.m. ET) May 17, 2017 ( Meeting from 9:00 a.m. -2:00 p.m. ET) Meeting/Hotel Location: DoubleTree by Hilton Hotel Metropolitan -New York City, 569 Lexington Avenue, New York, New York 10022 Dinner on May 15, 2017 at 6:30pm (ET) - The Modern; Address: 9 W 53rd St. New York, NY 10019 Dinner on May 16, 2017 at 6:30pm (ET) Source: https://www.industrydocuments.ucsf.edu/docs/mxcn0226 204 SAC Members Only - The Smith; Address: 956 2nd Ave, New York, NY 10022 NAFRA/ BSEF Members Only - Mitae: Address: 4 East 46th Street, New York, NY 10017 I look forward to seeing everyone next week and feel free to contact me if you have any questions. Kind Regards, Kimberly Wise White, Ph.I D. | American Chemistry Council Senior Director, Chemical Products & Technology Division Kimberly Whitelamericanchemistry.com 700 2nd Street NE Washington, DC | 20002 O: (202) 249-6707 C: (202) 341-7602 www.americanchemistry.com + This message may contain confidential information and is intended only for the individual named. If you are not the named addressee do not disseminate, distribute or copy this email. Please notify the sender immediately by email if you have received this email by mistake and delete this email from your system. E-mail transmission cannot be guaranteed to be secure or error-free as information could be intercepted, corrupted, lost, destroyed, arrive late or incomplete, or contain viruses. The sender therefore does not accept liability for any errors or omissions in the contents of this message which arise as a result of email transmission. American Chemistry Council, 700 - 2nd Street NE, Washington, DC 20002, www.americanchemistry.com Source: https://www.industrydocuments.ucsf.edu/docs/mxcn0226 Relative Toxicity of Combustion Products from Various Materials Effect of Flame Retardants T.G. Osimitz (Science Strategies) and M.S. Blais (Southwest Research Institute) April 18, 2017 Background Recent studies haves shown the presence of flame retardants (esp. polybrominated diphenyl ethers (PBDEs)) and/or possible flame retardant (FR) combustion products (halogenated dioxins and furans), and other polyaromatic hydrocarbons (PAHs) in the serum of firefighters and/or on their clothing (Shaw et al. 2013). In their study, polychlorinated and polybrominated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs and PBDD/Fs) were measured in the serum of twelve firefighters sampled after a fire event in San Francisco, California, along with PBDEs, polychlorinated biphenyls (PCBs), p,p'- DDE, hexachlorobenzene (HCB), perfluorinated chemicals (PFCs), bisphenol-A (BPA) and tetrabromobisphenol-A (TBBPA). Given the elevated rates of some cancers in firefighters and general concern about firefighter health, it is important to understand the significance of these findings. While it is not certain that the PBDEs can survive a fire and end up posing a potential exposure to firefighters as suggested by Shaw et al. (2013), halogenated dioxins and furans are known products of incomplete combustion. The extent to which the presence of halogenated flame retardants contribute to or accelerate the formation of the dioxins and furans in house fires is not clear. However, a recent report by Zhang et al. (Zhang, Buekens, and Li 2016) shows that an increase in the bromine content of electrical/electronic waste (presumably from flame retardants) is associated with an increase in the presence of halogenated dioxins and furans in the combustion products. They also state that: "Other forms of open burning (landfill fires and accidental fires) are also donors of PBDD/F emissions.' Although not surprising, this evidence will be used to support the general statement often made by opponents of flame retardants that flame retardants make smoke more toxic and that this poses an increased risk to firefighters. The Issue to Address There is widespread agreement that smoke (regardless of the presence of flame retardants) is acutely toxic and may contain numerous chemicals with the potential to cause chronic effects such as cancer. The unanswered question is: "Is smoke/soot from combustion of materials with flame retardants more toxic than smoke/soot from materials without flame retardants? 1 Source: https://www.industrydocuments.ucsf.edu/docs/mxcn0226 For the project being conducted here, we are not concerned with acute toxicity, which is reasonably well understood, but rather chronic effects including cancer. Numerous studies have documented the presence of poly aromatic hydrocarbons as well as polychlorinated and polybrominated dibenzodioxins and dibenzonfurans in smoke from combusted materials. The open question is whether flame retardants enhance the carcinogenicity and chronic toxicity of the already hazardous smoke from a fire. Experimental Approach We combusted four test articles. Smoke condensate was collected during the combustion and wipe samples of soot were collected after combustion. The samples were analyzed for a wide variety of chemicals commonly associated with combustion. The combustion and chemical analysis were performed at Southwest Research Institute (San Antonio, TX). The samples were also sent to Cyprotex Laboratories (Watertown, MA) for evaluation of the biological activity. We chose a battery of vitro assays that could be conducted quickly without the use of live animals. The hypothesis being tested was whether the biological activity of the smoke condensates and soot is identical and whether the combusted materials contain a flame retardant or not. Combustion of Materials and Collection and Analysis of Smoke and Soot In Phase I (Pilot Study), two materials were combusted: High Impact Polystyrene (HIPS) - without flame retardant and with the flame retardants decabromodipdhenylethane and antimony trioxide added. Br Br Br Br Br Br Br Br Br Br Flexible Poly Urethane Foam (PUF) - without flame retardant and with the flame retardant tris(dichloroisopropyl) phosphate (TDCP). 2 Source: https://www.industrydocuments.ucsf.edu/docs/mxcn0226 CI CI o ; +++++++++ CI o CI C CI Combustion took place in a National Bureau of Standards (NBS) smoke chamber at 50 kW/m² radiant energy. A 100 mm x100 mm x <50 mm piece of selected material was pyrolyzed. Smoke opacity was measured using a calibrated light source in the smoke chamber. Samples were collected through the heated sample transfer line (HSTL) at a fixed and measured flow rate and analyzed by Fourier transform infrared spectroscopy (FTIR) in a 2 meter gas cell. The FTIR particulate filter was analyzed for halogens. Samples were also collected through a separate HSTL, fitted with a stainless steel cooling line and cooled solvent impingers, from the chamber at a flow of 1 standard liters/minute (SLPM) over the duration of the burn (30 min). There were two impingers in series, the first impinger filled with DMSO and the second filled with water. Both impingers were chilled in a 0°C cold bath. The stainless steel cooled sample line was rinsed with dimethyl sulfoxide (DMSO) and rinsate added to the DMSO impinger solvent and mass measured of total solvent. A second wash with water was performed and the two rinsates added together and the total mass measured. Soot was collected from the inside surfaces of the smoke chamber by use of latex wipes. The DMSO and water rinsates as well as extracts from the wipes used to collect the soot were combined for each pyrolysis experiment and the combined materials were used for the characterization of biological activity (described below). Samples were frozen at a temperature of - -70°C and shipped overnight on dry ice to the biological testing laboratory. Note: All collection materials (such as the wipes, solvents and containers) were confirmed prior to use not to have been contaminated with any known FR by analysis of quality blanks. Results Chemical Analysis of Samples The comprehensive chemical analysis of the samples included: 3 Source: https://www.industrydocuments.ucsf.edu/docs/mxcn0226 A screen for over 200 volatile and semi-volatile target compounds in EPA method TO-15 (Target Compounds). In addition, any peak showing an area count greater than 1% of the sample was also tentatively identified (referred to as a Tentatively Identified Compound - TIC) and a semi-quantitative analysis was also performed; An array of both brominated and chlorinated dioxins and dibenzofurans. Note: Analytical difficulties beset the analysis of brominated dioxins and dibenzofurans. Thus, those data are not reported. Target Compounds Diethylphthalate was detected in approximately equal concentrations from both non-FR and FR HIPS samples. Other than benzoic acid (in DMSO samples from polyurethane foam (PUF) with FR), no other target chemicals were detected. In contrast to flexible PUF, numerous target compounds were detected from the combustion of HIPS. Although the FR and non-FR versions of HIPS produced some of the above chemicals, more such individual chemicals were produced in the presence of FR (Table 1). Moreover, for the chemicals detected in both FR and non-FR samples, concentrations were generally higher in the FR-containing samples. Nonetheless, this does not suggest that these differences are toxicologically significant. Table 1: Target Compounds - HIPS with and without FR FRI IIIPS HIPS 1 FRJ HIPS HIPS Impinger Impinger Rasio Impinger Impinger Raties DI 1120 DE 1120 FR/Non FR DMSO DAISO FR/Non FR Name (ug/l) (mg/l.) ND ND 26.2 ND 19.1 NO 46,7 13.4 3,5 76 23.3 3.3 160 56.8 3.8 39.6 20.4 1.9 89 56 135 50.6 2.7 377 146 1.9 26.6 ND 58.4 33.4 1.7 33 ND 28.6 23.5 1.3 Acid 37.6 NO 109 67.3 1.6 13.8 17.4 0.8 ND ND 319 29.3 7.3 429 78.1 5.5 43.6 ND 91,7 34,5 2.7 ND ND 14 ND 31.6 28.9 1.1 33 35.6 0.9 ND ND 38.5 ND 107 13,7 7.8 220 40 3,5 18.4 ND 50.6 18.5 2.7 ryyrene 87.8 19.3 4,6 195 56.1 3.5 (Naphthalene 20.7 NO NO ND 204 26.3 7,8 446 5.0 Pyreme 41.1 ND 80.5 22.4 3.6 TOTAL como (ug/L) 1142.00 229,78 5.0 171.60 3.1 Tentatively Identified Compounds (TIC) TDCP was detected in samples from the combustion products from both flexible PUF samples. No TIC were detected in the samples collected in water. 4 Source: https://www.industrydocuments.ucsf.edu/docs/mxcn0226 Table 2: Tentatively Identified Compounds - PUF with and without FR Tentativa compounds in Flexible PUF: DMSO Impinger and Wipe Samples Concentration in pg/l. Compound Name CAS # Flexible PUF FR Flexible PUF Trist 13674-87-8 536 1210 For HIPS, significantly more individual TICs were identified in the FR-containing material (Tables 3, 4). For the chemicals detected in both FR and non-FR samples; concentrations were generally higher in the FR-containing samples. As with the target compounds, it is not possible to make inferences about the toxicological significance of these results. Unexpectedly, TDCP was detected in samples from the combustion products from both HIPS samples. The source of the contamination is uncertain, although it can most likely be attributed to the experimental and sampling set up. In the future, special attention will be paid to scrupulously clean the apparatus to eliminate such confounding results. Table 3: Tentatively Identified Compounds - HIPS with and without FR (water collection) Tentative compounds in HIPS: DI Water Impinger and Wipe Samples Concentration in pg/L Compound Name HIPS I FRI HIPS 1-Propente, 22.4 686 58.4 528 Naphthalene, 2-phenyl- ND 464 ND 249 ND 144 Naphthalene, -pheny)- ND 128 Heracnemethanamine, 225 46.6 Bennene, ND 90.6 glycal in DMSO Finit 62.7 85.2 Pyrene, 1-phenyl- ND 85.2 4: Tentatively Identified Compounds - HIPS with and without FR (DMSO collection) Tentative compounds in HIPS: DMSO Impinger and Wipe Samples Concentration in mg/l. Compound Name HIPS 1 FR3 HIPS Tris(1,3-dichloroisopropyi)phosphatel 788 ND ND 1280 1,17:3', ND 1160 Naphthalene, ND 912 ND 779 5 Source: https://www.industrydocuments.ucsf.edu/docs/mxcn0226 Chlorinated Dioxins and Benzofurans For the Flexible PUF, only 3 of the 50 samples analyzed showed detectable levels of the analytes (data not presented). All values were below the Limit of Quantitation (LOQ). In contrast to the flexible PUF, many more individual chlorinated dioxins and furans were reported, most of them below the Limit of Quantitation (LOQ). Nonetheless, the total amounts of chlorinated dioxins and furans (collected in either water or DMSO) were essentially identical between FR and non-FR samples. Table 5 Chlorinated Dioxins and Benzofurans from HIPS with and without FR HIPS (blank cells are non-detects) Chiorinated Dinxins and in HIPS: DI Water Cblorinated Dioxins and Furans in HIPS: DMSO Impinger and Wipe Samples Impinges and Wipe Samples Concentration in us/T. Concentración in ug/L Compound Name HIPS 1 FR3 HIPS Compowad Name IIIPS 1 FR3 HIPS 2,3,7,8-TCDO 2,3,7,8-TCDD 1,2,3,7,8-PeCOD 1,2,3,7,8-PeCDD 1,2,3,4,7,8-MxCDD 1,2,3,4,7,8-HxCDO 1,2,3,6,7,8-HxCDD 1,2,3,7,8,9-HxCDO 1,2,3,7,8,9-HxCOD 1,2,3,4,6,7,8-HpC00 1,2,3,4,6,7,8-HpC00 OCDO OCDO 2,3,7,8-TCDF 1.05 1.2 2,3,7,8-TCDF 2.39 3.59 1,2,3,7,8-PeCDF -LOQ 1,2,3,7,8-PeCOF -LOQ 2,3,4,7,8-PeCOF 2,3,4,7,8-PeCDF HLOC 1,2,3,4,7,8-HxCDF <LOQ <LOQ 1,2,3,4,7,8-HxCDF KLOC <LOQ 1,2,3,6,7,8-HxCOF 1,2,3,6,7,8-HxCDF -LOQ 1,2,3,7,8,9-HxCOF 1,2,3,7,8,9-HxCDF 2,3,4,6,7,8-14xCDF <LOQ 1,2,3,4,6,7,8-HpCOF <LOQ 1,2,3,4,6,7,&-HpCDF <LOQ 1,2,3,4,7,8,9-HpCDF 1,2,3,4,7,8,9-HpCOF OCDF OCDF Total Tetra-Dioxins 0.838 Total Tetra-Dioxins 2.21 Total Penta-Diaxins Total Penta-Dioxins KLOC <LOC Total Hexa-Dioxins Total Hexa-Dioxins <LOQ Total Hepta-Dioxins Total Hepta-Dioxins LOQ Total Tetra-Furans 3.18 5.42 Total Tetra-Furans 12.9 22.1 Total Penta-Furans 3.41 2.46 Total Penta-Furans 7.97 9.66 Total Hexa-Furans <LOQ <LOQ Total Hexa-Furans 2.38 2.79 Total Hepta-Furans CLOQ Total Hepta-Furans 4,00 -LOQ Total a dioxins and furans 7.428 7.88 Total a dioxins and furans 25.46 34,55 No Change Decrease with FR (either >2X reduction or going to a non-detett) Increase with FR (>2X increase) 6 Source: https://www.industrydocuments.ucsf.edu/docs/mxcn0226 Assessment of Biological Activity (Cyrprotex Labortories) Genotoxicity In Vitro Micronucleus Screen (MNT) None of the test articles exhibited genotoxicity in the absence or presence of S9 metabolic activation. Ames Genotoxicity Screen (two test strains) No genotoxicity was observed for any of the test articles. Note: we ran Cyprotex's most popular option for non-GLP testing ("mini-Ames"). The two bacterial strains used allow for detection of two of the most common mutations (i.e. frame-shift mutations with strain TA98, and base-pair substitutions with strain TA100). Assessment of Indicators of General Toxicity CellCiphr TM Premier Tox Profiling CellCiphrTM was the Cellular Systems Biology approach used to screen compounds for broad-ranging toxic effects using tissue-specific cell models. The CellCiphrTM Profiling used a combination of toxicity-relevant cells and toxicity biomarkers to monitor the effects of test compounds on many cellular systems responses known to be correlated with toxic challenge. These were surveyed using primary rat hepatocytes (metabolically competent) and the HepG2 (human) cell line, to take advantage of the specific biology present in these cell types and the toxicity endpoints associated with them. The smoke condensate samples were profiled in an expanded CellCiphrTM panel which includes both HepG2 and primary rat hepatocytes at two time points. It also included a Glutathione assay, ROS assay and a 5-day toxicity assay in rat hepatocytes. A combined 21 toxicity endpoints at multiple time points were measured to create the CellCiphrTM profile (38 total measured endpoints). The output (when applicable) included the maximum tolerated dose, AC50 curves and rank order and safety risks for prioritization. A summary of the results is below in Table 6. 7 Source: https://www.industrydocuments.ucsf.edu/docs/mxcn0226 Table 6: Summary of CellCiphr Results - 0 NH Foam FR Ras O NO C : 049 1.08 (10% 1% Rat : * CA 31 : 1.29 07% 1% HepG2 8 72h NS : 1.10 (22% Mat 3 400 MIMIP : 0.00 (91% 1 0.5% C NO Riank Rat e NR C NR Rai o NR * 8 3 de - * The - - - - Res - No responses were see with the blank (as expected), PUF, and PUF with FR samples. Minimal responses were observed for HIPS and HIPS with FR. The responses are such that the effect of FR in either of the samples could not be distinguished. It is possible that this is a true reflection of the properties of the samples. But, more likely, the test samples may have been too diluted to produce a significant response. This is also suggested by the fact that, for several endpoints, the concentration-response curves began to develop at the highest concentrations (Figure 1). Figure 1: Representative Concentration-Response Curves Showing Apparent Onset of Effect at High Concentrations 48h 72h S a 2 2 18 8 & $ : * * & * $ 83 ses 8.8 : 0.00 88 (%) a ACA 31% 3° 0,778 No MEC MIN 8 Source: https://www.industrydocuments.ucsf.edu/docs/mxcn0226 Biological Indicators of Presence of Dioxins and Dibenzofurans Dioxins and furans have been shown to be carcinogenic, immunotoxic, and toxic to reproduction in various animal models. The Adverse Outcome Pathway for these effects begins with their high affinity binding of the chemical to the Aryl Hydrocarbon Receptor (AhR). Subsequent translocation of the complex into the nucleus of the cell, dimerization of the AhR with the AhR nuclear translocator (Arnt) protein, and binding of the ligand:AhR:1 complex to its DNA recognition sequence leads to increased transcription and translation of certain genes, including that of cytochrome P4501A1 (CYP1A1). All dioxin-like compounds are assumed to act through this AhR signal transduction pathway. The test system we used consisted of transformed tumor cells plated on 96-well microtiter plates. An expression vector harboring human AhR plus the appropriate enhancers and promoters linked to the luciferase reporter gene have been integrated into the tumor cells. Receptor activation was assessed by monitoring reporter gene activity, and by comparing the results to vehicle-treated cells. The results were reported as the fold increase in transcriptional activation of AhR above vehicle control for each test article. Foam FR, HIPS, and HIPS FR exhibited levels of AhR induction of approximately 5, 7, and 9-fold, respectively. The levels of activation for both HIPS and Flexible PUF correspond to less than 20% of the positive control compound (3- methylcholanthrene, at 10 M) as shown in Figures 2 and 3, respectively. Cyprotex, the testing laboratory, indicated that for drug discovery screening programs, they typically flag compounds that show >40% induction relative to the positive control. The maximum level of induction we observed could therefore be considered modest by such screening criteria standards. Thus, although there is an apparent increase in Ah Receptor activity in FR-containing samples but, because of the relatively low response, it is not possible to assess the toxicological significance, if any of these observations. 9 Source: https://www.industrydocuments.ucsf.edu/docs/mxcn0226 Figure 2: Ah Receptor Activation - HIPS with and without FR Ah Receptor Activity HIPS HIPS FR 100 80 60 40 16 20 8 9 12 1 1 2 2 4 4 6 6 - 0 - 0.03125 0.0625 0.125 0.25 0,5 1 Test Concentration Range (%) Figure 3: Ah Receptor Activation - Flexible PUF with and without FR Ah Receptor Actvity Flexible PUF Plexible POF FR 100 90 80 70 60 50 40 30 20 011 3 5 8 10 0 0 0 0 0 1 3 0 asse 0.03125 0.0625 0.125 0,25 0.5 1 Test Concentration Range (%) 10 Source: https://www.industrydocuments.ucsf.edu/docs/mxcn0226 Summary of Pilot Study and Future Needs No indication of adverse responses, but data are inconclusive due to need to optimize concentration of samples being tested; Sample collection and preparation needs to be revised to provide more concentrated sample for both analytical characterization and biological testing; Extra efforts will be undertaken to avoid contamination with FRs from other sources. Recommendations for Follow-up The pilot study provided important insight to steps we need to take to maximize the robustness of this program. In addition to the sampling and sample preparation (concentrating of samples) discussed above, we recommend moving from the CellCiphrTM assay to ToxTracker by Toxys. Why move to the Toxys System? Cells Used: Cyprotex uses HepG2 cells which are immortal human liver carcinoma line as well as rat hepatocytes. That is fine, but the stems cells used by Toxys are better, as they are less organ specific; Experience with Lipophilic Molecules: CellCiphrTM system has primarily been used for relatively water-soluble pharmaceuticals and not complex mixtures like we are dealing with. The Toxys system has been used with lipophilic mixtures as in the petroleum-related project; Regulatory Utility: The system is undergoing validation for screening for carcinogenicity be the European Union; ToxTracker generally predicts very well (>90%) the outcome of the standard battery of GLP in vitro genotoxicity (Ames, Mouse Lymphoma Assay, Micronucleus - In vitro, Chromosome aberrations). Proposed Project This is essentially a repeat of the pilot project with the same test articles (plus red oak). In contrast to the pilot study: Sampling volume and handling will be modified to produce a more concentrated sample to be sure that we are well within the dynamic range of the assays; Because of the special focus that Toxys has on carcinogenesis (by several modes of action - genotoxic and non-genotoxic), we will not run the Ames nor the micronucleus assays. We will still run the Ah Receptor assay as a sensitive biological indicator of halogenated dioxins and furans. 11 Source: https://www.industrydocuments.ucsf.edu/docs/mxcn0226 Budget: For 5 Test Articles - Phase 18 (definitive) Assay $/test Article Total Cost Combustion set up and collection 3,000 15,000 Analytical chemistry on the above 2,600 13,000 Cell Tracker 3,000 15,000 Ah Receptor 800 4,000 Subtotal Laboratory Costs 47,000 *Study management and oversight (0.2) 9,400 Total Project Cost 56,400 *Science Strategies Timing: Toxys offers a one week turnaround, depending upon availability. 12 Source: https://www.industrydocuments.ucsf.edu/docs/mxcn0226 References Shaw, S. D., M. L. Berger, J. H. Harris, S. H. Yun, Q. Wu, C. Liao, A. Blum, A. Stefani, and K. Kannan. 2013. 'Persistent organic pollutants including polychlorinated and polybrominated dibenzo-p-dioxins and dibenzofurans in firefighters from Northern California', Chemosphere, 91: 1386-94. Zhang, M., A. Buekens, and X. Li. 2016. 'Brominated flame retardants and the formation of dioxins and furans in fires and combustion', J Hazard Mater, 304: 26-39. 13 Source: https://www.industrydocuments.ucsf.edu/docs/mxcn0226

What is the handwritten date above the signature?

jhcn0226

jhcn0226_p25, jhcn0226_p26, jhcn0226_p27, jhcn0226_p28, jhcn0226_p29, jhcn0226_p30, jhcn0226_p31, jhcn0226_p32, jhcn0226_p33, jhcn0226_p34, jhcn0226_p35, jhcn0226_p36, jhcn0226_p37, jhcn0226_p38, jhcn0226_p39, jhcn0226_p40, jhcn0226_p41, jhcn0226_p42, jhcn0226_p43, jhcn0226_p44, jhcn0226_p45

3/29/2017, 3 / 29 / 2017

referenced in the final aggregate assessment for chlorpyrifos or the OP CRA. Petitioners do not otherwise explain whether and how these data support the revocation of tolerances or the cancellation of pesticide registrations. b. Agency Response. As explained in the previous section, the basis for seeking revocation of a tolerance is a showing that the pesticide is not "safe." Claiming that EPA failed to reference certain data in its risk assessment regarding carcinogenicity does not amount to illustrating that the tolerances are unsafe. To show a lack of safety, petitioners would have to present some fact-based argument demonstrating that aggregate exposure to chlorpyrifos poses an unsafe carcinogenic risk. Petitioners have not presented such an analysis. Accordingly, EPA is denying the Petition to revoke chlorpyrifos tolerances or cancel chlorpyrifos registrations to the extent the Petition relies on claims pertaining to carcinogenicity. Despite the inadequacy of petitioners' cancer claims, in the course of the Agency's review of chlorpyrifos, EPA has examined the Lee et al. study cited by petitioners (Ref. 17) among other lines of evidence. EPA has concluded that the Lee et al. investigation does not alter the Agency's weight of evidence determination concerning chlorpyrifos' carcinogenic potential, and therefore does not alter the Agency's current cancer classification for chlorpyrifos. Specifically, the Agency does not believe this evidence raises sufficient grounds for concern regarding chlorpyrifos that EPA should consider initiating action based upon this information that might lead to revocation of the chlorpyrifos tolerances or cancellation of the chlorpyrifos registrations. The Agency was aware of the December 2004 study cited by petitioners. While Lee et al. observed a possible association between chlorpyrifos use and the incidence of Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225 00000971-00025 lung cancer, the authors also stressed that further evaluation was necessary before concluding the association was causal in nature.(Ref. 17) Additional evaluation is necessary because of possible alternative explanations for the Lee et al. study, which include unmeasured confounding factors or confounding factors not fully accounted for in the analysis, and possible false positive results due to the performance of multiple statistical tests. EPA has been a collaborating agency with the AHS since 1993, and continues to closely monitor the AHS literature. The Agency is working closely with the AHS researchers to clearly understand the results of their research efforts to ensure the Agency appropriately interprets these data as future studies are published. Between 2003 and 2009 there have been six nested case-control analyses within the AHS which evaluated the use of a number of agricultural pesticides, including chlorpyrifos, in association with specific anatomical cancer sites, in addition to the previously published cohort study (Ref. 17) cited by the petitioners. As noted below, both the Agency and Health Canada have comprehensively reviewed these data. In accordance with the Agency's 2005 Guideline for Cancer Risk Assessment (Ref. 18), chlorpyrifos is classified as "Not Likely to be Carcinogenic to Humans" based on the lack of evidence of carcinogenicity in male or female mice and male or female rats. In chronic toxicity/ carcinogenicity studies, animals received chlorpyrifos in their feed every day of their lives (78 weeks for mice and 104 weeks for rats) at doses thousands of times greater than any anticipated exposure to humans from authorized uses. There was no evidence of cancer in the experimental animal studies. Additionally, available evidence from in vivo and in vitro assays did not support a mutagenic or Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225_00000971-00026 genotoxic potential of chlorpyrifos. Recently, the Agency conducted its own review of the six nested case-control analyses and one cohort study within the AHS concerning the carcinogenic potential of chlorpyrifos. (Ref. 19) EPA concluded with respect to the AHS lung cancer results that the findings are useful for generating hypotheses, but require confirmation in future studies. This conclusion is consistent with that of researchers from Health Canada. Specifically, Weichenthal et al. (2010) (Ref. 20) published a review article in Environmental Health Perspectives on pesticide exposure and cancer incidence in the AHS cohort. Their review of these same studies concluded that the weight of experimental toxicological evidence does not suggest that chlorpyrifos is carcinogenic, and that epidemiologic results currently available from the AHS are inconsistent, lack replication, and lack a coherent biologically plausible carcinogenic mode of action. The authors did note positive exposure-response associations for chlorpyrifos and lung cancer in two separate evaluations. In summary, while there is initial suggestive epidemiological evidence of an association between chlorpyrifos and lung cancer to only form a hypothesis as to a carcinogenic mode of action, additional research (including follow-up AHS research) is needed to test the hypothesis. Consequently, at this time it is reasonable to conclude chlorpyrifos is not a carcinogen in view of the lack of carcinogenicity in the rodent bioassays and the lack of a genotoxic or mutagenic potential. The Agency concludes that existing epidemiological data (including Lee et al.) do not change the current weight of the evidence conclusions. The Agency continues to believe there is not a sufficient basis to alter its assessment of chlorpyrifos as not likely to be carcinogenic to humans when Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225 00000971-00027 multiple lines of evidence are considered (e.g., epidemiology findings, rodent bioassay, genotoxicity); therefore, chlorpyrifos cancer risk would not be a factor in any potential Agency risk determination to revoke tolerances for chlorpyrifos. 4. CRA misrepresents risks, failed to apply FQPA10X Safety Factor a. Petitioners' claim. Petitioners assert that EPA relied on limited data and inaccurate interpretations of data to support its decision to remove the FQPA safety factor in the 2006 OP CRA. Specifically, the petitioners challenge the Agency's use of data from a paper by Zheng et al. (2000) (Ref. 21) claiming that, in contrast to the Agency's analysis of the study data, the data does show an obvious difference between juvenile and adult responses to chlorpyrifos. Petitioners conclude by asserting that the Zheng et al. study supports using a 10X safety factor for chlorpyrifos in the CRA. b. Agency Response. Petitioners' assertions do not provide a sufficient basis for revoking chlorpyrifos tolerances. As explained previously, the ground for seeking revocation of a tolerance is a showing that the pesticide is not "safe." The petitioners' claim that the data EPA relied upon support a different FQPA safety factor for chlorpyrifos in the CRA does not amount to a showing that chlorpyrifos tolerances are unsafe. To show a lack of safety, petitioners would have to present a factual analysis demonstrating that the lack of a 10X safety factor in the CRA for chlorpyrifos poses unsafe cumulative exposures to the OPs. Petitioners have not made such a showing. For this reason, EPA is denying the petitioners' request to revoke chlorpyrifos tolerances or cancel chlorpyrifos registrations to the extent that request relies on claims pertaining to EPA's failure to provide a 10X safety factor in the 2006 CRA based on the results of the Zheng et al. study. Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225_00000971-00028 Despite the inadequacy of petitioners' FQPA safety factor claims, EPA examined the evidence cited by petitioners for the purpose of evaluating whether the evidence raises sufficient grounds for concern regarding chlorpyrifos that EPA should consider initiating the actions sought by the petitioners. In general, when the Agency conducts a cumulative assessment, the scope of cumulative risk is limited to the common mechanism endpoint -- which in this case of the 2006 OP CRA, was cholinesterase inhibition, the primary toxicity mode of action for the OPs. As such, for the OP CRA, experimental toxicology data on AChE inhibition were used for developing relative potency estimates, points of departure, and informing the FQPA safety factor used in the OP CRA. EPA relied on brain AChE data from adult female rats dosed for 21 days or longer for estimating relative potency and points of departure. At approximately three weeks of oral exposure to OPs, AChE inhibition reaches steady state in the adult rat such that continued dosing does not result in increased inhibition. This timeframe of toxicity (21-days and longer) was selected as there was high confidence in the potency estimates derived from the steady state toxicology studies due to the stability of the AChE inhibition. The Agency's 2006 OP CRA contained EPA's complete FQPA safety factor analysis, (Ref. 22) which involved consideration of pre-natal and post-natal experimental toxicology studies, in addition to exposure infermation. In the OP CRA, pre-natal exposure AChE studies in rats show that the fetus is no more sensitive than the dam to AChE inhibition and the fetus is often less sensitive than the dam. Thus, evaluating the potential for increased toxicity of juveniles from post-natal exposure was a key Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225_00000971-00029 component in determining the magnitude of the FQPA safety factors in the OP CRA. Furthermore, because characteristics of children are directly accounted for in the cumulative exposure assessment, the Agency's methods did not underestimate exposure to OPs. In the 2006 OP CRA, each OP was assigned a 10X FQPA safety factor unless chemical-specific AChE data on young animals were available to generate a data derived safety factor. To best match the relative potency factor (RPF)s and PODs based on repeated dosing, the Agency used repeated dosing data in juveniles for developing the FQPA safety factors. For chlorpyrifos, at the time of the 2006 OP CRA, the only such data available were from the Zheng et al. literature study. The petitioners are correct that Dr. Carey Pope of Oklahoma State University provided the Agency with the raw data from the Zheng et al. study. These raw data were used to develop the plot in the 2006 OP CRA which was reproduced in the Petition. Petitioners accurately note that for other OPs a benchmark dose modeling approach was used and that no BMD values were reported for chlorpyrifos. In determining the FQPA safety factor, petitioners claim that the Agency misinterpreted the brain AChE data from Zheng et al. As shown in the plot reproduced on page 15 of the Petition, the dose-response data in the Zheng et al. study are variable and lack a monotonic shape at the low dose end of the dose response curve. The Agency acknowledges that at the high dose, the pups appear to be more sensitive. However, at the low dose end of the response curve, relevant for human exposures and, thus, the cumulative risk assessment (i.e., at or near the 10% inhibition level), little to no difference is observed. Therefore, despite the lack Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225 00000971-00030 of BMD estimates for the Zheng et al. study, the Agency is confident in the value used to address the common mechanism endpoint (AChE inhibition) addressed in the 2006 CRA. Since that time, the Agency attempted BMD modeling of the Zheng et al. data as part of the 2011 preliminary chlorpyrifos HHRA (Ref. 23) which yielded low confidence results due to the variability in the data. Dow AgroSciences submitted a comparative cholinesterase study (CCA) for chlorpyrifos. CCA studies are specially designed studies to compare the dose-response relationship in juvenile and adult rats. This CCA study includes two components: 1) acute, single dosing in post-natal day 11 and young adult rats and 2) 11-days of repeating dosing in rat pups from PND11-21 and 11-days of repeated dosing in adult rats. The CCA study for chlorpyrifos is considered by EPA to be high quality and well-designed. The preliminary risk assessment for chlorpyrifos' reports BMD estimates from this CCA study. Specifically, for the repeated dosing portion of the study, the BMD10s of 0.80 (0.69 BMDL10) and 1.0 (0.95 BMDL10) mg/kg/day respectively for female pups and adults support the FQPA safety factor of 1X for the AChE inhibition endpoint used in the 2006 OP CRA. As such, petitioners' claims regarding the CRA and FQPA safety factor is denied. 5. Over-reliance on registrant data. a. Petitioners' claims. Petitioners assert that in reregistering chlorpyrifos EPA "cherry picked" data, "ignoring robust, peer-reviewed data in favor of weak, industry- sponsored data to determine that chlorpyrifos could be re-registered and food tolerances be retained." As such, the Agency's reassessment decision is not scientifically defensible. Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225 00000971-00031 b. Agency response. This portion of the Petition does not purport to be an independent basis for revoking chlorpyrifos tolerances or cancelling chlorpyrifos registrations. Rather, this claim appears to underlie petitioners' arguments in other sections of the Petition. While petitioners claim that EP A ignored robust, peer-reviewed data in favor of weak, industry-sponsored data for the reregistration of chlorpyrifos, petitioners do not cite to any studies other than those used to support their other claims. In general, petitioners did not provide any studies in the Petition that EPA failed to evaluate. Since the specific studies cited by petitioners are not associated with this claim, but rather their other claims, EPA's response to the specific studies are, therefore, addressed in its responses to petitioners' other claims. However, EPA explains below why, as a general matter, the Agency does not believe it "over-relied" on registrant data in evaluating the risks of chlorpyrifos in its 2006 reregistration decision. In spite of petitioners' claim, the Agency does not ignore robust, peer-reviewed data in favor of industry-sponsored data. Further, EPA has a very public and well- documented set of procedures that it applies to the use and significance accorded all data utilized to inform risk management decisions. Registrant generated data, in response to FIFRA and FFDCA requirements, are conducted and evaluated in accordance with a series of internationally harmonized and scientifically peer-reviewed study protocols designed to maintain a high standard of scientific quality and reproducibility. (Refs. 23 and 24). Additionally, to further inform the Agency's risk assessment, EPA is committed to the consideration of other sources of information such as data identified in the open, peer-reviewed literature and information submitted by the public as part of the regulatory Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225 00000971-00032 evaluation of a pesticide. An important issue, when evaluating any study, is its scientific soundness and quality, and thus, the level of confidence in the study findings to contribute to the risk assessment. The literature was searched, fully considered, and provided additional information on, chlorpyrifos mode of action, pharmacokinetics, epidemiology, neurobehavioral effects in laboratory animals, and age dependent sensitivity to cholinesterase inhibition. Therefore, by evaluating registrant data in accordance with internationally harmonized and scientifically peer-reviewed study protocols, undertaking thorough open literature searches, and considering information provided by the public, the Agency is confident that its assessment for chlorpyrifos in 2006 was reasonably based upon the best available science at the time of the assessment. Previous sections of this response to petitioners' claims regarding the Agency's inadequate use of various data only further highlights and supports the scientifically defensible results of the Agency's assessment. Petitioners' claim that the Agency overly relies on registrant data is therefore denied. 6. EPA has failed to properly address the exporting hazard in foreign countries from chlorpyrifos. As noted in Unit II., in EPA's July 16, 2012 interim petition response EPA issued a final denial of this claim. That denial constituted final agency action and EPA is not reopening consideration of that claim. 7.-9. EPA failed to quantitatively incorporate data demonstrating long-lasting effects from early life exposure to chlorpyrifos in children; EPA disregarded data demonstrating that there is no evidence of a safe level of exposure during pre-birth and early life stages; EPA failed to cite or quantitatively incorporate studies and clinical Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225 00000971-00033 reports suggesting potential adverse effects below 10% cholinesterase inhibition. a. Petitioners' claims. The petitioners assert that human epidemiology and rodent developmental neurotoxicity data suggest that pre-natal and early life exposure to chlorpyrifos can result in long-lasting, possibly permanent damage to the nervous system and that these effects are likely occurring at exposure levels below 10% cholinesterase inhibition, EPA's existing regulatory standard for chlorpyrifos and other OPs. They assert that EPA has therefore used the wrong endpoint as a basis for regulation and that, taking into account the full spectrum of toxicity, chlorpyrifos does not meet the FFDCA safety standard or the FIFRA standard for registration. b. Agency response. EPA has grouped claims 7-9 together because they fundamentally all raise the same issue: whether the potential exists for chlorpyrifos to cause neurodevelopmental effects in infants and children from exposures (either to mothers during pregnancy or directly to infants and children) that are lower than those resulting in 10% cholinesterase inhibition - the basis for EPA's long-standing point of departure in regulating chlorpyrifos and other OPs. While petitioners may perhaps disagree, unlike the claims addressed above, these claims were not truly challenges to EPA's 2006 reregistration decision for chlorpyrifos, but rather, challenges to EPA's ongoing approval of chlorpyrifos under FIFRA and the FFDCA that rely in large measure on data published after EPA completed both its 2001 chlorpyrifos Interim Reregistration Decision and the 2006 OP CRA that concluded the reregistration process for chlorpyrifos and all other OPs. As matters that largely came to light after the completion of reregistration, these petition issues are issues to be addressed as part of the registration review of chlorpyrifos - the next round of re-evaluation under section 3(g) of FIFRA. As Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225_00000971-00034 petitioners are aware, past EPA administrations prioritized the registration review of the OPs in no small measure to begin to focus on the question of OP neurodevelopmental toxicity, which was, and remains, an issue at the cutting edge of science, involving significant uncertainties. EPA has three times presented approaches and proposals to the FIFRA SAP for evaluating recent epidemiologic data (some of which is cited in the Petition) exploring the possible connection between in utero and early childhood exposure to chlorpyrifos and adverse neurodevelopmental effects. The SAP's reports have rendered numerous recommendations for additional study and sometimes conflicting advice for how EPA should consider (or not consider) the epidemiology data in conducting EPA's registration review human health risk assessment for chlorpyrifos. While industry and public interest groups on both sides of this issue can debate what the recommendations mean and which recommendations should be followed, one thing should be clear to all persons following this issue: the science on this question is not resolved and would likely benefit from additional inquiry. EPA has, however, been unable to persuade the 9th Circuit Court of Appeals that further inquiry into this area of unsettled science should delay EPA's response to the Petition. Faced with an order requiring EPA to respond to the Petition, in October 2015, EPA chose to issue a proposed rule to revoke all chlorpyrifos tolerances based in part on the uncertain science surrounding neurodevelopmental toxicity suggested by certain epidemiology studies. The comments EPA has received on that proposal and on EPA's November 17, 2016 NODA suggest that there continue to be considerable areas of uncertainty with regard to what the epidemiology data show and deep disagreement over how those data should be considered in EPA's risk assessment. Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225 00000971-00035 Although not a legal consideration, it is important to recognize that for many decades chlorpyrifos has been and remains one of the most widely used pesticides in the United States, making any decision to retain or remove this pesticide from the market an extremely significant policy choice. In light of the significance of this decision and in light of the significant uncertainty that exists regarding the potential for chlorpyrifos to cause adverse neurodevelopmental effects, EPA's preference is to fully explore approaches raised by the SAP and commenters on the proposed rule, and possibly seek additional authoritative peer review of EPA's risk assessment prior to finalizing any regulatory action in the course of registration review. As the 9th Circuit has made clear in its August 12, 2016 order in PANNA v. EPA, EPA must provide a final response to the Petition by March 31, 2017, regardless of whether the science remains unsettled and irrespective of whatever options may exist for more a complete resolution of these issues during the registration review process. While EPA acknowledges its obligation to respond to the Petition as required by the court, the court's order does not and cannot compel EPA to complete the registration review of chlorpyrifos in advance of the October 1, 2022 deadline provided in section 3(g) of FIFRA, 7 U.S.C. 136a(g). Although past EPA administrations had chosen to attempt to complete that review several years in advance of the statutory deadline (and respond to the Petition on the same time frame), it has turned out that it is not possible to fully address these issues early in the registration review period. As a result, EPA has concluded that it should alter its priorities and adjust the schedule for chlorpyrifos so that it can complete its review of the science addressing neurodevelopmental effects prior to making a final registration review decision whether to retain, limit or remove Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225 00000971-00036 chlorpyrifos from the market. Accordingly, EPA is denying these Petition claims and intends to complete a full and appropriate review of the neurodevelopmental data before either finalizing the proposed rule of October 30, 2015, or taking an alternative regulatory path. EPA's denial of the Petition on the grounds provided above is wholly consistent with governing law. The petition provision in FFDCA section 408(d) does not address the timing for responding to this petition nor does it limit the extent to which EPA may coordinate its petition responses with the registration review provisions of FIFRA section 3(g). Further, provided EPA completes registration review by October 1, 2022, Congress otherwise gave the EPA Administrator the discretion to determine the schedule and timing for completing the review of the approximately over 1000 pesticide active ingredients currently subject to evaluation under section 3(g). EPA may lawfully re- prioritize the registration review schedule developed by earlier administrations provided that decision is consistent with law and an appropriate exercise of discretion. See Federal Communications Commission v. Fox Television Stations, 129 S.Ct. 1800 (2009) (Administrative Procedure Act does not require that a policy change be justified by reasons more substantial than those required to adopt a policy in the first instance). Nothing in FIFRA section 3(g) precludes EPA from altering a previously established registration review schedule. Given the absence of a clear statutory directive, pir RA and the FFDCA provide Eb A with discretion to take mup account EPA's registration review of a pesticide in determining how and when the Agency responds to FFDCA petitions to revoke tolerances. As outlined above, given the importance of this matter and the fact that critical questions remain regarding the significance of the data Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225 00000971-00037 addressing neurodevelopmental effects, EPA believes there is good reason to extend the registration review of chlorpyrifos and therefore to deny the Petition. To find otherwise would effectively give petitioners under the FFDCA the authority to re-order scheduling decisions regarding the FIFRA registration review process that Congress has vested in the Administrator. 10. Inhalation Exposure from Volatilization a. Petitioners' claim. Petitioners assert that when EPA completed its 2006 OP CRA, EPA failed to consider and incorporate significant exposures to chlorpyrifos- contaminated air that exist for some populations in communities where chlorpyrifos is applied. Petitioners assert that these exposures exceeded safe levels when considering cholinesterase inhibition as a point of departure and that developmental neurotoxicity may occur at even lower exposure levels than those resulting in cholinesterase inhibition. b. Agency response. To the extent petitioners are asserting that human exposure to chlorpyrifos spray drift and volatilized chlorpyrifos present neurodevelopmental risks for infants and children, EPA is denying this claim for the reasons stated above in our response to claims 7-9. As noted, EPA believes that, given the uncertainties associated with this identified risk concern, the appropriate course of action is for EPA to deny the Petition and work to further resolve this area of unsettled science in the time remaining for the completion of registration review under section 3(g) of FIFRA. With respect to petitioners' claim that exposures to spray drift and volatilized chlorpyrifos present a risk from cholinesterase inhibition, EPA is denying the Petition for the reasons previously identified in EPA's Spray Drift Mitigation Decision of July 16, 2012 [EPA-HQ-OPP-2008-0850] and EPA's interim response of July 15, 2014 [EPA- Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225 00000971-00038 HQ-OPP-2007-1005 addressing chlorpyrifos volatilization. In the Spray Drift Mitigation Decision, EPA determined that the chlorpyrifos registrants' adoption of label mitigation (in the form of label use rate reductions and no spray buffer zones) eliminated risk from cholinesterase inhibition as a result of spray drift. As for risks presented by volatilized chlorpyrifos that may occur following application, EPA's July 15, 2014 interim response to the Petition explained that recent vapor phase inhalation studies for both chlorpyrifos and chlorpyrifos-oxor made clear that neither vapor phase chlorpyrifos nor chlorpyrifos-oxon presents a risk of cholinesterase inhibition. Specifically, those studies, as indicated in EPA's memorandum, Chlorpyrifos: Reevaluation of the Potential Risks from Volatilization in Consideration of Chlorpyrifos Parent and Oxon Vapor Inhalation Toxicity Studies (Ref. 25), revealed that levels of chlorpyrifos and chlorpyrifos-oxon in vapor form are much lower than the levels seen in earlier aerosol studies that are better suited for evaluating spray drift. Indeed, no cholinesterase inhibition was observed in either volatility study. What is clear from these data is that the air cannot hold levels of volatilized chlorpyrifos or its oxon that are capable of causing adverse effects from cholinesterase inhibition. VI. Regulatory Assessment Requirements As indicated previously, this action announces the Agency's order denying a petition filed, in part, under section 408(d) of FFDCA. As such, this action is an adjudication and not a rule. The regulatory assessment requirements applicable to rulemaking do not, therefore, apply to this action. VII. Submission to Congress and the Comptroller General The Congressional Review Act, 5 U.S.C. 801 et seq., does not apply because this Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225 00000971-00039 action is not a rule for purposes of 5 U.S.C. 804(3). IX. References The following is a listing of the documents that are specifically referenced in this document. The docket includes these documents and other information considered by EPA, including documents that are referenced within the documents that are included in the docket, even if the referenced document is not physically located in the docket. For assistance in locating these other documents, please consult the technical person listed under FOR FURTHER INFORMATION CONTACT. 1. The Petition from NRDC and PANNA and EPA's various responses to it are available in docket number EPA-HQ-OPP-2007-1005 available at http://www.regulations.gov. 2. FIFRA Scientific Advisory Panel (2016). "Chlorpyrifos: Analysis of Biomonitoring Data". Available at: https://www.epa.gov/sap/meeting-materials-april-19- 1-2016-scientific-advisory-panel. 3. Furlong CE, Holland N, Richter RJ, Bradman A, Ho A, Eskenazi B (2006). PON1status of farmworker mothers and children as a predictor of organophosphate sensitivity. Pharmacogenet Genomics. 2006 Mar; 16(3):183-90. 4. Sultatos LG; Murphy SD, (1983). Kinetic Analysis Of The Microsomal Biotransformation Of The Phosphorothioate Insecticides Chlorpyrifos And Parathion. Fundemental and Applied Toxicology. 3:16-21. 5. U.S. EPA (2008). Draft Appendix E available at http://www.epa.gov/scipoly/sap/meetings/2008/september/appendixe.pdf. Draft Science Issue Paper: Chlorpyrifos Hazard and Dose Response Characterization. August 21, 2008. Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225 00000971-00040 Available at http://www.epa.gov/scipoly/sap/meetings/2008/september/chlorpyrifoscharacter.pdf. 6. Holland, N., Furlong, C., Bastaki, M., Richter, R., Bradman, A., Huen, K., Beckman, K., and Eskenazi, B. (2006). Paraoxonase polymorphisms, haplotypes, and enzyme activity in Latino mothers and newborns. Environ. Health Perspect. 114(7), 985- 991; Chen, J., Kumar, M., Chan, W., Berkowitz, G., and Wetmur, J. (2003). Increased Influence of Genetic Variation on PON1 Activity in Neonates. Environmental Health Perspective 111, 11:1403-9. 7. U.S. EPA (2008). Transmittal of Meeting Minutes of the FIFRA Scientific Advisory Panel Meeting Held September 16-18, 2008 on the Agency's Evaluation of the Toxicity Profile of Chlorpyrifos. Available at http://www.epa.gov/scipoly/sap/meetings/2008/september/sap0908report.pdf at 61. 8. Engel,S.M., Wetmur, J., Chen, J., Zhu, C., Boyd Barr, D., Canfield, R.L., Wolff, M.S., (2011) Prenatal Exposure to Organophosphates, Paraoxonase 1, and Cognitive Development in Childhood Environ Health Perspect 119:1182-1188 (2011). doi:10.1289/ehp.1003183 [Online 21 April 2011]. 9. Hofmann, J.N., Keifer, M.C., Furlong, C.E., De Roos, A.J., Farin., F.M., Fenske, R.A., van Belle, G., Checkoway, H. (2009) Serum Cholinesterase Inhibition in Relation to Paraoxonase-1 (PON1) Status among Organophosphate-Exposed Agricultural Pesticide Handlers./ Environ Health Perspect 117:1402-1408 (2009). doi:10.1289/ehp.0900682. Available at http://dx.doi.org/ [Online 9 June 2009]. 10. Eskenazi,B; Huen, K., Marks, A., Harley, K.G., Bradman, A., Boyd Barr, D., Holland, N. (2010) PONI and Neurodevelopment in Children from the CHAMACOS Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225 00000971-00041 Study Exposed to Organophosphate Pesticides in Utero. Environmental Health Perspectives. Vol 118 (12): 1775-1781). 11. Harley KG, Huen K, Schall RA, Holland NT, Bradman A, et al. (2011) Association of Organophosphate Pesticide Exposure and Paraoxonase with Birth Outcome in Mexican-American Women. PLoS ONE 6(8): e23923. doi:10.1371/journal.pone.0023923. 12. IPCS (International Programme on Chemical Safety) 2005. Chemical-Specific Adjustment Factors for Interspecies Differences and Human Variability: Guidance Document for Use of Data in Dose/Concentration-Response Assessment. Harmonization Project Document No. 2. World Health Organization, International Programme on Chemical Safety, Geneva, Switzerland. 13. U.S. EPA (2014). Guidance for Applying Quantitative Data to Develop Data- Derived Extrapolation Factors for Interspecies and Intraspecies Extrapolation. Available at https://www.epa.gov/risk/guidance-applying-quantitative-data-develop-data-derived- extrapolation-factors-interspecies-and. 14. For additional information on the Endocrine Disruptor Screening program see http://www.epa.gov/endo/. 15. For information related to the status of EDSP test orders/DCIs, status of EDSP OSRI: order recipient submissions and EPA responses, and other EDSP assay information see http://www.epa.gov/endo/pubs/toresources/index.htm 16. For available Data Evaluation Records (DERs) for EDSP Tier 1, see ttps://www.epa.gov/endocrine-disruption/endocrine-disruptor-screening-program-tier-1- Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225 00000971-00042 screening-determinations-and, 17. Hoppin JA, Lubin JH, Rusiecki JA, Sandler DP, Dosemeci M, Alavanja MC. (2004) Cancer incidence among pesticide applicators exposed to chlorpyrifos in the Agricultural Health Study. J Natl Cancer Inst, 96(23), 1781-1789. (hereinafter Lee et al. 2004). 18. U.S. EPA (2005). Guidelines for Carcinogen Risk Assessment. Available at http://www.epa.gov/raf/publications/pdfs/CANCER_GUIDELINES_FINAL_3-25- 05.PDF. 19. Christenson, C. (2011). D388167, Chlorpyrifos Carcinogenicity: Review of Evidence from the U.S. Agricultural Health Study (AHS) Epidemiologic Evaluations 2003-2009. 20. Weichenthal S, Moase C, Chan P (2010). A review of pesticide exposure and cancer incidence in the agricultural health study cohort. Cien Saude Colet. 2012 an;17(1):255-70. PubMed PMID: 22218559. 21. Zheng Q, Olivier K, Won YK, Pope CN. (2000). Comparative cholinergic neurotoxicity of oral chlorpyrifos exposures in pre-weaning and adult rats. Toxicological Sciences, 55(1): 124-132. 22. For additional information on the organophosphate cumulative risk assessment, see http://epa.gov/pesticides/cumulative/2006-op/op_cra_main.pdf. 23. U.S. EPA (2011). Chlorpyrifos: Preliminary Human Health Risk Assessment for Registration. Available in docket number EPA-HQ-OPP-2008-0850, ttp://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2008-0850-0025. (23) For additional information on EPA's Harmonized Test Guidelines and Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225_00000971-00043 international efforts at harmonization, see http://www.epa.gov/opp00001/science/guidelines.htm. (24) Available at http://www.regulations.gov in docket EPA-HQ-OPP-2008- 0850. Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225_00000971-00044 Administrator's Signature on page 45 of 45 pages; FRL- 9960-77: Chlorpyrifos; Order Denying PANNA and NRDC's Petition to Revoke Tolerances Authority: 7 U.S.C. 136 et seq. and 21 U.S.C. 346a. Dated: 3/24/2017 SUNDAR E. Scott Pruitt, Administrator. Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0206 001225_00000971-00045

What is the designation of E. Scott Pruitt?

jhcn0226

jhcn0226_p25, jhcn0226_p26, jhcn0226_p27, jhcn0226_p28, jhcn0226_p29, jhcn0226_p30, jhcn0226_p31, jhcn0226_p32, jhcn0226_p33, jhcn0226_p34, jhcn0226_p35, jhcn0226_p36, jhcn0226_p37, jhcn0226_p38, jhcn0226_p39, jhcn0226_p40, jhcn0226_p41, jhcn0226_p42, jhcn0226_p43, jhcn0226_p44, jhcn0226_p45

Administrator

referenced in the final aggregate assessment for chlorpyrifos or the OP CRA. Petitioners do not otherwise explain whether and how these data support the revocation of tolerances or the cancellation of pesticide registrations. b. Agency Response. As explained in the previous section, the basis for seeking revocation of a tolerance is a showing that the pesticide is not "safe." Claiming that EPA failed to reference certain data in its risk assessment regarding carcinogenicity does not amount to illustrating that the tolerances are unsafe. To show a lack of safety, petitioners would have to present some fact-based argument demonstrating that aggregate exposure to chlorpyrifos poses an unsafe carcinogenic risk. Petitioners have not presented such an analysis. Accordingly, EPA is denying the Petition to revoke chlorpyrifos tolerances or cancel chlorpyrifos registrations to the extent the Petition relies on claims pertaining to carcinogenicity. Despite the inadequacy of petitioners' cancer claims, in the course of the Agency's review of chlorpyrifos, EPA has examined the Lee et al. study cited by petitioners (Ref. 17) among other lines of evidence. EPA has concluded that the Lee et al. investigation does not alter the Agency's weight of evidence determination concerning chlorpyrifos' carcinogenic potential, and therefore does not alter the Agency's current cancer classification for chlorpyrifos. Specifically, the Agency does not believe this evidence raises sufficient grounds for concern regarding chlorpyrifos that EPA should consider initiating action based upon this information that might lead to revocation of the chlorpyrifos tolerances or cancellation of the chlorpyrifos registrations. The Agency was aware of the December 2004 study cited by petitioners. While Lee et al. observed a possible association between chlorpyrifos use and the incidence of Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225 00000971-00025 lung cancer, the authors also stressed that further evaluation was necessary before concluding the association was causal in nature.(Ref. 17) Additional evaluation is necessary because of possible alternative explanations for the Lee et al. study, which include unmeasured confounding factors or confounding factors not fully accounted for in the analysis, and possible false positive results due to the performance of multiple statistical tests. EPA has been a collaborating agency with the AHS since 1993, and continues to closely monitor the AHS literature. The Agency is working closely with the AHS researchers to clearly understand the results of their research efforts to ensure the Agency appropriately interprets these data as future studies are published. Between 2003 and 2009 there have been six nested case-control analyses within the AHS which evaluated the use of a number of agricultural pesticides, including chlorpyrifos, in association with specific anatomical cancer sites, in addition to the previously published cohort study (Ref. 17) cited by the petitioners. As noted below, both the Agency and Health Canada have comprehensively reviewed these data. In accordance with the Agency's 2005 Guideline for Cancer Risk Assessment (Ref. 18), chlorpyrifos is classified as "Not Likely to be Carcinogenic to Humans" based on the lack of evidence of carcinogenicity in male or female mice and male or female rats. In chronic toxicity/ carcinogenicity studies, animals received chlorpyrifos in their feed every day of their lives (78 weeks for mice and 104 weeks for rats) at doses thousands of times greater than any anticipated exposure to humans from authorized uses. There was no evidence of cancer in the experimental animal studies. Additionally, available evidence from in vivo and in vitro assays did not support a mutagenic or Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225_00000971-00026 genotoxic potential of chlorpyrifos. Recently, the Agency conducted its own review of the six nested case-control analyses and one cohort study within the AHS concerning the carcinogenic potential of chlorpyrifos. (Ref. 19) EPA concluded with respect to the AHS lung cancer results that the findings are useful for generating hypotheses, but require confirmation in future studies. This conclusion is consistent with that of researchers from Health Canada. Specifically, Weichenthal et al. (2010) (Ref. 20) published a review article in Environmental Health Perspectives on pesticide exposure and cancer incidence in the AHS cohort. Their review of these same studies concluded that the weight of experimental toxicological evidence does not suggest that chlorpyrifos is carcinogenic, and that epidemiologic results currently available from the AHS are inconsistent, lack replication, and lack a coherent biologically plausible carcinogenic mode of action. The authors did note positive exposure-response associations for chlorpyrifos and lung cancer in two separate evaluations. In summary, while there is initial suggestive epidemiological evidence of an association between chlorpyrifos and lung cancer to only form a hypothesis as to a carcinogenic mode of action, additional research (including follow-up AHS research) is needed to test the hypothesis. Consequently, at this time it is reasonable to conclude chlorpyrifos is not a carcinogen in view of the lack of carcinogenicity in the rodent bioassays and the lack of a genotoxic or mutagenic potential. The Agency concludes that existing epidemiological data (including Lee et al.) do not change the current weight of the evidence conclusions. The Agency continues to believe there is not a sufficient basis to alter its assessment of chlorpyrifos as not likely to be carcinogenic to humans when Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225 00000971-00027 multiple lines of evidence are considered (e.g., epidemiology findings, rodent bioassay, genotoxicity); therefore, chlorpyrifos cancer risk would not be a factor in any potential Agency risk determination to revoke tolerances for chlorpyrifos. 4. CRA misrepresents risks, failed to apply FQPA10X Safety Factor a. Petitioners' claim. Petitioners assert that EPA relied on limited data and inaccurate interpretations of data to support its decision to remove the FQPA safety factor in the 2006 OP CRA. Specifically, the petitioners challenge the Agency's use of data from a paper by Zheng et al. (2000) (Ref. 21) claiming that, in contrast to the Agency's analysis of the study data, the data does show an obvious difference between juvenile and adult responses to chlorpyrifos. Petitioners conclude by asserting that the Zheng et al. study supports using a 10X safety factor for chlorpyrifos in the CRA. b. Agency Response. Petitioners' assertions do not provide a sufficient basis for revoking chlorpyrifos tolerances. As explained previously, the ground for seeking revocation of a tolerance is a showing that the pesticide is not "safe." The petitioners' claim that the data EPA relied upon support a different FQPA safety factor for chlorpyrifos in the CRA does not amount to a showing that chlorpyrifos tolerances are unsafe. To show a lack of safety, petitioners would have to present a factual analysis demonstrating that the lack of a 10X safety factor in the CRA for chlorpyrifos poses unsafe cumulative exposures to the OPs. Petitioners have not made such a showing. For this reason, EPA is denying the petitioners' request to revoke chlorpyrifos tolerances or cancel chlorpyrifos registrations to the extent that request relies on claims pertaining to EPA's failure to provide a 10X safety factor in the 2006 CRA based on the results of the Zheng et al. study. Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225_00000971-00028 Despite the inadequacy of petitioners' FQPA safety factor claims, EPA examined the evidence cited by petitioners for the purpose of evaluating whether the evidence raises sufficient grounds for concern regarding chlorpyrifos that EPA should consider initiating the actions sought by the petitioners. In general, when the Agency conducts a cumulative assessment, the scope of cumulative risk is limited to the common mechanism endpoint -- which in this case of the 2006 OP CRA, was cholinesterase inhibition, the primary toxicity mode of action for the OPs. As such, for the OP CRA, experimental toxicology data on AChE inhibition were used for developing relative potency estimates, points of departure, and informing the FQPA safety factor used in the OP CRA. EPA relied on brain AChE data from adult female rats dosed for 21 days or longer for estimating relative potency and points of departure. At approximately three weeks of oral exposure to OPs, AChE inhibition reaches steady state in the adult rat such that continued dosing does not result in increased inhibition. This timeframe of toxicity (21-days and longer) was selected as there was high confidence in the potency estimates derived from the steady state toxicology studies due to the stability of the AChE inhibition. The Agency's 2006 OP CRA contained EPA's complete FQPA safety factor analysis, (Ref. 22) which involved consideration of pre-natal and post-natal experimental toxicology studies, in addition to exposure infermation. In the OP CRA, pre-natal exposure AChE studies in rats show that the fetus is no more sensitive than the dam to AChE inhibition and the fetus is often less sensitive than the dam. Thus, evaluating the potential for increased toxicity of juveniles from post-natal exposure was a key Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225_00000971-00029 component in determining the magnitude of the FQPA safety factors in the OP CRA. Furthermore, because characteristics of children are directly accounted for in the cumulative exposure assessment, the Agency's methods did not underestimate exposure to OPs. In the 2006 OP CRA, each OP was assigned a 10X FQPA safety factor unless chemical-specific AChE data on young animals were available to generate a data derived safety factor. To best match the relative potency factor (RPF)s and PODs based on repeated dosing, the Agency used repeated dosing data in juveniles for developing the FQPA safety factors. For chlorpyrifos, at the time of the 2006 OP CRA, the only such data available were from the Zheng et al. literature study. The petitioners are correct that Dr. Carey Pope of Oklahoma State University provided the Agency with the raw data from the Zheng et al. study. These raw data were used to develop the plot in the 2006 OP CRA which was reproduced in the Petition. Petitioners accurately note that for other OPs a benchmark dose modeling approach was used and that no BMD values were reported for chlorpyrifos. In determining the FQPA safety factor, petitioners claim that the Agency misinterpreted the brain AChE data from Zheng et al. As shown in the plot reproduced on page 15 of the Petition, the dose-response data in the Zheng et al. study are variable and lack a monotonic shape at the low dose end of the dose response curve. The Agency acknowledges that at the high dose, the pups appear to be more sensitive. However, at the low dose end of the response curve, relevant for human exposures and, thus, the cumulative risk assessment (i.e., at or near the 10% inhibition level), little to no difference is observed. Therefore, despite the lack Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225 00000971-00030 of BMD estimates for the Zheng et al. study, the Agency is confident in the value used to address the common mechanism endpoint (AChE inhibition) addressed in the 2006 CRA. Since that time, the Agency attempted BMD modeling of the Zheng et al. data as part of the 2011 preliminary chlorpyrifos HHRA (Ref. 23) which yielded low confidence results due to the variability in the data. Dow AgroSciences submitted a comparative cholinesterase study (CCA) for chlorpyrifos. CCA studies are specially designed studies to compare the dose-response relationship in juvenile and adult rats. This CCA study includes two components: 1) acute, single dosing in post-natal day 11 and young adult rats and 2) 11-days of repeating dosing in rat pups from PND11-21 and 11-days of repeated dosing in adult rats. The CCA study for chlorpyrifos is considered by EPA to be high quality and well-designed. The preliminary risk assessment for chlorpyrifos' reports BMD estimates from this CCA study. Specifically, for the repeated dosing portion of the study, the BMD10s of 0.80 (0.69 BMDL10) and 1.0 (0.95 BMDL10) mg/kg/day respectively for female pups and adults support the FQPA safety factor of 1X for the AChE inhibition endpoint used in the 2006 OP CRA. As such, petitioners' claims regarding the CRA and FQPA safety factor is denied. 5. Over-reliance on registrant data. a. Petitioners' claims. Petitioners assert that in reregistering chlorpyrifos EPA "cherry picked" data, "ignoring robust, peer-reviewed data in favor of weak, industry- sponsored data to determine that chlorpyrifos could be re-registered and food tolerances be retained." As such, the Agency's reassessment decision is not scientifically defensible. Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225 00000971-00031 b. Agency response. This portion of the Petition does not purport to be an independent basis for revoking chlorpyrifos tolerances or cancelling chlorpyrifos registrations. Rather, this claim appears to underlie petitioners' arguments in other sections of the Petition. While petitioners claim that EP A ignored robust, peer-reviewed data in favor of weak, industry-sponsored data for the reregistration of chlorpyrifos, petitioners do not cite to any studies other than those used to support their other claims. In general, petitioners did not provide any studies in the Petition that EPA failed to evaluate. Since the specific studies cited by petitioners are not associated with this claim, but rather their other claims, EPA's response to the specific studies are, therefore, addressed in its responses to petitioners' other claims. However, EPA explains below why, as a general matter, the Agency does not believe it "over-relied" on registrant data in evaluating the risks of chlorpyrifos in its 2006 reregistration decision. In spite of petitioners' claim, the Agency does not ignore robust, peer-reviewed data in favor of industry-sponsored data. Further, EPA has a very public and well- documented set of procedures that it applies to the use and significance accorded all data utilized to inform risk management decisions. Registrant generated data, in response to FIFRA and FFDCA requirements, are conducted and evaluated in accordance with a series of internationally harmonized and scientifically peer-reviewed study protocols designed to maintain a high standard of scientific quality and reproducibility. (Refs. 23 and 24). Additionally, to further inform the Agency's risk assessment, EPA is committed to the consideration of other sources of information such as data identified in the open, peer-reviewed literature and information submitted by the public as part of the regulatory Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225 00000971-00032 evaluation of a pesticide. An important issue, when evaluating any study, is its scientific soundness and quality, and thus, the level of confidence in the study findings to contribute to the risk assessment. The literature was searched, fully considered, and provided additional information on, chlorpyrifos mode of action, pharmacokinetics, epidemiology, neurobehavioral effects in laboratory animals, and age dependent sensitivity to cholinesterase inhibition. Therefore, by evaluating registrant data in accordance with internationally harmonized and scientifically peer-reviewed study protocols, undertaking thorough open literature searches, and considering information provided by the public, the Agency is confident that its assessment for chlorpyrifos in 2006 was reasonably based upon the best available science at the time of the assessment. Previous sections of this response to petitioners' claims regarding the Agency's inadequate use of various data only further highlights and supports the scientifically defensible results of the Agency's assessment. Petitioners' claim that the Agency overly relies on registrant data is therefore denied. 6. EPA has failed to properly address the exporting hazard in foreign countries from chlorpyrifos. As noted in Unit II., in EPA's July 16, 2012 interim petition response EPA issued a final denial of this claim. That denial constituted final agency action and EPA is not reopening consideration of that claim. 7.-9. EPA failed to quantitatively incorporate data demonstrating long-lasting effects from early life exposure to chlorpyrifos in children; EPA disregarded data demonstrating that there is no evidence of a safe level of exposure during pre-birth and early life stages; EPA failed to cite or quantitatively incorporate studies and clinical Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225 00000971-00033 reports suggesting potential adverse effects below 10% cholinesterase inhibition. a. Petitioners' claims. The petitioners assert that human epidemiology and rodent developmental neurotoxicity data suggest that pre-natal and early life exposure to chlorpyrifos can result in long-lasting, possibly permanent damage to the nervous system and that these effects are likely occurring at exposure levels below 10% cholinesterase inhibition, EPA's existing regulatory standard for chlorpyrifos and other OPs. They assert that EPA has therefore used the wrong endpoint as a basis for regulation and that, taking into account the full spectrum of toxicity, chlorpyrifos does not meet the FFDCA safety standard or the FIFRA standard for registration. b. Agency response. EPA has grouped claims 7-9 together because they fundamentally all raise the same issue: whether the potential exists for chlorpyrifos to cause neurodevelopmental effects in infants and children from exposures (either to mothers during pregnancy or directly to infants and children) that are lower than those resulting in 10% cholinesterase inhibition - the basis for EPA's long-standing point of departure in regulating chlorpyrifos and other OPs. While petitioners may perhaps disagree, unlike the claims addressed above, these claims were not truly challenges to EPA's 2006 reregistration decision for chlorpyrifos, but rather, challenges to EPA's ongoing approval of chlorpyrifos under FIFRA and the FFDCA that rely in large measure on data published after EPA completed both its 2001 chlorpyrifos Interim Reregistration Decision and the 2006 OP CRA that concluded the reregistration process for chlorpyrifos and all other OPs. As matters that largely came to light after the completion of reregistration, these petition issues are issues to be addressed as part of the registration review of chlorpyrifos - the next round of re-evaluation under section 3(g) of FIFRA. As Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225_00000971-00034 petitioners are aware, past EPA administrations prioritized the registration review of the OPs in no small measure to begin to focus on the question of OP neurodevelopmental toxicity, which was, and remains, an issue at the cutting edge of science, involving significant uncertainties. EPA has three times presented approaches and proposals to the FIFRA SAP for evaluating recent epidemiologic data (some of which is cited in the Petition) exploring the possible connection between in utero and early childhood exposure to chlorpyrifos and adverse neurodevelopmental effects. The SAP's reports have rendered numerous recommendations for additional study and sometimes conflicting advice for how EPA should consider (or not consider) the epidemiology data in conducting EPA's registration review human health risk assessment for chlorpyrifos. While industry and public interest groups on both sides of this issue can debate what the recommendations mean and which recommendations should be followed, one thing should be clear to all persons following this issue: the science on this question is not resolved and would likely benefit from additional inquiry. EPA has, however, been unable to persuade the 9th Circuit Court of Appeals that further inquiry into this area of unsettled science should delay EPA's response to the Petition. Faced with an order requiring EPA to respond to the Petition, in October 2015, EPA chose to issue a proposed rule to revoke all chlorpyrifos tolerances based in part on the uncertain science surrounding neurodevelopmental toxicity suggested by certain epidemiology studies. The comments EPA has received on that proposal and on EPA's November 17, 2016 NODA suggest that there continue to be considerable areas of uncertainty with regard to what the epidemiology data show and deep disagreement over how those data should be considered in EPA's risk assessment. Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225 00000971-00035 Although not a legal consideration, it is important to recognize that for many decades chlorpyrifos has been and remains one of the most widely used pesticides in the United States, making any decision to retain or remove this pesticide from the market an extremely significant policy choice. In light of the significance of this decision and in light of the significant uncertainty that exists regarding the potential for chlorpyrifos to cause adverse neurodevelopmental effects, EPA's preference is to fully explore approaches raised by the SAP and commenters on the proposed rule, and possibly seek additional authoritative peer review of EPA's risk assessment prior to finalizing any regulatory action in the course of registration review. As the 9th Circuit has made clear in its August 12, 2016 order in PANNA v. EPA, EPA must provide a final response to the Petition by March 31, 2017, regardless of whether the science remains unsettled and irrespective of whatever options may exist for more a complete resolution of these issues during the registration review process. While EPA acknowledges its obligation to respond to the Petition as required by the court, the court's order does not and cannot compel EPA to complete the registration review of chlorpyrifos in advance of the October 1, 2022 deadline provided in section 3(g) of FIFRA, 7 U.S.C. 136a(g). Although past EPA administrations had chosen to attempt to complete that review several years in advance of the statutory deadline (and respond to the Petition on the same time frame), it has turned out that it is not possible to fully address these issues early in the registration review period. As a result, EPA has concluded that it should alter its priorities and adjust the schedule for chlorpyrifos so that it can complete its review of the science addressing neurodevelopmental effects prior to making a final registration review decision whether to retain, limit or remove Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225 00000971-00036 chlorpyrifos from the market. Accordingly, EPA is denying these Petition claims and intends to complete a full and appropriate review of the neurodevelopmental data before either finalizing the proposed rule of October 30, 2015, or taking an alternative regulatory path. EPA's denial of the Petition on the grounds provided above is wholly consistent with governing law. The petition provision in FFDCA section 408(d) does not address the timing for responding to this petition nor does it limit the extent to which EPA may coordinate its petition responses with the registration review provisions of FIFRA section 3(g). Further, provided EPA completes registration review by October 1, 2022, Congress otherwise gave the EPA Administrator the discretion to determine the schedule and timing for completing the review of the approximately over 1000 pesticide active ingredients currently subject to evaluation under section 3(g). EPA may lawfully re- prioritize the registration review schedule developed by earlier administrations provided that decision is consistent with law and an appropriate exercise of discretion. See Federal Communications Commission v. Fox Television Stations, 129 S.Ct. 1800 (2009) (Administrative Procedure Act does not require that a policy change be justified by reasons more substantial than those required to adopt a policy in the first instance). Nothing in FIFRA section 3(g) precludes EPA from altering a previously established registration review schedule. Given the absence of a clear statutory directive, pir RA and the FFDCA provide Eb A with discretion to take mup account EPA's registration review of a pesticide in determining how and when the Agency responds to FFDCA petitions to revoke tolerances. As outlined above, given the importance of this matter and the fact that critical questions remain regarding the significance of the data Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225 00000971-00037 addressing neurodevelopmental effects, EPA believes there is good reason to extend the registration review of chlorpyrifos and therefore to deny the Petition. To find otherwise would effectively give petitioners under the FFDCA the authority to re-order scheduling decisions regarding the FIFRA registration review process that Congress has vested in the Administrator. 10. Inhalation Exposure from Volatilization a. Petitioners' claim. Petitioners assert that when EPA completed its 2006 OP CRA, EPA failed to consider and incorporate significant exposures to chlorpyrifos- contaminated air that exist for some populations in communities where chlorpyrifos is applied. Petitioners assert that these exposures exceeded safe levels when considering cholinesterase inhibition as a point of departure and that developmental neurotoxicity may occur at even lower exposure levels than those resulting in cholinesterase inhibition. b. Agency response. To the extent petitioners are asserting that human exposure to chlorpyrifos spray drift and volatilized chlorpyrifos present neurodevelopmental risks for infants and children, EPA is denying this claim for the reasons stated above in our response to claims 7-9. As noted, EPA believes that, given the uncertainties associated with this identified risk concern, the appropriate course of action is for EPA to deny the Petition and work to further resolve this area of unsettled science in the time remaining for the completion of registration review under section 3(g) of FIFRA. With respect to petitioners' claim that exposures to spray drift and volatilized chlorpyrifos present a risk from cholinesterase inhibition, EPA is denying the Petition for the reasons previously identified in EPA's Spray Drift Mitigation Decision of July 16, 2012 [EPA-HQ-OPP-2008-0850] and EPA's interim response of July 15, 2014 [EPA- Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225 00000971-00038 HQ-OPP-2007-1005 addressing chlorpyrifos volatilization. In the Spray Drift Mitigation Decision, EPA determined that the chlorpyrifos registrants' adoption of label mitigation (in the form of label use rate reductions and no spray buffer zones) eliminated risk from cholinesterase inhibition as a result of spray drift. As for risks presented by volatilized chlorpyrifos that may occur following application, EPA's July 15, 2014 interim response to the Petition explained that recent vapor phase inhalation studies for both chlorpyrifos and chlorpyrifos-oxor made clear that neither vapor phase chlorpyrifos nor chlorpyrifos-oxon presents a risk of cholinesterase inhibition. Specifically, those studies, as indicated in EPA's memorandum, Chlorpyrifos: Reevaluation of the Potential Risks from Volatilization in Consideration of Chlorpyrifos Parent and Oxon Vapor Inhalation Toxicity Studies (Ref. 25), revealed that levels of chlorpyrifos and chlorpyrifos-oxon in vapor form are much lower than the levels seen in earlier aerosol studies that are better suited for evaluating spray drift. Indeed, no cholinesterase inhibition was observed in either volatility study. What is clear from these data is that the air cannot hold levels of volatilized chlorpyrifos or its oxon that are capable of causing adverse effects from cholinesterase inhibition. VI. Regulatory Assessment Requirements As indicated previously, this action announces the Agency's order denying a petition filed, in part, under section 408(d) of FFDCA. As such, this action is an adjudication and not a rule. The regulatory assessment requirements applicable to rulemaking do not, therefore, apply to this action. VII. Submission to Congress and the Comptroller General The Congressional Review Act, 5 U.S.C. 801 et seq., does not apply because this Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225 00000971-00039 action is not a rule for purposes of 5 U.S.C. 804(3). IX. References The following is a listing of the documents that are specifically referenced in this document. The docket includes these documents and other information considered by EPA, including documents that are referenced within the documents that are included in the docket, even if the referenced document is not physically located in the docket. For assistance in locating these other documents, please consult the technical person listed under FOR FURTHER INFORMATION CONTACT. 1. The Petition from NRDC and PANNA and EPA's various responses to it are available in docket number EPA-HQ-OPP-2007-1005 available at http://www.regulations.gov. 2. FIFRA Scientific Advisory Panel (2016). "Chlorpyrifos: Analysis of Biomonitoring Data". Available at: https://www.epa.gov/sap/meeting-materials-april-19- 1-2016-scientific-advisory-panel. 3. Furlong CE, Holland N, Richter RJ, Bradman A, Ho A, Eskenazi B (2006). PON1status of farmworker mothers and children as a predictor of organophosphate sensitivity. Pharmacogenet Genomics. 2006 Mar; 16(3):183-90. 4. Sultatos LG; Murphy SD, (1983). Kinetic Analysis Of The Microsomal Biotransformation Of The Phosphorothioate Insecticides Chlorpyrifos And Parathion. Fundemental and Applied Toxicology. 3:16-21. 5. U.S. EPA (2008). Draft Appendix E available at http://www.epa.gov/scipoly/sap/meetings/2008/september/appendixe.pdf. Draft Science Issue Paper: Chlorpyrifos Hazard and Dose Response Characterization. August 21, 2008. Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225 00000971-00040 Available at http://www.epa.gov/scipoly/sap/meetings/2008/september/chlorpyrifoscharacter.pdf. 6. Holland, N., Furlong, C., Bastaki, M., Richter, R., Bradman, A., Huen, K., Beckman, K., and Eskenazi, B. (2006). Paraoxonase polymorphisms, haplotypes, and enzyme activity in Latino mothers and newborns. Environ. Health Perspect. 114(7), 985- 991; Chen, J., Kumar, M., Chan, W., Berkowitz, G., and Wetmur, J. (2003). Increased Influence of Genetic Variation on PON1 Activity in Neonates. Environmental Health Perspective 111, 11:1403-9. 7. U.S. EPA (2008). Transmittal of Meeting Minutes of the FIFRA Scientific Advisory Panel Meeting Held September 16-18, 2008 on the Agency's Evaluation of the Toxicity Profile of Chlorpyrifos. Available at http://www.epa.gov/scipoly/sap/meetings/2008/september/sap0908report.pdf at 61. 8. Engel,S.M., Wetmur, J., Chen, J., Zhu, C., Boyd Barr, D., Canfield, R.L., Wolff, M.S., (2011) Prenatal Exposure to Organophosphates, Paraoxonase 1, and Cognitive Development in Childhood Environ Health Perspect 119:1182-1188 (2011). doi:10.1289/ehp.1003183 [Online 21 April 2011]. 9. Hofmann, J.N., Keifer, M.C., Furlong, C.E., De Roos, A.J., Farin., F.M., Fenske, R.A., van Belle, G., Checkoway, H. (2009) Serum Cholinesterase Inhibition in Relation to Paraoxonase-1 (PON1) Status among Organophosphate-Exposed Agricultural Pesticide Handlers./ Environ Health Perspect 117:1402-1408 (2009). doi:10.1289/ehp.0900682. Available at http://dx.doi.org/ [Online 9 June 2009]. 10. Eskenazi,B; Huen, K., Marks, A., Harley, K.G., Bradman, A., Boyd Barr, D., Holland, N. (2010) PONI and Neurodevelopment in Children from the CHAMACOS Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225 00000971-00041 Study Exposed to Organophosphate Pesticides in Utero. Environmental Health Perspectives. Vol 118 (12): 1775-1781). 11. Harley KG, Huen K, Schall RA, Holland NT, Bradman A, et al. (2011) Association of Organophosphate Pesticide Exposure and Paraoxonase with Birth Outcome in Mexican-American Women. PLoS ONE 6(8): e23923. doi:10.1371/journal.pone.0023923. 12. IPCS (International Programme on Chemical Safety) 2005. Chemical-Specific Adjustment Factors for Interspecies Differences and Human Variability: Guidance Document for Use of Data in Dose/Concentration-Response Assessment. Harmonization Project Document No. 2. World Health Organization, International Programme on Chemical Safety, Geneva, Switzerland. 13. U.S. EPA (2014). Guidance for Applying Quantitative Data to Develop Data- Derived Extrapolation Factors for Interspecies and Intraspecies Extrapolation. Available at https://www.epa.gov/risk/guidance-applying-quantitative-data-develop-data-derived- extrapolation-factors-interspecies-and. 14. For additional information on the Endocrine Disruptor Screening program see http://www.epa.gov/endo/. 15. For information related to the status of EDSP test orders/DCIs, status of EDSP OSRI: order recipient submissions and EPA responses, and other EDSP assay information see http://www.epa.gov/endo/pubs/toresources/index.htm 16. For available Data Evaluation Records (DERs) for EDSP Tier 1, see ttps://www.epa.gov/endocrine-disruption/endocrine-disruptor-screening-program-tier-1- Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225 00000971-00042 screening-determinations-and, 17. Hoppin JA, Lubin JH, Rusiecki JA, Sandler DP, Dosemeci M, Alavanja MC. (2004) Cancer incidence among pesticide applicators exposed to chlorpyrifos in the Agricultural Health Study. J Natl Cancer Inst, 96(23), 1781-1789. (hereinafter Lee et al. 2004). 18. U.S. EPA (2005). Guidelines for Carcinogen Risk Assessment. Available at http://www.epa.gov/raf/publications/pdfs/CANCER_GUIDELINES_FINAL_3-25- 05.PDF. 19. Christenson, C. (2011). D388167, Chlorpyrifos Carcinogenicity: Review of Evidence from the U.S. Agricultural Health Study (AHS) Epidemiologic Evaluations 2003-2009. 20. Weichenthal S, Moase C, Chan P (2010). A review of pesticide exposure and cancer incidence in the agricultural health study cohort. Cien Saude Colet. 2012 an;17(1):255-70. PubMed PMID: 22218559. 21. Zheng Q, Olivier K, Won YK, Pope CN. (2000). Comparative cholinergic neurotoxicity of oral chlorpyrifos exposures in pre-weaning and adult rats. Toxicological Sciences, 55(1): 124-132. 22. For additional information on the organophosphate cumulative risk assessment, see http://epa.gov/pesticides/cumulative/2006-op/op_cra_main.pdf. 23. U.S. EPA (2011). Chlorpyrifos: Preliminary Human Health Risk Assessment for Registration. Available in docket number EPA-HQ-OPP-2008-0850, ttp://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2008-0850-0025. (23) For additional information on EPA's Harmonized Test Guidelines and Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225_00000971-00043 international efforts at harmonization, see http://www.epa.gov/opp00001/science/guidelines.htm. (24) Available at http://www.regulations.gov in docket EPA-HQ-OPP-2008- 0850. Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0226 001225_00000971-00044 Administrator's Signature on page 45 of 45 pages; FRL- 9960-77: Chlorpyrifos; Order Denying PANNA and NRDC's Petition to Revoke Tolerances Authority: 7 U.S.C. 136 et seq. and 21 U.S.C. 346a. Dated: 3/24/2017 SUNDAR E. Scott Pruitt, Administrator. Source: https://www.industrydocuments.ucsf.edu/docs/jhcn0206 001225_00000971-00045

What does Figure 1 represents?

hlcn0226

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Project Conceptual Approach

129 From: Jürgen Troitzsch To: Osimitz Thomas; Dr. Blais Matthew; Prof. Rein Guillermo; Dr. Hayes Wallace; Dourson. Michael (doursomi); Kacew Sam; Dr. Wise Kimberly Subject: Fwd: Project on FF PPE Cleaning Validation Date: Monday, June 12, 2017 1:11:46 PM Attachments: PROU PANEL - PPE Cleaning (33) pdf PROJ SUMMARY - PPE Cleaning (7) pot FLYER FF Contam Control Workshop (6) odf HOTELS - Contam Control Wrkshp on 2017Jul19.pd PROJS JMMARY- FE Cancer Cohort Study (4) odf Dear All, I came across this project, which may be of interest in the frame of our fire fighters cancer activities. Kind regards/Viele Grüße Jürgen Dr. Jürgen Troitzsch Fire and Environment Protection Service FEPS Via Patrizia 32 CH-6612 Ascona, Switzerland Mobile: +41 79 289 17 16 Phone: +41 91 791 14 22 Email: [email protected] Web: www.troitzsch.com De : Grant, Casey Envoyé : lundi 22 mai 2017 17:58 À : [email protected]; [email protected]. tis.com; mlambetamallN u.edu; dwardmecarthyebostengoy ark.a.miller@ehoen ix.gov; james.riley@bosta nagov; [email protected] Thomas [email protected]; ;timügearcleaningsolutions.s om [email protected]; Ken.Wiles @fire.jacounty.gov Farrell, Christopher cobtlogiobefiresuits.com; pattogiobefiresults.com; Diane.Hess@ Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 130 PBIProducts.com; Kebtonen@lionprotedscon leur.gouv.fr; GUILLAUME Eric <eric [email protected] ;[email protected]; mamiefortunes-collide.com Cc : lasonallendintertekeor [email protected]; [email protected] wlindslev@ cdc.gov; [email protected] [email protected]; [email protected]; ; istendice OY; Objet : Project on FF PPE Cleaning Validation To: Panel, Research Team and Liaisons for Project on "Fire Fighter PPE Cleaning Validation" It has been some time since we last spoke, and I have the following three items to be addressed: 1) A lot has been happening with our project and we want to hold a 90 minute conference call in early August 2017 to bring everyone up-to-date. I've created a scheduling poll to determine the optimum date/time Please respond before Noon ET on Wednesday 31/May/2017 so that we can get this on our calendars. I've attached the Project Roster and Project Summary in case anyone needs a refresher for this project addressing "how clean is clean". Thanks. 2) I've been asked to participate in a webinar tomorrow (23/Mav/2017) from noon ET to 1:30 pm ET on "Factors Relating to Cancer and Contamination in the US Fire Service". I've been assigned a portion of this webinar (among two other speakers) to address on-going research and I'm planning to address our project among several other on-going efforts. The link is on the NFPA home page at: FYI.. 3) Some of you are already aware of the Workshop in Columbus, Ohio on 19- 20/Julv/2017, and if not I want to call it to your attention. This is for the separate one year AFG project on "Campaign for Fire Service Contamination Control". Attached is a Flyer that provides additional details, and also attached is a list of hotels in the area to assist with travel. The workshop will be held from Noon to Noon on 19-20/July and we still have room if you would like to attend. In addition, the separate project (i.e., a third related project) on "Fire Fighter Cancer Cohort Study" will hold a separate planning meeting on the afternoon of 20/July from 1 pm to 5 pm (Project Summary is attached). All are welcome to attend this as well. If you are a fire service panel member we can cover your travel, and I can send follow-up instructions to you separately. For anyone interested in attending the Columbus meetings on 19-20/July, please let us know by email to [email protected] and Thanks.. Casey C. Grant, P.E. Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION "CAMPAIGN FOR FIRE SERVICE CONTAMINATION CONTROL" WORKSHOP Location: Columbus Fire Fighters Union Hall, 379 W Broad St, Columbus, OH 43215 Workshop Dates: 19-20 July 2017 (Last Updated: 21 April 2017; subject to update) Background: Exposure to chemical and biological contaminants on the fire ground is an increasing concern for long-term fire fighter health. Cancer and other diseases resulting from chronic exposures has become a leading concern for the fire service. This is presumed to be associated with fireground exposures relating to protection/hygiene practices and persistent harmful contamination found in fire fighter equipment, apparatus carrying that equipment, and stations where the equipment resides. Workshop Goal and Objectives: The goal of this Workshop is to identify concepts and materials that are or can be useful to control the spread of harmful fire ground contaminants, ultimately in support of improved fire fighter long-term health. The following objectives support this goal (and reflect anticipated deliverables): Identify, review and recommend baseline materials (existing and proposed) addressing best practices, standards, research, equipment, facilities, and other areas of focus. Identify and prioritize gaps that are barriers to enhancing best practices, standards, research, equipment, facilities, and other areas of focus. Identify and review key characteristics for effective promotion and communication. Clarify target audiences for outreach and consider stakeholder research prior to developing a comprehensive communications plan to improve outcome. Prioritize messages for year one. Agenda: Wed; 19/July 1:00 pm Day One: Welcome and Call to Order Casey Grant, FPRF 1:15 pm Overview of Baseline Materials and Review of Gaps Jeff Stull, IPP 2:00 pm Review of Outreach Peg, Paul, PPA 2:30 pm Case Study: Best Practice Information Beth Gallup, KFD 3:00 pm PM Break 3:15 pm Casey Study: Standards Revisions Dave Bernzweig, CFD 3:45 pm Case Study: Equipment & Facilities Paul Erickson, LEWA 4:15 pm Breakout Groups Workshop Attendees 5:00 pm Adjourn for Day One (& Evening Networking Reception) Thur; 20/July 8:30 am Day Two: Group Review of Baseline Materials Jeff Stull, IPP 8:45 am Breakout Groups Continue Workshop Attendees 9:45 am AM Break 10:00 am Breakout Group Report Workshop Attendees 11:00 am Plenary Discussion Workshop Attendees 11:30 am Workshop Wrap-up & Summary Observations Casey Grant, FPRF 12:00 pm Adjournment Registration: Workshop attendance is limited to the first 50 attendees, and others will be placed the on a waiting list. To request attendance or for more information, please contact [email protected]. After the Workshop a report will be available. This Workshop is funded through an AFG Fire Prevention & Safety Grant from U.S.DHS/FEMA. 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7281 Fax: +1.617.984.7010 Email: [email protected] www.NFPA.org/Foundation Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 WORKSHOP ON FIRE SERVICE CONTAMINATION CONTROL 19-20 July 2017 (Noon to Noon ET) Columbus Fire Fighters Union Hall 379 W Broad St, Columbus, OH 43215 Note: For flights, Workshop starts at Noon ET on 19/July/2017 and finishes at Noon ET on 20/July/2017 Drury Inn & Suites: 88 East Nationwide Blvd, Columbus, OH 43215 Phone: 1-614-221-7008 ttos://www.drurvhotels.com/locations/columbus-ob/drurv-inn-and-suites-columbus-convention: center Approximate Rate: $130 Distance (in miles) from Hotel to Columbus Union Hall: 1.3 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars. Red Roof Plus Columbus Downtown Convention Center 111 East Nationwide Blvd, Columbus, OH 43215 Phone: 1-614-224-6539 ittps://www.redroof.com/property/Columbus/OH/43215/Hotels-close-to-Greater-columbus- Convention-Center-US-23-1-670/RRI262/ Approximate Rate: $130 Distance (in miles) from Hotel to Columbus Union Hall: 1.4 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars. Sheraton Columbus Hotel at Capital Square 75 East State Street, Columbus, OH, 43215 Phone: 1-614-365-4500 http://www.sheratoncolumbuscapitolsquare.com/ Approximate Rate: $170 Distance (in miles) from Hotel to Columbus Union Hall: 0.8 Notes: Central downtown area Hampton Inn and Suites Columbus Downtown 501 North High Street, Columbus, OH 43215 Phone: 1-614-559-2000 htto://hamptoninns.bilton.com/en/hotels/ohio/hampton-inn-and-suites-columbus-downtown- CMHHSHK/index.htmi?WT.mc. Approximate Rate: $175 Distance (in miles) from Hotel to Columbus Union Hall: 1.3 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars. Page 1 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Courtyard Columbus Downtown 35 West Spring Street, Columbus, Ohio 43215 Phone: 1-614-228-3200 4d19-a255-54ba596febe2 Approximate Rate: $175 Distance (in miles) from Hotel to Columbus Union Hall: 0.8 Notes: Downtown west area; walkable Doubletree Suites by Hilton Columbus Downtown 50 South Front St, Columbus, Ohio, 43215-4145 Phone: 1-614-228-4600 CMHSBOT/index.htmi Approximate Rate: $200 Distance (in miles) from Hotel to Columbus Union Hall: 0.5 Notes: Closest hotel to meeting site; very short walk Residence Inn Columbus Downtown 36 East Gay Street, Columbus, Ohio 43215-3108 Phone: 1-614-222-2610 ec3-4d19-a255-54ba596febe2 Approximate Rate: $230 Distance (in miles) from Hotel to Columbus Union Hall: 0.8 Renaissance Columbus Downtown 50 North Third Street, Columbus, Ohio 43215 Phone: 1-614-228-5050 ttp://www.marriott.com/hotels/travel/cmhbr-renaissance-columbus-downtown-hotel/ Approximate Rate: $240 Distance (in miles) from Hotel to Columbus Union Hall: 1.0 Notes: Central downtown area Hilton Columbus Downtown 401 North High Street, Columbus, OH 43215 Phone: 1-614-384-8600 Approximate Rate: $240 Distance (in miles) from Hotel to Columbus Union Hall: 1.1 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars; New facility and nice. Page 2 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION PPE Cleaning Validation Validation of Cleaning Procedures for Fire Fighter Personal Protective Equipment (PPE) PROJECT CONTACTS Last Updated: 22 May 2017 Project Technical Panel Phone: 614-774-7446 David Bernzweig, Columbus Fire Department (OH) Email: [email protected] Phone: 780-496-3801 Ken Block, Edmonton Fire/Rescue & Metro Chiefs Representative Email: [email protected] Phone: 804-971-7983 Ken Brown, VA State Firefighter's Association & NVFC (Alt to B. McQueen) Email; [email protected] Phone: 510-839-5111 Cell: 213-321-9393 Roger Curtis, ECMS Curtis & Sons (CA) Email: [email protected] Phone: Paul Curtis, ECMS Curtis & Sons (CA) (Alt to Roger Curtis) Email: [email protected] Phone: 253-277-4131 Cell: 503-314-4832 Steve Lakey, Northwest Safety Clean (WA) Email: [email protected] Phone: 304-406-7479 Mark Lambert, WV Fire Academy & NAFTD (WV) Email: [email protected] Phone: 617-828-3978 Ed McCarthy, Boston Fire Department (MA) Email: [email protected] Phone: 315-736-7479 Cell: 315-552-8245 Brian McQueen, FASNY & National Volunteer Fire Council (NY) Email: [email protected] Phone: 602-534-2396 Mark Miller, Phoenix Fire Dept. (AZ) Email: [email protected] Phone: 919-524-1569 Bryan Ormond, NCSU (NC) Email: [email protected] Phone: Russ Osgood, Firefighter Cancer Support Network (NH) (Alt to Keith Tyson) Email: [email protected] Phone: Larry Petrick, IAFF (DC) Email: [email protected] Phone: 617-549-9850 Jim Riley, Boston Fire Department (MA) (Alt to E. McCarthy) Email: [email protected] Phone: 757-385-2892 Molly Riley, Virginia Beach Fire Dept. (VA) Email: [email protected] Phone: 718-999-2922 Thomas Smith, FDNY (NY) Email: [email protected] Phone: 214-774-2213 Cell: 940-300-5718 Tim Tomlinson, Gear Cleaning Solutions (TX) Email: [email protected] Phone: Robert Tutterow, NFPA Fire Service Section (NC) Email: [email protected] Phone: 786-351-3276 Keith Tyson, Firefighter Cancer Support Network (FL) Email: [email protected] Phone: 951-807-1914 Dick Weise, LA County Fire Dept. (CA) Email: [email protected] Phone: 949-291-0637 Ken Wiles, LA County Fire Dept. (CA) (Alt to Dick Weiss) Email: [email protected] Phone: 512-974-0286 Chris Youngblood, Austin Fire Dept. (TX) Email: [email protected] 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7281 Fax: +1.617.984.7010 Email: [email protected] www.NFPA.org/Foundation Source: :https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Phase 1 Project Contacts Phone: 330-723-0000, x365 Steve Allison, Fire-Dex (OH) Email: [email protected] Phone: 800-401-4780 Jack Binder, Edmar Chemical Company (OH) Email: [email protected] Phone: 920-570-0824 Bill Brooks, Alliance Corp. (WI) Email: [email protected] Phone: Charlie Dunn, TenCate Protective Fabrics Email: [email protected] Phone: 617-984-7325 Chris Farrell, NFPA & Staff Liaison for NFPA 1851 (MA) Email: [email protected] Phone: 800-232-8323 Rob Freese, Globe Manufacturing (NH) Email: [email protected] Phone: Pat Freeman, Globe Manufacturing (NH) (Alternate to Rob Freese) Email: [email protected] Phone: 704-554-3313 Diane Hess, PBI Performance Products (NC) Email: [email protected] Phone: 937-415-2932 Karen Lehtonen, LionFirst Responder Products (OH) Email: [email protected] Phone: 484-433-4072 Dan Silvestri, 9-1-1 Safety (PA) Email: [email protected] Liaison Contacts Phone: Pierre Carlotti, Ministry of Interior & Liaison for ISO TC92/SC3 (France) Email: [email protected] Phone: Eric Guillaume, Efectis & Liaison for ISO TC92/SC3 (France) Email: [email protected] Phone: Bill Haskell, NIOSH NPPTL (MA) Email: [email protected] Phone: James Hoar, Boston Fire Department (MA) Email: [email protected] Phone: 631-242-0621 Steve King, Chair NFPA 1851 (NY) Email: [email protected] Phone: +33(0)1.55.76.26.18 Fanny Rieunier, Ministry of Interior & Liaison for ISO TC92/SC3 (France) Email: [email protected] Phone: 612-247-6429 Marni Schmid, Fortunes Collide & Secretariat NFPA 1851 (MI) Email: [email protected] Page 2 of 3 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Core Research Team Phone: 607-758-6537 Cell: 607-423-5617 Jason Allen, Intertek (NY) Email: [email protected] Phone: 304-285-6076 Daniel Farcas, NIOSH HELD (WV) Email: [email protected] Phone: Crystal Forester, NIOSH NPPTL (WV) Email: [email protected] Phone: 617-984-7284 Cell: 617-659-1159 Casey Grant, Fire Protection Research Foundation (MA) Email: [email protected] Phone: Lee Greenawald, NIOSH NPPTL (WV) Email: [email protected] Phone: Bill Lindsley, NIOSH HELD (WV) Email: [email protected] Phone: Stephen Martin, NIOSH DRDS (WV) Email: [email protected] Phone: John Noti, NIOSH HELD (WV) Email: [email protected] Phone: Deborah Sbarra, NIOSH NPPTL (WV) Email: [email protected] Phone: 512-288-8272 cell: 512-623-9558 Jeff Stull, International Personal Protection (TX) Email: [email protected] Phone: 304-285-5858 cell: 681-209-2571 Jay Tarley, NIOSH NPPTL (WV) Email: [email protected] Additional Research Team Contacts Phone: 304-285-5884 Francoise Blachere, NIOSH HELD (WV) Email: [email protected] Phone: Renee Dotson, NIOSH HELD (WV) Email: [email protected] Phone: James Harris, NIOSH NPPTL (WV) Email: [email protected] Phone: Ryan Lebouf, NIOSH DRDS (WV) Email: [email protected] Phone: 617-984-7281 Eric Peterson, Fire Protection Research Foundation (MA) Email: [email protected] Phone: John Powers, NIOSH (WV) Email: [email protected] Phone: 412-386-4621 Cell: 412-463-9561 Heather Reed, NIOSH NPPTL (PA) Email: [email protected] Page 3 of 3 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION PPE Cleaning Validation Validation of Cleaning Procedures for Fire Fighter Personal Protective Equipment (PPE) (for more information see www.nfpa.org/PPECleaning) PROJECT SUMMARY Last updated: 5 February 2016 Background: Fire fighter exposure to personal protective equipment (PPE) that is dirty, soiled, and contaminated is an increasing concern for long-term fire fighter health. This exposure to persistent harmful contaminants in PPE is an extremely serious problem both on the fireground to highly toxic substances including a variety of carcinogens, and more insidiously to an increasing range of infectious pathogens that are encountered in patient care and different emergency operations. Fire fighter PPE becomes contaminated during these exposures and there are no industry standards that conclusively and reliably show that clothing is being adequately cleaned. While general cleaning procedures have been established in NFPA 1851, Standard on Selection, Care, and Maintenance of Protective Ensembles for Structural Fire Fighting and Proximity Fire Fighting, there are no procedures or requirements to demonstrate whether current cleaning practices, including those specified in NFPA 1851, will remove contaminants from fire fighter protective clothing. This project is intended to establish clear and definitive guidance to the fire service for applying cleaning and decontamination procedures that effectively remove both chemical and biological contaminants. Research Goal and Objectives, and Conceptual Approach: The overall goal of this project is to improve fire fighter safety and health by reducing continuing exposure to harmful contaminants in unclean or inadequately cleaned PPE. The objectives to achieve this goal are twofold: (1) To characterize fireground and emergency scene contamination leading to these exposures and develop the methodology for the consistent measurement of cleaning effectiveness; and (2) determine implementable cleaning, decontamination, and disinfection strategies that effectively reduce fire fighter exposures to persistent contaminants. The approach taken by this project is illustrated in Figure 1: Project Conceptual Approach. - Ensure Identify Devise Validate lab - - chemical and methods to methods - at biologicat conteminate againet field ses target clothing in contaminants laboratory exposures acceptance Project Direction Figure 1: Project Conceptual Approach 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7281 Fax: +1.617.984.7010 Email: [email protected] www.NFPA.org/Foundation Source: :ttps://www.industrydocuments.ucsf.edu/docs/hlcn0226 Project Phases and Tasks: This project involves the following four key phases of activity: 1) Identification of Contaminants: Confirm identification and ability to characterize persistent chemical and biological contaminants in fire fighter PPE through target substances and microorganisms. 2) Establishment of Soil and Chemical Contamination/Decontamination Procedures: Develop and validate specific procedures that determine the effectiveness of laundering and other cleaning methods in removing specific soils and chemical contaminants. 3) Establishment of Biological Contamination/Disinfection or Sanitization Procedures: Develop and validate specific procedures that determine the effectiveness of laundering or disinfection/sanitization processes that remove/deactivate biologically-based contaminants. 4) Creation of Overall Fire Service Guidance: Prepare clear and definitive information for the fire service industry (fire fighters, fire departments, clothing manufacturers, material suppliers, cleaning/care organizations, and cleaning agent or equipment manufacturers) on appropriate approaches for properly cleaning fire fighter protective clothing and equipment. The specific tasks of this project are based on these four phases of the project, and these are illustrated in Figure 2: Project Tasks. PHASE 2 PHASEZ Task 2.4 Task 2.5 Task 1.1 Task 2.1 Validate testsat Refine test Appoint Technical Select cleaning selected ISPS methodology Review Panel methods/agents (chemical) (chemical) PHASE $ Task 4.1 Task 1.2 Task 2.2 Write qualification Review Prigr Put together test plan methods studies/literature (chemical) Task 2.3 Task 4.2 Task 1.3 PHASE 3 Perform laboratory Establish cleaning Setup analytical chemical Task 3.3 acceptance criteria capabilities decontaminant Put together test plan testing (biological) Task 4.3 Task 1.4 Perform Task 3.4 Prepare public inputs for NFPA 1851 demonstration tests Task 3.1 Perform laboratory Task 3.6 Select study biological Refine test microorganisms decontaminant methodology Task 1.5 testing (biological) Task 4.4 Refine biological Prepare industry decontamination Task 3.2 Task 3.5 guidance document scope Select biological Validate testsat cleaning methods selected ISPs (biological) Task 1.6 Task 4,5 Establish cleanliness Prepare project final metrics report Figure 2: Project Tasks Implementation and Schedule: This three year project is due to be completed no later than " August 2018, and is funded through an AFG Fire Prevention & Safety Grant from the U.S. Department of Homeland Security / Federal Emergency Management Agency. The Research Foundation will lead a unique research team partnership composed of the FPRF, National Institute for Occupational Safety and Health (NIOSH), International Personal Protection (IPP), and Intertek. The research team, along with several Independent Service Providers (ISPs), will work with the fire service partners and others to validate and optimize fire fighter PPE cleaning validation methods. For more information see www.nfpa.org/PPECleaning. Page 2 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION Fire Fighter Cancer Cohort Study Full Title: The Firefighter Multicenter Cancer Cohort Study: Framework Development and Testing PROJECT SUMMARY Last Updated: 20 September 2016 Background: Cancer is a leading cause of fire service morbidity and mortality. Firefighter exposure to carcinogens occurs through skin contamination and through inhalation when respiratory protection is not worn when combustion products are present such as during overhaul, standby, and operation of apparatus, as well as through off-gassing of equipment and exposures in the fire station. However, we currently do not understand which exposures are responsible for cancer in firefighters, the mechanisms by which firefighter exposures cause cancer, nor the most effective means of reducing exposures. Since cancer has a long latency period, biomarkers are also needed that can measure the toxicological effects of carcinogen exposure well before the development of cancer, when interventions to prevent disease could be effective. Development of a large (>10,000 firefighter) multicenter firefighter cancer prospective cohort study will address these needs, but the framework for such a study needs to be first developed and tested among a smaller initial set of fire service partners. Implementation and Schedule: This research project is led by University of Arizona with collaborative support from multiple other research partners, including the University of Miami, National Institute for Occupational Safety and Health; National Fallen Firefighter Foundation, Fire Protection Research Foundation, and others. Initial funding for this project is through a 3-year DHS/FEMA Assistance to Fire Fighter (AFG) Fire Grant, with the intention to identify and obtain additional funding for the duration of the 30 year effort. The project start date is August 2016. The Principal Investigator for this project is: Jefferey L. Burgess, MD, MS, MPH, University of Arizona, email: [email protected]. Project Goal and Aims: The goal of the initial 3-year effort of this overall project is to develop and test a framework for establishing a long-term fire fighter multicenter prospective cohort study focused on carcinogenic exposures and effects. The specific aims are to: 1) Establish an oversight and planning board to provide study oversight, foster communication among fire organizations and help develop a long-term funding plan; 2) Create and test a cohort study data coordinating center and harmonized survey data protocols; 3) Develop and validate a firefighter carcinogen exposure matrix and data collection system; and 4) Create a biomarker assessment center and evaluate the association between cumulative firefighter exposures and epigenetic effects. For more information, contact: Casey Grant, Fire Protection Research Foundation 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7284 Fax: +1.617.984.7010 Email: [email protected] Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Project Methodology: This study will harmonize and build on recent and developing firefighter cancer prevention studies in Arizona, Florida and Massachusetts, adding volunteer fire departments. An oversight and planning board will be established by the Fire Protection Research Foundation (FPRF) in association with the National Fallen Firefighter Foundation (NFFF) Fire Service Occupational Cancer Alliance (FSOCA) to provide oversight of the study through collaboration among fire service organizations, academia, and government agencies, and develop a long-term funding and sustainability plan. A data coordination center team will design, develop and evaluate a framework for a multicenter prospective cohort study of firefighters and cancer risk, including standardized participant survey data collection tools and analysis protocols sufficient to address the short- and long-term study objectives as well as linkage with long-term outcome data including cancer development. An exposure assessment center team will develop a carcinogen exposure matrix and data collection system to provide improved occupational exposure data for comparison with epigenetic outcomes and eventual cancer outcomes. Carcinogen exposures associated with specific fire types will be evaluated across fire departments through industrial hygiene monitoring and analysis of urine for absorbed contaminants, supplementing existing FEMA-funded and other studies of firefighter exposures and allowing for participating fire departments to design interventions to reduce current exposures. Expansion of the National Fire Operations Reporting System (NFORS) will be explored as one option to uniformly collect incident and exposure data. Blood and buccal cells will be collected during annual medical surveillance evaluations, including both new recruits and incumbent firefighters. Pilot studies of epigenetic markers of cancer effect and cancer risk will be analyzed comparing municipal firefighters with high chronic exposures, volunteer firefighters with low chronic exposures, and non- firefighter friends of the municipal firefighters (serving as controls). Project Deliverables: The anticipated outcomes from this 3-year effort is to establish and test the framework necessary for the subsequent development of a large multicenter cohort study of cancer in the fire service. Page 2 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226

What is the fullform of PPE?

hlcn0226

hlcn0226_p0, hlcn0226_p1, hlcn0226_p2, hlcn0226_p3, hlcn0226_p4, hlcn0226_p5, hlcn0226_p6, hlcn0226_p7, hlcn0226_p8, hlcn0226_p9, hlcn0226_p10, hlcn0226_p11

Personal Protective Equipment

129 From: Jürgen Troitzsch To: Osimitz Thomas; Dr. Blais Matthew; Prof. Rein Guillermo; Dr. Hayes Wallace; Dourson. Michael (doursomi); Kacew Sam; Dr. Wise Kimberly Subject: Fwd: Project on FF PPE Cleaning Validation Date: Monday, June 12, 2017 1:11:46 PM Attachments: PROU PANEL - PPE Cleaning (33) pdf PROJ SUMMARY - PPE Cleaning (7) pot FLYER FF Contam Control Workshop (6) odf HOTELS - Contam Control Wrkshp on 2017Jul19.pd PROJS JMMARY- FE Cancer Cohort Study (4) odf Dear All, I came across this project, which may be of interest in the frame of our fire fighters cancer activities. Kind regards/Viele Grüße Jürgen Dr. Jürgen Troitzsch Fire and Environment Protection Service FEPS Via Patrizia 32 CH-6612 Ascona, Switzerland Mobile: +41 79 289 17 16 Phone: +41 91 791 14 22 Email: [email protected] Web: www.troitzsch.com De : Grant, Casey Envoyé : lundi 22 mai 2017 17:58 À : [email protected]; [email protected]. tis.com; mlambetamallN u.edu; dwardmecarthyebostengoy ark.a.miller@ehoen ix.gov; james.riley@bosta nagov; [email protected] Thomas [email protected]; ;timügearcleaningsolutions.s om [email protected]; Ken.Wiles @fire.jacounty.gov Farrell, Christopher cobtlogiobefiresuits.com; pattogiobefiresults.com; Diane.Hess@ Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 130 PBIProducts.com; Kebtonen@lionprotedscon leur.gouv.fr; GUILLAUME Eric <eric [email protected] ;[email protected]; mamiefortunes-collide.com Cc : lasonallendintertekeor [email protected]; [email protected] wlindslev@ cdc.gov; [email protected] [email protected]; [email protected]; ; istendice OY; Objet : Project on FF PPE Cleaning Validation To: Panel, Research Team and Liaisons for Project on "Fire Fighter PPE Cleaning Validation" It has been some time since we last spoke, and I have the following three items to be addressed: 1) A lot has been happening with our project and we want to hold a 90 minute conference call in early August 2017 to bring everyone up-to-date. I've created a scheduling poll to determine the optimum date/time Please respond before Noon ET on Wednesday 31/May/2017 so that we can get this on our calendars. I've attached the Project Roster and Project Summary in case anyone needs a refresher for this project addressing "how clean is clean". Thanks. 2) I've been asked to participate in a webinar tomorrow (23/Mav/2017) from noon ET to 1:30 pm ET on "Factors Relating to Cancer and Contamination in the US Fire Service". I've been assigned a portion of this webinar (among two other speakers) to address on-going research and I'm planning to address our project among several other on-going efforts. The link is on the NFPA home page at: FYI.. 3) Some of you are already aware of the Workshop in Columbus, Ohio on 19- 20/Julv/2017, and if not I want to call it to your attention. This is for the separate one year AFG project on "Campaign for Fire Service Contamination Control". Attached is a Flyer that provides additional details, and also attached is a list of hotels in the area to assist with travel. The workshop will be held from Noon to Noon on 19-20/July and we still have room if you would like to attend. In addition, the separate project (i.e., a third related project) on "Fire Fighter Cancer Cohort Study" will hold a separate planning meeting on the afternoon of 20/July from 1 pm to 5 pm (Project Summary is attached). All are welcome to attend this as well. If you are a fire service panel member we can cover your travel, and I can send follow-up instructions to you separately. For anyone interested in attending the Columbus meetings on 19-20/July, please let us know by email to [email protected] and Thanks.. Casey C. Grant, P.E. Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION "CAMPAIGN FOR FIRE SERVICE CONTAMINATION CONTROL" WORKSHOP Location: Columbus Fire Fighters Union Hall, 379 W Broad St, Columbus, OH 43215 Workshop Dates: 19-20 July 2017 (Last Updated: 21 April 2017; subject to update) Background: Exposure to chemical and biological contaminants on the fire ground is an increasing concern for long-term fire fighter health. Cancer and other diseases resulting from chronic exposures has become a leading concern for the fire service. This is presumed to be associated with fireground exposures relating to protection/hygiene practices and persistent harmful contamination found in fire fighter equipment, apparatus carrying that equipment, and stations where the equipment resides. Workshop Goal and Objectives: The goal of this Workshop is to identify concepts and materials that are or can be useful to control the spread of harmful fire ground contaminants, ultimately in support of improved fire fighter long-term health. The following objectives support this goal (and reflect anticipated deliverables): Identify, review and recommend baseline materials (existing and proposed) addressing best practices, standards, research, equipment, facilities, and other areas of focus. Identify and prioritize gaps that are barriers to enhancing best practices, standards, research, equipment, facilities, and other areas of focus. Identify and review key characteristics for effective promotion and communication. Clarify target audiences for outreach and consider stakeholder research prior to developing a comprehensive communications plan to improve outcome. Prioritize messages for year one. Agenda: Wed; 19/July 1:00 pm Day One: Welcome and Call to Order Casey Grant, FPRF 1:15 pm Overview of Baseline Materials and Review of Gaps Jeff Stull, IPP 2:00 pm Review of Outreach Peg, Paul, PPA 2:30 pm Case Study: Best Practice Information Beth Gallup, KFD 3:00 pm PM Break 3:15 pm Casey Study: Standards Revisions Dave Bernzweig, CFD 3:45 pm Case Study: Equipment & Facilities Paul Erickson, LEWA 4:15 pm Breakout Groups Workshop Attendees 5:00 pm Adjourn for Day One (& Evening Networking Reception) Thur; 20/July 8:30 am Day Two: Group Review of Baseline Materials Jeff Stull, IPP 8:45 am Breakout Groups Continue Workshop Attendees 9:45 am AM Break 10:00 am Breakout Group Report Workshop Attendees 11:00 am Plenary Discussion Workshop Attendees 11:30 am Workshop Wrap-up & Summary Observations Casey Grant, FPRF 12:00 pm Adjournment Registration: Workshop attendance is limited to the first 50 attendees, and others will be placed the on a waiting list. To request attendance or for more information, please contact [email protected]. After the Workshop a report will be available. This Workshop is funded through an AFG Fire Prevention & Safety Grant from U.S.DHS/FEMA. 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7281 Fax: +1.617.984.7010 Email: [email protected] www.NFPA.org/Foundation Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 WORKSHOP ON FIRE SERVICE CONTAMINATION CONTROL 19-20 July 2017 (Noon to Noon ET) Columbus Fire Fighters Union Hall 379 W Broad St, Columbus, OH 43215 Note: For flights, Workshop starts at Noon ET on 19/July/2017 and finishes at Noon ET on 20/July/2017 Drury Inn & Suites: 88 East Nationwide Blvd, Columbus, OH 43215 Phone: 1-614-221-7008 ttos://www.drurvhotels.com/locations/columbus-ob/drurv-inn-and-suites-columbus-convention: center Approximate Rate: $130 Distance (in miles) from Hotel to Columbus Union Hall: 1.3 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars. Red Roof Plus Columbus Downtown Convention Center 111 East Nationwide Blvd, Columbus, OH 43215 Phone: 1-614-224-6539 ittps://www.redroof.com/property/Columbus/OH/43215/Hotels-close-to-Greater-columbus- Convention-Center-US-23-1-670/RRI262/ Approximate Rate: $130 Distance (in miles) from Hotel to Columbus Union Hall: 1.4 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars. Sheraton Columbus Hotel at Capital Square 75 East State Street, Columbus, OH, 43215 Phone: 1-614-365-4500 http://www.sheratoncolumbuscapitolsquare.com/ Approximate Rate: $170 Distance (in miles) from Hotel to Columbus Union Hall: 0.8 Notes: Central downtown area Hampton Inn and Suites Columbus Downtown 501 North High Street, Columbus, OH 43215 Phone: 1-614-559-2000 htto://hamptoninns.bilton.com/en/hotels/ohio/hampton-inn-and-suites-columbus-downtown- CMHHSHK/index.htmi?WT.mc. Approximate Rate: $175 Distance (in miles) from Hotel to Columbus Union Hall: 1.3 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars. Page 1 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Courtyard Columbus Downtown 35 West Spring Street, Columbus, Ohio 43215 Phone: 1-614-228-3200 4d19-a255-54ba596febe2 Approximate Rate: $175 Distance (in miles) from Hotel to Columbus Union Hall: 0.8 Notes: Downtown west area; walkable Doubletree Suites by Hilton Columbus Downtown 50 South Front St, Columbus, Ohio, 43215-4145 Phone: 1-614-228-4600 CMHSBOT/index.htmi Approximate Rate: $200 Distance (in miles) from Hotel to Columbus Union Hall: 0.5 Notes: Closest hotel to meeting site; very short walk Residence Inn Columbus Downtown 36 East Gay Street, Columbus, Ohio 43215-3108 Phone: 1-614-222-2610 ec3-4d19-a255-54ba596febe2 Approximate Rate: $230 Distance (in miles) from Hotel to Columbus Union Hall: 0.8 Renaissance Columbus Downtown 50 North Third Street, Columbus, Ohio 43215 Phone: 1-614-228-5050 ttp://www.marriott.com/hotels/travel/cmhbr-renaissance-columbus-downtown-hotel/ Approximate Rate: $240 Distance (in miles) from Hotel to Columbus Union Hall: 1.0 Notes: Central downtown area Hilton Columbus Downtown 401 North High Street, Columbus, OH 43215 Phone: 1-614-384-8600 Approximate Rate: $240 Distance (in miles) from Hotel to Columbus Union Hall: 1.1 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars; New facility and nice. Page 2 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION PPE Cleaning Validation Validation of Cleaning Procedures for Fire Fighter Personal Protective Equipment (PPE) PROJECT CONTACTS Last Updated: 22 May 2017 Project Technical Panel Phone: 614-774-7446 David Bernzweig, Columbus Fire Department (OH) Email: [email protected] Phone: 780-496-3801 Ken Block, Edmonton Fire/Rescue & Metro Chiefs Representative Email: [email protected] Phone: 804-971-7983 Ken Brown, VA State Firefighter's Association & NVFC (Alt to B. McQueen) Email; [email protected] Phone: 510-839-5111 Cell: 213-321-9393 Roger Curtis, ECMS Curtis & Sons (CA) Email: [email protected] Phone: Paul Curtis, ECMS Curtis & Sons (CA) (Alt to Roger Curtis) Email: [email protected] Phone: 253-277-4131 Cell: 503-314-4832 Steve Lakey, Northwest Safety Clean (WA) Email: [email protected] Phone: 304-406-7479 Mark Lambert, WV Fire Academy & NAFTD (WV) Email: [email protected] Phone: 617-828-3978 Ed McCarthy, Boston Fire Department (MA) Email: [email protected] Phone: 315-736-7479 Cell: 315-552-8245 Brian McQueen, FASNY & National Volunteer Fire Council (NY) Email: [email protected] Phone: 602-534-2396 Mark Miller, Phoenix Fire Dept. (AZ) Email: [email protected] Phone: 919-524-1569 Bryan Ormond, NCSU (NC) Email: [email protected] Phone: Russ Osgood, Firefighter Cancer Support Network (NH) (Alt to Keith Tyson) Email: [email protected] Phone: Larry Petrick, IAFF (DC) Email: [email protected] Phone: 617-549-9850 Jim Riley, Boston Fire Department (MA) (Alt to E. McCarthy) Email: [email protected] Phone: 757-385-2892 Molly Riley, Virginia Beach Fire Dept. (VA) Email: [email protected] Phone: 718-999-2922 Thomas Smith, FDNY (NY) Email: [email protected] Phone: 214-774-2213 Cell: 940-300-5718 Tim Tomlinson, Gear Cleaning Solutions (TX) Email: [email protected] Phone: Robert Tutterow, NFPA Fire Service Section (NC) Email: [email protected] Phone: 786-351-3276 Keith Tyson, Firefighter Cancer Support Network (FL) Email: [email protected] Phone: 951-807-1914 Dick Weise, LA County Fire Dept. (CA) Email: [email protected] Phone: 949-291-0637 Ken Wiles, LA County Fire Dept. (CA) (Alt to Dick Weiss) Email: [email protected] Phone: 512-974-0286 Chris Youngblood, Austin Fire Dept. (TX) Email: [email protected] 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7281 Fax: +1.617.984.7010 Email: [email protected] www.NFPA.org/Foundation Source: :https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Phase 1 Project Contacts Phone: 330-723-0000, x365 Steve Allison, Fire-Dex (OH) Email: [email protected] Phone: 800-401-4780 Jack Binder, Edmar Chemical Company (OH) Email: [email protected] Phone: 920-570-0824 Bill Brooks, Alliance Corp. (WI) Email: [email protected] Phone: Charlie Dunn, TenCate Protective Fabrics Email: [email protected] Phone: 617-984-7325 Chris Farrell, NFPA & Staff Liaison for NFPA 1851 (MA) Email: [email protected] Phone: 800-232-8323 Rob Freese, Globe Manufacturing (NH) Email: [email protected] Phone: Pat Freeman, Globe Manufacturing (NH) (Alternate to Rob Freese) Email: [email protected] Phone: 704-554-3313 Diane Hess, PBI Performance Products (NC) Email: [email protected] Phone: 937-415-2932 Karen Lehtonen, LionFirst Responder Products (OH) Email: [email protected] Phone: 484-433-4072 Dan Silvestri, 9-1-1 Safety (PA) Email: [email protected] Liaison Contacts Phone: Pierre Carlotti, Ministry of Interior & Liaison for ISO TC92/SC3 (France) Email: [email protected] Phone: Eric Guillaume, Efectis & Liaison for ISO TC92/SC3 (France) Email: [email protected] Phone: Bill Haskell, NIOSH NPPTL (MA) Email: [email protected] Phone: James Hoar, Boston Fire Department (MA) Email: [email protected] Phone: 631-242-0621 Steve King, Chair NFPA 1851 (NY) Email: [email protected] Phone: +33(0)1.55.76.26.18 Fanny Rieunier, Ministry of Interior & Liaison for ISO TC92/SC3 (France) Email: [email protected] Phone: 612-247-6429 Marni Schmid, Fortunes Collide & Secretariat NFPA 1851 (MI) Email: [email protected] Page 2 of 3 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Core Research Team Phone: 607-758-6537 Cell: 607-423-5617 Jason Allen, Intertek (NY) Email: [email protected] Phone: 304-285-6076 Daniel Farcas, NIOSH HELD (WV) Email: [email protected] Phone: Crystal Forester, NIOSH NPPTL (WV) Email: [email protected] Phone: 617-984-7284 Cell: 617-659-1159 Casey Grant, Fire Protection Research Foundation (MA) Email: [email protected] Phone: Lee Greenawald, NIOSH NPPTL (WV) Email: [email protected] Phone: Bill Lindsley, NIOSH HELD (WV) Email: [email protected] Phone: Stephen Martin, NIOSH DRDS (WV) Email: [email protected] Phone: John Noti, NIOSH HELD (WV) Email: [email protected] Phone: Deborah Sbarra, NIOSH NPPTL (WV) Email: [email protected] Phone: 512-288-8272 cell: 512-623-9558 Jeff Stull, International Personal Protection (TX) Email: [email protected] Phone: 304-285-5858 cell: 681-209-2571 Jay Tarley, NIOSH NPPTL (WV) Email: [email protected] Additional Research Team Contacts Phone: 304-285-5884 Francoise Blachere, NIOSH HELD (WV) Email: [email protected] Phone: Renee Dotson, NIOSH HELD (WV) Email: [email protected] Phone: James Harris, NIOSH NPPTL (WV) Email: [email protected] Phone: Ryan Lebouf, NIOSH DRDS (WV) Email: [email protected] Phone: 617-984-7281 Eric Peterson, Fire Protection Research Foundation (MA) Email: [email protected] Phone: John Powers, NIOSH (WV) Email: [email protected] Phone: 412-386-4621 Cell: 412-463-9561 Heather Reed, NIOSH NPPTL (PA) Email: [email protected] Page 3 of 3 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION PPE Cleaning Validation Validation of Cleaning Procedures for Fire Fighter Personal Protective Equipment (PPE) (for more information see www.nfpa.org/PPECleaning) PROJECT SUMMARY Last updated: 5 February 2016 Background: Fire fighter exposure to personal protective equipment (PPE) that is dirty, soiled, and contaminated is an increasing concern for long-term fire fighter health. This exposure to persistent harmful contaminants in PPE is an extremely serious problem both on the fireground to highly toxic substances including a variety of carcinogens, and more insidiously to an increasing range of infectious pathogens that are encountered in patient care and different emergency operations. Fire fighter PPE becomes contaminated during these exposures and there are no industry standards that conclusively and reliably show that clothing is being adequately cleaned. While general cleaning procedures have been established in NFPA 1851, Standard on Selection, Care, and Maintenance of Protective Ensembles for Structural Fire Fighting and Proximity Fire Fighting, there are no procedures or requirements to demonstrate whether current cleaning practices, including those specified in NFPA 1851, will remove contaminants from fire fighter protective clothing. This project is intended to establish clear and definitive guidance to the fire service for applying cleaning and decontamination procedures that effectively remove both chemical and biological contaminants. Research Goal and Objectives, and Conceptual Approach: The overall goal of this project is to improve fire fighter safety and health by reducing continuing exposure to harmful contaminants in unclean or inadequately cleaned PPE. The objectives to achieve this goal are twofold: (1) To characterize fireground and emergency scene contamination leading to these exposures and develop the methodology for the consistent measurement of cleaning effectiveness; and (2) determine implementable cleaning, decontamination, and disinfection strategies that effectively reduce fire fighter exposures to persistent contaminants. The approach taken by this project is illustrated in Figure 1: Project Conceptual Approach. - Ensure Identify Devise Validate lab - - chemical and methods to methods - at biologicat conteminate againet field ses target clothing in contaminants laboratory exposures acceptance Project Direction Figure 1: Project Conceptual Approach 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7281 Fax: +1.617.984.7010 Email: [email protected] www.NFPA.org/Foundation Source: :ttps://www.industrydocuments.ucsf.edu/docs/hlcn0226 Project Phases and Tasks: This project involves the following four key phases of activity: 1) Identification of Contaminants: Confirm identification and ability to characterize persistent chemical and biological contaminants in fire fighter PPE through target substances and microorganisms. 2) Establishment of Soil and Chemical Contamination/Decontamination Procedures: Develop and validate specific procedures that determine the effectiveness of laundering and other cleaning methods in removing specific soils and chemical contaminants. 3) Establishment of Biological Contamination/Disinfection or Sanitization Procedures: Develop and validate specific procedures that determine the effectiveness of laundering or disinfection/sanitization processes that remove/deactivate biologically-based contaminants. 4) Creation of Overall Fire Service Guidance: Prepare clear and definitive information for the fire service industry (fire fighters, fire departments, clothing manufacturers, material suppliers, cleaning/care organizations, and cleaning agent or equipment manufacturers) on appropriate approaches for properly cleaning fire fighter protective clothing and equipment. The specific tasks of this project are based on these four phases of the project, and these are illustrated in Figure 2: Project Tasks. PHASE 2 PHASEZ Task 2.4 Task 2.5 Task 1.1 Task 2.1 Validate testsat Refine test Appoint Technical Select cleaning selected ISPS methodology Review Panel methods/agents (chemical) (chemical) PHASE $ Task 4.1 Task 1.2 Task 2.2 Write qualification Review Prigr Put together test plan methods studies/literature (chemical) Task 2.3 Task 4.2 Task 1.3 PHASE 3 Perform laboratory Establish cleaning Setup analytical chemical Task 3.3 acceptance criteria capabilities decontaminant Put together test plan testing (biological) Task 4.3 Task 1.4 Perform Task 3.4 Prepare public inputs for NFPA 1851 demonstration tests Task 3.1 Perform laboratory Task 3.6 Select study biological Refine test microorganisms decontaminant methodology Task 1.5 testing (biological) Task 4.4 Refine biological Prepare industry decontamination Task 3.2 Task 3.5 guidance document scope Select biological Validate testsat cleaning methods selected ISPs (biological) Task 1.6 Task 4,5 Establish cleanliness Prepare project final metrics report Figure 2: Project Tasks Implementation and Schedule: This three year project is due to be completed no later than " August 2018, and is funded through an AFG Fire Prevention & Safety Grant from the U.S. Department of Homeland Security / Federal Emergency Management Agency. The Research Foundation will lead a unique research team partnership composed of the FPRF, National Institute for Occupational Safety and Health (NIOSH), International Personal Protection (IPP), and Intertek. The research team, along with several Independent Service Providers (ISPs), will work with the fire service partners and others to validate and optimize fire fighter PPE cleaning validation methods. For more information see www.nfpa.org/PPECleaning. Page 2 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION Fire Fighter Cancer Cohort Study Full Title: The Firefighter Multicenter Cancer Cohort Study: Framework Development and Testing PROJECT SUMMARY Last Updated: 20 September 2016 Background: Cancer is a leading cause of fire service morbidity and mortality. Firefighter exposure to carcinogens occurs through skin contamination and through inhalation when respiratory protection is not worn when combustion products are present such as during overhaul, standby, and operation of apparatus, as well as through off-gassing of equipment and exposures in the fire station. However, we currently do not understand which exposures are responsible for cancer in firefighters, the mechanisms by which firefighter exposures cause cancer, nor the most effective means of reducing exposures. Since cancer has a long latency period, biomarkers are also needed that can measure the toxicological effects of carcinogen exposure well before the development of cancer, when interventions to prevent disease could be effective. Development of a large (>10,000 firefighter) multicenter firefighter cancer prospective cohort study will address these needs, but the framework for such a study needs to be first developed and tested among a smaller initial set of fire service partners. Implementation and Schedule: This research project is led by University of Arizona with collaborative support from multiple other research partners, including the University of Miami, National Institute for Occupational Safety and Health; National Fallen Firefighter Foundation, Fire Protection Research Foundation, and others. Initial funding for this project is through a 3-year DHS/FEMA Assistance to Fire Fighter (AFG) Fire Grant, with the intention to identify and obtain additional funding for the duration of the 30 year effort. The project start date is August 2016. The Principal Investigator for this project is: Jefferey L. Burgess, MD, MS, MPH, University of Arizona, email: [email protected]. Project Goal and Aims: The goal of the initial 3-year effort of this overall project is to develop and test a framework for establishing a long-term fire fighter multicenter prospective cohort study focused on carcinogenic exposures and effects. The specific aims are to: 1) Establish an oversight and planning board to provide study oversight, foster communication among fire organizations and help develop a long-term funding plan; 2) Create and test a cohort study data coordinating center and harmonized survey data protocols; 3) Develop and validate a firefighter carcinogen exposure matrix and data collection system; and 4) Create a biomarker assessment center and evaluate the association between cumulative firefighter exposures and epigenetic effects. For more information, contact: Casey Grant, Fire Protection Research Foundation 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7284 Fax: +1.617.984.7010 Email: [email protected] Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Project Methodology: This study will harmonize and build on recent and developing firefighter cancer prevention studies in Arizona, Florida and Massachusetts, adding volunteer fire departments. An oversight and planning board will be established by the Fire Protection Research Foundation (FPRF) in association with the National Fallen Firefighter Foundation (NFFF) Fire Service Occupational Cancer Alliance (FSOCA) to provide oversight of the study through collaboration among fire service organizations, academia, and government agencies, and develop a long-term funding and sustainability plan. A data coordination center team will design, develop and evaluate a framework for a multicenter prospective cohort study of firefighters and cancer risk, including standardized participant survey data collection tools and analysis protocols sufficient to address the short- and long-term study objectives as well as linkage with long-term outcome data including cancer development. An exposure assessment center team will develop a carcinogen exposure matrix and data collection system to provide improved occupational exposure data for comparison with epigenetic outcomes and eventual cancer outcomes. Carcinogen exposures associated with specific fire types will be evaluated across fire departments through industrial hygiene monitoring and analysis of urine for absorbed contaminants, supplementing existing FEMA-funded and other studies of firefighter exposures and allowing for participating fire departments to design interventions to reduce current exposures. Expansion of the National Fire Operations Reporting System (NFORS) will be explored as one option to uniformly collect incident and exposure data. Blood and buccal cells will be collected during annual medical surveillance evaluations, including both new recruits and incumbent firefighters. Pilot studies of epigenetic markers of cancer effect and cancer risk will be analyzed comparing municipal firefighters with high chronic exposures, volunteer firefighters with low chronic exposures, and non- firefighter friends of the municipal firefighters (serving as controls). Project Deliverables: The anticipated outcomes from this 3-year effort is to establish and test the framework necessary for the subsequent development of a large multicenter cohort study of cancer in the fire service. Page 2 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226

On which date is the senior steering committee meeting conducted?

prbn0226

prbn0226_p0, prbn0226_p1, prbn0226_p2, prbn0226_p3, prbn0226_p4, prbn0226_p5, prbn0226_p6

Thursday August 17, 2017

001 From: Wexier. Philip To: Farland, William H.: Susie "Masten; Dourson. Michael (doursomi); jeffrey.jenkins ([email protected]); Beck, Nancy: David Steup; [email protected] Cc: [email protected] Subject: Kids + Chemical Safety Date: Thursday, August 17, 2017 4:00:21 PM Attachments: Re President"s Task Force on Environmental Health Risks and Safety Pisks to Children Final Agenda and Meeting Materials for the August 17 Senior Staff Steering Committee Meeting mso RE President"s Task Force on Environmental Health Risks and Safety Risks to Children Final Agenda and Meeting Materials for the August 17 Senior Staff Steering Committee Meeting msg Bill - This seems like a worthwhile and relevant addition to the TEF site. I am wondering whether the Experts that were used would still be available to reply to questions from the public. There are some other groups working on children's environmental health and it strikes me that it might not hurt to try to link to them and/or coordinate efforts with them and/or get their take on the Kids + Chemical safety site and/or convene a conference call to at least share our respective perspectives on this issue. I am thinking specifically of: EPA's Office of Children's Health Protection (Ruth Etzel heads this up) and their main Web site addressing this issue - bttos://www.epa.gov/children Children's Environmental Health Network (CEHN) - http://cehn.org/ - Among other things, they were instrumental in the formation of an annual Children's Environmental Health Day, October 12, this year (see htto:/lcehn.org/cehdav/) Pediatric Environmental Health Specialty Units - http:llwww.pehsu.net/ - I met and subsequently exchanged a series of emails early this year with Jerry Paulson who is Medical Director for this program. He was enquiring about making their information somehow available via NLM but there didn't seem to be any interest here in following up. My last email to him was just prior to the SOT meeting. I directed him to the TEF site and asked if he thought this might be an alternative place for highlighting the PEHSUs but never heard back from him. Might be worth checking in with him again. President's Task Force on Environmental Health Risks and Safety Risks to Children (httos://otfceh.niehs.nib.gov/). - I have actually been on the mailing list for their (monthly?) meetings for some time (not sure why) and they periodically sent out announcements. I haven't really participated. There was, in fact, a meeting today. See attached emails. Anyway, just thought l'd itemize a few of the other activities going on in this area and reiterate that if TEF gets into the children's environmental health arena, it might be good to keep up with what's going on elsewhere. - Phil P.S. I have been getting some TEF email at my personal email address. Please correspond with me at Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 002 this, my office, address ([email protected]/ instead. Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 From: Coopwood, Theodore To: Howard Sandra (OS/OASH); Liv, Chanva (OS/OASH); Bizel. Buth Cc: Smith Kimberly (HHS'OASH); Jonas, Lori (ENRD); Alice Thaler; Amy Bodette; Andrea Grossman; Andrea Falken; Beverly Samuel; Birnbaum. Linda (NIH/NIEHS) (El; Brown, Sheila; Brevsse Patrick N. (CDC/ONDI EH/NCEH): Bruce. D [email protected] Chaney, Sascha LCDCIONDIEH/NCBDDD); Trent, Chris B; Obulas, William (ATSDR/OADS); Danielle Jones Powson, David; [email protected]: Eric Rosenfield; Erio Waldo; Erica Burrin; Frin Hoffman; Held. Sarah (DHHS/OS/OASH: Freemer. Michelle (NIH/NHLBI) Luber. George (COC/ONDIEH/NCEH): Herbert Bolton; James H [email protected]; Balbus, John (NIH/NIEHS) (E); Joshua Olsen; Judy Harvey; [email protected] Kiley, James (NIH/NHLBI)[E]: Co: Rodkey, Kitt; Lee Caron Lucas Radzinschi; Mark Glaze; Miller, Mark Berger, Martha; Matt Ammon; Michael Babich; Miller, Aubrey (NIH/NIEHS) LEI; Mortensen, Mary E (CDO/ONDIEH/NCEH); Peter Ashley; Roonev. Andrew (NIH/NIEHS) LEI; Sara Newman; Foster, Stiven; Fitzpatrick. Suzanne (FDA/CFSAN); Thigpen Tart, Kimberly (NIH/NIEHS) (El: Warren Friedman; Wexler. Philip (NIH/NLMLI Yasmin a Sani; Blandine Trouille; Broehm. Jason (OST): Goldsmith. Reese (ENRD); Shah, Manthan; Firestone, Michael; Smith. Kimberly (HHS/OASH); Ettinger, Adrienne (CDC/ONDIEH/NCEH); Nevel Amy (HHS/ASPE); [email protected] Hackel, Angela; Hauff. Amanda; Reed. Khesha; Jonas, Lori (ENRD); Lias. Courtney H.(FDA/CDRH); Brown. Sheila: Ricks, Sharon L (HHS'OASH); AGELLER@@hsph.harvard.edu Subject: Re: President"s Task Force on Environmental Health Risks and Safety Risks to Children: Final Agenda and Meeting Materials for the August 17 Senior Staff Steering Committee Meeting Date: Wednesday, August 16, 2017 6:35:38 AM Attachments: Agenda for the August 2017 Senior Steering Committe Meeting 8-16-17.docx Draft President"s Task Force Summary Notes Julv. 31.2017.doc Smoke free research 612lessonslearnedpart1.(2).do HUD Smoke free Home Presentation 8-16-17.pptx PTF Short Term Work Plan Actions Accommplishments Report 8-10-17 -clean version docx Good Morning, Attached are the final agenda and meeting materials for tomorrows Senior Staff Steering Committee meeting for the President's Task Force on Environmental Health Risks and Safety Risks to Children. The meeting time is 1:00pm and the location is the HHS Hubert Humphrey Building, 200 Independence Avenue S.W. room 325-A. The dial-in number is 866-299- 3188 and the participant code is 202-564-2754. If you are participating in person and have not informed me, please let me know by COB today. The point of contact if you have trouble entering the building is Chanya Liv at: 202-690-2470 Attached Meeting Materials Agenda for the August 17, 2017 Senior Staff Steering Committee Meeting Draft President's Task Force (PTF) Summary Notes from the July 2017 Meeting Smoke Free Homes Research Lessons Learned Document Slides for Smoke Free Housing Research Presentation Short Term Accomplishments Report Thanks in advance for your participation in the meeting. Ted Ted Coopwood Office of Children's Health Protection US EPA Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 1301 Constitution Ave. NW Washington, DC 201460 202-564-2197 [email protected] Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 For Internal Federal Partner Use Only-Please Do Not Cite or Quote President's Task Force on Environmental Health Risks and Safety Risks to Children Senior Steering Committee Meeting Thursday August 17, 2017 1:00pm - 3:00pm EST HHS Hubert Humphrey Building -Room 325A 200 Independence Avenue, SW Dial-In: 1-866-299-3188, Passcode: 202-564-2754 AGENDA I. Welcome 1:00PM - -1:03PM Ruth Etzel, EPA and Sandra Howard, HHS II. Roll call 1:03PM - -1:05PM Ted Coopwood, EPA III. Minutes and Action Items from July Steering Committee Meeting 1:05PM -1:10PM (Attachment) Ruth Etzel, EPA and Sandra Howard, HHS IV. Subcommittee Updates - Lead Subcommittee Update 1:10PM - 1:20PM Michael Firestone, EPA, Warren Friedman, HUD, Adrienne Ettinger, HHS (Other Subcommittees have no updates) VI. Other Agency Updates and Discussion Items 1:20PM - 1:40PM - Draft Work Plan Short Term Actions Accomplishments Report (Attachment) Ted Coopwood, EPA VII. Summary of Action items 1:40PM - 2:00PM VIII. Smoke Free Housing Research Presentation 2:00PM- - 2:30PM (Attachment) Alan Geller, Harvard University Adjourn Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 For Internal Federal Partner Use Only - Please Do Not Cite or Quote President's Task Force on Environmental Health Risks and Safety Risks to Children Senior Staff Steering Committee Meeting Draft Summary Notes for Thursday July 20, 2017 1:00pm - 3:00pm ET Meeting Participants HUD: Kitt Rodkey, Warren Friedman CPSC: Michael Babich EPA: Ruth Etzel, Manthan Shah, Angela Hackel, Amanda Hauff, Michael Firestone, Miranda Mitchell HHS/OASH: Sandra Howard, Sarah Field, Chanya Liv IHS: Stephen Piontkowski CDC/NCEH and ATSDR: Adrienne Ettinger, Bill Cibulas FDA: Suzanne Fitzpatrick NIH/NIEHS: Kimberly Thigpen-Tart, Andy Rooney NIH/NHLBI: Michelle Freemer OMB: Eric Rosenfield DOJ: Lori Jonas DOL: Tiffany Defoe Welcome and Roll call Ruth Etzel (EPA) and Sandra Howard (HHS) welcomed all members of the Steering Committee and Angela Hackel (EPA) conducted the roll call. Minutes and Action Items from the June Steering Committee Meeting The meeting minutes and action items from the June 2017 meeting were approved. Ted Coopwood (EPA) will distribute the approved minutes to the Senior Staff Steering Committee Members. Children's Environmental Health in Indian Country; Stephen Piontkowski, Indian Health Service A PowerPoint presentation was shared with the Senior Staff Steering Committee prior to the meeting. The Division of Environmental Health Services (DEHS) is part of the Office of Environmental Health and Engineering at the Indian Health Service (IHS). More than 70% of the DEHS staff work in tribal country, 20% work in an HHS Region, and 10% serve in administrative roles. DEHS monitors health through community injury and disease surveillance. Conducts public outreach about preventative health measures. Provides training and mobilizes partnerships. Works with emergency preparedness partners and addresses outbreaks. Evaluates effectiveness of services and interventions. Five focus areas include: children's environment, food safety, safe drinking water, vectorborne and communicable diseases, and healthy homes. Children's environmental health is a top priority (schools, Head Start, indoor air quality, fire safety, playground safety, injury prevention). Unintentional injuries are a leading cause of death. Motor vehicle crashes was noted as a leading injury type. To address this issue at a national level, car seat success stories are shared to illustrate a large body of work that has been done for traffic safety. Plus, the "Seatbelts. Just Wear 'em" campaign was launched. The campaign has been shown to be effective at reducing motor vehicle crashes. 1 Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 For Internal Federal Partner Use Only - Please Do Not Cite or Quote Regional initiatives include Rocky Mountain Spotted Fever in Arizona Tribal and state/federal partners (CDC) work together. 250 human cases, 20 fatalities; children under age of 10 most impacted. Cost of outbreak is $13.2 million and includes clinical-based response and community-based response. Local concerns include referrals for children's health issues. These include upper respiratory problems related to mold and elevated lead levels. Partnerships are important. DEHS works with tribal customers hand-in-hand and with state/county/federal partners. Questions/Conversation Ruth Etzel, EPA: How do you prioritize the local work? For example, how do you figure out which tribes have lead as a priority? Priorities are conducted at the national, regional and local level. When it comes to non-facility based work, we utilize the public health approach and make decisions based on the data. In some cases, people (the local tribal council) tell us what the work should be (e.g., set up an emergency preparedness operation center). Warren Friedman, HUD: Will send information regarding overcoming obstacles to implementing senior falls policies. Do you have enough data to indicate areas in which your program has been operating to address Rocky Mountain Spotted Fever? Has your approach been effective in reducing its prevalence? Yes, we do. Published reports on community-based work and surveillance. Regarding the effectiveness in reducing risk for rocky mountain fever, there are challenges in implementation and management that need to occur locally. Kitt Rodkey, HUD: will be following up with Stephen to get information on their outreach with Native American populations. How do you follow up with communities on lead? Bill Cibulas, ATSDR: Same follow up questions with lead. Have tribal councils pushed for testing in schools, including water? Screening that occurs by the clinics of the children is an indicator of the cases that exist amongst the children. Head Start performs routine testing to be conducted. Ruth Etzel, EPA: Is there a database that you keep of children's blood lead levels on Native lands? No, not that I am aware of. Sandra Howard, HHS: Does IHS have any recommendations for screening, apart from what is required by Medicaid and or by Head Start? That is out of the scope of work. Peter Ashley, HUD: Can you speak to trend in over-doses? Can you also speak to the causation between alcohol use and motor vehicle accidents? Seeing a new trend in over-doses. Poisoning is one of the top three causes of hospitalizations. Regarding the link between alcohol and motor vehicle accidents, we are comfortable in saying that it is a factor. We do have programs regarding alcohol and substance abuse. Sandra Howard, HHS: We understand that we cannot have one speaker (organization) talk on this issue. If there are other organizations that would like to present, please let us know. Some possible topics could be issues facing Alaska Native communities, lead exposure and Superfund sites (as they relate to tribes in general). 2 Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226

At what time is the senior steering committee meeting scheduled ?

prbn0226

prbn0226_p0, prbn0226_p1, prbn0226_p2, prbn0226_p3, prbn0226_p4, prbn0226_p5, prbn0226_p6

1:00pm - 3:00pm EST

001 From: Wexier. Philip To: Farland, William H.: Susie "Masten; Dourson. Michael (doursomi); jeffrey.jenkins ([email protected]); Beck, Nancy: David Steup; [email protected] Cc: [email protected] Subject: Kids + Chemical Safety Date: Thursday, August 17, 2017 4:00:21 PM Attachments: Re President"s Task Force on Environmental Health Risks and Safety Pisks to Children Final Agenda and Meeting Materials for the August 17 Senior Staff Steering Committee Meeting mso RE President"s Task Force on Environmental Health Risks and Safety Risks to Children Final Agenda and Meeting Materials for the August 17 Senior Staff Steering Committee Meeting msg Bill - This seems like a worthwhile and relevant addition to the TEF site. I am wondering whether the Experts that were used would still be available to reply to questions from the public. There are some other groups working on children's environmental health and it strikes me that it might not hurt to try to link to them and/or coordinate efforts with them and/or get their take on the Kids + Chemical safety site and/or convene a conference call to at least share our respective perspectives on this issue. I am thinking specifically of: EPA's Office of Children's Health Protection (Ruth Etzel heads this up) and their main Web site addressing this issue - bttos://www.epa.gov/children Children's Environmental Health Network (CEHN) - http://cehn.org/ - Among other things, they were instrumental in the formation of an annual Children's Environmental Health Day, October 12, this year (see htto:/lcehn.org/cehdav/) Pediatric Environmental Health Specialty Units - http:llwww.pehsu.net/ - I met and subsequently exchanged a series of emails early this year with Jerry Paulson who is Medical Director for this program. He was enquiring about making their information somehow available via NLM but there didn't seem to be any interest here in following up. My last email to him was just prior to the SOT meeting. I directed him to the TEF site and asked if he thought this might be an alternative place for highlighting the PEHSUs but never heard back from him. Might be worth checking in with him again. President's Task Force on Environmental Health Risks and Safety Risks to Children (httos://otfceh.niehs.nib.gov/). - I have actually been on the mailing list for their (monthly?) meetings for some time (not sure why) and they periodically sent out announcements. I haven't really participated. There was, in fact, a meeting today. See attached emails. Anyway, just thought l'd itemize a few of the other activities going on in this area and reiterate that if TEF gets into the children's environmental health arena, it might be good to keep up with what's going on elsewhere. - Phil P.S. I have been getting some TEF email at my personal email address. Please correspond with me at Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 002 this, my office, address ([email protected]/ instead. Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 From: Coopwood, Theodore To: Howard Sandra (OS/OASH); Liv, Chanva (OS/OASH); Bizel. Buth Cc: Smith Kimberly (HHS'OASH); Jonas, Lori (ENRD); Alice Thaler; Amy Bodette; Andrea Grossman; Andrea Falken; Beverly Samuel; Birnbaum. Linda (NIH/NIEHS) (El; Brown, Sheila; Brevsse Patrick N. (CDC/ONDI EH/NCEH): Bruce. D [email protected] Chaney, Sascha LCDCIONDIEH/NCBDDD); Trent, Chris B; Obulas, William (ATSDR/OADS); Danielle Jones Powson, David; [email protected]: Eric Rosenfield; Erio Waldo; Erica Burrin; Frin Hoffman; Held. Sarah (DHHS/OS/OASH: Freemer. Michelle (NIH/NHLBI) Luber. George (COC/ONDIEH/NCEH): Herbert Bolton; James H [email protected]; Balbus, John (NIH/NIEHS) (E); Joshua Olsen; Judy Harvey; [email protected] Kiley, James (NIH/NHLBI)[E]: Co: Rodkey, Kitt; Lee Caron Lucas Radzinschi; Mark Glaze; Miller, Mark Berger, Martha; Matt Ammon; Michael Babich; Miller, Aubrey (NIH/NIEHS) LEI; Mortensen, Mary E (CDO/ONDIEH/NCEH); Peter Ashley; Roonev. Andrew (NIH/NIEHS) LEI; Sara Newman; Foster, Stiven; Fitzpatrick. Suzanne (FDA/CFSAN); Thigpen Tart, Kimberly (NIH/NIEHS) (El: Warren Friedman; Wexler. Philip (NIH/NLMLI Yasmin a Sani; Blandine Trouille; Broehm. Jason (OST): Goldsmith. Reese (ENRD); Shah, Manthan; Firestone, Michael; Smith. Kimberly (HHS/OASH); Ettinger, Adrienne (CDC/ONDIEH/NCEH); Nevel Amy (HHS/ASPE); [email protected] Hackel, Angela; Hauff. Amanda; Reed. Khesha; Jonas, Lori (ENRD); Lias. Courtney H.(FDA/CDRH); Brown. Sheila: Ricks, Sharon L (HHS'OASH); AGELLER@@hsph.harvard.edu Subject: Re: President"s Task Force on Environmental Health Risks and Safety Risks to Children: Final Agenda and Meeting Materials for the August 17 Senior Staff Steering Committee Meeting Date: Wednesday, August 16, 2017 6:35:38 AM Attachments: Agenda for the August 2017 Senior Steering Committe Meeting 8-16-17.docx Draft President"s Task Force Summary Notes Julv. 31.2017.doc Smoke free research 612lessonslearnedpart1.(2).do HUD Smoke free Home Presentation 8-16-17.pptx PTF Short Term Work Plan Actions Accommplishments Report 8-10-17 -clean version docx Good Morning, Attached are the final agenda and meeting materials for tomorrows Senior Staff Steering Committee meeting for the President's Task Force on Environmental Health Risks and Safety Risks to Children. The meeting time is 1:00pm and the location is the HHS Hubert Humphrey Building, 200 Independence Avenue S.W. room 325-A. The dial-in number is 866-299- 3188 and the participant code is 202-564-2754. If you are participating in person and have not informed me, please let me know by COB today. The point of contact if you have trouble entering the building is Chanya Liv at: 202-690-2470 Attached Meeting Materials Agenda for the August 17, 2017 Senior Staff Steering Committee Meeting Draft President's Task Force (PTF) Summary Notes from the July 2017 Meeting Smoke Free Homes Research Lessons Learned Document Slides for Smoke Free Housing Research Presentation Short Term Accomplishments Report Thanks in advance for your participation in the meeting. Ted Ted Coopwood Office of Children's Health Protection US EPA Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 1301 Constitution Ave. NW Washington, DC 201460 202-564-2197 [email protected] Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 For Internal Federal Partner Use Only-Please Do Not Cite or Quote President's Task Force on Environmental Health Risks and Safety Risks to Children Senior Steering Committee Meeting Thursday August 17, 2017 1:00pm - 3:00pm EST HHS Hubert Humphrey Building -Room 325A 200 Independence Avenue, SW Dial-In: 1-866-299-3188, Passcode: 202-564-2754 AGENDA I. Welcome 1:00PM - -1:03PM Ruth Etzel, EPA and Sandra Howard, HHS II. Roll call 1:03PM - -1:05PM Ted Coopwood, EPA III. Minutes and Action Items from July Steering Committee Meeting 1:05PM -1:10PM (Attachment) Ruth Etzel, EPA and Sandra Howard, HHS IV. Subcommittee Updates - Lead Subcommittee Update 1:10PM - 1:20PM Michael Firestone, EPA, Warren Friedman, HUD, Adrienne Ettinger, HHS (Other Subcommittees have no updates) VI. Other Agency Updates and Discussion Items 1:20PM - 1:40PM - Draft Work Plan Short Term Actions Accomplishments Report (Attachment) Ted Coopwood, EPA VII. Summary of Action items 1:40PM - 2:00PM VIII. Smoke Free Housing Research Presentation 2:00PM- - 2:30PM (Attachment) Alan Geller, Harvard University Adjourn Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 For Internal Federal Partner Use Only - Please Do Not Cite or Quote President's Task Force on Environmental Health Risks and Safety Risks to Children Senior Staff Steering Committee Meeting Draft Summary Notes for Thursday July 20, 2017 1:00pm - 3:00pm ET Meeting Participants HUD: Kitt Rodkey, Warren Friedman CPSC: Michael Babich EPA: Ruth Etzel, Manthan Shah, Angela Hackel, Amanda Hauff, Michael Firestone, Miranda Mitchell HHS/OASH: Sandra Howard, Sarah Field, Chanya Liv IHS: Stephen Piontkowski CDC/NCEH and ATSDR: Adrienne Ettinger, Bill Cibulas FDA: Suzanne Fitzpatrick NIH/NIEHS: Kimberly Thigpen-Tart, Andy Rooney NIH/NHLBI: Michelle Freemer OMB: Eric Rosenfield DOJ: Lori Jonas DOL: Tiffany Defoe Welcome and Roll call Ruth Etzel (EPA) and Sandra Howard (HHS) welcomed all members of the Steering Committee and Angela Hackel (EPA) conducted the roll call. Minutes and Action Items from the June Steering Committee Meeting The meeting minutes and action items from the June 2017 meeting were approved. Ted Coopwood (EPA) will distribute the approved minutes to the Senior Staff Steering Committee Members. Children's Environmental Health in Indian Country; Stephen Piontkowski, Indian Health Service A PowerPoint presentation was shared with the Senior Staff Steering Committee prior to the meeting. The Division of Environmental Health Services (DEHS) is part of the Office of Environmental Health and Engineering at the Indian Health Service (IHS). More than 70% of the DEHS staff work in tribal country, 20% work in an HHS Region, and 10% serve in administrative roles. DEHS monitors health through community injury and disease surveillance. Conducts public outreach about preventative health measures. Provides training and mobilizes partnerships. Works with emergency preparedness partners and addresses outbreaks. Evaluates effectiveness of services and interventions. Five focus areas include: children's environment, food safety, safe drinking water, vectorborne and communicable diseases, and healthy homes. Children's environmental health is a top priority (schools, Head Start, indoor air quality, fire safety, playground safety, injury prevention). Unintentional injuries are a leading cause of death. Motor vehicle crashes was noted as a leading injury type. To address this issue at a national level, car seat success stories are shared to illustrate a large body of work that has been done for traffic safety. Plus, the "Seatbelts. Just Wear 'em" campaign was launched. The campaign has been shown to be effective at reducing motor vehicle crashes. 1 Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 For Internal Federal Partner Use Only - Please Do Not Cite or Quote Regional initiatives include Rocky Mountain Spotted Fever in Arizona Tribal and state/federal partners (CDC) work together. 250 human cases, 20 fatalities; children under age of 10 most impacted. Cost of outbreak is $13.2 million and includes clinical-based response and community-based response. Local concerns include referrals for children's health issues. These include upper respiratory problems related to mold and elevated lead levels. Partnerships are important. DEHS works with tribal customers hand-in-hand and with state/county/federal partners. Questions/Conversation Ruth Etzel, EPA: How do you prioritize the local work? For example, how do you figure out which tribes have lead as a priority? Priorities are conducted at the national, regional and local level. When it comes to non-facility based work, we utilize the public health approach and make decisions based on the data. In some cases, people (the local tribal council) tell us what the work should be (e.g., set up an emergency preparedness operation center). Warren Friedman, HUD: Will send information regarding overcoming obstacles to implementing senior falls policies. Do you have enough data to indicate areas in which your program has been operating to address Rocky Mountain Spotted Fever? Has your approach been effective in reducing its prevalence? Yes, we do. Published reports on community-based work and surveillance. Regarding the effectiveness in reducing risk for rocky mountain fever, there are challenges in implementation and management that need to occur locally. Kitt Rodkey, HUD: will be following up with Stephen to get information on their outreach with Native American populations. How do you follow up with communities on lead? Bill Cibulas, ATSDR: Same follow up questions with lead. Have tribal councils pushed for testing in schools, including water? Screening that occurs by the clinics of the children is an indicator of the cases that exist amongst the children. Head Start performs routine testing to be conducted. Ruth Etzel, EPA: Is there a database that you keep of children's blood lead levels on Native lands? No, not that I am aware of. Sandra Howard, HHS: Does IHS have any recommendations for screening, apart from what is required by Medicaid and or by Head Start? That is out of the scope of work. Peter Ashley, HUD: Can you speak to trend in over-doses? Can you also speak to the causation between alcohol use and motor vehicle accidents? Seeing a new trend in over-doses. Poisoning is one of the top three causes of hospitalizations. Regarding the link between alcohol and motor vehicle accidents, we are comfortable in saying that it is a factor. We do have programs regarding alcohol and substance abuse. Sandra Howard, HHS: We understand that we cannot have one speaker (organization) talk on this issue. If there are other organizations that would like to present, please let us know. Some possible topics could be issues facing Alaska Native communities, lead exposure and Superfund sites (as they relate to tribes in general). 2 Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226

between what timings the welcome is sheduled ?

prbn0226

prbn0226_p0, prbn0226_p1, prbn0226_p2, prbn0226_p3, prbn0226_p4, prbn0226_p5, prbn0226_p6

1:00pm-1:03pm, 1:00PM-1:03PM

001 From: Wexier. Philip To: Farland, William H.: Susie "Masten; Dourson. Michael (doursomi); jeffrey.jenkins ([email protected]); Beck, Nancy: David Steup; [email protected] Cc: [email protected] Subject: Kids + Chemical Safety Date: Thursday, August 17, 2017 4:00:21 PM Attachments: Re President"s Task Force on Environmental Health Risks and Safety Pisks to Children Final Agenda and Meeting Materials for the August 17 Senior Staff Steering Committee Meeting mso RE President"s Task Force on Environmental Health Risks and Safety Risks to Children Final Agenda and Meeting Materials for the August 17 Senior Staff Steering Committee Meeting msg Bill - This seems like a worthwhile and relevant addition to the TEF site. I am wondering whether the Experts that were used would still be available to reply to questions from the public. There are some other groups working on children's environmental health and it strikes me that it might not hurt to try to link to them and/or coordinate efforts with them and/or get their take on the Kids + Chemical safety site and/or convene a conference call to at least share our respective perspectives on this issue. I am thinking specifically of: EPA's Office of Children's Health Protection (Ruth Etzel heads this up) and their main Web site addressing this issue - bttos://www.epa.gov/children Children's Environmental Health Network (CEHN) - http://cehn.org/ - Among other things, they were instrumental in the formation of an annual Children's Environmental Health Day, October 12, this year (see htto:/lcehn.org/cehdav/) Pediatric Environmental Health Specialty Units - http:llwww.pehsu.net/ - I met and subsequently exchanged a series of emails early this year with Jerry Paulson who is Medical Director for this program. He was enquiring about making their information somehow available via NLM but there didn't seem to be any interest here in following up. My last email to him was just prior to the SOT meeting. I directed him to the TEF site and asked if he thought this might be an alternative place for highlighting the PEHSUs but never heard back from him. Might be worth checking in with him again. President's Task Force on Environmental Health Risks and Safety Risks to Children (httos://otfceh.niehs.nib.gov/). - I have actually been on the mailing list for their (monthly?) meetings for some time (not sure why) and they periodically sent out announcements. I haven't really participated. There was, in fact, a meeting today. See attached emails. Anyway, just thought l'd itemize a few of the other activities going on in this area and reiterate that if TEF gets into the children's environmental health arena, it might be good to keep up with what's going on elsewhere. - Phil P.S. I have been getting some TEF email at my personal email address. Please correspond with me at Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 002 this, my office, address ([email protected]/ instead. Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 From: Coopwood, Theodore To: Howard Sandra (OS/OASH); Liv, Chanva (OS/OASH); Bizel. Buth Cc: Smith Kimberly (HHS'OASH); Jonas, Lori (ENRD); Alice Thaler; Amy Bodette; Andrea Grossman; Andrea Falken; Beverly Samuel; Birnbaum. Linda (NIH/NIEHS) (El; Brown, Sheila; Brevsse Patrick N. (CDC/ONDI EH/NCEH): Bruce. D [email protected] Chaney, Sascha LCDCIONDIEH/NCBDDD); Trent, Chris B; Obulas, William (ATSDR/OADS); Danielle Jones Powson, David; [email protected]: Eric Rosenfield; Erio Waldo; Erica Burrin; Frin Hoffman; Held. Sarah (DHHS/OS/OASH: Freemer. Michelle (NIH/NHLBI) Luber. George (COC/ONDIEH/NCEH): Herbert Bolton; James H [email protected]; Balbus, John (NIH/NIEHS) (E); Joshua Olsen; Judy Harvey; [email protected] Kiley, James (NIH/NHLBI)[E]: Co: Rodkey, Kitt; Lee Caron Lucas Radzinschi; Mark Glaze; Miller, Mark Berger, Martha; Matt Ammon; Michael Babich; Miller, Aubrey (NIH/NIEHS) LEI; Mortensen, Mary E (CDO/ONDIEH/NCEH); Peter Ashley; Roonev. Andrew (NIH/NIEHS) LEI; Sara Newman; Foster, Stiven; Fitzpatrick. Suzanne (FDA/CFSAN); Thigpen Tart, Kimberly (NIH/NIEHS) (El: Warren Friedman; Wexler. Philip (NIH/NLMLI Yasmin a Sani; Blandine Trouille; Broehm. Jason (OST): Goldsmith. Reese (ENRD); Shah, Manthan; Firestone, Michael; Smith. Kimberly (HHS/OASH); Ettinger, Adrienne (CDC/ONDIEH/NCEH); Nevel Amy (HHS/ASPE); [email protected] Hackel, Angela; Hauff. Amanda; Reed. Khesha; Jonas, Lori (ENRD); Lias. Courtney H.(FDA/CDRH); Brown. Sheila: Ricks, Sharon L (HHS'OASH); AGELLER@@hsph.harvard.edu Subject: Re: President"s Task Force on Environmental Health Risks and Safety Risks to Children: Final Agenda and Meeting Materials for the August 17 Senior Staff Steering Committee Meeting Date: Wednesday, August 16, 2017 6:35:38 AM Attachments: Agenda for the August 2017 Senior Steering Committe Meeting 8-16-17.docx Draft President"s Task Force Summary Notes Julv. 31.2017.doc Smoke free research 612lessonslearnedpart1.(2).do HUD Smoke free Home Presentation 8-16-17.pptx PTF Short Term Work Plan Actions Accommplishments Report 8-10-17 -clean version docx Good Morning, Attached are the final agenda and meeting materials for tomorrows Senior Staff Steering Committee meeting for the President's Task Force on Environmental Health Risks and Safety Risks to Children. The meeting time is 1:00pm and the location is the HHS Hubert Humphrey Building, 200 Independence Avenue S.W. room 325-A. The dial-in number is 866-299- 3188 and the participant code is 202-564-2754. If you are participating in person and have not informed me, please let me know by COB today. The point of contact if you have trouble entering the building is Chanya Liv at: 202-690-2470 Attached Meeting Materials Agenda for the August 17, 2017 Senior Staff Steering Committee Meeting Draft President's Task Force (PTF) Summary Notes from the July 2017 Meeting Smoke Free Homes Research Lessons Learned Document Slides for Smoke Free Housing Research Presentation Short Term Accomplishments Report Thanks in advance for your participation in the meeting. Ted Ted Coopwood Office of Children's Health Protection US EPA Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 1301 Constitution Ave. NW Washington, DC 201460 202-564-2197 [email protected] Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 For Internal Federal Partner Use Only-Please Do Not Cite or Quote President's Task Force on Environmental Health Risks and Safety Risks to Children Senior Steering Committee Meeting Thursday August 17, 2017 1:00pm - 3:00pm EST HHS Hubert Humphrey Building -Room 325A 200 Independence Avenue, SW Dial-In: 1-866-299-3188, Passcode: 202-564-2754 AGENDA I. Welcome 1:00PM - -1:03PM Ruth Etzel, EPA and Sandra Howard, HHS II. Roll call 1:03PM - -1:05PM Ted Coopwood, EPA III. Minutes and Action Items from July Steering Committee Meeting 1:05PM -1:10PM (Attachment) Ruth Etzel, EPA and Sandra Howard, HHS IV. Subcommittee Updates - Lead Subcommittee Update 1:10PM - 1:20PM Michael Firestone, EPA, Warren Friedman, HUD, Adrienne Ettinger, HHS (Other Subcommittees have no updates) VI. Other Agency Updates and Discussion Items 1:20PM - 1:40PM - Draft Work Plan Short Term Actions Accomplishments Report (Attachment) Ted Coopwood, EPA VII. Summary of Action items 1:40PM - 2:00PM VIII. Smoke Free Housing Research Presentation 2:00PM- - 2:30PM (Attachment) Alan Geller, Harvard University Adjourn Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 For Internal Federal Partner Use Only - Please Do Not Cite or Quote President's Task Force on Environmental Health Risks and Safety Risks to Children Senior Staff Steering Committee Meeting Draft Summary Notes for Thursday July 20, 2017 1:00pm - 3:00pm ET Meeting Participants HUD: Kitt Rodkey, Warren Friedman CPSC: Michael Babich EPA: Ruth Etzel, Manthan Shah, Angela Hackel, Amanda Hauff, Michael Firestone, Miranda Mitchell HHS/OASH: Sandra Howard, Sarah Field, Chanya Liv IHS: Stephen Piontkowski CDC/NCEH and ATSDR: Adrienne Ettinger, Bill Cibulas FDA: Suzanne Fitzpatrick NIH/NIEHS: Kimberly Thigpen-Tart, Andy Rooney NIH/NHLBI: Michelle Freemer OMB: Eric Rosenfield DOJ: Lori Jonas DOL: Tiffany Defoe Welcome and Roll call Ruth Etzel (EPA) and Sandra Howard (HHS) welcomed all members of the Steering Committee and Angela Hackel (EPA) conducted the roll call. Minutes and Action Items from the June Steering Committee Meeting The meeting minutes and action items from the June 2017 meeting were approved. Ted Coopwood (EPA) will distribute the approved minutes to the Senior Staff Steering Committee Members. Children's Environmental Health in Indian Country; Stephen Piontkowski, Indian Health Service A PowerPoint presentation was shared with the Senior Staff Steering Committee prior to the meeting. The Division of Environmental Health Services (DEHS) is part of the Office of Environmental Health and Engineering at the Indian Health Service (IHS). More than 70% of the DEHS staff work in tribal country, 20% work in an HHS Region, and 10% serve in administrative roles. DEHS monitors health through community injury and disease surveillance. Conducts public outreach about preventative health measures. Provides training and mobilizes partnerships. Works with emergency preparedness partners and addresses outbreaks. Evaluates effectiveness of services and interventions. Five focus areas include: children's environment, food safety, safe drinking water, vectorborne and communicable diseases, and healthy homes. Children's environmental health is a top priority (schools, Head Start, indoor air quality, fire safety, playground safety, injury prevention). Unintentional injuries are a leading cause of death. Motor vehicle crashes was noted as a leading injury type. To address this issue at a national level, car seat success stories are shared to illustrate a large body of work that has been done for traffic safety. Plus, the "Seatbelts. Just Wear 'em" campaign was launched. The campaign has been shown to be effective at reducing motor vehicle crashes. 1 Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 For Internal Federal Partner Use Only - Please Do Not Cite or Quote Regional initiatives include Rocky Mountain Spotted Fever in Arizona Tribal and state/federal partners (CDC) work together. 250 human cases, 20 fatalities; children under age of 10 most impacted. Cost of outbreak is $13.2 million and includes clinical-based response and community-based response. Local concerns include referrals for children's health issues. These include upper respiratory problems related to mold and elevated lead levels. Partnerships are important. DEHS works with tribal customers hand-in-hand and with state/county/federal partners. Questions/Conversation Ruth Etzel, EPA: How do you prioritize the local work? For example, how do you figure out which tribes have lead as a priority? Priorities are conducted at the national, regional and local level. When it comes to non-facility based work, we utilize the public health approach and make decisions based on the data. In some cases, people (the local tribal council) tell us what the work should be (e.g., set up an emergency preparedness operation center). Warren Friedman, HUD: Will send information regarding overcoming obstacles to implementing senior falls policies. Do you have enough data to indicate areas in which your program has been operating to address Rocky Mountain Spotted Fever? Has your approach been effective in reducing its prevalence? Yes, we do. Published reports on community-based work and surveillance. Regarding the effectiveness in reducing risk for rocky mountain fever, there are challenges in implementation and management that need to occur locally. Kitt Rodkey, HUD: will be following up with Stephen to get information on their outreach with Native American populations. How do you follow up with communities on lead? Bill Cibulas, ATSDR: Same follow up questions with lead. Have tribal councils pushed for testing in schools, including water? Screening that occurs by the clinics of the children is an indicator of the cases that exist amongst the children. Head Start performs routine testing to be conducted. Ruth Etzel, EPA: Is there a database that you keep of children's blood lead levels on Native lands? No, not that I am aware of. Sandra Howard, HHS: Does IHS have any recommendations for screening, apart from what is required by Medicaid and or by Head Start? That is out of the scope of work. Peter Ashley, HUD: Can you speak to trend in over-doses? Can you also speak to the causation between alcohol use and motor vehicle accidents? Seeing a new trend in over-doses. Poisoning is one of the top three causes of hospitalizations. Regarding the link between alcohol and motor vehicle accidents, we are comfortable in saying that it is a factor. We do have programs regarding alcohol and substance abuse. Sandra Howard, HHS: We understand that we cannot have one speaker (organization) talk on this issue. If there are other organizations that would like to present, please let us know. Some possible topics could be issues facing Alaska Native communities, lead exposure and Superfund sites (as they relate to tribes in general). 2 Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226

What is the agenda between 1:03pm-1:05pm?

prbn0226

prbn0226_p0, prbn0226_p1, prbn0226_p2, prbn0226_p3, prbn0226_p4, prbn0226_p5, prbn0226_p6

Roll Call

001 From: Wexier. Philip To: Farland, William H.: Susie "Masten; Dourson. Michael (doursomi); jeffrey.jenkins ([email protected]); Beck, Nancy: David Steup; [email protected] Cc: [email protected] Subject: Kids + Chemical Safety Date: Thursday, August 17, 2017 4:00:21 PM Attachments: Re President"s Task Force on Environmental Health Risks and Safety Pisks to Children Final Agenda and Meeting Materials for the August 17 Senior Staff Steering Committee Meeting mso RE President"s Task Force on Environmental Health Risks and Safety Risks to Children Final Agenda and Meeting Materials for the August 17 Senior Staff Steering Committee Meeting msg Bill - This seems like a worthwhile and relevant addition to the TEF site. I am wondering whether the Experts that were used would still be available to reply to questions from the public. There are some other groups working on children's environmental health and it strikes me that it might not hurt to try to link to them and/or coordinate efforts with them and/or get their take on the Kids + Chemical safety site and/or convene a conference call to at least share our respective perspectives on this issue. I am thinking specifically of: EPA's Office of Children's Health Protection (Ruth Etzel heads this up) and their main Web site addressing this issue - bttos://www.epa.gov/children Children's Environmental Health Network (CEHN) - http://cehn.org/ - Among other things, they were instrumental in the formation of an annual Children's Environmental Health Day, October 12, this year (see htto:/lcehn.org/cehdav/) Pediatric Environmental Health Specialty Units - http:llwww.pehsu.net/ - I met and subsequently exchanged a series of emails early this year with Jerry Paulson who is Medical Director for this program. He was enquiring about making their information somehow available via NLM but there didn't seem to be any interest here in following up. My last email to him was just prior to the SOT meeting. I directed him to the TEF site and asked if he thought this might be an alternative place for highlighting the PEHSUs but never heard back from him. Might be worth checking in with him again. President's Task Force on Environmental Health Risks and Safety Risks to Children (httos://otfceh.niehs.nib.gov/). - I have actually been on the mailing list for their (monthly?) meetings for some time (not sure why) and they periodically sent out announcements. I haven't really participated. There was, in fact, a meeting today. See attached emails. Anyway, just thought l'd itemize a few of the other activities going on in this area and reiterate that if TEF gets into the children's environmental health arena, it might be good to keep up with what's going on elsewhere. - Phil P.S. I have been getting some TEF email at my personal email address. Please correspond with me at Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 002 this, my office, address ([email protected]/ instead. Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 From: Coopwood, Theodore To: Howard Sandra (OS/OASH); Liv, Chanva (OS/OASH); Bizel. Buth Cc: Smith Kimberly (HHS'OASH); Jonas, Lori (ENRD); Alice Thaler; Amy Bodette; Andrea Grossman; Andrea Falken; Beverly Samuel; Birnbaum. Linda (NIH/NIEHS) (El; Brown, Sheila; Brevsse Patrick N. (CDC/ONDI EH/NCEH): Bruce. D [email protected] Chaney, Sascha LCDCIONDIEH/NCBDDD); Trent, Chris B; Obulas, William (ATSDR/OADS); Danielle Jones Powson, David; [email protected]: Eric Rosenfield; Erio Waldo; Erica Burrin; Frin Hoffman; Held. Sarah (DHHS/OS/OASH: Freemer. Michelle (NIH/NHLBI) Luber. George (COC/ONDIEH/NCEH): Herbert Bolton; James H [email protected]; Balbus, John (NIH/NIEHS) (E); Joshua Olsen; Judy Harvey; [email protected] Kiley, James (NIH/NHLBI)[E]: Co: Rodkey, Kitt; Lee Caron Lucas Radzinschi; Mark Glaze; Miller, Mark Berger, Martha; Matt Ammon; Michael Babich; Miller, Aubrey (NIH/NIEHS) LEI; Mortensen, Mary E (CDO/ONDIEH/NCEH); Peter Ashley; Roonev. Andrew (NIH/NIEHS) LEI; Sara Newman; Foster, Stiven; Fitzpatrick. Suzanne (FDA/CFSAN); Thigpen Tart, Kimberly (NIH/NIEHS) (El: Warren Friedman; Wexler. Philip (NIH/NLMLI Yasmin a Sani; Blandine Trouille; Broehm. Jason (OST): Goldsmith. Reese (ENRD); Shah, Manthan; Firestone, Michael; Smith. Kimberly (HHS/OASH); Ettinger, Adrienne (CDC/ONDIEH/NCEH); Nevel Amy (HHS/ASPE); [email protected] Hackel, Angela; Hauff. Amanda; Reed. Khesha; Jonas, Lori (ENRD); Lias. Courtney H.(FDA/CDRH); Brown. Sheila: Ricks, Sharon L (HHS'OASH); AGELLER@@hsph.harvard.edu Subject: Re: President"s Task Force on Environmental Health Risks and Safety Risks to Children: Final Agenda and Meeting Materials for the August 17 Senior Staff Steering Committee Meeting Date: Wednesday, August 16, 2017 6:35:38 AM Attachments: Agenda for the August 2017 Senior Steering Committe Meeting 8-16-17.docx Draft President"s Task Force Summary Notes Julv. 31.2017.doc Smoke free research 612lessonslearnedpart1.(2).do HUD Smoke free Home Presentation 8-16-17.pptx PTF Short Term Work Plan Actions Accommplishments Report 8-10-17 -clean version docx Good Morning, Attached are the final agenda and meeting materials for tomorrows Senior Staff Steering Committee meeting for the President's Task Force on Environmental Health Risks and Safety Risks to Children. The meeting time is 1:00pm and the location is the HHS Hubert Humphrey Building, 200 Independence Avenue S.W. room 325-A. The dial-in number is 866-299- 3188 and the participant code is 202-564-2754. If you are participating in person and have not informed me, please let me know by COB today. The point of contact if you have trouble entering the building is Chanya Liv at: 202-690-2470 Attached Meeting Materials Agenda for the August 17, 2017 Senior Staff Steering Committee Meeting Draft President's Task Force (PTF) Summary Notes from the July 2017 Meeting Smoke Free Homes Research Lessons Learned Document Slides for Smoke Free Housing Research Presentation Short Term Accomplishments Report Thanks in advance for your participation in the meeting. Ted Ted Coopwood Office of Children's Health Protection US EPA Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 1301 Constitution Ave. NW Washington, DC 201460 202-564-2197 [email protected] Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 For Internal Federal Partner Use Only-Please Do Not Cite or Quote President's Task Force on Environmental Health Risks and Safety Risks to Children Senior Steering Committee Meeting Thursday August 17, 2017 1:00pm - 3:00pm EST HHS Hubert Humphrey Building -Room 325A 200 Independence Avenue, SW Dial-In: 1-866-299-3188, Passcode: 202-564-2754 AGENDA I. Welcome 1:00PM - -1:03PM Ruth Etzel, EPA and Sandra Howard, HHS II. Roll call 1:03PM - -1:05PM Ted Coopwood, EPA III. Minutes and Action Items from July Steering Committee Meeting 1:05PM -1:10PM (Attachment) Ruth Etzel, EPA and Sandra Howard, HHS IV. Subcommittee Updates - Lead Subcommittee Update 1:10PM - 1:20PM Michael Firestone, EPA, Warren Friedman, HUD, Adrienne Ettinger, HHS (Other Subcommittees have no updates) VI. Other Agency Updates and Discussion Items 1:20PM - 1:40PM - Draft Work Plan Short Term Actions Accomplishments Report (Attachment) Ted Coopwood, EPA VII. Summary of Action items 1:40PM - 2:00PM VIII. Smoke Free Housing Research Presentation 2:00PM- - 2:30PM (Attachment) Alan Geller, Harvard University Adjourn Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 For Internal Federal Partner Use Only - Please Do Not Cite or Quote President's Task Force on Environmental Health Risks and Safety Risks to Children Senior Staff Steering Committee Meeting Draft Summary Notes for Thursday July 20, 2017 1:00pm - 3:00pm ET Meeting Participants HUD: Kitt Rodkey, Warren Friedman CPSC: Michael Babich EPA: Ruth Etzel, Manthan Shah, Angela Hackel, Amanda Hauff, Michael Firestone, Miranda Mitchell HHS/OASH: Sandra Howard, Sarah Field, Chanya Liv IHS: Stephen Piontkowski CDC/NCEH and ATSDR: Adrienne Ettinger, Bill Cibulas FDA: Suzanne Fitzpatrick NIH/NIEHS: Kimberly Thigpen-Tart, Andy Rooney NIH/NHLBI: Michelle Freemer OMB: Eric Rosenfield DOJ: Lori Jonas DOL: Tiffany Defoe Welcome and Roll call Ruth Etzel (EPA) and Sandra Howard (HHS) welcomed all members of the Steering Committee and Angela Hackel (EPA) conducted the roll call. Minutes and Action Items from the June Steering Committee Meeting The meeting minutes and action items from the June 2017 meeting were approved. Ted Coopwood (EPA) will distribute the approved minutes to the Senior Staff Steering Committee Members. Children's Environmental Health in Indian Country; Stephen Piontkowski, Indian Health Service A PowerPoint presentation was shared with the Senior Staff Steering Committee prior to the meeting. The Division of Environmental Health Services (DEHS) is part of the Office of Environmental Health and Engineering at the Indian Health Service (IHS). More than 70% of the DEHS staff work in tribal country, 20% work in an HHS Region, and 10% serve in administrative roles. DEHS monitors health through community injury and disease surveillance. Conducts public outreach about preventative health measures. Provides training and mobilizes partnerships. Works with emergency preparedness partners and addresses outbreaks. Evaluates effectiveness of services and interventions. Five focus areas include: children's environment, food safety, safe drinking water, vectorborne and communicable diseases, and healthy homes. Children's environmental health is a top priority (schools, Head Start, indoor air quality, fire safety, playground safety, injury prevention). Unintentional injuries are a leading cause of death. Motor vehicle crashes was noted as a leading injury type. To address this issue at a national level, car seat success stories are shared to illustrate a large body of work that has been done for traffic safety. Plus, the "Seatbelts. Just Wear 'em" campaign was launched. The campaign has been shown to be effective at reducing motor vehicle crashes. 1 Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 For Internal Federal Partner Use Only - Please Do Not Cite or Quote Regional initiatives include Rocky Mountain Spotted Fever in Arizona Tribal and state/federal partners (CDC) work together. 250 human cases, 20 fatalities; children under age of 10 most impacted. Cost of outbreak is $13.2 million and includes clinical-based response and community-based response. Local concerns include referrals for children's health issues. These include upper respiratory problems related to mold and elevated lead levels. Partnerships are important. DEHS works with tribal customers hand-in-hand and with state/county/federal partners. Questions/Conversation Ruth Etzel, EPA: How do you prioritize the local work? For example, how do you figure out which tribes have lead as a priority? Priorities are conducted at the national, regional and local level. When it comes to non-facility based work, we utilize the public health approach and make decisions based on the data. In some cases, people (the local tribal council) tell us what the work should be (e.g., set up an emergency preparedness operation center). Warren Friedman, HUD: Will send information regarding overcoming obstacles to implementing senior falls policies. Do you have enough data to indicate areas in which your program has been operating to address Rocky Mountain Spotted Fever? Has your approach been effective in reducing its prevalence? Yes, we do. Published reports on community-based work and surveillance. Regarding the effectiveness in reducing risk for rocky mountain fever, there are challenges in implementation and management that need to occur locally. Kitt Rodkey, HUD: will be following up with Stephen to get information on their outreach with Native American populations. How do you follow up with communities on lead? Bill Cibulas, ATSDR: Same follow up questions with lead. Have tribal councils pushed for testing in schools, including water? Screening that occurs by the clinics of the children is an indicator of the cases that exist amongst the children. Head Start performs routine testing to be conducted. Ruth Etzel, EPA: Is there a database that you keep of children's blood lead levels on Native lands? No, not that I am aware of. Sandra Howard, HHS: Does IHS have any recommendations for screening, apart from what is required by Medicaid and or by Head Start? That is out of the scope of work. Peter Ashley, HUD: Can you speak to trend in over-doses? Can you also speak to the causation between alcohol use and motor vehicle accidents? Seeing a new trend in over-doses. Poisoning is one of the top three causes of hospitalizations. Regarding the link between alcohol and motor vehicle accidents, we are comfortable in saying that it is a factor. We do have programs regarding alcohol and substance abuse. Sandra Howard, HHS: We understand that we cannot have one speaker (organization) talk on this issue. If there are other organizations that would like to present, please let us know. Some possible topics could be issues facing Alaska Native communities, lead exposure and Superfund sites (as they relate to tribes in general). 2 Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226

What time is the subcommittee updates discussed?

prbn0226

prbn0226_p0, prbn0226_p1, prbn0226_p2, prbn0226_p3, prbn0226_p4, prbn0226_p5, prbn0226_p6

1:10PM - 1:20PM

001 From: Wexier. Philip To: Farland, William H.: Susie "Masten; Dourson. Michael (doursomi); jeffrey.jenkins ([email protected]); Beck, Nancy: David Steup; [email protected] Cc: [email protected] Subject: Kids + Chemical Safety Date: Thursday, August 17, 2017 4:00:21 PM Attachments: Re President"s Task Force on Environmental Health Risks and Safety Pisks to Children Final Agenda and Meeting Materials for the August 17 Senior Staff Steering Committee Meeting mso RE President"s Task Force on Environmental Health Risks and Safety Risks to Children Final Agenda and Meeting Materials for the August 17 Senior Staff Steering Committee Meeting msg Bill - This seems like a worthwhile and relevant addition to the TEF site. I am wondering whether the Experts that were used would still be available to reply to questions from the public. There are some other groups working on children's environmental health and it strikes me that it might not hurt to try to link to them and/or coordinate efforts with them and/or get their take on the Kids + Chemical safety site and/or convene a conference call to at least share our respective perspectives on this issue. I am thinking specifically of: EPA's Office of Children's Health Protection (Ruth Etzel heads this up) and their main Web site addressing this issue - bttos://www.epa.gov/children Children's Environmental Health Network (CEHN) - http://cehn.org/ - Among other things, they were instrumental in the formation of an annual Children's Environmental Health Day, October 12, this year (see htto:/lcehn.org/cehdav/) Pediatric Environmental Health Specialty Units - http:llwww.pehsu.net/ - I met and subsequently exchanged a series of emails early this year with Jerry Paulson who is Medical Director for this program. He was enquiring about making their information somehow available via NLM but there didn't seem to be any interest here in following up. My last email to him was just prior to the SOT meeting. I directed him to the TEF site and asked if he thought this might be an alternative place for highlighting the PEHSUs but never heard back from him. Might be worth checking in with him again. President's Task Force on Environmental Health Risks and Safety Risks to Children (httos://otfceh.niehs.nib.gov/). - I have actually been on the mailing list for their (monthly?) meetings for some time (not sure why) and they periodically sent out announcements. I haven't really participated. There was, in fact, a meeting today. See attached emails. Anyway, just thought l'd itemize a few of the other activities going on in this area and reiterate that if TEF gets into the children's environmental health arena, it might be good to keep up with what's going on elsewhere. - Phil P.S. I have been getting some TEF email at my personal email address. Please correspond with me at Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 002 this, my office, address ([email protected]/ instead. Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 From: Coopwood, Theodore To: Howard Sandra (OS/OASH); Liv, Chanva (OS/OASH); Bizel. Buth Cc: Smith Kimberly (HHS'OASH); Jonas, Lori (ENRD); Alice Thaler; Amy Bodette; Andrea Grossman; Andrea Falken; Beverly Samuel; Birnbaum. Linda (NIH/NIEHS) (El; Brown, Sheila; Brevsse Patrick N. (CDC/ONDI EH/NCEH): Bruce. D [email protected] Chaney, Sascha LCDCIONDIEH/NCBDDD); Trent, Chris B; Obulas, William (ATSDR/OADS); Danielle Jones Powson, David; [email protected]: Eric Rosenfield; Erio Waldo; Erica Burrin; Frin Hoffman; Held. Sarah (DHHS/OS/OASH: Freemer. Michelle (NIH/NHLBI) Luber. George (COC/ONDIEH/NCEH): Herbert Bolton; James H [email protected]; Balbus, John (NIH/NIEHS) (E); Joshua Olsen; Judy Harvey; [email protected] Kiley, James (NIH/NHLBI)[E]: Co: Rodkey, Kitt; Lee Caron Lucas Radzinschi; Mark Glaze; Miller, Mark Berger, Martha; Matt Ammon; Michael Babich; Miller, Aubrey (NIH/NIEHS) LEI; Mortensen, Mary E (CDO/ONDIEH/NCEH); Peter Ashley; Roonev. Andrew (NIH/NIEHS) LEI; Sara Newman; Foster, Stiven; Fitzpatrick. Suzanne (FDA/CFSAN); Thigpen Tart, Kimberly (NIH/NIEHS) (El: Warren Friedman; Wexler. Philip (NIH/NLMLI Yasmin a Sani; Blandine Trouille; Broehm. Jason (OST): Goldsmith. Reese (ENRD); Shah, Manthan; Firestone, Michael; Smith. Kimberly (HHS/OASH); Ettinger, Adrienne (CDC/ONDIEH/NCEH); Nevel Amy (HHS/ASPE); [email protected] Hackel, Angela; Hauff. Amanda; Reed. Khesha; Jonas, Lori (ENRD); Lias. Courtney H.(FDA/CDRH); Brown. Sheila: Ricks, Sharon L (HHS'OASH); AGELLER@@hsph.harvard.edu Subject: Re: President"s Task Force on Environmental Health Risks and Safety Risks to Children: Final Agenda and Meeting Materials for the August 17 Senior Staff Steering Committee Meeting Date: Wednesday, August 16, 2017 6:35:38 AM Attachments: Agenda for the August 2017 Senior Steering Committe Meeting 8-16-17.docx Draft President"s Task Force Summary Notes Julv. 31.2017.doc Smoke free research 612lessonslearnedpart1.(2).do HUD Smoke free Home Presentation 8-16-17.pptx PTF Short Term Work Plan Actions Accommplishments Report 8-10-17 -clean version docx Good Morning, Attached are the final agenda and meeting materials for tomorrows Senior Staff Steering Committee meeting for the President's Task Force on Environmental Health Risks and Safety Risks to Children. The meeting time is 1:00pm and the location is the HHS Hubert Humphrey Building, 200 Independence Avenue S.W. room 325-A. The dial-in number is 866-299- 3188 and the participant code is 202-564-2754. If you are participating in person and have not informed me, please let me know by COB today. The point of contact if you have trouble entering the building is Chanya Liv at: 202-690-2470 Attached Meeting Materials Agenda for the August 17, 2017 Senior Staff Steering Committee Meeting Draft President's Task Force (PTF) Summary Notes from the July 2017 Meeting Smoke Free Homes Research Lessons Learned Document Slides for Smoke Free Housing Research Presentation Short Term Accomplishments Report Thanks in advance for your participation in the meeting. Ted Ted Coopwood Office of Children's Health Protection US EPA Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 1301 Constitution Ave. NW Washington, DC 201460 202-564-2197 [email protected] Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 For Internal Federal Partner Use Only-Please Do Not Cite or Quote President's Task Force on Environmental Health Risks and Safety Risks to Children Senior Steering Committee Meeting Thursday August 17, 2017 1:00pm - 3:00pm EST HHS Hubert Humphrey Building -Room 325A 200 Independence Avenue, SW Dial-In: 1-866-299-3188, Passcode: 202-564-2754 AGENDA I. Welcome 1:00PM - -1:03PM Ruth Etzel, EPA and Sandra Howard, HHS II. Roll call 1:03PM - -1:05PM Ted Coopwood, EPA III. Minutes and Action Items from July Steering Committee Meeting 1:05PM -1:10PM (Attachment) Ruth Etzel, EPA and Sandra Howard, HHS IV. Subcommittee Updates - Lead Subcommittee Update 1:10PM - 1:20PM Michael Firestone, EPA, Warren Friedman, HUD, Adrienne Ettinger, HHS (Other Subcommittees have no updates) VI. Other Agency Updates and Discussion Items 1:20PM - 1:40PM - Draft Work Plan Short Term Actions Accomplishments Report (Attachment) Ted Coopwood, EPA VII. Summary of Action items 1:40PM - 2:00PM VIII. Smoke Free Housing Research Presentation 2:00PM- - 2:30PM (Attachment) Alan Geller, Harvard University Adjourn Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 For Internal Federal Partner Use Only - Please Do Not Cite or Quote President's Task Force on Environmental Health Risks and Safety Risks to Children Senior Staff Steering Committee Meeting Draft Summary Notes for Thursday July 20, 2017 1:00pm - 3:00pm ET Meeting Participants HUD: Kitt Rodkey, Warren Friedman CPSC: Michael Babich EPA: Ruth Etzel, Manthan Shah, Angela Hackel, Amanda Hauff, Michael Firestone, Miranda Mitchell HHS/OASH: Sandra Howard, Sarah Field, Chanya Liv IHS: Stephen Piontkowski CDC/NCEH and ATSDR: Adrienne Ettinger, Bill Cibulas FDA: Suzanne Fitzpatrick NIH/NIEHS: Kimberly Thigpen-Tart, Andy Rooney NIH/NHLBI: Michelle Freemer OMB: Eric Rosenfield DOJ: Lori Jonas DOL: Tiffany Defoe Welcome and Roll call Ruth Etzel (EPA) and Sandra Howard (HHS) welcomed all members of the Steering Committee and Angela Hackel (EPA) conducted the roll call. Minutes and Action Items from the June Steering Committee Meeting The meeting minutes and action items from the June 2017 meeting were approved. Ted Coopwood (EPA) will distribute the approved minutes to the Senior Staff Steering Committee Members. Children's Environmental Health in Indian Country; Stephen Piontkowski, Indian Health Service A PowerPoint presentation was shared with the Senior Staff Steering Committee prior to the meeting. The Division of Environmental Health Services (DEHS) is part of the Office of Environmental Health and Engineering at the Indian Health Service (IHS). More than 70% of the DEHS staff work in tribal country, 20% work in an HHS Region, and 10% serve in administrative roles. DEHS monitors health through community injury and disease surveillance. Conducts public outreach about preventative health measures. Provides training and mobilizes partnerships. Works with emergency preparedness partners and addresses outbreaks. Evaluates effectiveness of services and interventions. Five focus areas include: children's environment, food safety, safe drinking water, vectorborne and communicable diseases, and healthy homes. Children's environmental health is a top priority (schools, Head Start, indoor air quality, fire safety, playground safety, injury prevention). Unintentional injuries are a leading cause of death. Motor vehicle crashes was noted as a leading injury type. To address this issue at a national level, car seat success stories are shared to illustrate a large body of work that has been done for traffic safety. Plus, the "Seatbelts. Just Wear 'em" campaign was launched. The campaign has been shown to be effective at reducing motor vehicle crashes. 1 Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 For Internal Federal Partner Use Only - Please Do Not Cite or Quote Regional initiatives include Rocky Mountain Spotted Fever in Arizona Tribal and state/federal partners (CDC) work together. 250 human cases, 20 fatalities; children under age of 10 most impacted. Cost of outbreak is $13.2 million and includes clinical-based response and community-based response. Local concerns include referrals for children's health issues. These include upper respiratory problems related to mold and elevated lead levels. Partnerships are important. DEHS works with tribal customers hand-in-hand and with state/county/federal partners. Questions/Conversation Ruth Etzel, EPA: How do you prioritize the local work? For example, how do you figure out which tribes have lead as a priority? Priorities are conducted at the national, regional and local level. When it comes to non-facility based work, we utilize the public health approach and make decisions based on the data. In some cases, people (the local tribal council) tell us what the work should be (e.g., set up an emergency preparedness operation center). Warren Friedman, HUD: Will send information regarding overcoming obstacles to implementing senior falls policies. Do you have enough data to indicate areas in which your program has been operating to address Rocky Mountain Spotted Fever? Has your approach been effective in reducing its prevalence? Yes, we do. Published reports on community-based work and surveillance. Regarding the effectiveness in reducing risk for rocky mountain fever, there are challenges in implementation and management that need to occur locally. Kitt Rodkey, HUD: will be following up with Stephen to get information on their outreach with Native American populations. How do you follow up with communities on lead? Bill Cibulas, ATSDR: Same follow up questions with lead. Have tribal councils pushed for testing in schools, including water? Screening that occurs by the clinics of the children is an indicator of the cases that exist amongst the children. Head Start performs routine testing to be conducted. Ruth Etzel, EPA: Is there a database that you keep of children's blood lead levels on Native lands? No, not that I am aware of. Sandra Howard, HHS: Does IHS have any recommendations for screening, apart from what is required by Medicaid and or by Head Start? That is out of the scope of work. Peter Ashley, HUD: Can you speak to trend in over-doses? Can you also speak to the causation between alcohol use and motor vehicle accidents? Seeing a new trend in over-doses. Poisoning is one of the top three causes of hospitalizations. Regarding the link between alcohol and motor vehicle accidents, we are comfortable in saying that it is a factor. We do have programs regarding alcohol and substance abuse. Sandra Howard, HHS: We understand that we cannot have one speaker (organization) talk on this issue. If there are other organizations that would like to present, please let us know. Some possible topics could be issues facing Alaska Native communities, lead exposure and Superfund sites (as they relate to tribes in general). 2 Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226

what is the agenda between 1:40 pm-2:00 pm ?

prbn0226

prbn0226_p0, prbn0226_p1, prbn0226_p2, prbn0226_p3, prbn0226_p4, prbn0226_p5, prbn0226_p6

Summary of Action Items, summary of action items

001 From: Wexier. Philip To: Farland, William H.: Susie "Masten; Dourson. Michael (doursomi); jeffrey.jenkins ([email protected]); Beck, Nancy: David Steup; [email protected] Cc: [email protected] Subject: Kids + Chemical Safety Date: Thursday, August 17, 2017 4:00:21 PM Attachments: Re President"s Task Force on Environmental Health Risks and Safety Pisks to Children Final Agenda and Meeting Materials for the August 17 Senior Staff Steering Committee Meeting mso RE President"s Task Force on Environmental Health Risks and Safety Risks to Children Final Agenda and Meeting Materials for the August 17 Senior Staff Steering Committee Meeting msg Bill - This seems like a worthwhile and relevant addition to the TEF site. I am wondering whether the Experts that were used would still be available to reply to questions from the public. There are some other groups working on children's environmental health and it strikes me that it might not hurt to try to link to them and/or coordinate efforts with them and/or get their take on the Kids + Chemical safety site and/or convene a conference call to at least share our respective perspectives on this issue. I am thinking specifically of: EPA's Office of Children's Health Protection (Ruth Etzel heads this up) and their main Web site addressing this issue - bttos://www.epa.gov/children Children's Environmental Health Network (CEHN) - http://cehn.org/ - Among other things, they were instrumental in the formation of an annual Children's Environmental Health Day, October 12, this year (see htto:/lcehn.org/cehdav/) Pediatric Environmental Health Specialty Units - http:llwww.pehsu.net/ - I met and subsequently exchanged a series of emails early this year with Jerry Paulson who is Medical Director for this program. He was enquiring about making their information somehow available via NLM but there didn't seem to be any interest here in following up. My last email to him was just prior to the SOT meeting. I directed him to the TEF site and asked if he thought this might be an alternative place for highlighting the PEHSUs but never heard back from him. Might be worth checking in with him again. President's Task Force on Environmental Health Risks and Safety Risks to Children (httos://otfceh.niehs.nib.gov/). - I have actually been on the mailing list for their (monthly?) meetings for some time (not sure why) and they periodically sent out announcements. I haven't really participated. There was, in fact, a meeting today. See attached emails. Anyway, just thought l'd itemize a few of the other activities going on in this area and reiterate that if TEF gets into the children's environmental health arena, it might be good to keep up with what's going on elsewhere. - Phil P.S. I have been getting some TEF email at my personal email address. Please correspond with me at Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 002 this, my office, address ([email protected]/ instead. Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 From: Coopwood, Theodore To: Howard Sandra (OS/OASH); Liv, Chanva (OS/OASH); Bizel. Buth Cc: Smith Kimberly (HHS'OASH); Jonas, Lori (ENRD); Alice Thaler; Amy Bodette; Andrea Grossman; Andrea Falken; Beverly Samuel; Birnbaum. Linda (NIH/NIEHS) (El; Brown, Sheila; Brevsse Patrick N. (CDC/ONDI EH/NCEH): Bruce. D [email protected] Chaney, Sascha LCDCIONDIEH/NCBDDD); Trent, Chris B; Obulas, William (ATSDR/OADS); Danielle Jones Powson, David; [email protected]: Eric Rosenfield; Erio Waldo; Erica Burrin; Frin Hoffman; Held. Sarah (DHHS/OS/OASH: Freemer. Michelle (NIH/NHLBI) Luber. George (COC/ONDIEH/NCEH): Herbert Bolton; James H [email protected]; Balbus, John (NIH/NIEHS) (E); Joshua Olsen; Judy Harvey; [email protected] Kiley, James (NIH/NHLBI)[E]: Co: Rodkey, Kitt; Lee Caron Lucas Radzinschi; Mark Glaze; Miller, Mark Berger, Martha; Matt Ammon; Michael Babich; Miller, Aubrey (NIH/NIEHS) LEI; Mortensen, Mary E (CDO/ONDIEH/NCEH); Peter Ashley; Roonev. Andrew (NIH/NIEHS) LEI; Sara Newman; Foster, Stiven; Fitzpatrick. Suzanne (FDA/CFSAN); Thigpen Tart, Kimberly (NIH/NIEHS) (El: Warren Friedman; Wexler. Philip (NIH/NLMLI Yasmin a Sani; Blandine Trouille; Broehm. Jason (OST): Goldsmith. Reese (ENRD); Shah, Manthan; Firestone, Michael; Smith. Kimberly (HHS/OASH); Ettinger, Adrienne (CDC/ONDIEH/NCEH); Nevel Amy (HHS/ASPE); [email protected] Hackel, Angela; Hauff. Amanda; Reed. Khesha; Jonas, Lori (ENRD); Lias. Courtney H.(FDA/CDRH); Brown. Sheila: Ricks, Sharon L (HHS'OASH); AGELLER@@hsph.harvard.edu Subject: Re: President"s Task Force on Environmental Health Risks and Safety Risks to Children: Final Agenda and Meeting Materials for the August 17 Senior Staff Steering Committee Meeting Date: Wednesday, August 16, 2017 6:35:38 AM Attachments: Agenda for the August 2017 Senior Steering Committe Meeting 8-16-17.docx Draft President"s Task Force Summary Notes Julv. 31.2017.doc Smoke free research 612lessonslearnedpart1.(2).do HUD Smoke free Home Presentation 8-16-17.pptx PTF Short Term Work Plan Actions Accommplishments Report 8-10-17 -clean version docx Good Morning, Attached are the final agenda and meeting materials for tomorrows Senior Staff Steering Committee meeting for the President's Task Force on Environmental Health Risks and Safety Risks to Children. The meeting time is 1:00pm and the location is the HHS Hubert Humphrey Building, 200 Independence Avenue S.W. room 325-A. The dial-in number is 866-299- 3188 and the participant code is 202-564-2754. If you are participating in person and have not informed me, please let me know by COB today. The point of contact if you have trouble entering the building is Chanya Liv at: 202-690-2470 Attached Meeting Materials Agenda for the August 17, 2017 Senior Staff Steering Committee Meeting Draft President's Task Force (PTF) Summary Notes from the July 2017 Meeting Smoke Free Homes Research Lessons Learned Document Slides for Smoke Free Housing Research Presentation Short Term Accomplishments Report Thanks in advance for your participation in the meeting. Ted Ted Coopwood Office of Children's Health Protection US EPA Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 1301 Constitution Ave. NW Washington, DC 201460 202-564-2197 [email protected] Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 For Internal Federal Partner Use Only-Please Do Not Cite or Quote President's Task Force on Environmental Health Risks and Safety Risks to Children Senior Steering Committee Meeting Thursday August 17, 2017 1:00pm - 3:00pm EST HHS Hubert Humphrey Building -Room 325A 200 Independence Avenue, SW Dial-In: 1-866-299-3188, Passcode: 202-564-2754 AGENDA I. Welcome 1:00PM - -1:03PM Ruth Etzel, EPA and Sandra Howard, HHS II. Roll call 1:03PM - -1:05PM Ted Coopwood, EPA III. Minutes and Action Items from July Steering Committee Meeting 1:05PM -1:10PM (Attachment) Ruth Etzel, EPA and Sandra Howard, HHS IV. Subcommittee Updates - Lead Subcommittee Update 1:10PM - 1:20PM Michael Firestone, EPA, Warren Friedman, HUD, Adrienne Ettinger, HHS (Other Subcommittees have no updates) VI. Other Agency Updates and Discussion Items 1:20PM - 1:40PM - Draft Work Plan Short Term Actions Accomplishments Report (Attachment) Ted Coopwood, EPA VII. Summary of Action items 1:40PM - 2:00PM VIII. Smoke Free Housing Research Presentation 2:00PM- - 2:30PM (Attachment) Alan Geller, Harvard University Adjourn Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 For Internal Federal Partner Use Only - Please Do Not Cite or Quote President's Task Force on Environmental Health Risks and Safety Risks to Children Senior Staff Steering Committee Meeting Draft Summary Notes for Thursday July 20, 2017 1:00pm - 3:00pm ET Meeting Participants HUD: Kitt Rodkey, Warren Friedman CPSC: Michael Babich EPA: Ruth Etzel, Manthan Shah, Angela Hackel, Amanda Hauff, Michael Firestone, Miranda Mitchell HHS/OASH: Sandra Howard, Sarah Field, Chanya Liv IHS: Stephen Piontkowski CDC/NCEH and ATSDR: Adrienne Ettinger, Bill Cibulas FDA: Suzanne Fitzpatrick NIH/NIEHS: Kimberly Thigpen-Tart, Andy Rooney NIH/NHLBI: Michelle Freemer OMB: Eric Rosenfield DOJ: Lori Jonas DOL: Tiffany Defoe Welcome and Roll call Ruth Etzel (EPA) and Sandra Howard (HHS) welcomed all members of the Steering Committee and Angela Hackel (EPA) conducted the roll call. Minutes and Action Items from the June Steering Committee Meeting The meeting minutes and action items from the June 2017 meeting were approved. Ted Coopwood (EPA) will distribute the approved minutes to the Senior Staff Steering Committee Members. Children's Environmental Health in Indian Country; Stephen Piontkowski, Indian Health Service A PowerPoint presentation was shared with the Senior Staff Steering Committee prior to the meeting. The Division of Environmental Health Services (DEHS) is part of the Office of Environmental Health and Engineering at the Indian Health Service (IHS). More than 70% of the DEHS staff work in tribal country, 20% work in an HHS Region, and 10% serve in administrative roles. DEHS monitors health through community injury and disease surveillance. Conducts public outreach about preventative health measures. Provides training and mobilizes partnerships. Works with emergency preparedness partners and addresses outbreaks. Evaluates effectiveness of services and interventions. Five focus areas include: children's environment, food safety, safe drinking water, vectorborne and communicable diseases, and healthy homes. Children's environmental health is a top priority (schools, Head Start, indoor air quality, fire safety, playground safety, injury prevention). Unintentional injuries are a leading cause of death. Motor vehicle crashes was noted as a leading injury type. To address this issue at a national level, car seat success stories are shared to illustrate a large body of work that has been done for traffic safety. Plus, the "Seatbelts. Just Wear 'em" campaign was launched. The campaign has been shown to be effective at reducing motor vehicle crashes. 1 Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 For Internal Federal Partner Use Only - Please Do Not Cite or Quote Regional initiatives include Rocky Mountain Spotted Fever in Arizona Tribal and state/federal partners (CDC) work together. 250 human cases, 20 fatalities; children under age of 10 most impacted. Cost of outbreak is $13.2 million and includes clinical-based response and community-based response. Local concerns include referrals for children's health issues. These include upper respiratory problems related to mold and elevated lead levels. Partnerships are important. DEHS works with tribal customers hand-in-hand and with state/county/federal partners. Questions/Conversation Ruth Etzel, EPA: How do you prioritize the local work? For example, how do you figure out which tribes have lead as a priority? Priorities are conducted at the national, regional and local level. When it comes to non-facility based work, we utilize the public health approach and make decisions based on the data. In some cases, people (the local tribal council) tell us what the work should be (e.g., set up an emergency preparedness operation center). Warren Friedman, HUD: Will send information regarding overcoming obstacles to implementing senior falls policies. Do you have enough data to indicate areas in which your program has been operating to address Rocky Mountain Spotted Fever? Has your approach been effective in reducing its prevalence? Yes, we do. Published reports on community-based work and surveillance. Regarding the effectiveness in reducing risk for rocky mountain fever, there are challenges in implementation and management that need to occur locally. Kitt Rodkey, HUD: will be following up with Stephen to get information on their outreach with Native American populations. How do you follow up with communities on lead? Bill Cibulas, ATSDR: Same follow up questions with lead. Have tribal councils pushed for testing in schools, including water? Screening that occurs by the clinics of the children is an indicator of the cases that exist amongst the children. Head Start performs routine testing to be conducted. Ruth Etzel, EPA: Is there a database that you keep of children's blood lead levels on Native lands? No, not that I am aware of. Sandra Howard, HHS: Does IHS have any recommendations for screening, apart from what is required by Medicaid and or by Head Start? That is out of the scope of work. Peter Ashley, HUD: Can you speak to trend in over-doses? Can you also speak to the causation between alcohol use and motor vehicle accidents? Seeing a new trend in over-doses. Poisoning is one of the top three causes of hospitalizations. Regarding the link between alcohol and motor vehicle accidents, we are comfortable in saying that it is a factor. We do have programs regarding alcohol and substance abuse. Sandra Howard, HHS: We understand that we cannot have one speaker (organization) talk on this issue. If there are other organizations that would like to present, please let us know. Some possible topics could be issues facing Alaska Native communities, lead exposure and Superfund sites (as they relate to tribes in general). 2 Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226

what is the passcode number ?

prbn0226

prbn0226_p0, prbn0226_p1, prbn0226_p2, prbn0226_p3, prbn0226_p4, prbn0226_p5, prbn0226_p6

202-564-2754

001 From: Wexier. Philip To: Farland, William H.: Susie "Masten; Dourson. Michael (doursomi); jeffrey.jenkins ([email protected]); Beck, Nancy: David Steup; [email protected] Cc: [email protected] Subject: Kids + Chemical Safety Date: Thursday, August 17, 2017 4:00:21 PM Attachments: Re President"s Task Force on Environmental Health Risks and Safety Pisks to Children Final Agenda and Meeting Materials for the August 17 Senior Staff Steering Committee Meeting mso RE President"s Task Force on Environmental Health Risks and Safety Risks to Children Final Agenda and Meeting Materials for the August 17 Senior Staff Steering Committee Meeting msg Bill - This seems like a worthwhile and relevant addition to the TEF site. I am wondering whether the Experts that were used would still be available to reply to questions from the public. There are some other groups working on children's environmental health and it strikes me that it might not hurt to try to link to them and/or coordinate efforts with them and/or get their take on the Kids + Chemical safety site and/or convene a conference call to at least share our respective perspectives on this issue. I am thinking specifically of: EPA's Office of Children's Health Protection (Ruth Etzel heads this up) and their main Web site addressing this issue - bttos://www.epa.gov/children Children's Environmental Health Network (CEHN) - http://cehn.org/ - Among other things, they were instrumental in the formation of an annual Children's Environmental Health Day, October 12, this year (see htto:/lcehn.org/cehdav/) Pediatric Environmental Health Specialty Units - http:llwww.pehsu.net/ - I met and subsequently exchanged a series of emails early this year with Jerry Paulson who is Medical Director for this program. He was enquiring about making their information somehow available via NLM but there didn't seem to be any interest here in following up. My last email to him was just prior to the SOT meeting. I directed him to the TEF site and asked if he thought this might be an alternative place for highlighting the PEHSUs but never heard back from him. Might be worth checking in with him again. President's Task Force on Environmental Health Risks and Safety Risks to Children (httos://otfceh.niehs.nib.gov/). - I have actually been on the mailing list for their (monthly?) meetings for some time (not sure why) and they periodically sent out announcements. I haven't really participated. There was, in fact, a meeting today. See attached emails. Anyway, just thought l'd itemize a few of the other activities going on in this area and reiterate that if TEF gets into the children's environmental health arena, it might be good to keep up with what's going on elsewhere. - Phil P.S. I have been getting some TEF email at my personal email address. Please correspond with me at Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 002 this, my office, address ([email protected]/ instead. Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 From: Coopwood, Theodore To: Howard Sandra (OS/OASH); Liv, Chanva (OS/OASH); Bizel. Buth Cc: Smith Kimberly (HHS'OASH); Jonas, Lori (ENRD); Alice Thaler; Amy Bodette; Andrea Grossman; Andrea Falken; Beverly Samuel; Birnbaum. Linda (NIH/NIEHS) (El; Brown, Sheila; Brevsse Patrick N. (CDC/ONDI EH/NCEH): Bruce. D [email protected] Chaney, Sascha LCDCIONDIEH/NCBDDD); Trent, Chris B; Obulas, William (ATSDR/OADS); Danielle Jones Powson, David; [email protected]: Eric Rosenfield; Erio Waldo; Erica Burrin; Frin Hoffman; Held. Sarah (DHHS/OS/OASH: Freemer. Michelle (NIH/NHLBI) Luber. George (COC/ONDIEH/NCEH): Herbert Bolton; James H [email protected]; Balbus, John (NIH/NIEHS) (E); Joshua Olsen; Judy Harvey; [email protected] Kiley, James (NIH/NHLBI)[E]: Co: Rodkey, Kitt; Lee Caron Lucas Radzinschi; Mark Glaze; Miller, Mark Berger, Martha; Matt Ammon; Michael Babich; Miller, Aubrey (NIH/NIEHS) LEI; Mortensen, Mary E (CDO/ONDIEH/NCEH); Peter Ashley; Roonev. Andrew (NIH/NIEHS) LEI; Sara Newman; Foster, Stiven; Fitzpatrick. Suzanne (FDA/CFSAN); Thigpen Tart, Kimberly (NIH/NIEHS) (El: Warren Friedman; Wexler. Philip (NIH/NLMLI Yasmin a Sani; Blandine Trouille; Broehm. Jason (OST): Goldsmith. Reese (ENRD); Shah, Manthan; Firestone, Michael; Smith. Kimberly (HHS/OASH); Ettinger, Adrienne (CDC/ONDIEH/NCEH); Nevel Amy (HHS/ASPE); [email protected] Hackel, Angela; Hauff. Amanda; Reed. Khesha; Jonas, Lori (ENRD); Lias. Courtney H.(FDA/CDRH); Brown. Sheila: Ricks, Sharon L (HHS'OASH); AGELLER@@hsph.harvard.edu Subject: Re: President"s Task Force on Environmental Health Risks and Safety Risks to Children: Final Agenda and Meeting Materials for the August 17 Senior Staff Steering Committee Meeting Date: Wednesday, August 16, 2017 6:35:38 AM Attachments: Agenda for the August 2017 Senior Steering Committe Meeting 8-16-17.docx Draft President"s Task Force Summary Notes Julv. 31.2017.doc Smoke free research 612lessonslearnedpart1.(2).do HUD Smoke free Home Presentation 8-16-17.pptx PTF Short Term Work Plan Actions Accommplishments Report 8-10-17 -clean version docx Good Morning, Attached are the final agenda and meeting materials for tomorrows Senior Staff Steering Committee meeting for the President's Task Force on Environmental Health Risks and Safety Risks to Children. The meeting time is 1:00pm and the location is the HHS Hubert Humphrey Building, 200 Independence Avenue S.W. room 325-A. The dial-in number is 866-299- 3188 and the participant code is 202-564-2754. If you are participating in person and have not informed me, please let me know by COB today. The point of contact if you have trouble entering the building is Chanya Liv at: 202-690-2470 Attached Meeting Materials Agenda for the August 17, 2017 Senior Staff Steering Committee Meeting Draft President's Task Force (PTF) Summary Notes from the July 2017 Meeting Smoke Free Homes Research Lessons Learned Document Slides for Smoke Free Housing Research Presentation Short Term Accomplishments Report Thanks in advance for your participation in the meeting. Ted Ted Coopwood Office of Children's Health Protection US EPA Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 1301 Constitution Ave. NW Washington, DC 201460 202-564-2197 [email protected] Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 For Internal Federal Partner Use Only-Please Do Not Cite or Quote President's Task Force on Environmental Health Risks and Safety Risks to Children Senior Steering Committee Meeting Thursday August 17, 2017 1:00pm - 3:00pm EST HHS Hubert Humphrey Building -Room 325A 200 Independence Avenue, SW Dial-In: 1-866-299-3188, Passcode: 202-564-2754 AGENDA I. Welcome 1:00PM - -1:03PM Ruth Etzel, EPA and Sandra Howard, HHS II. Roll call 1:03PM - -1:05PM Ted Coopwood, EPA III. Minutes and Action Items from July Steering Committee Meeting 1:05PM -1:10PM (Attachment) Ruth Etzel, EPA and Sandra Howard, HHS IV. Subcommittee Updates - Lead Subcommittee Update 1:10PM - 1:20PM Michael Firestone, EPA, Warren Friedman, HUD, Adrienne Ettinger, HHS (Other Subcommittees have no updates) VI. Other Agency Updates and Discussion Items 1:20PM - 1:40PM - Draft Work Plan Short Term Actions Accomplishments Report (Attachment) Ted Coopwood, EPA VII. Summary of Action items 1:40PM - 2:00PM VIII. Smoke Free Housing Research Presentation 2:00PM- - 2:30PM (Attachment) Alan Geller, Harvard University Adjourn Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 For Internal Federal Partner Use Only - Please Do Not Cite or Quote President's Task Force on Environmental Health Risks and Safety Risks to Children Senior Staff Steering Committee Meeting Draft Summary Notes for Thursday July 20, 2017 1:00pm - 3:00pm ET Meeting Participants HUD: Kitt Rodkey, Warren Friedman CPSC: Michael Babich EPA: Ruth Etzel, Manthan Shah, Angela Hackel, Amanda Hauff, Michael Firestone, Miranda Mitchell HHS/OASH: Sandra Howard, Sarah Field, Chanya Liv IHS: Stephen Piontkowski CDC/NCEH and ATSDR: Adrienne Ettinger, Bill Cibulas FDA: Suzanne Fitzpatrick NIH/NIEHS: Kimberly Thigpen-Tart, Andy Rooney NIH/NHLBI: Michelle Freemer OMB: Eric Rosenfield DOJ: Lori Jonas DOL: Tiffany Defoe Welcome and Roll call Ruth Etzel (EPA) and Sandra Howard (HHS) welcomed all members of the Steering Committee and Angela Hackel (EPA) conducted the roll call. Minutes and Action Items from the June Steering Committee Meeting The meeting minutes and action items from the June 2017 meeting were approved. Ted Coopwood (EPA) will distribute the approved minutes to the Senior Staff Steering Committee Members. Children's Environmental Health in Indian Country; Stephen Piontkowski, Indian Health Service A PowerPoint presentation was shared with the Senior Staff Steering Committee prior to the meeting. The Division of Environmental Health Services (DEHS) is part of the Office of Environmental Health and Engineering at the Indian Health Service (IHS). More than 70% of the DEHS staff work in tribal country, 20% work in an HHS Region, and 10% serve in administrative roles. DEHS monitors health through community injury and disease surveillance. Conducts public outreach about preventative health measures. Provides training and mobilizes partnerships. Works with emergency preparedness partners and addresses outbreaks. Evaluates effectiveness of services and interventions. Five focus areas include: children's environment, food safety, safe drinking water, vectorborne and communicable diseases, and healthy homes. Children's environmental health is a top priority (schools, Head Start, indoor air quality, fire safety, playground safety, injury prevention). Unintentional injuries are a leading cause of death. Motor vehicle crashes was noted as a leading injury type. To address this issue at a national level, car seat success stories are shared to illustrate a large body of work that has been done for traffic safety. Plus, the "Seatbelts. Just Wear 'em" campaign was launched. The campaign has been shown to be effective at reducing motor vehicle crashes. 1 Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 For Internal Federal Partner Use Only - Please Do Not Cite or Quote Regional initiatives include Rocky Mountain Spotted Fever in Arizona Tribal and state/federal partners (CDC) work together. 250 human cases, 20 fatalities; children under age of 10 most impacted. Cost of outbreak is $13.2 million and includes clinical-based response and community-based response. Local concerns include referrals for children's health issues. These include upper respiratory problems related to mold and elevated lead levels. Partnerships are important. DEHS works with tribal customers hand-in-hand and with state/county/federal partners. Questions/Conversation Ruth Etzel, EPA: How do you prioritize the local work? For example, how do you figure out which tribes have lead as a priority? Priorities are conducted at the national, regional and local level. When it comes to non-facility based work, we utilize the public health approach and make decisions based on the data. In some cases, people (the local tribal council) tell us what the work should be (e.g., set up an emergency preparedness operation center). Warren Friedman, HUD: Will send information regarding overcoming obstacles to implementing senior falls policies. Do you have enough data to indicate areas in which your program has been operating to address Rocky Mountain Spotted Fever? Has your approach been effective in reducing its prevalence? Yes, we do. Published reports on community-based work and surveillance. Regarding the effectiveness in reducing risk for rocky mountain fever, there are challenges in implementation and management that need to occur locally. Kitt Rodkey, HUD: will be following up with Stephen to get information on their outreach with Native American populations. How do you follow up with communities on lead? Bill Cibulas, ATSDR: Same follow up questions with lead. Have tribal councils pushed for testing in schools, including water? Screening that occurs by the clinics of the children is an indicator of the cases that exist amongst the children. Head Start performs routine testing to be conducted. Ruth Etzel, EPA: Is there a database that you keep of children's blood lead levels on Native lands? No, not that I am aware of. Sandra Howard, HHS: Does IHS have any recommendations for screening, apart from what is required by Medicaid and or by Head Start? That is out of the scope of work. Peter Ashley, HUD: Can you speak to trend in over-doses? Can you also speak to the causation between alcohol use and motor vehicle accidents? Seeing a new trend in over-doses. Poisoning is one of the top three causes of hospitalizations. Regarding the link between alcohol and motor vehicle accidents, we are comfortable in saying that it is a factor. We do have programs regarding alcohol and substance abuse. Sandra Howard, HHS: We understand that we cannot have one speaker (organization) talk on this issue. If there are other organizations that would like to present, please let us know. Some possible topics could be issues facing Alaska Native communities, lead exposure and Superfund sites (as they relate to tribes in general). 2 Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226

Where is the senior steering committee meeting held?

prbn0226

prbn0226_p0, prbn0226_p1, prbn0226_p2, prbn0226_p3, prbn0226_p4, prbn0226_p5, prbn0226_p6

HHS Hubert Humphery building -Room 325A

001 From: Wexier. Philip To: Farland, William H.: Susie "Masten; Dourson. Michael (doursomi); jeffrey.jenkins ([email protected]); Beck, Nancy: David Steup; [email protected] Cc: [email protected] Subject: Kids + Chemical Safety Date: Thursday, August 17, 2017 4:00:21 PM Attachments: Re President"s Task Force on Environmental Health Risks and Safety Pisks to Children Final Agenda and Meeting Materials for the August 17 Senior Staff Steering Committee Meeting mso RE President"s Task Force on Environmental Health Risks and Safety Risks to Children Final Agenda and Meeting Materials for the August 17 Senior Staff Steering Committee Meeting msg Bill - This seems like a worthwhile and relevant addition to the TEF site. I am wondering whether the Experts that were used would still be available to reply to questions from the public. There are some other groups working on children's environmental health and it strikes me that it might not hurt to try to link to them and/or coordinate efforts with them and/or get their take on the Kids + Chemical safety site and/or convene a conference call to at least share our respective perspectives on this issue. I am thinking specifically of: EPA's Office of Children's Health Protection (Ruth Etzel heads this up) and their main Web site addressing this issue - bttos://www.epa.gov/children Children's Environmental Health Network (CEHN) - http://cehn.org/ - Among other things, they were instrumental in the formation of an annual Children's Environmental Health Day, October 12, this year (see htto:/lcehn.org/cehdav/) Pediatric Environmental Health Specialty Units - http:llwww.pehsu.net/ - I met and subsequently exchanged a series of emails early this year with Jerry Paulson who is Medical Director for this program. He was enquiring about making their information somehow available via NLM but there didn't seem to be any interest here in following up. My last email to him was just prior to the SOT meeting. I directed him to the TEF site and asked if he thought this might be an alternative place for highlighting the PEHSUs but never heard back from him. Might be worth checking in with him again. President's Task Force on Environmental Health Risks and Safety Risks to Children (httos://otfceh.niehs.nib.gov/). - I have actually been on the mailing list for their (monthly?) meetings for some time (not sure why) and they periodically sent out announcements. I haven't really participated. There was, in fact, a meeting today. See attached emails. Anyway, just thought l'd itemize a few of the other activities going on in this area and reiterate that if TEF gets into the children's environmental health arena, it might be good to keep up with what's going on elsewhere. - Phil P.S. I have been getting some TEF email at my personal email address. Please correspond with me at Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 002 this, my office, address ([email protected]/ instead. Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 From: Coopwood, Theodore To: Howard Sandra (OS/OASH); Liv, Chanva (OS/OASH); Bizel. Buth Cc: Smith Kimberly (HHS'OASH); Jonas, Lori (ENRD); Alice Thaler; Amy Bodette; Andrea Grossman; Andrea Falken; Beverly Samuel; Birnbaum. Linda (NIH/NIEHS) (El; Brown, Sheila; Brevsse Patrick N. (CDC/ONDI EH/NCEH): Bruce. D [email protected] Chaney, Sascha LCDCIONDIEH/NCBDDD); Trent, Chris B; Obulas, William (ATSDR/OADS); Danielle Jones Powson, David; [email protected]: Eric Rosenfield; Erio Waldo; Erica Burrin; Frin Hoffman; Held. Sarah (DHHS/OS/OASH: Freemer. Michelle (NIH/NHLBI) Luber. George (COC/ONDIEH/NCEH): Herbert Bolton; James H [email protected]; Balbus, John (NIH/NIEHS) (E); Joshua Olsen; Judy Harvey; [email protected] Kiley, James (NIH/NHLBI)[E]: Co: Rodkey, Kitt; Lee Caron Lucas Radzinschi; Mark Glaze; Miller, Mark Berger, Martha; Matt Ammon; Michael Babich; Miller, Aubrey (NIH/NIEHS) LEI; Mortensen, Mary E (CDO/ONDIEH/NCEH); Peter Ashley; Roonev. Andrew (NIH/NIEHS) LEI; Sara Newman; Foster, Stiven; Fitzpatrick. Suzanne (FDA/CFSAN); Thigpen Tart, Kimberly (NIH/NIEHS) (El: Warren Friedman; Wexler. Philip (NIH/NLMLI Yasmin a Sani; Blandine Trouille; Broehm. Jason (OST): Goldsmith. Reese (ENRD); Shah, Manthan; Firestone, Michael; Smith. Kimberly (HHS/OASH); Ettinger, Adrienne (CDC/ONDIEH/NCEH); Nevel Amy (HHS/ASPE); [email protected] Hackel, Angela; Hauff. Amanda; Reed. Khesha; Jonas, Lori (ENRD); Lias. Courtney H.(FDA/CDRH); Brown. Sheila: Ricks, Sharon L (HHS'OASH); AGELLER@@hsph.harvard.edu Subject: Re: President"s Task Force on Environmental Health Risks and Safety Risks to Children: Final Agenda and Meeting Materials for the August 17 Senior Staff Steering Committee Meeting Date: Wednesday, August 16, 2017 6:35:38 AM Attachments: Agenda for the August 2017 Senior Steering Committe Meeting 8-16-17.docx Draft President"s Task Force Summary Notes Julv. 31.2017.doc Smoke free research 612lessonslearnedpart1.(2).do HUD Smoke free Home Presentation 8-16-17.pptx PTF Short Term Work Plan Actions Accommplishments Report 8-10-17 -clean version docx Good Morning, Attached are the final agenda and meeting materials for tomorrows Senior Staff Steering Committee meeting for the President's Task Force on Environmental Health Risks and Safety Risks to Children. The meeting time is 1:00pm and the location is the HHS Hubert Humphrey Building, 200 Independence Avenue S.W. room 325-A. The dial-in number is 866-299- 3188 and the participant code is 202-564-2754. If you are participating in person and have not informed me, please let me know by COB today. The point of contact if you have trouble entering the building is Chanya Liv at: 202-690-2470 Attached Meeting Materials Agenda for the August 17, 2017 Senior Staff Steering Committee Meeting Draft President's Task Force (PTF) Summary Notes from the July 2017 Meeting Smoke Free Homes Research Lessons Learned Document Slides for Smoke Free Housing Research Presentation Short Term Accomplishments Report Thanks in advance for your participation in the meeting. Ted Ted Coopwood Office of Children's Health Protection US EPA Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 1301 Constitution Ave. NW Washington, DC 201460 202-564-2197 [email protected] Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 For Internal Federal Partner Use Only-Please Do Not Cite or Quote President's Task Force on Environmental Health Risks and Safety Risks to Children Senior Steering Committee Meeting Thursday August 17, 2017 1:00pm - 3:00pm EST HHS Hubert Humphrey Building -Room 325A 200 Independence Avenue, SW Dial-In: 1-866-299-3188, Passcode: 202-564-2754 AGENDA I. Welcome 1:00PM - -1:03PM Ruth Etzel, EPA and Sandra Howard, HHS II. Roll call 1:03PM - -1:05PM Ted Coopwood, EPA III. Minutes and Action Items from July Steering Committee Meeting 1:05PM -1:10PM (Attachment) Ruth Etzel, EPA and Sandra Howard, HHS IV. Subcommittee Updates - Lead Subcommittee Update 1:10PM - 1:20PM Michael Firestone, EPA, Warren Friedman, HUD, Adrienne Ettinger, HHS (Other Subcommittees have no updates) VI. Other Agency Updates and Discussion Items 1:20PM - 1:40PM - Draft Work Plan Short Term Actions Accomplishments Report (Attachment) Ted Coopwood, EPA VII. Summary of Action items 1:40PM - 2:00PM VIII. Smoke Free Housing Research Presentation 2:00PM- - 2:30PM (Attachment) Alan Geller, Harvard University Adjourn Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 For Internal Federal Partner Use Only - Please Do Not Cite or Quote President's Task Force on Environmental Health Risks and Safety Risks to Children Senior Staff Steering Committee Meeting Draft Summary Notes for Thursday July 20, 2017 1:00pm - 3:00pm ET Meeting Participants HUD: Kitt Rodkey, Warren Friedman CPSC: Michael Babich EPA: Ruth Etzel, Manthan Shah, Angela Hackel, Amanda Hauff, Michael Firestone, Miranda Mitchell HHS/OASH: Sandra Howard, Sarah Field, Chanya Liv IHS: Stephen Piontkowski CDC/NCEH and ATSDR: Adrienne Ettinger, Bill Cibulas FDA: Suzanne Fitzpatrick NIH/NIEHS: Kimberly Thigpen-Tart, Andy Rooney NIH/NHLBI: Michelle Freemer OMB: Eric Rosenfield DOJ: Lori Jonas DOL: Tiffany Defoe Welcome and Roll call Ruth Etzel (EPA) and Sandra Howard (HHS) welcomed all members of the Steering Committee and Angela Hackel (EPA) conducted the roll call. Minutes and Action Items from the June Steering Committee Meeting The meeting minutes and action items from the June 2017 meeting were approved. Ted Coopwood (EPA) will distribute the approved minutes to the Senior Staff Steering Committee Members. Children's Environmental Health in Indian Country; Stephen Piontkowski, Indian Health Service A PowerPoint presentation was shared with the Senior Staff Steering Committee prior to the meeting. The Division of Environmental Health Services (DEHS) is part of the Office of Environmental Health and Engineering at the Indian Health Service (IHS). More than 70% of the DEHS staff work in tribal country, 20% work in an HHS Region, and 10% serve in administrative roles. DEHS monitors health through community injury and disease surveillance. Conducts public outreach about preventative health measures. Provides training and mobilizes partnerships. Works with emergency preparedness partners and addresses outbreaks. Evaluates effectiveness of services and interventions. Five focus areas include: children's environment, food safety, safe drinking water, vectorborne and communicable diseases, and healthy homes. Children's environmental health is a top priority (schools, Head Start, indoor air quality, fire safety, playground safety, injury prevention). Unintentional injuries are a leading cause of death. Motor vehicle crashes was noted as a leading injury type. To address this issue at a national level, car seat success stories are shared to illustrate a large body of work that has been done for traffic safety. Plus, the "Seatbelts. Just Wear 'em" campaign was launched. The campaign has been shown to be effective at reducing motor vehicle crashes. 1 Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 For Internal Federal Partner Use Only - Please Do Not Cite or Quote Regional initiatives include Rocky Mountain Spotted Fever in Arizona Tribal and state/federal partners (CDC) work together. 250 human cases, 20 fatalities; children under age of 10 most impacted. Cost of outbreak is $13.2 million and includes clinical-based response and community-based response. Local concerns include referrals for children's health issues. These include upper respiratory problems related to mold and elevated lead levels. Partnerships are important. DEHS works with tribal customers hand-in-hand and with state/county/federal partners. Questions/Conversation Ruth Etzel, EPA: How do you prioritize the local work? For example, how do you figure out which tribes have lead as a priority? Priorities are conducted at the national, regional and local level. When it comes to non-facility based work, we utilize the public health approach and make decisions based on the data. In some cases, people (the local tribal council) tell us what the work should be (e.g., set up an emergency preparedness operation center). Warren Friedman, HUD: Will send information regarding overcoming obstacles to implementing senior falls policies. Do you have enough data to indicate areas in which your program has been operating to address Rocky Mountain Spotted Fever? Has your approach been effective in reducing its prevalence? Yes, we do. Published reports on community-based work and surveillance. Regarding the effectiveness in reducing risk for rocky mountain fever, there are challenges in implementation and management that need to occur locally. Kitt Rodkey, HUD: will be following up with Stephen to get information on their outreach with Native American populations. How do you follow up with communities on lead? Bill Cibulas, ATSDR: Same follow up questions with lead. Have tribal councils pushed for testing in schools, including water? Screening that occurs by the clinics of the children is an indicator of the cases that exist amongst the children. Head Start performs routine testing to be conducted. Ruth Etzel, EPA: Is there a database that you keep of children's blood lead levels on Native lands? No, not that I am aware of. Sandra Howard, HHS: Does IHS have any recommendations for screening, apart from what is required by Medicaid and or by Head Start? That is out of the scope of work. Peter Ashley, HUD: Can you speak to trend in over-doses? Can you also speak to the causation between alcohol use and motor vehicle accidents? Seeing a new trend in over-doses. Poisoning is one of the top three causes of hospitalizations. Regarding the link between alcohol and motor vehicle accidents, we are comfortable in saying that it is a factor. We do have programs regarding alcohol and substance abuse. Sandra Howard, HHS: We understand that we cannot have one speaker (organization) talk on this issue. If there are other organizations that would like to present, please let us know. Some possible topics could be issues facing Alaska Native communities, lead exposure and Superfund sites (as they relate to tribes in general). 2 Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226

What is the fullform of NASDA?

fgcn0226

fgcn0226_p0, fgcn0226_p1, fgcn0226_p2, fgcn0226_p3, fgcn0226_p4, fgcn0226_p5, fgcn0226_p6, fgcn0226_p7, fgcn0226_p8

National Association of State Departments of Agriculture, The National Association of State Departments of Agriculture

To: Nitsch, lad[[email protected]] Cc: Wagner, Kenneth[[email protected]]; Bangerter, Layne[[email protected]] From: Davis, Patrick Sent: Thur 3/30/2017 11:52:54 AM Subject: Re: NASDA Commends EPA Decision on Chlorpyrifos Petition [WARNING: SPF validation failed] Thank you Sent from my iPhone On Mar 30, 2017, at 7:41 AM, Nitsch, Chad <[email protected]> wrote: Patrick, Ken, and Layne, Please see attached statement on chlorpyrifos from NASDA. Thank you, Chad Nitsch State and Regional Partnerships | Office of the Administrator Environmental Protection Agency 202-564-4714 From: Dudley Hoskins [mailto:[email protected]] Sent: Wednesday, March 29, 2017 9:06 PM To: Nitsch, Chad <[email protected]>, Osinski, Michael <[email protected]>;! Dexter, Michael <[email protected]>; Bowles, Jack <[email protected]>; Barbery, Andrea <[email protected]> Cc: Nathan Bowen <[email protected]> Britt Aasmundstad <[email protected]> Subject: Fwd: NASDA Commends EPA Decision on Chlorpyrifos Petition [WARNING: SPF validation failed] Source: https://www.industrydocuments.ucsf.edu/docs/fgcn0226_001225_00000021-00001 Chad -- wanted to thank you again for today's meeting (more soon from our end on that front). In the interim, we wanted to share the below NASDA press release supporting EPA's science-based decision to deny petitioner's request to revoke chlorpyrifos tolerances (please share with Layne, Patrick, Ken and others from today's meeting who I may have inadvertently left off or not have email contact in front of me). Please let us know if you all have any questions or would like to discuss further at any points. Many thanks for all that you do! - dudley Sent from my iPhone Begin forwarded message: From: Amanda Culp <[email protected]> Date: March 29, 2017 at 8:06:20 PM EDT Subject: NASDA Commends EPA Decision on Chlorpyrifos Petition FOR IMMEDIATE RELEASE: March 29, 2017 Contact: Amanda Culp Director, Communications (202)296-9680 [email protected] NASDA Commends EPA Decision on Chlorpyrifos Petition The National Association of State Departments of Agriculture (NASDA) today applauded the U.S. Environmental Protection Agency's (EPA) decision to decline a petition to revoke tolerances for chlorpyrifos, which is integral for crop protection, Source: https://www.industrydocuments.ucsf.edu/docs/fgcn0226 001225 00000021-00002 including resistance management and integrated pest management (IPM) in more than 100 countries. NASDA President and Louisiana Commissioner of Agriculture & Forestry Dr. Mike Strain praised the EPA for sticking to its rigorous, scientific risk assessment and registration review process for crop protection tools. "We commend the EPA for its decision today that keeps an important insecticide available for farmers. By maintaining the Maximum Residue Limits (MRLs) for chlorpyrifos, agricultural use of this important tool will continue, significant disruption of international trade is avoided, and harmonization efforts may continue globally. As state regulatory partners with EPA, we look forward to continuing to work with the Agency to ensure current and future tools are reviewed in a rigorous, scientifically sound, and transparent manner." NASDA submitted comments to EPA in January 2016 requesting the Agency reevaluate its proposed tolerance revocations in compliance with the law and regulations that mandate a science-based review. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. NASDA grows and enhances agriculture by forging partnerships and creating consensus to achieve sound policy outcomes between state departments of agriculture, the federal government, and stakeholders. Learn more about NASDA at www.nasda.org. ### <Chlorpyrifos_EPA_03292017.pdf> Source: https://www.industrydocuments.ucsf.edu/docs/fgcn0226 001225_00000021-00003 To: Davis, Patrick[[email protected]]; Wagner, Kenneth[[email protected]] Bangerter, Layne[[email protected]] From: Nitsch, Chad Sent: Thur 3/30/2017 11:41:48 AM Subject: FW: NASDA Commends EPA Decision on Chlorpyrifos Petition [WARNING: SPF validation failed] Chlorpyrifos EPA 03292017.pd Patrick, Ken, and Layne, Please see attached statement on chlorpyrifos from NASDA. Thank you, Chad Nitsch State and Regional Partnerships I Office of the Administrator Environmental Protection Agency 202-564-4714 From: Dudley Hoskins [mailto:[email protected]] Sent: Wednesday, March 29, 2017 9:06 PM To: Nitsch, Chad <[email protected]>; Osinski, Michael <[email protected]>; Dexter, Michael <[email protected]>; Bowles, Jack <[email protected]>; Barbery, Andrea <Barbery [email protected]> Cc: Nathan Bowen <[email protected]>: Britt Aasmundstad <[email protected]> Subject: Fwd: NASDA Commends EPA Decision on Chlorpyrifos Petition [WARNING: SPF validation failed] Chad -- wanted to thank you again for today's meeting (more soon from our end on that front). In the interim, we wanted to share the below NASDA press release supporting EPA's science- based decision to deny petitioner's request to revoke chlorpyrifos tolerances (please share with Source: https://www.industrydocuments.ucsf.edu/docs/fgcn0226 001225 00000022-00001 Layne, Patrick, Ken and others from today's meeting who I may have inadvertently left off or not have email contact in front of me). Please let us know if you all have any questions or would like to discuss further at any points. Many thanks for all that you do! - dudley Sent from my iPhone Begin forwarded message: From: Amanda Culp <[email protected]> Date: March 29, 2017 at 8:06:20 PM EDT Subject: NASDA Commends EPA Decision on Chlorpyrifos Petition FOR IMMEDIATE RELEASE: March 29, 2017 Contact: Amanda Culp Director, Communications (202)296-9680 [email protected] NASDA Commends EPA Decision on Chlorpyrifos Petition The National Association of State Departments of Agriculture (NASDA) today applauded the U.S. Environmental Protection Agency's (EPA) decision to decline a petition to revoke tolerances for chlorpyrifos, which is integral for crop protection, including resistance management and integrated pest management (IPM) in more than 100 countries. NASDA President and Louisiana Commissioner of Agriculture & Forestry Dr. Mike Strain praised the EPA for sticking to its rigorous, scientific risk assessment and registration review process for crop protection tools. Source: https://www.industrydocuments.ucsf.edu/docs/fgcn0226 001225 00000022-00002 "We commend the EPA for its decision today that keeps an important insecticide available for farmers. By maintaining the Maximum Residue Limits (MRLs) for chlorpyrifos, agricultural use of this important tool will continue, significant disruption of international trade is avoided, and harmonization efforts may continue globally. As state regulatory partners with EPA, we look forward to continuing to work with the Agency to ensure current and future tools are reviewed in a rigorous, scientifically sound, and transparent manner. NASDA submitted comments to EPA in January 2016 requesting the Agency reevaluate its proposed tolerance revocations in compliance with the law and regulations that mandate a science-based review. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. NASDA grows and enhances agriculture by forging partnerships and creating consensus to achieve sound policy outcomes between state departments of agriculture, the federal government, and stakeholders. Learn more about NASDA at www.nasda.org. ### Source: https://www.industrydocuments.ucsf.edu/docs/fgcn0226 001225 00000022-00003 Contact: FOR IMMEDIATE RELEASE Amanda Culp March 29, 2017 Director, Communications (202) 296-9680 [email protected] NASDA Commends EPA Decision on Chlorpyrifos Petition The National Association of State Departments of Agriculture (NASDA) today applauded the U.S. Environmental Protection Agency's (EPA) decision to decline a petition to revoke tolerances for chlorpyrifos, which is integral for crop protection, including resistance management and integrated pest management (IPM) in more than 100 countries. NASDA President and Louisiana Commissioner of Agriculture & Forestry Dr. Mike Strain praised the EPA for sticking to its rigorous, scientific risk assessment and registration review process for crop protection tools. "We commend the EPA for its decision today that keeps an important insecticide available for farmers. By maintaining the Maximum Residue L imits (MRLs) for chlorpyrifos, agricultural use of this important tool will continue, significant disruption of international trade is avoided, and harmonization efforts may continue globally. As state regulatory partners with EPA, we look forward to continuing to work with the Agency to ensure current and future tools are review ed in a rigorous, scientifically sound , and transparent manner." - NASDA submitted comments to EPA in January 2016 requesting the Agency reevaluate its proposed tolerance revocations in compliance with the law and regulations that mandate a science-based review. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. NASDA grows and enhances agriculture by forging partnerships and creating consensus to achieve sound policy outcomes between state departments of agriculture, the federal government, and stakeholders. Learn more about NASDA at www.nasda.org. ### National Association of State Departments of Agriculture NASDA 4350 North Fairfax Drive #910 Arlington, VA 22203 Tel: 202-296-9680 www.nasda.org Source: https://www.industrydocuments.ucsf.edu/docs/fgcn0226 001225 00000023-00001 To: Bangerter, , Layne[[email protected]] From: U.S. EPA Media Relations Sent: Wed 3/29/2017 10:35:49 PM Subject: EPA Administrator Pruitt Denies Petition to Ban Widely Used Pesticide CONTACT: [email protected] FOR IMMEDIATE RELEASE March 29, 2017 EPA Administrator Pruitt Denies Petition to Ban Widely Used Pesticide Today, U.S. Environmental Protection Agency (EPA) Administrator Scott Pruitt signed an order denying a petition that sought to ban chlorpyrifos, a pesticide crucial to U.S. agriculture. "We need to provide regulatory certainty to the thousands of American farms that rely on chlorpyrifos, while still protecting human health and the environment," said EPA Administrator Pruitt. "By reversing the previous Administration's steps to ban one of the most widely used pesticides in the world, we are returning to using sound science in decision-making - rather than predetermined results.' "This is a welcome decision grounded in evidence and science," said Sheryl Kunickis, director of the Office of Pest Management Policy at the U.S. Department of Agriculture (USDA). "It means that this important pest management tool will remain available to growers, helping to ensure an abundant and affordable food supply for this nation and the world. This frees American farmers from significant trade disruptions that could have been caused by an unnecessary, unilateral revocation of chlorpyrifos tolerances in the United States. It is also great news for consumers, who will continue to have access to a full range of both domestic and imported fruits and vegetables. We thank our colleagues at EPA for their hard work." In October 2015, under the previous Administration, EPA proposed to revoke all food residue tolerances for chlorpyrifos, an active ingredient in insecticides. This proposal was issued in response to a petition from the Natural Resources Defense Council and Pesticide Action Network North America. The October 2015 proposal largely relied on certain epidemiological study outcomes, whose application is novel and uncertain, to reach its conclusions. The public record lays out serious scientific concerns and substantive process gaps in the proposal. Reliable data, overwhelming in both quantity and quality, contradicts the reliance on - and misapplication of - studies to establish the end points and conclusions used to rationalize the proposal. The USDA disagrees with the methodology used by the previous Administration. Similarly, the National Association of State Departments of Agriculture also objected to EPA's methodology. The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP) also expressed concerns with regard to EPA's previous reliance on certain data the Agency had used to support its proposal to ban the pesticide. The FIFRA SAP is a federal advisory committee operating in accordance with the Federal Advisory Committee Act and established under the provisions of FIFRA, as amended by the Food Quality Protection Act of 1996. It provides scientific advice, information and recommendations to the EPA Administrator on pesticides and pesticide-related issues regarding the impact of regulatory decisions on health and the environment. Source: https://www.industrydocuments.ucsf.edu/docs/fgcn0226 001225 00000024-00001 To view the petition: https://www.epa.gov/pesticides R044 If you would rather not receive future communications from Environmental Protection Agency, let us know by clicking here. Environmental Protection Agency, 1200 Pennsylvania Avenue NW, Washington, DC 20460 United States Source: https://www.industrydocuments.ucsf.edu/docs/fgcn0226 001225_00000024-00002

what is the given dail-in number ?

prbn0226

prbn0226_p0, prbn0226_p1, prbn0226_p2, prbn0226_p3, prbn0226_p4, prbn0226_p5, prbn0226_p6

1-866-299-3188

001 From: Wexier. Philip To: Farland, William H.: Susie "Masten; Dourson. Michael (doursomi); jeffrey.jenkins ([email protected]); Beck, Nancy: David Steup; [email protected] Cc: [email protected] Subject: Kids + Chemical Safety Date: Thursday, August 17, 2017 4:00:21 PM Attachments: Re President"s Task Force on Environmental Health Risks and Safety Pisks to Children Final Agenda and Meeting Materials for the August 17 Senior Staff Steering Committee Meeting mso RE President"s Task Force on Environmental Health Risks and Safety Risks to Children Final Agenda and Meeting Materials for the August 17 Senior Staff Steering Committee Meeting msg Bill - This seems like a worthwhile and relevant addition to the TEF site. I am wondering whether the Experts that were used would still be available to reply to questions from the public. There are some other groups working on children's environmental health and it strikes me that it might not hurt to try to link to them and/or coordinate efforts with them and/or get their take on the Kids + Chemical safety site and/or convene a conference call to at least share our respective perspectives on this issue. I am thinking specifically of: EPA's Office of Children's Health Protection (Ruth Etzel heads this up) and their main Web site addressing this issue - bttos://www.epa.gov/children Children's Environmental Health Network (CEHN) - http://cehn.org/ - Among other things, they were instrumental in the formation of an annual Children's Environmental Health Day, October 12, this year (see htto:/lcehn.org/cehdav/) Pediatric Environmental Health Specialty Units - http:llwww.pehsu.net/ - I met and subsequently exchanged a series of emails early this year with Jerry Paulson who is Medical Director for this program. He was enquiring about making their information somehow available via NLM but there didn't seem to be any interest here in following up. My last email to him was just prior to the SOT meeting. I directed him to the TEF site and asked if he thought this might be an alternative place for highlighting the PEHSUs but never heard back from him. Might be worth checking in with him again. President's Task Force on Environmental Health Risks and Safety Risks to Children (httos://otfceh.niehs.nib.gov/). - I have actually been on the mailing list for their (monthly?) meetings for some time (not sure why) and they periodically sent out announcements. I haven't really participated. There was, in fact, a meeting today. See attached emails. Anyway, just thought l'd itemize a few of the other activities going on in this area and reiterate that if TEF gets into the children's environmental health arena, it might be good to keep up with what's going on elsewhere. - Phil P.S. I have been getting some TEF email at my personal email address. Please correspond with me at Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 002 this, my office, address ([email protected]/ instead. Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 From: Coopwood, Theodore To: Howard Sandra (OS/OASH); Liv, Chanva (OS/OASH); Bizel. Buth Cc: Smith Kimberly (HHS'OASH); Jonas, Lori (ENRD); Alice Thaler; Amy Bodette; Andrea Grossman; Andrea Falken; Beverly Samuel; Birnbaum. Linda (NIH/NIEHS) (El; Brown, Sheila; Brevsse Patrick N. (CDC/ONDI EH/NCEH): Bruce. D [email protected] Chaney, Sascha LCDCIONDIEH/NCBDDD); Trent, Chris B; Obulas, William (ATSDR/OADS); Danielle Jones Powson, David; [email protected]: Eric Rosenfield; Erio Waldo; Erica Burrin; Frin Hoffman; Held. Sarah (DHHS/OS/OASH: Freemer. Michelle (NIH/NHLBI) Luber. George (COC/ONDIEH/NCEH): Herbert Bolton; James H [email protected]; Balbus, John (NIH/NIEHS) (E); Joshua Olsen; Judy Harvey; [email protected] Kiley, James (NIH/NHLBI)[E]: Co: Rodkey, Kitt; Lee Caron Lucas Radzinschi; Mark Glaze; Miller, Mark Berger, Martha; Matt Ammon; Michael Babich; Miller, Aubrey (NIH/NIEHS) LEI; Mortensen, Mary E (CDO/ONDIEH/NCEH); Peter Ashley; Roonev. Andrew (NIH/NIEHS) LEI; Sara Newman; Foster, Stiven; Fitzpatrick. Suzanne (FDA/CFSAN); Thigpen Tart, Kimberly (NIH/NIEHS) (El: Warren Friedman; Wexler. Philip (NIH/NLMLI Yasmin a Sani; Blandine Trouille; Broehm. Jason (OST): Goldsmith. Reese (ENRD); Shah, Manthan; Firestone, Michael; Smith. Kimberly (HHS/OASH); Ettinger, Adrienne (CDC/ONDIEH/NCEH); Nevel Amy (HHS/ASPE); [email protected] Hackel, Angela; Hauff. Amanda; Reed. Khesha; Jonas, Lori (ENRD); Lias. Courtney H.(FDA/CDRH); Brown. Sheila: Ricks, Sharon L (HHS'OASH); AGELLER@@hsph.harvard.edu Subject: Re: President"s Task Force on Environmental Health Risks and Safety Risks to Children: Final Agenda and Meeting Materials for the August 17 Senior Staff Steering Committee Meeting Date: Wednesday, August 16, 2017 6:35:38 AM Attachments: Agenda for the August 2017 Senior Steering Committe Meeting 8-16-17.docx Draft President"s Task Force Summary Notes Julv. 31.2017.doc Smoke free research 612lessonslearnedpart1.(2).do HUD Smoke free Home Presentation 8-16-17.pptx PTF Short Term Work Plan Actions Accommplishments Report 8-10-17 -clean version docx Good Morning, Attached are the final agenda and meeting materials for tomorrows Senior Staff Steering Committee meeting for the President's Task Force on Environmental Health Risks and Safety Risks to Children. The meeting time is 1:00pm and the location is the HHS Hubert Humphrey Building, 200 Independence Avenue S.W. room 325-A. The dial-in number is 866-299- 3188 and the participant code is 202-564-2754. If you are participating in person and have not informed me, please let me know by COB today. The point of contact if you have trouble entering the building is Chanya Liv at: 202-690-2470 Attached Meeting Materials Agenda for the August 17, 2017 Senior Staff Steering Committee Meeting Draft President's Task Force (PTF) Summary Notes from the July 2017 Meeting Smoke Free Homes Research Lessons Learned Document Slides for Smoke Free Housing Research Presentation Short Term Accomplishments Report Thanks in advance for your participation in the meeting. Ted Ted Coopwood Office of Children's Health Protection US EPA Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 1301 Constitution Ave. NW Washington, DC 201460 202-564-2197 [email protected] Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 For Internal Federal Partner Use Only-Please Do Not Cite or Quote President's Task Force on Environmental Health Risks and Safety Risks to Children Senior Steering Committee Meeting Thursday August 17, 2017 1:00pm - 3:00pm EST HHS Hubert Humphrey Building -Room 325A 200 Independence Avenue, SW Dial-In: 1-866-299-3188, Passcode: 202-564-2754 AGENDA I. Welcome 1:00PM - -1:03PM Ruth Etzel, EPA and Sandra Howard, HHS II. Roll call 1:03PM - -1:05PM Ted Coopwood, EPA III. Minutes and Action Items from July Steering Committee Meeting 1:05PM -1:10PM (Attachment) Ruth Etzel, EPA and Sandra Howard, HHS IV. Subcommittee Updates - Lead Subcommittee Update 1:10PM - 1:20PM Michael Firestone, EPA, Warren Friedman, HUD, Adrienne Ettinger, HHS (Other Subcommittees have no updates) VI. Other Agency Updates and Discussion Items 1:20PM - 1:40PM - Draft Work Plan Short Term Actions Accomplishments Report (Attachment) Ted Coopwood, EPA VII. Summary of Action items 1:40PM - 2:00PM VIII. Smoke Free Housing Research Presentation 2:00PM- - 2:30PM (Attachment) Alan Geller, Harvard University Adjourn Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 For Internal Federal Partner Use Only - Please Do Not Cite or Quote President's Task Force on Environmental Health Risks and Safety Risks to Children Senior Staff Steering Committee Meeting Draft Summary Notes for Thursday July 20, 2017 1:00pm - 3:00pm ET Meeting Participants HUD: Kitt Rodkey, Warren Friedman CPSC: Michael Babich EPA: Ruth Etzel, Manthan Shah, Angela Hackel, Amanda Hauff, Michael Firestone, Miranda Mitchell HHS/OASH: Sandra Howard, Sarah Field, Chanya Liv IHS: Stephen Piontkowski CDC/NCEH and ATSDR: Adrienne Ettinger, Bill Cibulas FDA: Suzanne Fitzpatrick NIH/NIEHS: Kimberly Thigpen-Tart, Andy Rooney NIH/NHLBI: Michelle Freemer OMB: Eric Rosenfield DOJ: Lori Jonas DOL: Tiffany Defoe Welcome and Roll call Ruth Etzel (EPA) and Sandra Howard (HHS) welcomed all members of the Steering Committee and Angela Hackel (EPA) conducted the roll call. Minutes and Action Items from the June Steering Committee Meeting The meeting minutes and action items from the June 2017 meeting were approved. Ted Coopwood (EPA) will distribute the approved minutes to the Senior Staff Steering Committee Members. Children's Environmental Health in Indian Country; Stephen Piontkowski, Indian Health Service A PowerPoint presentation was shared with the Senior Staff Steering Committee prior to the meeting. The Division of Environmental Health Services (DEHS) is part of the Office of Environmental Health and Engineering at the Indian Health Service (IHS). More than 70% of the DEHS staff work in tribal country, 20% work in an HHS Region, and 10% serve in administrative roles. DEHS monitors health through community injury and disease surveillance. Conducts public outreach about preventative health measures. Provides training and mobilizes partnerships. Works with emergency preparedness partners and addresses outbreaks. Evaluates effectiveness of services and interventions. Five focus areas include: children's environment, food safety, safe drinking water, vectorborne and communicable diseases, and healthy homes. Children's environmental health is a top priority (schools, Head Start, indoor air quality, fire safety, playground safety, injury prevention). Unintentional injuries are a leading cause of death. Motor vehicle crashes was noted as a leading injury type. To address this issue at a national level, car seat success stories are shared to illustrate a large body of work that has been done for traffic safety. Plus, the "Seatbelts. Just Wear 'em" campaign was launched. The campaign has been shown to be effective at reducing motor vehicle crashes. 1 Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226 For Internal Federal Partner Use Only - Please Do Not Cite or Quote Regional initiatives include Rocky Mountain Spotted Fever in Arizona Tribal and state/federal partners (CDC) work together. 250 human cases, 20 fatalities; children under age of 10 most impacted. Cost of outbreak is $13.2 million and includes clinical-based response and community-based response. Local concerns include referrals for children's health issues. These include upper respiratory problems related to mold and elevated lead levels. Partnerships are important. DEHS works with tribal customers hand-in-hand and with state/county/federal partners. Questions/Conversation Ruth Etzel, EPA: How do you prioritize the local work? For example, how do you figure out which tribes have lead as a priority? Priorities are conducted at the national, regional and local level. When it comes to non-facility based work, we utilize the public health approach and make decisions based on the data. In some cases, people (the local tribal council) tell us what the work should be (e.g., set up an emergency preparedness operation center). Warren Friedman, HUD: Will send information regarding overcoming obstacles to implementing senior falls policies. Do you have enough data to indicate areas in which your program has been operating to address Rocky Mountain Spotted Fever? Has your approach been effective in reducing its prevalence? Yes, we do. Published reports on community-based work and surveillance. Regarding the effectiveness in reducing risk for rocky mountain fever, there are challenges in implementation and management that need to occur locally. Kitt Rodkey, HUD: will be following up with Stephen to get information on their outreach with Native American populations. How do you follow up with communities on lead? Bill Cibulas, ATSDR: Same follow up questions with lead. Have tribal councils pushed for testing in schools, including water? Screening that occurs by the clinics of the children is an indicator of the cases that exist amongst the children. Head Start performs routine testing to be conducted. Ruth Etzel, EPA: Is there a database that you keep of children's blood lead levels on Native lands? No, not that I am aware of. Sandra Howard, HHS: Does IHS have any recommendations for screening, apart from what is required by Medicaid and or by Head Start? That is out of the scope of work. Peter Ashley, HUD: Can you speak to trend in over-doses? Can you also speak to the causation between alcohol use and motor vehicle accidents? Seeing a new trend in over-doses. Poisoning is one of the top three causes of hospitalizations. Regarding the link between alcohol and motor vehicle accidents, we are comfortable in saying that it is a factor. We do have programs regarding alcohol and substance abuse. Sandra Howard, HHS: We understand that we cannot have one speaker (organization) talk on this issue. If there are other organizations that would like to present, please let us know. Some possible topics could be issues facing Alaska Native communities, lead exposure and Superfund sites (as they relate to tribes in general). 2 Source: https://www.industrydocuments.ucsf.edu/docs/prbn0226

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145 From: Jürgen Troitzsch To: Dr. Wise Kimberly Cc: Admon. Smadar: Anderson Steven; Batoon, Audrev; Dr. Bradley Kevinx; de Lacy, Catharine: Elkan. Illan; Eraguntla, Neeraia: Goodman, Bryan; Hochschwender. Lane; Jacobi Svivia; Kannah Kasturirangan; Levan Steve; Leychik. Sergei; Little, Barbara; Manor, Orit; Prero, Judah; Dr. Rothenbacher Klaus; Saunders, Eric L.; Scherrer Stephen; Simon. Robert; Tavior Jennifer; Tenney Joel; Thorn. Amelia; West, Jav; Dr. Haves Wallace; Prof. Rein Guillermo; Dr. Blais Matthew; Dourson. Michael (doursoml); Kacew. Sam; Osimitz Thomas Subject: Re: For Review - Draft Record from May 2017 SAC Meeting Date: Sunday, June 4, 2017 10:05:03 AM Attachments: SAC ROM 05-16-17 and 05-17-17 - Draft doc Program 2017, pdf 170817AbsFurnitureFiresafety.do Dear Kimberly, Please find attached my comments to the meeting record, the program of the Copenhagen conference and my abstract. Kind regards/Viele Grüße Jürgen Dr. Jürgen Troitzsch Fire and Environment Protection Service FEPS Via Patrizia 32 CH-6612 Ascona, Switzerland Mobile: +41 79 289 17 16 Phone: +41 91 791 14 22 Email: [email protected] Web: www.troitzsch.com Am 02.06.2017 um 13:56 schrieb White, Kimberly <Kimberly [email protected]> Dear NAFRA, BSEF and SAC members: Attached is the record from the May 2017 Science Advisory Council meeting. Please review by June 9th and let me know if you have any additions or corrections. Kind Regards, Kimberly Wise White, Ph.D. | American Chemistry Council Senior Director, Chemical Products & Technology Division [email protected] Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 Furniture Fire Properties And Their Importance For Domestic Fire Safety Juergen H. Troitzsch Fire and Environment Protection Service FEPS Ascona, Switzerland [email protected] Keywords: Fire statistics, furniture regulations, reaction to fire stakeholders regarding adequate fire safety, the proposal was tests, barriers, flame retardants withdrawn. A second version is now under consideration and it Fire statistics show that residential fires caused by is unclear when the amended regulations will come in to force. upholstered furniture have continuously decreased in the U.S. These approaches have led to search for other possibilities /California and the UK in the last 20 years. This is due to to ensure adequate fire safety levels for upholstered furniture. stringent fire safety regulations and tests mandatory for Contrary to the past, where ignition and flammability tests upholstered furniture in these countries. However, upholstered were used to define fire safety. now the reduction of the heat furniture still remains the leading item first ignited by low release rate is seen as the key fire property most strongly energy ignition sources such as cigarettes, matches, lighters influencing fire hazard. and candles 1. A study on "Alternative strategies to the use of chemical The classical way to meet high fire safety requirements for flame retardants" 4 has shown that various combinations of upholstered furniture is to improve the fire safety level of its cover materials and fire barriers to protect flexible components by using flame retarded flexible polyurethane polyurethane foam can reduce the heat release rate of the foam, barriers and covers. systems tested and improve fire safety. With the exception of In recent years, due to health and environment concerns an intrinsically flame retarded (FR) polyester cover, no other about the use of certain flame retardants, California revised the components used contained conventional flame retardants. CA TB 117 cigarette test 2 used for upholstered furniture in the Another, earlier study on "upholstered furniture private domain. The former additional small flame test required flammability" 5 investigated the fire performance of different was eliminated because flame retardants had to be used to meet FR/non-FR barrier materials and flexible polyurethane foams it. with a non-FR polyester cover in material-level, mock-up and The new CA TB 117 only addresses smoldering fires, while full-size furniture experiments. The results showed that the fires associated with flaming ignition, which according to flame retarded barrier materials were very effective in reducing NFPA lead to an appreciable amount of fatalities, are no more heat release rate and, particularly in the full-size experiments, considered. Therefore, NFPA has been asked to develop a the fire growth rate of the upholstered chairs. flaming-ignition test for upholstered furniture and is currently These studies show that the best way to reduce the heat working on its own open-flame test to NFPA 277 3 based on release rate of upholstered furniture and to optimize fire safety heat release rate measurement. is the use of flame retarded fire barriers and covers. Adequate In Great Britain, "The Furniture and Furnishings (Fire fire barriers including the use of flame retardants based on the Safety) Regulations' address compulsory fire safety U.S. EPA Design for the Environment (DfE) alternatives requirements for upholstered furniture in private homes. In assessment method will help to enhance domestic fire safety 2014, the authorities proposed an alternative match test to and reduce the number of fatalities, injuries and property losses. simplify the regulation and to reduce levels of flame retardants in furniture without impacting on the current fire safety levels. Here, contrary to the California approach, the cigarette test was to be eliminated and only gas flames and the BS 5852 crib 5 tests remained. However, following strong concerns from the 1 J. Troitzsch, "Fires, statistics, ignition sources, and passive fire protection REFERENCES measures", Journal of Fire Sciences, 2016, 1-28. DOI: 10.1177/07349041 2 Technical Bulletin 117-2013 Requirements, Test Procedure and Apparatus for Testing the Smolder Resistance of Materials Used in Upholstered 4 K. Storesund, A. Steen-Hansen and A. Bergstrand, "Fire safe upholstered Furniture. January 2013 furniture. Alternative strategies to the use of chemical flame retardants," 3 Proposed Standard NFPA 277: Standard Methods of Tests for Evaluating SPFR Report A15 20124:2, December 2015. Fire and Ignition Resistance of Upholstered Furniture Using a Flaming 5 T. Fabian, "Upholstered furniture flammability,' Underwriters Laboratories Ignition Source Inc., Jul. 2013. Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 NFSD Nordic Fire & Safety Days Programme Day 1, 17th Augusti 2017 no Colico and Registration Welcome to the Nardini are and Safety Days Room: ACM15 Anne Dederichs 10.00 Key Leature Room: ACM15 Furniture fire properties and their importance for domestic fire safety. Dr. Jürgen Troitzsch, FEPS, Switzerland Panal Discussion Room: ACM15 Session Chair: Björn Sundström, SP Furniture fire properties and their importance for domestic fire safety. Dr. Jürgen Troitzsch, FEPS, Switzerland Egil Sundet, Head of the Sector furniture, interior and design for the federation of Norwegian Industry Dr. David Santillo, Honorary Research Fellow at Greenpeace Research Laboratories, Exeter University, UK, Dr. Anne Elise Steen-Hansen, Research manager at SP Fire Research, Norway Dr. Björn Karlsson, Professor at Iceland University and the Director General at Iceland Construction Authority. A! ********* - ****** NTNU 1 LUND of ****** ******** ******** DBI Source: https://wwww.industrydocuments.ucsf.edu/docs/gybn0226 NFSD Nordic Fire & Safety Days Parallet Session A Fire Dynamics 1 Risk 1 Evacuation Room: ACM15 1.001 Room: ACM15 1.008 Room: FKJ 12 0.06 Session Chair: Session Chair: Session Chair: Tuula Hakkarainen Frank Markert 11.00-11.15 Fire protection of Modelling approach for The effect of plattform- extensive green roofs the threat quantification and tunnel design on the A. Elias of cascading failures evacuation performance A. Helminen, T. of wheelchair users - A Hakkarainen qualitative study Eva-Sara Karlsson 11.20-11.35 USCG Fire simulation of Developing a risk and Reaction and decision water mist suppression capability assessments time of evacuees - A study using an ignition source methodology for the Baltic regarding the influence of E. A. Kolstad, B. P. Husted, Sea Region alcohol on the reaction LU - B. Karlsson and decision time P. B. Rask, A. Dederichs 11.40-11.55 Development tool for Fire safety decision Awareness of fire risk ETICS façade fire testing making under a systems- reduction among Cyprus M.S. McLaggan, M. theoretic safety paradigm international university Meinert, A. Dragsted, P. -H. Bjelland, O. Njã, A. (CIU) students van Hees W.Heskestad, G. S. Braut A. F. Gyasi 1000 Lunch 2 Exhibition the DO Parallal R Fire Dynamics 2 Fire safety science Transportation without borders Room: ACM15 1.001 Room: ACM15 1.008 Room: FKJ 12 0.06 Session Chair: Session Chair: Session Chair: Frida V Lundström Martyn S. McLaggan 13.00-13.15 Desensitisation of optical Fire safety science without Ventilation in tunnels: a flame detection in harsh borders numerical comparison external environments T., between different J. McNay K. H. Almand modelling approaches -P. Matteo 13.20-13.35 Heat release Fire safetys contribution Fire detection in engine characteristics of ethanol- to a sustainable society compartments - P. water mixtures T., Karlsson, O. Willstrand T. Hakkarainen K. H. Almand, NFPA 13.40-13.55 Fire-induced pressures in Det store brannlöftet - Verifying fire safety in tall modern airtight Dag Botnen timber buildings apartment building Fredrik Nystedt S. Hostikka Johan Norén 14 00 3 Enhibition OTU A! II'II ********* - - NTNU a 2 Landa of ******** ******** ******** 081 Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 NFSD Nordic Fire & Safety Days Parallet C Fire Dynamics 3 Fire Safety Engineering 1 Brokerage Event 1: Carpark fires Room: ACM15 1.001 Room: ACM15 1.008 Room: FKJ 12 0.06 Session Chair: Session Chair: Session Chair: Ulf Wickström Michael Stömgren 14.45- Measuring incident Performance based design and compilande Luisa Giuliani 15:00 heat flux and M. Strömgren adiabatic surface temperature with platse thermometers in ambient and high temperatures U. Wickström, J. Anderson, J. Sjöström 15.05- Modelling and Wildlandfires, F.V.Lundström, P. Andersson 15.20 stochastic analyses of travelling fires R. K. Janardhan, S. Hostikka 15.25-40 Photovoltaic A discussion on learning from fire installations on investigations; concepts and methodologies warehouse buildings - an experimental A. Borg, O. Njã study of the propagation of fire - J. Steemann Kristensen Conference 3 Exhibition Affer conferenze dinner OTU A! IIIII ********* - - - NTNU a 3 Luno of ******** ******** ******** 081 Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 NFSD NordicFire & Safety Days Programme Day 2, 18th August 2017 20.02.40 Welcome Key Leaure Room: ACM15 Fire brigade intervention method - accounting for the actions of the fire service Ed Claridge, Principal Fire Engineer, Auckland, New Zealand Pana Discussion Room: ACM15 Session Chair: Fire brigade intervention-accounting for the actions of the fire service Ed Claridge, Principal Fire Engineer, Auckland, New Zealand Rasmus Storgaard Petersen, CEO Emergency Service East, Denmark Cecilia Daae, Director of Directorate for Civil Protection and Emergency Planning, Norway Mia Kumm, Licentiate of engineering and researcher at SP/Rise and Mälardalen University, Sweden A! II-II: ********* - ****** - NTNU a 4 Luwo ****** DBI Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 NFSD Nordic Fire & Safety Days Parallel Session D Management of rescue Risk 2 Structural Fire Safety 1 service 1 Room: ACM15 1.001 Room: ACM15 1.008 Room: FKJ 12 0.06 Session Chair: Session Chair: Session Chair: 11.00-11.15 Accounting for the actions Resilient Buildings C-Fort, Risk analysis and of the rescue service - M. Kumm performance-based rescue from heights. structural fire expertise of Christian Ramm a semi-buried railway station - E. Tonicello, S. Deshanghere 11.20-11.35 Environmental impact of Firesafe - Study Experimental study on the structure fires and fire investigating cost effective mechanical properties of service response measures for reducing the fire exposed concrete F. Amon, L. Vylund risk from fires on ro-ro A. Zawadowska, L. passanger ships Giuliani, K. D. Hertz - J. Wikman, M. Rahm, F. Evegren, J. Leroux, A. Breuillard, M. Kjellberg, L. Gustin, F. Efraimsson 11.40-11.55 Part time firemen and False alarm - An Fire protection of wooden community resilience organizational study of houses in several floors -P. Almklov, M. Nilsen, G. the effects of false alarms J. N. Olsen, H. S.Fishman Gjøsund G. Gjøsund Petter Almklov Christian Sesseng Lundh R OTU A! IIIII ********* - - - *** - - NTNU " 5 Luno of ******** ******** ******** 081 Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 NFSD Nordic Fire & Safety Days Parallel R Management of rescue Fire safety engineering 2 Structural Fire Safety 2 service 2 Room: ACM15 1.001 Room: ACM15 1.008 Room: FKJ 12 0.06 Session Chair: Session Chair: Session Chair: 13.00-13.15 Security officers 99 years of standard fire - Furnace setup for responding to residential success of failure? preliminary fire resistance fire alarms: modelling the R. Jansson McNamee testing - effect on survival and P. Hejtmánek, V. Flídr, H. property damages Najmanová B. Sund, H. Jaldell 13.20-13.35 Three different fire Investigation of suppression approaches A swedish approach to eurocodes design used by Fire and Rescue define a standard for fire fires and national services safety design in BIM deviations- F. S. Särdqvist F. Nystedt, J. Norén Clausen, L. Giuliani 13.40-13.55 An operationalization of Nordic standard for Material capabilities for fire and review & control of fire modeling of rescue operations safety engineering concrete under M. Runefors F. Nystedt, J. Norén, M. compression and Strömgren high temperatures - A. F. Damkjaer, L. Giuliani, K. D. Hertz Coffee 3 Exhibition OTU A! IIIII ********* - - - *** - - NTNU " 6 Luno of ******** ******** ******** 081 Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 NFSD Nordic Fire & Safety Days Parallel Sersion : Residential Fires 1 Fire safety engineering 3 Fire Dynamics 4 Room: ACM15 1.001 Room: ACM15 1.008 Room: FKJ 12 0.06 Session Chair: Session Chair: Session Chair: 14.45-15.00 Socioeconomic Learning points from real Smouldering fires in wood differences in residential incidents - pellets: the effect of fire mortality in Sweden: a learning from what?- - M. varying the airflow case-control study Bøhm, Metropolitan V. R. Valdés,R. F. Mikalsen, A. Jonsson University College A. Steen-Hansen O.Njã, U. Stavanger 15.05-15.20 Fire fatalities in Norway Simulation of smouldering K. Storesund, C. Sesseng, combustion based on A. Steen-Hansen Integration of fire multi-layer cellular engineering tools and automata- calculation methodologies V. R. Valdés,R F. Mikalsen, P. Tofilo A. Steen-Hansen 15.25-15-40 Has fire-related mortality Learning fire and rescue Aerosols from smoldering in Sweden changed over work by experience- E. Villacorta time? - E. Lindahl, J. sharing Hedberg Ava Sadeghi OTU A! IIIII ********* - - - *** - - NTNU " 7 Luno of ******** ******** ******** 081 Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 NFSD Nordic Fire & Safety Days Paralial to Residential Fires 2 Structural Fire Safety 3 Fire Dynamics 5 Room: ACM15 1.001 Room: ACM15 1.008 Room: FKJ 12 0.06 Session Chair: Session Chair: Session Chair: Residential fires in On analysing structures USCG Fire simulation of Denmark based solely on human water mist suppression P.B. Gummesen safety using an ignition source A.S. Dederichs, RISE, DTU J.Sandström, J. Thor, R. Einar Arthur Kolstad Jansson McNamee,0. Bjarne P. Husted Lagerqvist, U.Wickström Residential fire solutions Post-earthquake Validation of FDS on the in the building sector fire behavior of SP retail store steel frames - Shamim Ahmed Bjarne P. Husted Part I: Collapse Mechanism - G. Risco, L. Giuliani, V. Zania Towards an evidence- Post-earthquake fire Validation of sub-grip based vision zero policy behavior of steel frames - scale particle model for on residential fires - an Part II: The effect of the cable fire spread update - R. Andersson insulation - A. Wrobel, , L. T. Sikanen, A. Matala, S. A. Jonsson Giuliani, V. Zania Hostikka Brokerage Event 2: Modern Building Fires Session Chair: Anne Dederichs Lars Schiøtt Sørensen, DTU OTU A! IIIII ********* - - - *** - - NTNU " 8 Luno of ******** ******** ******** 081 Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 AMERICAN CHEMISTRY COUNCIL NORTH AMERICAN FLAME RETARDANT ALLIANCE (NAFRA), BROMINATED SCIENCE ENVIRONMENTAL FORUM (BSEF) AND SCIENCE ADVISORY COUNCIL (SAC) RECORD of MEETING Draft Subject to Review and Approval Date: May 16, 2017 - May 17, 2017 Location: New York, NY Participants: Steve Anderson Albemarle Audrey Batoon Chemtura Matt Blais Southwest Research Institute Kevin Bradley Consultant to BSEF Patty Cardin* Chemtura Catharine DeLacy Albemarle Michael Dourson Toxicology Excellence for Risk Assessment Ilan Elkan ICL Neeraja Erraguntla American Chemistry Council Ofodike Ezekoye* University of Texas-Austin A. Wallace Hayes Harvard School of Public Health Steve Levan Albemarle Kevin Marr** University of Texas-Austin Tom Osimitz Science Strategies, LLC Guillermo Rein Imperial College London Klaus Rothenbacher Independent Consultant Eric Sanders Chemtura Steve Scherrer Chemtura Jürgen Troitzsch Fire and Environment Protection Services Jay West American Chemistry Council Kimberly White American Chemistry Council ** Denotes part time participation in-person on May 16th only. ** Denotes part time participation via conference call on May 16th only. 1.0 K. White reviewed meeting room site logistics, the tentative agenda for the meeting and the ACC's Antitrust Guidelines which remained in effect for the duration of the two-day meeting. 2.0 Participants conducted roundtable introductions and K. White reviewed the overall objectives for the meeting, which included: Discuss relevant regulatory and chemical assessment activities Discuss state of the science Identify short term and long term science priorities and activities Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 Record of Meeting 05/16/17 - 05/17-17 Page 2 3.0 K. White reviewed key take-away messages from the May 15th NAFRA Operating Committee meeting which included: (a) focusing core science activities on priority areas of focus and ensuring alignment with the strategic plan, (b) identify approaches to inform issues raised during state legislative hearings, (c) focus the scope and objectives for the next phase of the smoke toxicity study and (d) identify opportunities to address fire fighter exposures. 4.0 K. White, J. West and K. Rothenbacher reviewed notable regulatory/legislative activity in the US and abroad. Action Items K. Rothenbacher will distribute a copy of the TBBPA EU Denmark Decision J. West will distribute information from Maine that outlines notable toxicological endpoints related to flame retardant exposures. 5.0 Participants discussed the status of the ongoing science projects currently underway and had detailed project discussions by the researchers as follows: T. Osimitz provided an overview of the available literature for the-for dermal exposures M. Blais and T. Osimitz reviewed the protocol, scope and results from the phase I of the smoke toxicity study. Participants discussed the results, possible implications and opportunities to refine and focus the project moving forward. Participants recommended that the researchers provide a write-up of the project results, recommendations for next phase and associated cost then scheduled a project specific call to agree on the path -forward. K. Marr and O. Ezekoye reviewed the scope and progress to date on the project to evaluate combustion properties of baby monitors. Participants discussed the researchers focus on battery failure scenarios, recommended refining the scope and ensuring the combustion activities adequately address differences between flame retardant and non-flame retardant. Action Items T. Osimitz will provide a draft manuscript for the dermal exposure review by June 15th. SAC members will evaluate whether it's feasible to develop a BE for blood concentrations from flame retardant based on dermal exposures T. Osimitz and M. Blais will work with N. Erraguntla to refine the smoke toxicity project scope and next steps then schedule a call to discuss. K. White will solicit recommendations for possible next steps on the combustion of baby monitors project and will set a project specific call for more discussion with the researchers. K. White will distribute past scope of work and study updates related to the combustion of baby monitors project. 6.0 Members of the SAC provided updates on ongoing science activities that included the following: J. Troitzsch invitation- to be a speaker during anchair a flame retardants seminar at the AOFSM'2 Conference in Shenzhen, China, 27-29 October 2017 in conjunction with BSEF -meeting. Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 Record of Meeting 05/16/17 - 05/17-17 Page 3 J. Troitzsch has been invited as keynote speaker on the fire safety of upholstered furniture alerted-participants to the Nordic Fire & Safety Days Conference in Copenhagen, 17-18 August 2017. an-epeoming 2017 meeting in Copenhagen- The participants discussed thatwhere engagement by a toxicology expert may be useful. G. Rein alerted participants to ongoing activities in California and other state agencies to evaluate TB117 and exposure to flame retardants. The evaluation is anticipated to last 3-5 years and it was recommended to monitor the data outputs annually. Action Items J. Troitzsch will provide information regarding the 2017 Copenhagen meeting. 7.0 Participants reviewed a series of charge questions and recent flame retardant session information from the 2017 Society of Toxicology meeting to identify potential opportunities for future science activities. NAFRA and SAC members also met separately to discuss identified projects and identify additional opportunities for science engagement. Overall, participants recommended identifying key product sectors and priority issues of interest to address, then reviewing each potential project to determine what role it will play in providing additional information to respond to identified sectors and issues. A number of projects topics were identified for future discussion and refinement as follows: Conduct of full scale room burns In Vitro dermal exposure study Evaluation of neurobehavioral testing parameters and human relevance from animal models Collaboration opportunities with NFPA research foundation Evaluate opportunities related to wearable technologies and impacts for assessment of flame retardant exposures Action Items K. White will aligned product categories, priority issue areas and identify possible science gaps by June 16th. K. White will schedule a conference call in June with NAFRA/BSEF members to discuss the identify projects and their alignment with product categories and issue areas of interest. 8.0 Participants discussed past and present SAC meeting to identify opportunities to improve meeting outputs and coordination with the SAC. Several recommendations were noted that included: having more time in the agenda for project specific discussions and deliberation; provide more background information on each project under discussion; elimination of fire science and toxicology specific breakout so that all participants can actively contribute to all meeting discussion; build in sufficient time for SAC members and NAFRA members to meeting separately for deliberation; and develop a science repository of relevant scientific information on the MemberExchange site that includes abstracts and links to articles when available pending copyright restrictions. 9.0 The next meeting is scheduled for November 12th (Dinner) and a November 13-14, 2017 Meeting in London. The meeting was adjourned at approximately 12:22pm on May 17, 2017. Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 Record of Meeting 05/16/17 - 05/17-17 Page 4 Respectfully submitted, K. White Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226

who reviewed the overall objectives for the meeting ?

gybn0226

gybn0226_p0, gybn0226_p1, gybn0226_p2, gybn0226_p3, gybn0226_p4, gybn0226_p5, gybn0226_p6, gybn0226_p7, gybn0226_p8, gybn0226_p9, gybn0226_p10, gybn0226_p11, gybn0226_p12, gybn0226_p13, gybn0226_p14

K. White

145 From: Jürgen Troitzsch To: Dr. Wise Kimberly Cc: Admon. Smadar: Anderson Steven; Batoon, Audrev; Dr. Bradley Kevinx; de Lacy, Catharine: Elkan. Illan; Eraguntla, Neeraia: Goodman, Bryan; Hochschwender. Lane; Jacobi Svivia; Kannah Kasturirangan; Levan Steve; Leychik. Sergei; Little, Barbara; Manor, Orit; Prero, Judah; Dr. Rothenbacher Klaus; Saunders, Eric L.; Scherrer Stephen; Simon. Robert; Tavior Jennifer; Tenney Joel; Thorn. Amelia; West, Jav; Dr. Haves Wallace; Prof. Rein Guillermo; Dr. Blais Matthew; Dourson. Michael (doursoml); Kacew. Sam; Osimitz Thomas Subject: Re: For Review - Draft Record from May 2017 SAC Meeting Date: Sunday, June 4, 2017 10:05:03 AM Attachments: SAC ROM 05-16-17 and 05-17-17 - Draft doc Program 2017, pdf 170817AbsFurnitureFiresafety.do Dear Kimberly, Please find attached my comments to the meeting record, the program of the Copenhagen conference and my abstract. Kind regards/Viele Grüße Jürgen Dr. Jürgen Troitzsch Fire and Environment Protection Service FEPS Via Patrizia 32 CH-6612 Ascona, Switzerland Mobile: +41 79 289 17 16 Phone: +41 91 791 14 22 Email: [email protected] Web: www.troitzsch.com Am 02.06.2017 um 13:56 schrieb White, Kimberly <Kimberly [email protected]> Dear NAFRA, BSEF and SAC members: Attached is the record from the May 2017 Science Advisory Council meeting. Please review by June 9th and let me know if you have any additions or corrections. Kind Regards, Kimberly Wise White, Ph.D. | American Chemistry Council Senior Director, Chemical Products & Technology Division [email protected] Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 Furniture Fire Properties And Their Importance For Domestic Fire Safety Juergen H. Troitzsch Fire and Environment Protection Service FEPS Ascona, Switzerland [email protected] Keywords: Fire statistics, furniture regulations, reaction to fire stakeholders regarding adequate fire safety, the proposal was tests, barriers, flame retardants withdrawn. A second version is now under consideration and it Fire statistics show that residential fires caused by is unclear when the amended regulations will come in to force. upholstered furniture have continuously decreased in the U.S. These approaches have led to search for other possibilities /California and the UK in the last 20 years. This is due to to ensure adequate fire safety levels for upholstered furniture. stringent fire safety regulations and tests mandatory for Contrary to the past, where ignition and flammability tests upholstered furniture in these countries. However, upholstered were used to define fire safety. now the reduction of the heat furniture still remains the leading item first ignited by low release rate is seen as the key fire property most strongly energy ignition sources such as cigarettes, matches, lighters influencing fire hazard. and candles 1. A study on "Alternative strategies to the use of chemical The classical way to meet high fire safety requirements for flame retardants" 4 has shown that various combinations of upholstered furniture is to improve the fire safety level of its cover materials and fire barriers to protect flexible components by using flame retarded flexible polyurethane polyurethane foam can reduce the heat release rate of the foam, barriers and covers. systems tested and improve fire safety. With the exception of In recent years, due to health and environment concerns an intrinsically flame retarded (FR) polyester cover, no other about the use of certain flame retardants, California revised the components used contained conventional flame retardants. CA TB 117 cigarette test 2 used for upholstered furniture in the Another, earlier study on "upholstered furniture private domain. The former additional small flame test required flammability" 5 investigated the fire performance of different was eliminated because flame retardants had to be used to meet FR/non-FR barrier materials and flexible polyurethane foams it. with a non-FR polyester cover in material-level, mock-up and The new CA TB 117 only addresses smoldering fires, while full-size furniture experiments. The results showed that the fires associated with flaming ignition, which according to flame retarded barrier materials were very effective in reducing NFPA lead to an appreciable amount of fatalities, are no more heat release rate and, particularly in the full-size experiments, considered. Therefore, NFPA has been asked to develop a the fire growth rate of the upholstered chairs. flaming-ignition test for upholstered furniture and is currently These studies show that the best way to reduce the heat working on its own open-flame test to NFPA 277 3 based on release rate of upholstered furniture and to optimize fire safety heat release rate measurement. is the use of flame retarded fire barriers and covers. Adequate In Great Britain, "The Furniture and Furnishings (Fire fire barriers including the use of flame retardants based on the Safety) Regulations' address compulsory fire safety U.S. EPA Design for the Environment (DfE) alternatives requirements for upholstered furniture in private homes. In assessment method will help to enhance domestic fire safety 2014, the authorities proposed an alternative match test to and reduce the number of fatalities, injuries and property losses. simplify the regulation and to reduce levels of flame retardants in furniture without impacting on the current fire safety levels. Here, contrary to the California approach, the cigarette test was to be eliminated and only gas flames and the BS 5852 crib 5 tests remained. However, following strong concerns from the 1 J. Troitzsch, "Fires, statistics, ignition sources, and passive fire protection REFERENCES measures", Journal of Fire Sciences, 2016, 1-28. DOI: 10.1177/07349041 2 Technical Bulletin 117-2013 Requirements, Test Procedure and Apparatus for Testing the Smolder Resistance of Materials Used in Upholstered 4 K. Storesund, A. Steen-Hansen and A. Bergstrand, "Fire safe upholstered Furniture. January 2013 furniture. Alternative strategies to the use of chemical flame retardants," 3 Proposed Standard NFPA 277: Standard Methods of Tests for Evaluating SPFR Report A15 20124:2, December 2015. Fire and Ignition Resistance of Upholstered Furniture Using a Flaming 5 T. Fabian, "Upholstered furniture flammability,' Underwriters Laboratories Ignition Source Inc., Jul. 2013. Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 NFSD Nordic Fire & Safety Days Programme Day 1, 17th Augusti 2017 no Colico and Registration Welcome to the Nardini are and Safety Days Room: ACM15 Anne Dederichs 10.00 Key Leature Room: ACM15 Furniture fire properties and their importance for domestic fire safety. Dr. Jürgen Troitzsch, FEPS, Switzerland Panal Discussion Room: ACM15 Session Chair: Björn Sundström, SP Furniture fire properties and their importance for domestic fire safety. Dr. Jürgen Troitzsch, FEPS, Switzerland Egil Sundet, Head of the Sector furniture, interior and design for the federation of Norwegian Industry Dr. David Santillo, Honorary Research Fellow at Greenpeace Research Laboratories, Exeter University, UK, Dr. Anne Elise Steen-Hansen, Research manager at SP Fire Research, Norway Dr. Björn Karlsson, Professor at Iceland University and the Director General at Iceland Construction Authority. A! ********* - ****** NTNU 1 LUND of ****** ******** ******** DBI Source: https://wwww.industrydocuments.ucsf.edu/docs/gybn0226 NFSD Nordic Fire & Safety Days Parallet Session A Fire Dynamics 1 Risk 1 Evacuation Room: ACM15 1.001 Room: ACM15 1.008 Room: FKJ 12 0.06 Session Chair: Session Chair: Session Chair: Tuula Hakkarainen Frank Markert 11.00-11.15 Fire protection of Modelling approach for The effect of plattform- extensive green roofs the threat quantification and tunnel design on the A. Elias of cascading failures evacuation performance A. Helminen, T. of wheelchair users - A Hakkarainen qualitative study Eva-Sara Karlsson 11.20-11.35 USCG Fire simulation of Developing a risk and Reaction and decision water mist suppression capability assessments time of evacuees - A study using an ignition source methodology for the Baltic regarding the influence of E. A. Kolstad, B. P. Husted, Sea Region alcohol on the reaction LU - B. Karlsson and decision time P. B. Rask, A. Dederichs 11.40-11.55 Development tool for Fire safety decision Awareness of fire risk ETICS façade fire testing making under a systems- reduction among Cyprus M.S. McLaggan, M. theoretic safety paradigm international university Meinert, A. Dragsted, P. -H. Bjelland, O. Njã, A. (CIU) students van Hees W.Heskestad, G. S. Braut A. F. Gyasi 1000 Lunch 2 Exhibition the DO Parallal R Fire Dynamics 2 Fire safety science Transportation without borders Room: ACM15 1.001 Room: ACM15 1.008 Room: FKJ 12 0.06 Session Chair: Session Chair: Session Chair: Frida V Lundström Martyn S. McLaggan 13.00-13.15 Desensitisation of optical Fire safety science without Ventilation in tunnels: a flame detection in harsh borders numerical comparison external environments T., between different J. McNay K. H. Almand modelling approaches -P. Matteo 13.20-13.35 Heat release Fire safetys contribution Fire detection in engine characteristics of ethanol- to a sustainable society compartments - P. water mixtures T., Karlsson, O. Willstrand T. Hakkarainen K. H. Almand, NFPA 13.40-13.55 Fire-induced pressures in Det store brannlöftet - Verifying fire safety in tall modern airtight Dag Botnen timber buildings apartment building Fredrik Nystedt S. Hostikka Johan Norén 14 00 3 Enhibition OTU A! II'II ********* - - NTNU a 2 Landa of ******** ******** ******** 081 Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 NFSD Nordic Fire & Safety Days Parallet C Fire Dynamics 3 Fire Safety Engineering 1 Brokerage Event 1: Carpark fires Room: ACM15 1.001 Room: ACM15 1.008 Room: FKJ 12 0.06 Session Chair: Session Chair: Session Chair: Ulf Wickström Michael Stömgren 14.45- Measuring incident Performance based design and compilande Luisa Giuliani 15:00 heat flux and M. Strömgren adiabatic surface temperature with platse thermometers in ambient and high temperatures U. Wickström, J. Anderson, J. Sjöström 15.05- Modelling and Wildlandfires, F.V.Lundström, P. Andersson 15.20 stochastic analyses of travelling fires R. K. Janardhan, S. Hostikka 15.25-40 Photovoltaic A discussion on learning from fire installations on investigations; concepts and methodologies warehouse buildings - an experimental A. Borg, O. Njã study of the propagation of fire - J. Steemann Kristensen Conference 3 Exhibition Affer conferenze dinner OTU A! IIIII ********* - - - NTNU a 3 Luno of ******** ******** ******** 081 Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 NFSD NordicFire & Safety Days Programme Day 2, 18th August 2017 20.02.40 Welcome Key Leaure Room: ACM15 Fire brigade intervention method - accounting for the actions of the fire service Ed Claridge, Principal Fire Engineer, Auckland, New Zealand Pana Discussion Room: ACM15 Session Chair: Fire brigade intervention-accounting for the actions of the fire service Ed Claridge, Principal Fire Engineer, Auckland, New Zealand Rasmus Storgaard Petersen, CEO Emergency Service East, Denmark Cecilia Daae, Director of Directorate for Civil Protection and Emergency Planning, Norway Mia Kumm, Licentiate of engineering and researcher at SP/Rise and Mälardalen University, Sweden A! II-II: ********* - ****** - NTNU a 4 Luwo ****** DBI Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 NFSD Nordic Fire & Safety Days Parallel Session D Management of rescue Risk 2 Structural Fire Safety 1 service 1 Room: ACM15 1.001 Room: ACM15 1.008 Room: FKJ 12 0.06 Session Chair: Session Chair: Session Chair: 11.00-11.15 Accounting for the actions Resilient Buildings C-Fort, Risk analysis and of the rescue service - M. Kumm performance-based rescue from heights. structural fire expertise of Christian Ramm a semi-buried railway station - E. Tonicello, S. Deshanghere 11.20-11.35 Environmental impact of Firesafe - Study Experimental study on the structure fires and fire investigating cost effective mechanical properties of service response measures for reducing the fire exposed concrete F. Amon, L. Vylund risk from fires on ro-ro A. Zawadowska, L. passanger ships Giuliani, K. D. Hertz - J. Wikman, M. Rahm, F. Evegren, J. Leroux, A. Breuillard, M. Kjellberg, L. Gustin, F. Efraimsson 11.40-11.55 Part time firemen and False alarm - An Fire protection of wooden community resilience organizational study of houses in several floors -P. Almklov, M. Nilsen, G. the effects of false alarms J. N. Olsen, H. S.Fishman Gjøsund G. Gjøsund Petter Almklov Christian Sesseng Lundh R OTU A! IIIII ********* - - - *** - - NTNU " 5 Luno of ******** ******** ******** 081 Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 NFSD Nordic Fire & Safety Days Parallel R Management of rescue Fire safety engineering 2 Structural Fire Safety 2 service 2 Room: ACM15 1.001 Room: ACM15 1.008 Room: FKJ 12 0.06 Session Chair: Session Chair: Session Chair: 13.00-13.15 Security officers 99 years of standard fire - Furnace setup for responding to residential success of failure? preliminary fire resistance fire alarms: modelling the R. Jansson McNamee testing - effect on survival and P. Hejtmánek, V. Flídr, H. property damages Najmanová B. Sund, H. Jaldell 13.20-13.35 Three different fire Investigation of suppression approaches A swedish approach to eurocodes design used by Fire and Rescue define a standard for fire fires and national services safety design in BIM deviations- F. S. Särdqvist F. Nystedt, J. Norén Clausen, L. Giuliani 13.40-13.55 An operationalization of Nordic standard for Material capabilities for fire and review & control of fire modeling of rescue operations safety engineering concrete under M. Runefors F. Nystedt, J. Norén, M. compression and Strömgren high temperatures - A. F. Damkjaer, L. Giuliani, K. D. Hertz Coffee 3 Exhibition OTU A! IIIII ********* - - - *** - - NTNU " 6 Luno of ******** ******** ******** 081 Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 NFSD Nordic Fire & Safety Days Parallel Sersion : Residential Fires 1 Fire safety engineering 3 Fire Dynamics 4 Room: ACM15 1.001 Room: ACM15 1.008 Room: FKJ 12 0.06 Session Chair: Session Chair: Session Chair: 14.45-15.00 Socioeconomic Learning points from real Smouldering fires in wood differences in residential incidents - pellets: the effect of fire mortality in Sweden: a learning from what?- - M. varying the airflow case-control study Bøhm, Metropolitan V. R. Valdés,R. F. Mikalsen, A. Jonsson University College A. Steen-Hansen O.Njã, U. Stavanger 15.05-15.20 Fire fatalities in Norway Simulation of smouldering K. Storesund, C. Sesseng, combustion based on A. Steen-Hansen Integration of fire multi-layer cellular engineering tools and automata- calculation methodologies V. R. Valdés,R F. Mikalsen, P. Tofilo A. Steen-Hansen 15.25-15-40 Has fire-related mortality Learning fire and rescue Aerosols from smoldering in Sweden changed over work by experience- E. Villacorta time? - E. Lindahl, J. sharing Hedberg Ava Sadeghi OTU A! IIIII ********* - - - *** - - NTNU " 7 Luno of ******** ******** ******** 081 Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 NFSD Nordic Fire & Safety Days Paralial to Residential Fires 2 Structural Fire Safety 3 Fire Dynamics 5 Room: ACM15 1.001 Room: ACM15 1.008 Room: FKJ 12 0.06 Session Chair: Session Chair: Session Chair: Residential fires in On analysing structures USCG Fire simulation of Denmark based solely on human water mist suppression P.B. Gummesen safety using an ignition source A.S. Dederichs, RISE, DTU J.Sandström, J. Thor, R. Einar Arthur Kolstad Jansson McNamee,0. Bjarne P. Husted Lagerqvist, U.Wickström Residential fire solutions Post-earthquake Validation of FDS on the in the building sector fire behavior of SP retail store steel frames - Shamim Ahmed Bjarne P. Husted Part I: Collapse Mechanism - G. Risco, L. Giuliani, V. Zania Towards an evidence- Post-earthquake fire Validation of sub-grip based vision zero policy behavior of steel frames - scale particle model for on residential fires - an Part II: The effect of the cable fire spread update - R. Andersson insulation - A. Wrobel, , L. T. Sikanen, A. Matala, S. A. Jonsson Giuliani, V. Zania Hostikka Brokerage Event 2: Modern Building Fires Session Chair: Anne Dederichs Lars Schiøtt Sørensen, DTU OTU A! IIIII ********* - - - *** - - NTNU " 8 Luno of ******** ******** ******** 081 Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 AMERICAN CHEMISTRY COUNCIL NORTH AMERICAN FLAME RETARDANT ALLIANCE (NAFRA), BROMINATED SCIENCE ENVIRONMENTAL FORUM (BSEF) AND SCIENCE ADVISORY COUNCIL (SAC) RECORD of MEETING Draft Subject to Review and Approval Date: May 16, 2017 - May 17, 2017 Location: New York, NY Participants: Steve Anderson Albemarle Audrey Batoon Chemtura Matt Blais Southwest Research Institute Kevin Bradley Consultant to BSEF Patty Cardin* Chemtura Catharine DeLacy Albemarle Michael Dourson Toxicology Excellence for Risk Assessment Ilan Elkan ICL Neeraja Erraguntla American Chemistry Council Ofodike Ezekoye* University of Texas-Austin A. Wallace Hayes Harvard School of Public Health Steve Levan Albemarle Kevin Marr** University of Texas-Austin Tom Osimitz Science Strategies, LLC Guillermo Rein Imperial College London Klaus Rothenbacher Independent Consultant Eric Sanders Chemtura Steve Scherrer Chemtura Jürgen Troitzsch Fire and Environment Protection Services Jay West American Chemistry Council Kimberly White American Chemistry Council ** Denotes part time participation in-person on May 16th only. ** Denotes part time participation via conference call on May 16th only. 1.0 K. White reviewed meeting room site logistics, the tentative agenda for the meeting and the ACC's Antitrust Guidelines which remained in effect for the duration of the two-day meeting. 2.0 Participants conducted roundtable introductions and K. White reviewed the overall objectives for the meeting, which included: Discuss relevant regulatory and chemical assessment activities Discuss state of the science Identify short term and long term science priorities and activities Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 Record of Meeting 05/16/17 - 05/17-17 Page 2 3.0 K. White reviewed key take-away messages from the May 15th NAFRA Operating Committee meeting which included: (a) focusing core science activities on priority areas of focus and ensuring alignment with the strategic plan, (b) identify approaches to inform issues raised during state legislative hearings, (c) focus the scope and objectives for the next phase of the smoke toxicity study and (d) identify opportunities to address fire fighter exposures. 4.0 K. White, J. West and K. Rothenbacher reviewed notable regulatory/legislative activity in the US and abroad. Action Items K. Rothenbacher will distribute a copy of the TBBPA EU Denmark Decision J. West will distribute information from Maine that outlines notable toxicological endpoints related to flame retardant exposures. 5.0 Participants discussed the status of the ongoing science projects currently underway and had detailed project discussions by the researchers as follows: T. Osimitz provided an overview of the available literature for the-for dermal exposures M. Blais and T. Osimitz reviewed the protocol, scope and results from the phase I of the smoke toxicity study. Participants discussed the results, possible implications and opportunities to refine and focus the project moving forward. Participants recommended that the researchers provide a write-up of the project results, recommendations for next phase and associated cost then scheduled a project specific call to agree on the path -forward. K. Marr and O. Ezekoye reviewed the scope and progress to date on the project to evaluate combustion properties of baby monitors. Participants discussed the researchers focus on battery failure scenarios, recommended refining the scope and ensuring the combustion activities adequately address differences between flame retardant and non-flame retardant. Action Items T. Osimitz will provide a draft manuscript for the dermal exposure review by June 15th. SAC members will evaluate whether it's feasible to develop a BE for blood concentrations from flame retardant based on dermal exposures T. Osimitz and M. Blais will work with N. Erraguntla to refine the smoke toxicity project scope and next steps then schedule a call to discuss. K. White will solicit recommendations for possible next steps on the combustion of baby monitors project and will set a project specific call for more discussion with the researchers. K. White will distribute past scope of work and study updates related to the combustion of baby monitors project. 6.0 Members of the SAC provided updates on ongoing science activities that included the following: J. Troitzsch invitation- to be a speaker during anchair a flame retardants seminar at the AOFSM'2 Conference in Shenzhen, China, 27-29 October 2017 in conjunction with BSEF -meeting. Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 Record of Meeting 05/16/17 - 05/17-17 Page 3 J. Troitzsch has been invited as keynote speaker on the fire safety of upholstered furniture alerted-participants to the Nordic Fire & Safety Days Conference in Copenhagen, 17-18 August 2017. an-epeoming 2017 meeting in Copenhagen- The participants discussed thatwhere engagement by a toxicology expert may be useful. G. Rein alerted participants to ongoing activities in California and other state agencies to evaluate TB117 and exposure to flame retardants. The evaluation is anticipated to last 3-5 years and it was recommended to monitor the data outputs annually. Action Items J. Troitzsch will provide information regarding the 2017 Copenhagen meeting. 7.0 Participants reviewed a series of charge questions and recent flame retardant session information from the 2017 Society of Toxicology meeting to identify potential opportunities for future science activities. NAFRA and SAC members also met separately to discuss identified projects and identify additional opportunities for science engagement. Overall, participants recommended identifying key product sectors and priority issues of interest to address, then reviewing each potential project to determine what role it will play in providing additional information to respond to identified sectors and issues. A number of projects topics were identified for future discussion and refinement as follows: Conduct of full scale room burns In Vitro dermal exposure study Evaluation of neurobehavioral testing parameters and human relevance from animal models Collaboration opportunities with NFPA research foundation Evaluate opportunities related to wearable technologies and impacts for assessment of flame retardant exposures Action Items K. White will aligned product categories, priority issue areas and identify possible science gaps by June 16th. K. White will schedule a conference call in June with NAFRA/BSEF members to discuss the identify projects and their alignment with product categories and issue areas of interest. 8.0 Participants discussed past and present SAC meeting to identify opportunities to improve meeting outputs and coordination with the SAC. Several recommendations were noted that included: having more time in the agenda for project specific discussions and deliberation; provide more background information on each project under discussion; elimination of fire science and toxicology specific breakout so that all participants can actively contribute to all meeting discussion; build in sufficient time for SAC members and NAFRA members to meeting separately for deliberation; and develop a science repository of relevant scientific information on the MemberExchange site that includes abstracts and links to articles when available pending copyright restrictions. 9.0 The next meeting is scheduled for November 12th (Dinner) and a November 13-14, 2017 Meeting in London. The meeting was adjourned at approximately 12:22pm on May 17, 2017. Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 Record of Meeting 05/16/17 - 05/17-17 Page 4 Respectfully submitted, K. White Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226

what are the units of BW ?

fsbn0226

fsbn0226_p9, fsbn0226_p10, fsbn0226_p11, fsbn0226_p12, fsbn0226_p13, fsbn0226_p14, fsbn0226_p15, fsbn0226_p16, fsbn0226_p17, fsbn0226_p18, fsbn0226_p19, fsbn0226_p20, fsbn0226_p21, fsbn0226_p22, fsbn0226_p23, fsbn0226_p24, fsbn0226_p25, fsbn0226_p26, fsbn0226_p27, fsbn0226_p28, fsbn0226_p29, fsbn0226_p30, fsbn0226_p31, fsbn0226_p32, fsbn0226_p33, fsbn0226_p34

kg

Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 2 USEPA APPROACH FOR EVALUATING CANCER RISHS POSED BY ORAL EXPOSURE TO 1,4-DIOXANE USEPA's Integrated Risk Information System (IRIS) published the Toxicological Review for 1,4-dioxane, in which it describes their approach and justification for deriving an oral CSF for this constituent. Below is a summary of USEPA's evaluation of available human toxicological data, weight of evidence evaluation, key study identification, critical effect selection, dose-response assessment, and the low-dose extrapolation procedure used to derive 1,4-dioxane's CSF. 2.1 USEPA's Evaluation of Evidence of Cancer in Humans USEPA evaluated the degree to which data provide evidence of carcinogenicity in humans (USEPA 2010). USEPA relied on two human occupational studies in their evaluation of potential impacts related to long-term exposure to 1,4-dioxane (Thiess et al. 1976; Buffler et al. 1978). USEPA concluded that neither study provided evidence that 1, ,4-dioxane causes cancer in humans. However, they noted "the cohort size and number of reported cases were small." 2.2 USEPA's Evaluation of Evidence of Cancer in Animal Bioassays USEPA followed its Guidelines for Carcinogen Risk Assessment (USEPA 2005) to conclude that 1,4- dioxane is "likely to be carcinogenic to humans" based on "evidence of liver carcinogenicity in several 2- year bioassays conducted in three strains of rats, two strains of mice, and in guinea pigs.' USEPA provided several reasons to justify its conclusion. For instance, USEPA concluded that the "available evidence is inadequate to establish a MOA by which 1,4-dioxane induces liver tumors in rats and mice" (USEPA 2010). Specifically, USEPA noted the "[c]onflicting data from rat and mouse bioassays (Japan Bioassay Research Center [JBRC] 1998; Kociba et al., 1974) suggest that cytotoxicity may not be a required precursor event for 1,4-dioxane-induced cell proliferation." USEPA (2010) noted that "[a]vailable data also do not clearly identify whether 1,4-dioxane or one of its metabolites is responsible for the observed effects. However, USEPA also reported that "the generally negative results for 1,4-dioxane in a number of genotoxicity assays indicates the carcinogenicity of 1,4-dioxane may not be mediated by a mutagenic MOA" (USEPA 2010). 2.3 Key Study Identification (Kano et al. 2009), Critical Effect Selection, Dose-Response Assessment, and Low-Dose Extrapolation Procedure USEPA (2010) concluded that the MOA by which 1,4-dioxane produces liver tumors is "unknown, and available evidence in support of any hypothetical mode of carcinogenic action for 1,4-dioxane is inconclusive." With this conclusion in mind, USEPA (2010) identified a 2-year drinking water study performed by Kano et al. (2009) as the key study of the oral CSF for 1,4-dioxane. Note that Kano et al. (2009) published findings originally reported by the JBRC (1990a). Although USEPA (2010) concurrently evaluated two other studies (Kociba et al. 1974; National Cancer Institute [NCI] 1978), the Kano et al. (2009) study was ultimately selected as the key study because USEPA (2010) noted that "[c]alculation of arcadis.com 3 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications a CSF for 1,4-dioxane is based upon the dose-response data for the most sensitive species and gender." The study was performed in accordance with the Organization of Economic Development's Principles for Good Laboratory Practices and involved exposing groups of rats (50 animals of each sex for each dose) and mice (50 animals of each sex for each dose) to 1,4-dioxane (>99% pure) in drinking water for 2 years. Rats were exposed to 1,4-dioxane in drinking water at 0, 200, 1,000, or 5,000 milligrams per liter (mg/L), while mice were exposed at 0, 500, 2,000, or 8,000 mg/L in drinking water. As reported by USEPA (2010): "The investigators used data from water consumption and BW [body weight] to calculate an estimate of the daily intake of 1,4-dioxane (mg/kg-day) by male and female rats and mice. Kano et al. (2009) reported a calculated mean + standard deviation for the daily doses of 1,4-dioxane for the duration of the study. Male rats received doses of approximately 0, 11+1, 55+3, or 274+18 mg/kg-day and female rats received 0, 183, 83+14, or 429+69 mg/kg-day. Male mice received doses of 0, 49+5, 191+21, or 677+74 mg/kg-day and female mice received 0, 66=10, 278+40, or 964+88 mg/kg-day." "The study by Kano et al. (2009) was used for development of an oral CSF. This was a well- designed study, conducted in both sexes in two species (rats and mice) with a sufficient number (N=50) of animals per dose group. The number of test animals allocated among three dose levels and an untreated control group was adequate, with examination of appropriate toxicological endpoints in both sexes of rats and mice. Alternative bioassays (Kociba et al., 1974; NCI, 1978) were available and were fully considered for the derivation of the oral CSF." USEPA identified increased incidence of liver adenomas or carcinomas as the critical effect in rats and mice exposed to 1,4-dioxane in the Kano et al. (2009) study. Following standard dose adjustment to a human equivalent dose using a default body weight (BW) scaling factor (USEPA 2005), USEPA performed dose-response modeling using Benchmark Dose Software and fit the suite of models available in the program to the incidence data for "either hepatocellular carcinoma or adenoma" (USEPA 2010). USEPA concluded that female mice are "more sensitive to liver carcinogenicity induced by 1,4-dioxane compared to other species or tumor types" and identified the lower 95% confidence bound on the benchmark dose associated with a 50% extra risk (benchmark response [BMR]) of developing "either hepatocellular carcinoma or adenoma" (4.95 milligrams per kilogram per day [mg/kg/d]) as the point of departure (POD) for calculating the oral CSF via linear low-dose extrapolation, as shown in Equation (1), below. USEPA (2010) again justified a linear low-dose extrapolation approach based on their conclusion that 1,4-dioxane's MOA for production of hepatic tumors in rodents is "unknown." BMR 0.5 Equation (1) CSF = = 0.1 (mg/kg/d)1 POD 4.95 mg/kg/d 2.4 Comments Provided to USEPA During External Peer Review When USEPA's IRIS program derives toxicity values, the Toxicological Review undergoes critical evaluation by individuals from within and outside the agency. A result of the outside review efforts indicated several external peer review panel members believed that available information for 1,4-dioxane could "support the use of a nonlinear extrapolation approach to estimate human carcinogenic risk" and arcadis.con 4 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications that "such an approach should be presented in the Toxicological Review.' Specifically, the USEPA (2010) notes: "[N]umerous short-term in vitro and a few in vivo tests were nonpositive for 1,4-dioxane-induced genotoxicity". Results from two-stage mouse skin tumor bioassays "suggest that a potential mode of action for 1,4- dioxane-induced tumors may involve proliferation of cells initiated spontaneously, or by some other agent, to become tumors." Additionally, a public commenter noted: "Low-dose linear extrapolation for the oral CSF is not appropriate nor justified by the data. The weight of evidence supports a threshold (nonlinear) MOA when metabolic pathway is saturated at high doses. Nonlinear extrapolations should be evaluated and presented for 1,4-dioxane." These statements indicated that some reviewers felt the toxicological data for 1,4-dioxane indicated that it may not behave in a linear manner, but rather as a threshold carcinogen. Nonetheless, USEPA (2010) ultimately concluded that there was insufficient information available to support any of the proposed MOAs and proceeded to adopt, albeit imprecisely in hindsight, the default linear low-dose extrapolation approach. arcadis.com 5 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 3 DOURSON ET AL. (2014): MODE OF ACTION (MOA) ANALYSIS FOR LIVER TUMORS FROM ORAL 1,4- DIOXANE EXPOSURES AND EVIDENCE-BASED DOSE ss RESPONSE ASSESSMENT USEPA's (2010) conclusion to evaluate 1,4-dioxane as a non-threshold, linear, low-dose extrapolation carcinogen, was "based, in part, on the following: (1) apparent uncertainty in the toxic moiety for 1,4- dioxane; and, (2) apparent lack of noncancer toxicity data from several mouse bioassays at doses that evoke tumors, or that otherwise appear to have conflicting information concerning non-neoplastic lesions in the liver of rodents exposed orally to 1,4-dioxane" (Dourson et al. 2014). Recognizing that the key studies were performed over 3 decades, Dourson et al. (2014) hypothesized that "differences in histologic approaches for quantifying and reporting non-neoplastic changes may have been responsible for the differences noted across the studies" and would account for the apparent lack of non-cancer toxicity data reported in the key mouse bioassays. In addition to directly testing this hypothesis, Dourson et al. (2014) reviewed the database of genotoxicity studies, "which included DNA replication and promotion bioassays as well as mutation, initiation, and DNA repair studies," synthesized the genotoxicity database for 1,4- dioxane, and developed and analyzed a biologically plausible MOA for the formation of hepatic tumors in rodents by employing USEPA's (2005) carcinogen guidelines. Dourson et al.'s (2014) findings from the reread of the NCI (1978) mouse bioassay histopathology slides and review of the extensive genotoxicity database demonstrates that chronic exposure to 1,4-dioxane in drinking water is associated with a non-linear mode of carcinogenic action (threshold). which is contrary to USEPA's default linear low-dose extrapolation approach (non-threshold). The cancer MOA developed by Dourson et al. (2014) also afforded new data with which to perform an improved dose-response assessment for 1,4-dioxane using toxicological endpoints that protect against 1,4-dioxane's cancer MOA (refer to Appendix A for additional details). In regards to choosing a low-dose extrapolation approach, USEPA's Guidelines for Carcinogen Risk Assessment (2005) plainly state that "[a] nonlinear approach [i.e., derivation of a reference dose or concentration] should be selected when there are sufficient data to ascertain the mode of action and conclude that it is not linear at low doses and the agent does not demonstrate mutagenic or other activity consistent with linearity at low doses.' The information presented by USEPA (2010) and supplemented by the new information from Dourson et al. (2014) shows that: (1) 1,4-dioxane causes tumors at high doses through an MOA that involves cytotoxic effects, regenerative cell proliferation, and subsequent tumor formation; (2) the effects that precede tumor formation display non-linear dose-responses; and (3) 1,4- dioxane does not cause mutations at concentrations that are not cytotoxic. As a result, the RfD of 0.05 mg/kg/d developed by Dourson et al (2014) addressed key data gaps identified by USEPA (2010) and protects against the development of liver cancers following oral exposure to 1,4-dioxane. arcadis.com 6 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 4 DOURSON ET AL. (2016 IN PEER REVIEM: UPDATED MODE OF ACTION ANALYSIS (MOA) FOR LIVER TUMORS FROM ORAL ,4-DIOXANE EXPOSURES AND EVIDENCE-BASED DOSE-RESPONSE ASSESSMENT While Dourson et al. (2014) demonstrated that a threshold-based, regenerative cell proliferation MOA accounted for the tumor findings in the NCI (1978) mouse bioassay, questions still remained about the tumor findings from a 2-year oral mouse bioassay and a 13-week precursor study reported by the JBRC (1990a,b), subsequently published as Kano et al. (2008, 2009). Similar to the NCI (1978) mouse bioassay discussed in Dourson et al. (2014), the Japanese work provided few details or findings regarding non- cancer toxicity in the mouse liver after long-term exposure to 1,4-dioxane. To address the remaining questions regarding the apparently discordant findings between the tumor MOA in mice and rats and enhance the investigation of the threshold-based MOA for hepatic tumor formation, Dourson et al. (2016 in peer review) performed a detailed evaluation of the translated Japanese rodent bioassay reports (JBRC 1990a,b) and integrated the findings with other lines of evidence for the regenerative cell proliferation MOA. This effort is summarized in Appendix B. In addition to the detailed evaluation of the JBRC (1990a,b) bioassays, Dourson et al. (2016 in peer review) also solicited opinions from several pathologists regarding the conflicting findings from the mouse bioassays. Dourson et al. (2016 in peer review) reported: "Collectively these pathology opinions support the hypothesized MOA discussed in U.S. EPA (2013) and Dourson et al. (2014) that the liver tumors from oral exposure to 1,4-dioxane occur after metabolic saturation, accumulation of the parent 1,4-dioxane molecule, liver toxicity and a regenerative hyperplasia. While additional live experimental animal testing might add confirmatory findings, a threshold for these tumors is expected if metabolism of the parent compound is not saturated, since subsequent liver toxicity does not occur." By integrating all lines of evidence, Dourson et al. (2016 in peer review) concluded: "When the many lines of evidence are taken together, the reevaluation of the Japanese studies show consistent findings in rats and consistent findings in mice other than liver histopathology not being fully recorded in the second chronic study. However, based on the number of studies conducted, the well established metabolic saturation of 1,4-dioxane metabolism in humans and experimental animals, the effects of higher dose exposures on target organ toxicity, the presence of proliferative lesions, the effect of dose and time on the progression of lesions, the time of appearance of tumors, the spectrum of tumors developed, the number and incidence of tumors at organ sites with high or low background historical incidence, and the shapes of the dose-response curve for key events and tumors, all lead to the conclusion that a regenerative hyperplasia MOA is operating with 1,4-dioxane induced liver tumors." arcadis.con 7 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 5 IMPACT OF DOURSON ET AL.S UPDATED TOXICITY ASSESSMENT ON RISK-BASED DRINKING WATER CRITERIA An agency's choice to set risk-based criteria for 1,4-dioxane based on a threshold- or non-threshold- approach has the potential to drastically impact the value of the final criterion. An example of this is provided herein based on the approach used by the New Jersey Department of Environmental Protection (NJDEP) to derive groundwater quality criteria (NJDEP 2014). The risk-based equations NJDEP uses to derive groundwater criteria for threshold and non-threshold toxicants are shown below in Equations (2) and (3), respectively, while default exposure factors are shown in Table 1 below. Using the RfD of 0.05 mg/kg/d derived from Kociba et al. (1974) by Dourson et al. (2014) to protect against a regenerative cell proliferation MOA yields a risk-based criterion of 400 g/L Using USEPA's (2010) CSF of 0.1 (mg/kg/d)-¹ yields a risk-based criterion of 0.4 (0.35) g/L, corresponding to a 1 in 1,000,000 (1x10-6) excess lifetime cancer risk. Therefore, using the toxicity value derived based on a regenerative cell proliferation MOA (RfD, threshold approach) yields a criterion that is 1,000 times higher than the value derived using USEPA's CSF approach (linear low-dose extrapolation, non-threshold). The authors of this paper conclude that sites monitoring groundwater containing 1,4-dioxane at levels below 400 g/L would meet a reasonable groundwater quality criterion that is protective of human health. RfD x BW x CF x RSC Equation (2) Criterion = x UF BW x CF Equation (3) Criterion = x IRDW arcadis.com 8 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications Table 1. Toxicity Values and NJDEP's Exposure Factors for Calculating Risk-Based Groundwater Quality Criteria Exposure Pactor Units value bource RfD mg/kg/d 0.05 Dourson et al. (2014) CSF (mg/kg/d)-1 0.1 USEPA (2010) Target risk (TR) unitless 10-6 NJDEP default BW kg 70 NJDEP default Conversion factor (CF) g/mg 1,000 NJDEP default Relative source contribution (RSC) unitless 0.2 NJDEP default Drinking water ingestion rate (IRDw) L/d 2 NJDEP default Uncertainty factor (UF) unitless 1 NJDEP default Notes: kg = kilograms L/d = liters per day g/mg = micrograms per milligram arcadis.com 9 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 6 SUMMARY AND CONCLUSIONS To support several state regulatory agencies, Dourson et al. (2016 in peer review) recently undertook additional scientific investigations to address data gaps identified in USEPA's (2010) Toxicological Review regarding 1,4-dioxane's cancer MOA and assessment approach. Collectively, Dourson et al.'s (2014, 2016 in peer review) cancer MOA evaluations and dose-response assessments addressed USEPA's uncertainties and indeed demonstrate that chronic exposure to 1,4-dioxane in drinking water is associated with a non-linear mode of carcinogenic action (threshold). These additional scientific findings provide new information that resolve 1,4- dioxane's cancer MOA and support use of a non-linear dose response approach to protect against development of cancer following low-dose oral exposures. USEPA's (2010) cancer evaluation showed that 1,4-dioxane is not mutagenic or genotoxic at non- cytotoxic doses. However, USEPA ultimately chose to use a linear low-dose extrapolation approach for estimating human cancer risk from oral exposure to 1, 4-dioxane because they concluded that the MOA for tumor formation was unknown. The recent scientific investigations by Dourson et al. (2014, 2016 in peer review) provide new information to address data gaps identified by USEPA (2010) and demonstrate that 1,4-dioxane causes liver tumors in rodents through a regenerative cell proliferation MOA. The regenerative cell proliferation MOA is characterized by: (1) metabolic saturation and accumulation of parent compound; (2) cellular swelling, hypertrophy, and liver weight increase; (3) necrosis and/or inflammation; (4) increased DNA synthesis, hyperplasia development, and foci development; and (5) development of liver adenoma and carcinomas. Specifically, 1,4-dioxane must accumulate in the liver to levels that cause inflammation and cell damage before liver tumors can form. If the first key event does not occur (metabolic saturation), then liver tumors will not form. Therefore, there is a threshold of exposure for 1,4-dioxane below which tumors do not form and it is appropriate to use a non-linear low-dose extrapolation procedure for estimating risks. The RfD of 0.05 mg/kg/d derived by Dourson et al. (2014) is protective against tumor formation through this series of events (MOA) and was calculated using USEPA's preferred methods and best available scientific practices. Using Dourson et al.'s (2014) peer-reviewed RfD, based on a regenerative cell proliferation MOA to derive a groundwater drinking water criterion results in a criterion (400 g/L) that is 1,000 times greater than the concentration derived using USEPA's default CSF approach (0.4 g/L). Based on Dourson et al.'s (2014, 2016 in peer review) studies, it is reasonable to conclude that sites that monitor groundwater containing 1,4-dioxane at levels below 400 g/L would meet a reasonable groundwater quality criteria. The recent scientific findings summarized in this report have major implications for sites that are currently or will be managing water resources impacted by 1,4-dioxane. Considering that 1,4-dioxane is emerging as a water resource contaminant, in part due to USEPA's default linear low-dose cancer evaluation approach for liver tumors in rodents (USEPA 2010), the updated toxicology evidence that 1,4-dioxane is a threshold carcinogen is significant, and suggests that many current regulatory guidelines and standards are unnecessarily low. As such, the authors of this paper conclude that sites that monitor groundwater containing 1,4-dioxane at levels below 400 g/L would meet a reasonable groundwater quality criteria that is protective of human health. arcadis.con 10 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 7 REFERENCES ARA. 2016. 1,4-Dioxane Analysis. Available on line [Accessed Dec. 19] at: http://allianceforrisk.org/riskie- 2/. Buffler, P.A., S.M. Wood, L. Suarez, and D.J. Kilian. 1978. Mortality follow-up of workers exposed to 1,4- dioxane. J Occup Environ Med, 20: 255-259. Dourson, M., J. Reichard, P. Nance, H. Burleigh-Flayer, A. Parker, M. Vincent, and E.E. McConnell. 2014. Mode of action analysis for liver tumors from oral 1,4-dioxane exposures and evidence-based dose response assessment. Regul Toxicol Pharmacol. 68: 387-401. Dourson, M., J. Higginbotham, J. Crum, H. Burleigh-Flayer P, Nance, N. Forsberg, and M. Lafranconi. 2016 in peer review. Update: Mode of Action (MOA) for Liver Tumors Induced by Oral Exposure to 1,4-Dioxane. Regul Toxicol Pharmacol. Available online at: http://allianceforrisk.org/14-dioxane- analysis/. Health Canada. 2005. Drinking Water Guidance Value for 1,4-Dioxane. August 23. JBRC. 1990a. Report of Carcinogenicity Study by Oral Administration of 1,4-Dioxane (Mixed with Water) to Rats and Mice. Japan Industrial Safety and Health Association. December 28. JBRC. 1990b. Report of Preliminary Carcinogenicity Studies (Acute, Two-Week, and Thirteen-Week Studies) by Oral Administration of ,4-Dioxane (Mixed with Water) to Rats and Mice. Japan Industrial Safety and Health Association. December 28. Kano. H., Y. Umeda, M. Saito, H. Senoh, H. Ohbayashi, S. Aiso, K. Yamazaki, K. Nagano, and S. Fukushima. 2008. Thirteen-week oral toxicity of 1,4-dioxane in rats and mice. J Toxicol Sci. 33: 141- 153. Kano, H., Y, Umeda, T. Kasai, T. Sasaki, M. Matsumoto, K. Yamazaki, K. Nagano, H. Arito, and S. Fukushima. 2009. Carcinogenicity of 1,4-dioxane administered in drinking-water to rats and mice for 2 years. Food Chem Toxicol. 47:2776 - 2784. Kociba, R.J., S.B. McCollister, C. Park, T.R. Torkelson, and P.J. Gehring. 1974. 1,4-dioxane. I. Results of a 2-year ingestion study in rats. Toxicol Appl Pharmacol, 30: 275-286. doi:10.1016/0041- 008X(74)90099-4. McConnell, G. 2013. Report on the review of liver slides from the National Cancer Institute's Bioassay of 1,4-Dioxane for Possible Carcinogenicity Conducted in 1978 (NCI, 1978). Submitted to Toxicology Excellence for Risk Assessment. January/March 2013. NCI. 1978. Bioassay of 1,4-Dioxane for possible Carcinogenicity. Carcinogenesis Testing Program, Division of Cancer Cause and Prevention, National Cancer Institute. NIH, Bethesda, MD, 78-1330. Netherlands. 1999. Risk Assessment: 1, 4-Dioxane. Netherlands Organization for Applied Scientific Research (TNO) and the National Institute of Public Health and the Environment (RIVM). Chemical Substances Bureau, Ministry of Housing, Spatial Planning and the Environment (VROM), Netherlands, Final Version, 5 November, EINECS-No.: 204-661-8. arcadis.con 11 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications Neumann, H.G., H.W. Thielmann, J.G. Filser, H.P. Gelbke, H. Griem, H. Kappus, K.H. Norpoth, U. Reuter, S. Vamvakas, P. Wardenbach, and H.E. Wichmann. 1977. Proposed changes in the classification of carcinogenic chemicals in the work area. Reg. Toxicol. Pharmacol., 26:288-295. National Industrial Chemicals Notification and Assessment Scheme (NICNAS). 1998. Priority Existing Chemical Assessment Reports: 1,4-dioxane. Sydney, Australia: Australia Department of Health and Ageing. June. Available online at: NJDEP. 2014. Ground Water Quality Standards. N.J.A.C 7:9C. Available online at: http://www.nj.gov/dep/rules/rules/njac7_9c.pd Office of Environmental Health Hazard Assessment (OEHHA). 2002. Air Toxics Hot Spots Program. Risk Assessment Guidelines. Part II. Technical Support Document for Describing Available Cancer Potency Factors. Office of Environmental Health Hazard Assessment, California Environmental Protection Agency. December. Stickney, J.A., S.L. Sager, J.R. Clarkson, L.A. Smith, B.J. Locey, M.J. Bock, R. Hartung, and S.F. Olp. 2003. An updated evaluation of the carcinogenic potential of 1,4-dioxane. Regul Toxicol Pharmacol. 38(2):183-95. Thiess, A.M., E. Tress, and I. Fleig. 1976. Arbeitsmedizinische Untersuchungsergebnisse von Dioxan- exponierten Mitarbeitern [Industrial-medica investigation results in the case of workers exposed to dioxane]. Arbeitsmedizin, Sozialmedizin, Umweltmedizin, 11: 35-46. USEPA. 2005. Guidelines for carcinogen risk assessment, final report. EPA/630/P-03/001F. Risk Assessment Forum; U.S. Environmental Protection Agency. Washington, DC. March. USEPA. 2010. Toxicological Review of 1,4-Dioxane (CAS No. 123-91-1). EPA/635-R-09-005-F. Washington, D.C. August. USEPA. 2011. Recommended Use of Body Weight3/4 as the Default Method in Derivation of the Oral Reference Dose. EPA/100/R11/0001. Risk Assessment Forum. Washington, DC. USEPA. 2012. Benchmark Dose Technical Guidance. EPA/100/R-12/001. Risk Assessment Forum. Washington, DC. June 12. USEPA. 2013. Toxicological review of 1,4- Dioxane (with inhalation update) (CAS No. 123-91-1) in support of summary information on the Integrated Risk Information System (IRIS) [EPA Report]. (EPA-635/R-11/003-F). Washington, DC. USEPA. 2016a. Drinking Water Contaminant Candidate List 4 - Final. Federal Register Notice, Volume 81, No. 2222, Thursday, November 17. USEPA. 2016b. The Third Unregulated Contaminant Monitoring Rule (UCMR 3): Data Summary, July 2016. Office of Water (MS-140). EPA 815-S-16-004, Available at: USEPA. 2016c. Conducting a Human Health Risk Assessment, Dose-Response. Available at: arcadis.com 12 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 APPENDIX A Mode of Action Analysis for Liver Tumors Based on NCI Siide Reread and RfD Derivation (Dourson et al. 2014) Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 ARCADIS Gesign & for natural and built assets Appendix A MODE OF ACTION ANALYSIS FOR LIVER TUMORS BASED ON NCI SLIDE REREAD AND RFD DERIVATION (DOURSON ET AL. 2014) January 2017 Source: :ttps://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) CONTENTS Acronyms and Abbreviations ii 1 Reread of NCI (1978) Histopathology Slides and Mode of Action Evaluation for Hepatic Tumors in Mice 3 1.1 Review of 1,4-Dioxane's Genotoxicity Database 4 1.2 Mode of Action Analysis 4 1.2.1 Key Event 1: Accumulation of Parent Compound 5 1.2.2 Key Event 2: Liver Cell Hypertrophy and Necrosis 5 1.2.3 Key Event 3: DNA Synthesis 5 1.2.4 Key Event 4: Regenerative Cell Proliferation 5 1.2.5 Key Event 5: Promotion of Endogenously Initiated Tumors 6 1.3 Updated Dose-Response Assessment and Reference Dose Derivation for 1,4-Dioxane 6 2 References 8 arcadis.com i Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) ACRONYMS AND ABBREVIATIONS BMD benchmark dose-modeling CUF composite uncertainty factor EPL Experimental Pathology Laboratories JBRC Japan Bioassay Research Center mg/kg/d milligrams per kilogram body weight per day MOA mode of action NCI National Cancer Institute NOAEL no-observable-adverse-effect level POD point of departure RfD oral reference dose g/L micrograms per liter USEPA United States Environmental Protection Agency arcadis.com ii Source: https://wwww.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) 1 REREAD OF NCI (1978) HISTOPATHOLOGY SLIDES AND MODE OF ACTION EVALUATION FOR HEPATIC TUMORS IN MICE To test their hypothesis and better understand the "sequence of events that maybe have contributed to the MOA of the observed liver tumors," Dourson et al. (2014) and McConnell (2013) performed a blinded reread of the mouse National Cancer Institute (NCI) (1978) liver histopathology slides, because that study did not report non-neoplastic lesions in livers of the high-dose group. Note this is one of the two long-term oral mouse bioassays that exist for 1,4-dioxane; the other chronic mouse bioassay was performed by the Japan Bioassay Research Center (JBRC) and is reported most recently by Kano et al. (2009). As noted by Dourson et al. (2014): "Because terminology and practices for reporting liver lesions has changed since the time of the NCI study (1978), and because EPA (2005) is focusing more on an understanding of a chemical's Mode of Action (MOA) prior to any determination of its dose response, a re-review of the liver slides of mice from the NCI study (1978) was performed. This reanalysis was performed at the Experimental Pathology Laboratories (EPL), Research Triangle Park, NC during September through November 2012. The objective of the slide review was to determine if any non-neoplastic lesions in the liver were present in an effort to understand the sequence of events that may have contributed to the MOA of the observed liver tumors in mice. Another reason for the slide review was because at the time of the original slide review (i.e., 1978) the NCI typically recorded only the most severe diagnosis on a given slide, (e.g., adenoma or carcinoma). During this timeframe, the focus of cancer bioassays was to determine the potential carcinogenic activity of the chemical, not its potential chronic toxicity. For example, if an adenoma, carcinoma, and evidence of chronic toxicity (e.g., hepatocellular hypertrophy), were all present on a given slide, only the tumor response was typically recorded. Thus, it was unclear whether non-neoplastic lesions were present in the livers of mice but were not recorded in the NCI carcinogenicity study. McConnell's (2013) reread of the NCI (1978) mouse liver histopathology slides and Dourson et al.'s (2014) summary report demonstrate that chronic exposure to 1,4-dioxane in drinking water is associated with a non-linear mode of carcinogenic action (contrary to the United States Environmental Protection Agency's [USEPA's] low-dose extrapolation conclusion) based on several hepatotoxic effects that preceded tumor formation, including: Dose-dependent hepatocellular glycogen depletion Dose-dependent hepatocellular hypotrophy Dose-related hepatocellular necrosis Dose-dependent hepatocellular inflammation associated with necrosis Dose-related hyperplasia in several non-neoplastic cell types arcadis.com 3 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) Dourson et al. (2014) states: "The appearance of the liver toxicity follows the pattern where glycogen depletion occurs either concurrently with, or preceding, hypertrophy in both sexes. This was followed closely by necrosis and inflammation in males, but a high control incidence of necrosis and inflammation clouded this overall pattern found in females In terms of dose-response behavior, hypertrophy preceded the formation of foci, which appeared to precede formation of tumors. This pattern was also evident in an individual animal analysis." 1.1 Review of ,4-Dioxane's Genotoxicity Database As a component of their mode of action (MOA) analysis, Dourson et al. (2014) reviewed 1,4-dioxane's genotoxicity database using the information presented in USEPA's (2010) Toxicological Review for 1,4- dioxane. Dourson et al. (2014) noted: '1,4-dioxane has been tested for genotoxicity using in vitro assay systems with prokaryotic organisms, non-mammalian eukaryotic organisms, and mammalian cells, both with and without metabolic activation.' "[A]II fifteen mutagenicity tests reported (8 without activation and 7 with metabolic activation) were negative." "22 in vitro genotoxicity assays, and 9 in vivo genotoxicity assays were negative." "Eight genotoxicity assays were noted to be positive but only at high or noted cytotoxic doses." Based on their review of 1,4-dioxane's genotoxicity database, Dourson et al. (2014) states "1,4-dioxane does not cause point mutations, DNA repair, or [tumor] initiation" when administered at non-cytotoxic doses, which is in general agreement with USEPA's conclusions (USEPA 2010). The authors noted their conclusions were similar to USEPA's, but differ in that "if mutations are caused by 1,4-dioxane, it is only at high cytotoxic doses." The authors concluded: "1,4-dioxane does not cause mutagenicity as evidenced by uniformly negative results in standard in vitro and in vivo genotoxicity bioassays at levels that are not overtly toxic, but it may be a clastogen in vivo, in light of the mixed results in the micronucleus assays. It follows that mutations needed for tumor formation are then likely from the known endogenously available pool of mutations, and that a regenerative hyperplasia evokes more of these endogenous mutations to form tumors. Mutation potentially caused by 1,4-dioxane at high doses is precluded as a key event in tumor formation." 1.2 Mode of Action Analysis Dourson et al. (2014) proposed five key events in the non-mutagenic MOA resulting in hepatic tumors in rodents; they include: "(1) accumulation of parent compound [at concentrations that saturate metabolic processes], (2) liver cell hypertrophy and necrosis, (3) DNA synthesis, (4) regenerative cell proliferation, and (5) promotion of endogenously-initiated tumors.' The regenerative cell proliferation MOA has a threshold below which hepatic tumors are not formed. Evidence supporting each key event is presented below. arcadis.com 4 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) 1.2.1 Key Event 1: Accumulation of Parent Compound "Humans, rats, and mice extensively metabolize 1,4-dioxane.' "[M]etabolism is a capacity-limited process." "When dose of 1,4-dioxane approaches or exceeds the metabolizing capacity, the unmetabolized fraction of the dose increases and target organ toxicity occurs." "Thus, there appears to be a threshold below which metabolism and elimination are rapid and with less or perhaps without toxicological effects." "Human environmental exposures to 1,4-dioxane are unlikely to approach doses that saturate metabolizing enzymes and which produce liver and nasal tumors in rats." "Hence, since humans, like rats, efficiently metabolize 1,4-dioxane at low doses, enzyme saturation is negligible at low exposure levels." 1.2.2 Key Event 2: Liver Cell Hypertrophy and Necrosis "Liver cell hypertrophy and necrosis are key events in the 1,4-dioxane MOA leading to regenerative cell proliferation and, with chronic exposures, liver tumors.' "Liver changes including centrilobular swelling, single cell necrosis coincide exclusively with saturating doses of 1,4-dioxane and occur in as little as 11 weeks." "Evidence of hepatocellular damage preceding evidence of hepatocellular tumors caused by higher doses of 1,4-dioxane has been provided by several studies." 1.2.3 Key Event 3: DNA Synthesis USEPA (2010) reported "that 1,4-dioxane does not cause DNA repair activity in five standard in vitro and in vivo bioassays that tested for the presence of DNA repair in various model systems." "Conversely, 1,4-dioxane does cause DNA replication as evidenced by in vitro bioassays in rat hepatocytes" "DNA synthesis appears to be a key event for a regenerative cell proliferation and/or tumor promotion and can occur in either the presence or absence of cytotoxicity." "DNA synthesis provides evidence that 1,4-dioxane promotes cell proliferation through cytotoxicity." 1.2.4 Key Event 4: Regenerative Cell Proliferation "Dose-response and temporal data support the occurrence of cell proliferation and hyperplasia prior to the development of liver tumors in the rat model." "Cell proliferation appears to be an early response with significant changes (1.5- to 2-fold) occurring in rats with as little as 2 weeks of exposure." arcadis.com 5 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) "Given time, proliferative changes manifest as pre-neoplastic foci in studies where the histopathology of such changes are reported." 1.2.5 Key Event 5: Promotion of Endogenously Initiated Tumors "Three studies relevant to tumor initiation and promotion establish that 1,4-dioxane does not cause initiation in standard in vivo bioassays, in agreement with the absence of observed mutagenic or genotoxic activity." "[T]umor promotion was associated with significant toxicity in rats when administered by either dermal or oral routes." 1.3 Updated Dose-Response Assessment and Reference Dose Derivation for 1,4-Dioxane Dourson et al. (2014) and USEPA (2010) both relied on the dose-response data reported by Kociba et al. (1974). This study provided data for liver and kidney degeneration and necrosis in 6- to 8-week-old male and female Sherman rats (60/sex/dose group) that were exposed to 1, ,4-dioxane at 0, 0.01, 0.1, or 1% (i.e., 9.6, 94, and 1,015 milligrams per kilogram body weight per day [mg/kg/d] and 19, 148, and 1,599 mg/kg/d for males and females, respectively) in drinking water for up to 716 days. The study reported a no-observed-adverse-effect level (NOAEL) of 9.6 mg/kg/d and provides "the most sensitive measure of adverse effects by 1,4-dioxane" (USEPA 2010). USEPA's Toxicological Review for 1,4-dioxane (USEPA 2010) provides a reference dose (RfD) of 0.03 mg/kg/d. This RfD was derived using the NOAEL of 9.6 mg/kg/d for liver and kidney degeneration and necrosis in rats reported by Kociba et al. (1974) as the point of departure (POD), in combination with a composite uncertainty factor (CUF) of 300 (10 for interspecies extrapolation, 10 for intraspecies extrapolation, and 3 for database deficiencies associated with the lack of a multigenerational reproductive toxicity study). The lowest-observable-adverse-effect level for this study was 94 mg/kg/d (USEPA 2010). USEPA derived the RfD using the NOAEL reported by Kociba et al. (1974) because the published study did not report incidence data for these effects, and therefore, they were unable to perform benchmark dose-modeling (BMD). Alternatively, Dourson et al. (2014) reported an updated RfD of 0.05 mg/kg/d that was derived using incidence data (laboratory report for the published study was provided to Dourson et al. [2014] by The Dow Chemical Company) for hepatocellular necrosis (combined across sexes) and USEPA's preferred approaches¹. Specifically, Dourson et al. (2014) utilized USEPA's preferred BMD approach (USEPA 2012) to derive a POD of 20 mg/kg/d (95% lower bound on the dose associated with a 10% extra risk), USEPA's preferred default bodyweight scaling factor (USEPA 2011), to estimate a human equivalent 1 USEPA (2010) used the NOAEL from Kociba et al. (1974) based on liver and kidney degeneration to derive the RfD, specifically because Kociba et al. (1974) did not provide quantitative incidence or severity data for liver and kidney degeneration and necrosis. However, when appropriate data are available, USEPA prefers using BMD to define the POD (USEPA 2012). Had the incidence data from Kociba et al. (1974) been available at the time of their review, USEPA would have used it to derive a benchmark dose to use as the POD for setting the RfD. arcadis.com 6 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) dose, in combination with a CUF of 100 (3 for interspecies toxicodynamic extrapolation, 10 for intraspecies extrapolation, and 3 due to the lack of a 2-generation reproductive study) to derive an RfD of 0.05 mg/kg/d. Dourson et al. (2014) concluded that "the choice of this endpoint [hepatocellular necrosis] is protective, since liver toxicity, resulting in liver tumors, is the clear apical effect of greatest intensity in the available array of toxic effects." Dourson et al. (2014) calculated their RfD using standard approaches, as shown in Equation (1), below: POD 20 mg/kg/d Equation (1) RfD = = 0.05 mg/kg/d CUF 3x10x3 arcadis.com 7 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) 2 REFERENCES Dourson, M., J. Reichard, P. Nance, H. Burleigh-Flayer, A. Parker, M. Vincent, and E.E. McConnell. 2014. Mode of action analysis for liver tumors from oral 1,4-dioxane exposures and evidence-based dose response assessment. Regul Toxicol Pharmacol. 68: 387-401. Kano, H., Y, Umeda, T. Kasai, T. Sasaki, M. Matsumoto, K. Yamazaki, K. Nagano, H. Arito, and S. Fukushima. 2009. Carcinogenicity of 1,4-dioxane administered in drinking-water to rats and mice for 2 years. Food Chem Toxicol. 47:2776 - 2784. Kociba, R.J., S.B. McCollister, C. Park, T.R. Torkelson, and P.J. Gehring. 1974. 1,4-dioxane. I. Results of a 2-year ingestion study in rats. Toxicol Appl Pharmacol, 30: 275-286. oi:10.1016/0041- 008X(74)90099-4. McConnell, G. 2013. Report on the review of liver slides from the National Cancer Institute's Bioassay of 1,4-Dioxane for Possible Carcinogenicity Conducted in 1978 (NCI, 1978). Submitted to Toxicology Excellence for Risk Assessment. January/March 2013. NCI. 1978. Bioassay of 1,4-Dioxane for possible Carcinogenicity. Carcinogenesis Testing Program, Division of Cancer Cause and Prevention, National Cancer Institute. NIH, Bethesda, MD, 78-1330. USEPA. 2005. Guidelines for carcinogen risk assessment, final report. EPA/630/P-03/001F. Risk Assessment Forum; U.S. Environmental Protection Agency. Washington, DC. March. USEPA. 2010. Toxicological Review of 1,4-Dioxane (CAS No. 123-91-1). EPA/635-R-09-005-F. Washington, D.C. August. USEPA. 2012. Benchmark Dose Technical Guidance. EPA/100/R-12/001. Risk Assessment Forum. Washington, DC. June 12. arcadis.com 8 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 APPENDIX B Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) Source: https://www.industrydocuments.ucsf,edu/docs/fsbn0226 ARCADIS Desion & for natural and built assets Appendix B MODE OF ACTION ANALYSIS FOR LIVER TUMORS BASED ON JBRC REVIEW (DOURSONETAL.2016IN PEER REVIEW) January 2017 Source: :ttps://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) CONTENTS Acronyms and Abbreviations ii 1 Findings from Detailed Review of JBRC Rat Bioassays 3 1.1 Findings from Detailed Review of JBRC Mouse Bioassays 3 1.2 Integration of Evidence Supporting Regenerative Cell Proliferation MOA for 1,4-Dioxane 4 2 References 6 TABLES Table 1. Integration and Comparison of Rat and Mouse Bioassay Data (Adapted from Dourson et al., 2016 in peer review) 5 arcadis.com i Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) ACRONYMS AND ABEREVIATIONS JBRC Japan Bioassay Research Center mg/kg/d milligrams per kilogram body weight per day MOA mode of action NCI National Cancer Institute arcadis.com ii Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) 1 FINDINGS FROM DETAILED REVIEW OF JBRC RAT BIOASSAYS Changes in the liver found in the Japan Bioassay Research Center (JBRC) rat bioassays provide strong evidence that hepatic tumors were modulated by a threshold-based regenerative cell proliferation mode of action (MOA). Dourson et al. (2016 in peer review) found that effects observed in rats were in the expected dose-sequence for a regenerative cell proliferation MOA. Specifically, Dourson et al. (2016 in peer review) observed the following sequence of effects: Dose: 42-55 milligrams per kilogram body weight per day (mg/kg/d) - Effect: Liver swelling, hypertrophy, and liver weight increase Dose: 94-219 mg/kg/d - Effect: Necrosis Dose: 55-389 mg/kg/d - Effect: Hyperplasia and foci development Dose: >200 mg/kg/d - Effect: Increased levels of enzymes associated with liver damage Dose: 274-1015 mg/kg/d - Effect: Adenomas and carcinomas 1.1 Findings from Detailed Review of JBRC Mouse Bioassays Dourson et al. (2016 in peer review) observed the following sequence of effects in the JBRC (1990a) mouse bioassays: Dose: 190-200 mg/kg/d - Effect: Liver swelling, hypertrophy, and liver weight increase Dose: 190-200 mg/kg/d - Effect: Necrosis Dose: Not reported - Effect: Hyperplasia and foci development not reported Dose: 200 mg/kg/d - Effect: Increased levels of enzymes associated with liver damage Dose: 66-964 mg/kg/d - Effect: Adenomas and carcinomas, females Surprisingly, effects in the liver found in the JBRC mouse bioassays conflict with those clearly reported by Dourson et al. (2014) and McConnell (2013) for the reread of the National Cancer Institute (NCI) (1978) mouse bioassay histopathology slides. Additionally, the progression of effects reported by JBRC for the 2- year chronic study is inconsistent with enzymatic changes indicative of liver damage noted in the same study, as well as findings from a 13-week precursor study performed by the same laboratory. As noted by Dourson et al. (2016 in peer review), "the lack of noncancer histopathology in the chronic mouse study is not consistent with the changes in liver enzymes in this same chronic study, nor is this lack of noncancer arcadis.com 3 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) findings expected based on the histopathology of the precursor 13-week study" and "[n]or does the tumor response in the low dose female mice of JBRC (1990a) match the tumor findings in the McConnell (2013) re-read of NCI (1978). Dourson et al. (2016 in peer review) hypothesized that differences in mouse bioassay results between JBRC and McConnell (2013) may be due to differences in the interpretation of the histopathological data, and provided the following quote from JBRC (Kano et al. 2009) to substantiate their claim: "The hepatic hyperplasia of rats and mice diagnosed in the previous report (Yamazaki et al., 1994) [authors note: which was a presentation of the JBRC, 1990a] was re-examined histopathologically and changed to hepatocellular adenomas and altered hepatocellular foci including acidophilic, basophilic and clear cell foci in the present studies, according to the current diagnostic criteria of liver lesions in rats and mice." Unfortunately, slides from the original JBRC (1990a,b) bioassays were not available; therefore, the JBRC slides could not be reread as they were by McConnell (2013) for the NCI (1978) mouse liver slides. Additionally, JBRC did not archive sufficient numbers of pictures of histopathology slides to resolve the issue. While, it is impossible to know for sure from this dataset whether liver tumors formed prior to or following cytotoxic effects, the weight of evidence from the JBRC and NCI mouse bioassays supports a regenerative cell proliferation MOA. 1.2 Integration of Evidence Supporting Regenerative Cell Proliferation MOA for 1,4-Dioxane Following integration of key events from seven rat bioassays, three mouse bioassays, and 1,4-dioxane's genotoxicity profile, presented in Table 1 below, Dourson et al. (2016 in peer review) showed that 1,4- dioxane's toxicological database supports a threshold-based regenerative cell proliferation MOA for tumor formation in livers of rodents orally exposed to 1,4-dioxane. The authors reported that bioassay data for rats leads to the conclusion that "rat liver tumors are evoked by a regenerative hyperplasia," while the authors concluded the "sequence of events from two chronic mouse studies and a subchronic mouse study generally support the hypothesized regenerative hyperplasia MOA" (Dourson et al. 2016 in peer review). In regards to the conflicting mouse bioassay data (McConnell 2013; Dourson et al. 2014; JBRC 1990a), the difference is likely due in part to changes in the terminology and practices used for recording the liver lesions reported by Kano et al. (2009). arcadis.com 4 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226

what is the value CSF ?

fsbn0226

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0.1

Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 2 USEPA APPROACH FOR EVALUATING CANCER RISHS POSED BY ORAL EXPOSURE TO 1,4-DIOXANE USEPA's Integrated Risk Information System (IRIS) published the Toxicological Review for 1,4-dioxane, in which it describes their approach and justification for deriving an oral CSF for this constituent. Below is a summary of USEPA's evaluation of available human toxicological data, weight of evidence evaluation, key study identification, critical effect selection, dose-response assessment, and the low-dose extrapolation procedure used to derive 1,4-dioxane's CSF. 2.1 USEPA's Evaluation of Evidence of Cancer in Humans USEPA evaluated the degree to which data provide evidence of carcinogenicity in humans (USEPA 2010). USEPA relied on two human occupational studies in their evaluation of potential impacts related to long-term exposure to 1,4-dioxane (Thiess et al. 1976; Buffler et al. 1978). USEPA concluded that neither study provided evidence that 1, ,4-dioxane causes cancer in humans. However, they noted "the cohort size and number of reported cases were small." 2.2 USEPA's Evaluation of Evidence of Cancer in Animal Bioassays USEPA followed its Guidelines for Carcinogen Risk Assessment (USEPA 2005) to conclude that 1,4- dioxane is "likely to be carcinogenic to humans" based on "evidence of liver carcinogenicity in several 2- year bioassays conducted in three strains of rats, two strains of mice, and in guinea pigs.' USEPA provided several reasons to justify its conclusion. For instance, USEPA concluded that the "available evidence is inadequate to establish a MOA by which 1,4-dioxane induces liver tumors in rats and mice" (USEPA 2010). Specifically, USEPA noted the "[c]onflicting data from rat and mouse bioassays (Japan Bioassay Research Center [JBRC] 1998; Kociba et al., 1974) suggest that cytotoxicity may not be a required precursor event for 1,4-dioxane-induced cell proliferation." USEPA (2010) noted that "[a]vailable data also do not clearly identify whether 1,4-dioxane or one of its metabolites is responsible for the observed effects. However, USEPA also reported that "the generally negative results for 1,4-dioxane in a number of genotoxicity assays indicates the carcinogenicity of 1,4-dioxane may not be mediated by a mutagenic MOA" (USEPA 2010). 2.3 Key Study Identification (Kano et al. 2009), Critical Effect Selection, Dose-Response Assessment, and Low-Dose Extrapolation Procedure USEPA (2010) concluded that the MOA by which 1,4-dioxane produces liver tumors is "unknown, and available evidence in support of any hypothetical mode of carcinogenic action for 1,4-dioxane is inconclusive." With this conclusion in mind, USEPA (2010) identified a 2-year drinking water study performed by Kano et al. (2009) as the key study of the oral CSF for 1,4-dioxane. Note that Kano et al. (2009) published findings originally reported by the JBRC (1990a). Although USEPA (2010) concurrently evaluated two other studies (Kociba et al. 1974; National Cancer Institute [NCI] 1978), the Kano et al. (2009) study was ultimately selected as the key study because USEPA (2010) noted that "[c]alculation of arcadis.com 3 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications a CSF for 1,4-dioxane is based upon the dose-response data for the most sensitive species and gender." The study was performed in accordance with the Organization of Economic Development's Principles for Good Laboratory Practices and involved exposing groups of rats (50 animals of each sex for each dose) and mice (50 animals of each sex for each dose) to 1,4-dioxane (>99% pure) in drinking water for 2 years. Rats were exposed to 1,4-dioxane in drinking water at 0, 200, 1,000, or 5,000 milligrams per liter (mg/L), while mice were exposed at 0, 500, 2,000, or 8,000 mg/L in drinking water. As reported by USEPA (2010): "The investigators used data from water consumption and BW [body weight] to calculate an estimate of the daily intake of 1,4-dioxane (mg/kg-day) by male and female rats and mice. Kano et al. (2009) reported a calculated mean + standard deviation for the daily doses of 1,4-dioxane for the duration of the study. Male rats received doses of approximately 0, 11+1, 55+3, or 274+18 mg/kg-day and female rats received 0, 183, 83+14, or 429+69 mg/kg-day. Male mice received doses of 0, 49+5, 191+21, or 677+74 mg/kg-day and female mice received 0, 66=10, 278+40, or 964+88 mg/kg-day." "The study by Kano et al. (2009) was used for development of an oral CSF. This was a well- designed study, conducted in both sexes in two species (rats and mice) with a sufficient number (N=50) of animals per dose group. The number of test animals allocated among three dose levels and an untreated control group was adequate, with examination of appropriate toxicological endpoints in both sexes of rats and mice. Alternative bioassays (Kociba et al., 1974; NCI, 1978) were available and were fully considered for the derivation of the oral CSF." USEPA identified increased incidence of liver adenomas or carcinomas as the critical effect in rats and mice exposed to 1,4-dioxane in the Kano et al. (2009) study. Following standard dose adjustment to a human equivalent dose using a default body weight (BW) scaling factor (USEPA 2005), USEPA performed dose-response modeling using Benchmark Dose Software and fit the suite of models available in the program to the incidence data for "either hepatocellular carcinoma or adenoma" (USEPA 2010). USEPA concluded that female mice are "more sensitive to liver carcinogenicity induced by 1,4-dioxane compared to other species or tumor types" and identified the lower 95% confidence bound on the benchmark dose associated with a 50% extra risk (benchmark response [BMR]) of developing "either hepatocellular carcinoma or adenoma" (4.95 milligrams per kilogram per day [mg/kg/d]) as the point of departure (POD) for calculating the oral CSF via linear low-dose extrapolation, as shown in Equation (1), below. USEPA (2010) again justified a linear low-dose extrapolation approach based on their conclusion that 1,4-dioxane's MOA for production of hepatic tumors in rodents is "unknown." BMR 0.5 Equation (1) CSF = = 0.1 (mg/kg/d)1 POD 4.95 mg/kg/d 2.4 Comments Provided to USEPA During External Peer Review When USEPA's IRIS program derives toxicity values, the Toxicological Review undergoes critical evaluation by individuals from within and outside the agency. A result of the outside review efforts indicated several external peer review panel members believed that available information for 1,4-dioxane could "support the use of a nonlinear extrapolation approach to estimate human carcinogenic risk" and arcadis.con 4 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications that "such an approach should be presented in the Toxicological Review.' Specifically, the USEPA (2010) notes: "[N]umerous short-term in vitro and a few in vivo tests were nonpositive for 1,4-dioxane-induced genotoxicity". Results from two-stage mouse skin tumor bioassays "suggest that a potential mode of action for 1,4- dioxane-induced tumors may involve proliferation of cells initiated spontaneously, or by some other agent, to become tumors." Additionally, a public commenter noted: "Low-dose linear extrapolation for the oral CSF is not appropriate nor justified by the data. The weight of evidence supports a threshold (nonlinear) MOA when metabolic pathway is saturated at high doses. Nonlinear extrapolations should be evaluated and presented for 1,4-dioxane." These statements indicated that some reviewers felt the toxicological data for 1,4-dioxane indicated that it may not behave in a linear manner, but rather as a threshold carcinogen. Nonetheless, USEPA (2010) ultimately concluded that there was insufficient information available to support any of the proposed MOAs and proceeded to adopt, albeit imprecisely in hindsight, the default linear low-dose extrapolation approach. arcadis.com 5 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 3 DOURSON ET AL. (2014): MODE OF ACTION (MOA) ANALYSIS FOR LIVER TUMORS FROM ORAL 1,4- DIOXANE EXPOSURES AND EVIDENCE-BASED DOSE ss RESPONSE ASSESSMENT USEPA's (2010) conclusion to evaluate 1,4-dioxane as a non-threshold, linear, low-dose extrapolation carcinogen, was "based, in part, on the following: (1) apparent uncertainty in the toxic moiety for 1,4- dioxane; and, (2) apparent lack of noncancer toxicity data from several mouse bioassays at doses that evoke tumors, or that otherwise appear to have conflicting information concerning non-neoplastic lesions in the liver of rodents exposed orally to 1,4-dioxane" (Dourson et al. 2014). Recognizing that the key studies were performed over 3 decades, Dourson et al. (2014) hypothesized that "differences in histologic approaches for quantifying and reporting non-neoplastic changes may have been responsible for the differences noted across the studies" and would account for the apparent lack of non-cancer toxicity data reported in the key mouse bioassays. In addition to directly testing this hypothesis, Dourson et al. (2014) reviewed the database of genotoxicity studies, "which included DNA replication and promotion bioassays as well as mutation, initiation, and DNA repair studies," synthesized the genotoxicity database for 1,4- dioxane, and developed and analyzed a biologically plausible MOA for the formation of hepatic tumors in rodents by employing USEPA's (2005) carcinogen guidelines. Dourson et al.'s (2014) findings from the reread of the NCI (1978) mouse bioassay histopathology slides and review of the extensive genotoxicity database demonstrates that chronic exposure to 1,4-dioxane in drinking water is associated with a non-linear mode of carcinogenic action (threshold). which is contrary to USEPA's default linear low-dose extrapolation approach (non-threshold). The cancer MOA developed by Dourson et al. (2014) also afforded new data with which to perform an improved dose-response assessment for 1,4-dioxane using toxicological endpoints that protect against 1,4-dioxane's cancer MOA (refer to Appendix A for additional details). In regards to choosing a low-dose extrapolation approach, USEPA's Guidelines for Carcinogen Risk Assessment (2005) plainly state that "[a] nonlinear approach [i.e., derivation of a reference dose or concentration] should be selected when there are sufficient data to ascertain the mode of action and conclude that it is not linear at low doses and the agent does not demonstrate mutagenic or other activity consistent with linearity at low doses.' The information presented by USEPA (2010) and supplemented by the new information from Dourson et al. (2014) shows that: (1) 1,4-dioxane causes tumors at high doses through an MOA that involves cytotoxic effects, regenerative cell proliferation, and subsequent tumor formation; (2) the effects that precede tumor formation display non-linear dose-responses; and (3) 1,4- dioxane does not cause mutations at concentrations that are not cytotoxic. As a result, the RfD of 0.05 mg/kg/d developed by Dourson et al (2014) addressed key data gaps identified by USEPA (2010) and protects against the development of liver cancers following oral exposure to 1,4-dioxane. arcadis.com 6 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 4 DOURSON ET AL. (2016 IN PEER REVIEM: UPDATED MODE OF ACTION ANALYSIS (MOA) FOR LIVER TUMORS FROM ORAL ,4-DIOXANE EXPOSURES AND EVIDENCE-BASED DOSE-RESPONSE ASSESSMENT While Dourson et al. (2014) demonstrated that a threshold-based, regenerative cell proliferation MOA accounted for the tumor findings in the NCI (1978) mouse bioassay, questions still remained about the tumor findings from a 2-year oral mouse bioassay and a 13-week precursor study reported by the JBRC (1990a,b), subsequently published as Kano et al. (2008, 2009). Similar to the NCI (1978) mouse bioassay discussed in Dourson et al. (2014), the Japanese work provided few details or findings regarding non- cancer toxicity in the mouse liver after long-term exposure to 1,4-dioxane. To address the remaining questions regarding the apparently discordant findings between the tumor MOA in mice and rats and enhance the investigation of the threshold-based MOA for hepatic tumor formation, Dourson et al. (2016 in peer review) performed a detailed evaluation of the translated Japanese rodent bioassay reports (JBRC 1990a,b) and integrated the findings with other lines of evidence for the regenerative cell proliferation MOA. This effort is summarized in Appendix B. In addition to the detailed evaluation of the JBRC (1990a,b) bioassays, Dourson et al. (2016 in peer review) also solicited opinions from several pathologists regarding the conflicting findings from the mouse bioassays. Dourson et al. (2016 in peer review) reported: "Collectively these pathology opinions support the hypothesized MOA discussed in U.S. EPA (2013) and Dourson et al. (2014) that the liver tumors from oral exposure to 1,4-dioxane occur after metabolic saturation, accumulation of the parent 1,4-dioxane molecule, liver toxicity and a regenerative hyperplasia. While additional live experimental animal testing might add confirmatory findings, a threshold for these tumors is expected if metabolism of the parent compound is not saturated, since subsequent liver toxicity does not occur." By integrating all lines of evidence, Dourson et al. (2016 in peer review) concluded: "When the many lines of evidence are taken together, the reevaluation of the Japanese studies show consistent findings in rats and consistent findings in mice other than liver histopathology not being fully recorded in the second chronic study. However, based on the number of studies conducted, the well established metabolic saturation of 1,4-dioxane metabolism in humans and experimental animals, the effects of higher dose exposures on target organ toxicity, the presence of proliferative lesions, the effect of dose and time on the progression of lesions, the time of appearance of tumors, the spectrum of tumors developed, the number and incidence of tumors at organ sites with high or low background historical incidence, and the shapes of the dose-response curve for key events and tumors, all lead to the conclusion that a regenerative hyperplasia MOA is operating with 1,4-dioxane induced liver tumors." arcadis.con 7 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 5 IMPACT OF DOURSON ET AL.S UPDATED TOXICITY ASSESSMENT ON RISK-BASED DRINKING WATER CRITERIA An agency's choice to set risk-based criteria for 1,4-dioxane based on a threshold- or non-threshold- approach has the potential to drastically impact the value of the final criterion. An example of this is provided herein based on the approach used by the New Jersey Department of Environmental Protection (NJDEP) to derive groundwater quality criteria (NJDEP 2014). The risk-based equations NJDEP uses to derive groundwater criteria for threshold and non-threshold toxicants are shown below in Equations (2) and (3), respectively, while default exposure factors are shown in Table 1 below. Using the RfD of 0.05 mg/kg/d derived from Kociba et al. (1974) by Dourson et al. (2014) to protect against a regenerative cell proliferation MOA yields a risk-based criterion of 400 g/L Using USEPA's (2010) CSF of 0.1 (mg/kg/d)-¹ yields a risk-based criterion of 0.4 (0.35) g/L, corresponding to a 1 in 1,000,000 (1x10-6) excess lifetime cancer risk. Therefore, using the toxicity value derived based on a regenerative cell proliferation MOA (RfD, threshold approach) yields a criterion that is 1,000 times higher than the value derived using USEPA's CSF approach (linear low-dose extrapolation, non-threshold). The authors of this paper conclude that sites monitoring groundwater containing 1,4-dioxane at levels below 400 g/L would meet a reasonable groundwater quality criterion that is protective of human health. RfD x BW x CF x RSC Equation (2) Criterion = x UF BW x CF Equation (3) Criterion = x IRDW arcadis.com 8 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications Table 1. Toxicity Values and NJDEP's Exposure Factors for Calculating Risk-Based Groundwater Quality Criteria Exposure Pactor Units value bource RfD mg/kg/d 0.05 Dourson et al. (2014) CSF (mg/kg/d)-1 0.1 USEPA (2010) Target risk (TR) unitless 10-6 NJDEP default BW kg 70 NJDEP default Conversion factor (CF) g/mg 1,000 NJDEP default Relative source contribution (RSC) unitless 0.2 NJDEP default Drinking water ingestion rate (IRDw) L/d 2 NJDEP default Uncertainty factor (UF) unitless 1 NJDEP default Notes: kg = kilograms L/d = liters per day g/mg = micrograms per milligram arcadis.com 9 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 6 SUMMARY AND CONCLUSIONS To support several state regulatory agencies, Dourson et al. (2016 in peer review) recently undertook additional scientific investigations to address data gaps identified in USEPA's (2010) Toxicological Review regarding 1,4-dioxane's cancer MOA and assessment approach. Collectively, Dourson et al.'s (2014, 2016 in peer review) cancer MOA evaluations and dose-response assessments addressed USEPA's uncertainties and indeed demonstrate that chronic exposure to 1,4-dioxane in drinking water is associated with a non-linear mode of carcinogenic action (threshold). These additional scientific findings provide new information that resolve 1,4- dioxane's cancer MOA and support use of a non-linear dose response approach to protect against development of cancer following low-dose oral exposures. USEPA's (2010) cancer evaluation showed that 1,4-dioxane is not mutagenic or genotoxic at non- cytotoxic doses. However, USEPA ultimately chose to use a linear low-dose extrapolation approach for estimating human cancer risk from oral exposure to 1, 4-dioxane because they concluded that the MOA for tumor formation was unknown. The recent scientific investigations by Dourson et al. (2014, 2016 in peer review) provide new information to address data gaps identified by USEPA (2010) and demonstrate that 1,4-dioxane causes liver tumors in rodents through a regenerative cell proliferation MOA. The regenerative cell proliferation MOA is characterized by: (1) metabolic saturation and accumulation of parent compound; (2) cellular swelling, hypertrophy, and liver weight increase; (3) necrosis and/or inflammation; (4) increased DNA synthesis, hyperplasia development, and foci development; and (5) development of liver adenoma and carcinomas. Specifically, 1,4-dioxane must accumulate in the liver to levels that cause inflammation and cell damage before liver tumors can form. If the first key event does not occur (metabolic saturation), then liver tumors will not form. Therefore, there is a threshold of exposure for 1,4-dioxane below which tumors do not form and it is appropriate to use a non-linear low-dose extrapolation procedure for estimating risks. The RfD of 0.05 mg/kg/d derived by Dourson et al. (2014) is protective against tumor formation through this series of events (MOA) and was calculated using USEPA's preferred methods and best available scientific practices. Using Dourson et al.'s (2014) peer-reviewed RfD, based on a regenerative cell proliferation MOA to derive a groundwater drinking water criterion results in a criterion (400 g/L) that is 1,000 times greater than the concentration derived using USEPA's default CSF approach (0.4 g/L). Based on Dourson et al.'s (2014, 2016 in peer review) studies, it is reasonable to conclude that sites that monitor groundwater containing 1,4-dioxane at levels below 400 g/L would meet a reasonable groundwater quality criteria. The recent scientific findings summarized in this report have major implications for sites that are currently or will be managing water resources impacted by 1,4-dioxane. Considering that 1,4-dioxane is emerging as a water resource contaminant, in part due to USEPA's default linear low-dose cancer evaluation approach for liver tumors in rodents (USEPA 2010), the updated toxicology evidence that 1,4-dioxane is a threshold carcinogen is significant, and suggests that many current regulatory guidelines and standards are unnecessarily low. As such, the authors of this paper conclude that sites that monitor groundwater containing 1,4-dioxane at levels below 400 g/L would meet a reasonable groundwater quality criteria that is protective of human health. arcadis.con 10 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 7 REFERENCES ARA. 2016. 1,4-Dioxane Analysis. Available on line [Accessed Dec. 19] at: http://allianceforrisk.org/riskie- 2/. Buffler, P.A., S.M. Wood, L. Suarez, and D.J. Kilian. 1978. Mortality follow-up of workers exposed to 1,4- dioxane. J Occup Environ Med, 20: 255-259. Dourson, M., J. Reichard, P. Nance, H. Burleigh-Flayer, A. Parker, M. Vincent, and E.E. McConnell. 2014. Mode of action analysis for liver tumors from oral 1,4-dioxane exposures and evidence-based dose response assessment. Regul Toxicol Pharmacol. 68: 387-401. Dourson, M., J. Higginbotham, J. Crum, H. Burleigh-Flayer P, Nance, N. Forsberg, and M. Lafranconi. 2016 in peer review. Update: Mode of Action (MOA) for Liver Tumors Induced by Oral Exposure to 1,4-Dioxane. Regul Toxicol Pharmacol. Available online at: http://allianceforrisk.org/14-dioxane- analysis/. Health Canada. 2005. Drinking Water Guidance Value for 1,4-Dioxane. August 23. JBRC. 1990a. Report of Carcinogenicity Study by Oral Administration of 1,4-Dioxane (Mixed with Water) to Rats and Mice. Japan Industrial Safety and Health Association. December 28. JBRC. 1990b. Report of Preliminary Carcinogenicity Studies (Acute, Two-Week, and Thirteen-Week Studies) by Oral Administration of ,4-Dioxane (Mixed with Water) to Rats and Mice. Japan Industrial Safety and Health Association. December 28. Kano. H., Y. Umeda, M. Saito, H. Senoh, H. Ohbayashi, S. Aiso, K. Yamazaki, K. Nagano, and S. Fukushima. 2008. Thirteen-week oral toxicity of 1,4-dioxane in rats and mice. J Toxicol Sci. 33: 141- 153. Kano, H., Y, Umeda, T. Kasai, T. Sasaki, M. Matsumoto, K. Yamazaki, K. Nagano, H. Arito, and S. Fukushima. 2009. Carcinogenicity of 1,4-dioxane administered in drinking-water to rats and mice for 2 years. Food Chem Toxicol. 47:2776 - 2784. Kociba, R.J., S.B. McCollister, C. Park, T.R. Torkelson, and P.J. Gehring. 1974. 1,4-dioxane. I. Results of a 2-year ingestion study in rats. Toxicol Appl Pharmacol, 30: 275-286. doi:10.1016/0041- 008X(74)90099-4. McConnell, G. 2013. Report on the review of liver slides from the National Cancer Institute's Bioassay of 1,4-Dioxane for Possible Carcinogenicity Conducted in 1978 (NCI, 1978). Submitted to Toxicology Excellence for Risk Assessment. January/March 2013. NCI. 1978. Bioassay of 1,4-Dioxane for possible Carcinogenicity. Carcinogenesis Testing Program, Division of Cancer Cause and Prevention, National Cancer Institute. NIH, Bethesda, MD, 78-1330. Netherlands. 1999. Risk Assessment: 1, 4-Dioxane. Netherlands Organization for Applied Scientific Research (TNO) and the National Institute of Public Health and the Environment (RIVM). Chemical Substances Bureau, Ministry of Housing, Spatial Planning and the Environment (VROM), Netherlands, Final Version, 5 November, EINECS-No.: 204-661-8. arcadis.con 11 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications Neumann, H.G., H.W. Thielmann, J.G. Filser, H.P. Gelbke, H. Griem, H. Kappus, K.H. Norpoth, U. Reuter, S. Vamvakas, P. Wardenbach, and H.E. Wichmann. 1977. Proposed changes in the classification of carcinogenic chemicals in the work area. Reg. Toxicol. Pharmacol., 26:288-295. National Industrial Chemicals Notification and Assessment Scheme (NICNAS). 1998. Priority Existing Chemical Assessment Reports: 1,4-dioxane. Sydney, Australia: Australia Department of Health and Ageing. June. Available online at: NJDEP. 2014. Ground Water Quality Standards. N.J.A.C 7:9C. Available online at: http://www.nj.gov/dep/rules/rules/njac7_9c.pd Office of Environmental Health Hazard Assessment (OEHHA). 2002. Air Toxics Hot Spots Program. Risk Assessment Guidelines. Part II. Technical Support Document for Describing Available Cancer Potency Factors. Office of Environmental Health Hazard Assessment, California Environmental Protection Agency. December. Stickney, J.A., S.L. Sager, J.R. Clarkson, L.A. Smith, B.J. Locey, M.J. Bock, R. Hartung, and S.F. Olp. 2003. An updated evaluation of the carcinogenic potential of 1,4-dioxane. Regul Toxicol Pharmacol. 38(2):183-95. Thiess, A.M., E. Tress, and I. Fleig. 1976. Arbeitsmedizinische Untersuchungsergebnisse von Dioxan- exponierten Mitarbeitern [Industrial-medica investigation results in the case of workers exposed to dioxane]. Arbeitsmedizin, Sozialmedizin, Umweltmedizin, 11: 35-46. USEPA. 2005. Guidelines for carcinogen risk assessment, final report. EPA/630/P-03/001F. Risk Assessment Forum; U.S. Environmental Protection Agency. Washington, DC. March. USEPA. 2010. Toxicological Review of 1,4-Dioxane (CAS No. 123-91-1). EPA/635-R-09-005-F. Washington, D.C. August. USEPA. 2011. Recommended Use of Body Weight3/4 as the Default Method in Derivation of the Oral Reference Dose. EPA/100/R11/0001. Risk Assessment Forum. Washington, DC. USEPA. 2012. Benchmark Dose Technical Guidance. EPA/100/R-12/001. Risk Assessment Forum. Washington, DC. June 12. USEPA. 2013. Toxicological review of 1,4- Dioxane (with inhalation update) (CAS No. 123-91-1) in support of summary information on the Integrated Risk Information System (IRIS) [EPA Report]. (EPA-635/R-11/003-F). Washington, DC. USEPA. 2016a. Drinking Water Contaminant Candidate List 4 - Final. Federal Register Notice, Volume 81, No. 2222, Thursday, November 17. USEPA. 2016b. The Third Unregulated Contaminant Monitoring Rule (UCMR 3): Data Summary, July 2016. Office of Water (MS-140). EPA 815-S-16-004, Available at: USEPA. 2016c. Conducting a Human Health Risk Assessment, Dose-Response. Available at: arcadis.com 12 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 APPENDIX A Mode of Action Analysis for Liver Tumors Based on NCI Siide Reread and RfD Derivation (Dourson et al. 2014) Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 ARCADIS Gesign & for natural and built assets Appendix A MODE OF ACTION ANALYSIS FOR LIVER TUMORS BASED ON NCI SLIDE REREAD AND RFD DERIVATION (DOURSON ET AL. 2014) January 2017 Source: :ttps://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) CONTENTS Acronyms and Abbreviations ii 1 Reread of NCI (1978) Histopathology Slides and Mode of Action Evaluation for Hepatic Tumors in Mice 3 1.1 Review of 1,4-Dioxane's Genotoxicity Database 4 1.2 Mode of Action Analysis 4 1.2.1 Key Event 1: Accumulation of Parent Compound 5 1.2.2 Key Event 2: Liver Cell Hypertrophy and Necrosis 5 1.2.3 Key Event 3: DNA Synthesis 5 1.2.4 Key Event 4: Regenerative Cell Proliferation 5 1.2.5 Key Event 5: Promotion of Endogenously Initiated Tumors 6 1.3 Updated Dose-Response Assessment and Reference Dose Derivation for 1,4-Dioxane 6 2 References 8 arcadis.com i Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) ACRONYMS AND ABBREVIATIONS BMD benchmark dose-modeling CUF composite uncertainty factor EPL Experimental Pathology Laboratories JBRC Japan Bioassay Research Center mg/kg/d milligrams per kilogram body weight per day MOA mode of action NCI National Cancer Institute NOAEL no-observable-adverse-effect level POD point of departure RfD oral reference dose g/L micrograms per liter USEPA United States Environmental Protection Agency arcadis.com ii Source: https://wwww.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) 1 REREAD OF NCI (1978) HISTOPATHOLOGY SLIDES AND MODE OF ACTION EVALUATION FOR HEPATIC TUMORS IN MICE To test their hypothesis and better understand the "sequence of events that maybe have contributed to the MOA of the observed liver tumors," Dourson et al. (2014) and McConnell (2013) performed a blinded reread of the mouse National Cancer Institute (NCI) (1978) liver histopathology slides, because that study did not report non-neoplastic lesions in livers of the high-dose group. Note this is one of the two long-term oral mouse bioassays that exist for 1,4-dioxane; the other chronic mouse bioassay was performed by the Japan Bioassay Research Center (JBRC) and is reported most recently by Kano et al. (2009). As noted by Dourson et al. (2014): "Because terminology and practices for reporting liver lesions has changed since the time of the NCI study (1978), and because EPA (2005) is focusing more on an understanding of a chemical's Mode of Action (MOA) prior to any determination of its dose response, a re-review of the liver slides of mice from the NCI study (1978) was performed. This reanalysis was performed at the Experimental Pathology Laboratories (EPL), Research Triangle Park, NC during September through November 2012. The objective of the slide review was to determine if any non-neoplastic lesions in the liver were present in an effort to understand the sequence of events that may have contributed to the MOA of the observed liver tumors in mice. Another reason for the slide review was because at the time of the original slide review (i.e., 1978) the NCI typically recorded only the most severe diagnosis on a given slide, (e.g., adenoma or carcinoma). During this timeframe, the focus of cancer bioassays was to determine the potential carcinogenic activity of the chemical, not its potential chronic toxicity. For example, if an adenoma, carcinoma, and evidence of chronic toxicity (e.g., hepatocellular hypertrophy), were all present on a given slide, only the tumor response was typically recorded. Thus, it was unclear whether non-neoplastic lesions were present in the livers of mice but were not recorded in the NCI carcinogenicity study. McConnell's (2013) reread of the NCI (1978) mouse liver histopathology slides and Dourson et al.'s (2014) summary report demonstrate that chronic exposure to 1,4-dioxane in drinking water is associated with a non-linear mode of carcinogenic action (contrary to the United States Environmental Protection Agency's [USEPA's] low-dose extrapolation conclusion) based on several hepatotoxic effects that preceded tumor formation, including: Dose-dependent hepatocellular glycogen depletion Dose-dependent hepatocellular hypotrophy Dose-related hepatocellular necrosis Dose-dependent hepatocellular inflammation associated with necrosis Dose-related hyperplasia in several non-neoplastic cell types arcadis.com 3 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) Dourson et al. (2014) states: "The appearance of the liver toxicity follows the pattern where glycogen depletion occurs either concurrently with, or preceding, hypertrophy in both sexes. This was followed closely by necrosis and inflammation in males, but a high control incidence of necrosis and inflammation clouded this overall pattern found in females In terms of dose-response behavior, hypertrophy preceded the formation of foci, which appeared to precede formation of tumors. This pattern was also evident in an individual animal analysis." 1.1 Review of ,4-Dioxane's Genotoxicity Database As a component of their mode of action (MOA) analysis, Dourson et al. (2014) reviewed 1,4-dioxane's genotoxicity database using the information presented in USEPA's (2010) Toxicological Review for 1,4- dioxane. Dourson et al. (2014) noted: '1,4-dioxane has been tested for genotoxicity using in vitro assay systems with prokaryotic organisms, non-mammalian eukaryotic organisms, and mammalian cells, both with and without metabolic activation.' "[A]II fifteen mutagenicity tests reported (8 without activation and 7 with metabolic activation) were negative." "22 in vitro genotoxicity assays, and 9 in vivo genotoxicity assays were negative." "Eight genotoxicity assays were noted to be positive but only at high or noted cytotoxic doses." Based on their review of 1,4-dioxane's genotoxicity database, Dourson et al. (2014) states "1,4-dioxane does not cause point mutations, DNA repair, or [tumor] initiation" when administered at non-cytotoxic doses, which is in general agreement with USEPA's conclusions (USEPA 2010). The authors noted their conclusions were similar to USEPA's, but differ in that "if mutations are caused by 1,4-dioxane, it is only at high cytotoxic doses." The authors concluded: "1,4-dioxane does not cause mutagenicity as evidenced by uniformly negative results in standard in vitro and in vivo genotoxicity bioassays at levels that are not overtly toxic, but it may be a clastogen in vivo, in light of the mixed results in the micronucleus assays. It follows that mutations needed for tumor formation are then likely from the known endogenously available pool of mutations, and that a regenerative hyperplasia evokes more of these endogenous mutations to form tumors. Mutation potentially caused by 1,4-dioxane at high doses is precluded as a key event in tumor formation." 1.2 Mode of Action Analysis Dourson et al. (2014) proposed five key events in the non-mutagenic MOA resulting in hepatic tumors in rodents; they include: "(1) accumulation of parent compound [at concentrations that saturate metabolic processes], (2) liver cell hypertrophy and necrosis, (3) DNA synthesis, (4) regenerative cell proliferation, and (5) promotion of endogenously-initiated tumors.' The regenerative cell proliferation MOA has a threshold below which hepatic tumors are not formed. Evidence supporting each key event is presented below. arcadis.com 4 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) 1.2.1 Key Event 1: Accumulation of Parent Compound "Humans, rats, and mice extensively metabolize 1,4-dioxane.' "[M]etabolism is a capacity-limited process." "When dose of 1,4-dioxane approaches or exceeds the metabolizing capacity, the unmetabolized fraction of the dose increases and target organ toxicity occurs." "Thus, there appears to be a threshold below which metabolism and elimination are rapid and with less or perhaps without toxicological effects." "Human environmental exposures to 1,4-dioxane are unlikely to approach doses that saturate metabolizing enzymes and which produce liver and nasal tumors in rats." "Hence, since humans, like rats, efficiently metabolize 1,4-dioxane at low doses, enzyme saturation is negligible at low exposure levels." 1.2.2 Key Event 2: Liver Cell Hypertrophy and Necrosis "Liver cell hypertrophy and necrosis are key events in the 1,4-dioxane MOA leading to regenerative cell proliferation and, with chronic exposures, liver tumors.' "Liver changes including centrilobular swelling, single cell necrosis coincide exclusively with saturating doses of 1,4-dioxane and occur in as little as 11 weeks." "Evidence of hepatocellular damage preceding evidence of hepatocellular tumors caused by higher doses of 1,4-dioxane has been provided by several studies." 1.2.3 Key Event 3: DNA Synthesis USEPA (2010) reported "that 1,4-dioxane does not cause DNA repair activity in five standard in vitro and in vivo bioassays that tested for the presence of DNA repair in various model systems." "Conversely, 1,4-dioxane does cause DNA replication as evidenced by in vitro bioassays in rat hepatocytes" "DNA synthesis appears to be a key event for a regenerative cell proliferation and/or tumor promotion and can occur in either the presence or absence of cytotoxicity." "DNA synthesis provides evidence that 1,4-dioxane promotes cell proliferation through cytotoxicity." 1.2.4 Key Event 4: Regenerative Cell Proliferation "Dose-response and temporal data support the occurrence of cell proliferation and hyperplasia prior to the development of liver tumors in the rat model." "Cell proliferation appears to be an early response with significant changes (1.5- to 2-fold) occurring in rats with as little as 2 weeks of exposure." arcadis.com 5 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) "Given time, proliferative changes manifest as pre-neoplastic foci in studies where the histopathology of such changes are reported." 1.2.5 Key Event 5: Promotion of Endogenously Initiated Tumors "Three studies relevant to tumor initiation and promotion establish that 1,4-dioxane does not cause initiation in standard in vivo bioassays, in agreement with the absence of observed mutagenic or genotoxic activity." "[T]umor promotion was associated with significant toxicity in rats when administered by either dermal or oral routes." 1.3 Updated Dose-Response Assessment and Reference Dose Derivation for 1,4-Dioxane Dourson et al. (2014) and USEPA (2010) both relied on the dose-response data reported by Kociba et al. (1974). This study provided data for liver and kidney degeneration and necrosis in 6- to 8-week-old male and female Sherman rats (60/sex/dose group) that were exposed to 1, ,4-dioxane at 0, 0.01, 0.1, or 1% (i.e., 9.6, 94, and 1,015 milligrams per kilogram body weight per day [mg/kg/d] and 19, 148, and 1,599 mg/kg/d for males and females, respectively) in drinking water for up to 716 days. The study reported a no-observed-adverse-effect level (NOAEL) of 9.6 mg/kg/d and provides "the most sensitive measure of adverse effects by 1,4-dioxane" (USEPA 2010). USEPA's Toxicological Review for 1,4-dioxane (USEPA 2010) provides a reference dose (RfD) of 0.03 mg/kg/d. This RfD was derived using the NOAEL of 9.6 mg/kg/d for liver and kidney degeneration and necrosis in rats reported by Kociba et al. (1974) as the point of departure (POD), in combination with a composite uncertainty factor (CUF) of 300 (10 for interspecies extrapolation, 10 for intraspecies extrapolation, and 3 for database deficiencies associated with the lack of a multigenerational reproductive toxicity study). The lowest-observable-adverse-effect level for this study was 94 mg/kg/d (USEPA 2010). USEPA derived the RfD using the NOAEL reported by Kociba et al. (1974) because the published study did not report incidence data for these effects, and therefore, they were unable to perform benchmark dose-modeling (BMD). Alternatively, Dourson et al. (2014) reported an updated RfD of 0.05 mg/kg/d that was derived using incidence data (laboratory report for the published study was provided to Dourson et al. [2014] by The Dow Chemical Company) for hepatocellular necrosis (combined across sexes) and USEPA's preferred approaches¹. Specifically, Dourson et al. (2014) utilized USEPA's preferred BMD approach (USEPA 2012) to derive a POD of 20 mg/kg/d (95% lower bound on the dose associated with a 10% extra risk), USEPA's preferred default bodyweight scaling factor (USEPA 2011), to estimate a human equivalent 1 USEPA (2010) used the NOAEL from Kociba et al. (1974) based on liver and kidney degeneration to derive the RfD, specifically because Kociba et al. (1974) did not provide quantitative incidence or severity data for liver and kidney degeneration and necrosis. However, when appropriate data are available, USEPA prefers using BMD to define the POD (USEPA 2012). Had the incidence data from Kociba et al. (1974) been available at the time of their review, USEPA would have used it to derive a benchmark dose to use as the POD for setting the RfD. arcadis.com 6 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) dose, in combination with a CUF of 100 (3 for interspecies toxicodynamic extrapolation, 10 for intraspecies extrapolation, and 3 due to the lack of a 2-generation reproductive study) to derive an RfD of 0.05 mg/kg/d. Dourson et al. (2014) concluded that "the choice of this endpoint [hepatocellular necrosis] is protective, since liver toxicity, resulting in liver tumors, is the clear apical effect of greatest intensity in the available array of toxic effects." Dourson et al. (2014) calculated their RfD using standard approaches, as shown in Equation (1), below: POD 20 mg/kg/d Equation (1) RfD = = 0.05 mg/kg/d CUF 3x10x3 arcadis.com 7 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) 2 REFERENCES Dourson, M., J. Reichard, P. Nance, H. Burleigh-Flayer, A. Parker, M. Vincent, and E.E. McConnell. 2014. Mode of action analysis for liver tumors from oral 1,4-dioxane exposures and evidence-based dose response assessment. Regul Toxicol Pharmacol. 68: 387-401. Kano, H., Y, Umeda, T. Kasai, T. Sasaki, M. Matsumoto, K. Yamazaki, K. Nagano, H. Arito, and S. Fukushima. 2009. Carcinogenicity of 1,4-dioxane administered in drinking-water to rats and mice for 2 years. Food Chem Toxicol. 47:2776 - 2784. Kociba, R.J., S.B. McCollister, C. Park, T.R. Torkelson, and P.J. Gehring. 1974. 1,4-dioxane. I. Results of a 2-year ingestion study in rats. Toxicol Appl Pharmacol, 30: 275-286. oi:10.1016/0041- 008X(74)90099-4. McConnell, G. 2013. Report on the review of liver slides from the National Cancer Institute's Bioassay of 1,4-Dioxane for Possible Carcinogenicity Conducted in 1978 (NCI, 1978). Submitted to Toxicology Excellence for Risk Assessment. January/March 2013. NCI. 1978. Bioassay of 1,4-Dioxane for possible Carcinogenicity. Carcinogenesis Testing Program, Division of Cancer Cause and Prevention, National Cancer Institute. NIH, Bethesda, MD, 78-1330. USEPA. 2005. Guidelines for carcinogen risk assessment, final report. EPA/630/P-03/001F. Risk Assessment Forum; U.S. Environmental Protection Agency. Washington, DC. March. USEPA. 2010. Toxicological Review of 1,4-Dioxane (CAS No. 123-91-1). EPA/635-R-09-005-F. Washington, D.C. August. USEPA. 2012. Benchmark Dose Technical Guidance. EPA/100/R-12/001. Risk Assessment Forum. Washington, DC. June 12. arcadis.com 8 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 APPENDIX B Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) Source: https://www.industrydocuments.ucsf,edu/docs/fsbn0226 ARCADIS Desion & for natural and built assets Appendix B MODE OF ACTION ANALYSIS FOR LIVER TUMORS BASED ON JBRC REVIEW (DOURSONETAL.2016IN PEER REVIEW) January 2017 Source: :ttps://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) CONTENTS Acronyms and Abbreviations ii 1 Findings from Detailed Review of JBRC Rat Bioassays 3 1.1 Findings from Detailed Review of JBRC Mouse Bioassays 3 1.2 Integration of Evidence Supporting Regenerative Cell Proliferation MOA for 1,4-Dioxane 4 2 References 6 TABLES Table 1. Integration and Comparison of Rat and Mouse Bioassay Data (Adapted from Dourson et al., 2016 in peer review) 5 arcadis.com i Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) ACRONYMS AND ABEREVIATIONS JBRC Japan Bioassay Research Center mg/kg/d milligrams per kilogram body weight per day MOA mode of action NCI National Cancer Institute arcadis.com ii Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) 1 FINDINGS FROM DETAILED REVIEW OF JBRC RAT BIOASSAYS Changes in the liver found in the Japan Bioassay Research Center (JBRC) rat bioassays provide strong evidence that hepatic tumors were modulated by a threshold-based regenerative cell proliferation mode of action (MOA). Dourson et al. (2016 in peer review) found that effects observed in rats were in the expected dose-sequence for a regenerative cell proliferation MOA. Specifically, Dourson et al. (2016 in peer review) observed the following sequence of effects: Dose: 42-55 milligrams per kilogram body weight per day (mg/kg/d) - Effect: Liver swelling, hypertrophy, and liver weight increase Dose: 94-219 mg/kg/d - Effect: Necrosis Dose: 55-389 mg/kg/d - Effect: Hyperplasia and foci development Dose: >200 mg/kg/d - Effect: Increased levels of enzymes associated with liver damage Dose: 274-1015 mg/kg/d - Effect: Adenomas and carcinomas 1.1 Findings from Detailed Review of JBRC Mouse Bioassays Dourson et al. (2016 in peer review) observed the following sequence of effects in the JBRC (1990a) mouse bioassays: Dose: 190-200 mg/kg/d - Effect: Liver swelling, hypertrophy, and liver weight increase Dose: 190-200 mg/kg/d - Effect: Necrosis Dose: Not reported - Effect: Hyperplasia and foci development not reported Dose: 200 mg/kg/d - Effect: Increased levels of enzymes associated with liver damage Dose: 66-964 mg/kg/d - Effect: Adenomas and carcinomas, females Surprisingly, effects in the liver found in the JBRC mouse bioassays conflict with those clearly reported by Dourson et al. (2014) and McConnell (2013) for the reread of the National Cancer Institute (NCI) (1978) mouse bioassay histopathology slides. Additionally, the progression of effects reported by JBRC for the 2- year chronic study is inconsistent with enzymatic changes indicative of liver damage noted in the same study, as well as findings from a 13-week precursor study performed by the same laboratory. As noted by Dourson et al. (2016 in peer review), "the lack of noncancer histopathology in the chronic mouse study is not consistent with the changes in liver enzymes in this same chronic study, nor is this lack of noncancer arcadis.com 3 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) findings expected based on the histopathology of the precursor 13-week study" and "[n]or does the tumor response in the low dose female mice of JBRC (1990a) match the tumor findings in the McConnell (2013) re-read of NCI (1978). Dourson et al. (2016 in peer review) hypothesized that differences in mouse bioassay results between JBRC and McConnell (2013) may be due to differences in the interpretation of the histopathological data, and provided the following quote from JBRC (Kano et al. 2009) to substantiate their claim: "The hepatic hyperplasia of rats and mice diagnosed in the previous report (Yamazaki et al., 1994) [authors note: which was a presentation of the JBRC, 1990a] was re-examined histopathologically and changed to hepatocellular adenomas and altered hepatocellular foci including acidophilic, basophilic and clear cell foci in the present studies, according to the current diagnostic criteria of liver lesions in rats and mice." Unfortunately, slides from the original JBRC (1990a,b) bioassays were not available; therefore, the JBRC slides could not be reread as they were by McConnell (2013) for the NCI (1978) mouse liver slides. Additionally, JBRC did not archive sufficient numbers of pictures of histopathology slides to resolve the issue. While, it is impossible to know for sure from this dataset whether liver tumors formed prior to or following cytotoxic effects, the weight of evidence from the JBRC and NCI mouse bioassays supports a regenerative cell proliferation MOA. 1.2 Integration of Evidence Supporting Regenerative Cell Proliferation MOA for 1,4-Dioxane Following integration of key events from seven rat bioassays, three mouse bioassays, and 1,4-dioxane's genotoxicity profile, presented in Table 1 below, Dourson et al. (2016 in peer review) showed that 1,4- dioxane's toxicological database supports a threshold-based regenerative cell proliferation MOA for tumor formation in livers of rodents orally exposed to 1,4-dioxane. The authors reported that bioassay data for rats leads to the conclusion that "rat liver tumors are evoked by a regenerative hyperplasia," while the authors concluded the "sequence of events from two chronic mouse studies and a subchronic mouse study generally support the hypothesized regenerative hyperplasia MOA" (Dourson et al. 2016 in peer review). In regards to the conflicting mouse bioassay data (McConnell 2013; Dourson et al. 2014; JBRC 1990a), the difference is likely due in part to changes in the terminology and practices used for recording the liver lesions reported by Kano et al. (2009). arcadis.com 4 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226

what is NFSD?

gybn0226

gybn0226_p0, gybn0226_p1, gybn0226_p2, gybn0226_p3, gybn0226_p4, gybn0226_p5, gybn0226_p6, gybn0226_p7, gybn0226_p8, gybn0226_p9, gybn0226_p10, gybn0226_p11, gybn0226_p12, gybn0226_p13, gybn0226_p14

Nordic Fire & Safety Days, nordic fire & safety days

145 From: Jürgen Troitzsch To: Dr. Wise Kimberly Cc: Admon. Smadar: Anderson Steven; Batoon, Audrev; Dr. Bradley Kevinx; de Lacy, Catharine: Elkan. Illan; Eraguntla, Neeraia: Goodman, Bryan; Hochschwender. Lane; Jacobi Svivia; Kannah Kasturirangan; Levan Steve; Leychik. Sergei; Little, Barbara; Manor, Orit; Prero, Judah; Dr. Rothenbacher Klaus; Saunders, Eric L.; Scherrer Stephen; Simon. Robert; Tavior Jennifer; Tenney Joel; Thorn. Amelia; West, Jav; Dr. Haves Wallace; Prof. Rein Guillermo; Dr. Blais Matthew; Dourson. Michael (doursoml); Kacew. Sam; Osimitz Thomas Subject: Re: For Review - Draft Record from May 2017 SAC Meeting Date: Sunday, June 4, 2017 10:05:03 AM Attachments: SAC ROM 05-16-17 and 05-17-17 - Draft doc Program 2017, pdf 170817AbsFurnitureFiresafety.do Dear Kimberly, Please find attached my comments to the meeting record, the program of the Copenhagen conference and my abstract. Kind regards/Viele Grüße Jürgen Dr. Jürgen Troitzsch Fire and Environment Protection Service FEPS Via Patrizia 32 CH-6612 Ascona, Switzerland Mobile: +41 79 289 17 16 Phone: +41 91 791 14 22 Email: [email protected] Web: www.troitzsch.com Am 02.06.2017 um 13:56 schrieb White, Kimberly <Kimberly [email protected]> Dear NAFRA, BSEF and SAC members: Attached is the record from the May 2017 Science Advisory Council meeting. Please review by June 9th and let me know if you have any additions or corrections. Kind Regards, Kimberly Wise White, Ph.D. | American Chemistry Council Senior Director, Chemical Products & Technology Division [email protected] Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 Furniture Fire Properties And Their Importance For Domestic Fire Safety Juergen H. Troitzsch Fire and Environment Protection Service FEPS Ascona, Switzerland [email protected] Keywords: Fire statistics, furniture regulations, reaction to fire stakeholders regarding adequate fire safety, the proposal was tests, barriers, flame retardants withdrawn. A second version is now under consideration and it Fire statistics show that residential fires caused by is unclear when the amended regulations will come in to force. upholstered furniture have continuously decreased in the U.S. These approaches have led to search for other possibilities /California and the UK in the last 20 years. This is due to to ensure adequate fire safety levels for upholstered furniture. stringent fire safety regulations and tests mandatory for Contrary to the past, where ignition and flammability tests upholstered furniture in these countries. However, upholstered were used to define fire safety. now the reduction of the heat furniture still remains the leading item first ignited by low release rate is seen as the key fire property most strongly energy ignition sources such as cigarettes, matches, lighters influencing fire hazard. and candles 1. A study on "Alternative strategies to the use of chemical The classical way to meet high fire safety requirements for flame retardants" 4 has shown that various combinations of upholstered furniture is to improve the fire safety level of its cover materials and fire barriers to protect flexible components by using flame retarded flexible polyurethane polyurethane foam can reduce the heat release rate of the foam, barriers and covers. systems tested and improve fire safety. With the exception of In recent years, due to health and environment concerns an intrinsically flame retarded (FR) polyester cover, no other about the use of certain flame retardants, California revised the components used contained conventional flame retardants. CA TB 117 cigarette test 2 used for upholstered furniture in the Another, earlier study on "upholstered furniture private domain. The former additional small flame test required flammability" 5 investigated the fire performance of different was eliminated because flame retardants had to be used to meet FR/non-FR barrier materials and flexible polyurethane foams it. with a non-FR polyester cover in material-level, mock-up and The new CA TB 117 only addresses smoldering fires, while full-size furniture experiments. The results showed that the fires associated with flaming ignition, which according to flame retarded barrier materials were very effective in reducing NFPA lead to an appreciable amount of fatalities, are no more heat release rate and, particularly in the full-size experiments, considered. Therefore, NFPA has been asked to develop a the fire growth rate of the upholstered chairs. flaming-ignition test for upholstered furniture and is currently These studies show that the best way to reduce the heat working on its own open-flame test to NFPA 277 3 based on release rate of upholstered furniture and to optimize fire safety heat release rate measurement. is the use of flame retarded fire barriers and covers. Adequate In Great Britain, "The Furniture and Furnishings (Fire fire barriers including the use of flame retardants based on the Safety) Regulations' address compulsory fire safety U.S. EPA Design for the Environment (DfE) alternatives requirements for upholstered furniture in private homes. In assessment method will help to enhance domestic fire safety 2014, the authorities proposed an alternative match test to and reduce the number of fatalities, injuries and property losses. simplify the regulation and to reduce levels of flame retardants in furniture without impacting on the current fire safety levels. Here, contrary to the California approach, the cigarette test was to be eliminated and only gas flames and the BS 5852 crib 5 tests remained. However, following strong concerns from the 1 J. Troitzsch, "Fires, statistics, ignition sources, and passive fire protection REFERENCES measures", Journal of Fire Sciences, 2016, 1-28. DOI: 10.1177/07349041 2 Technical Bulletin 117-2013 Requirements, Test Procedure and Apparatus for Testing the Smolder Resistance of Materials Used in Upholstered 4 K. Storesund, A. Steen-Hansen and A. Bergstrand, "Fire safe upholstered Furniture. January 2013 furniture. Alternative strategies to the use of chemical flame retardants," 3 Proposed Standard NFPA 277: Standard Methods of Tests for Evaluating SPFR Report A15 20124:2, December 2015. Fire and Ignition Resistance of Upholstered Furniture Using a Flaming 5 T. Fabian, "Upholstered furniture flammability,' Underwriters Laboratories Ignition Source Inc., Jul. 2013. Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 NFSD Nordic Fire & Safety Days Programme Day 1, 17th Augusti 2017 no Colico and Registration Welcome to the Nardini are and Safety Days Room: ACM15 Anne Dederichs 10.00 Key Leature Room: ACM15 Furniture fire properties and their importance for domestic fire safety. Dr. Jürgen Troitzsch, FEPS, Switzerland Panal Discussion Room: ACM15 Session Chair: Björn Sundström, SP Furniture fire properties and their importance for domestic fire safety. Dr. Jürgen Troitzsch, FEPS, Switzerland Egil Sundet, Head of the Sector furniture, interior and design for the federation of Norwegian Industry Dr. David Santillo, Honorary Research Fellow at Greenpeace Research Laboratories, Exeter University, UK, Dr. Anne Elise Steen-Hansen, Research manager at SP Fire Research, Norway Dr. Björn Karlsson, Professor at Iceland University and the Director General at Iceland Construction Authority. A! ********* - ****** NTNU 1 LUND of ****** ******** ******** DBI Source: https://wwww.industrydocuments.ucsf.edu/docs/gybn0226 NFSD Nordic Fire & Safety Days Parallet Session A Fire Dynamics 1 Risk 1 Evacuation Room: ACM15 1.001 Room: ACM15 1.008 Room: FKJ 12 0.06 Session Chair: Session Chair: Session Chair: Tuula Hakkarainen Frank Markert 11.00-11.15 Fire protection of Modelling approach for The effect of plattform- extensive green roofs the threat quantification and tunnel design on the A. Elias of cascading failures evacuation performance A. Helminen, T. of wheelchair users - A Hakkarainen qualitative study Eva-Sara Karlsson 11.20-11.35 USCG Fire simulation of Developing a risk and Reaction and decision water mist suppression capability assessments time of evacuees - A study using an ignition source methodology for the Baltic regarding the influence of E. A. Kolstad, B. P. Husted, Sea Region alcohol on the reaction LU - B. Karlsson and decision time P. B. Rask, A. Dederichs 11.40-11.55 Development tool for Fire safety decision Awareness of fire risk ETICS façade fire testing making under a systems- reduction among Cyprus M.S. McLaggan, M. theoretic safety paradigm international university Meinert, A. Dragsted, P. -H. Bjelland, O. Njã, A. (CIU) students van Hees W.Heskestad, G. S. Braut A. F. Gyasi 1000 Lunch 2 Exhibition the DO Parallal R Fire Dynamics 2 Fire safety science Transportation without borders Room: ACM15 1.001 Room: ACM15 1.008 Room: FKJ 12 0.06 Session Chair: Session Chair: Session Chair: Frida V Lundström Martyn S. McLaggan 13.00-13.15 Desensitisation of optical Fire safety science without Ventilation in tunnels: a flame detection in harsh borders numerical comparison external environments T., between different J. McNay K. H. Almand modelling approaches -P. Matteo 13.20-13.35 Heat release Fire safetys contribution Fire detection in engine characteristics of ethanol- to a sustainable society compartments - P. water mixtures T., Karlsson, O. Willstrand T. Hakkarainen K. H. Almand, NFPA 13.40-13.55 Fire-induced pressures in Det store brannlöftet - Verifying fire safety in tall modern airtight Dag Botnen timber buildings apartment building Fredrik Nystedt S. Hostikka Johan Norén 14 00 3 Enhibition OTU A! II'II ********* - - NTNU a 2 Landa of ******** ******** ******** 081 Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 NFSD Nordic Fire & Safety Days Parallet C Fire Dynamics 3 Fire Safety Engineering 1 Brokerage Event 1: Carpark fires Room: ACM15 1.001 Room: ACM15 1.008 Room: FKJ 12 0.06 Session Chair: Session Chair: Session Chair: Ulf Wickström Michael Stömgren 14.45- Measuring incident Performance based design and compilande Luisa Giuliani 15:00 heat flux and M. Strömgren adiabatic surface temperature with platse thermometers in ambient and high temperatures U. Wickström, J. Anderson, J. Sjöström 15.05- Modelling and Wildlandfires, F.V.Lundström, P. Andersson 15.20 stochastic analyses of travelling fires R. K. Janardhan, S. Hostikka 15.25-40 Photovoltaic A discussion on learning from fire installations on investigations; concepts and methodologies warehouse buildings - an experimental A. Borg, O. Njã study of the propagation of fire - J. Steemann Kristensen Conference 3 Exhibition Affer conferenze dinner OTU A! IIIII ********* - - - NTNU a 3 Luno of ******** ******** ******** 081 Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 NFSD NordicFire & Safety Days Programme Day 2, 18th August 2017 20.02.40 Welcome Key Leaure Room: ACM15 Fire brigade intervention method - accounting for the actions of the fire service Ed Claridge, Principal Fire Engineer, Auckland, New Zealand Pana Discussion Room: ACM15 Session Chair: Fire brigade intervention-accounting for the actions of the fire service Ed Claridge, Principal Fire Engineer, Auckland, New Zealand Rasmus Storgaard Petersen, CEO Emergency Service East, Denmark Cecilia Daae, Director of Directorate for Civil Protection and Emergency Planning, Norway Mia Kumm, Licentiate of engineering and researcher at SP/Rise and Mälardalen University, Sweden A! II-II: ********* - ****** - NTNU a 4 Luwo ****** DBI Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 NFSD Nordic Fire & Safety Days Parallel Session D Management of rescue Risk 2 Structural Fire Safety 1 service 1 Room: ACM15 1.001 Room: ACM15 1.008 Room: FKJ 12 0.06 Session Chair: Session Chair: Session Chair: 11.00-11.15 Accounting for the actions Resilient Buildings C-Fort, Risk analysis and of the rescue service - M. Kumm performance-based rescue from heights. structural fire expertise of Christian Ramm a semi-buried railway station - E. Tonicello, S. Deshanghere 11.20-11.35 Environmental impact of Firesafe - Study Experimental study on the structure fires and fire investigating cost effective mechanical properties of service response measures for reducing the fire exposed concrete F. Amon, L. Vylund risk from fires on ro-ro A. Zawadowska, L. passanger ships Giuliani, K. D. Hertz - J. Wikman, M. Rahm, F. Evegren, J. Leroux, A. Breuillard, M. Kjellberg, L. Gustin, F. Efraimsson 11.40-11.55 Part time firemen and False alarm - An Fire protection of wooden community resilience organizational study of houses in several floors -P. Almklov, M. Nilsen, G. the effects of false alarms J. N. Olsen, H. S.Fishman Gjøsund G. Gjøsund Petter Almklov Christian Sesseng Lundh R OTU A! IIIII ********* - - - *** - - NTNU " 5 Luno of ******** ******** ******** 081 Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 NFSD Nordic Fire & Safety Days Parallel R Management of rescue Fire safety engineering 2 Structural Fire Safety 2 service 2 Room: ACM15 1.001 Room: ACM15 1.008 Room: FKJ 12 0.06 Session Chair: Session Chair: Session Chair: 13.00-13.15 Security officers 99 years of standard fire - Furnace setup for responding to residential success of failure? preliminary fire resistance fire alarms: modelling the R. Jansson McNamee testing - effect on survival and P. Hejtmánek, V. Flídr, H. property damages Najmanová B. Sund, H. Jaldell 13.20-13.35 Three different fire Investigation of suppression approaches A swedish approach to eurocodes design used by Fire and Rescue define a standard for fire fires and national services safety design in BIM deviations- F. S. Särdqvist F. Nystedt, J. Norén Clausen, L. Giuliani 13.40-13.55 An operationalization of Nordic standard for Material capabilities for fire and review & control of fire modeling of rescue operations safety engineering concrete under M. Runefors F. Nystedt, J. Norén, M. compression and Strömgren high temperatures - A. F. Damkjaer, L. Giuliani, K. D. Hertz Coffee 3 Exhibition OTU A! IIIII ********* - - - *** - - NTNU " 6 Luno of ******** ******** ******** 081 Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 NFSD Nordic Fire & Safety Days Parallel Sersion : Residential Fires 1 Fire safety engineering 3 Fire Dynamics 4 Room: ACM15 1.001 Room: ACM15 1.008 Room: FKJ 12 0.06 Session Chair: Session Chair: Session Chair: 14.45-15.00 Socioeconomic Learning points from real Smouldering fires in wood differences in residential incidents - pellets: the effect of fire mortality in Sweden: a learning from what?- - M. varying the airflow case-control study Bøhm, Metropolitan V. R. Valdés,R. F. Mikalsen, A. Jonsson University College A. Steen-Hansen O.Njã, U. Stavanger 15.05-15.20 Fire fatalities in Norway Simulation of smouldering K. Storesund, C. Sesseng, combustion based on A. Steen-Hansen Integration of fire multi-layer cellular engineering tools and automata- calculation methodologies V. R. Valdés,R F. Mikalsen, P. Tofilo A. Steen-Hansen 15.25-15-40 Has fire-related mortality Learning fire and rescue Aerosols from smoldering in Sweden changed over work by experience- E. Villacorta time? - E. Lindahl, J. sharing Hedberg Ava Sadeghi OTU A! IIIII ********* - - - *** - - NTNU " 7 Luno of ******** ******** ******** 081 Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 NFSD Nordic Fire & Safety Days Paralial to Residential Fires 2 Structural Fire Safety 3 Fire Dynamics 5 Room: ACM15 1.001 Room: ACM15 1.008 Room: FKJ 12 0.06 Session Chair: Session Chair: Session Chair: Residential fires in On analysing structures USCG Fire simulation of Denmark based solely on human water mist suppression P.B. Gummesen safety using an ignition source A.S. Dederichs, RISE, DTU J.Sandström, J. Thor, R. Einar Arthur Kolstad Jansson McNamee,0. Bjarne P. Husted Lagerqvist, U.Wickström Residential fire solutions Post-earthquake Validation of FDS on the in the building sector fire behavior of SP retail store steel frames - Shamim Ahmed Bjarne P. Husted Part I: Collapse Mechanism - G. Risco, L. Giuliani, V. Zania Towards an evidence- Post-earthquake fire Validation of sub-grip based vision zero policy behavior of steel frames - scale particle model for on residential fires - an Part II: The effect of the cable fire spread update - R. Andersson insulation - A. Wrobel, , L. T. Sikanen, A. Matala, S. A. Jonsson Giuliani, V. Zania Hostikka Brokerage Event 2: Modern Building Fires Session Chair: Anne Dederichs Lars Schiøtt Sørensen, DTU OTU A! IIIII ********* - - - *** - - NTNU " 8 Luno of ******** ******** ******** 081 Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 AMERICAN CHEMISTRY COUNCIL NORTH AMERICAN FLAME RETARDANT ALLIANCE (NAFRA), BROMINATED SCIENCE ENVIRONMENTAL FORUM (BSEF) AND SCIENCE ADVISORY COUNCIL (SAC) RECORD of MEETING Draft Subject to Review and Approval Date: May 16, 2017 - May 17, 2017 Location: New York, NY Participants: Steve Anderson Albemarle Audrey Batoon Chemtura Matt Blais Southwest Research Institute Kevin Bradley Consultant to BSEF Patty Cardin* Chemtura Catharine DeLacy Albemarle Michael Dourson Toxicology Excellence for Risk Assessment Ilan Elkan ICL Neeraja Erraguntla American Chemistry Council Ofodike Ezekoye* University of Texas-Austin A. Wallace Hayes Harvard School of Public Health Steve Levan Albemarle Kevin Marr** University of Texas-Austin Tom Osimitz Science Strategies, LLC Guillermo Rein Imperial College London Klaus Rothenbacher Independent Consultant Eric Sanders Chemtura Steve Scherrer Chemtura Jürgen Troitzsch Fire and Environment Protection Services Jay West American Chemistry Council Kimberly White American Chemistry Council ** Denotes part time participation in-person on May 16th only. ** Denotes part time participation via conference call on May 16th only. 1.0 K. White reviewed meeting room site logistics, the tentative agenda for the meeting and the ACC's Antitrust Guidelines which remained in effect for the duration of the two-day meeting. 2.0 Participants conducted roundtable introductions and K. White reviewed the overall objectives for the meeting, which included: Discuss relevant regulatory and chemical assessment activities Discuss state of the science Identify short term and long term science priorities and activities Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 Record of Meeting 05/16/17 - 05/17-17 Page 2 3.0 K. White reviewed key take-away messages from the May 15th NAFRA Operating Committee meeting which included: (a) focusing core science activities on priority areas of focus and ensuring alignment with the strategic plan, (b) identify approaches to inform issues raised during state legislative hearings, (c) focus the scope and objectives for the next phase of the smoke toxicity study and (d) identify opportunities to address fire fighter exposures. 4.0 K. White, J. West and K. Rothenbacher reviewed notable regulatory/legislative activity in the US and abroad. Action Items K. Rothenbacher will distribute a copy of the TBBPA EU Denmark Decision J. West will distribute information from Maine that outlines notable toxicological endpoints related to flame retardant exposures. 5.0 Participants discussed the status of the ongoing science projects currently underway and had detailed project discussions by the researchers as follows: T. Osimitz provided an overview of the available literature for the-for dermal exposures M. Blais and T. Osimitz reviewed the protocol, scope and results from the phase I of the smoke toxicity study. Participants discussed the results, possible implications and opportunities to refine and focus the project moving forward. Participants recommended that the researchers provide a write-up of the project results, recommendations for next phase and associated cost then scheduled a project specific call to agree on the path -forward. K. Marr and O. Ezekoye reviewed the scope and progress to date on the project to evaluate combustion properties of baby monitors. Participants discussed the researchers focus on battery failure scenarios, recommended refining the scope and ensuring the combustion activities adequately address differences between flame retardant and non-flame retardant. Action Items T. Osimitz will provide a draft manuscript for the dermal exposure review by June 15th. SAC members will evaluate whether it's feasible to develop a BE for blood concentrations from flame retardant based on dermal exposures T. Osimitz and M. Blais will work with N. Erraguntla to refine the smoke toxicity project scope and next steps then schedule a call to discuss. K. White will solicit recommendations for possible next steps on the combustion of baby monitors project and will set a project specific call for more discussion with the researchers. K. White will distribute past scope of work and study updates related to the combustion of baby monitors project. 6.0 Members of the SAC provided updates on ongoing science activities that included the following: J. Troitzsch invitation- to be a speaker during anchair a flame retardants seminar at the AOFSM'2 Conference in Shenzhen, China, 27-29 October 2017 in conjunction with BSEF -meeting. Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 Record of Meeting 05/16/17 - 05/17-17 Page 3 J. Troitzsch has been invited as keynote speaker on the fire safety of upholstered furniture alerted-participants to the Nordic Fire & Safety Days Conference in Copenhagen, 17-18 August 2017. an-epeoming 2017 meeting in Copenhagen- The participants discussed thatwhere engagement by a toxicology expert may be useful. G. Rein alerted participants to ongoing activities in California and other state agencies to evaluate TB117 and exposure to flame retardants. The evaluation is anticipated to last 3-5 years and it was recommended to monitor the data outputs annually. Action Items J. Troitzsch will provide information regarding the 2017 Copenhagen meeting. 7.0 Participants reviewed a series of charge questions and recent flame retardant session information from the 2017 Society of Toxicology meeting to identify potential opportunities for future science activities. NAFRA and SAC members also met separately to discuss identified projects and identify additional opportunities for science engagement. Overall, participants recommended identifying key product sectors and priority issues of interest to address, then reviewing each potential project to determine what role it will play in providing additional information to respond to identified sectors and issues. A number of projects topics were identified for future discussion and refinement as follows: Conduct of full scale room burns In Vitro dermal exposure study Evaluation of neurobehavioral testing parameters and human relevance from animal models Collaboration opportunities with NFPA research foundation Evaluate opportunities related to wearable technologies and impacts for assessment of flame retardant exposures Action Items K. White will aligned product categories, priority issue areas and identify possible science gaps by June 16th. K. White will schedule a conference call in June with NAFRA/BSEF members to discuss the identify projects and their alignment with product categories and issue areas of interest. 8.0 Participants discussed past and present SAC meeting to identify opportunities to improve meeting outputs and coordination with the SAC. Several recommendations were noted that included: having more time in the agenda for project specific discussions and deliberation; provide more background information on each project under discussion; elimination of fire science and toxicology specific breakout so that all participants can actively contribute to all meeting discussion; build in sufficient time for SAC members and NAFRA members to meeting separately for deliberation; and develop a science repository of relevant scientific information on the MemberExchange site that includes abstracts and links to articles when available pending copyright restrictions. 9.0 The next meeting is scheduled for November 12th (Dinner) and a November 13-14, 2017 Meeting in London. The meeting was adjourned at approximately 12:22pm on May 17, 2017. Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 Record of Meeting 05/16/17 - 05/17-17 Page 4 Respectfully submitted, K. White Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226

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Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 2 USEPA APPROACH FOR EVALUATING CANCER RISHS POSED BY ORAL EXPOSURE TO 1,4-DIOXANE USEPA's Integrated Risk Information System (IRIS) published the Toxicological Review for 1,4-dioxane, in which it describes their approach and justification for deriving an oral CSF for this constituent. Below is a summary of USEPA's evaluation of available human toxicological data, weight of evidence evaluation, key study identification, critical effect selection, dose-response assessment, and the low-dose extrapolation procedure used to derive 1,4-dioxane's CSF. 2.1 USEPA's Evaluation of Evidence of Cancer in Humans USEPA evaluated the degree to which data provide evidence of carcinogenicity in humans (USEPA 2010). USEPA relied on two human occupational studies in their evaluation of potential impacts related to long-term exposure to 1,4-dioxane (Thiess et al. 1976; Buffler et al. 1978). USEPA concluded that neither study provided evidence that 1, ,4-dioxane causes cancer in humans. However, they noted "the cohort size and number of reported cases were small." 2.2 USEPA's Evaluation of Evidence of Cancer in Animal Bioassays USEPA followed its Guidelines for Carcinogen Risk Assessment (USEPA 2005) to conclude that 1,4- dioxane is "likely to be carcinogenic to humans" based on "evidence of liver carcinogenicity in several 2- year bioassays conducted in three strains of rats, two strains of mice, and in guinea pigs.' USEPA provided several reasons to justify its conclusion. For instance, USEPA concluded that the "available evidence is inadequate to establish a MOA by which 1,4-dioxane induces liver tumors in rats and mice" (USEPA 2010). Specifically, USEPA noted the "[c]onflicting data from rat and mouse bioassays (Japan Bioassay Research Center [JBRC] 1998; Kociba et al., 1974) suggest that cytotoxicity may not be a required precursor event for 1,4-dioxane-induced cell proliferation." USEPA (2010) noted that "[a]vailable data also do not clearly identify whether 1,4-dioxane or one of its metabolites is responsible for the observed effects. However, USEPA also reported that "the generally negative results for 1,4-dioxane in a number of genotoxicity assays indicates the carcinogenicity of 1,4-dioxane may not be mediated by a mutagenic MOA" (USEPA 2010). 2.3 Key Study Identification (Kano et al. 2009), Critical Effect Selection, Dose-Response Assessment, and Low-Dose Extrapolation Procedure USEPA (2010) concluded that the MOA by which 1,4-dioxane produces liver tumors is "unknown, and available evidence in support of any hypothetical mode of carcinogenic action for 1,4-dioxane is inconclusive." With this conclusion in mind, USEPA (2010) identified a 2-year drinking water study performed by Kano et al. (2009) as the key study of the oral CSF for 1,4-dioxane. Note that Kano et al. (2009) published findings originally reported by the JBRC (1990a). Although USEPA (2010) concurrently evaluated two other studies (Kociba et al. 1974; National Cancer Institute [NCI] 1978), the Kano et al. (2009) study was ultimately selected as the key study because USEPA (2010) noted that "[c]alculation of arcadis.com 3 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications a CSF for 1,4-dioxane is based upon the dose-response data for the most sensitive species and gender." The study was performed in accordance with the Organization of Economic Development's Principles for Good Laboratory Practices and involved exposing groups of rats (50 animals of each sex for each dose) and mice (50 animals of each sex for each dose) to 1,4-dioxane (>99% pure) in drinking water for 2 years. Rats were exposed to 1,4-dioxane in drinking water at 0, 200, 1,000, or 5,000 milligrams per liter (mg/L), while mice were exposed at 0, 500, 2,000, or 8,000 mg/L in drinking water. As reported by USEPA (2010): "The investigators used data from water consumption and BW [body weight] to calculate an estimate of the daily intake of 1,4-dioxane (mg/kg-day) by male and female rats and mice. Kano et al. (2009) reported a calculated mean + standard deviation for the daily doses of 1,4-dioxane for the duration of the study. Male rats received doses of approximately 0, 11+1, 55+3, or 274+18 mg/kg-day and female rats received 0, 183, 83+14, or 429+69 mg/kg-day. Male mice received doses of 0, 49+5, 191+21, or 677+74 mg/kg-day and female mice received 0, 66=10, 278+40, or 964+88 mg/kg-day." "The study by Kano et al. (2009) was used for development of an oral CSF. This was a well- designed study, conducted in both sexes in two species (rats and mice) with a sufficient number (N=50) of animals per dose group. The number of test animals allocated among three dose levels and an untreated control group was adequate, with examination of appropriate toxicological endpoints in both sexes of rats and mice. Alternative bioassays (Kociba et al., 1974; NCI, 1978) were available and were fully considered for the derivation of the oral CSF." USEPA identified increased incidence of liver adenomas or carcinomas as the critical effect in rats and mice exposed to 1,4-dioxane in the Kano et al. (2009) study. Following standard dose adjustment to a human equivalent dose using a default body weight (BW) scaling factor (USEPA 2005), USEPA performed dose-response modeling using Benchmark Dose Software and fit the suite of models available in the program to the incidence data for "either hepatocellular carcinoma or adenoma" (USEPA 2010). USEPA concluded that female mice are "more sensitive to liver carcinogenicity induced by 1,4-dioxane compared to other species or tumor types" and identified the lower 95% confidence bound on the benchmark dose associated with a 50% extra risk (benchmark response [BMR]) of developing "either hepatocellular carcinoma or adenoma" (4.95 milligrams per kilogram per day [mg/kg/d]) as the point of departure (POD) for calculating the oral CSF via linear low-dose extrapolation, as shown in Equation (1), below. USEPA (2010) again justified a linear low-dose extrapolation approach based on their conclusion that 1,4-dioxane's MOA for production of hepatic tumors in rodents is "unknown." BMR 0.5 Equation (1) CSF = = 0.1 (mg/kg/d)1 POD 4.95 mg/kg/d 2.4 Comments Provided to USEPA During External Peer Review When USEPA's IRIS program derives toxicity values, the Toxicological Review undergoes critical evaluation by individuals from within and outside the agency. A result of the outside review efforts indicated several external peer review panel members believed that available information for 1,4-dioxane could "support the use of a nonlinear extrapolation approach to estimate human carcinogenic risk" and arcadis.con 4 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications that "such an approach should be presented in the Toxicological Review.' Specifically, the USEPA (2010) notes: "[N]umerous short-term in vitro and a few in vivo tests were nonpositive for 1,4-dioxane-induced genotoxicity". Results from two-stage mouse skin tumor bioassays "suggest that a potential mode of action for 1,4- dioxane-induced tumors may involve proliferation of cells initiated spontaneously, or by some other agent, to become tumors." Additionally, a public commenter noted: "Low-dose linear extrapolation for the oral CSF is not appropriate nor justified by the data. The weight of evidence supports a threshold (nonlinear) MOA when metabolic pathway is saturated at high doses. Nonlinear extrapolations should be evaluated and presented for 1,4-dioxane." These statements indicated that some reviewers felt the toxicological data for 1,4-dioxane indicated that it may not behave in a linear manner, but rather as a threshold carcinogen. Nonetheless, USEPA (2010) ultimately concluded that there was insufficient information available to support any of the proposed MOAs and proceeded to adopt, albeit imprecisely in hindsight, the default linear low-dose extrapolation approach. arcadis.com 5 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 3 DOURSON ET AL. (2014): MODE OF ACTION (MOA) ANALYSIS FOR LIVER TUMORS FROM ORAL 1,4- DIOXANE EXPOSURES AND EVIDENCE-BASED DOSE ss RESPONSE ASSESSMENT USEPA's (2010) conclusion to evaluate 1,4-dioxane as a non-threshold, linear, low-dose extrapolation carcinogen, was "based, in part, on the following: (1) apparent uncertainty in the toxic moiety for 1,4- dioxane; and, (2) apparent lack of noncancer toxicity data from several mouse bioassays at doses that evoke tumors, or that otherwise appear to have conflicting information concerning non-neoplastic lesions in the liver of rodents exposed orally to 1,4-dioxane" (Dourson et al. 2014). Recognizing that the key studies were performed over 3 decades, Dourson et al. (2014) hypothesized that "differences in histologic approaches for quantifying and reporting non-neoplastic changes may have been responsible for the differences noted across the studies" and would account for the apparent lack of non-cancer toxicity data reported in the key mouse bioassays. In addition to directly testing this hypothesis, Dourson et al. (2014) reviewed the database of genotoxicity studies, "which included DNA replication and promotion bioassays as well as mutation, initiation, and DNA repair studies," synthesized the genotoxicity database for 1,4- dioxane, and developed and analyzed a biologically plausible MOA for the formation of hepatic tumors in rodents by employing USEPA's (2005) carcinogen guidelines. Dourson et al.'s (2014) findings from the reread of the NCI (1978) mouse bioassay histopathology slides and review of the extensive genotoxicity database demonstrates that chronic exposure to 1,4-dioxane in drinking water is associated with a non-linear mode of carcinogenic action (threshold). which is contrary to USEPA's default linear low-dose extrapolation approach (non-threshold). The cancer MOA developed by Dourson et al. (2014) also afforded new data with which to perform an improved dose-response assessment for 1,4-dioxane using toxicological endpoints that protect against 1,4-dioxane's cancer MOA (refer to Appendix A for additional details). In regards to choosing a low-dose extrapolation approach, USEPA's Guidelines for Carcinogen Risk Assessment (2005) plainly state that "[a] nonlinear approach [i.e., derivation of a reference dose or concentration] should be selected when there are sufficient data to ascertain the mode of action and conclude that it is not linear at low doses and the agent does not demonstrate mutagenic or other activity consistent with linearity at low doses.' The information presented by USEPA (2010) and supplemented by the new information from Dourson et al. (2014) shows that: (1) 1,4-dioxane causes tumors at high doses through an MOA that involves cytotoxic effects, regenerative cell proliferation, and subsequent tumor formation; (2) the effects that precede tumor formation display non-linear dose-responses; and (3) 1,4- dioxane does not cause mutations at concentrations that are not cytotoxic. As a result, the RfD of 0.05 mg/kg/d developed by Dourson et al (2014) addressed key data gaps identified by USEPA (2010) and protects against the development of liver cancers following oral exposure to 1,4-dioxane. arcadis.com 6 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 4 DOURSON ET AL. (2016 IN PEER REVIEM: UPDATED MODE OF ACTION ANALYSIS (MOA) FOR LIVER TUMORS FROM ORAL ,4-DIOXANE EXPOSURES AND EVIDENCE-BASED DOSE-RESPONSE ASSESSMENT While Dourson et al. (2014) demonstrated that a threshold-based, regenerative cell proliferation MOA accounted for the tumor findings in the NCI (1978) mouse bioassay, questions still remained about the tumor findings from a 2-year oral mouse bioassay and a 13-week precursor study reported by the JBRC (1990a,b), subsequently published as Kano et al. (2008, 2009). Similar to the NCI (1978) mouse bioassay discussed in Dourson et al. (2014), the Japanese work provided few details or findings regarding non- cancer toxicity in the mouse liver after long-term exposure to 1,4-dioxane. To address the remaining questions regarding the apparently discordant findings between the tumor MOA in mice and rats and enhance the investigation of the threshold-based MOA for hepatic tumor formation, Dourson et al. (2016 in peer review) performed a detailed evaluation of the translated Japanese rodent bioassay reports (JBRC 1990a,b) and integrated the findings with other lines of evidence for the regenerative cell proliferation MOA. This effort is summarized in Appendix B. In addition to the detailed evaluation of the JBRC (1990a,b) bioassays, Dourson et al. (2016 in peer review) also solicited opinions from several pathologists regarding the conflicting findings from the mouse bioassays. Dourson et al. (2016 in peer review) reported: "Collectively these pathology opinions support the hypothesized MOA discussed in U.S. EPA (2013) and Dourson et al. (2014) that the liver tumors from oral exposure to 1,4-dioxane occur after metabolic saturation, accumulation of the parent 1,4-dioxane molecule, liver toxicity and a regenerative hyperplasia. While additional live experimental animal testing might add confirmatory findings, a threshold for these tumors is expected if metabolism of the parent compound is not saturated, since subsequent liver toxicity does not occur." By integrating all lines of evidence, Dourson et al. (2016 in peer review) concluded: "When the many lines of evidence are taken together, the reevaluation of the Japanese studies show consistent findings in rats and consistent findings in mice other than liver histopathology not being fully recorded in the second chronic study. However, based on the number of studies conducted, the well established metabolic saturation of 1,4-dioxane metabolism in humans and experimental animals, the effects of higher dose exposures on target organ toxicity, the presence of proliferative lesions, the effect of dose and time on the progression of lesions, the time of appearance of tumors, the spectrum of tumors developed, the number and incidence of tumors at organ sites with high or low background historical incidence, and the shapes of the dose-response curve for key events and tumors, all lead to the conclusion that a regenerative hyperplasia MOA is operating with 1,4-dioxane induced liver tumors." arcadis.con 7 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 5 IMPACT OF DOURSON ET AL.S UPDATED TOXICITY ASSESSMENT ON RISK-BASED DRINKING WATER CRITERIA An agency's choice to set risk-based criteria for 1,4-dioxane based on a threshold- or non-threshold- approach has the potential to drastically impact the value of the final criterion. An example of this is provided herein based on the approach used by the New Jersey Department of Environmental Protection (NJDEP) to derive groundwater quality criteria (NJDEP 2014). The risk-based equations NJDEP uses to derive groundwater criteria for threshold and non-threshold toxicants are shown below in Equations (2) and (3), respectively, while default exposure factors are shown in Table 1 below. Using the RfD of 0.05 mg/kg/d derived from Kociba et al. (1974) by Dourson et al. (2014) to protect against a regenerative cell proliferation MOA yields a risk-based criterion of 400 g/L Using USEPA's (2010) CSF of 0.1 (mg/kg/d)-¹ yields a risk-based criterion of 0.4 (0.35) g/L, corresponding to a 1 in 1,000,000 (1x10-6) excess lifetime cancer risk. Therefore, using the toxicity value derived based on a regenerative cell proliferation MOA (RfD, threshold approach) yields a criterion that is 1,000 times higher than the value derived using USEPA's CSF approach (linear low-dose extrapolation, non-threshold). The authors of this paper conclude that sites monitoring groundwater containing 1,4-dioxane at levels below 400 g/L would meet a reasonable groundwater quality criterion that is protective of human health. RfD x BW x CF x RSC Equation (2) Criterion = x UF BW x CF Equation (3) Criterion = x IRDW arcadis.com 8 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications Table 1. Toxicity Values and NJDEP's Exposure Factors for Calculating Risk-Based Groundwater Quality Criteria Exposure Pactor Units value bource RfD mg/kg/d 0.05 Dourson et al. (2014) CSF (mg/kg/d)-1 0.1 USEPA (2010) Target risk (TR) unitless 10-6 NJDEP default BW kg 70 NJDEP default Conversion factor (CF) g/mg 1,000 NJDEP default Relative source contribution (RSC) unitless 0.2 NJDEP default Drinking water ingestion rate (IRDw) L/d 2 NJDEP default Uncertainty factor (UF) unitless 1 NJDEP default Notes: kg = kilograms L/d = liters per day g/mg = micrograms per milligram arcadis.com 9 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 6 SUMMARY AND CONCLUSIONS To support several state regulatory agencies, Dourson et al. (2016 in peer review) recently undertook additional scientific investigations to address data gaps identified in USEPA's (2010) Toxicological Review regarding 1,4-dioxane's cancer MOA and assessment approach. Collectively, Dourson et al.'s (2014, 2016 in peer review) cancer MOA evaluations and dose-response assessments addressed USEPA's uncertainties and indeed demonstrate that chronic exposure to 1,4-dioxane in drinking water is associated with a non-linear mode of carcinogenic action (threshold). These additional scientific findings provide new information that resolve 1,4- dioxane's cancer MOA and support use of a non-linear dose response approach to protect against development of cancer following low-dose oral exposures. USEPA's (2010) cancer evaluation showed that 1,4-dioxane is not mutagenic or genotoxic at non- cytotoxic doses. However, USEPA ultimately chose to use a linear low-dose extrapolation approach for estimating human cancer risk from oral exposure to 1, 4-dioxane because they concluded that the MOA for tumor formation was unknown. The recent scientific investigations by Dourson et al. (2014, 2016 in peer review) provide new information to address data gaps identified by USEPA (2010) and demonstrate that 1,4-dioxane causes liver tumors in rodents through a regenerative cell proliferation MOA. The regenerative cell proliferation MOA is characterized by: (1) metabolic saturation and accumulation of parent compound; (2) cellular swelling, hypertrophy, and liver weight increase; (3) necrosis and/or inflammation; (4) increased DNA synthesis, hyperplasia development, and foci development; and (5) development of liver adenoma and carcinomas. Specifically, 1,4-dioxane must accumulate in the liver to levels that cause inflammation and cell damage before liver tumors can form. If the first key event does not occur (metabolic saturation), then liver tumors will not form. Therefore, there is a threshold of exposure for 1,4-dioxane below which tumors do not form and it is appropriate to use a non-linear low-dose extrapolation procedure for estimating risks. The RfD of 0.05 mg/kg/d derived by Dourson et al. (2014) is protective against tumor formation through this series of events (MOA) and was calculated using USEPA's preferred methods and best available scientific practices. Using Dourson et al.'s (2014) peer-reviewed RfD, based on a regenerative cell proliferation MOA to derive a groundwater drinking water criterion results in a criterion (400 g/L) that is 1,000 times greater than the concentration derived using USEPA's default CSF approach (0.4 g/L). Based on Dourson et al.'s (2014, 2016 in peer review) studies, it is reasonable to conclude that sites that monitor groundwater containing 1,4-dioxane at levels below 400 g/L would meet a reasonable groundwater quality criteria. The recent scientific findings summarized in this report have major implications for sites that are currently or will be managing water resources impacted by 1,4-dioxane. Considering that 1,4-dioxane is emerging as a water resource contaminant, in part due to USEPA's default linear low-dose cancer evaluation approach for liver tumors in rodents (USEPA 2010), the updated toxicology evidence that 1,4-dioxane is a threshold carcinogen is significant, and suggests that many current regulatory guidelines and standards are unnecessarily low. As such, the authors of this paper conclude that sites that monitor groundwater containing 1,4-dioxane at levels below 400 g/L would meet a reasonable groundwater quality criteria that is protective of human health. arcadis.con 10 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 7 REFERENCES ARA. 2016. 1,4-Dioxane Analysis. Available on line [Accessed Dec. 19] at: http://allianceforrisk.org/riskie- 2/. Buffler, P.A., S.M. Wood, L. Suarez, and D.J. Kilian. 1978. Mortality follow-up of workers exposed to 1,4- dioxane. J Occup Environ Med, 20: 255-259. Dourson, M., J. Reichard, P. Nance, H. Burleigh-Flayer, A. Parker, M. Vincent, and E.E. McConnell. 2014. Mode of action analysis for liver tumors from oral 1,4-dioxane exposures and evidence-based dose response assessment. Regul Toxicol Pharmacol. 68: 387-401. Dourson, M., J. Higginbotham, J. Crum, H. Burleigh-Flayer P, Nance, N. Forsberg, and M. Lafranconi. 2016 in peer review. Update: Mode of Action (MOA) for Liver Tumors Induced by Oral Exposure to 1,4-Dioxane. Regul Toxicol Pharmacol. Available online at: http://allianceforrisk.org/14-dioxane- analysis/. Health Canada. 2005. Drinking Water Guidance Value for 1,4-Dioxane. August 23. JBRC. 1990a. Report of Carcinogenicity Study by Oral Administration of 1,4-Dioxane (Mixed with Water) to Rats and Mice. Japan Industrial Safety and Health Association. December 28. JBRC. 1990b. Report of Preliminary Carcinogenicity Studies (Acute, Two-Week, and Thirteen-Week Studies) by Oral Administration of ,4-Dioxane (Mixed with Water) to Rats and Mice. Japan Industrial Safety and Health Association. December 28. Kano. H., Y. Umeda, M. Saito, H. Senoh, H. Ohbayashi, S. Aiso, K. Yamazaki, K. Nagano, and S. Fukushima. 2008. Thirteen-week oral toxicity of 1,4-dioxane in rats and mice. J Toxicol Sci. 33: 141- 153. Kano, H., Y, Umeda, T. Kasai, T. Sasaki, M. Matsumoto, K. Yamazaki, K. Nagano, H. Arito, and S. Fukushima. 2009. Carcinogenicity of 1,4-dioxane administered in drinking-water to rats and mice for 2 years. Food Chem Toxicol. 47:2776 - 2784. Kociba, R.J., S.B. McCollister, C. Park, T.R. Torkelson, and P.J. Gehring. 1974. 1,4-dioxane. I. Results of a 2-year ingestion study in rats. Toxicol Appl Pharmacol, 30: 275-286. doi:10.1016/0041- 008X(74)90099-4. McConnell, G. 2013. Report on the review of liver slides from the National Cancer Institute's Bioassay of 1,4-Dioxane for Possible Carcinogenicity Conducted in 1978 (NCI, 1978). Submitted to Toxicology Excellence for Risk Assessment. January/March 2013. NCI. 1978. Bioassay of 1,4-Dioxane for possible Carcinogenicity. Carcinogenesis Testing Program, Division of Cancer Cause and Prevention, National Cancer Institute. NIH, Bethesda, MD, 78-1330. Netherlands. 1999. Risk Assessment: 1, 4-Dioxane. Netherlands Organization for Applied Scientific Research (TNO) and the National Institute of Public Health and the Environment (RIVM). Chemical Substances Bureau, Ministry of Housing, Spatial Planning and the Environment (VROM), Netherlands, Final Version, 5 November, EINECS-No.: 204-661-8. arcadis.con 11 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications Neumann, H.G., H.W. Thielmann, J.G. Filser, H.P. Gelbke, H. Griem, H. Kappus, K.H. Norpoth, U. Reuter, S. Vamvakas, P. Wardenbach, and H.E. Wichmann. 1977. Proposed changes in the classification of carcinogenic chemicals in the work area. Reg. Toxicol. Pharmacol., 26:288-295. National Industrial Chemicals Notification and Assessment Scheme (NICNAS). 1998. Priority Existing Chemical Assessment Reports: 1,4-dioxane. Sydney, Australia: Australia Department of Health and Ageing. June. Available online at: NJDEP. 2014. Ground Water Quality Standards. N.J.A.C 7:9C. Available online at: http://www.nj.gov/dep/rules/rules/njac7_9c.pd Office of Environmental Health Hazard Assessment (OEHHA). 2002. Air Toxics Hot Spots Program. Risk Assessment Guidelines. Part II. Technical Support Document for Describing Available Cancer Potency Factors. Office of Environmental Health Hazard Assessment, California Environmental Protection Agency. December. Stickney, J.A., S.L. Sager, J.R. Clarkson, L.A. Smith, B.J. Locey, M.J. Bock, R. Hartung, and S.F. Olp. 2003. An updated evaluation of the carcinogenic potential of 1,4-dioxane. Regul Toxicol Pharmacol. 38(2):183-95. Thiess, A.M., E. Tress, and I. Fleig. 1976. Arbeitsmedizinische Untersuchungsergebnisse von Dioxan- exponierten Mitarbeitern [Industrial-medica investigation results in the case of workers exposed to dioxane]. Arbeitsmedizin, Sozialmedizin, Umweltmedizin, 11: 35-46. USEPA. 2005. Guidelines for carcinogen risk assessment, final report. EPA/630/P-03/001F. Risk Assessment Forum; U.S. Environmental Protection Agency. Washington, DC. March. USEPA. 2010. Toxicological Review of 1,4-Dioxane (CAS No. 123-91-1). EPA/635-R-09-005-F. Washington, D.C. August. USEPA. 2011. Recommended Use of Body Weight3/4 as the Default Method in Derivation of the Oral Reference Dose. EPA/100/R11/0001. Risk Assessment Forum. Washington, DC. USEPA. 2012. Benchmark Dose Technical Guidance. EPA/100/R-12/001. Risk Assessment Forum. Washington, DC. June 12. USEPA. 2013. Toxicological review of 1,4- Dioxane (with inhalation update) (CAS No. 123-91-1) in support of summary information on the Integrated Risk Information System (IRIS) [EPA Report]. (EPA-635/R-11/003-F). Washington, DC. USEPA. 2016a. Drinking Water Contaminant Candidate List 4 - Final. Federal Register Notice, Volume 81, No. 2222, Thursday, November 17. USEPA. 2016b. The Third Unregulated Contaminant Monitoring Rule (UCMR 3): Data Summary, July 2016. Office of Water (MS-140). EPA 815-S-16-004, Available at: USEPA. 2016c. Conducting a Human Health Risk Assessment, Dose-Response. Available at: arcadis.com 12 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 APPENDIX A Mode of Action Analysis for Liver Tumors Based on NCI Siide Reread and RfD Derivation (Dourson et al. 2014) Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 ARCADIS Gesign & for natural and built assets Appendix A MODE OF ACTION ANALYSIS FOR LIVER TUMORS BASED ON NCI SLIDE REREAD AND RFD DERIVATION (DOURSON ET AL. 2014) January 2017 Source: :ttps://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) CONTENTS Acronyms and Abbreviations ii 1 Reread of NCI (1978) Histopathology Slides and Mode of Action Evaluation for Hepatic Tumors in Mice 3 1.1 Review of 1,4-Dioxane's Genotoxicity Database 4 1.2 Mode of Action Analysis 4 1.2.1 Key Event 1: Accumulation of Parent Compound 5 1.2.2 Key Event 2: Liver Cell Hypertrophy and Necrosis 5 1.2.3 Key Event 3: DNA Synthesis 5 1.2.4 Key Event 4: Regenerative Cell Proliferation 5 1.2.5 Key Event 5: Promotion of Endogenously Initiated Tumors 6 1.3 Updated Dose-Response Assessment and Reference Dose Derivation for 1,4-Dioxane 6 2 References 8 arcadis.com i Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) ACRONYMS AND ABBREVIATIONS BMD benchmark dose-modeling CUF composite uncertainty factor EPL Experimental Pathology Laboratories JBRC Japan Bioassay Research Center mg/kg/d milligrams per kilogram body weight per day MOA mode of action NCI National Cancer Institute NOAEL no-observable-adverse-effect level POD point of departure RfD oral reference dose g/L micrograms per liter USEPA United States Environmental Protection Agency arcadis.com ii Source: https://wwww.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) 1 REREAD OF NCI (1978) HISTOPATHOLOGY SLIDES AND MODE OF ACTION EVALUATION FOR HEPATIC TUMORS IN MICE To test their hypothesis and better understand the "sequence of events that maybe have contributed to the MOA of the observed liver tumors," Dourson et al. (2014) and McConnell (2013) performed a blinded reread of the mouse National Cancer Institute (NCI) (1978) liver histopathology slides, because that study did not report non-neoplastic lesions in livers of the high-dose group. Note this is one of the two long-term oral mouse bioassays that exist for 1,4-dioxane; the other chronic mouse bioassay was performed by the Japan Bioassay Research Center (JBRC) and is reported most recently by Kano et al. (2009). As noted by Dourson et al. (2014): "Because terminology and practices for reporting liver lesions has changed since the time of the NCI study (1978), and because EPA (2005) is focusing more on an understanding of a chemical's Mode of Action (MOA) prior to any determination of its dose response, a re-review of the liver slides of mice from the NCI study (1978) was performed. This reanalysis was performed at the Experimental Pathology Laboratories (EPL), Research Triangle Park, NC during September through November 2012. The objective of the slide review was to determine if any non-neoplastic lesions in the liver were present in an effort to understand the sequence of events that may have contributed to the MOA of the observed liver tumors in mice. Another reason for the slide review was because at the time of the original slide review (i.e., 1978) the NCI typically recorded only the most severe diagnosis on a given slide, (e.g., adenoma or carcinoma). During this timeframe, the focus of cancer bioassays was to determine the potential carcinogenic activity of the chemical, not its potential chronic toxicity. For example, if an adenoma, carcinoma, and evidence of chronic toxicity (e.g., hepatocellular hypertrophy), were all present on a given slide, only the tumor response was typically recorded. Thus, it was unclear whether non-neoplastic lesions were present in the livers of mice but were not recorded in the NCI carcinogenicity study. McConnell's (2013) reread of the NCI (1978) mouse liver histopathology slides and Dourson et al.'s (2014) summary report demonstrate that chronic exposure to 1,4-dioxane in drinking water is associated with a non-linear mode of carcinogenic action (contrary to the United States Environmental Protection Agency's [USEPA's] low-dose extrapolation conclusion) based on several hepatotoxic effects that preceded tumor formation, including: Dose-dependent hepatocellular glycogen depletion Dose-dependent hepatocellular hypotrophy Dose-related hepatocellular necrosis Dose-dependent hepatocellular inflammation associated with necrosis Dose-related hyperplasia in several non-neoplastic cell types arcadis.com 3 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) Dourson et al. (2014) states: "The appearance of the liver toxicity follows the pattern where glycogen depletion occurs either concurrently with, or preceding, hypertrophy in both sexes. This was followed closely by necrosis and inflammation in males, but a high control incidence of necrosis and inflammation clouded this overall pattern found in females In terms of dose-response behavior, hypertrophy preceded the formation of foci, which appeared to precede formation of tumors. This pattern was also evident in an individual animal analysis." 1.1 Review of ,4-Dioxane's Genotoxicity Database As a component of their mode of action (MOA) analysis, Dourson et al. (2014) reviewed 1,4-dioxane's genotoxicity database using the information presented in USEPA's (2010) Toxicological Review for 1,4- dioxane. Dourson et al. (2014) noted: '1,4-dioxane has been tested for genotoxicity using in vitro assay systems with prokaryotic organisms, non-mammalian eukaryotic organisms, and mammalian cells, both with and without metabolic activation.' "[A]II fifteen mutagenicity tests reported (8 without activation and 7 with metabolic activation) were negative." "22 in vitro genotoxicity assays, and 9 in vivo genotoxicity assays were negative." "Eight genotoxicity assays were noted to be positive but only at high or noted cytotoxic doses." Based on their review of 1,4-dioxane's genotoxicity database, Dourson et al. (2014) states "1,4-dioxane does not cause point mutations, DNA repair, or [tumor] initiation" when administered at non-cytotoxic doses, which is in general agreement with USEPA's conclusions (USEPA 2010). The authors noted their conclusions were similar to USEPA's, but differ in that "if mutations are caused by 1,4-dioxane, it is only at high cytotoxic doses." The authors concluded: "1,4-dioxane does not cause mutagenicity as evidenced by uniformly negative results in standard in vitro and in vivo genotoxicity bioassays at levels that are not overtly toxic, but it may be a clastogen in vivo, in light of the mixed results in the micronucleus assays. It follows that mutations needed for tumor formation are then likely from the known endogenously available pool of mutations, and that a regenerative hyperplasia evokes more of these endogenous mutations to form tumors. Mutation potentially caused by 1,4-dioxane at high doses is precluded as a key event in tumor formation." 1.2 Mode of Action Analysis Dourson et al. (2014) proposed five key events in the non-mutagenic MOA resulting in hepatic tumors in rodents; they include: "(1) accumulation of parent compound [at concentrations that saturate metabolic processes], (2) liver cell hypertrophy and necrosis, (3) DNA synthesis, (4) regenerative cell proliferation, and (5) promotion of endogenously-initiated tumors.' The regenerative cell proliferation MOA has a threshold below which hepatic tumors are not formed. Evidence supporting each key event is presented below. arcadis.com 4 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) 1.2.1 Key Event 1: Accumulation of Parent Compound "Humans, rats, and mice extensively metabolize 1,4-dioxane.' "[M]etabolism is a capacity-limited process." "When dose of 1,4-dioxane approaches or exceeds the metabolizing capacity, the unmetabolized fraction of the dose increases and target organ toxicity occurs." "Thus, there appears to be a threshold below which metabolism and elimination are rapid and with less or perhaps without toxicological effects." "Human environmental exposures to 1,4-dioxane are unlikely to approach doses that saturate metabolizing enzymes and which produce liver and nasal tumors in rats." "Hence, since humans, like rats, efficiently metabolize 1,4-dioxane at low doses, enzyme saturation is negligible at low exposure levels." 1.2.2 Key Event 2: Liver Cell Hypertrophy and Necrosis "Liver cell hypertrophy and necrosis are key events in the 1,4-dioxane MOA leading to regenerative cell proliferation and, with chronic exposures, liver tumors.' "Liver changes including centrilobular swelling, single cell necrosis coincide exclusively with saturating doses of 1,4-dioxane and occur in as little as 11 weeks." "Evidence of hepatocellular damage preceding evidence of hepatocellular tumors caused by higher doses of 1,4-dioxane has been provided by several studies." 1.2.3 Key Event 3: DNA Synthesis USEPA (2010) reported "that 1,4-dioxane does not cause DNA repair activity in five standard in vitro and in vivo bioassays that tested for the presence of DNA repair in various model systems." "Conversely, 1,4-dioxane does cause DNA replication as evidenced by in vitro bioassays in rat hepatocytes" "DNA synthesis appears to be a key event for a regenerative cell proliferation and/or tumor promotion and can occur in either the presence or absence of cytotoxicity." "DNA synthesis provides evidence that 1,4-dioxane promotes cell proliferation through cytotoxicity." 1.2.4 Key Event 4: Regenerative Cell Proliferation "Dose-response and temporal data support the occurrence of cell proliferation and hyperplasia prior to the development of liver tumors in the rat model." "Cell proliferation appears to be an early response with significant changes (1.5- to 2-fold) occurring in rats with as little as 2 weeks of exposure." arcadis.com 5 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) "Given time, proliferative changes manifest as pre-neoplastic foci in studies where the histopathology of such changes are reported." 1.2.5 Key Event 5: Promotion of Endogenously Initiated Tumors "Three studies relevant to tumor initiation and promotion establish that 1,4-dioxane does not cause initiation in standard in vivo bioassays, in agreement with the absence of observed mutagenic or genotoxic activity." "[T]umor promotion was associated with significant toxicity in rats when administered by either dermal or oral routes." 1.3 Updated Dose-Response Assessment and Reference Dose Derivation for 1,4-Dioxane Dourson et al. (2014) and USEPA (2010) both relied on the dose-response data reported by Kociba et al. (1974). This study provided data for liver and kidney degeneration and necrosis in 6- to 8-week-old male and female Sherman rats (60/sex/dose group) that were exposed to 1, ,4-dioxane at 0, 0.01, 0.1, or 1% (i.e., 9.6, 94, and 1,015 milligrams per kilogram body weight per day [mg/kg/d] and 19, 148, and 1,599 mg/kg/d for males and females, respectively) in drinking water for up to 716 days. The study reported a no-observed-adverse-effect level (NOAEL) of 9.6 mg/kg/d and provides "the most sensitive measure of adverse effects by 1,4-dioxane" (USEPA 2010). USEPA's Toxicological Review for 1,4-dioxane (USEPA 2010) provides a reference dose (RfD) of 0.03 mg/kg/d. This RfD was derived using the NOAEL of 9.6 mg/kg/d for liver and kidney degeneration and necrosis in rats reported by Kociba et al. (1974) as the point of departure (POD), in combination with a composite uncertainty factor (CUF) of 300 (10 for interspecies extrapolation, 10 for intraspecies extrapolation, and 3 for database deficiencies associated with the lack of a multigenerational reproductive toxicity study). The lowest-observable-adverse-effect level for this study was 94 mg/kg/d (USEPA 2010). USEPA derived the RfD using the NOAEL reported by Kociba et al. (1974) because the published study did not report incidence data for these effects, and therefore, they were unable to perform benchmark dose-modeling (BMD). Alternatively, Dourson et al. (2014) reported an updated RfD of 0.05 mg/kg/d that was derived using incidence data (laboratory report for the published study was provided to Dourson et al. [2014] by The Dow Chemical Company) for hepatocellular necrosis (combined across sexes) and USEPA's preferred approaches¹. Specifically, Dourson et al. (2014) utilized USEPA's preferred BMD approach (USEPA 2012) to derive a POD of 20 mg/kg/d (95% lower bound on the dose associated with a 10% extra risk), USEPA's preferred default bodyweight scaling factor (USEPA 2011), to estimate a human equivalent 1 USEPA (2010) used the NOAEL from Kociba et al. (1974) based on liver and kidney degeneration to derive the RfD, specifically because Kociba et al. (1974) did not provide quantitative incidence or severity data for liver and kidney degeneration and necrosis. However, when appropriate data are available, USEPA prefers using BMD to define the POD (USEPA 2012). Had the incidence data from Kociba et al. (1974) been available at the time of their review, USEPA would have used it to derive a benchmark dose to use as the POD for setting the RfD. arcadis.com 6 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) dose, in combination with a CUF of 100 (3 for interspecies toxicodynamic extrapolation, 10 for intraspecies extrapolation, and 3 due to the lack of a 2-generation reproductive study) to derive an RfD of 0.05 mg/kg/d. Dourson et al. (2014) concluded that "the choice of this endpoint [hepatocellular necrosis] is protective, since liver toxicity, resulting in liver tumors, is the clear apical effect of greatest intensity in the available array of toxic effects." Dourson et al. (2014) calculated their RfD using standard approaches, as shown in Equation (1), below: POD 20 mg/kg/d Equation (1) RfD = = 0.05 mg/kg/d CUF 3x10x3 arcadis.com 7 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) 2 REFERENCES Dourson, M., J. Reichard, P. Nance, H. Burleigh-Flayer, A. Parker, M. Vincent, and E.E. McConnell. 2014. Mode of action analysis for liver tumors from oral 1,4-dioxane exposures and evidence-based dose response assessment. Regul Toxicol Pharmacol. 68: 387-401. Kano, H., Y, Umeda, T. Kasai, T. Sasaki, M. Matsumoto, K. Yamazaki, K. Nagano, H. Arito, and S. Fukushima. 2009. Carcinogenicity of 1,4-dioxane administered in drinking-water to rats and mice for 2 years. Food Chem Toxicol. 47:2776 - 2784. Kociba, R.J., S.B. McCollister, C. Park, T.R. Torkelson, and P.J. Gehring. 1974. 1,4-dioxane. I. Results of a 2-year ingestion study in rats. Toxicol Appl Pharmacol, 30: 275-286. oi:10.1016/0041- 008X(74)90099-4. McConnell, G. 2013. Report on the review of liver slides from the National Cancer Institute's Bioassay of 1,4-Dioxane for Possible Carcinogenicity Conducted in 1978 (NCI, 1978). Submitted to Toxicology Excellence for Risk Assessment. January/March 2013. NCI. 1978. Bioassay of 1,4-Dioxane for possible Carcinogenicity. Carcinogenesis Testing Program, Division of Cancer Cause and Prevention, National Cancer Institute. NIH, Bethesda, MD, 78-1330. USEPA. 2005. Guidelines for carcinogen risk assessment, final report. EPA/630/P-03/001F. Risk Assessment Forum; U.S. Environmental Protection Agency. Washington, DC. March. USEPA. 2010. Toxicological Review of 1,4-Dioxane (CAS No. 123-91-1). EPA/635-R-09-005-F. Washington, D.C. August. USEPA. 2012. Benchmark Dose Technical Guidance. EPA/100/R-12/001. Risk Assessment Forum. Washington, DC. June 12. arcadis.com 8 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 APPENDIX B Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) Source: https://www.industrydocuments.ucsf,edu/docs/fsbn0226 ARCADIS Desion & for natural and built assets Appendix B MODE OF ACTION ANALYSIS FOR LIVER TUMORS BASED ON JBRC REVIEW (DOURSONETAL.2016IN PEER REVIEW) January 2017 Source: :ttps://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) CONTENTS Acronyms and Abbreviations ii 1 Findings from Detailed Review of JBRC Rat Bioassays 3 1.1 Findings from Detailed Review of JBRC Mouse Bioassays 3 1.2 Integration of Evidence Supporting Regenerative Cell Proliferation MOA for 1,4-Dioxane 4 2 References 6 TABLES Table 1. Integration and Comparison of Rat and Mouse Bioassay Data (Adapted from Dourson et al., 2016 in peer review) 5 arcadis.com i Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) ACRONYMS AND ABEREVIATIONS JBRC Japan Bioassay Research Center mg/kg/d milligrams per kilogram body weight per day MOA mode of action NCI National Cancer Institute arcadis.com ii Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) 1 FINDINGS FROM DETAILED REVIEW OF JBRC RAT BIOASSAYS Changes in the liver found in the Japan Bioassay Research Center (JBRC) rat bioassays provide strong evidence that hepatic tumors were modulated by a threshold-based regenerative cell proliferation mode of action (MOA). Dourson et al. (2016 in peer review) found that effects observed in rats were in the expected dose-sequence for a regenerative cell proliferation MOA. Specifically, Dourson et al. (2016 in peer review) observed the following sequence of effects: Dose: 42-55 milligrams per kilogram body weight per day (mg/kg/d) - Effect: Liver swelling, hypertrophy, and liver weight increase Dose: 94-219 mg/kg/d - Effect: Necrosis Dose: 55-389 mg/kg/d - Effect: Hyperplasia and foci development Dose: >200 mg/kg/d - Effect: Increased levels of enzymes associated with liver damage Dose: 274-1015 mg/kg/d - Effect: Adenomas and carcinomas 1.1 Findings from Detailed Review of JBRC Mouse Bioassays Dourson et al. (2016 in peer review) observed the following sequence of effects in the JBRC (1990a) mouse bioassays: Dose: 190-200 mg/kg/d - Effect: Liver swelling, hypertrophy, and liver weight increase Dose: 190-200 mg/kg/d - Effect: Necrosis Dose: Not reported - Effect: Hyperplasia and foci development not reported Dose: 200 mg/kg/d - Effect: Increased levels of enzymes associated with liver damage Dose: 66-964 mg/kg/d - Effect: Adenomas and carcinomas, females Surprisingly, effects in the liver found in the JBRC mouse bioassays conflict with those clearly reported by Dourson et al. (2014) and McConnell (2013) for the reread of the National Cancer Institute (NCI) (1978) mouse bioassay histopathology slides. Additionally, the progression of effects reported by JBRC for the 2- year chronic study is inconsistent with enzymatic changes indicative of liver damage noted in the same study, as well as findings from a 13-week precursor study performed by the same laboratory. As noted by Dourson et al. (2016 in peer review), "the lack of noncancer histopathology in the chronic mouse study is not consistent with the changes in liver enzymes in this same chronic study, nor is this lack of noncancer arcadis.com 3 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) findings expected based on the histopathology of the precursor 13-week study" and "[n]or does the tumor response in the low dose female mice of JBRC (1990a) match the tumor findings in the McConnell (2013) re-read of NCI (1978). Dourson et al. (2016 in peer review) hypothesized that differences in mouse bioassay results between JBRC and McConnell (2013) may be due to differences in the interpretation of the histopathological data, and provided the following quote from JBRC (Kano et al. 2009) to substantiate their claim: "The hepatic hyperplasia of rats and mice diagnosed in the previous report (Yamazaki et al., 1994) [authors note: which was a presentation of the JBRC, 1990a] was re-examined histopathologically and changed to hepatocellular adenomas and altered hepatocellular foci including acidophilic, basophilic and clear cell foci in the present studies, according to the current diagnostic criteria of liver lesions in rats and mice." Unfortunately, slides from the original JBRC (1990a,b) bioassays were not available; therefore, the JBRC slides could not be reread as they were by McConnell (2013) for the NCI (1978) mouse liver slides. Additionally, JBRC did not archive sufficient numbers of pictures of histopathology slides to resolve the issue. While, it is impossible to know for sure from this dataset whether liver tumors formed prior to or following cytotoxic effects, the weight of evidence from the JBRC and NCI mouse bioassays supports a regenerative cell proliferation MOA. 1.2 Integration of Evidence Supporting Regenerative Cell Proliferation MOA for 1,4-Dioxane Following integration of key events from seven rat bioassays, three mouse bioassays, and 1,4-dioxane's genotoxicity profile, presented in Table 1 below, Dourson et al. (2016 in peer review) showed that 1,4- dioxane's toxicological database supports a threshold-based regenerative cell proliferation MOA for tumor formation in livers of rodents orally exposed to 1,4-dioxane. The authors reported that bioassay data for rats leads to the conclusion that "rat liver tumors are evoked by a regenerative hyperplasia," while the authors concluded the "sequence of events from two chronic mouse studies and a subchronic mouse study generally support the hypothesized regenerative hyperplasia MOA" (Dourson et al. 2016 in peer review). In regards to the conflicting mouse bioassay data (McConnell 2013; Dourson et al. 2014; JBRC 1990a), the difference is likely due in part to changes in the terminology and practices used for recording the liver lesions reported by Kano et al. (2009). arcadis.com 4 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226

what is L/d mentioned as ?

fsbn0226

fsbn0226_p9, fsbn0226_p10, fsbn0226_p11, fsbn0226_p12, fsbn0226_p13, fsbn0226_p14, fsbn0226_p15, fsbn0226_p16, fsbn0226_p17, fsbn0226_p18, fsbn0226_p19, fsbn0226_p20, fsbn0226_p21, fsbn0226_p22, fsbn0226_p23, fsbn0226_p24, fsbn0226_p25, fsbn0226_p26, fsbn0226_p27, fsbn0226_p28, fsbn0226_p29, fsbn0226_p30, fsbn0226_p31, fsbn0226_p32, fsbn0226_p33, fsbn0226_p34

Liters per day, liters per day

Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 2 USEPA APPROACH FOR EVALUATING CANCER RISHS POSED BY ORAL EXPOSURE TO 1,4-DIOXANE USEPA's Integrated Risk Information System (IRIS) published the Toxicological Review for 1,4-dioxane, in which it describes their approach and justification for deriving an oral CSF for this constituent. Below is a summary of USEPA's evaluation of available human toxicological data, weight of evidence evaluation, key study identification, critical effect selection, dose-response assessment, and the low-dose extrapolation procedure used to derive 1,4-dioxane's CSF. 2.1 USEPA's Evaluation of Evidence of Cancer in Humans USEPA evaluated the degree to which data provide evidence of carcinogenicity in humans (USEPA 2010). USEPA relied on two human occupational studies in their evaluation of potential impacts related to long-term exposure to 1,4-dioxane (Thiess et al. 1976; Buffler et al. 1978). USEPA concluded that neither study provided evidence that 1, ,4-dioxane causes cancer in humans. However, they noted "the cohort size and number of reported cases were small." 2.2 USEPA's Evaluation of Evidence of Cancer in Animal Bioassays USEPA followed its Guidelines for Carcinogen Risk Assessment (USEPA 2005) to conclude that 1,4- dioxane is "likely to be carcinogenic to humans" based on "evidence of liver carcinogenicity in several 2- year bioassays conducted in three strains of rats, two strains of mice, and in guinea pigs.' USEPA provided several reasons to justify its conclusion. For instance, USEPA concluded that the "available evidence is inadequate to establish a MOA by which 1,4-dioxane induces liver tumors in rats and mice" (USEPA 2010). Specifically, USEPA noted the "[c]onflicting data from rat and mouse bioassays (Japan Bioassay Research Center [JBRC] 1998; Kociba et al., 1974) suggest that cytotoxicity may not be a required precursor event for 1,4-dioxane-induced cell proliferation." USEPA (2010) noted that "[a]vailable data also do not clearly identify whether 1,4-dioxane or one of its metabolites is responsible for the observed effects. However, USEPA also reported that "the generally negative results for 1,4-dioxane in a number of genotoxicity assays indicates the carcinogenicity of 1,4-dioxane may not be mediated by a mutagenic MOA" (USEPA 2010). 2.3 Key Study Identification (Kano et al. 2009), Critical Effect Selection, Dose-Response Assessment, and Low-Dose Extrapolation Procedure USEPA (2010) concluded that the MOA by which 1,4-dioxane produces liver tumors is "unknown, and available evidence in support of any hypothetical mode of carcinogenic action for 1,4-dioxane is inconclusive." With this conclusion in mind, USEPA (2010) identified a 2-year drinking water study performed by Kano et al. (2009) as the key study of the oral CSF for 1,4-dioxane. Note that Kano et al. (2009) published findings originally reported by the JBRC (1990a). Although USEPA (2010) concurrently evaluated two other studies (Kociba et al. 1974; National Cancer Institute [NCI] 1978), the Kano et al. (2009) study was ultimately selected as the key study because USEPA (2010) noted that "[c]alculation of arcadis.com 3 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications a CSF for 1,4-dioxane is based upon the dose-response data for the most sensitive species and gender." The study was performed in accordance with the Organization of Economic Development's Principles for Good Laboratory Practices and involved exposing groups of rats (50 animals of each sex for each dose) and mice (50 animals of each sex for each dose) to 1,4-dioxane (>99% pure) in drinking water for 2 years. Rats were exposed to 1,4-dioxane in drinking water at 0, 200, 1,000, or 5,000 milligrams per liter (mg/L), while mice were exposed at 0, 500, 2,000, or 8,000 mg/L in drinking water. As reported by USEPA (2010): "The investigators used data from water consumption and BW [body weight] to calculate an estimate of the daily intake of 1,4-dioxane (mg/kg-day) by male and female rats and mice. Kano et al. (2009) reported a calculated mean + standard deviation for the daily doses of 1,4-dioxane for the duration of the study. Male rats received doses of approximately 0, 11+1, 55+3, or 274+18 mg/kg-day and female rats received 0, 183, 83+14, or 429+69 mg/kg-day. Male mice received doses of 0, 49+5, 191+21, or 677+74 mg/kg-day and female mice received 0, 66=10, 278+40, or 964+88 mg/kg-day." "The study by Kano et al. (2009) was used for development of an oral CSF. This was a well- designed study, conducted in both sexes in two species (rats and mice) with a sufficient number (N=50) of animals per dose group. The number of test animals allocated among three dose levels and an untreated control group was adequate, with examination of appropriate toxicological endpoints in both sexes of rats and mice. Alternative bioassays (Kociba et al., 1974; NCI, 1978) were available and were fully considered for the derivation of the oral CSF." USEPA identified increased incidence of liver adenomas or carcinomas as the critical effect in rats and mice exposed to 1,4-dioxane in the Kano et al. (2009) study. Following standard dose adjustment to a human equivalent dose using a default body weight (BW) scaling factor (USEPA 2005), USEPA performed dose-response modeling using Benchmark Dose Software and fit the suite of models available in the program to the incidence data for "either hepatocellular carcinoma or adenoma" (USEPA 2010). USEPA concluded that female mice are "more sensitive to liver carcinogenicity induced by 1,4-dioxane compared to other species or tumor types" and identified the lower 95% confidence bound on the benchmark dose associated with a 50% extra risk (benchmark response [BMR]) of developing "either hepatocellular carcinoma or adenoma" (4.95 milligrams per kilogram per day [mg/kg/d]) as the point of departure (POD) for calculating the oral CSF via linear low-dose extrapolation, as shown in Equation (1), below. USEPA (2010) again justified a linear low-dose extrapolation approach based on their conclusion that 1,4-dioxane's MOA for production of hepatic tumors in rodents is "unknown." BMR 0.5 Equation (1) CSF = = 0.1 (mg/kg/d)1 POD 4.95 mg/kg/d 2.4 Comments Provided to USEPA During External Peer Review When USEPA's IRIS program derives toxicity values, the Toxicological Review undergoes critical evaluation by individuals from within and outside the agency. A result of the outside review efforts indicated several external peer review panel members believed that available information for 1,4-dioxane could "support the use of a nonlinear extrapolation approach to estimate human carcinogenic risk" and arcadis.con 4 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications that "such an approach should be presented in the Toxicological Review.' Specifically, the USEPA (2010) notes: "[N]umerous short-term in vitro and a few in vivo tests were nonpositive for 1,4-dioxane-induced genotoxicity". Results from two-stage mouse skin tumor bioassays "suggest that a potential mode of action for 1,4- dioxane-induced tumors may involve proliferation of cells initiated spontaneously, or by some other agent, to become tumors." Additionally, a public commenter noted: "Low-dose linear extrapolation for the oral CSF is not appropriate nor justified by the data. The weight of evidence supports a threshold (nonlinear) MOA when metabolic pathway is saturated at high doses. Nonlinear extrapolations should be evaluated and presented for 1,4-dioxane." These statements indicated that some reviewers felt the toxicological data for 1,4-dioxane indicated that it may not behave in a linear manner, but rather as a threshold carcinogen. Nonetheless, USEPA (2010) ultimately concluded that there was insufficient information available to support any of the proposed MOAs and proceeded to adopt, albeit imprecisely in hindsight, the default linear low-dose extrapolation approach. arcadis.com 5 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 3 DOURSON ET AL. (2014): MODE OF ACTION (MOA) ANALYSIS FOR LIVER TUMORS FROM ORAL 1,4- DIOXANE EXPOSURES AND EVIDENCE-BASED DOSE ss RESPONSE ASSESSMENT USEPA's (2010) conclusion to evaluate 1,4-dioxane as a non-threshold, linear, low-dose extrapolation carcinogen, was "based, in part, on the following: (1) apparent uncertainty in the toxic moiety for 1,4- dioxane; and, (2) apparent lack of noncancer toxicity data from several mouse bioassays at doses that evoke tumors, or that otherwise appear to have conflicting information concerning non-neoplastic lesions in the liver of rodents exposed orally to 1,4-dioxane" (Dourson et al. 2014). Recognizing that the key studies were performed over 3 decades, Dourson et al. (2014) hypothesized that "differences in histologic approaches for quantifying and reporting non-neoplastic changes may have been responsible for the differences noted across the studies" and would account for the apparent lack of non-cancer toxicity data reported in the key mouse bioassays. In addition to directly testing this hypothesis, Dourson et al. (2014) reviewed the database of genotoxicity studies, "which included DNA replication and promotion bioassays as well as mutation, initiation, and DNA repair studies," synthesized the genotoxicity database for 1,4- dioxane, and developed and analyzed a biologically plausible MOA for the formation of hepatic tumors in rodents by employing USEPA's (2005) carcinogen guidelines. Dourson et al.'s (2014) findings from the reread of the NCI (1978) mouse bioassay histopathology slides and review of the extensive genotoxicity database demonstrates that chronic exposure to 1,4-dioxane in drinking water is associated with a non-linear mode of carcinogenic action (threshold). which is contrary to USEPA's default linear low-dose extrapolation approach (non-threshold). The cancer MOA developed by Dourson et al. (2014) also afforded new data with which to perform an improved dose-response assessment for 1,4-dioxane using toxicological endpoints that protect against 1,4-dioxane's cancer MOA (refer to Appendix A for additional details). In regards to choosing a low-dose extrapolation approach, USEPA's Guidelines for Carcinogen Risk Assessment (2005) plainly state that "[a] nonlinear approach [i.e., derivation of a reference dose or concentration] should be selected when there are sufficient data to ascertain the mode of action and conclude that it is not linear at low doses and the agent does not demonstrate mutagenic or other activity consistent with linearity at low doses.' The information presented by USEPA (2010) and supplemented by the new information from Dourson et al. (2014) shows that: (1) 1,4-dioxane causes tumors at high doses through an MOA that involves cytotoxic effects, regenerative cell proliferation, and subsequent tumor formation; (2) the effects that precede tumor formation display non-linear dose-responses; and (3) 1,4- dioxane does not cause mutations at concentrations that are not cytotoxic. As a result, the RfD of 0.05 mg/kg/d developed by Dourson et al (2014) addressed key data gaps identified by USEPA (2010) and protects against the development of liver cancers following oral exposure to 1,4-dioxane. arcadis.com 6 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 4 DOURSON ET AL. (2016 IN PEER REVIEM: UPDATED MODE OF ACTION ANALYSIS (MOA) FOR LIVER TUMORS FROM ORAL ,4-DIOXANE EXPOSURES AND EVIDENCE-BASED DOSE-RESPONSE ASSESSMENT While Dourson et al. (2014) demonstrated that a threshold-based, regenerative cell proliferation MOA accounted for the tumor findings in the NCI (1978) mouse bioassay, questions still remained about the tumor findings from a 2-year oral mouse bioassay and a 13-week precursor study reported by the JBRC (1990a,b), subsequently published as Kano et al. (2008, 2009). Similar to the NCI (1978) mouse bioassay discussed in Dourson et al. (2014), the Japanese work provided few details or findings regarding non- cancer toxicity in the mouse liver after long-term exposure to 1,4-dioxane. To address the remaining questions regarding the apparently discordant findings between the tumor MOA in mice and rats and enhance the investigation of the threshold-based MOA for hepatic tumor formation, Dourson et al. (2016 in peer review) performed a detailed evaluation of the translated Japanese rodent bioassay reports (JBRC 1990a,b) and integrated the findings with other lines of evidence for the regenerative cell proliferation MOA. This effort is summarized in Appendix B. In addition to the detailed evaluation of the JBRC (1990a,b) bioassays, Dourson et al. (2016 in peer review) also solicited opinions from several pathologists regarding the conflicting findings from the mouse bioassays. Dourson et al. (2016 in peer review) reported: "Collectively these pathology opinions support the hypothesized MOA discussed in U.S. EPA (2013) and Dourson et al. (2014) that the liver tumors from oral exposure to 1,4-dioxane occur after metabolic saturation, accumulation of the parent 1,4-dioxane molecule, liver toxicity and a regenerative hyperplasia. While additional live experimental animal testing might add confirmatory findings, a threshold for these tumors is expected if metabolism of the parent compound is not saturated, since subsequent liver toxicity does not occur." By integrating all lines of evidence, Dourson et al. (2016 in peer review) concluded: "When the many lines of evidence are taken together, the reevaluation of the Japanese studies show consistent findings in rats and consistent findings in mice other than liver histopathology not being fully recorded in the second chronic study. However, based on the number of studies conducted, the well established metabolic saturation of 1,4-dioxane metabolism in humans and experimental animals, the effects of higher dose exposures on target organ toxicity, the presence of proliferative lesions, the effect of dose and time on the progression of lesions, the time of appearance of tumors, the spectrum of tumors developed, the number and incidence of tumors at organ sites with high or low background historical incidence, and the shapes of the dose-response curve for key events and tumors, all lead to the conclusion that a regenerative hyperplasia MOA is operating with 1,4-dioxane induced liver tumors." arcadis.con 7 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 5 IMPACT OF DOURSON ET AL.S UPDATED TOXICITY ASSESSMENT ON RISK-BASED DRINKING WATER CRITERIA An agency's choice to set risk-based criteria for 1,4-dioxane based on a threshold- or non-threshold- approach has the potential to drastically impact the value of the final criterion. An example of this is provided herein based on the approach used by the New Jersey Department of Environmental Protection (NJDEP) to derive groundwater quality criteria (NJDEP 2014). The risk-based equations NJDEP uses to derive groundwater criteria for threshold and non-threshold toxicants are shown below in Equations (2) and (3), respectively, while default exposure factors are shown in Table 1 below. Using the RfD of 0.05 mg/kg/d derived from Kociba et al. (1974) by Dourson et al. (2014) to protect against a regenerative cell proliferation MOA yields a risk-based criterion of 400 g/L Using USEPA's (2010) CSF of 0.1 (mg/kg/d)-¹ yields a risk-based criterion of 0.4 (0.35) g/L, corresponding to a 1 in 1,000,000 (1x10-6) excess lifetime cancer risk. Therefore, using the toxicity value derived based on a regenerative cell proliferation MOA (RfD, threshold approach) yields a criterion that is 1,000 times higher than the value derived using USEPA's CSF approach (linear low-dose extrapolation, non-threshold). The authors of this paper conclude that sites monitoring groundwater containing 1,4-dioxane at levels below 400 g/L would meet a reasonable groundwater quality criterion that is protective of human health. RfD x BW x CF x RSC Equation (2) Criterion = x UF BW x CF Equation (3) Criterion = x IRDW arcadis.com 8 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications Table 1. Toxicity Values and NJDEP's Exposure Factors for Calculating Risk-Based Groundwater Quality Criteria Exposure Pactor Units value bource RfD mg/kg/d 0.05 Dourson et al. (2014) CSF (mg/kg/d)-1 0.1 USEPA (2010) Target risk (TR) unitless 10-6 NJDEP default BW kg 70 NJDEP default Conversion factor (CF) g/mg 1,000 NJDEP default Relative source contribution (RSC) unitless 0.2 NJDEP default Drinking water ingestion rate (IRDw) L/d 2 NJDEP default Uncertainty factor (UF) unitless 1 NJDEP default Notes: kg = kilograms L/d = liters per day g/mg = micrograms per milligram arcadis.com 9 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 6 SUMMARY AND CONCLUSIONS To support several state regulatory agencies, Dourson et al. (2016 in peer review) recently undertook additional scientific investigations to address data gaps identified in USEPA's (2010) Toxicological Review regarding 1,4-dioxane's cancer MOA and assessment approach. Collectively, Dourson et al.'s (2014, 2016 in peer review) cancer MOA evaluations and dose-response assessments addressed USEPA's uncertainties and indeed demonstrate that chronic exposure to 1,4-dioxane in drinking water is associated with a non-linear mode of carcinogenic action (threshold). These additional scientific findings provide new information that resolve 1,4- dioxane's cancer MOA and support use of a non-linear dose response approach to protect against development of cancer following low-dose oral exposures. USEPA's (2010) cancer evaluation showed that 1,4-dioxane is not mutagenic or genotoxic at non- cytotoxic doses. However, USEPA ultimately chose to use a linear low-dose extrapolation approach for estimating human cancer risk from oral exposure to 1, 4-dioxane because they concluded that the MOA for tumor formation was unknown. The recent scientific investigations by Dourson et al. (2014, 2016 in peer review) provide new information to address data gaps identified by USEPA (2010) and demonstrate that 1,4-dioxane causes liver tumors in rodents through a regenerative cell proliferation MOA. The regenerative cell proliferation MOA is characterized by: (1) metabolic saturation and accumulation of parent compound; (2) cellular swelling, hypertrophy, and liver weight increase; (3) necrosis and/or inflammation; (4) increased DNA synthesis, hyperplasia development, and foci development; and (5) development of liver adenoma and carcinomas. Specifically, 1,4-dioxane must accumulate in the liver to levels that cause inflammation and cell damage before liver tumors can form. If the first key event does not occur (metabolic saturation), then liver tumors will not form. Therefore, there is a threshold of exposure for 1,4-dioxane below which tumors do not form and it is appropriate to use a non-linear low-dose extrapolation procedure for estimating risks. The RfD of 0.05 mg/kg/d derived by Dourson et al. (2014) is protective against tumor formation through this series of events (MOA) and was calculated using USEPA's preferred methods and best available scientific practices. Using Dourson et al.'s (2014) peer-reviewed RfD, based on a regenerative cell proliferation MOA to derive a groundwater drinking water criterion results in a criterion (400 g/L) that is 1,000 times greater than the concentration derived using USEPA's default CSF approach (0.4 g/L). Based on Dourson et al.'s (2014, 2016 in peer review) studies, it is reasonable to conclude that sites that monitor groundwater containing 1,4-dioxane at levels below 400 g/L would meet a reasonable groundwater quality criteria. The recent scientific findings summarized in this report have major implications for sites that are currently or will be managing water resources impacted by 1,4-dioxane. Considering that 1,4-dioxane is emerging as a water resource contaminant, in part due to USEPA's default linear low-dose cancer evaluation approach for liver tumors in rodents (USEPA 2010), the updated toxicology evidence that 1,4-dioxane is a threshold carcinogen is significant, and suggests that many current regulatory guidelines and standards are unnecessarily low. As such, the authors of this paper conclude that sites that monitor groundwater containing 1,4-dioxane at levels below 400 g/L would meet a reasonable groundwater quality criteria that is protective of human health. arcadis.con 10 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 7 REFERENCES ARA. 2016. 1,4-Dioxane Analysis. Available on line [Accessed Dec. 19] at: http://allianceforrisk.org/riskie- 2/. Buffler, P.A., S.M. Wood, L. Suarez, and D.J. Kilian. 1978. Mortality follow-up of workers exposed to 1,4- dioxane. J Occup Environ Med, 20: 255-259. Dourson, M., J. Reichard, P. Nance, H. Burleigh-Flayer, A. Parker, M. Vincent, and E.E. McConnell. 2014. Mode of action analysis for liver tumors from oral 1,4-dioxane exposures and evidence-based dose response assessment. Regul Toxicol Pharmacol. 68: 387-401. Dourson, M., J. Higginbotham, J. Crum, H. Burleigh-Flayer P, Nance, N. Forsberg, and M. Lafranconi. 2016 in peer review. Update: Mode of Action (MOA) for Liver Tumors Induced by Oral Exposure to 1,4-Dioxane. Regul Toxicol Pharmacol. Available online at: http://allianceforrisk.org/14-dioxane- analysis/. Health Canada. 2005. Drinking Water Guidance Value for 1,4-Dioxane. August 23. JBRC. 1990a. Report of Carcinogenicity Study by Oral Administration of 1,4-Dioxane (Mixed with Water) to Rats and Mice. Japan Industrial Safety and Health Association. December 28. JBRC. 1990b. Report of Preliminary Carcinogenicity Studies (Acute, Two-Week, and Thirteen-Week Studies) by Oral Administration of ,4-Dioxane (Mixed with Water) to Rats and Mice. Japan Industrial Safety and Health Association. December 28. Kano. H., Y. Umeda, M. Saito, H. Senoh, H. Ohbayashi, S. Aiso, K. Yamazaki, K. Nagano, and S. Fukushima. 2008. Thirteen-week oral toxicity of 1,4-dioxane in rats and mice. J Toxicol Sci. 33: 141- 153. Kano, H., Y, Umeda, T. Kasai, T. Sasaki, M. Matsumoto, K. Yamazaki, K. Nagano, H. Arito, and S. Fukushima. 2009. Carcinogenicity of 1,4-dioxane administered in drinking-water to rats and mice for 2 years. Food Chem Toxicol. 47:2776 - 2784. Kociba, R.J., S.B. McCollister, C. Park, T.R. Torkelson, and P.J. Gehring. 1974. 1,4-dioxane. I. Results of a 2-year ingestion study in rats. Toxicol Appl Pharmacol, 30: 275-286. doi:10.1016/0041- 008X(74)90099-4. McConnell, G. 2013. Report on the review of liver slides from the National Cancer Institute's Bioassay of 1,4-Dioxane for Possible Carcinogenicity Conducted in 1978 (NCI, 1978). Submitted to Toxicology Excellence for Risk Assessment. January/March 2013. NCI. 1978. Bioassay of 1,4-Dioxane for possible Carcinogenicity. Carcinogenesis Testing Program, Division of Cancer Cause and Prevention, National Cancer Institute. NIH, Bethesda, MD, 78-1330. Netherlands. 1999. Risk Assessment: 1, 4-Dioxane. Netherlands Organization for Applied Scientific Research (TNO) and the National Institute of Public Health and the Environment (RIVM). Chemical Substances Bureau, Ministry of Housing, Spatial Planning and the Environment (VROM), Netherlands, Final Version, 5 November, EINECS-No.: 204-661-8. arcadis.con 11 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications Neumann, H.G., H.W. Thielmann, J.G. Filser, H.P. Gelbke, H. Griem, H. Kappus, K.H. Norpoth, U. Reuter, S. Vamvakas, P. Wardenbach, and H.E. Wichmann. 1977. Proposed changes in the classification of carcinogenic chemicals in the work area. Reg. Toxicol. Pharmacol., 26:288-295. National Industrial Chemicals Notification and Assessment Scheme (NICNAS). 1998. Priority Existing Chemical Assessment Reports: 1,4-dioxane. Sydney, Australia: Australia Department of Health and Ageing. June. Available online at: NJDEP. 2014. Ground Water Quality Standards. N.J.A.C 7:9C. Available online at: http://www.nj.gov/dep/rules/rules/njac7_9c.pd Office of Environmental Health Hazard Assessment (OEHHA). 2002. Air Toxics Hot Spots Program. Risk Assessment Guidelines. Part II. Technical Support Document for Describing Available Cancer Potency Factors. Office of Environmental Health Hazard Assessment, California Environmental Protection Agency. December. Stickney, J.A., S.L. Sager, J.R. Clarkson, L.A. Smith, B.J. Locey, M.J. Bock, R. Hartung, and S.F. Olp. 2003. An updated evaluation of the carcinogenic potential of 1,4-dioxane. Regul Toxicol Pharmacol. 38(2):183-95. Thiess, A.M., E. Tress, and I. Fleig. 1976. Arbeitsmedizinische Untersuchungsergebnisse von Dioxan- exponierten Mitarbeitern [Industrial-medica investigation results in the case of workers exposed to dioxane]. Arbeitsmedizin, Sozialmedizin, Umweltmedizin, 11: 35-46. USEPA. 2005. Guidelines for carcinogen risk assessment, final report. EPA/630/P-03/001F. Risk Assessment Forum; U.S. Environmental Protection Agency. Washington, DC. March. USEPA. 2010. Toxicological Review of 1,4-Dioxane (CAS No. 123-91-1). EPA/635-R-09-005-F. Washington, D.C. August. USEPA. 2011. Recommended Use of Body Weight3/4 as the Default Method in Derivation of the Oral Reference Dose. EPA/100/R11/0001. Risk Assessment Forum. Washington, DC. USEPA. 2012. Benchmark Dose Technical Guidance. EPA/100/R-12/001. Risk Assessment Forum. Washington, DC. June 12. USEPA. 2013. Toxicological review of 1,4- Dioxane (with inhalation update) (CAS No. 123-91-1) in support of summary information on the Integrated Risk Information System (IRIS) [EPA Report]. (EPA-635/R-11/003-F). Washington, DC. USEPA. 2016a. Drinking Water Contaminant Candidate List 4 - Final. Federal Register Notice, Volume 81, No. 2222, Thursday, November 17. USEPA. 2016b. The Third Unregulated Contaminant Monitoring Rule (UCMR 3): Data Summary, July 2016. Office of Water (MS-140). EPA 815-S-16-004, Available at: USEPA. 2016c. Conducting a Human Health Risk Assessment, Dose-Response. Available at: arcadis.com 12 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 APPENDIX A Mode of Action Analysis for Liver Tumors Based on NCI Siide Reread and RfD Derivation (Dourson et al. 2014) Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 ARCADIS Gesign & for natural and built assets Appendix A MODE OF ACTION ANALYSIS FOR LIVER TUMORS BASED ON NCI SLIDE REREAD AND RFD DERIVATION (DOURSON ET AL. 2014) January 2017 Source: :ttps://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) CONTENTS Acronyms and Abbreviations ii 1 Reread of NCI (1978) Histopathology Slides and Mode of Action Evaluation for Hepatic Tumors in Mice 3 1.1 Review of 1,4-Dioxane's Genotoxicity Database 4 1.2 Mode of Action Analysis 4 1.2.1 Key Event 1: Accumulation of Parent Compound 5 1.2.2 Key Event 2: Liver Cell Hypertrophy and Necrosis 5 1.2.3 Key Event 3: DNA Synthesis 5 1.2.4 Key Event 4: Regenerative Cell Proliferation 5 1.2.5 Key Event 5: Promotion of Endogenously Initiated Tumors 6 1.3 Updated Dose-Response Assessment and Reference Dose Derivation for 1,4-Dioxane 6 2 References 8 arcadis.com i Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) ACRONYMS AND ABBREVIATIONS BMD benchmark dose-modeling CUF composite uncertainty factor EPL Experimental Pathology Laboratories JBRC Japan Bioassay Research Center mg/kg/d milligrams per kilogram body weight per day MOA mode of action NCI National Cancer Institute NOAEL no-observable-adverse-effect level POD point of departure RfD oral reference dose g/L micrograms per liter USEPA United States Environmental Protection Agency arcadis.com ii Source: https://wwww.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) 1 REREAD OF NCI (1978) HISTOPATHOLOGY SLIDES AND MODE OF ACTION EVALUATION FOR HEPATIC TUMORS IN MICE To test their hypothesis and better understand the "sequence of events that maybe have contributed to the MOA of the observed liver tumors," Dourson et al. (2014) and McConnell (2013) performed a blinded reread of the mouse National Cancer Institute (NCI) (1978) liver histopathology slides, because that study did not report non-neoplastic lesions in livers of the high-dose group. Note this is one of the two long-term oral mouse bioassays that exist for 1,4-dioxane; the other chronic mouse bioassay was performed by the Japan Bioassay Research Center (JBRC) and is reported most recently by Kano et al. (2009). As noted by Dourson et al. (2014): "Because terminology and practices for reporting liver lesions has changed since the time of the NCI study (1978), and because EPA (2005) is focusing more on an understanding of a chemical's Mode of Action (MOA) prior to any determination of its dose response, a re-review of the liver slides of mice from the NCI study (1978) was performed. This reanalysis was performed at the Experimental Pathology Laboratories (EPL), Research Triangle Park, NC during September through November 2012. The objective of the slide review was to determine if any non-neoplastic lesions in the liver were present in an effort to understand the sequence of events that may have contributed to the MOA of the observed liver tumors in mice. Another reason for the slide review was because at the time of the original slide review (i.e., 1978) the NCI typically recorded only the most severe diagnosis on a given slide, (e.g., adenoma or carcinoma). During this timeframe, the focus of cancer bioassays was to determine the potential carcinogenic activity of the chemical, not its potential chronic toxicity. For example, if an adenoma, carcinoma, and evidence of chronic toxicity (e.g., hepatocellular hypertrophy), were all present on a given slide, only the tumor response was typically recorded. Thus, it was unclear whether non-neoplastic lesions were present in the livers of mice but were not recorded in the NCI carcinogenicity study. McConnell's (2013) reread of the NCI (1978) mouse liver histopathology slides and Dourson et al.'s (2014) summary report demonstrate that chronic exposure to 1,4-dioxane in drinking water is associated with a non-linear mode of carcinogenic action (contrary to the United States Environmental Protection Agency's [USEPA's] low-dose extrapolation conclusion) based on several hepatotoxic effects that preceded tumor formation, including: Dose-dependent hepatocellular glycogen depletion Dose-dependent hepatocellular hypotrophy Dose-related hepatocellular necrosis Dose-dependent hepatocellular inflammation associated with necrosis Dose-related hyperplasia in several non-neoplastic cell types arcadis.com 3 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) Dourson et al. (2014) states: "The appearance of the liver toxicity follows the pattern where glycogen depletion occurs either concurrently with, or preceding, hypertrophy in both sexes. This was followed closely by necrosis and inflammation in males, but a high control incidence of necrosis and inflammation clouded this overall pattern found in females In terms of dose-response behavior, hypertrophy preceded the formation of foci, which appeared to precede formation of tumors. This pattern was also evident in an individual animal analysis." 1.1 Review of ,4-Dioxane's Genotoxicity Database As a component of their mode of action (MOA) analysis, Dourson et al. (2014) reviewed 1,4-dioxane's genotoxicity database using the information presented in USEPA's (2010) Toxicological Review for 1,4- dioxane. Dourson et al. (2014) noted: '1,4-dioxane has been tested for genotoxicity using in vitro assay systems with prokaryotic organisms, non-mammalian eukaryotic organisms, and mammalian cells, both with and without metabolic activation.' "[A]II fifteen mutagenicity tests reported (8 without activation and 7 with metabolic activation) were negative." "22 in vitro genotoxicity assays, and 9 in vivo genotoxicity assays were negative." "Eight genotoxicity assays were noted to be positive but only at high or noted cytotoxic doses." Based on their review of 1,4-dioxane's genotoxicity database, Dourson et al. (2014) states "1,4-dioxane does not cause point mutations, DNA repair, or [tumor] initiation" when administered at non-cytotoxic doses, which is in general agreement with USEPA's conclusions (USEPA 2010). The authors noted their conclusions were similar to USEPA's, but differ in that "if mutations are caused by 1,4-dioxane, it is only at high cytotoxic doses." The authors concluded: "1,4-dioxane does not cause mutagenicity as evidenced by uniformly negative results in standard in vitro and in vivo genotoxicity bioassays at levels that are not overtly toxic, but it may be a clastogen in vivo, in light of the mixed results in the micronucleus assays. It follows that mutations needed for tumor formation are then likely from the known endogenously available pool of mutations, and that a regenerative hyperplasia evokes more of these endogenous mutations to form tumors. Mutation potentially caused by 1,4-dioxane at high doses is precluded as a key event in tumor formation." 1.2 Mode of Action Analysis Dourson et al. (2014) proposed five key events in the non-mutagenic MOA resulting in hepatic tumors in rodents; they include: "(1) accumulation of parent compound [at concentrations that saturate metabolic processes], (2) liver cell hypertrophy and necrosis, (3) DNA synthesis, (4) regenerative cell proliferation, and (5) promotion of endogenously-initiated tumors.' The regenerative cell proliferation MOA has a threshold below which hepatic tumors are not formed. Evidence supporting each key event is presented below. arcadis.com 4 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) 1.2.1 Key Event 1: Accumulation of Parent Compound "Humans, rats, and mice extensively metabolize 1,4-dioxane.' "[M]etabolism is a capacity-limited process." "When dose of 1,4-dioxane approaches or exceeds the metabolizing capacity, the unmetabolized fraction of the dose increases and target organ toxicity occurs." "Thus, there appears to be a threshold below which metabolism and elimination are rapid and with less or perhaps without toxicological effects." "Human environmental exposures to 1,4-dioxane are unlikely to approach doses that saturate metabolizing enzymes and which produce liver and nasal tumors in rats." "Hence, since humans, like rats, efficiently metabolize 1,4-dioxane at low doses, enzyme saturation is negligible at low exposure levels." 1.2.2 Key Event 2: Liver Cell Hypertrophy and Necrosis "Liver cell hypertrophy and necrosis are key events in the 1,4-dioxane MOA leading to regenerative cell proliferation and, with chronic exposures, liver tumors.' "Liver changes including centrilobular swelling, single cell necrosis coincide exclusively with saturating doses of 1,4-dioxane and occur in as little as 11 weeks." "Evidence of hepatocellular damage preceding evidence of hepatocellular tumors caused by higher doses of 1,4-dioxane has been provided by several studies." 1.2.3 Key Event 3: DNA Synthesis USEPA (2010) reported "that 1,4-dioxane does not cause DNA repair activity in five standard in vitro and in vivo bioassays that tested for the presence of DNA repair in various model systems." "Conversely, 1,4-dioxane does cause DNA replication as evidenced by in vitro bioassays in rat hepatocytes" "DNA synthesis appears to be a key event for a regenerative cell proliferation and/or tumor promotion and can occur in either the presence or absence of cytotoxicity." "DNA synthesis provides evidence that 1,4-dioxane promotes cell proliferation through cytotoxicity." 1.2.4 Key Event 4: Regenerative Cell Proliferation "Dose-response and temporal data support the occurrence of cell proliferation and hyperplasia prior to the development of liver tumors in the rat model." "Cell proliferation appears to be an early response with significant changes (1.5- to 2-fold) occurring in rats with as little as 2 weeks of exposure." arcadis.com 5 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) "Given time, proliferative changes manifest as pre-neoplastic foci in studies where the histopathology of such changes are reported." 1.2.5 Key Event 5: Promotion of Endogenously Initiated Tumors "Three studies relevant to tumor initiation and promotion establish that 1,4-dioxane does not cause initiation in standard in vivo bioassays, in agreement with the absence of observed mutagenic or genotoxic activity." "[T]umor promotion was associated with significant toxicity in rats when administered by either dermal or oral routes." 1.3 Updated Dose-Response Assessment and Reference Dose Derivation for 1,4-Dioxane Dourson et al. (2014) and USEPA (2010) both relied on the dose-response data reported by Kociba et al. (1974). This study provided data for liver and kidney degeneration and necrosis in 6- to 8-week-old male and female Sherman rats (60/sex/dose group) that were exposed to 1, ,4-dioxane at 0, 0.01, 0.1, or 1% (i.e., 9.6, 94, and 1,015 milligrams per kilogram body weight per day [mg/kg/d] and 19, 148, and 1,599 mg/kg/d for males and females, respectively) in drinking water for up to 716 days. The study reported a no-observed-adverse-effect level (NOAEL) of 9.6 mg/kg/d and provides "the most sensitive measure of adverse effects by 1,4-dioxane" (USEPA 2010). USEPA's Toxicological Review for 1,4-dioxane (USEPA 2010) provides a reference dose (RfD) of 0.03 mg/kg/d. This RfD was derived using the NOAEL of 9.6 mg/kg/d for liver and kidney degeneration and necrosis in rats reported by Kociba et al. (1974) as the point of departure (POD), in combination with a composite uncertainty factor (CUF) of 300 (10 for interspecies extrapolation, 10 for intraspecies extrapolation, and 3 for database deficiencies associated with the lack of a multigenerational reproductive toxicity study). The lowest-observable-adverse-effect level for this study was 94 mg/kg/d (USEPA 2010). USEPA derived the RfD using the NOAEL reported by Kociba et al. (1974) because the published study did not report incidence data for these effects, and therefore, they were unable to perform benchmark dose-modeling (BMD). Alternatively, Dourson et al. (2014) reported an updated RfD of 0.05 mg/kg/d that was derived using incidence data (laboratory report for the published study was provided to Dourson et al. [2014] by The Dow Chemical Company) for hepatocellular necrosis (combined across sexes) and USEPA's preferred approaches¹. Specifically, Dourson et al. (2014) utilized USEPA's preferred BMD approach (USEPA 2012) to derive a POD of 20 mg/kg/d (95% lower bound on the dose associated with a 10% extra risk), USEPA's preferred default bodyweight scaling factor (USEPA 2011), to estimate a human equivalent 1 USEPA (2010) used the NOAEL from Kociba et al. (1974) based on liver and kidney degeneration to derive the RfD, specifically because Kociba et al. (1974) did not provide quantitative incidence or severity data for liver and kidney degeneration and necrosis. However, when appropriate data are available, USEPA prefers using BMD to define the POD (USEPA 2012). Had the incidence data from Kociba et al. (1974) been available at the time of their review, USEPA would have used it to derive a benchmark dose to use as the POD for setting the RfD. arcadis.com 6 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) dose, in combination with a CUF of 100 (3 for interspecies toxicodynamic extrapolation, 10 for intraspecies extrapolation, and 3 due to the lack of a 2-generation reproductive study) to derive an RfD of 0.05 mg/kg/d. Dourson et al. (2014) concluded that "the choice of this endpoint [hepatocellular necrosis] is protective, since liver toxicity, resulting in liver tumors, is the clear apical effect of greatest intensity in the available array of toxic effects." Dourson et al. (2014) calculated their RfD using standard approaches, as shown in Equation (1), below: POD 20 mg/kg/d Equation (1) RfD = = 0.05 mg/kg/d CUF 3x10x3 arcadis.com 7 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) 2 REFERENCES Dourson, M., J. Reichard, P. Nance, H. Burleigh-Flayer, A. Parker, M. Vincent, and E.E. McConnell. 2014. Mode of action analysis for liver tumors from oral 1,4-dioxane exposures and evidence-based dose response assessment. Regul Toxicol Pharmacol. 68: 387-401. Kano, H., Y, Umeda, T. Kasai, T. Sasaki, M. Matsumoto, K. Yamazaki, K. Nagano, H. Arito, and S. Fukushima. 2009. Carcinogenicity of 1,4-dioxane administered in drinking-water to rats and mice for 2 years. Food Chem Toxicol. 47:2776 - 2784. Kociba, R.J., S.B. McCollister, C. Park, T.R. Torkelson, and P.J. Gehring. 1974. 1,4-dioxane. I. Results of a 2-year ingestion study in rats. Toxicol Appl Pharmacol, 30: 275-286. oi:10.1016/0041- 008X(74)90099-4. McConnell, G. 2013. Report on the review of liver slides from the National Cancer Institute's Bioassay of 1,4-Dioxane for Possible Carcinogenicity Conducted in 1978 (NCI, 1978). Submitted to Toxicology Excellence for Risk Assessment. January/March 2013. NCI. 1978. Bioassay of 1,4-Dioxane for possible Carcinogenicity. Carcinogenesis Testing Program, Division of Cancer Cause and Prevention, National Cancer Institute. NIH, Bethesda, MD, 78-1330. USEPA. 2005. Guidelines for carcinogen risk assessment, final report. EPA/630/P-03/001F. Risk Assessment Forum; U.S. Environmental Protection Agency. Washington, DC. March. USEPA. 2010. Toxicological Review of 1,4-Dioxane (CAS No. 123-91-1). EPA/635-R-09-005-F. Washington, D.C. August. USEPA. 2012. Benchmark Dose Technical Guidance. EPA/100/R-12/001. Risk Assessment Forum. Washington, DC. June 12. arcadis.com 8 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 APPENDIX B Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) Source: https://www.industrydocuments.ucsf,edu/docs/fsbn0226 ARCADIS Desion & for natural and built assets Appendix B MODE OF ACTION ANALYSIS FOR LIVER TUMORS BASED ON JBRC REVIEW (DOURSONETAL.2016IN PEER REVIEW) January 2017 Source: :ttps://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) CONTENTS Acronyms and Abbreviations ii 1 Findings from Detailed Review of JBRC Rat Bioassays 3 1.1 Findings from Detailed Review of JBRC Mouse Bioassays 3 1.2 Integration of Evidence Supporting Regenerative Cell Proliferation MOA for 1,4-Dioxane 4 2 References 6 TABLES Table 1. Integration and Comparison of Rat and Mouse Bioassay Data (Adapted from Dourson et al., 2016 in peer review) 5 arcadis.com i Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) ACRONYMS AND ABEREVIATIONS JBRC Japan Bioassay Research Center mg/kg/d milligrams per kilogram body weight per day MOA mode of action NCI National Cancer Institute arcadis.com ii Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) 1 FINDINGS FROM DETAILED REVIEW OF JBRC RAT BIOASSAYS Changes in the liver found in the Japan Bioassay Research Center (JBRC) rat bioassays provide strong evidence that hepatic tumors were modulated by a threshold-based regenerative cell proliferation mode of action (MOA). Dourson et al. (2016 in peer review) found that effects observed in rats were in the expected dose-sequence for a regenerative cell proliferation MOA. Specifically, Dourson et al. (2016 in peer review) observed the following sequence of effects: Dose: 42-55 milligrams per kilogram body weight per day (mg/kg/d) - Effect: Liver swelling, hypertrophy, and liver weight increase Dose: 94-219 mg/kg/d - Effect: Necrosis Dose: 55-389 mg/kg/d - Effect: Hyperplasia and foci development Dose: >200 mg/kg/d - Effect: Increased levels of enzymes associated with liver damage Dose: 274-1015 mg/kg/d - Effect: Adenomas and carcinomas 1.1 Findings from Detailed Review of JBRC Mouse Bioassays Dourson et al. (2016 in peer review) observed the following sequence of effects in the JBRC (1990a) mouse bioassays: Dose: 190-200 mg/kg/d - Effect: Liver swelling, hypertrophy, and liver weight increase Dose: 190-200 mg/kg/d - Effect: Necrosis Dose: Not reported - Effect: Hyperplasia and foci development not reported Dose: 200 mg/kg/d - Effect: Increased levels of enzymes associated with liver damage Dose: 66-964 mg/kg/d - Effect: Adenomas and carcinomas, females Surprisingly, effects in the liver found in the JBRC mouse bioassays conflict with those clearly reported by Dourson et al. (2014) and McConnell (2013) for the reread of the National Cancer Institute (NCI) (1978) mouse bioassay histopathology slides. Additionally, the progression of effects reported by JBRC for the 2- year chronic study is inconsistent with enzymatic changes indicative of liver damage noted in the same study, as well as findings from a 13-week precursor study performed by the same laboratory. As noted by Dourson et al. (2016 in peer review), "the lack of noncancer histopathology in the chronic mouse study is not consistent with the changes in liver enzymes in this same chronic study, nor is this lack of noncancer arcadis.com 3 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) findings expected based on the histopathology of the precursor 13-week study" and "[n]or does the tumor response in the low dose female mice of JBRC (1990a) match the tumor findings in the McConnell (2013) re-read of NCI (1978). Dourson et al. (2016 in peer review) hypothesized that differences in mouse bioassay results between JBRC and McConnell (2013) may be due to differences in the interpretation of the histopathological data, and provided the following quote from JBRC (Kano et al. 2009) to substantiate their claim: "The hepatic hyperplasia of rats and mice diagnosed in the previous report (Yamazaki et al., 1994) [authors note: which was a presentation of the JBRC, 1990a] was re-examined histopathologically and changed to hepatocellular adenomas and altered hepatocellular foci including acidophilic, basophilic and clear cell foci in the present studies, according to the current diagnostic criteria of liver lesions in rats and mice." Unfortunately, slides from the original JBRC (1990a,b) bioassays were not available; therefore, the JBRC slides could not be reread as they were by McConnell (2013) for the NCI (1978) mouse liver slides. Additionally, JBRC did not archive sufficient numbers of pictures of histopathology slides to resolve the issue. While, it is impossible to know for sure from this dataset whether liver tumors formed prior to or following cytotoxic effects, the weight of evidence from the JBRC and NCI mouse bioassays supports a regenerative cell proliferation MOA. 1.2 Integration of Evidence Supporting Regenerative Cell Proliferation MOA for 1,4-Dioxane Following integration of key events from seven rat bioassays, three mouse bioassays, and 1,4-dioxane's genotoxicity profile, presented in Table 1 below, Dourson et al. (2016 in peer review) showed that 1,4- dioxane's toxicological database supports a threshold-based regenerative cell proliferation MOA for tumor formation in livers of rodents orally exposed to 1,4-dioxane. The authors reported that bioassay data for rats leads to the conclusion that "rat liver tumors are evoked by a regenerative hyperplasia," while the authors concluded the "sequence of events from two chronic mouse studies and a subchronic mouse study generally support the hypothesized regenerative hyperplasia MOA" (Dourson et al. 2016 in peer review). In regards to the conflicting mouse bioassay data (McConnell 2013; Dourson et al. 2014; JBRC 1990a), the difference is likely due in part to changes in the terminology and practices used for recording the liver lesions reported by Kano et al. (2009). arcadis.com 4 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226

when does the session end?

gybn0226

gybn0226_p0, gybn0226_p1, gybn0226_p2, gybn0226_p3, gybn0226_p4, gybn0226_p5, gybn0226_p6, gybn0226_p7, gybn0226_p8, gybn0226_p9, gybn0226_p10, gybn0226_p11, gybn0226_p12, gybn0226_p13, gybn0226_p14

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145 From: Jürgen Troitzsch To: Dr. Wise Kimberly Cc: Admon. Smadar: Anderson Steven; Batoon, Audrev; Dr. Bradley Kevinx; de Lacy, Catharine: Elkan. Illan; Eraguntla, Neeraia: Goodman, Bryan; Hochschwender. Lane; Jacobi Svivia; Kannah Kasturirangan; Levan Steve; Leychik. Sergei; Little, Barbara; Manor, Orit; Prero, Judah; Dr. Rothenbacher Klaus; Saunders, Eric L.; Scherrer Stephen; Simon. Robert; Tavior Jennifer; Tenney Joel; Thorn. Amelia; West, Jav; Dr. Haves Wallace; Prof. Rein Guillermo; Dr. Blais Matthew; Dourson. Michael (doursoml); Kacew. Sam; Osimitz Thomas Subject: Re: For Review - Draft Record from May 2017 SAC Meeting Date: Sunday, June 4, 2017 10:05:03 AM Attachments: SAC ROM 05-16-17 and 05-17-17 - Draft doc Program 2017, pdf 170817AbsFurnitureFiresafety.do Dear Kimberly, Please find attached my comments to the meeting record, the program of the Copenhagen conference and my abstract. Kind regards/Viele Grüße Jürgen Dr. Jürgen Troitzsch Fire and Environment Protection Service FEPS Via Patrizia 32 CH-6612 Ascona, Switzerland Mobile: +41 79 289 17 16 Phone: +41 91 791 14 22 Email: [email protected] Web: www.troitzsch.com Am 02.06.2017 um 13:56 schrieb White, Kimberly <Kimberly [email protected]> Dear NAFRA, BSEF and SAC members: Attached is the record from the May 2017 Science Advisory Council meeting. Please review by June 9th and let me know if you have any additions or corrections. Kind Regards, Kimberly Wise White, Ph.D. | American Chemistry Council Senior Director, Chemical Products & Technology Division [email protected] Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 Furniture Fire Properties And Their Importance For Domestic Fire Safety Juergen H. Troitzsch Fire and Environment Protection Service FEPS Ascona, Switzerland [email protected] Keywords: Fire statistics, furniture regulations, reaction to fire stakeholders regarding adequate fire safety, the proposal was tests, barriers, flame retardants withdrawn. A second version is now under consideration and it Fire statistics show that residential fires caused by is unclear when the amended regulations will come in to force. upholstered furniture have continuously decreased in the U.S. These approaches have led to search for other possibilities /California and the UK in the last 20 years. This is due to to ensure adequate fire safety levels for upholstered furniture. stringent fire safety regulations and tests mandatory for Contrary to the past, where ignition and flammability tests upholstered furniture in these countries. However, upholstered were used to define fire safety. now the reduction of the heat furniture still remains the leading item first ignited by low release rate is seen as the key fire property most strongly energy ignition sources such as cigarettes, matches, lighters influencing fire hazard. and candles 1. A study on "Alternative strategies to the use of chemical The classical way to meet high fire safety requirements for flame retardants" 4 has shown that various combinations of upholstered furniture is to improve the fire safety level of its cover materials and fire barriers to protect flexible components by using flame retarded flexible polyurethane polyurethane foam can reduce the heat release rate of the foam, barriers and covers. systems tested and improve fire safety. With the exception of In recent years, due to health and environment concerns an intrinsically flame retarded (FR) polyester cover, no other about the use of certain flame retardants, California revised the components used contained conventional flame retardants. CA TB 117 cigarette test 2 used for upholstered furniture in the Another, earlier study on "upholstered furniture private domain. The former additional small flame test required flammability" 5 investigated the fire performance of different was eliminated because flame retardants had to be used to meet FR/non-FR barrier materials and flexible polyurethane foams it. with a non-FR polyester cover in material-level, mock-up and The new CA TB 117 only addresses smoldering fires, while full-size furniture experiments. The results showed that the fires associated with flaming ignition, which according to flame retarded barrier materials were very effective in reducing NFPA lead to an appreciable amount of fatalities, are no more heat release rate and, particularly in the full-size experiments, considered. Therefore, NFPA has been asked to develop a the fire growth rate of the upholstered chairs. flaming-ignition test for upholstered furniture and is currently These studies show that the best way to reduce the heat working on its own open-flame test to NFPA 277 3 based on release rate of upholstered furniture and to optimize fire safety heat release rate measurement. is the use of flame retarded fire barriers and covers. Adequate In Great Britain, "The Furniture and Furnishings (Fire fire barriers including the use of flame retardants based on the Safety) Regulations' address compulsory fire safety U.S. EPA Design for the Environment (DfE) alternatives requirements for upholstered furniture in private homes. In assessment method will help to enhance domestic fire safety 2014, the authorities proposed an alternative match test to and reduce the number of fatalities, injuries and property losses. simplify the regulation and to reduce levels of flame retardants in furniture without impacting on the current fire safety levels. Here, contrary to the California approach, the cigarette test was to be eliminated and only gas flames and the BS 5852 crib 5 tests remained. However, following strong concerns from the 1 J. Troitzsch, "Fires, statistics, ignition sources, and passive fire protection REFERENCES measures", Journal of Fire Sciences, 2016, 1-28. DOI: 10.1177/07349041 2 Technical Bulletin 117-2013 Requirements, Test Procedure and Apparatus for Testing the Smolder Resistance of Materials Used in Upholstered 4 K. Storesund, A. Steen-Hansen and A. Bergstrand, "Fire safe upholstered Furniture. January 2013 furniture. Alternative strategies to the use of chemical flame retardants," 3 Proposed Standard NFPA 277: Standard Methods of Tests for Evaluating SPFR Report A15 20124:2, December 2015. Fire and Ignition Resistance of Upholstered Furniture Using a Flaming 5 T. Fabian, "Upholstered furniture flammability,' Underwriters Laboratories Ignition Source Inc., Jul. 2013. Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 NFSD Nordic Fire & Safety Days Programme Day 1, 17th Augusti 2017 no Colico and Registration Welcome to the Nardini are and Safety Days Room: ACM15 Anne Dederichs 10.00 Key Leature Room: ACM15 Furniture fire properties and their importance for domestic fire safety. Dr. Jürgen Troitzsch, FEPS, Switzerland Panal Discussion Room: ACM15 Session Chair: Björn Sundström, SP Furniture fire properties and their importance for domestic fire safety. Dr. Jürgen Troitzsch, FEPS, Switzerland Egil Sundet, Head of the Sector furniture, interior and design for the federation of Norwegian Industry Dr. David Santillo, Honorary Research Fellow at Greenpeace Research Laboratories, Exeter University, UK, Dr. Anne Elise Steen-Hansen, Research manager at SP Fire Research, Norway Dr. Björn Karlsson, Professor at Iceland University and the Director General at Iceland Construction Authority. A! ********* - ****** NTNU 1 LUND of ****** ******** ******** DBI Source: https://wwww.industrydocuments.ucsf.edu/docs/gybn0226 NFSD Nordic Fire & Safety Days Parallet Session A Fire Dynamics 1 Risk 1 Evacuation Room: ACM15 1.001 Room: ACM15 1.008 Room: FKJ 12 0.06 Session Chair: Session Chair: Session Chair: Tuula Hakkarainen Frank Markert 11.00-11.15 Fire protection of Modelling approach for The effect of plattform- extensive green roofs the threat quantification and tunnel design on the A. Elias of cascading failures evacuation performance A. Helminen, T. of wheelchair users - A Hakkarainen qualitative study Eva-Sara Karlsson 11.20-11.35 USCG Fire simulation of Developing a risk and Reaction and decision water mist suppression capability assessments time of evacuees - A study using an ignition source methodology for the Baltic regarding the influence of E. A. Kolstad, B. P. Husted, Sea Region alcohol on the reaction LU - B. Karlsson and decision time P. B. Rask, A. Dederichs 11.40-11.55 Development tool for Fire safety decision Awareness of fire risk ETICS façade fire testing making under a systems- reduction among Cyprus M.S. McLaggan, M. theoretic safety paradigm international university Meinert, A. Dragsted, P. -H. Bjelland, O. Njã, A. (CIU) students van Hees W.Heskestad, G. S. Braut A. F. Gyasi 1000 Lunch 2 Exhibition the DO Parallal R Fire Dynamics 2 Fire safety science Transportation without borders Room: ACM15 1.001 Room: ACM15 1.008 Room: FKJ 12 0.06 Session Chair: Session Chair: Session Chair: Frida V Lundström Martyn S. McLaggan 13.00-13.15 Desensitisation of optical Fire safety science without Ventilation in tunnels: a flame detection in harsh borders numerical comparison external environments T., between different J. McNay K. H. Almand modelling approaches -P. Matteo 13.20-13.35 Heat release Fire safetys contribution Fire detection in engine characteristics of ethanol- to a sustainable society compartments - P. water mixtures T., Karlsson, O. Willstrand T. Hakkarainen K. H. Almand, NFPA 13.40-13.55 Fire-induced pressures in Det store brannlöftet - Verifying fire safety in tall modern airtight Dag Botnen timber buildings apartment building Fredrik Nystedt S. Hostikka Johan Norén 14 00 3 Enhibition OTU A! II'II ********* - - NTNU a 2 Landa of ******** ******** ******** 081 Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 NFSD Nordic Fire & Safety Days Parallet C Fire Dynamics 3 Fire Safety Engineering 1 Brokerage Event 1: Carpark fires Room: ACM15 1.001 Room: ACM15 1.008 Room: FKJ 12 0.06 Session Chair: Session Chair: Session Chair: Ulf Wickström Michael Stömgren 14.45- Measuring incident Performance based design and compilande Luisa Giuliani 15:00 heat flux and M. Strömgren adiabatic surface temperature with platse thermometers in ambient and high temperatures U. Wickström, J. Anderson, J. Sjöström 15.05- Modelling and Wildlandfires, F.V.Lundström, P. Andersson 15.20 stochastic analyses of travelling fires R. K. Janardhan, S. Hostikka 15.25-40 Photovoltaic A discussion on learning from fire installations on investigations; concepts and methodologies warehouse buildings - an experimental A. Borg, O. Njã study of the propagation of fire - J. Steemann Kristensen Conference 3 Exhibition Affer conferenze dinner OTU A! IIIII ********* - - - NTNU a 3 Luno of ******** ******** ******** 081 Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 NFSD NordicFire & Safety Days Programme Day 2, 18th August 2017 20.02.40 Welcome Key Leaure Room: ACM15 Fire brigade intervention method - accounting for the actions of the fire service Ed Claridge, Principal Fire Engineer, Auckland, New Zealand Pana Discussion Room: ACM15 Session Chair: Fire brigade intervention-accounting for the actions of the fire service Ed Claridge, Principal Fire Engineer, Auckland, New Zealand Rasmus Storgaard Petersen, CEO Emergency Service East, Denmark Cecilia Daae, Director of Directorate for Civil Protection and Emergency Planning, Norway Mia Kumm, Licentiate of engineering and researcher at SP/Rise and Mälardalen University, Sweden A! II-II: ********* - ****** - NTNU a 4 Luwo ****** DBI Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 NFSD Nordic Fire & Safety Days Parallel Session D Management of rescue Risk 2 Structural Fire Safety 1 service 1 Room: ACM15 1.001 Room: ACM15 1.008 Room: FKJ 12 0.06 Session Chair: Session Chair: Session Chair: 11.00-11.15 Accounting for the actions Resilient Buildings C-Fort, Risk analysis and of the rescue service - M. Kumm performance-based rescue from heights. structural fire expertise of Christian Ramm a semi-buried railway station - E. Tonicello, S. Deshanghere 11.20-11.35 Environmental impact of Firesafe - Study Experimental study on the structure fires and fire investigating cost effective mechanical properties of service response measures for reducing the fire exposed concrete F. Amon, L. Vylund risk from fires on ro-ro A. Zawadowska, L. passanger ships Giuliani, K. D. Hertz - J. Wikman, M. Rahm, F. Evegren, J. Leroux, A. Breuillard, M. Kjellberg, L. Gustin, F. Efraimsson 11.40-11.55 Part time firemen and False alarm - An Fire protection of wooden community resilience organizational study of houses in several floors -P. Almklov, M. Nilsen, G. the effects of false alarms J. N. Olsen, H. S.Fishman Gjøsund G. Gjøsund Petter Almklov Christian Sesseng Lundh R OTU A! IIIII ********* - - - *** - - NTNU " 5 Luno of ******** ******** ******** 081 Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 NFSD Nordic Fire & Safety Days Parallel R Management of rescue Fire safety engineering 2 Structural Fire Safety 2 service 2 Room: ACM15 1.001 Room: ACM15 1.008 Room: FKJ 12 0.06 Session Chair: Session Chair: Session Chair: 13.00-13.15 Security officers 99 years of standard fire - Furnace setup for responding to residential success of failure? preliminary fire resistance fire alarms: modelling the R. Jansson McNamee testing - effect on survival and P. Hejtmánek, V. Flídr, H. property damages Najmanová B. Sund, H. Jaldell 13.20-13.35 Three different fire Investigation of suppression approaches A swedish approach to eurocodes design used by Fire and Rescue define a standard for fire fires and national services safety design in BIM deviations- F. S. Särdqvist F. Nystedt, J. Norén Clausen, L. Giuliani 13.40-13.55 An operationalization of Nordic standard for Material capabilities for fire and review & control of fire modeling of rescue operations safety engineering concrete under M. Runefors F. Nystedt, J. Norén, M. compression and Strömgren high temperatures - A. F. Damkjaer, L. Giuliani, K. D. Hertz Coffee 3 Exhibition OTU A! IIIII ********* - - - *** - - NTNU " 6 Luno of ******** ******** ******** 081 Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 NFSD Nordic Fire & Safety Days Parallel Sersion : Residential Fires 1 Fire safety engineering 3 Fire Dynamics 4 Room: ACM15 1.001 Room: ACM15 1.008 Room: FKJ 12 0.06 Session Chair: Session Chair: Session Chair: 14.45-15.00 Socioeconomic Learning points from real Smouldering fires in wood differences in residential incidents - pellets: the effect of fire mortality in Sweden: a learning from what?- - M. varying the airflow case-control study Bøhm, Metropolitan V. R. Valdés,R. F. Mikalsen, A. Jonsson University College A. Steen-Hansen O.Njã, U. Stavanger 15.05-15.20 Fire fatalities in Norway Simulation of smouldering K. Storesund, C. Sesseng, combustion based on A. Steen-Hansen Integration of fire multi-layer cellular engineering tools and automata- calculation methodologies V. R. Valdés,R F. Mikalsen, P. Tofilo A. Steen-Hansen 15.25-15-40 Has fire-related mortality Learning fire and rescue Aerosols from smoldering in Sweden changed over work by experience- E. Villacorta time? - E. Lindahl, J. sharing Hedberg Ava Sadeghi OTU A! IIIII ********* - - - *** - - NTNU " 7 Luno of ******** ******** ******** 081 Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 NFSD Nordic Fire & Safety Days Paralial to Residential Fires 2 Structural Fire Safety 3 Fire Dynamics 5 Room: ACM15 1.001 Room: ACM15 1.008 Room: FKJ 12 0.06 Session Chair: Session Chair: Session Chair: Residential fires in On analysing structures USCG Fire simulation of Denmark based solely on human water mist suppression P.B. Gummesen safety using an ignition source A.S. Dederichs, RISE, DTU J.Sandström, J. Thor, R. Einar Arthur Kolstad Jansson McNamee,0. Bjarne P. Husted Lagerqvist, U.Wickström Residential fire solutions Post-earthquake Validation of FDS on the in the building sector fire behavior of SP retail store steel frames - Shamim Ahmed Bjarne P. Husted Part I: Collapse Mechanism - G. Risco, L. Giuliani, V. Zania Towards an evidence- Post-earthquake fire Validation of sub-grip based vision zero policy behavior of steel frames - scale particle model for on residential fires - an Part II: The effect of the cable fire spread update - R. Andersson insulation - A. Wrobel, , L. T. Sikanen, A. Matala, S. A. Jonsson Giuliani, V. Zania Hostikka Brokerage Event 2: Modern Building Fires Session Chair: Anne Dederichs Lars Schiøtt Sørensen, DTU OTU A! IIIII ********* - - - *** - - NTNU " 8 Luno of ******** ******** ******** 081 Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 AMERICAN CHEMISTRY COUNCIL NORTH AMERICAN FLAME RETARDANT ALLIANCE (NAFRA), BROMINATED SCIENCE ENVIRONMENTAL FORUM (BSEF) AND SCIENCE ADVISORY COUNCIL (SAC) RECORD of MEETING Draft Subject to Review and Approval Date: May 16, 2017 - May 17, 2017 Location: New York, NY Participants: Steve Anderson Albemarle Audrey Batoon Chemtura Matt Blais Southwest Research Institute Kevin Bradley Consultant to BSEF Patty Cardin* Chemtura Catharine DeLacy Albemarle Michael Dourson Toxicology Excellence for Risk Assessment Ilan Elkan ICL Neeraja Erraguntla American Chemistry Council Ofodike Ezekoye* University of Texas-Austin A. Wallace Hayes Harvard School of Public Health Steve Levan Albemarle Kevin Marr** University of Texas-Austin Tom Osimitz Science Strategies, LLC Guillermo Rein Imperial College London Klaus Rothenbacher Independent Consultant Eric Sanders Chemtura Steve Scherrer Chemtura Jürgen Troitzsch Fire and Environment Protection Services Jay West American Chemistry Council Kimberly White American Chemistry Council ** Denotes part time participation in-person on May 16th only. ** Denotes part time participation via conference call on May 16th only. 1.0 K. White reviewed meeting room site logistics, the tentative agenda for the meeting and the ACC's Antitrust Guidelines which remained in effect for the duration of the two-day meeting. 2.0 Participants conducted roundtable introductions and K. White reviewed the overall objectives for the meeting, which included: Discuss relevant regulatory and chemical assessment activities Discuss state of the science Identify short term and long term science priorities and activities Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 Record of Meeting 05/16/17 - 05/17-17 Page 2 3.0 K. White reviewed key take-away messages from the May 15th NAFRA Operating Committee meeting which included: (a) focusing core science activities on priority areas of focus and ensuring alignment with the strategic plan, (b) identify approaches to inform issues raised during state legislative hearings, (c) focus the scope and objectives for the next phase of the smoke toxicity study and (d) identify opportunities to address fire fighter exposures. 4.0 K. White, J. West and K. Rothenbacher reviewed notable regulatory/legislative activity in the US and abroad. Action Items K. Rothenbacher will distribute a copy of the TBBPA EU Denmark Decision J. West will distribute information from Maine that outlines notable toxicological endpoints related to flame retardant exposures. 5.0 Participants discussed the status of the ongoing science projects currently underway and had detailed project discussions by the researchers as follows: T. Osimitz provided an overview of the available literature for the-for dermal exposures M. Blais and T. Osimitz reviewed the protocol, scope and results from the phase I of the smoke toxicity study. Participants discussed the results, possible implications and opportunities to refine and focus the project moving forward. Participants recommended that the researchers provide a write-up of the project results, recommendations for next phase and associated cost then scheduled a project specific call to agree on the path -forward. K. Marr and O. Ezekoye reviewed the scope and progress to date on the project to evaluate combustion properties of baby monitors. Participants discussed the researchers focus on battery failure scenarios, recommended refining the scope and ensuring the combustion activities adequately address differences between flame retardant and non-flame retardant. Action Items T. Osimitz will provide a draft manuscript for the dermal exposure review by June 15th. SAC members will evaluate whether it's feasible to develop a BE for blood concentrations from flame retardant based on dermal exposures T. Osimitz and M. Blais will work with N. Erraguntla to refine the smoke toxicity project scope and next steps then schedule a call to discuss. K. White will solicit recommendations for possible next steps on the combustion of baby monitors project and will set a project specific call for more discussion with the researchers. K. White will distribute past scope of work and study updates related to the combustion of baby monitors project. 6.0 Members of the SAC provided updates on ongoing science activities that included the following: J. Troitzsch invitation- to be a speaker during anchair a flame retardants seminar at the AOFSM'2 Conference in Shenzhen, China, 27-29 October 2017 in conjunction with BSEF -meeting. Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 Record of Meeting 05/16/17 - 05/17-17 Page 3 J. Troitzsch has been invited as keynote speaker on the fire safety of upholstered furniture alerted-participants to the Nordic Fire & Safety Days Conference in Copenhagen, 17-18 August 2017. an-epeoming 2017 meeting in Copenhagen- The participants discussed thatwhere engagement by a toxicology expert may be useful. G. Rein alerted participants to ongoing activities in California and other state agencies to evaluate TB117 and exposure to flame retardants. The evaluation is anticipated to last 3-5 years and it was recommended to monitor the data outputs annually. Action Items J. Troitzsch will provide information regarding the 2017 Copenhagen meeting. 7.0 Participants reviewed a series of charge questions and recent flame retardant session information from the 2017 Society of Toxicology meeting to identify potential opportunities for future science activities. NAFRA and SAC members also met separately to discuss identified projects and identify additional opportunities for science engagement. Overall, participants recommended identifying key product sectors and priority issues of interest to address, then reviewing each potential project to determine what role it will play in providing additional information to respond to identified sectors and issues. A number of projects topics were identified for future discussion and refinement as follows: Conduct of full scale room burns In Vitro dermal exposure study Evaluation of neurobehavioral testing parameters and human relevance from animal models Collaboration opportunities with NFPA research foundation Evaluate opportunities related to wearable technologies and impacts for assessment of flame retardant exposures Action Items K. White will aligned product categories, priority issue areas and identify possible science gaps by June 16th. K. White will schedule a conference call in June with NAFRA/BSEF members to discuss the identify projects and their alignment with product categories and issue areas of interest. 8.0 Participants discussed past and present SAC meeting to identify opportunities to improve meeting outputs and coordination with the SAC. Several recommendations were noted that included: having more time in the agenda for project specific discussions and deliberation; provide more background information on each project under discussion; elimination of fire science and toxicology specific breakout so that all participants can actively contribute to all meeting discussion; build in sufficient time for SAC members and NAFRA members to meeting separately for deliberation; and develop a science repository of relevant scientific information on the MemberExchange site that includes abstracts and links to articles when available pending copyright restrictions. 9.0 The next meeting is scheduled for November 12th (Dinner) and a November 13-14, 2017 Meeting in London. The meeting was adjourned at approximately 12:22pm on May 17, 2017. Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226 Record of Meeting 05/16/17 - 05/17-17 Page 4 Respectfully submitted, K. White Source: https://www.industrydocuments.ucsf.edu/docs/gybn0226

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Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 2 USEPA APPROACH FOR EVALUATING CANCER RISHS POSED BY ORAL EXPOSURE TO 1,4-DIOXANE USEPA's Integrated Risk Information System (IRIS) published the Toxicological Review for 1,4-dioxane, in which it describes their approach and justification for deriving an oral CSF for this constituent. Below is a summary of USEPA's evaluation of available human toxicological data, weight of evidence evaluation, key study identification, critical effect selection, dose-response assessment, and the low-dose extrapolation procedure used to derive 1,4-dioxane's CSF. 2.1 USEPA's Evaluation of Evidence of Cancer in Humans USEPA evaluated the degree to which data provide evidence of carcinogenicity in humans (USEPA 2010). USEPA relied on two human occupational studies in their evaluation of potential impacts related to long-term exposure to 1,4-dioxane (Thiess et al. 1976; Buffler et al. 1978). USEPA concluded that neither study provided evidence that 1, ,4-dioxane causes cancer in humans. However, they noted "the cohort size and number of reported cases were small." 2.2 USEPA's Evaluation of Evidence of Cancer in Animal Bioassays USEPA followed its Guidelines for Carcinogen Risk Assessment (USEPA 2005) to conclude that 1,4- dioxane is "likely to be carcinogenic to humans" based on "evidence of liver carcinogenicity in several 2- year bioassays conducted in three strains of rats, two strains of mice, and in guinea pigs.' USEPA provided several reasons to justify its conclusion. For instance, USEPA concluded that the "available evidence is inadequate to establish a MOA by which 1,4-dioxane induces liver tumors in rats and mice" (USEPA 2010). Specifically, USEPA noted the "[c]onflicting data from rat and mouse bioassays (Japan Bioassay Research Center [JBRC] 1998; Kociba et al., 1974) suggest that cytotoxicity may not be a required precursor event for 1,4-dioxane-induced cell proliferation." USEPA (2010) noted that "[a]vailable data also do not clearly identify whether 1,4-dioxane or one of its metabolites is responsible for the observed effects. However, USEPA also reported that "the generally negative results for 1,4-dioxane in a number of genotoxicity assays indicates the carcinogenicity of 1,4-dioxane may not be mediated by a mutagenic MOA" (USEPA 2010). 2.3 Key Study Identification (Kano et al. 2009), Critical Effect Selection, Dose-Response Assessment, and Low-Dose Extrapolation Procedure USEPA (2010) concluded that the MOA by which 1,4-dioxane produces liver tumors is "unknown, and available evidence in support of any hypothetical mode of carcinogenic action for 1,4-dioxane is inconclusive." With this conclusion in mind, USEPA (2010) identified a 2-year drinking water study performed by Kano et al. (2009) as the key study of the oral CSF for 1,4-dioxane. Note that Kano et al. (2009) published findings originally reported by the JBRC (1990a). Although USEPA (2010) concurrently evaluated two other studies (Kociba et al. 1974; National Cancer Institute [NCI] 1978), the Kano et al. (2009) study was ultimately selected as the key study because USEPA (2010) noted that "[c]alculation of arcadis.com 3 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications a CSF for 1,4-dioxane is based upon the dose-response data for the most sensitive species and gender." The study was performed in accordance with the Organization of Economic Development's Principles for Good Laboratory Practices and involved exposing groups of rats (50 animals of each sex for each dose) and mice (50 animals of each sex for each dose) to 1,4-dioxane (>99% pure) in drinking water for 2 years. Rats were exposed to 1,4-dioxane in drinking water at 0, 200, 1,000, or 5,000 milligrams per liter (mg/L), while mice were exposed at 0, 500, 2,000, or 8,000 mg/L in drinking water. As reported by USEPA (2010): "The investigators used data from water consumption and BW [body weight] to calculate an estimate of the daily intake of 1,4-dioxane (mg/kg-day) by male and female rats and mice. Kano et al. (2009) reported a calculated mean + standard deviation for the daily doses of 1,4-dioxane for the duration of the study. Male rats received doses of approximately 0, 11+1, 55+3, or 274+18 mg/kg-day and female rats received 0, 183, 83+14, or 429+69 mg/kg-day. Male mice received doses of 0, 49+5, 191+21, or 677+74 mg/kg-day and female mice received 0, 66=10, 278+40, or 964+88 mg/kg-day." "The study by Kano et al. (2009) was used for development of an oral CSF. This was a well- designed study, conducted in both sexes in two species (rats and mice) with a sufficient number (N=50) of animals per dose group. The number of test animals allocated among three dose levels and an untreated control group was adequate, with examination of appropriate toxicological endpoints in both sexes of rats and mice. Alternative bioassays (Kociba et al., 1974; NCI, 1978) were available and were fully considered for the derivation of the oral CSF." USEPA identified increased incidence of liver adenomas or carcinomas as the critical effect in rats and mice exposed to 1,4-dioxane in the Kano et al. (2009) study. Following standard dose adjustment to a human equivalent dose using a default body weight (BW) scaling factor (USEPA 2005), USEPA performed dose-response modeling using Benchmark Dose Software and fit the suite of models available in the program to the incidence data for "either hepatocellular carcinoma or adenoma" (USEPA 2010). USEPA concluded that female mice are "more sensitive to liver carcinogenicity induced by 1,4-dioxane compared to other species or tumor types" and identified the lower 95% confidence bound on the benchmark dose associated with a 50% extra risk (benchmark response [BMR]) of developing "either hepatocellular carcinoma or adenoma" (4.95 milligrams per kilogram per day [mg/kg/d]) as the point of departure (POD) for calculating the oral CSF via linear low-dose extrapolation, as shown in Equation (1), below. USEPA (2010) again justified a linear low-dose extrapolation approach based on their conclusion that 1,4-dioxane's MOA for production of hepatic tumors in rodents is "unknown." BMR 0.5 Equation (1) CSF = = 0.1 (mg/kg/d)1 POD 4.95 mg/kg/d 2.4 Comments Provided to USEPA During External Peer Review When USEPA's IRIS program derives toxicity values, the Toxicological Review undergoes critical evaluation by individuals from within and outside the agency. A result of the outside review efforts indicated several external peer review panel members believed that available information for 1,4-dioxane could "support the use of a nonlinear extrapolation approach to estimate human carcinogenic risk" and arcadis.con 4 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications that "such an approach should be presented in the Toxicological Review.' Specifically, the USEPA (2010) notes: "[N]umerous short-term in vitro and a few in vivo tests were nonpositive for 1,4-dioxane-induced genotoxicity". Results from two-stage mouse skin tumor bioassays "suggest that a potential mode of action for 1,4- dioxane-induced tumors may involve proliferation of cells initiated spontaneously, or by some other agent, to become tumors." Additionally, a public commenter noted: "Low-dose linear extrapolation for the oral CSF is not appropriate nor justified by the data. The weight of evidence supports a threshold (nonlinear) MOA when metabolic pathway is saturated at high doses. Nonlinear extrapolations should be evaluated and presented for 1,4-dioxane." These statements indicated that some reviewers felt the toxicological data for 1,4-dioxane indicated that it may not behave in a linear manner, but rather as a threshold carcinogen. Nonetheless, USEPA (2010) ultimately concluded that there was insufficient information available to support any of the proposed MOAs and proceeded to adopt, albeit imprecisely in hindsight, the default linear low-dose extrapolation approach. arcadis.com 5 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 3 DOURSON ET AL. (2014): MODE OF ACTION (MOA) ANALYSIS FOR LIVER TUMORS FROM ORAL 1,4- DIOXANE EXPOSURES AND EVIDENCE-BASED DOSE ss RESPONSE ASSESSMENT USEPA's (2010) conclusion to evaluate 1,4-dioxane as a non-threshold, linear, low-dose extrapolation carcinogen, was "based, in part, on the following: (1) apparent uncertainty in the toxic moiety for 1,4- dioxane; and, (2) apparent lack of noncancer toxicity data from several mouse bioassays at doses that evoke tumors, or that otherwise appear to have conflicting information concerning non-neoplastic lesions in the liver of rodents exposed orally to 1,4-dioxane" (Dourson et al. 2014). Recognizing that the key studies were performed over 3 decades, Dourson et al. (2014) hypothesized that "differences in histologic approaches for quantifying and reporting non-neoplastic changes may have been responsible for the differences noted across the studies" and would account for the apparent lack of non-cancer toxicity data reported in the key mouse bioassays. In addition to directly testing this hypothesis, Dourson et al. (2014) reviewed the database of genotoxicity studies, "which included DNA replication and promotion bioassays as well as mutation, initiation, and DNA repair studies," synthesized the genotoxicity database for 1,4- dioxane, and developed and analyzed a biologically plausible MOA for the formation of hepatic tumors in rodents by employing USEPA's (2005) carcinogen guidelines. Dourson et al.'s (2014) findings from the reread of the NCI (1978) mouse bioassay histopathology slides and review of the extensive genotoxicity database demonstrates that chronic exposure to 1,4-dioxane in drinking water is associated with a non-linear mode of carcinogenic action (threshold). which is contrary to USEPA's default linear low-dose extrapolation approach (non-threshold). The cancer MOA developed by Dourson et al. (2014) also afforded new data with which to perform an improved dose-response assessment for 1,4-dioxane using toxicological endpoints that protect against 1,4-dioxane's cancer MOA (refer to Appendix A for additional details). In regards to choosing a low-dose extrapolation approach, USEPA's Guidelines for Carcinogen Risk Assessment (2005) plainly state that "[a] nonlinear approach [i.e., derivation of a reference dose or concentration] should be selected when there are sufficient data to ascertain the mode of action and conclude that it is not linear at low doses and the agent does not demonstrate mutagenic or other activity consistent with linearity at low doses.' The information presented by USEPA (2010) and supplemented by the new information from Dourson et al. (2014) shows that: (1) 1,4-dioxane causes tumors at high doses through an MOA that involves cytotoxic effects, regenerative cell proliferation, and subsequent tumor formation; (2) the effects that precede tumor formation display non-linear dose-responses; and (3) 1,4- dioxane does not cause mutations at concentrations that are not cytotoxic. As a result, the RfD of 0.05 mg/kg/d developed by Dourson et al (2014) addressed key data gaps identified by USEPA (2010) and protects against the development of liver cancers following oral exposure to 1,4-dioxane. arcadis.com 6 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 4 DOURSON ET AL. (2016 IN PEER REVIEM: UPDATED MODE OF ACTION ANALYSIS (MOA) FOR LIVER TUMORS FROM ORAL ,4-DIOXANE EXPOSURES AND EVIDENCE-BASED DOSE-RESPONSE ASSESSMENT While Dourson et al. (2014) demonstrated that a threshold-based, regenerative cell proliferation MOA accounted for the tumor findings in the NCI (1978) mouse bioassay, questions still remained about the tumor findings from a 2-year oral mouse bioassay and a 13-week precursor study reported by the JBRC (1990a,b), subsequently published as Kano et al. (2008, 2009). Similar to the NCI (1978) mouse bioassay discussed in Dourson et al. (2014), the Japanese work provided few details or findings regarding non- cancer toxicity in the mouse liver after long-term exposure to 1,4-dioxane. To address the remaining questions regarding the apparently discordant findings between the tumor MOA in mice and rats and enhance the investigation of the threshold-based MOA for hepatic tumor formation, Dourson et al. (2016 in peer review) performed a detailed evaluation of the translated Japanese rodent bioassay reports (JBRC 1990a,b) and integrated the findings with other lines of evidence for the regenerative cell proliferation MOA. This effort is summarized in Appendix B. In addition to the detailed evaluation of the JBRC (1990a,b) bioassays, Dourson et al. (2016 in peer review) also solicited opinions from several pathologists regarding the conflicting findings from the mouse bioassays. Dourson et al. (2016 in peer review) reported: "Collectively these pathology opinions support the hypothesized MOA discussed in U.S. EPA (2013) and Dourson et al. (2014) that the liver tumors from oral exposure to 1,4-dioxane occur after metabolic saturation, accumulation of the parent 1,4-dioxane molecule, liver toxicity and a regenerative hyperplasia. While additional live experimental animal testing might add confirmatory findings, a threshold for these tumors is expected if metabolism of the parent compound is not saturated, since subsequent liver toxicity does not occur." By integrating all lines of evidence, Dourson et al. (2016 in peer review) concluded: "When the many lines of evidence are taken together, the reevaluation of the Japanese studies show consistent findings in rats and consistent findings in mice other than liver histopathology not being fully recorded in the second chronic study. However, based on the number of studies conducted, the well established metabolic saturation of 1,4-dioxane metabolism in humans and experimental animals, the effects of higher dose exposures on target organ toxicity, the presence of proliferative lesions, the effect of dose and time on the progression of lesions, the time of appearance of tumors, the spectrum of tumors developed, the number and incidence of tumors at organ sites with high or low background historical incidence, and the shapes of the dose-response curve for key events and tumors, all lead to the conclusion that a regenerative hyperplasia MOA is operating with 1,4-dioxane induced liver tumors." arcadis.con 7 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 5 IMPACT OF DOURSON ET AL.S UPDATED TOXICITY ASSESSMENT ON RISK-BASED DRINKING WATER CRITERIA An agency's choice to set risk-based criteria for 1,4-dioxane based on a threshold- or non-threshold- approach has the potential to drastically impact the value of the final criterion. An example of this is provided herein based on the approach used by the New Jersey Department of Environmental Protection (NJDEP) to derive groundwater quality criteria (NJDEP 2014). The risk-based equations NJDEP uses to derive groundwater criteria for threshold and non-threshold toxicants are shown below in Equations (2) and (3), respectively, while default exposure factors are shown in Table 1 below. Using the RfD of 0.05 mg/kg/d derived from Kociba et al. (1974) by Dourson et al. (2014) to protect against a regenerative cell proliferation MOA yields a risk-based criterion of 400 g/L Using USEPA's (2010) CSF of 0.1 (mg/kg/d)-¹ yields a risk-based criterion of 0.4 (0.35) g/L, corresponding to a 1 in 1,000,000 (1x10-6) excess lifetime cancer risk. Therefore, using the toxicity value derived based on a regenerative cell proliferation MOA (RfD, threshold approach) yields a criterion that is 1,000 times higher than the value derived using USEPA's CSF approach (linear low-dose extrapolation, non-threshold). The authors of this paper conclude that sites monitoring groundwater containing 1,4-dioxane at levels below 400 g/L would meet a reasonable groundwater quality criterion that is protective of human health. RfD x BW x CF x RSC Equation (2) Criterion = x UF BW x CF Equation (3) Criterion = x IRDW arcadis.com 8 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications Table 1. Toxicity Values and NJDEP's Exposure Factors for Calculating Risk-Based Groundwater Quality Criteria Exposure Pactor Units value bource RfD mg/kg/d 0.05 Dourson et al. (2014) CSF (mg/kg/d)-1 0.1 USEPA (2010) Target risk (TR) unitless 10-6 NJDEP default BW kg 70 NJDEP default Conversion factor (CF) g/mg 1,000 NJDEP default Relative source contribution (RSC) unitless 0.2 NJDEP default Drinking water ingestion rate (IRDw) L/d 2 NJDEP default Uncertainty factor (UF) unitless 1 NJDEP default Notes: kg = kilograms L/d = liters per day g/mg = micrograms per milligram arcadis.com 9 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 6 SUMMARY AND CONCLUSIONS To support several state regulatory agencies, Dourson et al. (2016 in peer review) recently undertook additional scientific investigations to address data gaps identified in USEPA's (2010) Toxicological Review regarding 1,4-dioxane's cancer MOA and assessment approach. Collectively, Dourson et al.'s (2014, 2016 in peer review) cancer MOA evaluations and dose-response assessments addressed USEPA's uncertainties and indeed demonstrate that chronic exposure to 1,4-dioxane in drinking water is associated with a non-linear mode of carcinogenic action (threshold). These additional scientific findings provide new information that resolve 1,4- dioxane's cancer MOA and support use of a non-linear dose response approach to protect against development of cancer following low-dose oral exposures. USEPA's (2010) cancer evaluation showed that 1,4-dioxane is not mutagenic or genotoxic at non- cytotoxic doses. However, USEPA ultimately chose to use a linear low-dose extrapolation approach for estimating human cancer risk from oral exposure to 1, 4-dioxane because they concluded that the MOA for tumor formation was unknown. The recent scientific investigations by Dourson et al. (2014, 2016 in peer review) provide new information to address data gaps identified by USEPA (2010) and demonstrate that 1,4-dioxane causes liver tumors in rodents through a regenerative cell proliferation MOA. The regenerative cell proliferation MOA is characterized by: (1) metabolic saturation and accumulation of parent compound; (2) cellular swelling, hypertrophy, and liver weight increase; (3) necrosis and/or inflammation; (4) increased DNA synthesis, hyperplasia development, and foci development; and (5) development of liver adenoma and carcinomas. Specifically, 1,4-dioxane must accumulate in the liver to levels that cause inflammation and cell damage before liver tumors can form. If the first key event does not occur (metabolic saturation), then liver tumors will not form. Therefore, there is a threshold of exposure for 1,4-dioxane below which tumors do not form and it is appropriate to use a non-linear low-dose extrapolation procedure for estimating risks. The RfD of 0.05 mg/kg/d derived by Dourson et al. (2014) is protective against tumor formation through this series of events (MOA) and was calculated using USEPA's preferred methods and best available scientific practices. Using Dourson et al.'s (2014) peer-reviewed RfD, based on a regenerative cell proliferation MOA to derive a groundwater drinking water criterion results in a criterion (400 g/L) that is 1,000 times greater than the concentration derived using USEPA's default CSF approach (0.4 g/L). Based on Dourson et al.'s (2014, 2016 in peer review) studies, it is reasonable to conclude that sites that monitor groundwater containing 1,4-dioxane at levels below 400 g/L would meet a reasonable groundwater quality criteria. The recent scientific findings summarized in this report have major implications for sites that are currently or will be managing water resources impacted by 1,4-dioxane. Considering that 1,4-dioxane is emerging as a water resource contaminant, in part due to USEPA's default linear low-dose cancer evaluation approach for liver tumors in rodents (USEPA 2010), the updated toxicology evidence that 1,4-dioxane is a threshold carcinogen is significant, and suggests that many current regulatory guidelines and standards are unnecessarily low. As such, the authors of this paper conclude that sites that monitor groundwater containing 1,4-dioxane at levels below 400 g/L would meet a reasonable groundwater quality criteria that is protective of human health. arcadis.con 10 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 7 REFERENCES ARA. 2016. 1,4-Dioxane Analysis. Available on line [Accessed Dec. 19] at: http://allianceforrisk.org/riskie- 2/. Buffler, P.A., S.M. Wood, L. Suarez, and D.J. Kilian. 1978. Mortality follow-up of workers exposed to 1,4- dioxane. J Occup Environ Med, 20: 255-259. Dourson, M., J. Reichard, P. Nance, H. Burleigh-Flayer, A. Parker, M. Vincent, and E.E. McConnell. 2014. Mode of action analysis for liver tumors from oral 1,4-dioxane exposures and evidence-based dose response assessment. Regul Toxicol Pharmacol. 68: 387-401. Dourson, M., J. Higginbotham, J. Crum, H. Burleigh-Flayer P, Nance, N. Forsberg, and M. Lafranconi. 2016 in peer review. Update: Mode of Action (MOA) for Liver Tumors Induced by Oral Exposure to 1,4-Dioxane. Regul Toxicol Pharmacol. Available online at: http://allianceforrisk.org/14-dioxane- analysis/. Health Canada. 2005. Drinking Water Guidance Value for 1,4-Dioxane. August 23. JBRC. 1990a. Report of Carcinogenicity Study by Oral Administration of 1,4-Dioxane (Mixed with Water) to Rats and Mice. Japan Industrial Safety and Health Association. December 28. JBRC. 1990b. Report of Preliminary Carcinogenicity Studies (Acute, Two-Week, and Thirteen-Week Studies) by Oral Administration of ,4-Dioxane (Mixed with Water) to Rats and Mice. Japan Industrial Safety and Health Association. December 28. Kano. H., Y. Umeda, M. Saito, H. Senoh, H. Ohbayashi, S. Aiso, K. Yamazaki, K. Nagano, and S. Fukushima. 2008. Thirteen-week oral toxicity of 1,4-dioxane in rats and mice. J Toxicol Sci. 33: 141- 153. Kano, H., Y, Umeda, T. Kasai, T. Sasaki, M. Matsumoto, K. Yamazaki, K. Nagano, H. Arito, and S. Fukushima. 2009. Carcinogenicity of 1,4-dioxane administered in drinking-water to rats and mice for 2 years. Food Chem Toxicol. 47:2776 - 2784. Kociba, R.J., S.B. McCollister, C. Park, T.R. Torkelson, and P.J. Gehring. 1974. 1,4-dioxane. I. Results of a 2-year ingestion study in rats. Toxicol Appl Pharmacol, 30: 275-286. doi:10.1016/0041- 008X(74)90099-4. McConnell, G. 2013. Report on the review of liver slides from the National Cancer Institute's Bioassay of 1,4-Dioxane for Possible Carcinogenicity Conducted in 1978 (NCI, 1978). Submitted to Toxicology Excellence for Risk Assessment. January/March 2013. NCI. 1978. Bioassay of 1,4-Dioxane for possible Carcinogenicity. Carcinogenesis Testing Program, Division of Cancer Cause and Prevention, National Cancer Institute. NIH, Bethesda, MD, 78-1330. Netherlands. 1999. Risk Assessment: 1, 4-Dioxane. Netherlands Organization for Applied Scientific Research (TNO) and the National Institute of Public Health and the Environment (RIVM). Chemical Substances Bureau, Ministry of Housing, Spatial Planning and the Environment (VROM), Netherlands, Final Version, 5 November, EINECS-No.: 204-661-8. arcadis.con 11 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications Neumann, H.G., H.W. Thielmann, J.G. Filser, H.P. Gelbke, H. Griem, H. Kappus, K.H. Norpoth, U. Reuter, S. Vamvakas, P. Wardenbach, and H.E. Wichmann. 1977. Proposed changes in the classification of carcinogenic chemicals in the work area. Reg. Toxicol. Pharmacol., 26:288-295. National Industrial Chemicals Notification and Assessment Scheme (NICNAS). 1998. Priority Existing Chemical Assessment Reports: 1,4-dioxane. Sydney, Australia: Australia Department of Health and Ageing. June. Available online at: NJDEP. 2014. Ground Water Quality Standards. N.J.A.C 7:9C. Available online at: http://www.nj.gov/dep/rules/rules/njac7_9c.pd Office of Environmental Health Hazard Assessment (OEHHA). 2002. Air Toxics Hot Spots Program. Risk Assessment Guidelines. Part II. Technical Support Document for Describing Available Cancer Potency Factors. Office of Environmental Health Hazard Assessment, California Environmental Protection Agency. December. Stickney, J.A., S.L. Sager, J.R. Clarkson, L.A. Smith, B.J. Locey, M.J. Bock, R. Hartung, and S.F. Olp. 2003. An updated evaluation of the carcinogenic potential of 1,4-dioxane. Regul Toxicol Pharmacol. 38(2):183-95. Thiess, A.M., E. Tress, and I. Fleig. 1976. Arbeitsmedizinische Untersuchungsergebnisse von Dioxan- exponierten Mitarbeitern [Industrial-medica investigation results in the case of workers exposed to dioxane]. Arbeitsmedizin, Sozialmedizin, Umweltmedizin, 11: 35-46. USEPA. 2005. Guidelines for carcinogen risk assessment, final report. EPA/630/P-03/001F. Risk Assessment Forum; U.S. Environmental Protection Agency. Washington, DC. March. USEPA. 2010. Toxicological Review of 1,4-Dioxane (CAS No. 123-91-1). EPA/635-R-09-005-F. Washington, D.C. August. USEPA. 2011. Recommended Use of Body Weight3/4 as the Default Method in Derivation of the Oral Reference Dose. EPA/100/R11/0001. Risk Assessment Forum. Washington, DC. USEPA. 2012. Benchmark Dose Technical Guidance. EPA/100/R-12/001. Risk Assessment Forum. Washington, DC. June 12. USEPA. 2013. Toxicological review of 1,4- Dioxane (with inhalation update) (CAS No. 123-91-1) in support of summary information on the Integrated Risk Information System (IRIS) [EPA Report]. (EPA-635/R-11/003-F). Washington, DC. USEPA. 2016a. Drinking Water Contaminant Candidate List 4 - Final. Federal Register Notice, Volume 81, No. 2222, Thursday, November 17. USEPA. 2016b. The Third Unregulated Contaminant Monitoring Rule (UCMR 3): Data Summary, July 2016. Office of Water (MS-140). EPA 815-S-16-004, Available at: USEPA. 2016c. Conducting a Human Health Risk Assessment, Dose-Response. Available at: arcadis.com 12 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 APPENDIX A Mode of Action Analysis for Liver Tumors Based on NCI Siide Reread and RfD Derivation (Dourson et al. 2014) Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 ARCADIS Gesign & for natural and built assets Appendix A MODE OF ACTION ANALYSIS FOR LIVER TUMORS BASED ON NCI SLIDE REREAD AND RFD DERIVATION (DOURSON ET AL. 2014) January 2017 Source: :ttps://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) CONTENTS Acronyms and Abbreviations ii 1 Reread of NCI (1978) Histopathology Slides and Mode of Action Evaluation for Hepatic Tumors in Mice 3 1.1 Review of 1,4-Dioxane's Genotoxicity Database 4 1.2 Mode of Action Analysis 4 1.2.1 Key Event 1: Accumulation of Parent Compound 5 1.2.2 Key Event 2: Liver Cell Hypertrophy and Necrosis 5 1.2.3 Key Event 3: DNA Synthesis 5 1.2.4 Key Event 4: Regenerative Cell Proliferation 5 1.2.5 Key Event 5: Promotion of Endogenously Initiated Tumors 6 1.3 Updated Dose-Response Assessment and Reference Dose Derivation for 1,4-Dioxane 6 2 References 8 arcadis.com i Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) ACRONYMS AND ABBREVIATIONS BMD benchmark dose-modeling CUF composite uncertainty factor EPL Experimental Pathology Laboratories JBRC Japan Bioassay Research Center mg/kg/d milligrams per kilogram body weight per day MOA mode of action NCI National Cancer Institute NOAEL no-observable-adverse-effect level POD point of departure RfD oral reference dose g/L micrograms per liter USEPA United States Environmental Protection Agency arcadis.com ii Source: https://wwww.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) 1 REREAD OF NCI (1978) HISTOPATHOLOGY SLIDES AND MODE OF ACTION EVALUATION FOR HEPATIC TUMORS IN MICE To test their hypothesis and better understand the "sequence of events that maybe have contributed to the MOA of the observed liver tumors," Dourson et al. (2014) and McConnell (2013) performed a blinded reread of the mouse National Cancer Institute (NCI) (1978) liver histopathology slides, because that study did not report non-neoplastic lesions in livers of the high-dose group. Note this is one of the two long-term oral mouse bioassays that exist for 1,4-dioxane; the other chronic mouse bioassay was performed by the Japan Bioassay Research Center (JBRC) and is reported most recently by Kano et al. (2009). As noted by Dourson et al. (2014): "Because terminology and practices for reporting liver lesions has changed since the time of the NCI study (1978), and because EPA (2005) is focusing more on an understanding of a chemical's Mode of Action (MOA) prior to any determination of its dose response, a re-review of the liver slides of mice from the NCI study (1978) was performed. This reanalysis was performed at the Experimental Pathology Laboratories (EPL), Research Triangle Park, NC during September through November 2012. The objective of the slide review was to determine if any non-neoplastic lesions in the liver were present in an effort to understand the sequence of events that may have contributed to the MOA of the observed liver tumors in mice. Another reason for the slide review was because at the time of the original slide review (i.e., 1978) the NCI typically recorded only the most severe diagnosis on a given slide, (e.g., adenoma or carcinoma). During this timeframe, the focus of cancer bioassays was to determine the potential carcinogenic activity of the chemical, not its potential chronic toxicity. For example, if an adenoma, carcinoma, and evidence of chronic toxicity (e.g., hepatocellular hypertrophy), were all present on a given slide, only the tumor response was typically recorded. Thus, it was unclear whether non-neoplastic lesions were present in the livers of mice but were not recorded in the NCI carcinogenicity study. McConnell's (2013) reread of the NCI (1978) mouse liver histopathology slides and Dourson et al.'s (2014) summary report demonstrate that chronic exposure to 1,4-dioxane in drinking water is associated with a non-linear mode of carcinogenic action (contrary to the United States Environmental Protection Agency's [USEPA's] low-dose extrapolation conclusion) based on several hepatotoxic effects that preceded tumor formation, including: Dose-dependent hepatocellular glycogen depletion Dose-dependent hepatocellular hypotrophy Dose-related hepatocellular necrosis Dose-dependent hepatocellular inflammation associated with necrosis Dose-related hyperplasia in several non-neoplastic cell types arcadis.com 3 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) Dourson et al. (2014) states: "The appearance of the liver toxicity follows the pattern where glycogen depletion occurs either concurrently with, or preceding, hypertrophy in both sexes. This was followed closely by necrosis and inflammation in males, but a high control incidence of necrosis and inflammation clouded this overall pattern found in females In terms of dose-response behavior, hypertrophy preceded the formation of foci, which appeared to precede formation of tumors. This pattern was also evident in an individual animal analysis." 1.1 Review of ,4-Dioxane's Genotoxicity Database As a component of their mode of action (MOA) analysis, Dourson et al. (2014) reviewed 1,4-dioxane's genotoxicity database using the information presented in USEPA's (2010) Toxicological Review for 1,4- dioxane. Dourson et al. (2014) noted: '1,4-dioxane has been tested for genotoxicity using in vitro assay systems with prokaryotic organisms, non-mammalian eukaryotic organisms, and mammalian cells, both with and without metabolic activation.' "[A]II fifteen mutagenicity tests reported (8 without activation and 7 with metabolic activation) were negative." "22 in vitro genotoxicity assays, and 9 in vivo genotoxicity assays were negative." "Eight genotoxicity assays were noted to be positive but only at high or noted cytotoxic doses." Based on their review of 1,4-dioxane's genotoxicity database, Dourson et al. (2014) states "1,4-dioxane does not cause point mutations, DNA repair, or [tumor] initiation" when administered at non-cytotoxic doses, which is in general agreement with USEPA's conclusions (USEPA 2010). The authors noted their conclusions were similar to USEPA's, but differ in that "if mutations are caused by 1,4-dioxane, it is only at high cytotoxic doses." The authors concluded: "1,4-dioxane does not cause mutagenicity as evidenced by uniformly negative results in standard in vitro and in vivo genotoxicity bioassays at levels that are not overtly toxic, but it may be a clastogen in vivo, in light of the mixed results in the micronucleus assays. It follows that mutations needed for tumor formation are then likely from the known endogenously available pool of mutations, and that a regenerative hyperplasia evokes more of these endogenous mutations to form tumors. Mutation potentially caused by 1,4-dioxane at high doses is precluded as a key event in tumor formation." 1.2 Mode of Action Analysis Dourson et al. (2014) proposed five key events in the non-mutagenic MOA resulting in hepatic tumors in rodents; they include: "(1) accumulation of parent compound [at concentrations that saturate metabolic processes], (2) liver cell hypertrophy and necrosis, (3) DNA synthesis, (4) regenerative cell proliferation, and (5) promotion of endogenously-initiated tumors.' The regenerative cell proliferation MOA has a threshold below which hepatic tumors are not formed. Evidence supporting each key event is presented below. arcadis.com 4 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) 1.2.1 Key Event 1: Accumulation of Parent Compound "Humans, rats, and mice extensively metabolize 1,4-dioxane.' "[M]etabolism is a capacity-limited process." "When dose of 1,4-dioxane approaches or exceeds the metabolizing capacity, the unmetabolized fraction of the dose increases and target organ toxicity occurs." "Thus, there appears to be a threshold below which metabolism and elimination are rapid and with less or perhaps without toxicological effects." "Human environmental exposures to 1,4-dioxane are unlikely to approach doses that saturate metabolizing enzymes and which produce liver and nasal tumors in rats." "Hence, since humans, like rats, efficiently metabolize 1,4-dioxane at low doses, enzyme saturation is negligible at low exposure levels." 1.2.2 Key Event 2: Liver Cell Hypertrophy and Necrosis "Liver cell hypertrophy and necrosis are key events in the 1,4-dioxane MOA leading to regenerative cell proliferation and, with chronic exposures, liver tumors.' "Liver changes including centrilobular swelling, single cell necrosis coincide exclusively with saturating doses of 1,4-dioxane and occur in as little as 11 weeks." "Evidence of hepatocellular damage preceding evidence of hepatocellular tumors caused by higher doses of 1,4-dioxane has been provided by several studies." 1.2.3 Key Event 3: DNA Synthesis USEPA (2010) reported "that 1,4-dioxane does not cause DNA repair activity in five standard in vitro and in vivo bioassays that tested for the presence of DNA repair in various model systems." "Conversely, 1,4-dioxane does cause DNA replication as evidenced by in vitro bioassays in rat hepatocytes" "DNA synthesis appears to be a key event for a regenerative cell proliferation and/or tumor promotion and can occur in either the presence or absence of cytotoxicity." "DNA synthesis provides evidence that 1,4-dioxane promotes cell proliferation through cytotoxicity." 1.2.4 Key Event 4: Regenerative Cell Proliferation "Dose-response and temporal data support the occurrence of cell proliferation and hyperplasia prior to the development of liver tumors in the rat model." "Cell proliferation appears to be an early response with significant changes (1.5- to 2-fold) occurring in rats with as little as 2 weeks of exposure." arcadis.com 5 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) "Given time, proliferative changes manifest as pre-neoplastic foci in studies where the histopathology of such changes are reported." 1.2.5 Key Event 5: Promotion of Endogenously Initiated Tumors "Three studies relevant to tumor initiation and promotion establish that 1,4-dioxane does not cause initiation in standard in vivo bioassays, in agreement with the absence of observed mutagenic or genotoxic activity." "[T]umor promotion was associated with significant toxicity in rats when administered by either dermal or oral routes." 1.3 Updated Dose-Response Assessment and Reference Dose Derivation for 1,4-Dioxane Dourson et al. (2014) and USEPA (2010) both relied on the dose-response data reported by Kociba et al. (1974). This study provided data for liver and kidney degeneration and necrosis in 6- to 8-week-old male and female Sherman rats (60/sex/dose group) that were exposed to 1, ,4-dioxane at 0, 0.01, 0.1, or 1% (i.e., 9.6, 94, and 1,015 milligrams per kilogram body weight per day [mg/kg/d] and 19, 148, and 1,599 mg/kg/d for males and females, respectively) in drinking water for up to 716 days. The study reported a no-observed-adverse-effect level (NOAEL) of 9.6 mg/kg/d and provides "the most sensitive measure of adverse effects by 1,4-dioxane" (USEPA 2010). USEPA's Toxicological Review for 1,4-dioxane (USEPA 2010) provides a reference dose (RfD) of 0.03 mg/kg/d. This RfD was derived using the NOAEL of 9.6 mg/kg/d for liver and kidney degeneration and necrosis in rats reported by Kociba et al. (1974) as the point of departure (POD), in combination with a composite uncertainty factor (CUF) of 300 (10 for interspecies extrapolation, 10 for intraspecies extrapolation, and 3 for database deficiencies associated with the lack of a multigenerational reproductive toxicity study). The lowest-observable-adverse-effect level for this study was 94 mg/kg/d (USEPA 2010). USEPA derived the RfD using the NOAEL reported by Kociba et al. (1974) because the published study did not report incidence data for these effects, and therefore, they were unable to perform benchmark dose-modeling (BMD). Alternatively, Dourson et al. (2014) reported an updated RfD of 0.05 mg/kg/d that was derived using incidence data (laboratory report for the published study was provided to Dourson et al. [2014] by The Dow Chemical Company) for hepatocellular necrosis (combined across sexes) and USEPA's preferred approaches¹. Specifically, Dourson et al. (2014) utilized USEPA's preferred BMD approach (USEPA 2012) to derive a POD of 20 mg/kg/d (95% lower bound on the dose associated with a 10% extra risk), USEPA's preferred default bodyweight scaling factor (USEPA 2011), to estimate a human equivalent 1 USEPA (2010) used the NOAEL from Kociba et al. (1974) based on liver and kidney degeneration to derive the RfD, specifically because Kociba et al. (1974) did not provide quantitative incidence or severity data for liver and kidney degeneration and necrosis. However, when appropriate data are available, USEPA prefers using BMD to define the POD (USEPA 2012). Had the incidence data from Kociba et al. (1974) been available at the time of their review, USEPA would have used it to derive a benchmark dose to use as the POD for setting the RfD. arcadis.com 6 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) dose, in combination with a CUF of 100 (3 for interspecies toxicodynamic extrapolation, 10 for intraspecies extrapolation, and 3 due to the lack of a 2-generation reproductive study) to derive an RfD of 0.05 mg/kg/d. Dourson et al. (2014) concluded that "the choice of this endpoint [hepatocellular necrosis] is protective, since liver toxicity, resulting in liver tumors, is the clear apical effect of greatest intensity in the available array of toxic effects." Dourson et al. (2014) calculated their RfD using standard approaches, as shown in Equation (1), below: POD 20 mg/kg/d Equation (1) RfD = = 0.05 mg/kg/d CUF 3x10x3 arcadis.com 7 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) 2 REFERENCES Dourson, M., J. Reichard, P. Nance, H. Burleigh-Flayer, A. Parker, M. Vincent, and E.E. McConnell. 2014. Mode of action analysis for liver tumors from oral 1,4-dioxane exposures and evidence-based dose response assessment. Regul Toxicol Pharmacol. 68: 387-401. Kano, H., Y, Umeda, T. Kasai, T. Sasaki, M. Matsumoto, K. Yamazaki, K. Nagano, H. Arito, and S. Fukushima. 2009. Carcinogenicity of 1,4-dioxane administered in drinking-water to rats and mice for 2 years. Food Chem Toxicol. 47:2776 - 2784. Kociba, R.J., S.B. McCollister, C. Park, T.R. Torkelson, and P.J. Gehring. 1974. 1,4-dioxane. I. Results of a 2-year ingestion study in rats. Toxicol Appl Pharmacol, 30: 275-286. oi:10.1016/0041- 008X(74)90099-4. McConnell, G. 2013. Report on the review of liver slides from the National Cancer Institute's Bioassay of 1,4-Dioxane for Possible Carcinogenicity Conducted in 1978 (NCI, 1978). Submitted to Toxicology Excellence for Risk Assessment. January/March 2013. NCI. 1978. Bioassay of 1,4-Dioxane for possible Carcinogenicity. Carcinogenesis Testing Program, Division of Cancer Cause and Prevention, National Cancer Institute. NIH, Bethesda, MD, 78-1330. USEPA. 2005. Guidelines for carcinogen risk assessment, final report. EPA/630/P-03/001F. Risk Assessment Forum; U.S. Environmental Protection Agency. Washington, DC. March. USEPA. 2010. Toxicological Review of 1,4-Dioxane (CAS No. 123-91-1). EPA/635-R-09-005-F. Washington, D.C. August. USEPA. 2012. Benchmark Dose Technical Guidance. EPA/100/R-12/001. Risk Assessment Forum. Washington, DC. June 12. arcadis.com 8 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 APPENDIX B Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) Source: https://www.industrydocuments.ucsf,edu/docs/fsbn0226 ARCADIS Desion & for natural and built assets Appendix B MODE OF ACTION ANALYSIS FOR LIVER TUMORS BASED ON JBRC REVIEW (DOURSONETAL.2016IN PEER REVIEW) January 2017 Source: :ttps://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) CONTENTS Acronyms and Abbreviations ii 1 Findings from Detailed Review of JBRC Rat Bioassays 3 1.1 Findings from Detailed Review of JBRC Mouse Bioassays 3 1.2 Integration of Evidence Supporting Regenerative Cell Proliferation MOA for 1,4-Dioxane 4 2 References 6 TABLES Table 1. Integration and Comparison of Rat and Mouse Bioassay Data (Adapted from Dourson et al., 2016 in peer review) 5 arcadis.com i Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) ACRONYMS AND ABEREVIATIONS JBRC Japan Bioassay Research Center mg/kg/d milligrams per kilogram body weight per day MOA mode of action NCI National Cancer Institute arcadis.com ii Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) 1 FINDINGS FROM DETAILED REVIEW OF JBRC RAT BIOASSAYS Changes in the liver found in the Japan Bioassay Research Center (JBRC) rat bioassays provide strong evidence that hepatic tumors were modulated by a threshold-based regenerative cell proliferation mode of action (MOA). Dourson et al. (2016 in peer review) found that effects observed in rats were in the expected dose-sequence for a regenerative cell proliferation MOA. Specifically, Dourson et al. (2016 in peer review) observed the following sequence of effects: Dose: 42-55 milligrams per kilogram body weight per day (mg/kg/d) - Effect: Liver swelling, hypertrophy, and liver weight increase Dose: 94-219 mg/kg/d - Effect: Necrosis Dose: 55-389 mg/kg/d - Effect: Hyperplasia and foci development Dose: >200 mg/kg/d - Effect: Increased levels of enzymes associated with liver damage Dose: 274-1015 mg/kg/d - Effect: Adenomas and carcinomas 1.1 Findings from Detailed Review of JBRC Mouse Bioassays Dourson et al. (2016 in peer review) observed the following sequence of effects in the JBRC (1990a) mouse bioassays: Dose: 190-200 mg/kg/d - Effect: Liver swelling, hypertrophy, and liver weight increase Dose: 190-200 mg/kg/d - Effect: Necrosis Dose: Not reported - Effect: Hyperplasia and foci development not reported Dose: 200 mg/kg/d - Effect: Increased levels of enzymes associated with liver damage Dose: 66-964 mg/kg/d - Effect: Adenomas and carcinomas, females Surprisingly, effects in the liver found in the JBRC mouse bioassays conflict with those clearly reported by Dourson et al. (2014) and McConnell (2013) for the reread of the National Cancer Institute (NCI) (1978) mouse bioassay histopathology slides. Additionally, the progression of effects reported by JBRC for the 2- year chronic study is inconsistent with enzymatic changes indicative of liver damage noted in the same study, as well as findings from a 13-week precursor study performed by the same laboratory. As noted by Dourson et al. (2016 in peer review), "the lack of noncancer histopathology in the chronic mouse study is not consistent with the changes in liver enzymes in this same chronic study, nor is this lack of noncancer arcadis.com 3 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) findings expected based on the histopathology of the precursor 13-week study" and "[n]or does the tumor response in the low dose female mice of JBRC (1990a) match the tumor findings in the McConnell (2013) re-read of NCI (1978). Dourson et al. (2016 in peer review) hypothesized that differences in mouse bioassay results between JBRC and McConnell (2013) may be due to differences in the interpretation of the histopathological data, and provided the following quote from JBRC (Kano et al. 2009) to substantiate their claim: "The hepatic hyperplasia of rats and mice diagnosed in the previous report (Yamazaki et al., 1994) [authors note: which was a presentation of the JBRC, 1990a] was re-examined histopathologically and changed to hepatocellular adenomas and altered hepatocellular foci including acidophilic, basophilic and clear cell foci in the present studies, according to the current diagnostic criteria of liver lesions in rats and mice." Unfortunately, slides from the original JBRC (1990a,b) bioassays were not available; therefore, the JBRC slides could not be reread as they were by McConnell (2013) for the NCI (1978) mouse liver slides. Additionally, JBRC did not archive sufficient numbers of pictures of histopathology slides to resolve the issue. While, it is impossible to know for sure from this dataset whether liver tumors formed prior to or following cytotoxic effects, the weight of evidence from the JBRC and NCI mouse bioassays supports a regenerative cell proliferation MOA. 1.2 Integration of Evidence Supporting Regenerative Cell Proliferation MOA for 1,4-Dioxane Following integration of key events from seven rat bioassays, three mouse bioassays, and 1,4-dioxane's genotoxicity profile, presented in Table 1 below, Dourson et al. (2016 in peer review) showed that 1,4- dioxane's toxicological database supports a threshold-based regenerative cell proliferation MOA for tumor formation in livers of rodents orally exposed to 1,4-dioxane. The authors reported that bioassay data for rats leads to the conclusion that "rat liver tumors are evoked by a regenerative hyperplasia," while the authors concluded the "sequence of events from two chronic mouse studies and a subchronic mouse study generally support the hypothesized regenerative hyperplasia MOA" (Dourson et al. 2016 in peer review). In regards to the conflicting mouse bioassay data (McConnell 2013; Dourson et al. 2014; JBRC 1990a), the difference is likely due in part to changes in the terminology and practices used for recording the liver lesions reported by Kano et al. (2009). arcadis.com 4 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226

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fsbn0226_p9, fsbn0226_p10, fsbn0226_p11, fsbn0226_p12, fsbn0226_p13, fsbn0226_p14, fsbn0226_p15, fsbn0226_p16, fsbn0226_p17, fsbn0226_p18, fsbn0226_p19, fsbn0226_p20, fsbn0226_p21, fsbn0226_p22, fsbn0226_p23, fsbn0226_p24, fsbn0226_p25, fsbn0226_p26, fsbn0226_p27, fsbn0226_p28, fsbn0226_p29, fsbn0226_p30, fsbn0226_p31, fsbn0226_p32, fsbn0226_p33, fsbn0226_p34

relative source contribution, Relative Source Contribution

Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 2 USEPA APPROACH FOR EVALUATING CANCER RISHS POSED BY ORAL EXPOSURE TO 1,4-DIOXANE USEPA's Integrated Risk Information System (IRIS) published the Toxicological Review for 1,4-dioxane, in which it describes their approach and justification for deriving an oral CSF for this constituent. Below is a summary of USEPA's evaluation of available human toxicological data, weight of evidence evaluation, key study identification, critical effect selection, dose-response assessment, and the low-dose extrapolation procedure used to derive 1,4-dioxane's CSF. 2.1 USEPA's Evaluation of Evidence of Cancer in Humans USEPA evaluated the degree to which data provide evidence of carcinogenicity in humans (USEPA 2010). USEPA relied on two human occupational studies in their evaluation of potential impacts related to long-term exposure to 1,4-dioxane (Thiess et al. 1976; Buffler et al. 1978). USEPA concluded that neither study provided evidence that 1, ,4-dioxane causes cancer in humans. However, they noted "the cohort size and number of reported cases were small." 2.2 USEPA's Evaluation of Evidence of Cancer in Animal Bioassays USEPA followed its Guidelines for Carcinogen Risk Assessment (USEPA 2005) to conclude that 1,4- dioxane is "likely to be carcinogenic to humans" based on "evidence of liver carcinogenicity in several 2- year bioassays conducted in three strains of rats, two strains of mice, and in guinea pigs.' USEPA provided several reasons to justify its conclusion. For instance, USEPA concluded that the "available evidence is inadequate to establish a MOA by which 1,4-dioxane induces liver tumors in rats and mice" (USEPA 2010). Specifically, USEPA noted the "[c]onflicting data from rat and mouse bioassays (Japan Bioassay Research Center [JBRC] 1998; Kociba et al., 1974) suggest that cytotoxicity may not be a required precursor event for 1,4-dioxane-induced cell proliferation." USEPA (2010) noted that "[a]vailable data also do not clearly identify whether 1,4-dioxane or one of its metabolites is responsible for the observed effects. However, USEPA also reported that "the generally negative results for 1,4-dioxane in a number of genotoxicity assays indicates the carcinogenicity of 1,4-dioxane may not be mediated by a mutagenic MOA" (USEPA 2010). 2.3 Key Study Identification (Kano et al. 2009), Critical Effect Selection, Dose-Response Assessment, and Low-Dose Extrapolation Procedure USEPA (2010) concluded that the MOA by which 1,4-dioxane produces liver tumors is "unknown, and available evidence in support of any hypothetical mode of carcinogenic action for 1,4-dioxane is inconclusive." With this conclusion in mind, USEPA (2010) identified a 2-year drinking water study performed by Kano et al. (2009) as the key study of the oral CSF for 1,4-dioxane. Note that Kano et al. (2009) published findings originally reported by the JBRC (1990a). Although USEPA (2010) concurrently evaluated two other studies (Kociba et al. 1974; National Cancer Institute [NCI] 1978), the Kano et al. (2009) study was ultimately selected as the key study because USEPA (2010) noted that "[c]alculation of arcadis.com 3 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications a CSF for 1,4-dioxane is based upon the dose-response data for the most sensitive species and gender." The study was performed in accordance with the Organization of Economic Development's Principles for Good Laboratory Practices and involved exposing groups of rats (50 animals of each sex for each dose) and mice (50 animals of each sex for each dose) to 1,4-dioxane (>99% pure) in drinking water for 2 years. Rats were exposed to 1,4-dioxane in drinking water at 0, 200, 1,000, or 5,000 milligrams per liter (mg/L), while mice were exposed at 0, 500, 2,000, or 8,000 mg/L in drinking water. As reported by USEPA (2010): "The investigators used data from water consumption and BW [body weight] to calculate an estimate of the daily intake of 1,4-dioxane (mg/kg-day) by male and female rats and mice. Kano et al. (2009) reported a calculated mean + standard deviation for the daily doses of 1,4-dioxane for the duration of the study. Male rats received doses of approximately 0, 11+1, 55+3, or 274+18 mg/kg-day and female rats received 0, 183, 83+14, or 429+69 mg/kg-day. Male mice received doses of 0, 49+5, 191+21, or 677+74 mg/kg-day and female mice received 0, 66=10, 278+40, or 964+88 mg/kg-day." "The study by Kano et al. (2009) was used for development of an oral CSF. This was a well- designed study, conducted in both sexes in two species (rats and mice) with a sufficient number (N=50) of animals per dose group. The number of test animals allocated among three dose levels and an untreated control group was adequate, with examination of appropriate toxicological endpoints in both sexes of rats and mice. Alternative bioassays (Kociba et al., 1974; NCI, 1978) were available and were fully considered for the derivation of the oral CSF." USEPA identified increased incidence of liver adenomas or carcinomas as the critical effect in rats and mice exposed to 1,4-dioxane in the Kano et al. (2009) study. Following standard dose adjustment to a human equivalent dose using a default body weight (BW) scaling factor (USEPA 2005), USEPA performed dose-response modeling using Benchmark Dose Software and fit the suite of models available in the program to the incidence data for "either hepatocellular carcinoma or adenoma" (USEPA 2010). USEPA concluded that female mice are "more sensitive to liver carcinogenicity induced by 1,4-dioxane compared to other species or tumor types" and identified the lower 95% confidence bound on the benchmark dose associated with a 50% extra risk (benchmark response [BMR]) of developing "either hepatocellular carcinoma or adenoma" (4.95 milligrams per kilogram per day [mg/kg/d]) as the point of departure (POD) for calculating the oral CSF via linear low-dose extrapolation, as shown in Equation (1), below. USEPA (2010) again justified a linear low-dose extrapolation approach based on their conclusion that 1,4-dioxane's MOA for production of hepatic tumors in rodents is "unknown." BMR 0.5 Equation (1) CSF = = 0.1 (mg/kg/d)1 POD 4.95 mg/kg/d 2.4 Comments Provided to USEPA During External Peer Review When USEPA's IRIS program derives toxicity values, the Toxicological Review undergoes critical evaluation by individuals from within and outside the agency. A result of the outside review efforts indicated several external peer review panel members believed that available information for 1,4-dioxane could "support the use of a nonlinear extrapolation approach to estimate human carcinogenic risk" and arcadis.con 4 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications that "such an approach should be presented in the Toxicological Review.' Specifically, the USEPA (2010) notes: "[N]umerous short-term in vitro and a few in vivo tests were nonpositive for 1,4-dioxane-induced genotoxicity". Results from two-stage mouse skin tumor bioassays "suggest that a potential mode of action for 1,4- dioxane-induced tumors may involve proliferation of cells initiated spontaneously, or by some other agent, to become tumors." Additionally, a public commenter noted: "Low-dose linear extrapolation for the oral CSF is not appropriate nor justified by the data. The weight of evidence supports a threshold (nonlinear) MOA when metabolic pathway is saturated at high doses. Nonlinear extrapolations should be evaluated and presented for 1,4-dioxane." These statements indicated that some reviewers felt the toxicological data for 1,4-dioxane indicated that it may not behave in a linear manner, but rather as a threshold carcinogen. Nonetheless, USEPA (2010) ultimately concluded that there was insufficient information available to support any of the proposed MOAs and proceeded to adopt, albeit imprecisely in hindsight, the default linear low-dose extrapolation approach. arcadis.com 5 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 3 DOURSON ET AL. (2014): MODE OF ACTION (MOA) ANALYSIS FOR LIVER TUMORS FROM ORAL 1,4- DIOXANE EXPOSURES AND EVIDENCE-BASED DOSE ss RESPONSE ASSESSMENT USEPA's (2010) conclusion to evaluate 1,4-dioxane as a non-threshold, linear, low-dose extrapolation carcinogen, was "based, in part, on the following: (1) apparent uncertainty in the toxic moiety for 1,4- dioxane; and, (2) apparent lack of noncancer toxicity data from several mouse bioassays at doses that evoke tumors, or that otherwise appear to have conflicting information concerning non-neoplastic lesions in the liver of rodents exposed orally to 1,4-dioxane" (Dourson et al. 2014). Recognizing that the key studies were performed over 3 decades, Dourson et al. (2014) hypothesized that "differences in histologic approaches for quantifying and reporting non-neoplastic changes may have been responsible for the differences noted across the studies" and would account for the apparent lack of non-cancer toxicity data reported in the key mouse bioassays. In addition to directly testing this hypothesis, Dourson et al. (2014) reviewed the database of genotoxicity studies, "which included DNA replication and promotion bioassays as well as mutation, initiation, and DNA repair studies," synthesized the genotoxicity database for 1,4- dioxane, and developed and analyzed a biologically plausible MOA for the formation of hepatic tumors in rodents by employing USEPA's (2005) carcinogen guidelines. Dourson et al.'s (2014) findings from the reread of the NCI (1978) mouse bioassay histopathology slides and review of the extensive genotoxicity database demonstrates that chronic exposure to 1,4-dioxane in drinking water is associated with a non-linear mode of carcinogenic action (threshold). which is contrary to USEPA's default linear low-dose extrapolation approach (non-threshold). The cancer MOA developed by Dourson et al. (2014) also afforded new data with which to perform an improved dose-response assessment for 1,4-dioxane using toxicological endpoints that protect against 1,4-dioxane's cancer MOA (refer to Appendix A for additional details). In regards to choosing a low-dose extrapolation approach, USEPA's Guidelines for Carcinogen Risk Assessment (2005) plainly state that "[a] nonlinear approach [i.e., derivation of a reference dose or concentration] should be selected when there are sufficient data to ascertain the mode of action and conclude that it is not linear at low doses and the agent does not demonstrate mutagenic or other activity consistent with linearity at low doses.' The information presented by USEPA (2010) and supplemented by the new information from Dourson et al. (2014) shows that: (1) 1,4-dioxane causes tumors at high doses through an MOA that involves cytotoxic effects, regenerative cell proliferation, and subsequent tumor formation; (2) the effects that precede tumor formation display non-linear dose-responses; and (3) 1,4- dioxane does not cause mutations at concentrations that are not cytotoxic. As a result, the RfD of 0.05 mg/kg/d developed by Dourson et al (2014) addressed key data gaps identified by USEPA (2010) and protects against the development of liver cancers following oral exposure to 1,4-dioxane. arcadis.com 6 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 4 DOURSON ET AL. (2016 IN PEER REVIEM: UPDATED MODE OF ACTION ANALYSIS (MOA) FOR LIVER TUMORS FROM ORAL ,4-DIOXANE EXPOSURES AND EVIDENCE-BASED DOSE-RESPONSE ASSESSMENT While Dourson et al. (2014) demonstrated that a threshold-based, regenerative cell proliferation MOA accounted for the tumor findings in the NCI (1978) mouse bioassay, questions still remained about the tumor findings from a 2-year oral mouse bioassay and a 13-week precursor study reported by the JBRC (1990a,b), subsequently published as Kano et al. (2008, 2009). Similar to the NCI (1978) mouse bioassay discussed in Dourson et al. (2014), the Japanese work provided few details or findings regarding non- cancer toxicity in the mouse liver after long-term exposure to 1,4-dioxane. To address the remaining questions regarding the apparently discordant findings between the tumor MOA in mice and rats and enhance the investigation of the threshold-based MOA for hepatic tumor formation, Dourson et al. (2016 in peer review) performed a detailed evaluation of the translated Japanese rodent bioassay reports (JBRC 1990a,b) and integrated the findings with other lines of evidence for the regenerative cell proliferation MOA. This effort is summarized in Appendix B. In addition to the detailed evaluation of the JBRC (1990a,b) bioassays, Dourson et al. (2016 in peer review) also solicited opinions from several pathologists regarding the conflicting findings from the mouse bioassays. Dourson et al. (2016 in peer review) reported: "Collectively these pathology opinions support the hypothesized MOA discussed in U.S. EPA (2013) and Dourson et al. (2014) that the liver tumors from oral exposure to 1,4-dioxane occur after metabolic saturation, accumulation of the parent 1,4-dioxane molecule, liver toxicity and a regenerative hyperplasia. While additional live experimental animal testing might add confirmatory findings, a threshold for these tumors is expected if metabolism of the parent compound is not saturated, since subsequent liver toxicity does not occur." By integrating all lines of evidence, Dourson et al. (2016 in peer review) concluded: "When the many lines of evidence are taken together, the reevaluation of the Japanese studies show consistent findings in rats and consistent findings in mice other than liver histopathology not being fully recorded in the second chronic study. However, based on the number of studies conducted, the well established metabolic saturation of 1,4-dioxane metabolism in humans and experimental animals, the effects of higher dose exposures on target organ toxicity, the presence of proliferative lesions, the effect of dose and time on the progression of lesions, the time of appearance of tumors, the spectrum of tumors developed, the number and incidence of tumors at organ sites with high or low background historical incidence, and the shapes of the dose-response curve for key events and tumors, all lead to the conclusion that a regenerative hyperplasia MOA is operating with 1,4-dioxane induced liver tumors." arcadis.con 7 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 5 IMPACT OF DOURSON ET AL.S UPDATED TOXICITY ASSESSMENT ON RISK-BASED DRINKING WATER CRITERIA An agency's choice to set risk-based criteria for 1,4-dioxane based on a threshold- or non-threshold- approach has the potential to drastically impact the value of the final criterion. An example of this is provided herein based on the approach used by the New Jersey Department of Environmental Protection (NJDEP) to derive groundwater quality criteria (NJDEP 2014). The risk-based equations NJDEP uses to derive groundwater criteria for threshold and non-threshold toxicants are shown below in Equations (2) and (3), respectively, while default exposure factors are shown in Table 1 below. Using the RfD of 0.05 mg/kg/d derived from Kociba et al. (1974) by Dourson et al. (2014) to protect against a regenerative cell proliferation MOA yields a risk-based criterion of 400 g/L Using USEPA's (2010) CSF of 0.1 (mg/kg/d)-¹ yields a risk-based criterion of 0.4 (0.35) g/L, corresponding to a 1 in 1,000,000 (1x10-6) excess lifetime cancer risk. Therefore, using the toxicity value derived based on a regenerative cell proliferation MOA (RfD, threshold approach) yields a criterion that is 1,000 times higher than the value derived using USEPA's CSF approach (linear low-dose extrapolation, non-threshold). The authors of this paper conclude that sites monitoring groundwater containing 1,4-dioxane at levels below 400 g/L would meet a reasonable groundwater quality criterion that is protective of human health. RfD x BW x CF x RSC Equation (2) Criterion = x UF BW x CF Equation (3) Criterion = x IRDW arcadis.com 8 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications Table 1. Toxicity Values and NJDEP's Exposure Factors for Calculating Risk-Based Groundwater Quality Criteria Exposure Pactor Units value bource RfD mg/kg/d 0.05 Dourson et al. (2014) CSF (mg/kg/d)-1 0.1 USEPA (2010) Target risk (TR) unitless 10-6 NJDEP default BW kg 70 NJDEP default Conversion factor (CF) g/mg 1,000 NJDEP default Relative source contribution (RSC) unitless 0.2 NJDEP default Drinking water ingestion rate (IRDw) L/d 2 NJDEP default Uncertainty factor (UF) unitless 1 NJDEP default Notes: kg = kilograms L/d = liters per day g/mg = micrograms per milligram arcadis.com 9 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 6 SUMMARY AND CONCLUSIONS To support several state regulatory agencies, Dourson et al. (2016 in peer review) recently undertook additional scientific investigations to address data gaps identified in USEPA's (2010) Toxicological Review regarding 1,4-dioxane's cancer MOA and assessment approach. Collectively, Dourson et al.'s (2014, 2016 in peer review) cancer MOA evaluations and dose-response assessments addressed USEPA's uncertainties and indeed demonstrate that chronic exposure to 1,4-dioxane in drinking water is associated with a non-linear mode of carcinogenic action (threshold). These additional scientific findings provide new information that resolve 1,4- dioxane's cancer MOA and support use of a non-linear dose response approach to protect against development of cancer following low-dose oral exposures. USEPA's (2010) cancer evaluation showed that 1,4-dioxane is not mutagenic or genotoxic at non- cytotoxic doses. However, USEPA ultimately chose to use a linear low-dose extrapolation approach for estimating human cancer risk from oral exposure to 1, 4-dioxane because they concluded that the MOA for tumor formation was unknown. The recent scientific investigations by Dourson et al. (2014, 2016 in peer review) provide new information to address data gaps identified by USEPA (2010) and demonstrate that 1,4-dioxane causes liver tumors in rodents through a regenerative cell proliferation MOA. The regenerative cell proliferation MOA is characterized by: (1) metabolic saturation and accumulation of parent compound; (2) cellular swelling, hypertrophy, and liver weight increase; (3) necrosis and/or inflammation; (4) increased DNA synthesis, hyperplasia development, and foci development; and (5) development of liver adenoma and carcinomas. Specifically, 1,4-dioxane must accumulate in the liver to levels that cause inflammation and cell damage before liver tumors can form. If the first key event does not occur (metabolic saturation), then liver tumors will not form. Therefore, there is a threshold of exposure for 1,4-dioxane below which tumors do not form and it is appropriate to use a non-linear low-dose extrapolation procedure for estimating risks. The RfD of 0.05 mg/kg/d derived by Dourson et al. (2014) is protective against tumor formation through this series of events (MOA) and was calculated using USEPA's preferred methods and best available scientific practices. Using Dourson et al.'s (2014) peer-reviewed RfD, based on a regenerative cell proliferation MOA to derive a groundwater drinking water criterion results in a criterion (400 g/L) that is 1,000 times greater than the concentration derived using USEPA's default CSF approach (0.4 g/L). Based on Dourson et al.'s (2014, 2016 in peer review) studies, it is reasonable to conclude that sites that monitor groundwater containing 1,4-dioxane at levels below 400 g/L would meet a reasonable groundwater quality criteria. The recent scientific findings summarized in this report have major implications for sites that are currently or will be managing water resources impacted by 1,4-dioxane. Considering that 1,4-dioxane is emerging as a water resource contaminant, in part due to USEPA's default linear low-dose cancer evaluation approach for liver tumors in rodents (USEPA 2010), the updated toxicology evidence that 1,4-dioxane is a threshold carcinogen is significant, and suggests that many current regulatory guidelines and standards are unnecessarily low. As such, the authors of this paper conclude that sites that monitor groundwater containing 1,4-dioxane at levels below 400 g/L would meet a reasonable groundwater quality criteria that is protective of human health. arcadis.con 10 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 7 REFERENCES ARA. 2016. 1,4-Dioxane Analysis. Available on line [Accessed Dec. 19] at: http://allianceforrisk.org/riskie- 2/. Buffler, P.A., S.M. Wood, L. Suarez, and D.J. Kilian. 1978. Mortality follow-up of workers exposed to 1,4- dioxane. J Occup Environ Med, 20: 255-259. Dourson, M., J. Reichard, P. Nance, H. Burleigh-Flayer, A. Parker, M. Vincent, and E.E. McConnell. 2014. Mode of action analysis for liver tumors from oral 1,4-dioxane exposures and evidence-based dose response assessment. Regul Toxicol Pharmacol. 68: 387-401. Dourson, M., J. Higginbotham, J. Crum, H. Burleigh-Flayer P, Nance, N. Forsberg, and M. Lafranconi. 2016 in peer review. Update: Mode of Action (MOA) for Liver Tumors Induced by Oral Exposure to 1,4-Dioxane. Regul Toxicol Pharmacol. Available online at: http://allianceforrisk.org/14-dioxane- analysis/. Health Canada. 2005. Drinking Water Guidance Value for 1,4-Dioxane. August 23. JBRC. 1990a. Report of Carcinogenicity Study by Oral Administration of 1,4-Dioxane (Mixed with Water) to Rats and Mice. Japan Industrial Safety and Health Association. December 28. JBRC. 1990b. Report of Preliminary Carcinogenicity Studies (Acute, Two-Week, and Thirteen-Week Studies) by Oral Administration of ,4-Dioxane (Mixed with Water) to Rats and Mice. Japan Industrial Safety and Health Association. December 28. Kano. H., Y. Umeda, M. Saito, H. Senoh, H. Ohbayashi, S. Aiso, K. Yamazaki, K. Nagano, and S. Fukushima. 2008. Thirteen-week oral toxicity of 1,4-dioxane in rats and mice. J Toxicol Sci. 33: 141- 153. Kano, H., Y, Umeda, T. Kasai, T. Sasaki, M. Matsumoto, K. Yamazaki, K. Nagano, H. Arito, and S. Fukushima. 2009. Carcinogenicity of 1,4-dioxane administered in drinking-water to rats and mice for 2 years. Food Chem Toxicol. 47:2776 - 2784. Kociba, R.J., S.B. McCollister, C. Park, T.R. Torkelson, and P.J. Gehring. 1974. 1,4-dioxane. I. Results of a 2-year ingestion study in rats. Toxicol Appl Pharmacol, 30: 275-286. doi:10.1016/0041- 008X(74)90099-4. McConnell, G. 2013. Report on the review of liver slides from the National Cancer Institute's Bioassay of 1,4-Dioxane for Possible Carcinogenicity Conducted in 1978 (NCI, 1978). Submitted to Toxicology Excellence for Risk Assessment. January/March 2013. NCI. 1978. Bioassay of 1,4-Dioxane for possible Carcinogenicity. Carcinogenesis Testing Program, Division of Cancer Cause and Prevention, National Cancer Institute. NIH, Bethesda, MD, 78-1330. Netherlands. 1999. Risk Assessment: 1, 4-Dioxane. Netherlands Organization for Applied Scientific Research (TNO) and the National Institute of Public Health and the Environment (RIVM). Chemical Substances Bureau, Ministry of Housing, Spatial Planning and the Environment (VROM), Netherlands, Final Version, 5 November, EINECS-No.: 204-661-8. arcadis.con 11 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications Neumann, H.G., H.W. Thielmann, J.G. Filser, H.P. Gelbke, H. Griem, H. Kappus, K.H. Norpoth, U. Reuter, S. Vamvakas, P. Wardenbach, and H.E. Wichmann. 1977. Proposed changes in the classification of carcinogenic chemicals in the work area. Reg. Toxicol. Pharmacol., 26:288-295. National Industrial Chemicals Notification and Assessment Scheme (NICNAS). 1998. Priority Existing Chemical Assessment Reports: 1,4-dioxane. Sydney, Australia: Australia Department of Health and Ageing. June. Available online at: NJDEP. 2014. Ground Water Quality Standards. N.J.A.C 7:9C. Available online at: http://www.nj.gov/dep/rules/rules/njac7_9c.pd Office of Environmental Health Hazard Assessment (OEHHA). 2002. Air Toxics Hot Spots Program. Risk Assessment Guidelines. Part II. Technical Support Document for Describing Available Cancer Potency Factors. Office of Environmental Health Hazard Assessment, California Environmental Protection Agency. December. Stickney, J.A., S.L. Sager, J.R. Clarkson, L.A. Smith, B.J. Locey, M.J. Bock, R. Hartung, and S.F. Olp. 2003. An updated evaluation of the carcinogenic potential of 1,4-dioxane. Regul Toxicol Pharmacol. 38(2):183-95. Thiess, A.M., E. Tress, and I. Fleig. 1976. Arbeitsmedizinische Untersuchungsergebnisse von Dioxan- exponierten Mitarbeitern [Industrial-medica investigation results in the case of workers exposed to dioxane]. Arbeitsmedizin, Sozialmedizin, Umweltmedizin, 11: 35-46. USEPA. 2005. Guidelines for carcinogen risk assessment, final report. EPA/630/P-03/001F. Risk Assessment Forum; U.S. Environmental Protection Agency. Washington, DC. March. USEPA. 2010. Toxicological Review of 1,4-Dioxane (CAS No. 123-91-1). EPA/635-R-09-005-F. Washington, D.C. August. USEPA. 2011. Recommended Use of Body Weight3/4 as the Default Method in Derivation of the Oral Reference Dose. EPA/100/R11/0001. Risk Assessment Forum. Washington, DC. USEPA. 2012. Benchmark Dose Technical Guidance. EPA/100/R-12/001. Risk Assessment Forum. Washington, DC. June 12. USEPA. 2013. Toxicological review of 1,4- Dioxane (with inhalation update) (CAS No. 123-91-1) in support of summary information on the Integrated Risk Information System (IRIS) [EPA Report]. (EPA-635/R-11/003-F). Washington, DC. USEPA. 2016a. Drinking Water Contaminant Candidate List 4 - Final. Federal Register Notice, Volume 81, No. 2222, Thursday, November 17. USEPA. 2016b. The Third Unregulated Contaminant Monitoring Rule (UCMR 3): Data Summary, July 2016. Office of Water (MS-140). EPA 815-S-16-004, Available at: USEPA. 2016c. Conducting a Human Health Risk Assessment, Dose-Response. Available at: arcadis.com 12 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 APPENDIX A Mode of Action Analysis for Liver Tumors Based on NCI Siide Reread and RfD Derivation (Dourson et al. 2014) Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 ARCADIS Gesign & for natural and built assets Appendix A MODE OF ACTION ANALYSIS FOR LIVER TUMORS BASED ON NCI SLIDE REREAD AND RFD DERIVATION (DOURSON ET AL. 2014) January 2017 Source: :ttps://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) CONTENTS Acronyms and Abbreviations ii 1 Reread of NCI (1978) Histopathology Slides and Mode of Action Evaluation for Hepatic Tumors in Mice 3 1.1 Review of 1,4-Dioxane's Genotoxicity Database 4 1.2 Mode of Action Analysis 4 1.2.1 Key Event 1: Accumulation of Parent Compound 5 1.2.2 Key Event 2: Liver Cell Hypertrophy and Necrosis 5 1.2.3 Key Event 3: DNA Synthesis 5 1.2.4 Key Event 4: Regenerative Cell Proliferation 5 1.2.5 Key Event 5: Promotion of Endogenously Initiated Tumors 6 1.3 Updated Dose-Response Assessment and Reference Dose Derivation for 1,4-Dioxane 6 2 References 8 arcadis.com i Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) ACRONYMS AND ABBREVIATIONS BMD benchmark dose-modeling CUF composite uncertainty factor EPL Experimental Pathology Laboratories JBRC Japan Bioassay Research Center mg/kg/d milligrams per kilogram body weight per day MOA mode of action NCI National Cancer Institute NOAEL no-observable-adverse-effect level POD point of departure RfD oral reference dose g/L micrograms per liter USEPA United States Environmental Protection Agency arcadis.com ii Source: https://wwww.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) 1 REREAD OF NCI (1978) HISTOPATHOLOGY SLIDES AND MODE OF ACTION EVALUATION FOR HEPATIC TUMORS IN MICE To test their hypothesis and better understand the "sequence of events that maybe have contributed to the MOA of the observed liver tumors," Dourson et al. (2014) and McConnell (2013) performed a blinded reread of the mouse National Cancer Institute (NCI) (1978) liver histopathology slides, because that study did not report non-neoplastic lesions in livers of the high-dose group. Note this is one of the two long-term oral mouse bioassays that exist for 1,4-dioxane; the other chronic mouse bioassay was performed by the Japan Bioassay Research Center (JBRC) and is reported most recently by Kano et al. (2009). As noted by Dourson et al. (2014): "Because terminology and practices for reporting liver lesions has changed since the time of the NCI study (1978), and because EPA (2005) is focusing more on an understanding of a chemical's Mode of Action (MOA) prior to any determination of its dose response, a re-review of the liver slides of mice from the NCI study (1978) was performed. This reanalysis was performed at the Experimental Pathology Laboratories (EPL), Research Triangle Park, NC during September through November 2012. The objective of the slide review was to determine if any non-neoplastic lesions in the liver were present in an effort to understand the sequence of events that may have contributed to the MOA of the observed liver tumors in mice. Another reason for the slide review was because at the time of the original slide review (i.e., 1978) the NCI typically recorded only the most severe diagnosis on a given slide, (e.g., adenoma or carcinoma). During this timeframe, the focus of cancer bioassays was to determine the potential carcinogenic activity of the chemical, not its potential chronic toxicity. For example, if an adenoma, carcinoma, and evidence of chronic toxicity (e.g., hepatocellular hypertrophy), were all present on a given slide, only the tumor response was typically recorded. Thus, it was unclear whether non-neoplastic lesions were present in the livers of mice but were not recorded in the NCI carcinogenicity study. McConnell's (2013) reread of the NCI (1978) mouse liver histopathology slides and Dourson et al.'s (2014) summary report demonstrate that chronic exposure to 1,4-dioxane in drinking water is associated with a non-linear mode of carcinogenic action (contrary to the United States Environmental Protection Agency's [USEPA's] low-dose extrapolation conclusion) based on several hepatotoxic effects that preceded tumor formation, including: Dose-dependent hepatocellular glycogen depletion Dose-dependent hepatocellular hypotrophy Dose-related hepatocellular necrosis Dose-dependent hepatocellular inflammation associated with necrosis Dose-related hyperplasia in several non-neoplastic cell types arcadis.com 3 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) Dourson et al. (2014) states: "The appearance of the liver toxicity follows the pattern where glycogen depletion occurs either concurrently with, or preceding, hypertrophy in both sexes. This was followed closely by necrosis and inflammation in males, but a high control incidence of necrosis and inflammation clouded this overall pattern found in females In terms of dose-response behavior, hypertrophy preceded the formation of foci, which appeared to precede formation of tumors. This pattern was also evident in an individual animal analysis." 1.1 Review of ,4-Dioxane's Genotoxicity Database As a component of their mode of action (MOA) analysis, Dourson et al. (2014) reviewed 1,4-dioxane's genotoxicity database using the information presented in USEPA's (2010) Toxicological Review for 1,4- dioxane. Dourson et al. (2014) noted: '1,4-dioxane has been tested for genotoxicity using in vitro assay systems with prokaryotic organisms, non-mammalian eukaryotic organisms, and mammalian cells, both with and without metabolic activation.' "[A]II fifteen mutagenicity tests reported (8 without activation and 7 with metabolic activation) were negative." "22 in vitro genotoxicity assays, and 9 in vivo genotoxicity assays were negative." "Eight genotoxicity assays were noted to be positive but only at high or noted cytotoxic doses." Based on their review of 1,4-dioxane's genotoxicity database, Dourson et al. (2014) states "1,4-dioxane does not cause point mutations, DNA repair, or [tumor] initiation" when administered at non-cytotoxic doses, which is in general agreement with USEPA's conclusions (USEPA 2010). The authors noted their conclusions were similar to USEPA's, but differ in that "if mutations are caused by 1,4-dioxane, it is only at high cytotoxic doses." The authors concluded: "1,4-dioxane does not cause mutagenicity as evidenced by uniformly negative results in standard in vitro and in vivo genotoxicity bioassays at levels that are not overtly toxic, but it may be a clastogen in vivo, in light of the mixed results in the micronucleus assays. It follows that mutations needed for tumor formation are then likely from the known endogenously available pool of mutations, and that a regenerative hyperplasia evokes more of these endogenous mutations to form tumors. Mutation potentially caused by 1,4-dioxane at high doses is precluded as a key event in tumor formation." 1.2 Mode of Action Analysis Dourson et al. (2014) proposed five key events in the non-mutagenic MOA resulting in hepatic tumors in rodents; they include: "(1) accumulation of parent compound [at concentrations that saturate metabolic processes], (2) liver cell hypertrophy and necrosis, (3) DNA synthesis, (4) regenerative cell proliferation, and (5) promotion of endogenously-initiated tumors.' The regenerative cell proliferation MOA has a threshold below which hepatic tumors are not formed. Evidence supporting each key event is presented below. arcadis.com 4 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) 1.2.1 Key Event 1: Accumulation of Parent Compound "Humans, rats, and mice extensively metabolize 1,4-dioxane.' "[M]etabolism is a capacity-limited process." "When dose of 1,4-dioxane approaches or exceeds the metabolizing capacity, the unmetabolized fraction of the dose increases and target organ toxicity occurs." "Thus, there appears to be a threshold below which metabolism and elimination are rapid and with less or perhaps without toxicological effects." "Human environmental exposures to 1,4-dioxane are unlikely to approach doses that saturate metabolizing enzymes and which produce liver and nasal tumors in rats." "Hence, since humans, like rats, efficiently metabolize 1,4-dioxane at low doses, enzyme saturation is negligible at low exposure levels." 1.2.2 Key Event 2: Liver Cell Hypertrophy and Necrosis "Liver cell hypertrophy and necrosis are key events in the 1,4-dioxane MOA leading to regenerative cell proliferation and, with chronic exposures, liver tumors.' "Liver changes including centrilobular swelling, single cell necrosis coincide exclusively with saturating doses of 1,4-dioxane and occur in as little as 11 weeks." "Evidence of hepatocellular damage preceding evidence of hepatocellular tumors caused by higher doses of 1,4-dioxane has been provided by several studies." 1.2.3 Key Event 3: DNA Synthesis USEPA (2010) reported "that 1,4-dioxane does not cause DNA repair activity in five standard in vitro and in vivo bioassays that tested for the presence of DNA repair in various model systems." "Conversely, 1,4-dioxane does cause DNA replication as evidenced by in vitro bioassays in rat hepatocytes" "DNA synthesis appears to be a key event for a regenerative cell proliferation and/or tumor promotion and can occur in either the presence or absence of cytotoxicity." "DNA synthesis provides evidence that 1,4-dioxane promotes cell proliferation through cytotoxicity." 1.2.4 Key Event 4: Regenerative Cell Proliferation "Dose-response and temporal data support the occurrence of cell proliferation and hyperplasia prior to the development of liver tumors in the rat model." "Cell proliferation appears to be an early response with significant changes (1.5- to 2-fold) occurring in rats with as little as 2 weeks of exposure." arcadis.com 5 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) "Given time, proliferative changes manifest as pre-neoplastic foci in studies where the histopathology of such changes are reported." 1.2.5 Key Event 5: Promotion of Endogenously Initiated Tumors "Three studies relevant to tumor initiation and promotion establish that 1,4-dioxane does not cause initiation in standard in vivo bioassays, in agreement with the absence of observed mutagenic or genotoxic activity." "[T]umor promotion was associated with significant toxicity in rats when administered by either dermal or oral routes." 1.3 Updated Dose-Response Assessment and Reference Dose Derivation for 1,4-Dioxane Dourson et al. (2014) and USEPA (2010) both relied on the dose-response data reported by Kociba et al. (1974). This study provided data for liver and kidney degeneration and necrosis in 6- to 8-week-old male and female Sherman rats (60/sex/dose group) that were exposed to 1, ,4-dioxane at 0, 0.01, 0.1, or 1% (i.e., 9.6, 94, and 1,015 milligrams per kilogram body weight per day [mg/kg/d] and 19, 148, and 1,599 mg/kg/d for males and females, respectively) in drinking water for up to 716 days. The study reported a no-observed-adverse-effect level (NOAEL) of 9.6 mg/kg/d and provides "the most sensitive measure of adverse effects by 1,4-dioxane" (USEPA 2010). USEPA's Toxicological Review for 1,4-dioxane (USEPA 2010) provides a reference dose (RfD) of 0.03 mg/kg/d. This RfD was derived using the NOAEL of 9.6 mg/kg/d for liver and kidney degeneration and necrosis in rats reported by Kociba et al. (1974) as the point of departure (POD), in combination with a composite uncertainty factor (CUF) of 300 (10 for interspecies extrapolation, 10 for intraspecies extrapolation, and 3 for database deficiencies associated with the lack of a multigenerational reproductive toxicity study). The lowest-observable-adverse-effect level for this study was 94 mg/kg/d (USEPA 2010). USEPA derived the RfD using the NOAEL reported by Kociba et al. (1974) because the published study did not report incidence data for these effects, and therefore, they were unable to perform benchmark dose-modeling (BMD). Alternatively, Dourson et al. (2014) reported an updated RfD of 0.05 mg/kg/d that was derived using incidence data (laboratory report for the published study was provided to Dourson et al. [2014] by The Dow Chemical Company) for hepatocellular necrosis (combined across sexes) and USEPA's preferred approaches¹. Specifically, Dourson et al. (2014) utilized USEPA's preferred BMD approach (USEPA 2012) to derive a POD of 20 mg/kg/d (95% lower bound on the dose associated with a 10% extra risk), USEPA's preferred default bodyweight scaling factor (USEPA 2011), to estimate a human equivalent 1 USEPA (2010) used the NOAEL from Kociba et al. (1974) based on liver and kidney degeneration to derive the RfD, specifically because Kociba et al. (1974) did not provide quantitative incidence or severity data for liver and kidney degeneration and necrosis. However, when appropriate data are available, USEPA prefers using BMD to define the POD (USEPA 2012). Had the incidence data from Kociba et al. (1974) been available at the time of their review, USEPA would have used it to derive a benchmark dose to use as the POD for setting the RfD. arcadis.com 6 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) dose, in combination with a CUF of 100 (3 for interspecies toxicodynamic extrapolation, 10 for intraspecies extrapolation, and 3 due to the lack of a 2-generation reproductive study) to derive an RfD of 0.05 mg/kg/d. Dourson et al. (2014) concluded that "the choice of this endpoint [hepatocellular necrosis] is protective, since liver toxicity, resulting in liver tumors, is the clear apical effect of greatest intensity in the available array of toxic effects." Dourson et al. (2014) calculated their RfD using standard approaches, as shown in Equation (1), below: POD 20 mg/kg/d Equation (1) RfD = = 0.05 mg/kg/d CUF 3x10x3 arcadis.com 7 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) 2 REFERENCES Dourson, M., J. Reichard, P. Nance, H. Burleigh-Flayer, A. Parker, M. Vincent, and E.E. McConnell. 2014. Mode of action analysis for liver tumors from oral 1,4-dioxane exposures and evidence-based dose response assessment. Regul Toxicol Pharmacol. 68: 387-401. Kano, H., Y, Umeda, T. Kasai, T. Sasaki, M. Matsumoto, K. Yamazaki, K. Nagano, H. Arito, and S. Fukushima. 2009. Carcinogenicity of 1,4-dioxane administered in drinking-water to rats and mice for 2 years. Food Chem Toxicol. 47:2776 - 2784. Kociba, R.J., S.B. McCollister, C. Park, T.R. Torkelson, and P.J. Gehring. 1974. 1,4-dioxane. I. Results of a 2-year ingestion study in rats. Toxicol Appl Pharmacol, 30: 275-286. oi:10.1016/0041- 008X(74)90099-4. McConnell, G. 2013. Report on the review of liver slides from the National Cancer Institute's Bioassay of 1,4-Dioxane for Possible Carcinogenicity Conducted in 1978 (NCI, 1978). Submitted to Toxicology Excellence for Risk Assessment. January/March 2013. NCI. 1978. Bioassay of 1,4-Dioxane for possible Carcinogenicity. Carcinogenesis Testing Program, Division of Cancer Cause and Prevention, National Cancer Institute. NIH, Bethesda, MD, 78-1330. USEPA. 2005. Guidelines for carcinogen risk assessment, final report. EPA/630/P-03/001F. Risk Assessment Forum; U.S. Environmental Protection Agency. Washington, DC. March. USEPA. 2010. Toxicological Review of 1,4-Dioxane (CAS No. 123-91-1). EPA/635-R-09-005-F. Washington, D.C. August. USEPA. 2012. Benchmark Dose Technical Guidance. EPA/100/R-12/001. Risk Assessment Forum. Washington, DC. June 12. arcadis.com 8 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 APPENDIX B Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) Source: https://www.industrydocuments.ucsf,edu/docs/fsbn0226 ARCADIS Desion & for natural and built assets Appendix B MODE OF ACTION ANALYSIS FOR LIVER TUMORS BASED ON JBRC REVIEW (DOURSONETAL.2016IN PEER REVIEW) January 2017 Source: :ttps://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) CONTENTS Acronyms and Abbreviations ii 1 Findings from Detailed Review of JBRC Rat Bioassays 3 1.1 Findings from Detailed Review of JBRC Mouse Bioassays 3 1.2 Integration of Evidence Supporting Regenerative Cell Proliferation MOA for 1,4-Dioxane 4 2 References 6 TABLES Table 1. Integration and Comparison of Rat and Mouse Bioassay Data (Adapted from Dourson et al., 2016 in peer review) 5 arcadis.com i Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) ACRONYMS AND ABEREVIATIONS JBRC Japan Bioassay Research Center mg/kg/d milligrams per kilogram body weight per day MOA mode of action NCI National Cancer Institute arcadis.com ii Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) 1 FINDINGS FROM DETAILED REVIEW OF JBRC RAT BIOASSAYS Changes in the liver found in the Japan Bioassay Research Center (JBRC) rat bioassays provide strong evidence that hepatic tumors were modulated by a threshold-based regenerative cell proliferation mode of action (MOA). Dourson et al. (2016 in peer review) found that effects observed in rats were in the expected dose-sequence for a regenerative cell proliferation MOA. Specifically, Dourson et al. (2016 in peer review) observed the following sequence of effects: Dose: 42-55 milligrams per kilogram body weight per day (mg/kg/d) - Effect: Liver swelling, hypertrophy, and liver weight increase Dose: 94-219 mg/kg/d - Effect: Necrosis Dose: 55-389 mg/kg/d - Effect: Hyperplasia and foci development Dose: >200 mg/kg/d - Effect: Increased levels of enzymes associated with liver damage Dose: 274-1015 mg/kg/d - Effect: Adenomas and carcinomas 1.1 Findings from Detailed Review of JBRC Mouse Bioassays Dourson et al. (2016 in peer review) observed the following sequence of effects in the JBRC (1990a) mouse bioassays: Dose: 190-200 mg/kg/d - Effect: Liver swelling, hypertrophy, and liver weight increase Dose: 190-200 mg/kg/d - Effect: Necrosis Dose: Not reported - Effect: Hyperplasia and foci development not reported Dose: 200 mg/kg/d - Effect: Increased levels of enzymes associated with liver damage Dose: 66-964 mg/kg/d - Effect: Adenomas and carcinomas, females Surprisingly, effects in the liver found in the JBRC mouse bioassays conflict with those clearly reported by Dourson et al. (2014) and McConnell (2013) for the reread of the National Cancer Institute (NCI) (1978) mouse bioassay histopathology slides. Additionally, the progression of effects reported by JBRC for the 2- year chronic study is inconsistent with enzymatic changes indicative of liver damage noted in the same study, as well as findings from a 13-week precursor study performed by the same laboratory. As noted by Dourson et al. (2016 in peer review), "the lack of noncancer histopathology in the chronic mouse study is not consistent with the changes in liver enzymes in this same chronic study, nor is this lack of noncancer arcadis.com 3 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) findings expected based on the histopathology of the precursor 13-week study" and "[n]or does the tumor response in the low dose female mice of JBRC (1990a) match the tumor findings in the McConnell (2013) re-read of NCI (1978). Dourson et al. (2016 in peer review) hypothesized that differences in mouse bioassay results between JBRC and McConnell (2013) may be due to differences in the interpretation of the histopathological data, and provided the following quote from JBRC (Kano et al. 2009) to substantiate their claim: "The hepatic hyperplasia of rats and mice diagnosed in the previous report (Yamazaki et al., 1994) [authors note: which was a presentation of the JBRC, 1990a] was re-examined histopathologically and changed to hepatocellular adenomas and altered hepatocellular foci including acidophilic, basophilic and clear cell foci in the present studies, according to the current diagnostic criteria of liver lesions in rats and mice." Unfortunately, slides from the original JBRC (1990a,b) bioassays were not available; therefore, the JBRC slides could not be reread as they were by McConnell (2013) for the NCI (1978) mouse liver slides. Additionally, JBRC did not archive sufficient numbers of pictures of histopathology slides to resolve the issue. While, it is impossible to know for sure from this dataset whether liver tumors formed prior to or following cytotoxic effects, the weight of evidence from the JBRC and NCI mouse bioassays supports a regenerative cell proliferation MOA. 1.2 Integration of Evidence Supporting Regenerative Cell Proliferation MOA for 1,4-Dioxane Following integration of key events from seven rat bioassays, three mouse bioassays, and 1,4-dioxane's genotoxicity profile, presented in Table 1 below, Dourson et al. (2016 in peer review) showed that 1,4- dioxane's toxicological database supports a threshold-based regenerative cell proliferation MOA for tumor formation in livers of rodents orally exposed to 1,4-dioxane. The authors reported that bioassay data for rats leads to the conclusion that "rat liver tumors are evoked by a regenerative hyperplasia," while the authors concluded the "sequence of events from two chronic mouse studies and a subchronic mouse study generally support the hypothesized regenerative hyperplasia MOA" (Dourson et al. 2016 in peer review). In regards to the conflicting mouse bioassay data (McConnell 2013; Dourson et al. 2014; JBRC 1990a), the difference is likely due in part to changes in the terminology and practices used for recording the liver lesions reported by Kano et al. (2009). arcadis.com 4 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226

what is the P&B score for persistent and bioaccumulative

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endpoints, criteria are similarly available for both acute and chronic classification. The use of one common system allows for appropriate assessment of all substances. GHS classification information is readily available for all substances, as U.S. manufacturers have developed GHS classifications for their products to meet international requirements. ACC's support of the GHS criteria for purposes of this prioritization tool is not a categorical endorsement of the GHS criteria for any other purpose. ACC has been an active participant in the development of GHS and supports the system in principle. The GHS has not been broadly implemented to date in the U.S., although the Occupational Safety and Health Administration (OSHA) has indicated an intent to publish a regulation applying GHS in the workplace. ACC's December 29, 2009, comments on OSHA's proposed rule to modify the existing Hazard Communication Standard (HCS) to reflect the GHS urged that implementation of the GHS adhere to certain principles (e.g., continued application of the "Building Block Approach" of the Purple Book). ACC made specific recommendations concerning details of the Hazard Classification definitions, cut-off values, among others. ACC stands behind those comments. In ACC's view, the use of GHS criteria in a screening-level prioritization of chemicals can materially assist in determining which chemicals receive additional evaluation by the Environmental Protection Agency, but does not necessarily preclude the use of other appropriate, applicable criteria developed under other systems. To classify a chemical in a hazard based priority ranking where there is not direct data on the chemical, EPA can employ the full range of approaches, such as QSAR, SAR, read- across and other modeling tools in which EPA has confidence based on molecular structure. In those situations where there still remains insufficient information on either environmental or human health hazards, the chemical would be classified as "high" for its environmental or health ranking. 1. Environmental Ranking Table 1 provides a summary of how GHS criteria could be logically used for chemical management prioritization. Table 1. Environmental Safety - Hazard Ranking GHS Classification - Ranking Environmental Rank Environmental Score Acute I or Chronic I or Insufficient Information to High 4 Classify Acute II or Chronic II Medium High 3 Acute III or Chronic III/IV or Medium 2 none Not classified Low 1 August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 2. Human Health Ranking Table 2. Human Health - Hazard Ranking Health Rank GHS Classification - Human Health Ranking Score GHS CMR Cat 1a, 1b; OR Repeat Dose </= 10 mg/kg/day (oral); </= 20 mg/kg/day (dermal); </= 50 ppm/6hr/day (gas inhalation); High 4 <<= 0.2 mg/1/6h/day (vapour inhalation); </= 0.02 mg/l/6h/day (dust mist fume inhal). OR insufficient information to classify GHS CMR Cat 2; OR Repeat Dose 10 - 100 mg/kg/day (oral); 20 - 200 mg/kg/day (dermal); Medium High 50 - 250 ppm/6hr/day (gas inhalation); 3 0.2 - 1.0 mg/l/6h/day (vapour inhalation); 0.02 - 0.2 mg/l/6h/day (dust mist fume inhal). Not carcinogen/mutagen/repro/develop;OR Repeat Dose 100 - 1000 mg/kg/day (oral); 200 - 2000 mg/kg/day (dermal); Medium 250 - 1000 ppm/6hr/day (gas inhalation); 2 1.0 - 5.0 mg/l/6h/day (vapour inhalation); 0.2 - 1.0 mg/l/6h/day (dust mist fume inhal). Not carcinogen/mutagen/repro/develop; OR Repeat Dose >1000 mg/kg/day (oral); > 2000 mg/kg/day (dermal); Low > 1000 ppm/6hr/day (gas inhalation); 1 >5.0 mg/l/6h/day (vapour inhalation); > 1.0 mg/l/6h/day (dust mist fume inhal). It is important to note that specific concerns about children's health (specifically potential hazards and adverse effects on the nervous system) and those caused by endocrine disruption mechanisms are addressed in this prioritization process: The GHS CMR "R" classification includes specific evaluation of effects on development in utero and upon growth, maturation and reproduction. ("R" stands for reproductive toxicity and includes adverse effects on sexual function and fertility, as well as developmental toxicity in offspring). Endocrine activity is not a distinct toxicological hazard per se, but rather a measure of a compound's ability to interact with components of the endocrine system. The prioritization process evaluates data and information on relevant apical tests, including tests for reproduction and developmental toxicity (potential endocrine pathways). Thus, even if specific August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 screening for potential endocrine activity has not yet been conducted on certain compounds, hazard identification based on observable outcomes from apical toxicity tests (e.g., outcomes such as pathologic states indicative of disease conditions) covers all modes of action, including endocrine pathways. The toxicity information evaluated (CMR and repeat dose toxicity) is directly relevant to evaluating potential hazards to all individuals, including children. Such data typically includes: 1) identification and definition of possible hazards upon all major organ systems from both acute and repeated exposures, including the nervous system; 2) detection of potential hazards arising from in utero exposures, including possible effects on the nervous system; 3) evaluation of potential of a substance to affect reproduction; and 4) evaluation of the potential of a substance to damage DNA. Integration of Hazard Elements: Each of the environmental and human health classifications is assigned a numeric value based upon its ranking, with 1 being the lowest value and 4 the highest. The greatest ranking (highest hazard potential score) of either Environmental or Human Health is used in a substance- specific priority ranking. The numeric value does not imply relative weighting, but rather a numerical order of priority. B. Exposure Potential Ranking The screening method allows for an initial indication of the extent of exposure potential by considering: 1. The chemical's uses and use pattern(s) 2. Production volume as a first pass indicator of relative emission/release potential since magnitude and route (i.e. air, water, soil) of emissions is not available for all substances. 3. Persistence and bioaccumulation characteristics of the substance. Together the 3 elements are used to rank exposure potential. 1. Use Patterns The proposed approach applies the most current 2006 TSCA Inventory Update Reporting rule (IUR, now called the Chemical Data Reporting rule (CDR) data. To keep the initial prioritization simple and transparent, the approach "bins" different use patterns to align with general exposure potential - intermediates, industrial use, commercial use and consumer use. These patterns are the same as those reported in the IUR and are consistent with REACH exposure categories (intermediates, worker, professional, consumer). Chemicals with consumer product use are likely to have widespread potential for general population exposures and are given high priority ranking within the approach. For the initial prioritization approach, child specific products are captured under general consumer products and all consumer products are weighted equally (see additional discussion below under Second Tier Considerations). Intermediates will have low general population exposures, since these substances are consumed, by definition, within the workplace. Therefore, they are given the lowest priority ranking within the approach. In the context of the proposed approach, the intermediates category includes both intermediates and non-isolated intermediates. A chemical used in multiple use patterns is August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 assigned the priority of the highest use, e.g., a chemical in both industrial and commercial uses would be assigned the commercial Medium-High rank. Table 3. Use Patterns - Exposure Ranking Use Pattern Ranking Use Pattern Score Consumer High 4 Commercial Medium-High 3 Industrial Medium 2 Intermediates Low 1 The IUR Definitions of these terms are (40 CFR 710.3, 710.43): "consumer use" means the use of a chemical substance or a mixture containing a chemical substance (including as part of article) when sold to or made available to consumers for their use. "commercial use" means the use of a chemical substance or a mixture containing a chemical substance (including as part of an article) in a commercial enterprise providing saleable goods or services. "industrial use" means use at a site at which one or more chemical substances or mixtures are manufactured (including imported). "intermediate" means any chemical substance: which is intentionally removed from the equipment in which it is manufactured, and which either is consumed in whole or in part in chemical reaction(s) used for the intentional manufacture of other chemical substance(s) or mixture(s), or is intentionally present for the purpose of altering the rate of such chemical reaction(s) "non-isolated intermediate" means any intermediate that is not intentionally removed from the equipment in which is it manufactured, including the reaction vessel in which it is manufactured, equipment which is ancillary to the reaction vessel, and any equipment through which the substance passes during a continuous flow process, but not including tanks or other vessels in which the substance is stored after its manufacture. 2. Production Volume Recognizing that detailed exposure information will not be available for all substances to be screened, the proposed approach uses production volume as an indicator of exposure, which is widely used in many prioritization schemes. As production volume is just a rough surrogate of emissions, ACC suggests only very broad categories, covering about two orders of magnitude each. It may be useful to consider how additional exposure estimates may be applied in the second tier assessment. Table 4. Production Volume as Emission Surrogate - Exposure Ranking Production Volume as Emission Surrogate Ranking Volume Score >= 100,000,000 lbs national aggregate High 4 1,000,000 lbs to < 100,000,000 lbs national Medium - High 3 aggregate August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 >= 25,000 lbs to < 1,000,000 lbs national Medium 2 aggregate < 25,000 lbs (below IUR site reporting limit) Low 1 3. Persistence and Bioaccumulation Persistence and bioaccumulation are viewed as indicators of exposure, and therefore are considered under the exposure axis of the approach. A persistent substance that is emitted to the environment at the same rate as a non-persistent substance with similar partitioning properties will result in higher exposure to humans and the environment. In fact, multimedia modeling clearly indicates that environmental persistence in the compartment to which a substance partitions is a good indicator of human exposure potential (MacLeod & McKone et al. 2004). Similarly, substances that are not subject to biotransformation by higher organisms will exhibit a high bioaccumulation potential that results in higher exposures via the food chain (Arnot et al. 2010). Therefore, it is recommended to apply the proposed persistence and bioaccumulation criteria in assessment of exposure potential as described below. The persistent and bioaccumulative (P&B) criteria of the proposed approach are targeted toward organic chemicals. Separate assessment criteria are likely needed for P&B evaluation for inorganics/metals, as in the approach taken by Canada's Chemical Management Program (CMP). For assessing persistence, based upon recent expert consensus (Boethling et al., 2009) it is recommended to distinguish persistent from non-persistent chemicals using the following criteria: Volatile chemicals can be defined using a vapor pressure cut-off (i.e., > 1000 Pa) For volatile chemicals, persistent versus non-persistent chemicals are differentiated using a half-life cut-off in air (e.g., a substance is not persistent if air half life is < 2 days). For non-volatile chemicals, non-persistent substances can be defined as substances that are deemed: readily or inherently biodegradable using standard biodegradation tests (OECD 301, 302, 306 test guidelines) or SAR or read across from measured data on a related substance, show an equivalent degree of degradation (i.e. >20% in 28 days) via an abiotic degradation mechanism such as photolysis (OECD 316) or hydrolysi (OECD 111), evaluation of simulation data from transformation in soil, marine water/sediment, brackish water/sediment, surface water/sediment, oceanic water die away (e.g. OECD 308/309) have half lives below 180 days, OR if data are lacking, evaluation via BIOWIN model (EPIWEB 4) Non-volatile substances that are not biodegradable or subject to abiotic losses based on the above criteria would be considered persistent. For assessing bioaccumulation, the key question for screening is the potential for biomagnification based on recent expert consensus (Gobas et al. 2009). To determine if a substance has the potential to biomagnify the following metrics have been agreed: Trophic Magnification Factor (TMF)>1, fish Biomagnification Factor (BMF)>1 fish Bioaccumulation Factor (BAF)/Bioconcentration Factor (BCF) > 5000. These metrics can be August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 derived using lab or field measurements (where available) or recently improved computational models that are included in EPA's EPIWEB model that can be freely downloaded at www.epa.gov/oppt/exposure/pubs/episuite.htm. This approach allows all organics to be addressed and is a scientifically updated version of the approach used in Canada's CMP. Based on the above recommendations, substances can be grouped with regard to persistence and bioaccumulation as follows: Table 5. Persistence and Bioaccumulation - Exposure Ranking Persistence and P&B Ranking P&B Score Bioaccumulation Persistent and High 5 Bioaccumulative Persistent and Not Medium 3 Bioaccumulative OR Not Persistent and Bioaccumulative Not Persistent and Not Low 1 Bioaccumulative Integration of Exposure Elements: As demonstrated in the tables, each factor (use pattern, P&B, and production volume) would be assigned a numeric score based upon its ranking. All 3 factors are added to arrive at an overall value. These values are then separated into categories from low to high exposure potential. A proposed "banding" approach is illustrated in Table 6. Table 6. Integration of Exposure Rankings Combined Score - All 3 Exposure Rank Exposure Ranking elements Score 11 13 High 5 9 10 Medium High 4 7 8 Medium 3 5 6 Medium Low 2 3 4 Low 1 Overall Priority Grouping: In the overall approach, both hazard and exposure elements are considered when placing a substance in a risk-based prioritization ranking. The overall prioritization score for priority grouping and risk evaluation is based on the combined consideration of the hazard and exposure rankings. Priority Groups 7, 8, and 9 are deemed High Priority; Priority Groups 4, 5, and 6 are Medium Priority; and Priority Groups 2 and 3 are Low Priority. August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Review and Comment: It is important that screening be done in an open and transparent way and that the best available information be used. When screening for thousands of chemicals, EPA may not have access to all available information. The process should provide an opportunity for review and comment on initial rankings and an opportunity to submit additional relevant data and information to update proposed rankings with improved information. III. Second Tier Considerations: After the initial screening, some substances within individual priority groupings may require further rank ordering, particularly where a large number of chemicals are in the same priority group. Listed below are the types of information that will be useful to consider in this Second Tier rank ordering: Biomonitoring/Environmental Monitoring Data: Mere detection of chemicals in humans or the environment, i.e., "found in biomonitoring (CDC), found in water (NCOD), and found in air", while providing an indication of exposure, does not provide a useful criterion for exposure potential because almost any industrial or commercial chemical could be detected at trace levels, given increasingly sensitive analytical methods. Therefore, detection alone primarily reflects only the fact that a specific chemical was included in a measurement program. This criterion will also tend to bias the prioritization of chemicals for which well-established analytical methods are available. Consequently, this criterion is not used in the initial prioritization scheme. However, within a particular priority grouping, reliable monitoring information should be considered for Second Tier rank ordering within a quantitative process that assesses if the data is above a level of concern (i.e., places it in a risk context). Use in Children's Products: Protection of childrens' health is a top priority and, in the initial ranking, child-specific products are captured under general consumer products and all consumer products are weighted equally. The specific IUR reporting of information on chemical use in products intended for children would be considered further within a particular priority grouping for Second Tier rank ordering, noting the following points: the IUR definition is based upon use in a child specific product rather than child specific exposure potential¹ (see below). Without knowing a specific product type, it is difficult to understand if 1 IUR definition (Federal Register Volume 75, Number 156, Friday August 30, 2010, p. 49686): Intended for use by children means the chemical substance or mixture is used in or on a product that is specifically intended for use by children age 14 or younger. A chemical substance or mixture is intended for use by children when the submitter answers "yes" to at least on of the following questions for the product into which the submitter's chemical substance or mixture is incorporated: (1) Is the product commonly recognized (i.e., by a reasonable person) as being intended for children age 14 or younger? (2) Does the manufacturer of the product state through product labeling or other written materials that the product is intended for or will be used by children age 14 or younger? (3) Is the advertising, promotion, or marketing of the product aimed at children age 14 or younger? August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 potential child exposure is greater than for a non-child specific product. For example, how does child exposure to a general use cleaner compare to exposure from use in a child's raincoat. In the VCCEP assessments, there are examples for inhalation exposures where estimates of passive child exposure during adult product use exceeded conservative estimates of child exposure during active use of a child-specific product (such as a hobby product) - differences were related to the amount of product used and substance concentration within the product (MEK VCCEP Submission). the IUR definition targets children age 14 and younger. Younger children may be exposed to a variety of non-child specific products that are in general household use. Older children may be exposed to a variety of additional products. the IUR information request is targeted to manufacturers, which may not have direct knowledge of all uses, particularly the presence in products for specific subpopulations, such as children. Therefore, it is not clear that the information requested for the IUR information would be consistently available across all substances being screened. Ideally, this information should be requested from formulators of child-specific products. Therefore, for the initial prioritization approach, which represents a broad, unrefined categorization, child specific products are captured under general consumer products and all consumer products are weighted equally. The IUR information on child specific use would be utilized within a particular priority grouping for Second Tier rank ordering. If the IUR information is utilized, it is important that the limitations above be considered in its application. Emissions Data: Production volume, which is readily available for substances, is used in this proposed approach, but only serves as a surrogate for environmental emissions. For further prioritization, data or estimates of environmental emissions can be used to refine prioritization. Estimates of environmental emissions will be available for some substances (e.g., TRI data). When TRI data are utilized it should be recognized that it addresses only emissions that result from industrial and not wide dispersive uses. In other cases, emissions estimates can be developed as a percentage of production volume based upon consideration of use categories. Within a particular priority grouping, available emissions information can be considered for Second Tier rank ordering, with the understanding that emissions information is not an indicator of actual exposure. Similarly, non-isolated system intermediates, by definition, would have de minimis exposure potential. Therefore, this IUR information could be considered within a particular priority grouping for Second Tier rank ordering. International Risk Management Actions: An initial screening approach for chemical prioritization should be based upon consistent application of specific hazard and exposure science elements that define risk potential. The hazard and exposure elements should be applicable across all substances being evaluated. For initial screening, existence of international risk management action plans should not be a factor that determines priority grouping. Risk management plans may be based upon many factors, including political drivers. It is unclear how factors, their relative weighting, and the rigor of the evaluation may vary across agencies and substances. For initial screening August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 purposes, the same science-based criteria should be used to rank all substances. Consideration of existing international risk management plans could be utilized to check the functioning of the approach and could be considered within a particular priority grouping for Second Tier rank ordering with the possible effect of moving a chemical up in a grouping if actions are being taken internationally. IV. Summary ACC's prioritization approach is an example of a risk-based screening prioritization process that implements the general principles outlined at the outset of this document. It is based upon widely available information that can be utilized to understand the relative priority of chemicals for further evaluation from a risk perspective, i.e., integrating both hazard and exposure elements. Implementation of the screening framework will be most effective when utilizing the best available information. When conducting screening for thousands of chemicals, EPA may not have access to all available information. An open and iterative process that includes an opportunity for review and comment on initial rankings, together with the information that led to the result, and an opportunity to update the ranking with improved information will create a transparent and scientifically sound process. V. References Arnot, J.A., D. Mackay, T. F. Parkerton, R. T. Zaleski, C.S. Warren (2010), Multimedia modeling of human exposure to chemical substances: The roles of food web biomagnification and biotransformation, Environmental Toxicology and Chemistry 29(1):45-55. Boethling, R., K. Fenner, P. Howard, G. Klecka, T. Madsen, J.R. Snape, M.J. Whelan (2009). Environmental persistence of organic pollutants: guidance for development and review of POP risk profiles. Integrated Environmental Assessment and Management 5(4): 539 - 556. Gobas, F.A.P.C, W. de Wolf, L. P Burkhard, E. Verbruggen, K. Plotzke (2009). Revisiting Bioaccumulation Criteria for POPs and PBT Assessments Integrated Environmental Assessment and Management, 5(4):624-637. MacLeod, M., T. E. McKone (2004). Multimedia persistence as an indicator of potential for population-level intake of environmental contaminants, Environmental Toxicology and Chemistry 23(10):2465-2472. van Wijk,D., R. Chénier, T. Henry, M. D Hernando, C. Schulte (2009). Integrated Approach to PBT and POP Prioritization and Risk Assessment' Integrated Environmental Assessment and Management, 5(4):697-711. August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Proposed Prioritization Approach DRAFT May & 2011 Exposure Elements nat commental consumer 20 2 3 a 33 3 not 8 or Persuntence S not 3 mai 35 a & not 3 Pas $ 3 S the iss = the Tormages RUN $ 3 3 SUM - P8 - Tavamage ranow 3 -13 Expesure Ramking $5 Based os Sum (UN# + pa * Townage PRIORITY GROUPING - Hazard * Expasure Ramkings - 1-8 3-10 11-13 mad Jow Hazard - Highter and Human $ 3 3 & $ Human Mazard Not on Dase 3 low mai * anou % 1000 numour 3 1.8 (duet Nume " 3 & 3 8 Not 100 Acure mi os : 3 A 2000 and not data) 280 v 1000 (pas 1.0 8.0 nomour 8.3 miss Nome 3 & % x CMR Cat 2, on Dawe Call 3: 10 - 3 is # 200 50 ase Igas 0.3 1.0 0.0% - 0.2 mis forme * # $ y GMS CMR Can on OHS Clowe Clat % Repeat Close 10 § on 8 on insurticient 20 information to - - - 0.3 wis 0,00 mist on information to $ 3 a $ August 29, 2011 Source: :https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Hazard and Exposure Criteria for Prioritization Approach HAZARD EXPOSURE Environment and Human Health Classifications based upon GHS Use Elements - based upon IUR Intermediate consumed during industrial processing Envirommental: industrial (not intermediate) - used in an industrial setting From GHS classification guidance document: commercial occupational use in nonindustrial setting Table 4.1.2: scheme for substances hazardous so the aquatic environment. consumer general population residential use Clacufication Persistence: Loag-term Votalile substance (VPS 1000 Pax: Not Persistent if air half life <2 days a (Nate 2) Nonvolatile (VP < 1000 Pa): Not Persistent if: Adequate dass Adequnte voriciny dasa aux a) ready biodegradability (OBCD 301) Rapidly 3 b) inherent biodegradability (OBCD 301, 302, 306) degredable 0) read across from measured data on a related substance. 28 (Note. 3) d) equivalent degree of degradation (i.e. >20% in 28 days) via an abjotic Arute 3 Categorys Chronic 1 Categury: 1 Categasy: I degradation mechanism such as photolysis (OBCD 316) or hydrolysis (OBCD NOEC ar ECA 0.1 NOE - EC cass L 1.00 md of maid 111) and/ar BCF a 200 OR, a substance is Not Persistent if: if e) evaluation of simulation data from transformation in soil, marine water/sediment, Caregusy: Acore 2 Category: Chronic 2 Caregury: Chrumin 2 Caregusy: Chruaic 2 brackish water/sediment, surface water/sediment, oceanic water die away (e.g., OECD 3.00 s: s 10.9 0.1 - NOEC er EC. 13 0.00 <: NOEC - EC, 502 3.00 L(EXC) 10.8 and of andies 308/309) have half lives below 180 days. BCF = 500 as if K. 2 4 OR, if data are lacking: Caregusy: Arnie 3 Caregury: 3 Chrinia 3 f) evaluation via BIOWIN model (EPIWEB 4) 01 EC. : 30,00 1- 100 and fack of Bioaccomulation: stapoid andier BOF: Re 300 if absent log x 3 4 A substance is not bioaccumulative if: 4 4) a) measured TMF < 1 (field study) 3) b) measured fish BMF <1 (lab study) Ne tericity and lack of and BCF 2 500 ase, lag E 4, c) measured fish BCF < 5000 (lab study) MOECA 1 mal d) predicted BCP< 5000 using the BCFBAF model included in EPIWIN 4 The above order reflects the preference for use in decision- making NOTE -- P&B CRITERIA ARB FOR ORGANICS Tonnage - based upon JUR reporting ranges <. 25,000 lbs (below IUR site reporting limit) Human Health: 25.000 - <1 MM lbs national aggregate As above, based upon GHS 1MM - <100 MM lbs national aggregate >100 MM lbs national aggregate August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Risk-Based Prioritization Matrix Ancreasing Exposure Two-Step towest Prionies Prioritization Process Incregaling Second Tier Rank Ordering within Priority Groups Biomonitoring / Environmental Monitoring Use in Children's Products Emissions (e.g. TRI) International Risk Management Actions Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226

what is TR stands for ?

fsbn0226

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Target Risk, target risk

Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 2 USEPA APPROACH FOR EVALUATING CANCER RISHS POSED BY ORAL EXPOSURE TO 1,4-DIOXANE USEPA's Integrated Risk Information System (IRIS) published the Toxicological Review for 1,4-dioxane, in which it describes their approach and justification for deriving an oral CSF for this constituent. Below is a summary of USEPA's evaluation of available human toxicological data, weight of evidence evaluation, key study identification, critical effect selection, dose-response assessment, and the low-dose extrapolation procedure used to derive 1,4-dioxane's CSF. 2.1 USEPA's Evaluation of Evidence of Cancer in Humans USEPA evaluated the degree to which data provide evidence of carcinogenicity in humans (USEPA 2010). USEPA relied on two human occupational studies in their evaluation of potential impacts related to long-term exposure to 1,4-dioxane (Thiess et al. 1976; Buffler et al. 1978). USEPA concluded that neither study provided evidence that 1, ,4-dioxane causes cancer in humans. However, they noted "the cohort size and number of reported cases were small." 2.2 USEPA's Evaluation of Evidence of Cancer in Animal Bioassays USEPA followed its Guidelines for Carcinogen Risk Assessment (USEPA 2005) to conclude that 1,4- dioxane is "likely to be carcinogenic to humans" based on "evidence of liver carcinogenicity in several 2- year bioassays conducted in three strains of rats, two strains of mice, and in guinea pigs.' USEPA provided several reasons to justify its conclusion. For instance, USEPA concluded that the "available evidence is inadequate to establish a MOA by which 1,4-dioxane induces liver tumors in rats and mice" (USEPA 2010). Specifically, USEPA noted the "[c]onflicting data from rat and mouse bioassays (Japan Bioassay Research Center [JBRC] 1998; Kociba et al., 1974) suggest that cytotoxicity may not be a required precursor event for 1,4-dioxane-induced cell proliferation." USEPA (2010) noted that "[a]vailable data also do not clearly identify whether 1,4-dioxane or one of its metabolites is responsible for the observed effects. However, USEPA also reported that "the generally negative results for 1,4-dioxane in a number of genotoxicity assays indicates the carcinogenicity of 1,4-dioxane may not be mediated by a mutagenic MOA" (USEPA 2010). 2.3 Key Study Identification (Kano et al. 2009), Critical Effect Selection, Dose-Response Assessment, and Low-Dose Extrapolation Procedure USEPA (2010) concluded that the MOA by which 1,4-dioxane produces liver tumors is "unknown, and available evidence in support of any hypothetical mode of carcinogenic action for 1,4-dioxane is inconclusive." With this conclusion in mind, USEPA (2010) identified a 2-year drinking water study performed by Kano et al. (2009) as the key study of the oral CSF for 1,4-dioxane. Note that Kano et al. (2009) published findings originally reported by the JBRC (1990a). Although USEPA (2010) concurrently evaluated two other studies (Kociba et al. 1974; National Cancer Institute [NCI] 1978), the Kano et al. (2009) study was ultimately selected as the key study because USEPA (2010) noted that "[c]alculation of arcadis.com 3 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications a CSF for 1,4-dioxane is based upon the dose-response data for the most sensitive species and gender." The study was performed in accordance with the Organization of Economic Development's Principles for Good Laboratory Practices and involved exposing groups of rats (50 animals of each sex for each dose) and mice (50 animals of each sex for each dose) to 1,4-dioxane (>99% pure) in drinking water for 2 years. Rats were exposed to 1,4-dioxane in drinking water at 0, 200, 1,000, or 5,000 milligrams per liter (mg/L), while mice were exposed at 0, 500, 2,000, or 8,000 mg/L in drinking water. As reported by USEPA (2010): "The investigators used data from water consumption and BW [body weight] to calculate an estimate of the daily intake of 1,4-dioxane (mg/kg-day) by male and female rats and mice. Kano et al. (2009) reported a calculated mean + standard deviation for the daily doses of 1,4-dioxane for the duration of the study. Male rats received doses of approximately 0, 11+1, 55+3, or 274+18 mg/kg-day and female rats received 0, 183, 83+14, or 429+69 mg/kg-day. Male mice received doses of 0, 49+5, 191+21, or 677+74 mg/kg-day and female mice received 0, 66=10, 278+40, or 964+88 mg/kg-day." "The study by Kano et al. (2009) was used for development of an oral CSF. This was a well- designed study, conducted in both sexes in two species (rats and mice) with a sufficient number (N=50) of animals per dose group. The number of test animals allocated among three dose levels and an untreated control group was adequate, with examination of appropriate toxicological endpoints in both sexes of rats and mice. Alternative bioassays (Kociba et al., 1974; NCI, 1978) were available and were fully considered for the derivation of the oral CSF." USEPA identified increased incidence of liver adenomas or carcinomas as the critical effect in rats and mice exposed to 1,4-dioxane in the Kano et al. (2009) study. Following standard dose adjustment to a human equivalent dose using a default body weight (BW) scaling factor (USEPA 2005), USEPA performed dose-response modeling using Benchmark Dose Software and fit the suite of models available in the program to the incidence data for "either hepatocellular carcinoma or adenoma" (USEPA 2010). USEPA concluded that female mice are "more sensitive to liver carcinogenicity induced by 1,4-dioxane compared to other species or tumor types" and identified the lower 95% confidence bound on the benchmark dose associated with a 50% extra risk (benchmark response [BMR]) of developing "either hepatocellular carcinoma or adenoma" (4.95 milligrams per kilogram per day [mg/kg/d]) as the point of departure (POD) for calculating the oral CSF via linear low-dose extrapolation, as shown in Equation (1), below. USEPA (2010) again justified a linear low-dose extrapolation approach based on their conclusion that 1,4-dioxane's MOA for production of hepatic tumors in rodents is "unknown." BMR 0.5 Equation (1) CSF = = 0.1 (mg/kg/d)1 POD 4.95 mg/kg/d 2.4 Comments Provided to USEPA During External Peer Review When USEPA's IRIS program derives toxicity values, the Toxicological Review undergoes critical evaluation by individuals from within and outside the agency. A result of the outside review efforts indicated several external peer review panel members believed that available information for 1,4-dioxane could "support the use of a nonlinear extrapolation approach to estimate human carcinogenic risk" and arcadis.con 4 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications that "such an approach should be presented in the Toxicological Review.' Specifically, the USEPA (2010) notes: "[N]umerous short-term in vitro and a few in vivo tests were nonpositive for 1,4-dioxane-induced genotoxicity". Results from two-stage mouse skin tumor bioassays "suggest that a potential mode of action for 1,4- dioxane-induced tumors may involve proliferation of cells initiated spontaneously, or by some other agent, to become tumors." Additionally, a public commenter noted: "Low-dose linear extrapolation for the oral CSF is not appropriate nor justified by the data. The weight of evidence supports a threshold (nonlinear) MOA when metabolic pathway is saturated at high doses. Nonlinear extrapolations should be evaluated and presented for 1,4-dioxane." These statements indicated that some reviewers felt the toxicological data for 1,4-dioxane indicated that it may not behave in a linear manner, but rather as a threshold carcinogen. Nonetheless, USEPA (2010) ultimately concluded that there was insufficient information available to support any of the proposed MOAs and proceeded to adopt, albeit imprecisely in hindsight, the default linear low-dose extrapolation approach. arcadis.com 5 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 3 DOURSON ET AL. (2014): MODE OF ACTION (MOA) ANALYSIS FOR LIVER TUMORS FROM ORAL 1,4- DIOXANE EXPOSURES AND EVIDENCE-BASED DOSE ss RESPONSE ASSESSMENT USEPA's (2010) conclusion to evaluate 1,4-dioxane as a non-threshold, linear, low-dose extrapolation carcinogen, was "based, in part, on the following: (1) apparent uncertainty in the toxic moiety for 1,4- dioxane; and, (2) apparent lack of noncancer toxicity data from several mouse bioassays at doses that evoke tumors, or that otherwise appear to have conflicting information concerning non-neoplastic lesions in the liver of rodents exposed orally to 1,4-dioxane" (Dourson et al. 2014). Recognizing that the key studies were performed over 3 decades, Dourson et al. (2014) hypothesized that "differences in histologic approaches for quantifying and reporting non-neoplastic changes may have been responsible for the differences noted across the studies" and would account for the apparent lack of non-cancer toxicity data reported in the key mouse bioassays. In addition to directly testing this hypothesis, Dourson et al. (2014) reviewed the database of genotoxicity studies, "which included DNA replication and promotion bioassays as well as mutation, initiation, and DNA repair studies," synthesized the genotoxicity database for 1,4- dioxane, and developed and analyzed a biologically plausible MOA for the formation of hepatic tumors in rodents by employing USEPA's (2005) carcinogen guidelines. Dourson et al.'s (2014) findings from the reread of the NCI (1978) mouse bioassay histopathology slides and review of the extensive genotoxicity database demonstrates that chronic exposure to 1,4-dioxane in drinking water is associated with a non-linear mode of carcinogenic action (threshold). which is contrary to USEPA's default linear low-dose extrapolation approach (non-threshold). The cancer MOA developed by Dourson et al. (2014) also afforded new data with which to perform an improved dose-response assessment for 1,4-dioxane using toxicological endpoints that protect against 1,4-dioxane's cancer MOA (refer to Appendix A for additional details). In regards to choosing a low-dose extrapolation approach, USEPA's Guidelines for Carcinogen Risk Assessment (2005) plainly state that "[a] nonlinear approach [i.e., derivation of a reference dose or concentration] should be selected when there are sufficient data to ascertain the mode of action and conclude that it is not linear at low doses and the agent does not demonstrate mutagenic or other activity consistent with linearity at low doses.' The information presented by USEPA (2010) and supplemented by the new information from Dourson et al. (2014) shows that: (1) 1,4-dioxane causes tumors at high doses through an MOA that involves cytotoxic effects, regenerative cell proliferation, and subsequent tumor formation; (2) the effects that precede tumor formation display non-linear dose-responses; and (3) 1,4- dioxane does not cause mutations at concentrations that are not cytotoxic. As a result, the RfD of 0.05 mg/kg/d developed by Dourson et al (2014) addressed key data gaps identified by USEPA (2010) and protects against the development of liver cancers following oral exposure to 1,4-dioxane. arcadis.com 6 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 4 DOURSON ET AL. (2016 IN PEER REVIEM: UPDATED MODE OF ACTION ANALYSIS (MOA) FOR LIVER TUMORS FROM ORAL ,4-DIOXANE EXPOSURES AND EVIDENCE-BASED DOSE-RESPONSE ASSESSMENT While Dourson et al. (2014) demonstrated that a threshold-based, regenerative cell proliferation MOA accounted for the tumor findings in the NCI (1978) mouse bioassay, questions still remained about the tumor findings from a 2-year oral mouse bioassay and a 13-week precursor study reported by the JBRC (1990a,b), subsequently published as Kano et al. (2008, 2009). Similar to the NCI (1978) mouse bioassay discussed in Dourson et al. (2014), the Japanese work provided few details or findings regarding non- cancer toxicity in the mouse liver after long-term exposure to 1,4-dioxane. To address the remaining questions regarding the apparently discordant findings between the tumor MOA in mice and rats and enhance the investigation of the threshold-based MOA for hepatic tumor formation, Dourson et al. (2016 in peer review) performed a detailed evaluation of the translated Japanese rodent bioassay reports (JBRC 1990a,b) and integrated the findings with other lines of evidence for the regenerative cell proliferation MOA. This effort is summarized in Appendix B. In addition to the detailed evaluation of the JBRC (1990a,b) bioassays, Dourson et al. (2016 in peer review) also solicited opinions from several pathologists regarding the conflicting findings from the mouse bioassays. Dourson et al. (2016 in peer review) reported: "Collectively these pathology opinions support the hypothesized MOA discussed in U.S. EPA (2013) and Dourson et al. (2014) that the liver tumors from oral exposure to 1,4-dioxane occur after metabolic saturation, accumulation of the parent 1,4-dioxane molecule, liver toxicity and a regenerative hyperplasia. While additional live experimental animal testing might add confirmatory findings, a threshold for these tumors is expected if metabolism of the parent compound is not saturated, since subsequent liver toxicity does not occur." By integrating all lines of evidence, Dourson et al. (2016 in peer review) concluded: "When the many lines of evidence are taken together, the reevaluation of the Japanese studies show consistent findings in rats and consistent findings in mice other than liver histopathology not being fully recorded in the second chronic study. However, based on the number of studies conducted, the well established metabolic saturation of 1,4-dioxane metabolism in humans and experimental animals, the effects of higher dose exposures on target organ toxicity, the presence of proliferative lesions, the effect of dose and time on the progression of lesions, the time of appearance of tumors, the spectrum of tumors developed, the number and incidence of tumors at organ sites with high or low background historical incidence, and the shapes of the dose-response curve for key events and tumors, all lead to the conclusion that a regenerative hyperplasia MOA is operating with 1,4-dioxane induced liver tumors." arcadis.con 7 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 5 IMPACT OF DOURSON ET AL.S UPDATED TOXICITY ASSESSMENT ON RISK-BASED DRINKING WATER CRITERIA An agency's choice to set risk-based criteria for 1,4-dioxane based on a threshold- or non-threshold- approach has the potential to drastically impact the value of the final criterion. An example of this is provided herein based on the approach used by the New Jersey Department of Environmental Protection (NJDEP) to derive groundwater quality criteria (NJDEP 2014). The risk-based equations NJDEP uses to derive groundwater criteria for threshold and non-threshold toxicants are shown below in Equations (2) and (3), respectively, while default exposure factors are shown in Table 1 below. Using the RfD of 0.05 mg/kg/d derived from Kociba et al. (1974) by Dourson et al. (2014) to protect against a regenerative cell proliferation MOA yields a risk-based criterion of 400 g/L Using USEPA's (2010) CSF of 0.1 (mg/kg/d)-¹ yields a risk-based criterion of 0.4 (0.35) g/L, corresponding to a 1 in 1,000,000 (1x10-6) excess lifetime cancer risk. Therefore, using the toxicity value derived based on a regenerative cell proliferation MOA (RfD, threshold approach) yields a criterion that is 1,000 times higher than the value derived using USEPA's CSF approach (linear low-dose extrapolation, non-threshold). The authors of this paper conclude that sites monitoring groundwater containing 1,4-dioxane at levels below 400 g/L would meet a reasonable groundwater quality criterion that is protective of human health. RfD x BW x CF x RSC Equation (2) Criterion = x UF BW x CF Equation (3) Criterion = x IRDW arcadis.com 8 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications Table 1. Toxicity Values and NJDEP's Exposure Factors for Calculating Risk-Based Groundwater Quality Criteria Exposure Pactor Units value bource RfD mg/kg/d 0.05 Dourson et al. (2014) CSF (mg/kg/d)-1 0.1 USEPA (2010) Target risk (TR) unitless 10-6 NJDEP default BW kg 70 NJDEP default Conversion factor (CF) g/mg 1,000 NJDEP default Relative source contribution (RSC) unitless 0.2 NJDEP default Drinking water ingestion rate (IRDw) L/d 2 NJDEP default Uncertainty factor (UF) unitless 1 NJDEP default Notes: kg = kilograms L/d = liters per day g/mg = micrograms per milligram arcadis.com 9 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 6 SUMMARY AND CONCLUSIONS To support several state regulatory agencies, Dourson et al. (2016 in peer review) recently undertook additional scientific investigations to address data gaps identified in USEPA's (2010) Toxicological Review regarding 1,4-dioxane's cancer MOA and assessment approach. Collectively, Dourson et al.'s (2014, 2016 in peer review) cancer MOA evaluations and dose-response assessments addressed USEPA's uncertainties and indeed demonstrate that chronic exposure to 1,4-dioxane in drinking water is associated with a non-linear mode of carcinogenic action (threshold). These additional scientific findings provide new information that resolve 1,4- dioxane's cancer MOA and support use of a non-linear dose response approach to protect against development of cancer following low-dose oral exposures. USEPA's (2010) cancer evaluation showed that 1,4-dioxane is not mutagenic or genotoxic at non- cytotoxic doses. However, USEPA ultimately chose to use a linear low-dose extrapolation approach for estimating human cancer risk from oral exposure to 1, 4-dioxane because they concluded that the MOA for tumor formation was unknown. The recent scientific investigations by Dourson et al. (2014, 2016 in peer review) provide new information to address data gaps identified by USEPA (2010) and demonstrate that 1,4-dioxane causes liver tumors in rodents through a regenerative cell proliferation MOA. The regenerative cell proliferation MOA is characterized by: (1) metabolic saturation and accumulation of parent compound; (2) cellular swelling, hypertrophy, and liver weight increase; (3) necrosis and/or inflammation; (4) increased DNA synthesis, hyperplasia development, and foci development; and (5) development of liver adenoma and carcinomas. Specifically, 1,4-dioxane must accumulate in the liver to levels that cause inflammation and cell damage before liver tumors can form. If the first key event does not occur (metabolic saturation), then liver tumors will not form. Therefore, there is a threshold of exposure for 1,4-dioxane below which tumors do not form and it is appropriate to use a non-linear low-dose extrapolation procedure for estimating risks. The RfD of 0.05 mg/kg/d derived by Dourson et al. (2014) is protective against tumor formation through this series of events (MOA) and was calculated using USEPA's preferred methods and best available scientific practices. Using Dourson et al.'s (2014) peer-reviewed RfD, based on a regenerative cell proliferation MOA to derive a groundwater drinking water criterion results in a criterion (400 g/L) that is 1,000 times greater than the concentration derived using USEPA's default CSF approach (0.4 g/L). Based on Dourson et al.'s (2014, 2016 in peer review) studies, it is reasonable to conclude that sites that monitor groundwater containing 1,4-dioxane at levels below 400 g/L would meet a reasonable groundwater quality criteria. The recent scientific findings summarized in this report have major implications for sites that are currently or will be managing water resources impacted by 1,4-dioxane. Considering that 1,4-dioxane is emerging as a water resource contaminant, in part due to USEPA's default linear low-dose cancer evaluation approach for liver tumors in rodents (USEPA 2010), the updated toxicology evidence that 1,4-dioxane is a threshold carcinogen is significant, and suggests that many current regulatory guidelines and standards are unnecessarily low. As such, the authors of this paper conclude that sites that monitor groundwater containing 1,4-dioxane at levels below 400 g/L would meet a reasonable groundwater quality criteria that is protective of human health. arcadis.con 10 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 7 REFERENCES ARA. 2016. 1,4-Dioxane Analysis. Available on line [Accessed Dec. 19] at: http://allianceforrisk.org/riskie- 2/. Buffler, P.A., S.M. Wood, L. Suarez, and D.J. Kilian. 1978. Mortality follow-up of workers exposed to 1,4- dioxane. J Occup Environ Med, 20: 255-259. Dourson, M., J. Reichard, P. Nance, H. Burleigh-Flayer, A. Parker, M. Vincent, and E.E. McConnell. 2014. Mode of action analysis for liver tumors from oral 1,4-dioxane exposures and evidence-based dose response assessment. Regul Toxicol Pharmacol. 68: 387-401. Dourson, M., J. Higginbotham, J. Crum, H. Burleigh-Flayer P, Nance, N. Forsberg, and M. Lafranconi. 2016 in peer review. Update: Mode of Action (MOA) for Liver Tumors Induced by Oral Exposure to 1,4-Dioxane. Regul Toxicol Pharmacol. Available online at: http://allianceforrisk.org/14-dioxane- analysis/. Health Canada. 2005. Drinking Water Guidance Value for 1,4-Dioxane. August 23. JBRC. 1990a. Report of Carcinogenicity Study by Oral Administration of 1,4-Dioxane (Mixed with Water) to Rats and Mice. Japan Industrial Safety and Health Association. December 28. JBRC. 1990b. Report of Preliminary Carcinogenicity Studies (Acute, Two-Week, and Thirteen-Week Studies) by Oral Administration of ,4-Dioxane (Mixed with Water) to Rats and Mice. Japan Industrial Safety and Health Association. December 28. Kano. H., Y. Umeda, M. Saito, H. Senoh, H. Ohbayashi, S. Aiso, K. Yamazaki, K. Nagano, and S. Fukushima. 2008. Thirteen-week oral toxicity of 1,4-dioxane in rats and mice. J Toxicol Sci. 33: 141- 153. Kano, H., Y, Umeda, T. Kasai, T. Sasaki, M. Matsumoto, K. Yamazaki, K. Nagano, H. Arito, and S. Fukushima. 2009. Carcinogenicity of 1,4-dioxane administered in drinking-water to rats and mice for 2 years. Food Chem Toxicol. 47:2776 - 2784. Kociba, R.J., S.B. McCollister, C. Park, T.R. Torkelson, and P.J. Gehring. 1974. 1,4-dioxane. I. Results of a 2-year ingestion study in rats. Toxicol Appl Pharmacol, 30: 275-286. doi:10.1016/0041- 008X(74)90099-4. McConnell, G. 2013. Report on the review of liver slides from the National Cancer Institute's Bioassay of 1,4-Dioxane for Possible Carcinogenicity Conducted in 1978 (NCI, 1978). Submitted to Toxicology Excellence for Risk Assessment. January/March 2013. NCI. 1978. Bioassay of 1,4-Dioxane for possible Carcinogenicity. Carcinogenesis Testing Program, Division of Cancer Cause and Prevention, National Cancer Institute. NIH, Bethesda, MD, 78-1330. Netherlands. 1999. Risk Assessment: 1, 4-Dioxane. Netherlands Organization for Applied Scientific Research (TNO) and the National Institute of Public Health and the Environment (RIVM). Chemical Substances Bureau, Ministry of Housing, Spatial Planning and the Environment (VROM), Netherlands, Final Version, 5 November, EINECS-No.: 204-661-8. arcadis.con 11 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications Neumann, H.G., H.W. Thielmann, J.G. Filser, H.P. Gelbke, H. Griem, H. Kappus, K.H. Norpoth, U. Reuter, S. Vamvakas, P. Wardenbach, and H.E. Wichmann. 1977. Proposed changes in the classification of carcinogenic chemicals in the work area. Reg. Toxicol. Pharmacol., 26:288-295. National Industrial Chemicals Notification and Assessment Scheme (NICNAS). 1998. Priority Existing Chemical Assessment Reports: 1,4-dioxane. Sydney, Australia: Australia Department of Health and Ageing. June. Available online at: NJDEP. 2014. Ground Water Quality Standards. N.J.A.C 7:9C. Available online at: http://www.nj.gov/dep/rules/rules/njac7_9c.pd Office of Environmental Health Hazard Assessment (OEHHA). 2002. Air Toxics Hot Spots Program. Risk Assessment Guidelines. Part II. Technical Support Document for Describing Available Cancer Potency Factors. Office of Environmental Health Hazard Assessment, California Environmental Protection Agency. December. Stickney, J.A., S.L. Sager, J.R. Clarkson, L.A. Smith, B.J. Locey, M.J. Bock, R. Hartung, and S.F. Olp. 2003. An updated evaluation of the carcinogenic potential of 1,4-dioxane. Regul Toxicol Pharmacol. 38(2):183-95. Thiess, A.M., E. Tress, and I. Fleig. 1976. Arbeitsmedizinische Untersuchungsergebnisse von Dioxan- exponierten Mitarbeitern [Industrial-medica investigation results in the case of workers exposed to dioxane]. Arbeitsmedizin, Sozialmedizin, Umweltmedizin, 11: 35-46. USEPA. 2005. Guidelines for carcinogen risk assessment, final report. EPA/630/P-03/001F. Risk Assessment Forum; U.S. Environmental Protection Agency. Washington, DC. March. USEPA. 2010. Toxicological Review of 1,4-Dioxane (CAS No. 123-91-1). EPA/635-R-09-005-F. Washington, D.C. August. USEPA. 2011. Recommended Use of Body Weight3/4 as the Default Method in Derivation of the Oral Reference Dose. EPA/100/R11/0001. Risk Assessment Forum. Washington, DC. USEPA. 2012. Benchmark Dose Technical Guidance. EPA/100/R-12/001. Risk Assessment Forum. Washington, DC. June 12. USEPA. 2013. Toxicological review of 1,4- Dioxane (with inhalation update) (CAS No. 123-91-1) in support of summary information on the Integrated Risk Information System (IRIS) [EPA Report]. (EPA-635/R-11/003-F). Washington, DC. USEPA. 2016a. Drinking Water Contaminant Candidate List 4 - Final. Federal Register Notice, Volume 81, No. 2222, Thursday, November 17. USEPA. 2016b. The Third Unregulated Contaminant Monitoring Rule (UCMR 3): Data Summary, July 2016. Office of Water (MS-140). EPA 815-S-16-004, Available at: USEPA. 2016c. Conducting a Human Health Risk Assessment, Dose-Response. Available at: arcadis.com 12 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 APPENDIX A Mode of Action Analysis for Liver Tumors Based on NCI Siide Reread and RfD Derivation (Dourson et al. 2014) Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 ARCADIS Gesign & for natural and built assets Appendix A MODE OF ACTION ANALYSIS FOR LIVER TUMORS BASED ON NCI SLIDE REREAD AND RFD DERIVATION (DOURSON ET AL. 2014) January 2017 Source: :ttps://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) CONTENTS Acronyms and Abbreviations ii 1 Reread of NCI (1978) Histopathology Slides and Mode of Action Evaluation for Hepatic Tumors in Mice 3 1.1 Review of 1,4-Dioxane's Genotoxicity Database 4 1.2 Mode of Action Analysis 4 1.2.1 Key Event 1: Accumulation of Parent Compound 5 1.2.2 Key Event 2: Liver Cell Hypertrophy and Necrosis 5 1.2.3 Key Event 3: DNA Synthesis 5 1.2.4 Key Event 4: Regenerative Cell Proliferation 5 1.2.5 Key Event 5: Promotion of Endogenously Initiated Tumors 6 1.3 Updated Dose-Response Assessment and Reference Dose Derivation for 1,4-Dioxane 6 2 References 8 arcadis.com i Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) ACRONYMS AND ABBREVIATIONS BMD benchmark dose-modeling CUF composite uncertainty factor EPL Experimental Pathology Laboratories JBRC Japan Bioassay Research Center mg/kg/d milligrams per kilogram body weight per day MOA mode of action NCI National Cancer Institute NOAEL no-observable-adverse-effect level POD point of departure RfD oral reference dose g/L micrograms per liter USEPA United States Environmental Protection Agency arcadis.com ii Source: https://wwww.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) 1 REREAD OF NCI (1978) HISTOPATHOLOGY SLIDES AND MODE OF ACTION EVALUATION FOR HEPATIC TUMORS IN MICE To test their hypothesis and better understand the "sequence of events that maybe have contributed to the MOA of the observed liver tumors," Dourson et al. (2014) and McConnell (2013) performed a blinded reread of the mouse National Cancer Institute (NCI) (1978) liver histopathology slides, because that study did not report non-neoplastic lesions in livers of the high-dose group. Note this is one of the two long-term oral mouse bioassays that exist for 1,4-dioxane; the other chronic mouse bioassay was performed by the Japan Bioassay Research Center (JBRC) and is reported most recently by Kano et al. (2009). As noted by Dourson et al. (2014): "Because terminology and practices for reporting liver lesions has changed since the time of the NCI study (1978), and because EPA (2005) is focusing more on an understanding of a chemical's Mode of Action (MOA) prior to any determination of its dose response, a re-review of the liver slides of mice from the NCI study (1978) was performed. This reanalysis was performed at the Experimental Pathology Laboratories (EPL), Research Triangle Park, NC during September through November 2012. The objective of the slide review was to determine if any non-neoplastic lesions in the liver were present in an effort to understand the sequence of events that may have contributed to the MOA of the observed liver tumors in mice. Another reason for the slide review was because at the time of the original slide review (i.e., 1978) the NCI typically recorded only the most severe diagnosis on a given slide, (e.g., adenoma or carcinoma). During this timeframe, the focus of cancer bioassays was to determine the potential carcinogenic activity of the chemical, not its potential chronic toxicity. For example, if an adenoma, carcinoma, and evidence of chronic toxicity (e.g., hepatocellular hypertrophy), were all present on a given slide, only the tumor response was typically recorded. Thus, it was unclear whether non-neoplastic lesions were present in the livers of mice but were not recorded in the NCI carcinogenicity study. McConnell's (2013) reread of the NCI (1978) mouse liver histopathology slides and Dourson et al.'s (2014) summary report demonstrate that chronic exposure to 1,4-dioxane in drinking water is associated with a non-linear mode of carcinogenic action (contrary to the United States Environmental Protection Agency's [USEPA's] low-dose extrapolation conclusion) based on several hepatotoxic effects that preceded tumor formation, including: Dose-dependent hepatocellular glycogen depletion Dose-dependent hepatocellular hypotrophy Dose-related hepatocellular necrosis Dose-dependent hepatocellular inflammation associated with necrosis Dose-related hyperplasia in several non-neoplastic cell types arcadis.com 3 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) Dourson et al. (2014) states: "The appearance of the liver toxicity follows the pattern where glycogen depletion occurs either concurrently with, or preceding, hypertrophy in both sexes. This was followed closely by necrosis and inflammation in males, but a high control incidence of necrosis and inflammation clouded this overall pattern found in females In terms of dose-response behavior, hypertrophy preceded the formation of foci, which appeared to precede formation of tumors. This pattern was also evident in an individual animal analysis." 1.1 Review of ,4-Dioxane's Genotoxicity Database As a component of their mode of action (MOA) analysis, Dourson et al. (2014) reviewed 1,4-dioxane's genotoxicity database using the information presented in USEPA's (2010) Toxicological Review for 1,4- dioxane. Dourson et al. (2014) noted: '1,4-dioxane has been tested for genotoxicity using in vitro assay systems with prokaryotic organisms, non-mammalian eukaryotic organisms, and mammalian cells, both with and without metabolic activation.' "[A]II fifteen mutagenicity tests reported (8 without activation and 7 with metabolic activation) were negative." "22 in vitro genotoxicity assays, and 9 in vivo genotoxicity assays were negative." "Eight genotoxicity assays were noted to be positive but only at high or noted cytotoxic doses." Based on their review of 1,4-dioxane's genotoxicity database, Dourson et al. (2014) states "1,4-dioxane does not cause point mutations, DNA repair, or [tumor] initiation" when administered at non-cytotoxic doses, which is in general agreement with USEPA's conclusions (USEPA 2010). The authors noted their conclusions were similar to USEPA's, but differ in that "if mutations are caused by 1,4-dioxane, it is only at high cytotoxic doses." The authors concluded: "1,4-dioxane does not cause mutagenicity as evidenced by uniformly negative results in standard in vitro and in vivo genotoxicity bioassays at levels that are not overtly toxic, but it may be a clastogen in vivo, in light of the mixed results in the micronucleus assays. It follows that mutations needed for tumor formation are then likely from the known endogenously available pool of mutations, and that a regenerative hyperplasia evokes more of these endogenous mutations to form tumors. Mutation potentially caused by 1,4-dioxane at high doses is precluded as a key event in tumor formation." 1.2 Mode of Action Analysis Dourson et al. (2014) proposed five key events in the non-mutagenic MOA resulting in hepatic tumors in rodents; they include: "(1) accumulation of parent compound [at concentrations that saturate metabolic processes], (2) liver cell hypertrophy and necrosis, (3) DNA synthesis, (4) regenerative cell proliferation, and (5) promotion of endogenously-initiated tumors.' The regenerative cell proliferation MOA has a threshold below which hepatic tumors are not formed. Evidence supporting each key event is presented below. arcadis.com 4 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) 1.2.1 Key Event 1: Accumulation of Parent Compound "Humans, rats, and mice extensively metabolize 1,4-dioxane.' "[M]etabolism is a capacity-limited process." "When dose of 1,4-dioxane approaches or exceeds the metabolizing capacity, the unmetabolized fraction of the dose increases and target organ toxicity occurs." "Thus, there appears to be a threshold below which metabolism and elimination are rapid and with less or perhaps without toxicological effects." "Human environmental exposures to 1,4-dioxane are unlikely to approach doses that saturate metabolizing enzymes and which produce liver and nasal tumors in rats." "Hence, since humans, like rats, efficiently metabolize 1,4-dioxane at low doses, enzyme saturation is negligible at low exposure levels." 1.2.2 Key Event 2: Liver Cell Hypertrophy and Necrosis "Liver cell hypertrophy and necrosis are key events in the 1,4-dioxane MOA leading to regenerative cell proliferation and, with chronic exposures, liver tumors.' "Liver changes including centrilobular swelling, single cell necrosis coincide exclusively with saturating doses of 1,4-dioxane and occur in as little as 11 weeks." "Evidence of hepatocellular damage preceding evidence of hepatocellular tumors caused by higher doses of 1,4-dioxane has been provided by several studies." 1.2.3 Key Event 3: DNA Synthesis USEPA (2010) reported "that 1,4-dioxane does not cause DNA repair activity in five standard in vitro and in vivo bioassays that tested for the presence of DNA repair in various model systems." "Conversely, 1,4-dioxane does cause DNA replication as evidenced by in vitro bioassays in rat hepatocytes" "DNA synthesis appears to be a key event for a regenerative cell proliferation and/or tumor promotion and can occur in either the presence or absence of cytotoxicity." "DNA synthesis provides evidence that 1,4-dioxane promotes cell proliferation through cytotoxicity." 1.2.4 Key Event 4: Regenerative Cell Proliferation "Dose-response and temporal data support the occurrence of cell proliferation and hyperplasia prior to the development of liver tumors in the rat model." "Cell proliferation appears to be an early response with significant changes (1.5- to 2-fold) occurring in rats with as little as 2 weeks of exposure." arcadis.com 5 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) "Given time, proliferative changes manifest as pre-neoplastic foci in studies where the histopathology of such changes are reported." 1.2.5 Key Event 5: Promotion of Endogenously Initiated Tumors "Three studies relevant to tumor initiation and promotion establish that 1,4-dioxane does not cause initiation in standard in vivo bioassays, in agreement with the absence of observed mutagenic or genotoxic activity." "[T]umor promotion was associated with significant toxicity in rats when administered by either dermal or oral routes." 1.3 Updated Dose-Response Assessment and Reference Dose Derivation for 1,4-Dioxane Dourson et al. (2014) and USEPA (2010) both relied on the dose-response data reported by Kociba et al. (1974). This study provided data for liver and kidney degeneration and necrosis in 6- to 8-week-old male and female Sherman rats (60/sex/dose group) that were exposed to 1, ,4-dioxane at 0, 0.01, 0.1, or 1% (i.e., 9.6, 94, and 1,015 milligrams per kilogram body weight per day [mg/kg/d] and 19, 148, and 1,599 mg/kg/d for males and females, respectively) in drinking water for up to 716 days. The study reported a no-observed-adverse-effect level (NOAEL) of 9.6 mg/kg/d and provides "the most sensitive measure of adverse effects by 1,4-dioxane" (USEPA 2010). USEPA's Toxicological Review for 1,4-dioxane (USEPA 2010) provides a reference dose (RfD) of 0.03 mg/kg/d. This RfD was derived using the NOAEL of 9.6 mg/kg/d for liver and kidney degeneration and necrosis in rats reported by Kociba et al. (1974) as the point of departure (POD), in combination with a composite uncertainty factor (CUF) of 300 (10 for interspecies extrapolation, 10 for intraspecies extrapolation, and 3 for database deficiencies associated with the lack of a multigenerational reproductive toxicity study). The lowest-observable-adverse-effect level for this study was 94 mg/kg/d (USEPA 2010). USEPA derived the RfD using the NOAEL reported by Kociba et al. (1974) because the published study did not report incidence data for these effects, and therefore, they were unable to perform benchmark dose-modeling (BMD). Alternatively, Dourson et al. (2014) reported an updated RfD of 0.05 mg/kg/d that was derived using incidence data (laboratory report for the published study was provided to Dourson et al. [2014] by The Dow Chemical Company) for hepatocellular necrosis (combined across sexes) and USEPA's preferred approaches¹. Specifically, Dourson et al. (2014) utilized USEPA's preferred BMD approach (USEPA 2012) to derive a POD of 20 mg/kg/d (95% lower bound on the dose associated with a 10% extra risk), USEPA's preferred default bodyweight scaling factor (USEPA 2011), to estimate a human equivalent 1 USEPA (2010) used the NOAEL from Kociba et al. (1974) based on liver and kidney degeneration to derive the RfD, specifically because Kociba et al. (1974) did not provide quantitative incidence or severity data for liver and kidney degeneration and necrosis. However, when appropriate data are available, USEPA prefers using BMD to define the POD (USEPA 2012). Had the incidence data from Kociba et al. (1974) been available at the time of their review, USEPA would have used it to derive a benchmark dose to use as the POD for setting the RfD. arcadis.com 6 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) dose, in combination with a CUF of 100 (3 for interspecies toxicodynamic extrapolation, 10 for intraspecies extrapolation, and 3 due to the lack of a 2-generation reproductive study) to derive an RfD of 0.05 mg/kg/d. Dourson et al. (2014) concluded that "the choice of this endpoint [hepatocellular necrosis] is protective, since liver toxicity, resulting in liver tumors, is the clear apical effect of greatest intensity in the available array of toxic effects." Dourson et al. (2014) calculated their RfD using standard approaches, as shown in Equation (1), below: POD 20 mg/kg/d Equation (1) RfD = = 0.05 mg/kg/d CUF 3x10x3 arcadis.com 7 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) 2 REFERENCES Dourson, M., J. Reichard, P. Nance, H. Burleigh-Flayer, A. Parker, M. Vincent, and E.E. McConnell. 2014. Mode of action analysis for liver tumors from oral 1,4-dioxane exposures and evidence-based dose response assessment. Regul Toxicol Pharmacol. 68: 387-401. Kano, H., Y, Umeda, T. Kasai, T. Sasaki, M. Matsumoto, K. Yamazaki, K. Nagano, H. Arito, and S. Fukushima. 2009. Carcinogenicity of 1,4-dioxane administered in drinking-water to rats and mice for 2 years. Food Chem Toxicol. 47:2776 - 2784. Kociba, R.J., S.B. McCollister, C. Park, T.R. Torkelson, and P.J. Gehring. 1974. 1,4-dioxane. I. Results of a 2-year ingestion study in rats. Toxicol Appl Pharmacol, 30: 275-286. oi:10.1016/0041- 008X(74)90099-4. McConnell, G. 2013. Report on the review of liver slides from the National Cancer Institute's Bioassay of 1,4-Dioxane for Possible Carcinogenicity Conducted in 1978 (NCI, 1978). Submitted to Toxicology Excellence for Risk Assessment. January/March 2013. NCI. 1978. Bioassay of 1,4-Dioxane for possible Carcinogenicity. Carcinogenesis Testing Program, Division of Cancer Cause and Prevention, National Cancer Institute. NIH, Bethesda, MD, 78-1330. USEPA. 2005. Guidelines for carcinogen risk assessment, final report. EPA/630/P-03/001F. Risk Assessment Forum; U.S. Environmental Protection Agency. Washington, DC. March. USEPA. 2010. Toxicological Review of 1,4-Dioxane (CAS No. 123-91-1). EPA/635-R-09-005-F. Washington, D.C. August. USEPA. 2012. Benchmark Dose Technical Guidance. EPA/100/R-12/001. Risk Assessment Forum. Washington, DC. June 12. arcadis.com 8 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 APPENDIX B Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) Source: https://www.industrydocuments.ucsf,edu/docs/fsbn0226 ARCADIS Desion & for natural and built assets Appendix B MODE OF ACTION ANALYSIS FOR LIVER TUMORS BASED ON JBRC REVIEW (DOURSONETAL.2016IN PEER REVIEW) January 2017 Source: :ttps://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) CONTENTS Acronyms and Abbreviations ii 1 Findings from Detailed Review of JBRC Rat Bioassays 3 1.1 Findings from Detailed Review of JBRC Mouse Bioassays 3 1.2 Integration of Evidence Supporting Regenerative Cell Proliferation MOA for 1,4-Dioxane 4 2 References 6 TABLES Table 1. Integration and Comparison of Rat and Mouse Bioassay Data (Adapted from Dourson et al., 2016 in peer review) 5 arcadis.com i Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) ACRONYMS AND ABEREVIATIONS JBRC Japan Bioassay Research Center mg/kg/d milligrams per kilogram body weight per day MOA mode of action NCI National Cancer Institute arcadis.com ii Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) 1 FINDINGS FROM DETAILED REVIEW OF JBRC RAT BIOASSAYS Changes in the liver found in the Japan Bioassay Research Center (JBRC) rat bioassays provide strong evidence that hepatic tumors were modulated by a threshold-based regenerative cell proliferation mode of action (MOA). Dourson et al. (2016 in peer review) found that effects observed in rats were in the expected dose-sequence for a regenerative cell proliferation MOA. Specifically, Dourson et al. (2016 in peer review) observed the following sequence of effects: Dose: 42-55 milligrams per kilogram body weight per day (mg/kg/d) - Effect: Liver swelling, hypertrophy, and liver weight increase Dose: 94-219 mg/kg/d - Effect: Necrosis Dose: 55-389 mg/kg/d - Effect: Hyperplasia and foci development Dose: >200 mg/kg/d - Effect: Increased levels of enzymes associated with liver damage Dose: 274-1015 mg/kg/d - Effect: Adenomas and carcinomas 1.1 Findings from Detailed Review of JBRC Mouse Bioassays Dourson et al. (2016 in peer review) observed the following sequence of effects in the JBRC (1990a) mouse bioassays: Dose: 190-200 mg/kg/d - Effect: Liver swelling, hypertrophy, and liver weight increase Dose: 190-200 mg/kg/d - Effect: Necrosis Dose: Not reported - Effect: Hyperplasia and foci development not reported Dose: 200 mg/kg/d - Effect: Increased levels of enzymes associated with liver damage Dose: 66-964 mg/kg/d - Effect: Adenomas and carcinomas, females Surprisingly, effects in the liver found in the JBRC mouse bioassays conflict with those clearly reported by Dourson et al. (2014) and McConnell (2013) for the reread of the National Cancer Institute (NCI) (1978) mouse bioassay histopathology slides. Additionally, the progression of effects reported by JBRC for the 2- year chronic study is inconsistent with enzymatic changes indicative of liver damage noted in the same study, as well as findings from a 13-week precursor study performed by the same laboratory. As noted by Dourson et al. (2016 in peer review), "the lack of noncancer histopathology in the chronic mouse study is not consistent with the changes in liver enzymes in this same chronic study, nor is this lack of noncancer arcadis.com 3 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) findings expected based on the histopathology of the precursor 13-week study" and "[n]or does the tumor response in the low dose female mice of JBRC (1990a) match the tumor findings in the McConnell (2013) re-read of NCI (1978). Dourson et al. (2016 in peer review) hypothesized that differences in mouse bioassay results between JBRC and McConnell (2013) may be due to differences in the interpretation of the histopathological data, and provided the following quote from JBRC (Kano et al. 2009) to substantiate their claim: "The hepatic hyperplasia of rats and mice diagnosed in the previous report (Yamazaki et al., 1994) [authors note: which was a presentation of the JBRC, 1990a] was re-examined histopathologically and changed to hepatocellular adenomas and altered hepatocellular foci including acidophilic, basophilic and clear cell foci in the present studies, according to the current diagnostic criteria of liver lesions in rats and mice." Unfortunately, slides from the original JBRC (1990a,b) bioassays were not available; therefore, the JBRC slides could not be reread as they were by McConnell (2013) for the NCI (1978) mouse liver slides. Additionally, JBRC did not archive sufficient numbers of pictures of histopathology slides to resolve the issue. While, it is impossible to know for sure from this dataset whether liver tumors formed prior to or following cytotoxic effects, the weight of evidence from the JBRC and NCI mouse bioassays supports a regenerative cell proliferation MOA. 1.2 Integration of Evidence Supporting Regenerative Cell Proliferation MOA for 1,4-Dioxane Following integration of key events from seven rat bioassays, three mouse bioassays, and 1,4-dioxane's genotoxicity profile, presented in Table 1 below, Dourson et al. (2016 in peer review) showed that 1,4- dioxane's toxicological database supports a threshold-based regenerative cell proliferation MOA for tumor formation in livers of rodents orally exposed to 1,4-dioxane. The authors reported that bioassay data for rats leads to the conclusion that "rat liver tumors are evoked by a regenerative hyperplasia," while the authors concluded the "sequence of events from two chronic mouse studies and a subchronic mouse study generally support the hypothesized regenerative hyperplasia MOA" (Dourson et al. 2016 in peer review). In regards to the conflicting mouse bioassay data (McConnell 2013; Dourson et al. 2014; JBRC 1990a), the difference is likely due in part to changes in the terminology and practices used for recording the liver lesions reported by Kano et al. (2009). arcadis.com 4 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226

what is the p&B ranking for not persistent and not bioaccumulative

jzbn0226

jzbn0226_p28, jzbn0226_p29, jzbn0226_p30, jzbn0226_p31, jzbn0226_p32, jzbn0226_p33, jzbn0226_p34, jzbn0226_p35, jzbn0226_p36, jzbn0226_p37, jzbn0226_p38, jzbn0226_p39

Low, low

endpoints, criteria are similarly available for both acute and chronic classification. The use of one common system allows for appropriate assessment of all substances. GHS classification information is readily available for all substances, as U.S. manufacturers have developed GHS classifications for their products to meet international requirements. ACC's support of the GHS criteria for purposes of this prioritization tool is not a categorical endorsement of the GHS criteria for any other purpose. ACC has been an active participant in the development of GHS and supports the system in principle. The GHS has not been broadly implemented to date in the U.S., although the Occupational Safety and Health Administration (OSHA) has indicated an intent to publish a regulation applying GHS in the workplace. ACC's December 29, 2009, comments on OSHA's proposed rule to modify the existing Hazard Communication Standard (HCS) to reflect the GHS urged that implementation of the GHS adhere to certain principles (e.g., continued application of the "Building Block Approach" of the Purple Book). ACC made specific recommendations concerning details of the Hazard Classification definitions, cut-off values, among others. ACC stands behind those comments. In ACC's view, the use of GHS criteria in a screening-level prioritization of chemicals can materially assist in determining which chemicals receive additional evaluation by the Environmental Protection Agency, but does not necessarily preclude the use of other appropriate, applicable criteria developed under other systems. To classify a chemical in a hazard based priority ranking where there is not direct data on the chemical, EPA can employ the full range of approaches, such as QSAR, SAR, read- across and other modeling tools in which EPA has confidence based on molecular structure. In those situations where there still remains insufficient information on either environmental or human health hazards, the chemical would be classified as "high" for its environmental or health ranking. 1. Environmental Ranking Table 1 provides a summary of how GHS criteria could be logically used for chemical management prioritization. Table 1. Environmental Safety - Hazard Ranking GHS Classification - Ranking Environmental Rank Environmental Score Acute I or Chronic I or Insufficient Information to High 4 Classify Acute II or Chronic II Medium High 3 Acute III or Chronic III/IV or Medium 2 none Not classified Low 1 August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 2. Human Health Ranking Table 2. Human Health - Hazard Ranking Health Rank GHS Classification - Human Health Ranking Score GHS CMR Cat 1a, 1b; OR Repeat Dose </= 10 mg/kg/day (oral); </= 20 mg/kg/day (dermal); </= 50 ppm/6hr/day (gas inhalation); High 4 <<= 0.2 mg/1/6h/day (vapour inhalation); </= 0.02 mg/l/6h/day (dust mist fume inhal). OR insufficient information to classify GHS CMR Cat 2; OR Repeat Dose 10 - 100 mg/kg/day (oral); 20 - 200 mg/kg/day (dermal); Medium High 50 - 250 ppm/6hr/day (gas inhalation); 3 0.2 - 1.0 mg/l/6h/day (vapour inhalation); 0.02 - 0.2 mg/l/6h/day (dust mist fume inhal). Not carcinogen/mutagen/repro/develop;OR Repeat Dose 100 - 1000 mg/kg/day (oral); 200 - 2000 mg/kg/day (dermal); Medium 250 - 1000 ppm/6hr/day (gas inhalation); 2 1.0 - 5.0 mg/l/6h/day (vapour inhalation); 0.2 - 1.0 mg/l/6h/day (dust mist fume inhal). Not carcinogen/mutagen/repro/develop; OR Repeat Dose >1000 mg/kg/day (oral); > 2000 mg/kg/day (dermal); Low > 1000 ppm/6hr/day (gas inhalation); 1 >5.0 mg/l/6h/day (vapour inhalation); > 1.0 mg/l/6h/day (dust mist fume inhal). It is important to note that specific concerns about children's health (specifically potential hazards and adverse effects on the nervous system) and those caused by endocrine disruption mechanisms are addressed in this prioritization process: The GHS CMR "R" classification includes specific evaluation of effects on development in utero and upon growth, maturation and reproduction. ("R" stands for reproductive toxicity and includes adverse effects on sexual function and fertility, as well as developmental toxicity in offspring). Endocrine activity is not a distinct toxicological hazard per se, but rather a measure of a compound's ability to interact with components of the endocrine system. The prioritization process evaluates data and information on relevant apical tests, including tests for reproduction and developmental toxicity (potential endocrine pathways). Thus, even if specific August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 screening for potential endocrine activity has not yet been conducted on certain compounds, hazard identification based on observable outcomes from apical toxicity tests (e.g., outcomes such as pathologic states indicative of disease conditions) covers all modes of action, including endocrine pathways. The toxicity information evaluated (CMR and repeat dose toxicity) is directly relevant to evaluating potential hazards to all individuals, including children. Such data typically includes: 1) identification and definition of possible hazards upon all major organ systems from both acute and repeated exposures, including the nervous system; 2) detection of potential hazards arising from in utero exposures, including possible effects on the nervous system; 3) evaluation of potential of a substance to affect reproduction; and 4) evaluation of the potential of a substance to damage DNA. Integration of Hazard Elements: Each of the environmental and human health classifications is assigned a numeric value based upon its ranking, with 1 being the lowest value and 4 the highest. The greatest ranking (highest hazard potential score) of either Environmental or Human Health is used in a substance- specific priority ranking. The numeric value does not imply relative weighting, but rather a numerical order of priority. B. Exposure Potential Ranking The screening method allows for an initial indication of the extent of exposure potential by considering: 1. The chemical's uses and use pattern(s) 2. Production volume as a first pass indicator of relative emission/release potential since magnitude and route (i.e. air, water, soil) of emissions is not available for all substances. 3. Persistence and bioaccumulation characteristics of the substance. Together the 3 elements are used to rank exposure potential. 1. Use Patterns The proposed approach applies the most current 2006 TSCA Inventory Update Reporting rule (IUR, now called the Chemical Data Reporting rule (CDR) data. To keep the initial prioritization simple and transparent, the approach "bins" different use patterns to align with general exposure potential - intermediates, industrial use, commercial use and consumer use. These patterns are the same as those reported in the IUR and are consistent with REACH exposure categories (intermediates, worker, professional, consumer). Chemicals with consumer product use are likely to have widespread potential for general population exposures and are given high priority ranking within the approach. For the initial prioritization approach, child specific products are captured under general consumer products and all consumer products are weighted equally (see additional discussion below under Second Tier Considerations). Intermediates will have low general population exposures, since these substances are consumed, by definition, within the workplace. Therefore, they are given the lowest priority ranking within the approach. In the context of the proposed approach, the intermediates category includes both intermediates and non-isolated intermediates. A chemical used in multiple use patterns is August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 assigned the priority of the highest use, e.g., a chemical in both industrial and commercial uses would be assigned the commercial Medium-High rank. Table 3. Use Patterns - Exposure Ranking Use Pattern Ranking Use Pattern Score Consumer High 4 Commercial Medium-High 3 Industrial Medium 2 Intermediates Low 1 The IUR Definitions of these terms are (40 CFR 710.3, 710.43): "consumer use" means the use of a chemical substance or a mixture containing a chemical substance (including as part of article) when sold to or made available to consumers for their use. "commercial use" means the use of a chemical substance or a mixture containing a chemical substance (including as part of an article) in a commercial enterprise providing saleable goods or services. "industrial use" means use at a site at which one or more chemical substances or mixtures are manufactured (including imported). "intermediate" means any chemical substance: which is intentionally removed from the equipment in which it is manufactured, and which either is consumed in whole or in part in chemical reaction(s) used for the intentional manufacture of other chemical substance(s) or mixture(s), or is intentionally present for the purpose of altering the rate of such chemical reaction(s) "non-isolated intermediate" means any intermediate that is not intentionally removed from the equipment in which is it manufactured, including the reaction vessel in which it is manufactured, equipment which is ancillary to the reaction vessel, and any equipment through which the substance passes during a continuous flow process, but not including tanks or other vessels in which the substance is stored after its manufacture. 2. Production Volume Recognizing that detailed exposure information will not be available for all substances to be screened, the proposed approach uses production volume as an indicator of exposure, which is widely used in many prioritization schemes. As production volume is just a rough surrogate of emissions, ACC suggests only very broad categories, covering about two orders of magnitude each. It may be useful to consider how additional exposure estimates may be applied in the second tier assessment. Table 4. Production Volume as Emission Surrogate - Exposure Ranking Production Volume as Emission Surrogate Ranking Volume Score >= 100,000,000 lbs national aggregate High 4 1,000,000 lbs to < 100,000,000 lbs national Medium - High 3 aggregate August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 >= 25,000 lbs to < 1,000,000 lbs national Medium 2 aggregate < 25,000 lbs (below IUR site reporting limit) Low 1 3. Persistence and Bioaccumulation Persistence and bioaccumulation are viewed as indicators of exposure, and therefore are considered under the exposure axis of the approach. A persistent substance that is emitted to the environment at the same rate as a non-persistent substance with similar partitioning properties will result in higher exposure to humans and the environment. In fact, multimedia modeling clearly indicates that environmental persistence in the compartment to which a substance partitions is a good indicator of human exposure potential (MacLeod & McKone et al. 2004). Similarly, substances that are not subject to biotransformation by higher organisms will exhibit a high bioaccumulation potential that results in higher exposures via the food chain (Arnot et al. 2010). Therefore, it is recommended to apply the proposed persistence and bioaccumulation criteria in assessment of exposure potential as described below. The persistent and bioaccumulative (P&B) criteria of the proposed approach are targeted toward organic chemicals. Separate assessment criteria are likely needed for P&B evaluation for inorganics/metals, as in the approach taken by Canada's Chemical Management Program (CMP). For assessing persistence, based upon recent expert consensus (Boethling et al., 2009) it is recommended to distinguish persistent from non-persistent chemicals using the following criteria: Volatile chemicals can be defined using a vapor pressure cut-off (i.e., > 1000 Pa) For volatile chemicals, persistent versus non-persistent chemicals are differentiated using a half-life cut-off in air (e.g., a substance is not persistent if air half life is < 2 days). For non-volatile chemicals, non-persistent substances can be defined as substances that are deemed: readily or inherently biodegradable using standard biodegradation tests (OECD 301, 302, 306 test guidelines) or SAR or read across from measured data on a related substance, show an equivalent degree of degradation (i.e. >20% in 28 days) via an abiotic degradation mechanism such as photolysis (OECD 316) or hydrolysi (OECD 111), evaluation of simulation data from transformation in soil, marine water/sediment, brackish water/sediment, surface water/sediment, oceanic water die away (e.g. OECD 308/309) have half lives below 180 days, OR if data are lacking, evaluation via BIOWIN model (EPIWEB 4) Non-volatile substances that are not biodegradable or subject to abiotic losses based on the above criteria would be considered persistent. For assessing bioaccumulation, the key question for screening is the potential for biomagnification based on recent expert consensus (Gobas et al. 2009). To determine if a substance has the potential to biomagnify the following metrics have been agreed: Trophic Magnification Factor (TMF)>1, fish Biomagnification Factor (BMF)>1 fish Bioaccumulation Factor (BAF)/Bioconcentration Factor (BCF) > 5000. These metrics can be August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 derived using lab or field measurements (where available) or recently improved computational models that are included in EPA's EPIWEB model that can be freely downloaded at www.epa.gov/oppt/exposure/pubs/episuite.htm. This approach allows all organics to be addressed and is a scientifically updated version of the approach used in Canada's CMP. Based on the above recommendations, substances can be grouped with regard to persistence and bioaccumulation as follows: Table 5. Persistence and Bioaccumulation - Exposure Ranking Persistence and P&B Ranking P&B Score Bioaccumulation Persistent and High 5 Bioaccumulative Persistent and Not Medium 3 Bioaccumulative OR Not Persistent and Bioaccumulative Not Persistent and Not Low 1 Bioaccumulative Integration of Exposure Elements: As demonstrated in the tables, each factor (use pattern, P&B, and production volume) would be assigned a numeric score based upon its ranking. All 3 factors are added to arrive at an overall value. These values are then separated into categories from low to high exposure potential. A proposed "banding" approach is illustrated in Table 6. Table 6. Integration of Exposure Rankings Combined Score - All 3 Exposure Rank Exposure Ranking elements Score 11 13 High 5 9 10 Medium High 4 7 8 Medium 3 5 6 Medium Low 2 3 4 Low 1 Overall Priority Grouping: In the overall approach, both hazard and exposure elements are considered when placing a substance in a risk-based prioritization ranking. The overall prioritization score for priority grouping and risk evaluation is based on the combined consideration of the hazard and exposure rankings. Priority Groups 7, 8, and 9 are deemed High Priority; Priority Groups 4, 5, and 6 are Medium Priority; and Priority Groups 2 and 3 are Low Priority. August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Review and Comment: It is important that screening be done in an open and transparent way and that the best available information be used. When screening for thousands of chemicals, EPA may not have access to all available information. The process should provide an opportunity for review and comment on initial rankings and an opportunity to submit additional relevant data and information to update proposed rankings with improved information. III. Second Tier Considerations: After the initial screening, some substances within individual priority groupings may require further rank ordering, particularly where a large number of chemicals are in the same priority group. Listed below are the types of information that will be useful to consider in this Second Tier rank ordering: Biomonitoring/Environmental Monitoring Data: Mere detection of chemicals in humans or the environment, i.e., "found in biomonitoring (CDC), found in water (NCOD), and found in air", while providing an indication of exposure, does not provide a useful criterion for exposure potential because almost any industrial or commercial chemical could be detected at trace levels, given increasingly sensitive analytical methods. Therefore, detection alone primarily reflects only the fact that a specific chemical was included in a measurement program. This criterion will also tend to bias the prioritization of chemicals for which well-established analytical methods are available. Consequently, this criterion is not used in the initial prioritization scheme. However, within a particular priority grouping, reliable monitoring information should be considered for Second Tier rank ordering within a quantitative process that assesses if the data is above a level of concern (i.e., places it in a risk context). Use in Children's Products: Protection of childrens' health is a top priority and, in the initial ranking, child-specific products are captured under general consumer products and all consumer products are weighted equally. The specific IUR reporting of information on chemical use in products intended for children would be considered further within a particular priority grouping for Second Tier rank ordering, noting the following points: the IUR definition is based upon use in a child specific product rather than child specific exposure potential¹ (see below). Without knowing a specific product type, it is difficult to understand if 1 IUR definition (Federal Register Volume 75, Number 156, Friday August 30, 2010, p. 49686): Intended for use by children means the chemical substance or mixture is used in or on a product that is specifically intended for use by children age 14 or younger. A chemical substance or mixture is intended for use by children when the submitter answers "yes" to at least on of the following questions for the product into which the submitter's chemical substance or mixture is incorporated: (1) Is the product commonly recognized (i.e., by a reasonable person) as being intended for children age 14 or younger? (2) Does the manufacturer of the product state through product labeling or other written materials that the product is intended for or will be used by children age 14 or younger? (3) Is the advertising, promotion, or marketing of the product aimed at children age 14 or younger? August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 potential child exposure is greater than for a non-child specific product. For example, how does child exposure to a general use cleaner compare to exposure from use in a child's raincoat. In the VCCEP assessments, there are examples for inhalation exposures where estimates of passive child exposure during adult product use exceeded conservative estimates of child exposure during active use of a child-specific product (such as a hobby product) - differences were related to the amount of product used and substance concentration within the product (MEK VCCEP Submission). the IUR definition targets children age 14 and younger. Younger children may be exposed to a variety of non-child specific products that are in general household use. Older children may be exposed to a variety of additional products. the IUR information request is targeted to manufacturers, which may not have direct knowledge of all uses, particularly the presence in products for specific subpopulations, such as children. Therefore, it is not clear that the information requested for the IUR information would be consistently available across all substances being screened. Ideally, this information should be requested from formulators of child-specific products. Therefore, for the initial prioritization approach, which represents a broad, unrefined categorization, child specific products are captured under general consumer products and all consumer products are weighted equally. The IUR information on child specific use would be utilized within a particular priority grouping for Second Tier rank ordering. If the IUR information is utilized, it is important that the limitations above be considered in its application. Emissions Data: Production volume, which is readily available for substances, is used in this proposed approach, but only serves as a surrogate for environmental emissions. For further prioritization, data or estimates of environmental emissions can be used to refine prioritization. Estimates of environmental emissions will be available for some substances (e.g., TRI data). When TRI data are utilized it should be recognized that it addresses only emissions that result from industrial and not wide dispersive uses. In other cases, emissions estimates can be developed as a percentage of production volume based upon consideration of use categories. Within a particular priority grouping, available emissions information can be considered for Second Tier rank ordering, with the understanding that emissions information is not an indicator of actual exposure. Similarly, non-isolated system intermediates, by definition, would have de minimis exposure potential. Therefore, this IUR information could be considered within a particular priority grouping for Second Tier rank ordering. International Risk Management Actions: An initial screening approach for chemical prioritization should be based upon consistent application of specific hazard and exposure science elements that define risk potential. The hazard and exposure elements should be applicable across all substances being evaluated. For initial screening, existence of international risk management action plans should not be a factor that determines priority grouping. Risk management plans may be based upon many factors, including political drivers. It is unclear how factors, their relative weighting, and the rigor of the evaluation may vary across agencies and substances. For initial screening August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 purposes, the same science-based criteria should be used to rank all substances. Consideration of existing international risk management plans could be utilized to check the functioning of the approach and could be considered within a particular priority grouping for Second Tier rank ordering with the possible effect of moving a chemical up in a grouping if actions are being taken internationally. IV. Summary ACC's prioritization approach is an example of a risk-based screening prioritization process that implements the general principles outlined at the outset of this document. It is based upon widely available information that can be utilized to understand the relative priority of chemicals for further evaluation from a risk perspective, i.e., integrating both hazard and exposure elements. Implementation of the screening framework will be most effective when utilizing the best available information. When conducting screening for thousands of chemicals, EPA may not have access to all available information. An open and iterative process that includes an opportunity for review and comment on initial rankings, together with the information that led to the result, and an opportunity to update the ranking with improved information will create a transparent and scientifically sound process. V. References Arnot, J.A., D. Mackay, T. F. Parkerton, R. T. Zaleski, C.S. Warren (2010), Multimedia modeling of human exposure to chemical substances: The roles of food web biomagnification and biotransformation, Environmental Toxicology and Chemistry 29(1):45-55. Boethling, R., K. Fenner, P. Howard, G. Klecka, T. Madsen, J.R. Snape, M.J. Whelan (2009). Environmental persistence of organic pollutants: guidance for development and review of POP risk profiles. Integrated Environmental Assessment and Management 5(4): 539 - 556. Gobas, F.A.P.C, W. de Wolf, L. P Burkhard, E. Verbruggen, K. Plotzke (2009). Revisiting Bioaccumulation Criteria for POPs and PBT Assessments Integrated Environmental Assessment and Management, 5(4):624-637. MacLeod, M., T. E. McKone (2004). Multimedia persistence as an indicator of potential for population-level intake of environmental contaminants, Environmental Toxicology and Chemistry 23(10):2465-2472. van Wijk,D., R. Chénier, T. Henry, M. D Hernando, C. Schulte (2009). Integrated Approach to PBT and POP Prioritization and Risk Assessment' Integrated Environmental Assessment and Management, 5(4):697-711. August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Proposed Prioritization Approach DRAFT May & 2011 Exposure Elements nat commental consumer 20 2 3 a 33 3 not 8 or Persuntence S not 3 mai 35 a & not 3 Pas $ 3 S the iss = the Tormages RUN $ 3 3 SUM - P8 - Tavamage ranow 3 -13 Expesure Ramking $5 Based os Sum (UN# + pa * Townage PRIORITY GROUPING - Hazard * Expasure Ramkings - 1-8 3-10 11-13 mad Jow Hazard - Highter and Human $ 3 3 & $ Human Mazard Not on Dase 3 low mai * anou % 1000 numour 3 1.8 (duet Nume " 3 & 3 8 Not 100 Acure mi os : 3 A 2000 and not data) 280 v 1000 (pas 1.0 8.0 nomour 8.3 miss Nome 3 & % x CMR Cat 2, on Dawe Call 3: 10 - 3 is # 200 50 ase Igas 0.3 1.0 0.0% - 0.2 mis forme * # $ y GMS CMR Can on OHS Clowe Clat % Repeat Close 10 § on 8 on insurticient 20 information to - - - 0.3 wis 0,00 mist on information to $ 3 a $ August 29, 2011 Source: :https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Hazard and Exposure Criteria for Prioritization Approach HAZARD EXPOSURE Environment and Human Health Classifications based upon GHS Use Elements - based upon IUR Intermediate consumed during industrial processing Envirommental: industrial (not intermediate) - used in an industrial setting From GHS classification guidance document: commercial occupational use in nonindustrial setting Table 4.1.2: scheme for substances hazardous so the aquatic environment. consumer general population residential use Clacufication Persistence: Loag-term Votalile substance (VPS 1000 Pax: Not Persistent if air half life <2 days a (Nate 2) Nonvolatile (VP < 1000 Pa): Not Persistent if: Adequate dass Adequnte voriciny dasa aux a) ready biodegradability (OBCD 301) Rapidly 3 b) inherent biodegradability (OBCD 301, 302, 306) degredable 0) read across from measured data on a related substance. 28 (Note. 3) d) equivalent degree of degradation (i.e. >20% in 28 days) via an abjotic Arute 3 Categorys Chronic 1 Categury: 1 Categasy: I degradation mechanism such as photolysis (OBCD 316) or hydrolysis (OBCD NOEC ar ECA 0.1 NOE - EC cass L 1.00 md of maid 111) and/ar BCF a 200 OR, a substance is Not Persistent if: if e) evaluation of simulation data from transformation in soil, marine water/sediment, Caregusy: Acore 2 Category: Chronic 2 Caregury: Chrumin 2 Caregusy: Chruaic 2 brackish water/sediment, surface water/sediment, oceanic water die away (e.g., OECD 3.00 s: s 10.9 0.1 - NOEC er EC. 13 0.00 <: NOEC - EC, 502 3.00 L(EXC) 10.8 and of andies 308/309) have half lives below 180 days. BCF = 500 as if K. 2 4 OR, if data are lacking: Caregusy: Arnie 3 Caregury: 3 Chrinia 3 f) evaluation via BIOWIN model (EPIWEB 4) 01 EC. : 30,00 1- 100 and fack of Bioaccomulation: stapoid andier BOF: Re 300 if absent log x 3 4 A substance is not bioaccumulative if: 4 4) a) measured TMF < 1 (field study) 3) b) measured fish BMF <1 (lab study) Ne tericity and lack of and BCF 2 500 ase, lag E 4, c) measured fish BCF < 5000 (lab study) MOECA 1 mal d) predicted BCP< 5000 using the BCFBAF model included in EPIWIN 4 The above order reflects the preference for use in decision- making NOTE -- P&B CRITERIA ARB FOR ORGANICS Tonnage - based upon JUR reporting ranges <. 25,000 lbs (below IUR site reporting limit) Human Health: 25.000 - <1 MM lbs national aggregate As above, based upon GHS 1MM - <100 MM lbs national aggregate >100 MM lbs national aggregate August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Risk-Based Prioritization Matrix Ancreasing Exposure Two-Step towest Prionies Prioritization Process Incregaling Second Tier Rank Ordering within Priority Groups Biomonitoring / Environmental Monitoring Use in Children's Products Emissions (e.g. TRI) International Risk Management Actions Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226

what is the unit of uncertainty factor ?

fsbn0226

fsbn0226_p9, fsbn0226_p10, fsbn0226_p11, fsbn0226_p12, fsbn0226_p13, fsbn0226_p14, fsbn0226_p15, fsbn0226_p16, fsbn0226_p17, fsbn0226_p18, fsbn0226_p19, fsbn0226_p20, fsbn0226_p21, fsbn0226_p22, fsbn0226_p23, fsbn0226_p24, fsbn0226_p25, fsbn0226_p26, fsbn0226_p27, fsbn0226_p28, fsbn0226_p29, fsbn0226_p30, fsbn0226_p31, fsbn0226_p32, fsbn0226_p33, fsbn0226_p34

unitless, Unitless

Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 2 USEPA APPROACH FOR EVALUATING CANCER RISHS POSED BY ORAL EXPOSURE TO 1,4-DIOXANE USEPA's Integrated Risk Information System (IRIS) published the Toxicological Review for 1,4-dioxane, in which it describes their approach and justification for deriving an oral CSF for this constituent. Below is a summary of USEPA's evaluation of available human toxicological data, weight of evidence evaluation, key study identification, critical effect selection, dose-response assessment, and the low-dose extrapolation procedure used to derive 1,4-dioxane's CSF. 2.1 USEPA's Evaluation of Evidence of Cancer in Humans USEPA evaluated the degree to which data provide evidence of carcinogenicity in humans (USEPA 2010). USEPA relied on two human occupational studies in their evaluation of potential impacts related to long-term exposure to 1,4-dioxane (Thiess et al. 1976; Buffler et al. 1978). USEPA concluded that neither study provided evidence that 1, ,4-dioxane causes cancer in humans. However, they noted "the cohort size and number of reported cases were small." 2.2 USEPA's Evaluation of Evidence of Cancer in Animal Bioassays USEPA followed its Guidelines for Carcinogen Risk Assessment (USEPA 2005) to conclude that 1,4- dioxane is "likely to be carcinogenic to humans" based on "evidence of liver carcinogenicity in several 2- year bioassays conducted in three strains of rats, two strains of mice, and in guinea pigs.' USEPA provided several reasons to justify its conclusion. For instance, USEPA concluded that the "available evidence is inadequate to establish a MOA by which 1,4-dioxane induces liver tumors in rats and mice" (USEPA 2010). Specifically, USEPA noted the "[c]onflicting data from rat and mouse bioassays (Japan Bioassay Research Center [JBRC] 1998; Kociba et al., 1974) suggest that cytotoxicity may not be a required precursor event for 1,4-dioxane-induced cell proliferation." USEPA (2010) noted that "[a]vailable data also do not clearly identify whether 1,4-dioxane or one of its metabolites is responsible for the observed effects. However, USEPA also reported that "the generally negative results for 1,4-dioxane in a number of genotoxicity assays indicates the carcinogenicity of 1,4-dioxane may not be mediated by a mutagenic MOA" (USEPA 2010). 2.3 Key Study Identification (Kano et al. 2009), Critical Effect Selection, Dose-Response Assessment, and Low-Dose Extrapolation Procedure USEPA (2010) concluded that the MOA by which 1,4-dioxane produces liver tumors is "unknown, and available evidence in support of any hypothetical mode of carcinogenic action for 1,4-dioxane is inconclusive." With this conclusion in mind, USEPA (2010) identified a 2-year drinking water study performed by Kano et al. (2009) as the key study of the oral CSF for 1,4-dioxane. Note that Kano et al. (2009) published findings originally reported by the JBRC (1990a). Although USEPA (2010) concurrently evaluated two other studies (Kociba et al. 1974; National Cancer Institute [NCI] 1978), the Kano et al. (2009) study was ultimately selected as the key study because USEPA (2010) noted that "[c]alculation of arcadis.com 3 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications a CSF for 1,4-dioxane is based upon the dose-response data for the most sensitive species and gender." The study was performed in accordance with the Organization of Economic Development's Principles for Good Laboratory Practices and involved exposing groups of rats (50 animals of each sex for each dose) and mice (50 animals of each sex for each dose) to 1,4-dioxane (>99% pure) in drinking water for 2 years. Rats were exposed to 1,4-dioxane in drinking water at 0, 200, 1,000, or 5,000 milligrams per liter (mg/L), while mice were exposed at 0, 500, 2,000, or 8,000 mg/L in drinking water. As reported by USEPA (2010): "The investigators used data from water consumption and BW [body weight] to calculate an estimate of the daily intake of 1,4-dioxane (mg/kg-day) by male and female rats and mice. Kano et al. (2009) reported a calculated mean + standard deviation for the daily doses of 1,4-dioxane for the duration of the study. Male rats received doses of approximately 0, 11+1, 55+3, or 274+18 mg/kg-day and female rats received 0, 183, 83+14, or 429+69 mg/kg-day. Male mice received doses of 0, 49+5, 191+21, or 677+74 mg/kg-day and female mice received 0, 66=10, 278+40, or 964+88 mg/kg-day." "The study by Kano et al. (2009) was used for development of an oral CSF. This was a well- designed study, conducted in both sexes in two species (rats and mice) with a sufficient number (N=50) of animals per dose group. The number of test animals allocated among three dose levels and an untreated control group was adequate, with examination of appropriate toxicological endpoints in both sexes of rats and mice. Alternative bioassays (Kociba et al., 1974; NCI, 1978) were available and were fully considered for the derivation of the oral CSF." USEPA identified increased incidence of liver adenomas or carcinomas as the critical effect in rats and mice exposed to 1,4-dioxane in the Kano et al. (2009) study. Following standard dose adjustment to a human equivalent dose using a default body weight (BW) scaling factor (USEPA 2005), USEPA performed dose-response modeling using Benchmark Dose Software and fit the suite of models available in the program to the incidence data for "either hepatocellular carcinoma or adenoma" (USEPA 2010). USEPA concluded that female mice are "more sensitive to liver carcinogenicity induced by 1,4-dioxane compared to other species or tumor types" and identified the lower 95% confidence bound on the benchmark dose associated with a 50% extra risk (benchmark response [BMR]) of developing "either hepatocellular carcinoma or adenoma" (4.95 milligrams per kilogram per day [mg/kg/d]) as the point of departure (POD) for calculating the oral CSF via linear low-dose extrapolation, as shown in Equation (1), below. USEPA (2010) again justified a linear low-dose extrapolation approach based on their conclusion that 1,4-dioxane's MOA for production of hepatic tumors in rodents is "unknown." BMR 0.5 Equation (1) CSF = = 0.1 (mg/kg/d)1 POD 4.95 mg/kg/d 2.4 Comments Provided to USEPA During External Peer Review When USEPA's IRIS program derives toxicity values, the Toxicological Review undergoes critical evaluation by individuals from within and outside the agency. A result of the outside review efforts indicated several external peer review panel members believed that available information for 1,4-dioxane could "support the use of a nonlinear extrapolation approach to estimate human carcinogenic risk" and arcadis.con 4 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications that "such an approach should be presented in the Toxicological Review.' Specifically, the USEPA (2010) notes: "[N]umerous short-term in vitro and a few in vivo tests were nonpositive for 1,4-dioxane-induced genotoxicity". Results from two-stage mouse skin tumor bioassays "suggest that a potential mode of action for 1,4- dioxane-induced tumors may involve proliferation of cells initiated spontaneously, or by some other agent, to become tumors." Additionally, a public commenter noted: "Low-dose linear extrapolation for the oral CSF is not appropriate nor justified by the data. The weight of evidence supports a threshold (nonlinear) MOA when metabolic pathway is saturated at high doses. Nonlinear extrapolations should be evaluated and presented for 1,4-dioxane." These statements indicated that some reviewers felt the toxicological data for 1,4-dioxane indicated that it may not behave in a linear manner, but rather as a threshold carcinogen. Nonetheless, USEPA (2010) ultimately concluded that there was insufficient information available to support any of the proposed MOAs and proceeded to adopt, albeit imprecisely in hindsight, the default linear low-dose extrapolation approach. arcadis.com 5 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 3 DOURSON ET AL. (2014): MODE OF ACTION (MOA) ANALYSIS FOR LIVER TUMORS FROM ORAL 1,4- DIOXANE EXPOSURES AND EVIDENCE-BASED DOSE ss RESPONSE ASSESSMENT USEPA's (2010) conclusion to evaluate 1,4-dioxane as a non-threshold, linear, low-dose extrapolation carcinogen, was "based, in part, on the following: (1) apparent uncertainty in the toxic moiety for 1,4- dioxane; and, (2) apparent lack of noncancer toxicity data from several mouse bioassays at doses that evoke tumors, or that otherwise appear to have conflicting information concerning non-neoplastic lesions in the liver of rodents exposed orally to 1,4-dioxane" (Dourson et al. 2014). Recognizing that the key studies were performed over 3 decades, Dourson et al. (2014) hypothesized that "differences in histologic approaches for quantifying and reporting non-neoplastic changes may have been responsible for the differences noted across the studies" and would account for the apparent lack of non-cancer toxicity data reported in the key mouse bioassays. In addition to directly testing this hypothesis, Dourson et al. (2014) reviewed the database of genotoxicity studies, "which included DNA replication and promotion bioassays as well as mutation, initiation, and DNA repair studies," synthesized the genotoxicity database for 1,4- dioxane, and developed and analyzed a biologically plausible MOA for the formation of hepatic tumors in rodents by employing USEPA's (2005) carcinogen guidelines. Dourson et al.'s (2014) findings from the reread of the NCI (1978) mouse bioassay histopathology slides and review of the extensive genotoxicity database demonstrates that chronic exposure to 1,4-dioxane in drinking water is associated with a non-linear mode of carcinogenic action (threshold). which is contrary to USEPA's default linear low-dose extrapolation approach (non-threshold). The cancer MOA developed by Dourson et al. (2014) also afforded new data with which to perform an improved dose-response assessment for 1,4-dioxane using toxicological endpoints that protect against 1,4-dioxane's cancer MOA (refer to Appendix A for additional details). In regards to choosing a low-dose extrapolation approach, USEPA's Guidelines for Carcinogen Risk Assessment (2005) plainly state that "[a] nonlinear approach [i.e., derivation of a reference dose or concentration] should be selected when there are sufficient data to ascertain the mode of action and conclude that it is not linear at low doses and the agent does not demonstrate mutagenic or other activity consistent with linearity at low doses.' The information presented by USEPA (2010) and supplemented by the new information from Dourson et al. (2014) shows that: (1) 1,4-dioxane causes tumors at high doses through an MOA that involves cytotoxic effects, regenerative cell proliferation, and subsequent tumor formation; (2) the effects that precede tumor formation display non-linear dose-responses; and (3) 1,4- dioxane does not cause mutations at concentrations that are not cytotoxic. As a result, the RfD of 0.05 mg/kg/d developed by Dourson et al (2014) addressed key data gaps identified by USEPA (2010) and protects against the development of liver cancers following oral exposure to 1,4-dioxane. arcadis.com 6 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 4 DOURSON ET AL. (2016 IN PEER REVIEM: UPDATED MODE OF ACTION ANALYSIS (MOA) FOR LIVER TUMORS FROM ORAL ,4-DIOXANE EXPOSURES AND EVIDENCE-BASED DOSE-RESPONSE ASSESSMENT While Dourson et al. (2014) demonstrated that a threshold-based, regenerative cell proliferation MOA accounted for the tumor findings in the NCI (1978) mouse bioassay, questions still remained about the tumor findings from a 2-year oral mouse bioassay and a 13-week precursor study reported by the JBRC (1990a,b), subsequently published as Kano et al. (2008, 2009). Similar to the NCI (1978) mouse bioassay discussed in Dourson et al. (2014), the Japanese work provided few details or findings regarding non- cancer toxicity in the mouse liver after long-term exposure to 1,4-dioxane. To address the remaining questions regarding the apparently discordant findings between the tumor MOA in mice and rats and enhance the investigation of the threshold-based MOA for hepatic tumor formation, Dourson et al. (2016 in peer review) performed a detailed evaluation of the translated Japanese rodent bioassay reports (JBRC 1990a,b) and integrated the findings with other lines of evidence for the regenerative cell proliferation MOA. This effort is summarized in Appendix B. In addition to the detailed evaluation of the JBRC (1990a,b) bioassays, Dourson et al. (2016 in peer review) also solicited opinions from several pathologists regarding the conflicting findings from the mouse bioassays. Dourson et al. (2016 in peer review) reported: "Collectively these pathology opinions support the hypothesized MOA discussed in U.S. EPA (2013) and Dourson et al. (2014) that the liver tumors from oral exposure to 1,4-dioxane occur after metabolic saturation, accumulation of the parent 1,4-dioxane molecule, liver toxicity and a regenerative hyperplasia. While additional live experimental animal testing might add confirmatory findings, a threshold for these tumors is expected if metabolism of the parent compound is not saturated, since subsequent liver toxicity does not occur." By integrating all lines of evidence, Dourson et al. (2016 in peer review) concluded: "When the many lines of evidence are taken together, the reevaluation of the Japanese studies show consistent findings in rats and consistent findings in mice other than liver histopathology not being fully recorded in the second chronic study. However, based on the number of studies conducted, the well established metabolic saturation of 1,4-dioxane metabolism in humans and experimental animals, the effects of higher dose exposures on target organ toxicity, the presence of proliferative lesions, the effect of dose and time on the progression of lesions, the time of appearance of tumors, the spectrum of tumors developed, the number and incidence of tumors at organ sites with high or low background historical incidence, and the shapes of the dose-response curve for key events and tumors, all lead to the conclusion that a regenerative hyperplasia MOA is operating with 1,4-dioxane induced liver tumors." arcadis.con 7 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 5 IMPACT OF DOURSON ET AL.S UPDATED TOXICITY ASSESSMENT ON RISK-BASED DRINKING WATER CRITERIA An agency's choice to set risk-based criteria for 1,4-dioxane based on a threshold- or non-threshold- approach has the potential to drastically impact the value of the final criterion. An example of this is provided herein based on the approach used by the New Jersey Department of Environmental Protection (NJDEP) to derive groundwater quality criteria (NJDEP 2014). The risk-based equations NJDEP uses to derive groundwater criteria for threshold and non-threshold toxicants are shown below in Equations (2) and (3), respectively, while default exposure factors are shown in Table 1 below. Using the RfD of 0.05 mg/kg/d derived from Kociba et al. (1974) by Dourson et al. (2014) to protect against a regenerative cell proliferation MOA yields a risk-based criterion of 400 g/L Using USEPA's (2010) CSF of 0.1 (mg/kg/d)-¹ yields a risk-based criterion of 0.4 (0.35) g/L, corresponding to a 1 in 1,000,000 (1x10-6) excess lifetime cancer risk. Therefore, using the toxicity value derived based on a regenerative cell proliferation MOA (RfD, threshold approach) yields a criterion that is 1,000 times higher than the value derived using USEPA's CSF approach (linear low-dose extrapolation, non-threshold). The authors of this paper conclude that sites monitoring groundwater containing 1,4-dioxane at levels below 400 g/L would meet a reasonable groundwater quality criterion that is protective of human health. RfD x BW x CF x RSC Equation (2) Criterion = x UF BW x CF Equation (3) Criterion = x IRDW arcadis.com 8 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications Table 1. Toxicity Values and NJDEP's Exposure Factors for Calculating Risk-Based Groundwater Quality Criteria Exposure Pactor Units value bource RfD mg/kg/d 0.05 Dourson et al. (2014) CSF (mg/kg/d)-1 0.1 USEPA (2010) Target risk (TR) unitless 10-6 NJDEP default BW kg 70 NJDEP default Conversion factor (CF) g/mg 1,000 NJDEP default Relative source contribution (RSC) unitless 0.2 NJDEP default Drinking water ingestion rate (IRDw) L/d 2 NJDEP default Uncertainty factor (UF) unitless 1 NJDEP default Notes: kg = kilograms L/d = liters per day g/mg = micrograms per milligram arcadis.com 9 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 6 SUMMARY AND CONCLUSIONS To support several state regulatory agencies, Dourson et al. (2016 in peer review) recently undertook additional scientific investigations to address data gaps identified in USEPA's (2010) Toxicological Review regarding 1,4-dioxane's cancer MOA and assessment approach. Collectively, Dourson et al.'s (2014, 2016 in peer review) cancer MOA evaluations and dose-response assessments addressed USEPA's uncertainties and indeed demonstrate that chronic exposure to 1,4-dioxane in drinking water is associated with a non-linear mode of carcinogenic action (threshold). These additional scientific findings provide new information that resolve 1,4- dioxane's cancer MOA and support use of a non-linear dose response approach to protect against development of cancer following low-dose oral exposures. USEPA's (2010) cancer evaluation showed that 1,4-dioxane is not mutagenic or genotoxic at non- cytotoxic doses. However, USEPA ultimately chose to use a linear low-dose extrapolation approach for estimating human cancer risk from oral exposure to 1, 4-dioxane because they concluded that the MOA for tumor formation was unknown. The recent scientific investigations by Dourson et al. (2014, 2016 in peer review) provide new information to address data gaps identified by USEPA (2010) and demonstrate that 1,4-dioxane causes liver tumors in rodents through a regenerative cell proliferation MOA. The regenerative cell proliferation MOA is characterized by: (1) metabolic saturation and accumulation of parent compound; (2) cellular swelling, hypertrophy, and liver weight increase; (3) necrosis and/or inflammation; (4) increased DNA synthesis, hyperplasia development, and foci development; and (5) development of liver adenoma and carcinomas. Specifically, 1,4-dioxane must accumulate in the liver to levels that cause inflammation and cell damage before liver tumors can form. If the first key event does not occur (metabolic saturation), then liver tumors will not form. Therefore, there is a threshold of exposure for 1,4-dioxane below which tumors do not form and it is appropriate to use a non-linear low-dose extrapolation procedure for estimating risks. The RfD of 0.05 mg/kg/d derived by Dourson et al. (2014) is protective against tumor formation through this series of events (MOA) and was calculated using USEPA's preferred methods and best available scientific practices. Using Dourson et al.'s (2014) peer-reviewed RfD, based on a regenerative cell proliferation MOA to derive a groundwater drinking water criterion results in a criterion (400 g/L) that is 1,000 times greater than the concentration derived using USEPA's default CSF approach (0.4 g/L). Based on Dourson et al.'s (2014, 2016 in peer review) studies, it is reasonable to conclude that sites that monitor groundwater containing 1,4-dioxane at levels below 400 g/L would meet a reasonable groundwater quality criteria. The recent scientific findings summarized in this report have major implications for sites that are currently or will be managing water resources impacted by 1,4-dioxane. Considering that 1,4-dioxane is emerging as a water resource contaminant, in part due to USEPA's default linear low-dose cancer evaluation approach for liver tumors in rodents (USEPA 2010), the updated toxicology evidence that 1,4-dioxane is a threshold carcinogen is significant, and suggests that many current regulatory guidelines and standards are unnecessarily low. As such, the authors of this paper conclude that sites that monitor groundwater containing 1,4-dioxane at levels below 400 g/L would meet a reasonable groundwater quality criteria that is protective of human health. arcadis.con 10 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications 7 REFERENCES ARA. 2016. 1,4-Dioxane Analysis. Available on line [Accessed Dec. 19] at: http://allianceforrisk.org/riskie- 2/. Buffler, P.A., S.M. Wood, L. Suarez, and D.J. Kilian. 1978. Mortality follow-up of workers exposed to 1,4- dioxane. J Occup Environ Med, 20: 255-259. Dourson, M., J. Reichard, P. Nance, H. Burleigh-Flayer, A. Parker, M. Vincent, and E.E. McConnell. 2014. Mode of action analysis for liver tumors from oral 1,4-dioxane exposures and evidence-based dose response assessment. Regul Toxicol Pharmacol. 68: 387-401. Dourson, M., J. Higginbotham, J. Crum, H. Burleigh-Flayer P, Nance, N. Forsberg, and M. Lafranconi. 2016 in peer review. Update: Mode of Action (MOA) for Liver Tumors Induced by Oral Exposure to 1,4-Dioxane. Regul Toxicol Pharmacol. Available online at: http://allianceforrisk.org/14-dioxane- analysis/. Health Canada. 2005. Drinking Water Guidance Value for 1,4-Dioxane. August 23. JBRC. 1990a. Report of Carcinogenicity Study by Oral Administration of 1,4-Dioxane (Mixed with Water) to Rats and Mice. Japan Industrial Safety and Health Association. December 28. JBRC. 1990b. Report of Preliminary Carcinogenicity Studies (Acute, Two-Week, and Thirteen-Week Studies) by Oral Administration of ,4-Dioxane (Mixed with Water) to Rats and Mice. Japan Industrial Safety and Health Association. December 28. Kano. H., Y. Umeda, M. Saito, H. Senoh, H. Ohbayashi, S. Aiso, K. Yamazaki, K. Nagano, and S. Fukushima. 2008. Thirteen-week oral toxicity of 1,4-dioxane in rats and mice. J Toxicol Sci. 33: 141- 153. Kano, H., Y, Umeda, T. Kasai, T. Sasaki, M. Matsumoto, K. Yamazaki, K. Nagano, H. Arito, and S. Fukushima. 2009. Carcinogenicity of 1,4-dioxane administered in drinking-water to rats and mice for 2 years. Food Chem Toxicol. 47:2776 - 2784. Kociba, R.J., S.B. McCollister, C. Park, T.R. Torkelson, and P.J. Gehring. 1974. 1,4-dioxane. I. Results of a 2-year ingestion study in rats. Toxicol Appl Pharmacol, 30: 275-286. doi:10.1016/0041- 008X(74)90099-4. McConnell, G. 2013. Report on the review of liver slides from the National Cancer Institute's Bioassay of 1,4-Dioxane for Possible Carcinogenicity Conducted in 1978 (NCI, 1978). Submitted to Toxicology Excellence for Risk Assessment. January/March 2013. NCI. 1978. Bioassay of 1,4-Dioxane for possible Carcinogenicity. Carcinogenesis Testing Program, Division of Cancer Cause and Prevention, National Cancer Institute. NIH, Bethesda, MD, 78-1330. Netherlands. 1999. Risk Assessment: 1, 4-Dioxane. Netherlands Organization for Applied Scientific Research (TNO) and the National Institute of Public Health and the Environment (RIVM). Chemical Substances Bureau, Ministry of Housing, Spatial Planning and the Environment (VROM), Netherlands, Final Version, 5 November, EINECS-No.: 204-661-8. arcadis.con 11 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Update on Toxicity of 1,4-Dioxane and Potential Regulatory Implications Neumann, H.G., H.W. Thielmann, J.G. Filser, H.P. Gelbke, H. Griem, H. Kappus, K.H. Norpoth, U. Reuter, S. Vamvakas, P. Wardenbach, and H.E. Wichmann. 1977. Proposed changes in the classification of carcinogenic chemicals in the work area. Reg. Toxicol. Pharmacol., 26:288-295. National Industrial Chemicals Notification and Assessment Scheme (NICNAS). 1998. Priority Existing Chemical Assessment Reports: 1,4-dioxane. Sydney, Australia: Australia Department of Health and Ageing. June. Available online at: NJDEP. 2014. Ground Water Quality Standards. N.J.A.C 7:9C. Available online at: http://www.nj.gov/dep/rules/rules/njac7_9c.pd Office of Environmental Health Hazard Assessment (OEHHA). 2002. Air Toxics Hot Spots Program. Risk Assessment Guidelines. Part II. Technical Support Document for Describing Available Cancer Potency Factors. Office of Environmental Health Hazard Assessment, California Environmental Protection Agency. December. Stickney, J.A., S.L. Sager, J.R. Clarkson, L.A. Smith, B.J. Locey, M.J. Bock, R. Hartung, and S.F. Olp. 2003. An updated evaluation of the carcinogenic potential of 1,4-dioxane. Regul Toxicol Pharmacol. 38(2):183-95. Thiess, A.M., E. Tress, and I. Fleig. 1976. Arbeitsmedizinische Untersuchungsergebnisse von Dioxan- exponierten Mitarbeitern [Industrial-medica investigation results in the case of workers exposed to dioxane]. Arbeitsmedizin, Sozialmedizin, Umweltmedizin, 11: 35-46. USEPA. 2005. Guidelines for carcinogen risk assessment, final report. EPA/630/P-03/001F. Risk Assessment Forum; U.S. Environmental Protection Agency. Washington, DC. March. USEPA. 2010. Toxicological Review of 1,4-Dioxane (CAS No. 123-91-1). EPA/635-R-09-005-F. Washington, D.C. August. USEPA. 2011. Recommended Use of Body Weight3/4 as the Default Method in Derivation of the Oral Reference Dose. EPA/100/R11/0001. Risk Assessment Forum. Washington, DC. USEPA. 2012. Benchmark Dose Technical Guidance. EPA/100/R-12/001. Risk Assessment Forum. Washington, DC. June 12. USEPA. 2013. Toxicological review of 1,4- Dioxane (with inhalation update) (CAS No. 123-91-1) in support of summary information on the Integrated Risk Information System (IRIS) [EPA Report]. (EPA-635/R-11/003-F). Washington, DC. USEPA. 2016a. Drinking Water Contaminant Candidate List 4 - Final. Federal Register Notice, Volume 81, No. 2222, Thursday, November 17. USEPA. 2016b. The Third Unregulated Contaminant Monitoring Rule (UCMR 3): Data Summary, July 2016. Office of Water (MS-140). EPA 815-S-16-004, Available at: USEPA. 2016c. Conducting a Human Health Risk Assessment, Dose-Response. Available at: arcadis.com 12 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 APPENDIX A Mode of Action Analysis for Liver Tumors Based on NCI Siide Reread and RfD Derivation (Dourson et al. 2014) Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 ARCADIS Gesign & for natural and built assets Appendix A MODE OF ACTION ANALYSIS FOR LIVER TUMORS BASED ON NCI SLIDE REREAD AND RFD DERIVATION (DOURSON ET AL. 2014) January 2017 Source: :ttps://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) CONTENTS Acronyms and Abbreviations ii 1 Reread of NCI (1978) Histopathology Slides and Mode of Action Evaluation for Hepatic Tumors in Mice 3 1.1 Review of 1,4-Dioxane's Genotoxicity Database 4 1.2 Mode of Action Analysis 4 1.2.1 Key Event 1: Accumulation of Parent Compound 5 1.2.2 Key Event 2: Liver Cell Hypertrophy and Necrosis 5 1.2.3 Key Event 3: DNA Synthesis 5 1.2.4 Key Event 4: Regenerative Cell Proliferation 5 1.2.5 Key Event 5: Promotion of Endogenously Initiated Tumors 6 1.3 Updated Dose-Response Assessment and Reference Dose Derivation for 1,4-Dioxane 6 2 References 8 arcadis.com i Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) ACRONYMS AND ABBREVIATIONS BMD benchmark dose-modeling CUF composite uncertainty factor EPL Experimental Pathology Laboratories JBRC Japan Bioassay Research Center mg/kg/d milligrams per kilogram body weight per day MOA mode of action NCI National Cancer Institute NOAEL no-observable-adverse-effect level POD point of departure RfD oral reference dose g/L micrograms per liter USEPA United States Environmental Protection Agency arcadis.com ii Source: https://wwww.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) 1 REREAD OF NCI (1978) HISTOPATHOLOGY SLIDES AND MODE OF ACTION EVALUATION FOR HEPATIC TUMORS IN MICE To test their hypothesis and better understand the "sequence of events that maybe have contributed to the MOA of the observed liver tumors," Dourson et al. (2014) and McConnell (2013) performed a blinded reread of the mouse National Cancer Institute (NCI) (1978) liver histopathology slides, because that study did not report non-neoplastic lesions in livers of the high-dose group. Note this is one of the two long-term oral mouse bioassays that exist for 1,4-dioxane; the other chronic mouse bioassay was performed by the Japan Bioassay Research Center (JBRC) and is reported most recently by Kano et al. (2009). As noted by Dourson et al. (2014): "Because terminology and practices for reporting liver lesions has changed since the time of the NCI study (1978), and because EPA (2005) is focusing more on an understanding of a chemical's Mode of Action (MOA) prior to any determination of its dose response, a re-review of the liver slides of mice from the NCI study (1978) was performed. This reanalysis was performed at the Experimental Pathology Laboratories (EPL), Research Triangle Park, NC during September through November 2012. The objective of the slide review was to determine if any non-neoplastic lesions in the liver were present in an effort to understand the sequence of events that may have contributed to the MOA of the observed liver tumors in mice. Another reason for the slide review was because at the time of the original slide review (i.e., 1978) the NCI typically recorded only the most severe diagnosis on a given slide, (e.g., adenoma or carcinoma). During this timeframe, the focus of cancer bioassays was to determine the potential carcinogenic activity of the chemical, not its potential chronic toxicity. For example, if an adenoma, carcinoma, and evidence of chronic toxicity (e.g., hepatocellular hypertrophy), were all present on a given slide, only the tumor response was typically recorded. Thus, it was unclear whether non-neoplastic lesions were present in the livers of mice but were not recorded in the NCI carcinogenicity study. McConnell's (2013) reread of the NCI (1978) mouse liver histopathology slides and Dourson et al.'s (2014) summary report demonstrate that chronic exposure to 1,4-dioxane in drinking water is associated with a non-linear mode of carcinogenic action (contrary to the United States Environmental Protection Agency's [USEPA's] low-dose extrapolation conclusion) based on several hepatotoxic effects that preceded tumor formation, including: Dose-dependent hepatocellular glycogen depletion Dose-dependent hepatocellular hypotrophy Dose-related hepatocellular necrosis Dose-dependent hepatocellular inflammation associated with necrosis Dose-related hyperplasia in several non-neoplastic cell types arcadis.com 3 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) Dourson et al. (2014) states: "The appearance of the liver toxicity follows the pattern where glycogen depletion occurs either concurrently with, or preceding, hypertrophy in both sexes. This was followed closely by necrosis and inflammation in males, but a high control incidence of necrosis and inflammation clouded this overall pattern found in females In terms of dose-response behavior, hypertrophy preceded the formation of foci, which appeared to precede formation of tumors. This pattern was also evident in an individual animal analysis." 1.1 Review of ,4-Dioxane's Genotoxicity Database As a component of their mode of action (MOA) analysis, Dourson et al. (2014) reviewed 1,4-dioxane's genotoxicity database using the information presented in USEPA's (2010) Toxicological Review for 1,4- dioxane. Dourson et al. (2014) noted: '1,4-dioxane has been tested for genotoxicity using in vitro assay systems with prokaryotic organisms, non-mammalian eukaryotic organisms, and mammalian cells, both with and without metabolic activation.' "[A]II fifteen mutagenicity tests reported (8 without activation and 7 with metabolic activation) were negative." "22 in vitro genotoxicity assays, and 9 in vivo genotoxicity assays were negative." "Eight genotoxicity assays were noted to be positive but only at high or noted cytotoxic doses." Based on their review of 1,4-dioxane's genotoxicity database, Dourson et al. (2014) states "1,4-dioxane does not cause point mutations, DNA repair, or [tumor] initiation" when administered at non-cytotoxic doses, which is in general agreement with USEPA's conclusions (USEPA 2010). The authors noted their conclusions were similar to USEPA's, but differ in that "if mutations are caused by 1,4-dioxane, it is only at high cytotoxic doses." The authors concluded: "1,4-dioxane does not cause mutagenicity as evidenced by uniformly negative results in standard in vitro and in vivo genotoxicity bioassays at levels that are not overtly toxic, but it may be a clastogen in vivo, in light of the mixed results in the micronucleus assays. It follows that mutations needed for tumor formation are then likely from the known endogenously available pool of mutations, and that a regenerative hyperplasia evokes more of these endogenous mutations to form tumors. Mutation potentially caused by 1,4-dioxane at high doses is precluded as a key event in tumor formation." 1.2 Mode of Action Analysis Dourson et al. (2014) proposed five key events in the non-mutagenic MOA resulting in hepatic tumors in rodents; they include: "(1) accumulation of parent compound [at concentrations that saturate metabolic processes], (2) liver cell hypertrophy and necrosis, (3) DNA synthesis, (4) regenerative cell proliferation, and (5) promotion of endogenously-initiated tumors.' The regenerative cell proliferation MOA has a threshold below which hepatic tumors are not formed. Evidence supporting each key event is presented below. arcadis.com 4 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) 1.2.1 Key Event 1: Accumulation of Parent Compound "Humans, rats, and mice extensively metabolize 1,4-dioxane.' "[M]etabolism is a capacity-limited process." "When dose of 1,4-dioxane approaches or exceeds the metabolizing capacity, the unmetabolized fraction of the dose increases and target organ toxicity occurs." "Thus, there appears to be a threshold below which metabolism and elimination are rapid and with less or perhaps without toxicological effects." "Human environmental exposures to 1,4-dioxane are unlikely to approach doses that saturate metabolizing enzymes and which produce liver and nasal tumors in rats." "Hence, since humans, like rats, efficiently metabolize 1,4-dioxane at low doses, enzyme saturation is negligible at low exposure levels." 1.2.2 Key Event 2: Liver Cell Hypertrophy and Necrosis "Liver cell hypertrophy and necrosis are key events in the 1,4-dioxane MOA leading to regenerative cell proliferation and, with chronic exposures, liver tumors.' "Liver changes including centrilobular swelling, single cell necrosis coincide exclusively with saturating doses of 1,4-dioxane and occur in as little as 11 weeks." "Evidence of hepatocellular damage preceding evidence of hepatocellular tumors caused by higher doses of 1,4-dioxane has been provided by several studies." 1.2.3 Key Event 3: DNA Synthesis USEPA (2010) reported "that 1,4-dioxane does not cause DNA repair activity in five standard in vitro and in vivo bioassays that tested for the presence of DNA repair in various model systems." "Conversely, 1,4-dioxane does cause DNA replication as evidenced by in vitro bioassays in rat hepatocytes" "DNA synthesis appears to be a key event for a regenerative cell proliferation and/or tumor promotion and can occur in either the presence or absence of cytotoxicity." "DNA synthesis provides evidence that 1,4-dioxane promotes cell proliferation through cytotoxicity." 1.2.4 Key Event 4: Regenerative Cell Proliferation "Dose-response and temporal data support the occurrence of cell proliferation and hyperplasia prior to the development of liver tumors in the rat model." "Cell proliferation appears to be an early response with significant changes (1.5- to 2-fold) occurring in rats with as little as 2 weeks of exposure." arcadis.com 5 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) "Given time, proliferative changes manifest as pre-neoplastic foci in studies where the histopathology of such changes are reported." 1.2.5 Key Event 5: Promotion of Endogenously Initiated Tumors "Three studies relevant to tumor initiation and promotion establish that 1,4-dioxane does not cause initiation in standard in vivo bioassays, in agreement with the absence of observed mutagenic or genotoxic activity." "[T]umor promotion was associated with significant toxicity in rats when administered by either dermal or oral routes." 1.3 Updated Dose-Response Assessment and Reference Dose Derivation for 1,4-Dioxane Dourson et al. (2014) and USEPA (2010) both relied on the dose-response data reported by Kociba et al. (1974). This study provided data for liver and kidney degeneration and necrosis in 6- to 8-week-old male and female Sherman rats (60/sex/dose group) that were exposed to 1, ,4-dioxane at 0, 0.01, 0.1, or 1% (i.e., 9.6, 94, and 1,015 milligrams per kilogram body weight per day [mg/kg/d] and 19, 148, and 1,599 mg/kg/d for males and females, respectively) in drinking water for up to 716 days. The study reported a no-observed-adverse-effect level (NOAEL) of 9.6 mg/kg/d and provides "the most sensitive measure of adverse effects by 1,4-dioxane" (USEPA 2010). USEPA's Toxicological Review for 1,4-dioxane (USEPA 2010) provides a reference dose (RfD) of 0.03 mg/kg/d. This RfD was derived using the NOAEL of 9.6 mg/kg/d for liver and kidney degeneration and necrosis in rats reported by Kociba et al. (1974) as the point of departure (POD), in combination with a composite uncertainty factor (CUF) of 300 (10 for interspecies extrapolation, 10 for intraspecies extrapolation, and 3 for database deficiencies associated with the lack of a multigenerational reproductive toxicity study). The lowest-observable-adverse-effect level for this study was 94 mg/kg/d (USEPA 2010). USEPA derived the RfD using the NOAEL reported by Kociba et al. (1974) because the published study did not report incidence data for these effects, and therefore, they were unable to perform benchmark dose-modeling (BMD). Alternatively, Dourson et al. (2014) reported an updated RfD of 0.05 mg/kg/d that was derived using incidence data (laboratory report for the published study was provided to Dourson et al. [2014] by The Dow Chemical Company) for hepatocellular necrosis (combined across sexes) and USEPA's preferred approaches¹. Specifically, Dourson et al. (2014) utilized USEPA's preferred BMD approach (USEPA 2012) to derive a POD of 20 mg/kg/d (95% lower bound on the dose associated with a 10% extra risk), USEPA's preferred default bodyweight scaling factor (USEPA 2011), to estimate a human equivalent 1 USEPA (2010) used the NOAEL from Kociba et al. (1974) based on liver and kidney degeneration to derive the RfD, specifically because Kociba et al. (1974) did not provide quantitative incidence or severity data for liver and kidney degeneration and necrosis. However, when appropriate data are available, USEPA prefers using BMD to define the POD (USEPA 2012). Had the incidence data from Kociba et al. (1974) been available at the time of their review, USEPA would have used it to derive a benchmark dose to use as the POD for setting the RfD. arcadis.com 6 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) dose, in combination with a CUF of 100 (3 for interspecies toxicodynamic extrapolation, 10 for intraspecies extrapolation, and 3 due to the lack of a 2-generation reproductive study) to derive an RfD of 0.05 mg/kg/d. Dourson et al. (2014) concluded that "the choice of this endpoint [hepatocellular necrosis] is protective, since liver toxicity, resulting in liver tumors, is the clear apical effect of greatest intensity in the available array of toxic effects." Dourson et al. (2014) calculated their RfD using standard approaches, as shown in Equation (1), below: POD 20 mg/kg/d Equation (1) RfD = = 0.05 mg/kg/d CUF 3x10x3 arcadis.com 7 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix A - Mode of Action Analysis for Liver Tumors Based on NCI Slide Reread and RfD Derivation (Dourson et al. 2014) 2 REFERENCES Dourson, M., J. Reichard, P. Nance, H. Burleigh-Flayer, A. Parker, M. Vincent, and E.E. McConnell. 2014. Mode of action analysis for liver tumors from oral 1,4-dioxane exposures and evidence-based dose response assessment. Regul Toxicol Pharmacol. 68: 387-401. Kano, H., Y, Umeda, T. Kasai, T. Sasaki, M. Matsumoto, K. Yamazaki, K. Nagano, H. Arito, and S. Fukushima. 2009. Carcinogenicity of 1,4-dioxane administered in drinking-water to rats and mice for 2 years. Food Chem Toxicol. 47:2776 - 2784. Kociba, R.J., S.B. McCollister, C. Park, T.R. Torkelson, and P.J. Gehring. 1974. 1,4-dioxane. I. Results of a 2-year ingestion study in rats. Toxicol Appl Pharmacol, 30: 275-286. oi:10.1016/0041- 008X(74)90099-4. McConnell, G. 2013. Report on the review of liver slides from the National Cancer Institute's Bioassay of 1,4-Dioxane for Possible Carcinogenicity Conducted in 1978 (NCI, 1978). Submitted to Toxicology Excellence for Risk Assessment. January/March 2013. NCI. 1978. Bioassay of 1,4-Dioxane for possible Carcinogenicity. Carcinogenesis Testing Program, Division of Cancer Cause and Prevention, National Cancer Institute. NIH, Bethesda, MD, 78-1330. USEPA. 2005. Guidelines for carcinogen risk assessment, final report. EPA/630/P-03/001F. Risk Assessment Forum; U.S. Environmental Protection Agency. Washington, DC. March. USEPA. 2010. Toxicological Review of 1,4-Dioxane (CAS No. 123-91-1). EPA/635-R-09-005-F. Washington, D.C. August. USEPA. 2012. Benchmark Dose Technical Guidance. EPA/100/R-12/001. Risk Assessment Forum. Washington, DC. June 12. arcadis.com 8 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 APPENDIX B Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) Source: https://www.industrydocuments.ucsf,edu/docs/fsbn0226 ARCADIS Desion & for natural and built assets Appendix B MODE OF ACTION ANALYSIS FOR LIVER TUMORS BASED ON JBRC REVIEW (DOURSONETAL.2016IN PEER REVIEW) January 2017 Source: :ttps://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) CONTENTS Acronyms and Abbreviations ii 1 Findings from Detailed Review of JBRC Rat Bioassays 3 1.1 Findings from Detailed Review of JBRC Mouse Bioassays 3 1.2 Integration of Evidence Supporting Regenerative Cell Proliferation MOA for 1,4-Dioxane 4 2 References 6 TABLES Table 1. Integration and Comparison of Rat and Mouse Bioassay Data (Adapted from Dourson et al., 2016 in peer review) 5 arcadis.com i Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) ACRONYMS AND ABEREVIATIONS JBRC Japan Bioassay Research Center mg/kg/d milligrams per kilogram body weight per day MOA mode of action NCI National Cancer Institute arcadis.com ii Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) 1 FINDINGS FROM DETAILED REVIEW OF JBRC RAT BIOASSAYS Changes in the liver found in the Japan Bioassay Research Center (JBRC) rat bioassays provide strong evidence that hepatic tumors were modulated by a threshold-based regenerative cell proliferation mode of action (MOA). Dourson et al. (2016 in peer review) found that effects observed in rats were in the expected dose-sequence for a regenerative cell proliferation MOA. Specifically, Dourson et al. (2016 in peer review) observed the following sequence of effects: Dose: 42-55 milligrams per kilogram body weight per day (mg/kg/d) - Effect: Liver swelling, hypertrophy, and liver weight increase Dose: 94-219 mg/kg/d - Effect: Necrosis Dose: 55-389 mg/kg/d - Effect: Hyperplasia and foci development Dose: >200 mg/kg/d - Effect: Increased levels of enzymes associated with liver damage Dose: 274-1015 mg/kg/d - Effect: Adenomas and carcinomas 1.1 Findings from Detailed Review of JBRC Mouse Bioassays Dourson et al. (2016 in peer review) observed the following sequence of effects in the JBRC (1990a) mouse bioassays: Dose: 190-200 mg/kg/d - Effect: Liver swelling, hypertrophy, and liver weight increase Dose: 190-200 mg/kg/d - Effect: Necrosis Dose: Not reported - Effect: Hyperplasia and foci development not reported Dose: 200 mg/kg/d - Effect: Increased levels of enzymes associated with liver damage Dose: 66-964 mg/kg/d - Effect: Adenomas and carcinomas, females Surprisingly, effects in the liver found in the JBRC mouse bioassays conflict with those clearly reported by Dourson et al. (2014) and McConnell (2013) for the reread of the National Cancer Institute (NCI) (1978) mouse bioassay histopathology slides. Additionally, the progression of effects reported by JBRC for the 2- year chronic study is inconsistent with enzymatic changes indicative of liver damage noted in the same study, as well as findings from a 13-week precursor study performed by the same laboratory. As noted by Dourson et al. (2016 in peer review), "the lack of noncancer histopathology in the chronic mouse study is not consistent with the changes in liver enzymes in this same chronic study, nor is this lack of noncancer arcadis.com 3 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226 Appendix B - Mode of Action Analysis for Liver Tumors Based on JBRC Review (Dourson et al. 2016 in peer review) findings expected based on the histopathology of the precursor 13-week study" and "[n]or does the tumor response in the low dose female mice of JBRC (1990a) match the tumor findings in the McConnell (2013) re-read of NCI (1978). Dourson et al. (2016 in peer review) hypothesized that differences in mouse bioassay results between JBRC and McConnell (2013) may be due to differences in the interpretation of the histopathological data, and provided the following quote from JBRC (Kano et al. 2009) to substantiate their claim: "The hepatic hyperplasia of rats and mice diagnosed in the previous report (Yamazaki et al., 1994) [authors note: which was a presentation of the JBRC, 1990a] was re-examined histopathologically and changed to hepatocellular adenomas and altered hepatocellular foci including acidophilic, basophilic and clear cell foci in the present studies, according to the current diagnostic criteria of liver lesions in rats and mice." Unfortunately, slides from the original JBRC (1990a,b) bioassays were not available; therefore, the JBRC slides could not be reread as they were by McConnell (2013) for the NCI (1978) mouse liver slides. Additionally, JBRC did not archive sufficient numbers of pictures of histopathology slides to resolve the issue. While, it is impossible to know for sure from this dataset whether liver tumors formed prior to or following cytotoxic effects, the weight of evidence from the JBRC and NCI mouse bioassays supports a regenerative cell proliferation MOA. 1.2 Integration of Evidence Supporting Regenerative Cell Proliferation MOA for 1,4-Dioxane Following integration of key events from seven rat bioassays, three mouse bioassays, and 1,4-dioxane's genotoxicity profile, presented in Table 1 below, Dourson et al. (2016 in peer review) showed that 1,4- dioxane's toxicological database supports a threshold-based regenerative cell proliferation MOA for tumor formation in livers of rodents orally exposed to 1,4-dioxane. The authors reported that bioassay data for rats leads to the conclusion that "rat liver tumors are evoked by a regenerative hyperplasia," while the authors concluded the "sequence of events from two chronic mouse studies and a subchronic mouse study generally support the hypothesized regenerative hyperplasia MOA" (Dourson et al. 2016 in peer review). In regards to the conflicting mouse bioassay data (McConnell 2013; Dourson et al. 2014; JBRC 1990a), the difference is likely due in part to changes in the terminology and practices used for recording the liver lesions reported by Kano et al. (2009). arcadis.com 4 Source: https://www.industrydocuments.ucsf.edu/docs/fsbn0226

what is the date mentioned in this invoice?

hrbn0226

hrbn0226_p0, hrbn0226_p1, hrbn0226_p2, hrbn0226_p3, hrbn0226_p4, hrbn0226_p5

June 24, 2016

168 From: Ehrhardt. Clinton (ehrharon) To: Risotto, Steve Cc: Dourson, Michael (doursomi); Javior, Jennifer; Haber. Lynne (haberit) Subject: RE: ACC TCE Systematic Review Invoice (Contract 6957) Date: Thursday, May 25, 2017 4:08:58 PM Attachments: ACCCCMav17.pdf ACCTCESvstem.tulv.pd Hi Mr. Risotto, See attached invoice for the costs to date. I've also marked off the previous invoice from last year. Please let me know if you have any questions. Thank you, Clinton Ehrhardt Grant Administrator University of Cincinnati, College of Medicine Department of Environmental Health 3223 Eden Ave PO Box 670056 Cincinnati, OH 45267-0056 (513) 558-5067 [email protected] From: Haber, Lynne (haberlt) Sent: Wednesday, May 17, 2017 4:10 PM To: Risotto, Steve <[email protected]>; Taylor, Jennifer <[email protected]>; Ehrhardt, Clinton (ehrharcn) <[email protected]> Cc: Dourson, Michael (doursoml) <[email protected]> Subject: RE: ACC TCE Systematic Review Invoice (Contract 6957) Thanks Steve. This sounds like a reasonable and fair approach. TII work with Clint to develop a revised invoice. Lynne From: Risotto, Steve (mailto:Steve Sent: Wednesday, May 17, 2017 3:27 PM To: Taylor, Jennifer; Ehrhardt, Clinton (ehrharcn) Cc: Haber, Lynne (haberlt); Dourson, Michael (doursoml) Subject: RE: ACC TCE Systematic Review Invoice (Contract 6957) Clinton --- As I recall from my conversation with Dr. Dourson (and as indicated on the June 24 invoice), ACC provided the funds to "pay forward" the costs of Risk Sciences Center (RSC) staff time to be spent on the systematic review project. As a result of circumstances beyond either ACC or RSC's control, however, the project has stalled and it is not clear to me how much time staff have spent at this point. Source: https://www.industrydocuments.ucsf.edu/docs/hrbn0226 169 As I informed Lynne yesterday, my group has decided not to proceed with the project and will be notilying UC officially in the next few days. In light of that decision, we are prepared to pay for the time spent on the project to date - and for any costs incurred with the involvement of the independent panel. To do that, however, I will need a new invoice that describes those costs. The decision to terminate the project is based on an interest in focusing our limited resources elsewhere, and is not the result of dissatisfaction with RSC. Please let me know if you have any questions. Thanks. Steve Steve Risotto | American Chemistry Council Senior Director, Chemical Products & Technology Division scisotto@americanchemistrvcom O: (202) 249-6727 C: (571) 255-0381 bttos:llwww.americanchemistrvcom From: Taylor, Jennifer Sent: Wednesday, May 17, 2017 1:31 PM To: Ehrhardt, Clinton (ehrharcn) Cc: Haber, Lynne (haberlt); Risotto, Steve Subject: RE: ACC TCE Systematic Review Invoice (Contract 6957) Hi, Clinton: I will check into this one, as well, and get back to you. Jennifer From: Ehrhardt, Clinton (ehrharcn) Sent: Wednesday, May 17, 2017 1:27 PM To: Taylor, Jennifer <lennifer Taxor@americanchemistrvcom> Cc: Haber, Lynne (haberlt) <[email protected] Subject: RE: ACC TCE Systematic Review Invoice (Contract 6957) Hi Jennifer, We received payment for ACCTCESystemJun16 as indicated below, but not for ACCTCESystemJul16 Attached is the correspondence for this one. Can you let me know if a check was sent for the second one? Thanks! Clinton Ehrhardt Grant Administrator University of Cincinnati, College of Medicine Source: https://www.industrydocuments.ucsf.edu/docs/hrbn0226 170 Department of Environmental Health 3223 Eden Ave PO Box 670056 Cincinnati, OH 45267-0056 (513)558-5067 [email protected] From: Taylor, Jennifer mailto: Jennifer [email protected]] Sent: Wednesday, May 17, 2017 12:34 PM To: Haber, Lynne (haberlt); Risotto, Steve Subject: RE: ACC TCE Systematic Review Invoice (Contract 6957) Dear Lynn: Our records show that a payment was made to the University Environmental Health Foundation on June 23, 2016 for Invoice # ACCTCESystemJun16, and that the check was cleared on July 1, 2016/deposited to Fifth Third Bank. Please let me know if you have any additional questions. Jennifer From: Haber, Lynne (haberlt) [mailto:habertaucmalluc.edu Sent: Tuesday, May 16, 2017 5:29 PM To: Risotto, Steve <Steve Risotto@americanchemistocom> Cc: Taylor, Jennifer Klennifer [email protected] Subject: RE: ACC TCE Systematic Review Invoice (Contract 6957) Thanks. That is good to hear. It would help to have the documentation so I can send that forward to our business office. (Things are a bit complicated, since there were two invoices of the same amount, with the second one dated June 24, but apparently the business office has a record of the second one being paid.) Lynne From: Risotto, Steve [mailto: Steve Sent: Tuesday, May 16, 2017 5:07 PM To: Haber, Lynne (haberlt) Cc: Taylor, Jennifer Subject: RE: ACC TCE Systematic Review Invoice (Contract 6957) Lynne --- Our records show that a payment in that amount was issued on June 23. Let us know if you need supporting information. Steve Steve Risotto | American Chemistry Council Senior Director, Chemical Products & Technology Division Source: https://www.industrydocuments.ucsf.edu/docs/hrbn0226 171 [email protected] O: (202)249-6727 C: (571) 255-0381 From: Haber, Lynne (haberlt) [mailto:[email protected] Sent: Tuesday, May 16, 2017 4:43 PM To: Risotto, Steve Subject: FW: ACC TCE Systematic Review Invoice (Contract 6957) Thanks in advance for taking care of this! Lynne From: Ehrhardt, Clinton (ehrharcn) Sent: Friday, June 3, 2016 3:44 PM To: Steve Bisottolamericanchemistrv.com Cc: Haber, Lynne (haberlt); Dourson, Michael (doursoml); Maier, Michael (maierma); Ayers, Valerie (ayersvj) Subject: ACC TCE Systematic Review Invoice (Contract 6957) Hi Mr. Risotto, Attached you will find an ACC TCE Systematic Review invoice for contract 6957 with Dr. Dourson. Please let me know if anything else is needed. Thank you, Clinton Ehrhardt Grant Administrator University of Cincinnati, College of Medicine Department of Environmental Health 3223 Eden Ave PO Box 670056 Cincinnati, OH 45267-0056 (513)558-5067 dintonehrhardtaucedu This message may contain confidential information and is intended only for the individual named. If you are not the named addressee do not disseminate, distribute or copy this email. Please notify the sender immediately by email if you have received this email by mistake and delete this email from your system. E-mail transmission cannot be guaranteed to be secure or error-free as information could be intercepted, corrupted, lost, destroyed, arrive late or incomplete, or contain viruses. The sender therefore does not accept liability for any errors or omissions in the contents of this message which arise as a result of email transmission. American Chemistry Council, 700 - 2nd Street NE, Washington, DC 20002, www.americanchemistry.com This message may contain confidential information and is intended only for the individual named. If you are not the named addressee do not disseminate, distribute or copy this email. Please notify the sender immediately by email if you have received this email by mistake and delete this email from your system. E-mail Source: https://www.industrydocuments.ucsf.edu/docs/hrbn0226 University of Cincinnati INVOICE Physicians Company University Environmental Health Foundation Invoice# ACCTCEMay2017 Date: May 25, 2017 To: For: Project: Support for ACC TCE Systematic review, Contract Mr. Steve Risotto 6957 American Chemistry Council 700 2nd Street NE Washington DC, 20002 DESCRIPTION RATE HOURS AMOUNT Support for ACC TCE Systematic review through 5/17/17 Michael Dourson, PhD $ 294.00 14 $ 4,116.00 Lynne Haber, PhD $ 241.00 123 $ 29,643.00 Jerry Ovesen, PhD $ 145.00 16 $ 2,320.00 Jacqueline Patterson, M En $ 261.00 38 $ 9,918.00 Alison Pecquet. M Sc $ 108.00 23.5 $ 2,538.00 Reena Sandhu, PhD $ 230.00 5 $ 1,150.00 Melissa Vincent, MS $ 101.00 19 $ 1,919.00 Honoraria for expert panelists $ 3,250.00 Less: Previous payments for Contract 6957 $ (34,433.50) TOTAL $20,420.50 Please make Checks payable to: Mail Checks to: University Environmental Health Foundation Department of Environmental Health ATTN: Clinton Ehrhardt Phone: 513 558-5067 University of Cincinnati PO Box 670056 Cincinnati, OH 45267-0056 Source: https://www.industrydocuments.ucsf.edu/docs/hrbn0226 University of Cincinnati INVOICE Physicians Company University Environmental Health Foundation Invoice# ACCTCESystemJul16 Date: June 24, 2016 To: For: Mr. Steve Risotto Project: Support for ACC TCE Systematic review, Contract 6957 American Chemistry Council 700 2nd Street, NE Washington, DC 20002 DESCRIPTION RATE HOURS AMOUNT Support for ACC TCE Systematic review Contract 6957 Additional work with panel members to be conducted; Invoice reflects the remaining 1/2 of the TERA Center effort $ 27,600.00 CANCELLED TOTAL $27,600.00 Please make Checks payable to: University Environmental Health Foundation Mail Checks to: Department of Environmental Health University of Cincinnati PO Box 670056 Cincinnati, OH 45267-0056 Source: https://www.industrydocuments.ucsf.edu/docs/hrbn0226

what is the total amount of the invoice?

hrbn0226

hrbn0226_p0, hrbn0226_p1, hrbn0226_p2, hrbn0226_p3, hrbn0226_p4, hrbn0226_p5

$27,600.00

168 From: Ehrhardt. Clinton (ehrharon) To: Risotto, Steve Cc: Dourson, Michael (doursomi); Javior, Jennifer; Haber. Lynne (haberit) Subject: RE: ACC TCE Systematic Review Invoice (Contract 6957) Date: Thursday, May 25, 2017 4:08:58 PM Attachments: ACCCCMav17.pdf ACCTCESvstem.tulv.pd Hi Mr. Risotto, See attached invoice for the costs to date. I've also marked off the previous invoice from last year. Please let me know if you have any questions. Thank you, Clinton Ehrhardt Grant Administrator University of Cincinnati, College of Medicine Department of Environmental Health 3223 Eden Ave PO Box 670056 Cincinnati, OH 45267-0056 (513) 558-5067 [email protected] From: Haber, Lynne (haberlt) Sent: Wednesday, May 17, 2017 4:10 PM To: Risotto, Steve <[email protected]>; Taylor, Jennifer <[email protected]>; Ehrhardt, Clinton (ehrharcn) <[email protected]> Cc: Dourson, Michael (doursoml) <[email protected]> Subject: RE: ACC TCE Systematic Review Invoice (Contract 6957) Thanks Steve. This sounds like a reasonable and fair approach. TII work with Clint to develop a revised invoice. Lynne From: Risotto, Steve (mailto:Steve Sent: Wednesday, May 17, 2017 3:27 PM To: Taylor, Jennifer; Ehrhardt, Clinton (ehrharcn) Cc: Haber, Lynne (haberlt); Dourson, Michael (doursoml) Subject: RE: ACC TCE Systematic Review Invoice (Contract 6957) Clinton --- As I recall from my conversation with Dr. Dourson (and as indicated on the June 24 invoice), ACC provided the funds to "pay forward" the costs of Risk Sciences Center (RSC) staff time to be spent on the systematic review project. As a result of circumstances beyond either ACC or RSC's control, however, the project has stalled and it is not clear to me how much time staff have spent at this point. Source: https://www.industrydocuments.ucsf.edu/docs/hrbn0226 169 As I informed Lynne yesterday, my group has decided not to proceed with the project and will be notilying UC officially in the next few days. In light of that decision, we are prepared to pay for the time spent on the project to date - and for any costs incurred with the involvement of the independent panel. To do that, however, I will need a new invoice that describes those costs. The decision to terminate the project is based on an interest in focusing our limited resources elsewhere, and is not the result of dissatisfaction with RSC. Please let me know if you have any questions. Thanks. Steve Steve Risotto | American Chemistry Council Senior Director, Chemical Products & Technology Division scisotto@americanchemistrvcom O: (202) 249-6727 C: (571) 255-0381 bttos:llwww.americanchemistrvcom From: Taylor, Jennifer Sent: Wednesday, May 17, 2017 1:31 PM To: Ehrhardt, Clinton (ehrharcn) Cc: Haber, Lynne (haberlt); Risotto, Steve Subject: RE: ACC TCE Systematic Review Invoice (Contract 6957) Hi, Clinton: I will check into this one, as well, and get back to you. Jennifer From: Ehrhardt, Clinton (ehrharcn) Sent: Wednesday, May 17, 2017 1:27 PM To: Taylor, Jennifer <lennifer Taxor@americanchemistrvcom> Cc: Haber, Lynne (haberlt) <[email protected] Subject: RE: ACC TCE Systematic Review Invoice (Contract 6957) Hi Jennifer, We received payment for ACCTCESystemJun16 as indicated below, but not for ACCTCESystemJul16 Attached is the correspondence for this one. Can you let me know if a check was sent for the second one? Thanks! Clinton Ehrhardt Grant Administrator University of Cincinnati, College of Medicine Source: https://www.industrydocuments.ucsf.edu/docs/hrbn0226 170 Department of Environmental Health 3223 Eden Ave PO Box 670056 Cincinnati, OH 45267-0056 (513)558-5067 [email protected] From: Taylor, Jennifer mailto: Jennifer [email protected]] Sent: Wednesday, May 17, 2017 12:34 PM To: Haber, Lynne (haberlt); Risotto, Steve Subject: RE: ACC TCE Systematic Review Invoice (Contract 6957) Dear Lynn: Our records show that a payment was made to the University Environmental Health Foundation on June 23, 2016 for Invoice # ACCTCESystemJun16, and that the check was cleared on July 1, 2016/deposited to Fifth Third Bank. Please let me know if you have any additional questions. Jennifer From: Haber, Lynne (haberlt) [mailto:habertaucmalluc.edu Sent: Tuesday, May 16, 2017 5:29 PM To: Risotto, Steve <Steve Risotto@americanchemistocom> Cc: Taylor, Jennifer Klennifer [email protected] Subject: RE: ACC TCE Systematic Review Invoice (Contract 6957) Thanks. That is good to hear. It would help to have the documentation so I can send that forward to our business office. (Things are a bit complicated, since there were two invoices of the same amount, with the second one dated June 24, but apparently the business office has a record of the second one being paid.) Lynne From: Risotto, Steve [mailto: Steve Sent: Tuesday, May 16, 2017 5:07 PM To: Haber, Lynne (haberlt) Cc: Taylor, Jennifer Subject: RE: ACC TCE Systematic Review Invoice (Contract 6957) Lynne --- Our records show that a payment in that amount was issued on June 23. Let us know if you need supporting information. Steve Steve Risotto | American Chemistry Council Senior Director, Chemical Products & Technology Division Source: https://www.industrydocuments.ucsf.edu/docs/hrbn0226 171 [email protected] O: (202)249-6727 C: (571) 255-0381 From: Haber, Lynne (haberlt) [mailto:[email protected] Sent: Tuesday, May 16, 2017 4:43 PM To: Risotto, Steve Subject: FW: ACC TCE Systematic Review Invoice (Contract 6957) Thanks in advance for taking care of this! Lynne From: Ehrhardt, Clinton (ehrharcn) Sent: Friday, June 3, 2016 3:44 PM To: Steve Bisottolamericanchemistrv.com Cc: Haber, Lynne (haberlt); Dourson, Michael (doursoml); Maier, Michael (maierma); Ayers, Valerie (ayersvj) Subject: ACC TCE Systematic Review Invoice (Contract 6957) Hi Mr. Risotto, Attached you will find an ACC TCE Systematic Review invoice for contract 6957 with Dr. Dourson. Please let me know if anything else is needed. Thank you, Clinton Ehrhardt Grant Administrator University of Cincinnati, College of Medicine Department of Environmental Health 3223 Eden Ave PO Box 670056 Cincinnati, OH 45267-0056 (513)558-5067 dintonehrhardtaucedu This message may contain confidential information and is intended only for the individual named. If you are not the named addressee do not disseminate, distribute or copy this email. Please notify the sender immediately by email if you have received this email by mistake and delete this email from your system. E-mail transmission cannot be guaranteed to be secure or error-free as information could be intercepted, corrupted, lost, destroyed, arrive late or incomplete, or contain viruses. The sender therefore does not accept liability for any errors or omissions in the contents of this message which arise as a result of email transmission. American Chemistry Council, 700 - 2nd Street NE, Washington, DC 20002, www.americanchemistry.com This message may contain confidential information and is intended only for the individual named. If you are not the named addressee do not disseminate, distribute or copy this email. Please notify the sender immediately by email if you have received this email by mistake and delete this email from your system. E-mail Source: https://www.industrydocuments.ucsf.edu/docs/hrbn0226 University of Cincinnati INVOICE Physicians Company University Environmental Health Foundation Invoice# ACCTCEMay2017 Date: May 25, 2017 To: For: Project: Support for ACC TCE Systematic review, Contract Mr. Steve Risotto 6957 American Chemistry Council 700 2nd Street NE Washington DC, 20002 DESCRIPTION RATE HOURS AMOUNT Support for ACC TCE Systematic review through 5/17/17 Michael Dourson, PhD $ 294.00 14 $ 4,116.00 Lynne Haber, PhD $ 241.00 123 $ 29,643.00 Jerry Ovesen, PhD $ 145.00 16 $ 2,320.00 Jacqueline Patterson, M En $ 261.00 38 $ 9,918.00 Alison Pecquet. M Sc $ 108.00 23.5 $ 2,538.00 Reena Sandhu, PhD $ 230.00 5 $ 1,150.00 Melissa Vincent, MS $ 101.00 19 $ 1,919.00 Honoraria for expert panelists $ 3,250.00 Less: Previous payments for Contract 6957 $ (34,433.50) TOTAL $20,420.50 Please make Checks payable to: Mail Checks to: University Environmental Health Foundation Department of Environmental Health ATTN: Clinton Ehrhardt Phone: 513 558-5067 University of Cincinnati PO Box 670056 Cincinnati, OH 45267-0056 Source: https://www.industrydocuments.ucsf.edu/docs/hrbn0226 University of Cincinnati INVOICE Physicians Company University Environmental Health Foundation Invoice# ACCTCESystemJul16 Date: June 24, 2016 To: For: Mr. Steve Risotto Project: Support for ACC TCE Systematic review, Contract 6957 American Chemistry Council 700 2nd Street, NE Washington, DC 20002 DESCRIPTION RATE HOURS AMOUNT Support for ACC TCE Systematic review Contract 6957 Additional work with panel members to be conducted; Invoice reflects the remaining 1/2 of the TERA Center effort $ 27,600.00 CANCELLED TOTAL $27,600.00 Please make Checks payable to: University Environmental Health Foundation Mail Checks to: Department of Environmental Health University of Cincinnati PO Box 670056 Cincinnati, OH 45267-0056 Source: https://www.industrydocuments.ucsf.edu/docs/hrbn0226

what is the exposure rank for the combined score-All 3 elements 11-13

jzbn0226

jzbn0226_p28, jzbn0226_p29, jzbn0226_p30, jzbn0226_p31, jzbn0226_p32, jzbn0226_p33, jzbn0226_p34, jzbn0226_p35, jzbn0226_p36, jzbn0226_p37, jzbn0226_p38, jzbn0226_p39

high, High

endpoints, criteria are similarly available for both acute and chronic classification. The use of one common system allows for appropriate assessment of all substances. GHS classification information is readily available for all substances, as U.S. manufacturers have developed GHS classifications for their products to meet international requirements. ACC's support of the GHS criteria for purposes of this prioritization tool is not a categorical endorsement of the GHS criteria for any other purpose. ACC has been an active participant in the development of GHS and supports the system in principle. The GHS has not been broadly implemented to date in the U.S., although the Occupational Safety and Health Administration (OSHA) has indicated an intent to publish a regulation applying GHS in the workplace. ACC's December 29, 2009, comments on OSHA's proposed rule to modify the existing Hazard Communication Standard (HCS) to reflect the GHS urged that implementation of the GHS adhere to certain principles (e.g., continued application of the "Building Block Approach" of the Purple Book). ACC made specific recommendations concerning details of the Hazard Classification definitions, cut-off values, among others. ACC stands behind those comments. In ACC's view, the use of GHS criteria in a screening-level prioritization of chemicals can materially assist in determining which chemicals receive additional evaluation by the Environmental Protection Agency, but does not necessarily preclude the use of other appropriate, applicable criteria developed under other systems. To classify a chemical in a hazard based priority ranking where there is not direct data on the chemical, EPA can employ the full range of approaches, such as QSAR, SAR, read- across and other modeling tools in which EPA has confidence based on molecular structure. In those situations where there still remains insufficient information on either environmental or human health hazards, the chemical would be classified as "high" for its environmental or health ranking. 1. Environmental Ranking Table 1 provides a summary of how GHS criteria could be logically used for chemical management prioritization. Table 1. Environmental Safety - Hazard Ranking GHS Classification - Ranking Environmental Rank Environmental Score Acute I or Chronic I or Insufficient Information to High 4 Classify Acute II or Chronic II Medium High 3 Acute III or Chronic III/IV or Medium 2 none Not classified Low 1 August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 2. Human Health Ranking Table 2. Human Health - Hazard Ranking Health Rank GHS Classification - Human Health Ranking Score GHS CMR Cat 1a, 1b; OR Repeat Dose </= 10 mg/kg/day (oral); </= 20 mg/kg/day (dermal); </= 50 ppm/6hr/day (gas inhalation); High 4 <<= 0.2 mg/1/6h/day (vapour inhalation); </= 0.02 mg/l/6h/day (dust mist fume inhal). OR insufficient information to classify GHS CMR Cat 2; OR Repeat Dose 10 - 100 mg/kg/day (oral); 20 - 200 mg/kg/day (dermal); Medium High 50 - 250 ppm/6hr/day (gas inhalation); 3 0.2 - 1.0 mg/l/6h/day (vapour inhalation); 0.02 - 0.2 mg/l/6h/day (dust mist fume inhal). Not carcinogen/mutagen/repro/develop;OR Repeat Dose 100 - 1000 mg/kg/day (oral); 200 - 2000 mg/kg/day (dermal); Medium 250 - 1000 ppm/6hr/day (gas inhalation); 2 1.0 - 5.0 mg/l/6h/day (vapour inhalation); 0.2 - 1.0 mg/l/6h/day (dust mist fume inhal). Not carcinogen/mutagen/repro/develop; OR Repeat Dose >1000 mg/kg/day (oral); > 2000 mg/kg/day (dermal); Low > 1000 ppm/6hr/day (gas inhalation); 1 >5.0 mg/l/6h/day (vapour inhalation); > 1.0 mg/l/6h/day (dust mist fume inhal). It is important to note that specific concerns about children's health (specifically potential hazards and adverse effects on the nervous system) and those caused by endocrine disruption mechanisms are addressed in this prioritization process: The GHS CMR "R" classification includes specific evaluation of effects on development in utero and upon growth, maturation and reproduction. ("R" stands for reproductive toxicity and includes adverse effects on sexual function and fertility, as well as developmental toxicity in offspring). Endocrine activity is not a distinct toxicological hazard per se, but rather a measure of a compound's ability to interact with components of the endocrine system. The prioritization process evaluates data and information on relevant apical tests, including tests for reproduction and developmental toxicity (potential endocrine pathways). Thus, even if specific August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 screening for potential endocrine activity has not yet been conducted on certain compounds, hazard identification based on observable outcomes from apical toxicity tests (e.g., outcomes such as pathologic states indicative of disease conditions) covers all modes of action, including endocrine pathways. The toxicity information evaluated (CMR and repeat dose toxicity) is directly relevant to evaluating potential hazards to all individuals, including children. Such data typically includes: 1) identification and definition of possible hazards upon all major organ systems from both acute and repeated exposures, including the nervous system; 2) detection of potential hazards arising from in utero exposures, including possible effects on the nervous system; 3) evaluation of potential of a substance to affect reproduction; and 4) evaluation of the potential of a substance to damage DNA. Integration of Hazard Elements: Each of the environmental and human health classifications is assigned a numeric value based upon its ranking, with 1 being the lowest value and 4 the highest. The greatest ranking (highest hazard potential score) of either Environmental or Human Health is used in a substance- specific priority ranking. The numeric value does not imply relative weighting, but rather a numerical order of priority. B. Exposure Potential Ranking The screening method allows for an initial indication of the extent of exposure potential by considering: 1. The chemical's uses and use pattern(s) 2. Production volume as a first pass indicator of relative emission/release potential since magnitude and route (i.e. air, water, soil) of emissions is not available for all substances. 3. Persistence and bioaccumulation characteristics of the substance. Together the 3 elements are used to rank exposure potential. 1. Use Patterns The proposed approach applies the most current 2006 TSCA Inventory Update Reporting rule (IUR, now called the Chemical Data Reporting rule (CDR) data. To keep the initial prioritization simple and transparent, the approach "bins" different use patterns to align with general exposure potential - intermediates, industrial use, commercial use and consumer use. These patterns are the same as those reported in the IUR and are consistent with REACH exposure categories (intermediates, worker, professional, consumer). Chemicals with consumer product use are likely to have widespread potential for general population exposures and are given high priority ranking within the approach. For the initial prioritization approach, child specific products are captured under general consumer products and all consumer products are weighted equally (see additional discussion below under Second Tier Considerations). Intermediates will have low general population exposures, since these substances are consumed, by definition, within the workplace. Therefore, they are given the lowest priority ranking within the approach. In the context of the proposed approach, the intermediates category includes both intermediates and non-isolated intermediates. A chemical used in multiple use patterns is August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 assigned the priority of the highest use, e.g., a chemical in both industrial and commercial uses would be assigned the commercial Medium-High rank. Table 3. Use Patterns - Exposure Ranking Use Pattern Ranking Use Pattern Score Consumer High 4 Commercial Medium-High 3 Industrial Medium 2 Intermediates Low 1 The IUR Definitions of these terms are (40 CFR 710.3, 710.43): "consumer use" means the use of a chemical substance or a mixture containing a chemical substance (including as part of article) when sold to or made available to consumers for their use. "commercial use" means the use of a chemical substance or a mixture containing a chemical substance (including as part of an article) in a commercial enterprise providing saleable goods or services. "industrial use" means use at a site at which one or more chemical substances or mixtures are manufactured (including imported). "intermediate" means any chemical substance: which is intentionally removed from the equipment in which it is manufactured, and which either is consumed in whole or in part in chemical reaction(s) used for the intentional manufacture of other chemical substance(s) or mixture(s), or is intentionally present for the purpose of altering the rate of such chemical reaction(s) "non-isolated intermediate" means any intermediate that is not intentionally removed from the equipment in which is it manufactured, including the reaction vessel in which it is manufactured, equipment which is ancillary to the reaction vessel, and any equipment through which the substance passes during a continuous flow process, but not including tanks or other vessels in which the substance is stored after its manufacture. 2. Production Volume Recognizing that detailed exposure information will not be available for all substances to be screened, the proposed approach uses production volume as an indicator of exposure, which is widely used in many prioritization schemes. As production volume is just a rough surrogate of emissions, ACC suggests only very broad categories, covering about two orders of magnitude each. It may be useful to consider how additional exposure estimates may be applied in the second tier assessment. Table 4. Production Volume as Emission Surrogate - Exposure Ranking Production Volume as Emission Surrogate Ranking Volume Score >= 100,000,000 lbs national aggregate High 4 1,000,000 lbs to < 100,000,000 lbs national Medium - High 3 aggregate August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 >= 25,000 lbs to < 1,000,000 lbs national Medium 2 aggregate < 25,000 lbs (below IUR site reporting limit) Low 1 3. Persistence and Bioaccumulation Persistence and bioaccumulation are viewed as indicators of exposure, and therefore are considered under the exposure axis of the approach. A persistent substance that is emitted to the environment at the same rate as a non-persistent substance with similar partitioning properties will result in higher exposure to humans and the environment. In fact, multimedia modeling clearly indicates that environmental persistence in the compartment to which a substance partitions is a good indicator of human exposure potential (MacLeod & McKone et al. 2004). Similarly, substances that are not subject to biotransformation by higher organisms will exhibit a high bioaccumulation potential that results in higher exposures via the food chain (Arnot et al. 2010). Therefore, it is recommended to apply the proposed persistence and bioaccumulation criteria in assessment of exposure potential as described below. The persistent and bioaccumulative (P&B) criteria of the proposed approach are targeted toward organic chemicals. Separate assessment criteria are likely needed for P&B evaluation for inorganics/metals, as in the approach taken by Canada's Chemical Management Program (CMP). For assessing persistence, based upon recent expert consensus (Boethling et al., 2009) it is recommended to distinguish persistent from non-persistent chemicals using the following criteria: Volatile chemicals can be defined using a vapor pressure cut-off (i.e., > 1000 Pa) For volatile chemicals, persistent versus non-persistent chemicals are differentiated using a half-life cut-off in air (e.g., a substance is not persistent if air half life is < 2 days). For non-volatile chemicals, non-persistent substances can be defined as substances that are deemed: readily or inherently biodegradable using standard biodegradation tests (OECD 301, 302, 306 test guidelines) or SAR or read across from measured data on a related substance, show an equivalent degree of degradation (i.e. >20% in 28 days) via an abiotic degradation mechanism such as photolysis (OECD 316) or hydrolysi (OECD 111), evaluation of simulation data from transformation in soil, marine water/sediment, brackish water/sediment, surface water/sediment, oceanic water die away (e.g. OECD 308/309) have half lives below 180 days, OR if data are lacking, evaluation via BIOWIN model (EPIWEB 4) Non-volatile substances that are not biodegradable or subject to abiotic losses based on the above criteria would be considered persistent. For assessing bioaccumulation, the key question for screening is the potential for biomagnification based on recent expert consensus (Gobas et al. 2009). To determine if a substance has the potential to biomagnify the following metrics have been agreed: Trophic Magnification Factor (TMF)>1, fish Biomagnification Factor (BMF)>1 fish Bioaccumulation Factor (BAF)/Bioconcentration Factor (BCF) > 5000. These metrics can be August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 derived using lab or field measurements (where available) or recently improved computational models that are included in EPA's EPIWEB model that can be freely downloaded at www.epa.gov/oppt/exposure/pubs/episuite.htm. This approach allows all organics to be addressed and is a scientifically updated version of the approach used in Canada's CMP. Based on the above recommendations, substances can be grouped with regard to persistence and bioaccumulation as follows: Table 5. Persistence and Bioaccumulation - Exposure Ranking Persistence and P&B Ranking P&B Score Bioaccumulation Persistent and High 5 Bioaccumulative Persistent and Not Medium 3 Bioaccumulative OR Not Persistent and Bioaccumulative Not Persistent and Not Low 1 Bioaccumulative Integration of Exposure Elements: As demonstrated in the tables, each factor (use pattern, P&B, and production volume) would be assigned a numeric score based upon its ranking. All 3 factors are added to arrive at an overall value. These values are then separated into categories from low to high exposure potential. A proposed "banding" approach is illustrated in Table 6. Table 6. Integration of Exposure Rankings Combined Score - All 3 Exposure Rank Exposure Ranking elements Score 11 13 High 5 9 10 Medium High 4 7 8 Medium 3 5 6 Medium Low 2 3 4 Low 1 Overall Priority Grouping: In the overall approach, both hazard and exposure elements are considered when placing a substance in a risk-based prioritization ranking. The overall prioritization score for priority grouping and risk evaluation is based on the combined consideration of the hazard and exposure rankings. Priority Groups 7, 8, and 9 are deemed High Priority; Priority Groups 4, 5, and 6 are Medium Priority; and Priority Groups 2 and 3 are Low Priority. August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Review and Comment: It is important that screening be done in an open and transparent way and that the best available information be used. When screening for thousands of chemicals, EPA may not have access to all available information. The process should provide an opportunity for review and comment on initial rankings and an opportunity to submit additional relevant data and information to update proposed rankings with improved information. III. Second Tier Considerations: After the initial screening, some substances within individual priority groupings may require further rank ordering, particularly where a large number of chemicals are in the same priority group. Listed below are the types of information that will be useful to consider in this Second Tier rank ordering: Biomonitoring/Environmental Monitoring Data: Mere detection of chemicals in humans or the environment, i.e., "found in biomonitoring (CDC), found in water (NCOD), and found in air", while providing an indication of exposure, does not provide a useful criterion for exposure potential because almost any industrial or commercial chemical could be detected at trace levels, given increasingly sensitive analytical methods. Therefore, detection alone primarily reflects only the fact that a specific chemical was included in a measurement program. This criterion will also tend to bias the prioritization of chemicals for which well-established analytical methods are available. Consequently, this criterion is not used in the initial prioritization scheme. However, within a particular priority grouping, reliable monitoring information should be considered for Second Tier rank ordering within a quantitative process that assesses if the data is above a level of concern (i.e., places it in a risk context). Use in Children's Products: Protection of childrens' health is a top priority and, in the initial ranking, child-specific products are captured under general consumer products and all consumer products are weighted equally. The specific IUR reporting of information on chemical use in products intended for children would be considered further within a particular priority grouping for Second Tier rank ordering, noting the following points: the IUR definition is based upon use in a child specific product rather than child specific exposure potential¹ (see below). Without knowing a specific product type, it is difficult to understand if 1 IUR definition (Federal Register Volume 75, Number 156, Friday August 30, 2010, p. 49686): Intended for use by children means the chemical substance or mixture is used in or on a product that is specifically intended for use by children age 14 or younger. A chemical substance or mixture is intended for use by children when the submitter answers "yes" to at least on of the following questions for the product into which the submitter's chemical substance or mixture is incorporated: (1) Is the product commonly recognized (i.e., by a reasonable person) as being intended for children age 14 or younger? (2) Does the manufacturer of the product state through product labeling or other written materials that the product is intended for or will be used by children age 14 or younger? (3) Is the advertising, promotion, or marketing of the product aimed at children age 14 or younger? August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 potential child exposure is greater than for a non-child specific product. For example, how does child exposure to a general use cleaner compare to exposure from use in a child's raincoat. In the VCCEP assessments, there are examples for inhalation exposures where estimates of passive child exposure during adult product use exceeded conservative estimates of child exposure during active use of a child-specific product (such as a hobby product) - differences were related to the amount of product used and substance concentration within the product (MEK VCCEP Submission). the IUR definition targets children age 14 and younger. Younger children may be exposed to a variety of non-child specific products that are in general household use. Older children may be exposed to a variety of additional products. the IUR information request is targeted to manufacturers, which may not have direct knowledge of all uses, particularly the presence in products for specific subpopulations, such as children. Therefore, it is not clear that the information requested for the IUR information would be consistently available across all substances being screened. Ideally, this information should be requested from formulators of child-specific products. Therefore, for the initial prioritization approach, which represents a broad, unrefined categorization, child specific products are captured under general consumer products and all consumer products are weighted equally. The IUR information on child specific use would be utilized within a particular priority grouping for Second Tier rank ordering. If the IUR information is utilized, it is important that the limitations above be considered in its application. Emissions Data: Production volume, which is readily available for substances, is used in this proposed approach, but only serves as a surrogate for environmental emissions. For further prioritization, data or estimates of environmental emissions can be used to refine prioritization. Estimates of environmental emissions will be available for some substances (e.g., TRI data). When TRI data are utilized it should be recognized that it addresses only emissions that result from industrial and not wide dispersive uses. In other cases, emissions estimates can be developed as a percentage of production volume based upon consideration of use categories. Within a particular priority grouping, available emissions information can be considered for Second Tier rank ordering, with the understanding that emissions information is not an indicator of actual exposure. Similarly, non-isolated system intermediates, by definition, would have de minimis exposure potential. Therefore, this IUR information could be considered within a particular priority grouping for Second Tier rank ordering. International Risk Management Actions: An initial screening approach for chemical prioritization should be based upon consistent application of specific hazard and exposure science elements that define risk potential. The hazard and exposure elements should be applicable across all substances being evaluated. For initial screening, existence of international risk management action plans should not be a factor that determines priority grouping. Risk management plans may be based upon many factors, including political drivers. It is unclear how factors, their relative weighting, and the rigor of the evaluation may vary across agencies and substances. For initial screening August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 purposes, the same science-based criteria should be used to rank all substances. Consideration of existing international risk management plans could be utilized to check the functioning of the approach and could be considered within a particular priority grouping for Second Tier rank ordering with the possible effect of moving a chemical up in a grouping if actions are being taken internationally. IV. Summary ACC's prioritization approach is an example of a risk-based screening prioritization process that implements the general principles outlined at the outset of this document. It is based upon widely available information that can be utilized to understand the relative priority of chemicals for further evaluation from a risk perspective, i.e., integrating both hazard and exposure elements. Implementation of the screening framework will be most effective when utilizing the best available information. When conducting screening for thousands of chemicals, EPA may not have access to all available information. An open and iterative process that includes an opportunity for review and comment on initial rankings, together with the information that led to the result, and an opportunity to update the ranking with improved information will create a transparent and scientifically sound process. V. References Arnot, J.A., D. Mackay, T. F. Parkerton, R. T. Zaleski, C.S. Warren (2010), Multimedia modeling of human exposure to chemical substances: The roles of food web biomagnification and biotransformation, Environmental Toxicology and Chemistry 29(1):45-55. Boethling, R., K. Fenner, P. Howard, G. Klecka, T. Madsen, J.R. Snape, M.J. Whelan (2009). Environmental persistence of organic pollutants: guidance for development and review of POP risk profiles. Integrated Environmental Assessment and Management 5(4): 539 - 556. Gobas, F.A.P.C, W. de Wolf, L. P Burkhard, E. Verbruggen, K. Plotzke (2009). Revisiting Bioaccumulation Criteria for POPs and PBT Assessments Integrated Environmental Assessment and Management, 5(4):624-637. MacLeod, M., T. E. McKone (2004). Multimedia persistence as an indicator of potential for population-level intake of environmental contaminants, Environmental Toxicology and Chemistry 23(10):2465-2472. van Wijk,D., R. Chénier, T. Henry, M. D Hernando, C. Schulte (2009). Integrated Approach to PBT and POP Prioritization and Risk Assessment' Integrated Environmental Assessment and Management, 5(4):697-711. August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Proposed Prioritization Approach DRAFT May & 2011 Exposure Elements nat commental consumer 20 2 3 a 33 3 not 8 or Persuntence S not 3 mai 35 a & not 3 Pas $ 3 S the iss = the Tormages RUN $ 3 3 SUM - P8 - Tavamage ranow 3 -13 Expesure Ramking $5 Based os Sum (UN# + pa * Townage PRIORITY GROUPING - Hazard * Expasure Ramkings - 1-8 3-10 11-13 mad Jow Hazard - Highter and Human $ 3 3 & $ Human Mazard Not on Dase 3 low mai * anou % 1000 numour 3 1.8 (duet Nume " 3 & 3 8 Not 100 Acure mi os : 3 A 2000 and not data) 280 v 1000 (pas 1.0 8.0 nomour 8.3 miss Nome 3 & % x CMR Cat 2, on Dawe Call 3: 10 - 3 is # 200 50 ase Igas 0.3 1.0 0.0% - 0.2 mis forme * # $ y GMS CMR Can on OHS Clowe Clat % Repeat Close 10 § on 8 on insurticient 20 information to - - - 0.3 wis 0,00 mist on information to $ 3 a $ August 29, 2011 Source: :https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Hazard and Exposure Criteria for Prioritization Approach HAZARD EXPOSURE Environment and Human Health Classifications based upon GHS Use Elements - based upon IUR Intermediate consumed during industrial processing Envirommental: industrial (not intermediate) - used in an industrial setting From GHS classification guidance document: commercial occupational use in nonindustrial setting Table 4.1.2: scheme for substances hazardous so the aquatic environment. consumer general population residential use Clacufication Persistence: Loag-term Votalile substance (VPS 1000 Pax: Not Persistent if air half life <2 days a (Nate 2) Nonvolatile (VP < 1000 Pa): Not Persistent if: Adequate dass Adequnte voriciny dasa aux a) ready biodegradability (OBCD 301) Rapidly 3 b) inherent biodegradability (OBCD 301, 302, 306) degredable 0) read across from measured data on a related substance. 28 (Note. 3) d) equivalent degree of degradation (i.e. >20% in 28 days) via an abjotic Arute 3 Categorys Chronic 1 Categury: 1 Categasy: I degradation mechanism such as photolysis (OBCD 316) or hydrolysis (OBCD NOEC ar ECA 0.1 NOE - EC cass L 1.00 md of maid 111) and/ar BCF a 200 OR, a substance is Not Persistent if: if e) evaluation of simulation data from transformation in soil, marine water/sediment, Caregusy: Acore 2 Category: Chronic 2 Caregury: Chrumin 2 Caregusy: Chruaic 2 brackish water/sediment, surface water/sediment, oceanic water die away (e.g., OECD 3.00 s: s 10.9 0.1 - NOEC er EC. 13 0.00 <: NOEC - EC, 502 3.00 L(EXC) 10.8 and of andies 308/309) have half lives below 180 days. BCF = 500 as if K. 2 4 OR, if data are lacking: Caregusy: Arnie 3 Caregury: 3 Chrinia 3 f) evaluation via BIOWIN model (EPIWEB 4) 01 EC. : 30,00 1- 100 and fack of Bioaccomulation: stapoid andier BOF: Re 300 if absent log x 3 4 A substance is not bioaccumulative if: 4 4) a) measured TMF < 1 (field study) 3) b) measured fish BMF <1 (lab study) Ne tericity and lack of and BCF 2 500 ase, lag E 4, c) measured fish BCF < 5000 (lab study) MOECA 1 mal d) predicted BCP< 5000 using the BCFBAF model included in EPIWIN 4 The above order reflects the preference for use in decision- making NOTE -- P&B CRITERIA ARB FOR ORGANICS Tonnage - based upon JUR reporting ranges <. 25,000 lbs (below IUR site reporting limit) Human Health: 25.000 - <1 MM lbs national aggregate As above, based upon GHS 1MM - <100 MM lbs national aggregate >100 MM lbs national aggregate August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Risk-Based Prioritization Matrix Ancreasing Exposure Two-Step towest Prionies Prioritization Process Incregaling Second Tier Rank Ordering within Priority Groups Biomonitoring / Environmental Monitoring Use in Children's Products Emissions (e.g. TRI) International Risk Management Actions Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226

When did NASDA submitted comments to EPA?

fgcn0226

fgcn0226_p0, fgcn0226_p1, fgcn0226_p2, fgcn0226_p3, fgcn0226_p4, fgcn0226_p5, fgcn0226_p6, fgcn0226_p7, fgcn0226_p8

January 2016

To: Nitsch, lad[[email protected]] Cc: Wagner, Kenneth[[email protected]]; Bangerter, Layne[[email protected]] From: Davis, Patrick Sent: Thur 3/30/2017 11:52:54 AM Subject: Re: NASDA Commends EPA Decision on Chlorpyrifos Petition [WARNING: SPF validation failed] Thank you Sent from my iPhone On Mar 30, 2017, at 7:41 AM, Nitsch, Chad <[email protected]> wrote: Patrick, Ken, and Layne, Please see attached statement on chlorpyrifos from NASDA. Thank you, Chad Nitsch State and Regional Partnerships | Office of the Administrator Environmental Protection Agency 202-564-4714 From: Dudley Hoskins [mailto:[email protected]] Sent: Wednesday, March 29, 2017 9:06 PM To: Nitsch, Chad <[email protected]>, Osinski, Michael <[email protected]>;! Dexter, Michael <[email protected]>; Bowles, Jack <[email protected]>; Barbery, Andrea <[email protected]> Cc: Nathan Bowen <[email protected]> Britt Aasmundstad <[email protected]> Subject: Fwd: NASDA Commends EPA Decision on Chlorpyrifos Petition [WARNING: SPF validation failed] Source: https://www.industrydocuments.ucsf.edu/docs/fgcn0226_001225_00000021-00001 Chad -- wanted to thank you again for today's meeting (more soon from our end on that front). In the interim, we wanted to share the below NASDA press release supporting EPA's science-based decision to deny petitioner's request to revoke chlorpyrifos tolerances (please share with Layne, Patrick, Ken and others from today's meeting who I may have inadvertently left off or not have email contact in front of me). Please let us know if you all have any questions or would like to discuss further at any points. Many thanks for all that you do! - dudley Sent from my iPhone Begin forwarded message: From: Amanda Culp <[email protected]> Date: March 29, 2017 at 8:06:20 PM EDT Subject: NASDA Commends EPA Decision on Chlorpyrifos Petition FOR IMMEDIATE RELEASE: March 29, 2017 Contact: Amanda Culp Director, Communications (202)296-9680 [email protected] NASDA Commends EPA Decision on Chlorpyrifos Petition The National Association of State Departments of Agriculture (NASDA) today applauded the U.S. Environmental Protection Agency's (EPA) decision to decline a petition to revoke tolerances for chlorpyrifos, which is integral for crop protection, Source: https://www.industrydocuments.ucsf.edu/docs/fgcn0226 001225 00000021-00002 including resistance management and integrated pest management (IPM) in more than 100 countries. NASDA President and Louisiana Commissioner of Agriculture & Forestry Dr. Mike Strain praised the EPA for sticking to its rigorous, scientific risk assessment and registration review process for crop protection tools. "We commend the EPA for its decision today that keeps an important insecticide available for farmers. By maintaining the Maximum Residue Limits (MRLs) for chlorpyrifos, agricultural use of this important tool will continue, significant disruption of international trade is avoided, and harmonization efforts may continue globally. As state regulatory partners with EPA, we look forward to continuing to work with the Agency to ensure current and future tools are reviewed in a rigorous, scientifically sound, and transparent manner." NASDA submitted comments to EPA in January 2016 requesting the Agency reevaluate its proposed tolerance revocations in compliance with the law and regulations that mandate a science-based review. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. NASDA grows and enhances agriculture by forging partnerships and creating consensus to achieve sound policy outcomes between state departments of agriculture, the federal government, and stakeholders. Learn more about NASDA at www.nasda.org. ### <Chlorpyrifos_EPA_03292017.pdf> Source: https://www.industrydocuments.ucsf.edu/docs/fgcn0226 001225_00000021-00003 To: Davis, Patrick[[email protected]]; Wagner, Kenneth[[email protected]] Bangerter, Layne[[email protected]] From: Nitsch, Chad Sent: Thur 3/30/2017 11:41:48 AM Subject: FW: NASDA Commends EPA Decision on Chlorpyrifos Petition [WARNING: SPF validation failed] Chlorpyrifos EPA 03292017.pd Patrick, Ken, and Layne, Please see attached statement on chlorpyrifos from NASDA. Thank you, Chad Nitsch State and Regional Partnerships I Office of the Administrator Environmental Protection Agency 202-564-4714 From: Dudley Hoskins [mailto:[email protected]] Sent: Wednesday, March 29, 2017 9:06 PM To: Nitsch, Chad <[email protected]>; Osinski, Michael <[email protected]>; Dexter, Michael <[email protected]>; Bowles, Jack <[email protected]>; Barbery, Andrea <Barbery [email protected]> Cc: Nathan Bowen <[email protected]>: Britt Aasmundstad <[email protected]> Subject: Fwd: NASDA Commends EPA Decision on Chlorpyrifos Petition [WARNING: SPF validation failed] Chad -- wanted to thank you again for today's meeting (more soon from our end on that front). In the interim, we wanted to share the below NASDA press release supporting EPA's science- based decision to deny petitioner's request to revoke chlorpyrifos tolerances (please share with Source: https://www.industrydocuments.ucsf.edu/docs/fgcn0226 001225 00000022-00001 Layne, Patrick, Ken and others from today's meeting who I may have inadvertently left off or not have email contact in front of me). Please let us know if you all have any questions or would like to discuss further at any points. Many thanks for all that you do! - dudley Sent from my iPhone Begin forwarded message: From: Amanda Culp <[email protected]> Date: March 29, 2017 at 8:06:20 PM EDT Subject: NASDA Commends EPA Decision on Chlorpyrifos Petition FOR IMMEDIATE RELEASE: March 29, 2017 Contact: Amanda Culp Director, Communications (202)296-9680 [email protected] NASDA Commends EPA Decision on Chlorpyrifos Petition The National Association of State Departments of Agriculture (NASDA) today applauded the U.S. Environmental Protection Agency's (EPA) decision to decline a petition to revoke tolerances for chlorpyrifos, which is integral for crop protection, including resistance management and integrated pest management (IPM) in more than 100 countries. NASDA President and Louisiana Commissioner of Agriculture & Forestry Dr. Mike Strain praised the EPA for sticking to its rigorous, scientific risk assessment and registration review process for crop protection tools. Source: https://www.industrydocuments.ucsf.edu/docs/fgcn0226 001225 00000022-00002 "We commend the EPA for its decision today that keeps an important insecticide available for farmers. By maintaining the Maximum Residue Limits (MRLs) for chlorpyrifos, agricultural use of this important tool will continue, significant disruption of international trade is avoided, and harmonization efforts may continue globally. As state regulatory partners with EPA, we look forward to continuing to work with the Agency to ensure current and future tools are reviewed in a rigorous, scientifically sound, and transparent manner. NASDA submitted comments to EPA in January 2016 requesting the Agency reevaluate its proposed tolerance revocations in compliance with the law and regulations that mandate a science-based review. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. NASDA grows and enhances agriculture by forging partnerships and creating consensus to achieve sound policy outcomes between state departments of agriculture, the federal government, and stakeholders. Learn more about NASDA at www.nasda.org. ### Source: https://www.industrydocuments.ucsf.edu/docs/fgcn0226 001225 00000022-00003 Contact: FOR IMMEDIATE RELEASE Amanda Culp March 29, 2017 Director, Communications (202) 296-9680 [email protected] NASDA Commends EPA Decision on Chlorpyrifos Petition The National Association of State Departments of Agriculture (NASDA) today applauded the U.S. Environmental Protection Agency's (EPA) decision to decline a petition to revoke tolerances for chlorpyrifos, which is integral for crop protection, including resistance management and integrated pest management (IPM) in more than 100 countries. NASDA President and Louisiana Commissioner of Agriculture & Forestry Dr. Mike Strain praised the EPA for sticking to its rigorous, scientific risk assessment and registration review process for crop protection tools. "We commend the EPA for its decision today that keeps an important insecticide available for farmers. By maintaining the Maximum Residue L imits (MRLs) for chlorpyrifos, agricultural use of this important tool will continue, significant disruption of international trade is avoided, and harmonization efforts may continue globally. As state regulatory partners with EPA, we look forward to continuing to work with the Agency to ensure current and future tools are review ed in a rigorous, scientifically sound , and transparent manner." - NASDA submitted comments to EPA in January 2016 requesting the Agency reevaluate its proposed tolerance revocations in compliance with the law and regulations that mandate a science-based review. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. NASDA grows and enhances agriculture by forging partnerships and creating consensus to achieve sound policy outcomes between state departments of agriculture, the federal government, and stakeholders. Learn more about NASDA at www.nasda.org. ### National Association of State Departments of Agriculture NASDA 4350 North Fairfax Drive #910 Arlington, VA 22203 Tel: 202-296-9680 www.nasda.org Source: https://www.industrydocuments.ucsf.edu/docs/fgcn0226 001225 00000023-00001 To: Bangerter, , Layne[[email protected]] From: U.S. EPA Media Relations Sent: Wed 3/29/2017 10:35:49 PM Subject: EPA Administrator Pruitt Denies Petition to Ban Widely Used Pesticide CONTACT: [email protected] FOR IMMEDIATE RELEASE March 29, 2017 EPA Administrator Pruitt Denies Petition to Ban Widely Used Pesticide Today, U.S. Environmental Protection Agency (EPA) Administrator Scott Pruitt signed an order denying a petition that sought to ban chlorpyrifos, a pesticide crucial to U.S. agriculture. "We need to provide regulatory certainty to the thousands of American farms that rely on chlorpyrifos, while still protecting human health and the environment," said EPA Administrator Pruitt. "By reversing the previous Administration's steps to ban one of the most widely used pesticides in the world, we are returning to using sound science in decision-making - rather than predetermined results.' "This is a welcome decision grounded in evidence and science," said Sheryl Kunickis, director of the Office of Pest Management Policy at the U.S. Department of Agriculture (USDA). "It means that this important pest management tool will remain available to growers, helping to ensure an abundant and affordable food supply for this nation and the world. This frees American farmers from significant trade disruptions that could have been caused by an unnecessary, unilateral revocation of chlorpyrifos tolerances in the United States. It is also great news for consumers, who will continue to have access to a full range of both domestic and imported fruits and vegetables. We thank our colleagues at EPA for their hard work." In October 2015, under the previous Administration, EPA proposed to revoke all food residue tolerances for chlorpyrifos, an active ingredient in insecticides. This proposal was issued in response to a petition from the Natural Resources Defense Council and Pesticide Action Network North America. The October 2015 proposal largely relied on certain epidemiological study outcomes, whose application is novel and uncertain, to reach its conclusions. The public record lays out serious scientific concerns and substantive process gaps in the proposal. Reliable data, overwhelming in both quantity and quality, contradicts the reliance on - and misapplication of - studies to establish the end points and conclusions used to rationalize the proposal. The USDA disagrees with the methodology used by the previous Administration. Similarly, the National Association of State Departments of Agriculture also objected to EPA's methodology. The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP) also expressed concerns with regard to EPA's previous reliance on certain data the Agency had used to support its proposal to ban the pesticide. The FIFRA SAP is a federal advisory committee operating in accordance with the Federal Advisory Committee Act and established under the provisions of FIFRA, as amended by the Food Quality Protection Act of 1996. It provides scientific advice, information and recommendations to the EPA Administrator on pesticides and pesticide-related issues regarding the impact of regulatory decisions on health and the environment. Source: https://www.industrydocuments.ucsf.edu/docs/fgcn0226 001225 00000024-00001 To view the petition: https://www.epa.gov/pesticides R044 If you would rather not receive future communications from Environmental Protection Agency, let us know by clicking here. Environmental Protection Agency, 1200 Pennsylvania Avenue NW, Washington, DC 20460 United States Source: https://www.industrydocuments.ucsf.edu/docs/fgcn0226 001225_00000024-00002

which priority groups are deemed as high priority groups?

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jzbn0226_p28, jzbn0226_p29, jzbn0226_p30, jzbn0226_p31, jzbn0226_p32, jzbn0226_p33, jzbn0226_p34, jzbn0226_p35, jzbn0226_p36, jzbn0226_p37, jzbn0226_p38, jzbn0226_p39

priority groups 7,8, and 9

endpoints, criteria are similarly available for both acute and chronic classification. The use of one common system allows for appropriate assessment of all substances. GHS classification information is readily available for all substances, as U.S. manufacturers have developed GHS classifications for their products to meet international requirements. ACC's support of the GHS criteria for purposes of this prioritization tool is not a categorical endorsement of the GHS criteria for any other purpose. ACC has been an active participant in the development of GHS and supports the system in principle. The GHS has not been broadly implemented to date in the U.S., although the Occupational Safety and Health Administration (OSHA) has indicated an intent to publish a regulation applying GHS in the workplace. ACC's December 29, 2009, comments on OSHA's proposed rule to modify the existing Hazard Communication Standard (HCS) to reflect the GHS urged that implementation of the GHS adhere to certain principles (e.g., continued application of the "Building Block Approach" of the Purple Book). ACC made specific recommendations concerning details of the Hazard Classification definitions, cut-off values, among others. ACC stands behind those comments. In ACC's view, the use of GHS criteria in a screening-level prioritization of chemicals can materially assist in determining which chemicals receive additional evaluation by the Environmental Protection Agency, but does not necessarily preclude the use of other appropriate, applicable criteria developed under other systems. To classify a chemical in a hazard based priority ranking where there is not direct data on the chemical, EPA can employ the full range of approaches, such as QSAR, SAR, read- across and other modeling tools in which EPA has confidence based on molecular structure. In those situations where there still remains insufficient information on either environmental or human health hazards, the chemical would be classified as "high" for its environmental or health ranking. 1. Environmental Ranking Table 1 provides a summary of how GHS criteria could be logically used for chemical management prioritization. Table 1. Environmental Safety - Hazard Ranking GHS Classification - Ranking Environmental Rank Environmental Score Acute I or Chronic I or Insufficient Information to High 4 Classify Acute II or Chronic II Medium High 3 Acute III or Chronic III/IV or Medium 2 none Not classified Low 1 August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 2. Human Health Ranking Table 2. Human Health - Hazard Ranking Health Rank GHS Classification - Human Health Ranking Score GHS CMR Cat 1a, 1b; OR Repeat Dose </= 10 mg/kg/day (oral); </= 20 mg/kg/day (dermal); </= 50 ppm/6hr/day (gas inhalation); High 4 <<= 0.2 mg/1/6h/day (vapour inhalation); </= 0.02 mg/l/6h/day (dust mist fume inhal). OR insufficient information to classify GHS CMR Cat 2; OR Repeat Dose 10 - 100 mg/kg/day (oral); 20 - 200 mg/kg/day (dermal); Medium High 50 - 250 ppm/6hr/day (gas inhalation); 3 0.2 - 1.0 mg/l/6h/day (vapour inhalation); 0.02 - 0.2 mg/l/6h/day (dust mist fume inhal). Not carcinogen/mutagen/repro/develop;OR Repeat Dose 100 - 1000 mg/kg/day (oral); 200 - 2000 mg/kg/day (dermal); Medium 250 - 1000 ppm/6hr/day (gas inhalation); 2 1.0 - 5.0 mg/l/6h/day (vapour inhalation); 0.2 - 1.0 mg/l/6h/day (dust mist fume inhal). Not carcinogen/mutagen/repro/develop; OR Repeat Dose >1000 mg/kg/day (oral); > 2000 mg/kg/day (dermal); Low > 1000 ppm/6hr/day (gas inhalation); 1 >5.0 mg/l/6h/day (vapour inhalation); > 1.0 mg/l/6h/day (dust mist fume inhal). It is important to note that specific concerns about children's health (specifically potential hazards and adverse effects on the nervous system) and those caused by endocrine disruption mechanisms are addressed in this prioritization process: The GHS CMR "R" classification includes specific evaluation of effects on development in utero and upon growth, maturation and reproduction. ("R" stands for reproductive toxicity and includes adverse effects on sexual function and fertility, as well as developmental toxicity in offspring). Endocrine activity is not a distinct toxicological hazard per se, but rather a measure of a compound's ability to interact with components of the endocrine system. The prioritization process evaluates data and information on relevant apical tests, including tests for reproduction and developmental toxicity (potential endocrine pathways). Thus, even if specific August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 screening for potential endocrine activity has not yet been conducted on certain compounds, hazard identification based on observable outcomes from apical toxicity tests (e.g., outcomes such as pathologic states indicative of disease conditions) covers all modes of action, including endocrine pathways. The toxicity information evaluated (CMR and repeat dose toxicity) is directly relevant to evaluating potential hazards to all individuals, including children. Such data typically includes: 1) identification and definition of possible hazards upon all major organ systems from both acute and repeated exposures, including the nervous system; 2) detection of potential hazards arising from in utero exposures, including possible effects on the nervous system; 3) evaluation of potential of a substance to affect reproduction; and 4) evaluation of the potential of a substance to damage DNA. Integration of Hazard Elements: Each of the environmental and human health classifications is assigned a numeric value based upon its ranking, with 1 being the lowest value and 4 the highest. The greatest ranking (highest hazard potential score) of either Environmental or Human Health is used in a substance- specific priority ranking. The numeric value does not imply relative weighting, but rather a numerical order of priority. B. Exposure Potential Ranking The screening method allows for an initial indication of the extent of exposure potential by considering: 1. The chemical's uses and use pattern(s) 2. Production volume as a first pass indicator of relative emission/release potential since magnitude and route (i.e. air, water, soil) of emissions is not available for all substances. 3. Persistence and bioaccumulation characteristics of the substance. Together the 3 elements are used to rank exposure potential. 1. Use Patterns The proposed approach applies the most current 2006 TSCA Inventory Update Reporting rule (IUR, now called the Chemical Data Reporting rule (CDR) data. To keep the initial prioritization simple and transparent, the approach "bins" different use patterns to align with general exposure potential - intermediates, industrial use, commercial use and consumer use. These patterns are the same as those reported in the IUR and are consistent with REACH exposure categories (intermediates, worker, professional, consumer). Chemicals with consumer product use are likely to have widespread potential for general population exposures and are given high priority ranking within the approach. For the initial prioritization approach, child specific products are captured under general consumer products and all consumer products are weighted equally (see additional discussion below under Second Tier Considerations). Intermediates will have low general population exposures, since these substances are consumed, by definition, within the workplace. Therefore, they are given the lowest priority ranking within the approach. In the context of the proposed approach, the intermediates category includes both intermediates and non-isolated intermediates. A chemical used in multiple use patterns is August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 assigned the priority of the highest use, e.g., a chemical in both industrial and commercial uses would be assigned the commercial Medium-High rank. Table 3. Use Patterns - Exposure Ranking Use Pattern Ranking Use Pattern Score Consumer High 4 Commercial Medium-High 3 Industrial Medium 2 Intermediates Low 1 The IUR Definitions of these terms are (40 CFR 710.3, 710.43): "consumer use" means the use of a chemical substance or a mixture containing a chemical substance (including as part of article) when sold to or made available to consumers for their use. "commercial use" means the use of a chemical substance or a mixture containing a chemical substance (including as part of an article) in a commercial enterprise providing saleable goods or services. "industrial use" means use at a site at which one or more chemical substances or mixtures are manufactured (including imported). "intermediate" means any chemical substance: which is intentionally removed from the equipment in which it is manufactured, and which either is consumed in whole or in part in chemical reaction(s) used for the intentional manufacture of other chemical substance(s) or mixture(s), or is intentionally present for the purpose of altering the rate of such chemical reaction(s) "non-isolated intermediate" means any intermediate that is not intentionally removed from the equipment in which is it manufactured, including the reaction vessel in which it is manufactured, equipment which is ancillary to the reaction vessel, and any equipment through which the substance passes during a continuous flow process, but not including tanks or other vessels in which the substance is stored after its manufacture. 2. Production Volume Recognizing that detailed exposure information will not be available for all substances to be screened, the proposed approach uses production volume as an indicator of exposure, which is widely used in many prioritization schemes. As production volume is just a rough surrogate of emissions, ACC suggests only very broad categories, covering about two orders of magnitude each. It may be useful to consider how additional exposure estimates may be applied in the second tier assessment. Table 4. Production Volume as Emission Surrogate - Exposure Ranking Production Volume as Emission Surrogate Ranking Volume Score >= 100,000,000 lbs national aggregate High 4 1,000,000 lbs to < 100,000,000 lbs national Medium - High 3 aggregate August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 >= 25,000 lbs to < 1,000,000 lbs national Medium 2 aggregate < 25,000 lbs (below IUR site reporting limit) Low 1 3. Persistence and Bioaccumulation Persistence and bioaccumulation are viewed as indicators of exposure, and therefore are considered under the exposure axis of the approach. A persistent substance that is emitted to the environment at the same rate as a non-persistent substance with similar partitioning properties will result in higher exposure to humans and the environment. In fact, multimedia modeling clearly indicates that environmental persistence in the compartment to which a substance partitions is a good indicator of human exposure potential (MacLeod & McKone et al. 2004). Similarly, substances that are not subject to biotransformation by higher organisms will exhibit a high bioaccumulation potential that results in higher exposures via the food chain (Arnot et al. 2010). Therefore, it is recommended to apply the proposed persistence and bioaccumulation criteria in assessment of exposure potential as described below. The persistent and bioaccumulative (P&B) criteria of the proposed approach are targeted toward organic chemicals. Separate assessment criteria are likely needed for P&B evaluation for inorganics/metals, as in the approach taken by Canada's Chemical Management Program (CMP). For assessing persistence, based upon recent expert consensus (Boethling et al., 2009) it is recommended to distinguish persistent from non-persistent chemicals using the following criteria: Volatile chemicals can be defined using a vapor pressure cut-off (i.e., > 1000 Pa) For volatile chemicals, persistent versus non-persistent chemicals are differentiated using a half-life cut-off in air (e.g., a substance is not persistent if air half life is < 2 days). For non-volatile chemicals, non-persistent substances can be defined as substances that are deemed: readily or inherently biodegradable using standard biodegradation tests (OECD 301, 302, 306 test guidelines) or SAR or read across from measured data on a related substance, show an equivalent degree of degradation (i.e. >20% in 28 days) via an abiotic degradation mechanism such as photolysis (OECD 316) or hydrolysi (OECD 111), evaluation of simulation data from transformation in soil, marine water/sediment, brackish water/sediment, surface water/sediment, oceanic water die away (e.g. OECD 308/309) have half lives below 180 days, OR if data are lacking, evaluation via BIOWIN model (EPIWEB 4) Non-volatile substances that are not biodegradable or subject to abiotic losses based on the above criteria would be considered persistent. For assessing bioaccumulation, the key question for screening is the potential for biomagnification based on recent expert consensus (Gobas et al. 2009). To determine if a substance has the potential to biomagnify the following metrics have been agreed: Trophic Magnification Factor (TMF)>1, fish Biomagnification Factor (BMF)>1 fish Bioaccumulation Factor (BAF)/Bioconcentration Factor (BCF) > 5000. These metrics can be August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 derived using lab or field measurements (where available) or recently improved computational models that are included in EPA's EPIWEB model that can be freely downloaded at www.epa.gov/oppt/exposure/pubs/episuite.htm. This approach allows all organics to be addressed and is a scientifically updated version of the approach used in Canada's CMP. Based on the above recommendations, substances can be grouped with regard to persistence and bioaccumulation as follows: Table 5. Persistence and Bioaccumulation - Exposure Ranking Persistence and P&B Ranking P&B Score Bioaccumulation Persistent and High 5 Bioaccumulative Persistent and Not Medium 3 Bioaccumulative OR Not Persistent and Bioaccumulative Not Persistent and Not Low 1 Bioaccumulative Integration of Exposure Elements: As demonstrated in the tables, each factor (use pattern, P&B, and production volume) would be assigned a numeric score based upon its ranking. All 3 factors are added to arrive at an overall value. These values are then separated into categories from low to high exposure potential. A proposed "banding" approach is illustrated in Table 6. Table 6. Integration of Exposure Rankings Combined Score - All 3 Exposure Rank Exposure Ranking elements Score 11 13 High 5 9 10 Medium High 4 7 8 Medium 3 5 6 Medium Low 2 3 4 Low 1 Overall Priority Grouping: In the overall approach, both hazard and exposure elements are considered when placing a substance in a risk-based prioritization ranking. The overall prioritization score for priority grouping and risk evaluation is based on the combined consideration of the hazard and exposure rankings. Priority Groups 7, 8, and 9 are deemed High Priority; Priority Groups 4, 5, and 6 are Medium Priority; and Priority Groups 2 and 3 are Low Priority. August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Review and Comment: It is important that screening be done in an open and transparent way and that the best available information be used. When screening for thousands of chemicals, EPA may not have access to all available information. The process should provide an opportunity for review and comment on initial rankings and an opportunity to submit additional relevant data and information to update proposed rankings with improved information. III. Second Tier Considerations: After the initial screening, some substances within individual priority groupings may require further rank ordering, particularly where a large number of chemicals are in the same priority group. Listed below are the types of information that will be useful to consider in this Second Tier rank ordering: Biomonitoring/Environmental Monitoring Data: Mere detection of chemicals in humans or the environment, i.e., "found in biomonitoring (CDC), found in water (NCOD), and found in air", while providing an indication of exposure, does not provide a useful criterion for exposure potential because almost any industrial or commercial chemical could be detected at trace levels, given increasingly sensitive analytical methods. Therefore, detection alone primarily reflects only the fact that a specific chemical was included in a measurement program. This criterion will also tend to bias the prioritization of chemicals for which well-established analytical methods are available. Consequently, this criterion is not used in the initial prioritization scheme. However, within a particular priority grouping, reliable monitoring information should be considered for Second Tier rank ordering within a quantitative process that assesses if the data is above a level of concern (i.e., places it in a risk context). Use in Children's Products: Protection of childrens' health is a top priority and, in the initial ranking, child-specific products are captured under general consumer products and all consumer products are weighted equally. The specific IUR reporting of information on chemical use in products intended for children would be considered further within a particular priority grouping for Second Tier rank ordering, noting the following points: the IUR definition is based upon use in a child specific product rather than child specific exposure potential¹ (see below). Without knowing a specific product type, it is difficult to understand if 1 IUR definition (Federal Register Volume 75, Number 156, Friday August 30, 2010, p. 49686): Intended for use by children means the chemical substance or mixture is used in or on a product that is specifically intended for use by children age 14 or younger. A chemical substance or mixture is intended for use by children when the submitter answers "yes" to at least on of the following questions for the product into which the submitter's chemical substance or mixture is incorporated: (1) Is the product commonly recognized (i.e., by a reasonable person) as being intended for children age 14 or younger? (2) Does the manufacturer of the product state through product labeling or other written materials that the product is intended for or will be used by children age 14 or younger? (3) Is the advertising, promotion, or marketing of the product aimed at children age 14 or younger? August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 potential child exposure is greater than for a non-child specific product. For example, how does child exposure to a general use cleaner compare to exposure from use in a child's raincoat. In the VCCEP assessments, there are examples for inhalation exposures where estimates of passive child exposure during adult product use exceeded conservative estimates of child exposure during active use of a child-specific product (such as a hobby product) - differences were related to the amount of product used and substance concentration within the product (MEK VCCEP Submission). the IUR definition targets children age 14 and younger. Younger children may be exposed to a variety of non-child specific products that are in general household use. Older children may be exposed to a variety of additional products. the IUR information request is targeted to manufacturers, which may not have direct knowledge of all uses, particularly the presence in products for specific subpopulations, such as children. Therefore, it is not clear that the information requested for the IUR information would be consistently available across all substances being screened. Ideally, this information should be requested from formulators of child-specific products. Therefore, for the initial prioritization approach, which represents a broad, unrefined categorization, child specific products are captured under general consumer products and all consumer products are weighted equally. The IUR information on child specific use would be utilized within a particular priority grouping for Second Tier rank ordering. If the IUR information is utilized, it is important that the limitations above be considered in its application. Emissions Data: Production volume, which is readily available for substances, is used in this proposed approach, but only serves as a surrogate for environmental emissions. For further prioritization, data or estimates of environmental emissions can be used to refine prioritization. Estimates of environmental emissions will be available for some substances (e.g., TRI data). When TRI data are utilized it should be recognized that it addresses only emissions that result from industrial and not wide dispersive uses. In other cases, emissions estimates can be developed as a percentage of production volume based upon consideration of use categories. Within a particular priority grouping, available emissions information can be considered for Second Tier rank ordering, with the understanding that emissions information is not an indicator of actual exposure. Similarly, non-isolated system intermediates, by definition, would have de minimis exposure potential. Therefore, this IUR information could be considered within a particular priority grouping for Second Tier rank ordering. International Risk Management Actions: An initial screening approach for chemical prioritization should be based upon consistent application of specific hazard and exposure science elements that define risk potential. The hazard and exposure elements should be applicable across all substances being evaluated. For initial screening, existence of international risk management action plans should not be a factor that determines priority grouping. Risk management plans may be based upon many factors, including political drivers. It is unclear how factors, their relative weighting, and the rigor of the evaluation may vary across agencies and substances. For initial screening August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 purposes, the same science-based criteria should be used to rank all substances. Consideration of existing international risk management plans could be utilized to check the functioning of the approach and could be considered within a particular priority grouping for Second Tier rank ordering with the possible effect of moving a chemical up in a grouping if actions are being taken internationally. IV. Summary ACC's prioritization approach is an example of a risk-based screening prioritization process that implements the general principles outlined at the outset of this document. It is based upon widely available information that can be utilized to understand the relative priority of chemicals for further evaluation from a risk perspective, i.e., integrating both hazard and exposure elements. Implementation of the screening framework will be most effective when utilizing the best available information. When conducting screening for thousands of chemicals, EPA may not have access to all available information. An open and iterative process that includes an opportunity for review and comment on initial rankings, together with the information that led to the result, and an opportunity to update the ranking with improved information will create a transparent and scientifically sound process. V. References Arnot, J.A., D. Mackay, T. F. Parkerton, R. T. Zaleski, C.S. Warren (2010), Multimedia modeling of human exposure to chemical substances: The roles of food web biomagnification and biotransformation, Environmental Toxicology and Chemistry 29(1):45-55. Boethling, R., K. Fenner, P. Howard, G. Klecka, T. Madsen, J.R. Snape, M.J. Whelan (2009). Environmental persistence of organic pollutants: guidance for development and review of POP risk profiles. Integrated Environmental Assessment and Management 5(4): 539 - 556. Gobas, F.A.P.C, W. de Wolf, L. P Burkhard, E. Verbruggen, K. Plotzke (2009). Revisiting Bioaccumulation Criteria for POPs and PBT Assessments Integrated Environmental Assessment and Management, 5(4):624-637. MacLeod, M., T. E. McKone (2004). Multimedia persistence as an indicator of potential for population-level intake of environmental contaminants, Environmental Toxicology and Chemistry 23(10):2465-2472. van Wijk,D., R. Chénier, T. Henry, M. D Hernando, C. Schulte (2009). Integrated Approach to PBT and POP Prioritization and Risk Assessment' Integrated Environmental Assessment and Management, 5(4):697-711. August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Proposed Prioritization Approach DRAFT May & 2011 Exposure Elements nat commental consumer 20 2 3 a 33 3 not 8 or Persuntence S not 3 mai 35 a & not 3 Pas $ 3 S the iss = the Tormages RUN $ 3 3 SUM - P8 - Tavamage ranow 3 -13 Expesure Ramking $5 Based os Sum (UN# + pa * Townage PRIORITY GROUPING - Hazard * Expasure Ramkings - 1-8 3-10 11-13 mad Jow Hazard - Highter and Human $ 3 3 & $ Human Mazard Not on Dase 3 low mai * anou % 1000 numour 3 1.8 (duet Nume " 3 & 3 8 Not 100 Acure mi os : 3 A 2000 and not data) 280 v 1000 (pas 1.0 8.0 nomour 8.3 miss Nome 3 & % x CMR Cat 2, on Dawe Call 3: 10 - 3 is # 200 50 ase Igas 0.3 1.0 0.0% - 0.2 mis forme * # $ y GMS CMR Can on OHS Clowe Clat % Repeat Close 10 § on 8 on insurticient 20 information to - - - 0.3 wis 0,00 mist on information to $ 3 a $ August 29, 2011 Source: :https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Hazard and Exposure Criteria for Prioritization Approach HAZARD EXPOSURE Environment and Human Health Classifications based upon GHS Use Elements - based upon IUR Intermediate consumed during industrial processing Envirommental: industrial (not intermediate) - used in an industrial setting From GHS classification guidance document: commercial occupational use in nonindustrial setting Table 4.1.2: scheme for substances hazardous so the aquatic environment. consumer general population residential use Clacufication Persistence: Loag-term Votalile substance (VPS 1000 Pax: Not Persistent if air half life <2 days a (Nate 2) Nonvolatile (VP < 1000 Pa): Not Persistent if: Adequate dass Adequnte voriciny dasa aux a) ready biodegradability (OBCD 301) Rapidly 3 b) inherent biodegradability (OBCD 301, 302, 306) degredable 0) read across from measured data on a related substance. 28 (Note. 3) d) equivalent degree of degradation (i.e. >20% in 28 days) via an abjotic Arute 3 Categorys Chronic 1 Categury: 1 Categasy: I degradation mechanism such as photolysis (OBCD 316) or hydrolysis (OBCD NOEC ar ECA 0.1 NOE - EC cass L 1.00 md of maid 111) and/ar BCF a 200 OR, a substance is Not Persistent if: if e) evaluation of simulation data from transformation in soil, marine water/sediment, Caregusy: Acore 2 Category: Chronic 2 Caregury: Chrumin 2 Caregusy: Chruaic 2 brackish water/sediment, surface water/sediment, oceanic water die away (e.g., OECD 3.00 s: s 10.9 0.1 - NOEC er EC. 13 0.00 <: NOEC - EC, 502 3.00 L(EXC) 10.8 and of andies 308/309) have half lives below 180 days. BCF = 500 as if K. 2 4 OR, if data are lacking: Caregusy: Arnie 3 Caregury: 3 Chrinia 3 f) evaluation via BIOWIN model (EPIWEB 4) 01 EC. : 30,00 1- 100 and fack of Bioaccomulation: stapoid andier BOF: Re 300 if absent log x 3 4 A substance is not bioaccumulative if: 4 4) a) measured TMF < 1 (field study) 3) b) measured fish BMF <1 (lab study) Ne tericity and lack of and BCF 2 500 ase, lag E 4, c) measured fish BCF < 5000 (lab study) MOECA 1 mal d) predicted BCP< 5000 using the BCFBAF model included in EPIWIN 4 The above order reflects the preference for use in decision- making NOTE -- P&B CRITERIA ARB FOR ORGANICS Tonnage - based upon JUR reporting ranges <. 25,000 lbs (below IUR site reporting limit) Human Health: 25.000 - <1 MM lbs national aggregate As above, based upon GHS 1MM - <100 MM lbs national aggregate >100 MM lbs national aggregate August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Risk-Based Prioritization Matrix Ancreasing Exposure Two-Step towest Prionies Prioritization Process Incregaling Second Tier Rank Ordering within Priority Groups Biomonitoring / Environmental Monitoring Use in Children's Products Emissions (e.g. TRI) International Risk Management Actions Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226

What does FR stand for?

qrbn0226

qrbn0226_p0, qrbn0226_p1, qrbn0226_p2, qrbn0226_p3, qrbn0226_p4

fire retardant

189 From: White, Kimberly To: Admon. Smadar: Anderson Steven; Batoon, Audrey; Bradley, Kevin; de Lacy Catharine; Blkan, llan; Erraguntia. Neeraja: Goodman. Bryan; Hochschwender, Lane: Jacobi. Sylvia.B. Kannah. Kasturirangan; Levan Steve; Levchik. Sergei; Little Barbara: Manor. Orit: Prero. Judab; Rothenbacher, Klaus; Saunders. Eric L Scherrer. Steve; Simon Robert: Tavior. Jennifer; Tenney, Joel: Thorn Amelia: West Jay; White Kimberly; Haves, A Wallace; Rein. Guillermo; [email protected] Troitzsch. Jurgen; Blais. Matthew; Dourson. Michael (doursoml); Kacew Sam; Osimitz. Thomas Subject: Request to Schedule a Call on Baby Monitor Combustion Project Date: Thursday, May 18, 2017 10:32:45 AM Attachments: Baby Monitor Plastic Flammability Proposal finalpdi Dear NAFRA Science Workgroup Members and Science Advisory Council Members: In follow-up to this week's discussion regarding the current status and next steps for the Baby Monit or Combustion Project, we'd like to schedule a call with members and the researchers. Please access the poll below by 5pm (ET) Monday, May 22nd Note all times in the poll are in Eastern Daylight Time. Poll: http://doodle.com/poll/2piythmxu23tugsd. As well below is a summary of the May meeting discussion as provided by Drs. Ezekoye and Marr and attached or in links below are relevant documents. Please review this information and provide any initial additional thoughts you may have regarding the project next steps. Relevant Documents Baby Monitor Combustion Project Proposal (attached) Link to Baby Monitor Combustion Project Update Summary Report in PDF-March 2017 Link to Baby Monitor Combustion PowerPoint Project Update Presented on May 16, 2017 Summary of Discussion by Drs. Ezekoye and Marr Here are some of the commentsf from our conference call. There were two threads: better characterization of the baby monitor cases and developing more representative failure scenarios. The suggestions related to characterizing the baby monitor cases included: - Use X-Ray Photoelectron Spectroscopy (XPS) to look for bromine in the OEM baby monitor cases - Measure the critical heat flux of the OEM and surrogate baby monitor plastics - Create our own FRtreated cases using FR ABS The suggestions related to developing more representative (lower HRR) failures included: - Explore scaling down the failure mode of the existing batteries - Use a cartridge heater as the heat source After the call, Drs. Ezekoye and Marr also discussed another alternative of scaling down the battery size to get different effective failure energies and HRRs. Kind Regards, Kimberly Wise White, Ph. D. | American Chemistry Council Senior Director, Chemical Products & Technology Division Kimberly [email protected] 700 2nd Street NE Washington, DC | 20002 O: (202) 249-6707 C: (202) 341-7602 www.americanchemistry.com This message may contain confidential information and is intended only for the individual named. If you are not the named addressee do not disseminate, distribute or copy this email. Please notify the sender immediately by email if you have received this email by mistake and delete this email from your system. E-mail Source: https://www.industrydocuments.ucsf.edu/docs/qrbn0226 COCKRELL SCHOOL OF ENGINEERING THE UNIVERSITY OF TEXAS AT AUSTIN the 5 Department of Mechanical Engineering . ETC II 5.160 . http://www.me.utexas.edu 1 University Station C2200 . Austin, Texas . 78712-0292 . (512)471-1131 . Fax (512)471-8727 August 3, 2016 Joel Tenney Director of Advocacy ICL-IP America Subject: Baby Monitor Thermal and Flammability Testing Dear Mr. Tenney, Thank you for your interest in working with UT Fire Research Group (UTFRG) to characterize the thermal stability and fire hazards posed by baby monitors. The appended project whitepaper presents our current understanding of the scope of services sought and terms of the engagement. Once you've reviewed this statement of work, please let me know how you would like to proceed. Sincerely, O.A. ('DK') Ezekoye, Ph.D., P.E. W.R. Woolrich Professor Department of Mechanical Engineering & Department of Civil, Arch. and Environ. Engineering Program Director, Online M.S. in Mechanical Engineering Source: https://www.industrydocuments.ucsf.edu/docs/qrbn0226 UTFRG Recall Testing Whitepaper August 3, 2016 Thermal and Flammability Testing of a Recalled Baby Monitor University of Texas Fire Research Group Summary The proposed scope of work is to conduct experimental testing to investigate the thermal characteristics and flammability of baby monitors. Currently, fire retardant (FR) plastics are used in many products (toys, chairs, electronics, etc.) to reduce the risk of fire and burn hazards. Flame retardants are considered by fire scientists to be an integral part of the management and mitigation of fire and burn hazards. It is understood in fire science that addition of flame retardants in polymeric materials can reduce the ignitability and flame spread characteristics of the material. Some detractors of FRs argue that the environmental and public health impact of flame retardants outweigh their potential fire mitigation capability. For portable electronics accessories such as baby monitors that are powered by lithium-ion batteries the fire risk is greater than passive (i.e., unpowered) baby products. Recently several baby monitors branded by Lorex were recalled due to potential burn hazards related to battery failures. Figure 1 shows images of the Lorex baby monitor and battery, and Figure 2 shows images of a failed battery from the Lorex baby monitor. The swollen battery shown in Figure 2 is the result of the battery overheating and producing flammable gas. Although in this case, there were no reports of fires, if enough flammable gas is produced, the battery casing can fail releasing the gas, which can potentially ignited surrounding materials and cause a fire. In the event of a battery thermal failure, FR is likely to reduce the risk of ignition and fire of the baby monitor plastic. - - - Figure 1. Images of the recalled Lorex baby monitor and the lithium-ion battery. Source: https://www.industrydocuments.ucsf.edu/docs/qrbn0226 UTFRG Recall Testing Whitepaper August 3, 2016 Figure 2. Images of swollen battery from a Lorex baby monitor that had failed. The purpose of the proposed work is to investigate the effectiveness of FR on a representative electronic baby accessory. In this study a baby monitor will be used as the representative exemplar. UTFRG proposes that our services be divided into the following tasks: Task A-Fabricate Replica Baby Monitors $10,000.00 ($15,600 w/ overhead) The scope of Task A is to design and fabricate three replicas of a baby monitor. It is UTFRG's understanding that one possible model of interest is manufactured by Lorex (Model No. WL3520, WL4320, and WL3401). As discussed above, these models have been recalled and are currently unavailable from United States retailers. However, it may be possible to obtain exemplar units from international retailers or third-party resellers. If available, UTFRG will procure exemplar baby monitors. If the make and model is commercially unavailable, an alternative make and model may be used. Any alternative model will be agreed upon in discussions with the sponsor prior to procurement. An exemplar baby monitor housing will be laser scanned and three replicas will be fabricated using a 3-D printer. The replica housings will be constructed of material that does not contain fire retardants. One filament system available for testing for the Makerbot systems is PLA 3D Printer Filament/ MakerBot PLA. Makerbot has information on their website about the flammability concerns of their products Figure 3. Makerbot flammability warning video at http://www.makerbot.com/blog/2010/11/29/makerbot-psa-fire-and-abs-pla-dont-mix Source: https://www.industrydocuments.ucsf.edu/docs/qrbn0226 UTFRG Recall Testing Whitepaper August 3, 2016 UTFRG will evaluate the housing material, and replica housings will be printed using the same material type. Components including the LCD, electronics and battery will be extracted from exemplar units and re-installed in the replica housings. Upon completion of this task, UTFRG will provide the sponsor with a report detailing the procurement process, CAD design details, and photographs of the reassembled baby monitors. Electronic CAD files can also be provided upon request. Task A is expected to take five (5) weeks to complete. The cost estimate for this task includes salary for students and research engineer, student tuition and fees, fringe benefits, and supplies. The cost of procuring exemplar monitors is also included. If the work is routed through the University as a contract as compared to a gift, a 1.56 overhead multiplier takes the nominal cost from $10K to $15.6K. Task B-Thermal & Flammability Testing $20,000.00 ($31,200 w/ overhead) Upon completion of Task A, UTFRG will develop and implement a test program to assess the effectiveness of FR on electronic baby products. The testing will include small scale ignition tests on the base plastics and full system flammability experiments on six (6) baby monitors: three (3) exemplar monitors and three (3) replica monitors. In the full system experiments, fire will be induced by thermally failing the battery. The battery will be charged to 100% state-of- charge (SOC) prior to thermal failure. In actual use scenarios, batteries often fail due to internal shorts from manufacturing defects, mechanical damage overcharging. Because of the stochastic nature of thermal failures, simulating an internal short in a lab setting can be challenging. The most reliable method to thermally fail a battery is to apply external heat; however, external heat may lead to heat damage or potentially ignition of the housing prior to the battery thermal failure. UTFRG will investigate and develop a reliable failure method to fail the battery while minimizing collateral damage during said failure. Testing will be photo-documented and video recorded. Additional measurements will also made. These measurements include, but are not limited to, surface temperature of the baby monitor housing, battery and electronic circuit board, heat release from the induced fire, and thermal imaging of the induced fire. Upon completion of this Task, UTFRG will provide a report and presentation-style report. Raw data and videos will be provided upon request. Task B is expected to take ten (10) weeks to complete. The cost estimate for this task includes salary for students and research engineer, student tuition and fees, fringe benefits, and supplies. The cost of procuring exemplar monitors is also included. If the work is routed through the University as a contract as compared to a gift, a 1.56 overhead multiplier takes the nominal cost from $20K to $31.2K. Source: https://www.industrydocuments.ucsf.edu/docs/qrbn0226

What is the invoice# given?

hrbn0226

hrbn0226_p0, hrbn0226_p1, hrbn0226_p2, hrbn0226_p3, hrbn0226_p4, hrbn0226_p5

ACCTCESystemJul16

168 From: Ehrhardt. Clinton (ehrharon) To: Risotto, Steve Cc: Dourson, Michael (doursomi); Javior, Jennifer; Haber. Lynne (haberit) Subject: RE: ACC TCE Systematic Review Invoice (Contract 6957) Date: Thursday, May 25, 2017 4:08:58 PM Attachments: ACCCCMav17.pdf ACCTCESvstem.tulv.pd Hi Mr. Risotto, See attached invoice for the costs to date. I've also marked off the previous invoice from last year. Please let me know if you have any questions. Thank you, Clinton Ehrhardt Grant Administrator University of Cincinnati, College of Medicine Department of Environmental Health 3223 Eden Ave PO Box 670056 Cincinnati, OH 45267-0056 (513) 558-5067 [email protected] From: Haber, Lynne (haberlt) Sent: Wednesday, May 17, 2017 4:10 PM To: Risotto, Steve <[email protected]>; Taylor, Jennifer <[email protected]>; Ehrhardt, Clinton (ehrharcn) <[email protected]> Cc: Dourson, Michael (doursoml) <[email protected]> Subject: RE: ACC TCE Systematic Review Invoice (Contract 6957) Thanks Steve. This sounds like a reasonable and fair approach. TII work with Clint to develop a revised invoice. Lynne From: Risotto, Steve (mailto:Steve Sent: Wednesday, May 17, 2017 3:27 PM To: Taylor, Jennifer; Ehrhardt, Clinton (ehrharcn) Cc: Haber, Lynne (haberlt); Dourson, Michael (doursoml) Subject: RE: ACC TCE Systematic Review Invoice (Contract 6957) Clinton --- As I recall from my conversation with Dr. Dourson (and as indicated on the June 24 invoice), ACC provided the funds to "pay forward" the costs of Risk Sciences Center (RSC) staff time to be spent on the systematic review project. As a result of circumstances beyond either ACC or RSC's control, however, the project has stalled and it is not clear to me how much time staff have spent at this point. Source: https://www.industrydocuments.ucsf.edu/docs/hrbn0226 169 As I informed Lynne yesterday, my group has decided not to proceed with the project and will be notilying UC officially in the next few days. In light of that decision, we are prepared to pay for the time spent on the project to date - and for any costs incurred with the involvement of the independent panel. To do that, however, I will need a new invoice that describes those costs. The decision to terminate the project is based on an interest in focusing our limited resources elsewhere, and is not the result of dissatisfaction with RSC. Please let me know if you have any questions. Thanks. Steve Steve Risotto | American Chemistry Council Senior Director, Chemical Products & Technology Division scisotto@americanchemistrvcom O: (202) 249-6727 C: (571) 255-0381 bttos:llwww.americanchemistrvcom From: Taylor, Jennifer Sent: Wednesday, May 17, 2017 1:31 PM To: Ehrhardt, Clinton (ehrharcn) Cc: Haber, Lynne (haberlt); Risotto, Steve Subject: RE: ACC TCE Systematic Review Invoice (Contract 6957) Hi, Clinton: I will check into this one, as well, and get back to you. Jennifer From: Ehrhardt, Clinton (ehrharcn) Sent: Wednesday, May 17, 2017 1:27 PM To: Taylor, Jennifer <lennifer Taxor@americanchemistrvcom> Cc: Haber, Lynne (haberlt) <[email protected] Subject: RE: ACC TCE Systematic Review Invoice (Contract 6957) Hi Jennifer, We received payment for ACCTCESystemJun16 as indicated below, but not for ACCTCESystemJul16 Attached is the correspondence for this one. Can you let me know if a check was sent for the second one? Thanks! Clinton Ehrhardt Grant Administrator University of Cincinnati, College of Medicine Source: https://www.industrydocuments.ucsf.edu/docs/hrbn0226 170 Department of Environmental Health 3223 Eden Ave PO Box 670056 Cincinnati, OH 45267-0056 (513)558-5067 [email protected] From: Taylor, Jennifer mailto: Jennifer [email protected]] Sent: Wednesday, May 17, 2017 12:34 PM To: Haber, Lynne (haberlt); Risotto, Steve Subject: RE: ACC TCE Systematic Review Invoice (Contract 6957) Dear Lynn: Our records show that a payment was made to the University Environmental Health Foundation on June 23, 2016 for Invoice # ACCTCESystemJun16, and that the check was cleared on July 1, 2016/deposited to Fifth Third Bank. Please let me know if you have any additional questions. Jennifer From: Haber, Lynne (haberlt) [mailto:habertaucmalluc.edu Sent: Tuesday, May 16, 2017 5:29 PM To: Risotto, Steve <Steve Risotto@americanchemistocom> Cc: Taylor, Jennifer Klennifer [email protected] Subject: RE: ACC TCE Systematic Review Invoice (Contract 6957) Thanks. That is good to hear. It would help to have the documentation so I can send that forward to our business office. (Things are a bit complicated, since there were two invoices of the same amount, with the second one dated June 24, but apparently the business office has a record of the second one being paid.) Lynne From: Risotto, Steve [mailto: Steve Sent: Tuesday, May 16, 2017 5:07 PM To: Haber, Lynne (haberlt) Cc: Taylor, Jennifer Subject: RE: ACC TCE Systematic Review Invoice (Contract 6957) Lynne --- Our records show that a payment in that amount was issued on June 23. Let us know if you need supporting information. Steve Steve Risotto | American Chemistry Council Senior Director, Chemical Products & Technology Division Source: https://www.industrydocuments.ucsf.edu/docs/hrbn0226 171 [email protected] O: (202)249-6727 C: (571) 255-0381 From: Haber, Lynne (haberlt) [mailto:[email protected] Sent: Tuesday, May 16, 2017 4:43 PM To: Risotto, Steve Subject: FW: ACC TCE Systematic Review Invoice (Contract 6957) Thanks in advance for taking care of this! Lynne From: Ehrhardt, Clinton (ehrharcn) Sent: Friday, June 3, 2016 3:44 PM To: Steve Bisottolamericanchemistrv.com Cc: Haber, Lynne (haberlt); Dourson, Michael (doursoml); Maier, Michael (maierma); Ayers, Valerie (ayersvj) Subject: ACC TCE Systematic Review Invoice (Contract 6957) Hi Mr. Risotto, Attached you will find an ACC TCE Systematic Review invoice for contract 6957 with Dr. Dourson. Please let me know if anything else is needed. Thank you, Clinton Ehrhardt Grant Administrator University of Cincinnati, College of Medicine Department of Environmental Health 3223 Eden Ave PO Box 670056 Cincinnati, OH 45267-0056 (513)558-5067 dintonehrhardtaucedu This message may contain confidential information and is intended only for the individual named. If you are not the named addressee do not disseminate, distribute or copy this email. Please notify the sender immediately by email if you have received this email by mistake and delete this email from your system. E-mail transmission cannot be guaranteed to be secure or error-free as information could be intercepted, corrupted, lost, destroyed, arrive late or incomplete, or contain viruses. The sender therefore does not accept liability for any errors or omissions in the contents of this message which arise as a result of email transmission. American Chemistry Council, 700 - 2nd Street NE, Washington, DC 20002, www.americanchemistry.com This message may contain confidential information and is intended only for the individual named. If you are not the named addressee do not disseminate, distribute or copy this email. Please notify the sender immediately by email if you have received this email by mistake and delete this email from your system. E-mail Source: https://www.industrydocuments.ucsf.edu/docs/hrbn0226 University of Cincinnati INVOICE Physicians Company University Environmental Health Foundation Invoice# ACCTCEMay2017 Date: May 25, 2017 To: For: Project: Support for ACC TCE Systematic review, Contract Mr. Steve Risotto 6957 American Chemistry Council 700 2nd Street NE Washington DC, 20002 DESCRIPTION RATE HOURS AMOUNT Support for ACC TCE Systematic review through 5/17/17 Michael Dourson, PhD $ 294.00 14 $ 4,116.00 Lynne Haber, PhD $ 241.00 123 $ 29,643.00 Jerry Ovesen, PhD $ 145.00 16 $ 2,320.00 Jacqueline Patterson, M En $ 261.00 38 $ 9,918.00 Alison Pecquet. M Sc $ 108.00 23.5 $ 2,538.00 Reena Sandhu, PhD $ 230.00 5 $ 1,150.00 Melissa Vincent, MS $ 101.00 19 $ 1,919.00 Honoraria for expert panelists $ 3,250.00 Less: Previous payments for Contract 6957 $ (34,433.50) TOTAL $20,420.50 Please make Checks payable to: Mail Checks to: University Environmental Health Foundation Department of Environmental Health ATTN: Clinton Ehrhardt Phone: 513 558-5067 University of Cincinnati PO Box 670056 Cincinnati, OH 45267-0056 Source: https://www.industrydocuments.ucsf.edu/docs/hrbn0226 University of Cincinnati INVOICE Physicians Company University Environmental Health Foundation Invoice# ACCTCESystemJul16 Date: June 24, 2016 To: For: Mr. Steve Risotto Project: Support for ACC TCE Systematic review, Contract 6957 American Chemistry Council 700 2nd Street, NE Washington, DC 20002 DESCRIPTION RATE HOURS AMOUNT Support for ACC TCE Systematic review Contract 6957 Additional work with panel members to be conducted; Invoice reflects the remaining 1/2 of the TERA Center effort $ 27,600.00 CANCELLED TOTAL $27,600.00 Please make Checks payable to: University Environmental Health Foundation Mail Checks to: Department of Environmental Health University of Cincinnati PO Box 670056 Cincinnati, OH 45267-0056 Source: https://www.industrydocuments.ucsf.edu/docs/hrbn0226

which priority groups are deemed as medium priority groups?

jzbn0226

jzbn0226_p28, jzbn0226_p29, jzbn0226_p30, jzbn0226_p31, jzbn0226_p32, jzbn0226_p33, jzbn0226_p34, jzbn0226_p35, jzbn0226_p36, jzbn0226_p37, jzbn0226_p38, jzbn0226_p39

priority groups 4,5, and 6

endpoints, criteria are similarly available for both acute and chronic classification. The use of one common system allows for appropriate assessment of all substances. GHS classification information is readily available for all substances, as U.S. manufacturers have developed GHS classifications for their products to meet international requirements. ACC's support of the GHS criteria for purposes of this prioritization tool is not a categorical endorsement of the GHS criteria for any other purpose. ACC has been an active participant in the development of GHS and supports the system in principle. The GHS has not been broadly implemented to date in the U.S., although the Occupational Safety and Health Administration (OSHA) has indicated an intent to publish a regulation applying GHS in the workplace. ACC's December 29, 2009, comments on OSHA's proposed rule to modify the existing Hazard Communication Standard (HCS) to reflect the GHS urged that implementation of the GHS adhere to certain principles (e.g., continued application of the "Building Block Approach" of the Purple Book). ACC made specific recommendations concerning details of the Hazard Classification definitions, cut-off values, among others. ACC stands behind those comments. In ACC's view, the use of GHS criteria in a screening-level prioritization of chemicals can materially assist in determining which chemicals receive additional evaluation by the Environmental Protection Agency, but does not necessarily preclude the use of other appropriate, applicable criteria developed under other systems. To classify a chemical in a hazard based priority ranking where there is not direct data on the chemical, EPA can employ the full range of approaches, such as QSAR, SAR, read- across and other modeling tools in which EPA has confidence based on molecular structure. In those situations where there still remains insufficient information on either environmental or human health hazards, the chemical would be classified as "high" for its environmental or health ranking. 1. Environmental Ranking Table 1 provides a summary of how GHS criteria could be logically used for chemical management prioritization. Table 1. Environmental Safety - Hazard Ranking GHS Classification - Ranking Environmental Rank Environmental Score Acute I or Chronic I or Insufficient Information to High 4 Classify Acute II or Chronic II Medium High 3 Acute III or Chronic III/IV or Medium 2 none Not classified Low 1 August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 2. Human Health Ranking Table 2. Human Health - Hazard Ranking Health Rank GHS Classification - Human Health Ranking Score GHS CMR Cat 1a, 1b; OR Repeat Dose </= 10 mg/kg/day (oral); </= 20 mg/kg/day (dermal); </= 50 ppm/6hr/day (gas inhalation); High 4 <<= 0.2 mg/1/6h/day (vapour inhalation); </= 0.02 mg/l/6h/day (dust mist fume inhal). OR insufficient information to classify GHS CMR Cat 2; OR Repeat Dose 10 - 100 mg/kg/day (oral); 20 - 200 mg/kg/day (dermal); Medium High 50 - 250 ppm/6hr/day (gas inhalation); 3 0.2 - 1.0 mg/l/6h/day (vapour inhalation); 0.02 - 0.2 mg/l/6h/day (dust mist fume inhal). Not carcinogen/mutagen/repro/develop;OR Repeat Dose 100 - 1000 mg/kg/day (oral); 200 - 2000 mg/kg/day (dermal); Medium 250 - 1000 ppm/6hr/day (gas inhalation); 2 1.0 - 5.0 mg/l/6h/day (vapour inhalation); 0.2 - 1.0 mg/l/6h/day (dust mist fume inhal). Not carcinogen/mutagen/repro/develop; OR Repeat Dose >1000 mg/kg/day (oral); > 2000 mg/kg/day (dermal); Low > 1000 ppm/6hr/day (gas inhalation); 1 >5.0 mg/l/6h/day (vapour inhalation); > 1.0 mg/l/6h/day (dust mist fume inhal). It is important to note that specific concerns about children's health (specifically potential hazards and adverse effects on the nervous system) and those caused by endocrine disruption mechanisms are addressed in this prioritization process: The GHS CMR "R" classification includes specific evaluation of effects on development in utero and upon growth, maturation and reproduction. ("R" stands for reproductive toxicity and includes adverse effects on sexual function and fertility, as well as developmental toxicity in offspring). Endocrine activity is not a distinct toxicological hazard per se, but rather a measure of a compound's ability to interact with components of the endocrine system. The prioritization process evaluates data and information on relevant apical tests, including tests for reproduction and developmental toxicity (potential endocrine pathways). Thus, even if specific August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 screening for potential endocrine activity has not yet been conducted on certain compounds, hazard identification based on observable outcomes from apical toxicity tests (e.g., outcomes such as pathologic states indicative of disease conditions) covers all modes of action, including endocrine pathways. The toxicity information evaluated (CMR and repeat dose toxicity) is directly relevant to evaluating potential hazards to all individuals, including children. Such data typically includes: 1) identification and definition of possible hazards upon all major organ systems from both acute and repeated exposures, including the nervous system; 2) detection of potential hazards arising from in utero exposures, including possible effects on the nervous system; 3) evaluation of potential of a substance to affect reproduction; and 4) evaluation of the potential of a substance to damage DNA. Integration of Hazard Elements: Each of the environmental and human health classifications is assigned a numeric value based upon its ranking, with 1 being the lowest value and 4 the highest. The greatest ranking (highest hazard potential score) of either Environmental or Human Health is used in a substance- specific priority ranking. The numeric value does not imply relative weighting, but rather a numerical order of priority. B. Exposure Potential Ranking The screening method allows for an initial indication of the extent of exposure potential by considering: 1. The chemical's uses and use pattern(s) 2. Production volume as a first pass indicator of relative emission/release potential since magnitude and route (i.e. air, water, soil) of emissions is not available for all substances. 3. Persistence and bioaccumulation characteristics of the substance. Together the 3 elements are used to rank exposure potential. 1. Use Patterns The proposed approach applies the most current 2006 TSCA Inventory Update Reporting rule (IUR, now called the Chemical Data Reporting rule (CDR) data. To keep the initial prioritization simple and transparent, the approach "bins" different use patterns to align with general exposure potential - intermediates, industrial use, commercial use and consumer use. These patterns are the same as those reported in the IUR and are consistent with REACH exposure categories (intermediates, worker, professional, consumer). Chemicals with consumer product use are likely to have widespread potential for general population exposures and are given high priority ranking within the approach. For the initial prioritization approach, child specific products are captured under general consumer products and all consumer products are weighted equally (see additional discussion below under Second Tier Considerations). Intermediates will have low general population exposures, since these substances are consumed, by definition, within the workplace. Therefore, they are given the lowest priority ranking within the approach. In the context of the proposed approach, the intermediates category includes both intermediates and non-isolated intermediates. A chemical used in multiple use patterns is August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 assigned the priority of the highest use, e.g., a chemical in both industrial and commercial uses would be assigned the commercial Medium-High rank. Table 3. Use Patterns - Exposure Ranking Use Pattern Ranking Use Pattern Score Consumer High 4 Commercial Medium-High 3 Industrial Medium 2 Intermediates Low 1 The IUR Definitions of these terms are (40 CFR 710.3, 710.43): "consumer use" means the use of a chemical substance or a mixture containing a chemical substance (including as part of article) when sold to or made available to consumers for their use. "commercial use" means the use of a chemical substance or a mixture containing a chemical substance (including as part of an article) in a commercial enterprise providing saleable goods or services. "industrial use" means use at a site at which one or more chemical substances or mixtures are manufactured (including imported). "intermediate" means any chemical substance: which is intentionally removed from the equipment in which it is manufactured, and which either is consumed in whole or in part in chemical reaction(s) used for the intentional manufacture of other chemical substance(s) or mixture(s), or is intentionally present for the purpose of altering the rate of such chemical reaction(s) "non-isolated intermediate" means any intermediate that is not intentionally removed from the equipment in which is it manufactured, including the reaction vessel in which it is manufactured, equipment which is ancillary to the reaction vessel, and any equipment through which the substance passes during a continuous flow process, but not including tanks or other vessels in which the substance is stored after its manufacture. 2. Production Volume Recognizing that detailed exposure information will not be available for all substances to be screened, the proposed approach uses production volume as an indicator of exposure, which is widely used in many prioritization schemes. As production volume is just a rough surrogate of emissions, ACC suggests only very broad categories, covering about two orders of magnitude each. It may be useful to consider how additional exposure estimates may be applied in the second tier assessment. Table 4. Production Volume as Emission Surrogate - Exposure Ranking Production Volume as Emission Surrogate Ranking Volume Score >= 100,000,000 lbs national aggregate High 4 1,000,000 lbs to < 100,000,000 lbs national Medium - High 3 aggregate August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 >= 25,000 lbs to < 1,000,000 lbs national Medium 2 aggregate < 25,000 lbs (below IUR site reporting limit) Low 1 3. Persistence and Bioaccumulation Persistence and bioaccumulation are viewed as indicators of exposure, and therefore are considered under the exposure axis of the approach. A persistent substance that is emitted to the environment at the same rate as a non-persistent substance with similar partitioning properties will result in higher exposure to humans and the environment. In fact, multimedia modeling clearly indicates that environmental persistence in the compartment to which a substance partitions is a good indicator of human exposure potential (MacLeod & McKone et al. 2004). Similarly, substances that are not subject to biotransformation by higher organisms will exhibit a high bioaccumulation potential that results in higher exposures via the food chain (Arnot et al. 2010). Therefore, it is recommended to apply the proposed persistence and bioaccumulation criteria in assessment of exposure potential as described below. The persistent and bioaccumulative (P&B) criteria of the proposed approach are targeted toward organic chemicals. Separate assessment criteria are likely needed for P&B evaluation for inorganics/metals, as in the approach taken by Canada's Chemical Management Program (CMP). For assessing persistence, based upon recent expert consensus (Boethling et al., 2009) it is recommended to distinguish persistent from non-persistent chemicals using the following criteria: Volatile chemicals can be defined using a vapor pressure cut-off (i.e., > 1000 Pa) For volatile chemicals, persistent versus non-persistent chemicals are differentiated using a half-life cut-off in air (e.g., a substance is not persistent if air half life is < 2 days). For non-volatile chemicals, non-persistent substances can be defined as substances that are deemed: readily or inherently biodegradable using standard biodegradation tests (OECD 301, 302, 306 test guidelines) or SAR or read across from measured data on a related substance, show an equivalent degree of degradation (i.e. >20% in 28 days) via an abiotic degradation mechanism such as photolysis (OECD 316) or hydrolysi (OECD 111), evaluation of simulation data from transformation in soil, marine water/sediment, brackish water/sediment, surface water/sediment, oceanic water die away (e.g. OECD 308/309) have half lives below 180 days, OR if data are lacking, evaluation via BIOWIN model (EPIWEB 4) Non-volatile substances that are not biodegradable or subject to abiotic losses based on the above criteria would be considered persistent. For assessing bioaccumulation, the key question for screening is the potential for biomagnification based on recent expert consensus (Gobas et al. 2009). To determine if a substance has the potential to biomagnify the following metrics have been agreed: Trophic Magnification Factor (TMF)>1, fish Biomagnification Factor (BMF)>1 fish Bioaccumulation Factor (BAF)/Bioconcentration Factor (BCF) > 5000. These metrics can be August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 derived using lab or field measurements (where available) or recently improved computational models that are included in EPA's EPIWEB model that can be freely downloaded at www.epa.gov/oppt/exposure/pubs/episuite.htm. This approach allows all organics to be addressed and is a scientifically updated version of the approach used in Canada's CMP. Based on the above recommendations, substances can be grouped with regard to persistence and bioaccumulation as follows: Table 5. Persistence and Bioaccumulation - Exposure Ranking Persistence and P&B Ranking P&B Score Bioaccumulation Persistent and High 5 Bioaccumulative Persistent and Not Medium 3 Bioaccumulative OR Not Persistent and Bioaccumulative Not Persistent and Not Low 1 Bioaccumulative Integration of Exposure Elements: As demonstrated in the tables, each factor (use pattern, P&B, and production volume) would be assigned a numeric score based upon its ranking. All 3 factors are added to arrive at an overall value. These values are then separated into categories from low to high exposure potential. A proposed "banding" approach is illustrated in Table 6. Table 6. Integration of Exposure Rankings Combined Score - All 3 Exposure Rank Exposure Ranking elements Score 11 13 High 5 9 10 Medium High 4 7 8 Medium 3 5 6 Medium Low 2 3 4 Low 1 Overall Priority Grouping: In the overall approach, both hazard and exposure elements are considered when placing a substance in a risk-based prioritization ranking. The overall prioritization score for priority grouping and risk evaluation is based on the combined consideration of the hazard and exposure rankings. Priority Groups 7, 8, and 9 are deemed High Priority; Priority Groups 4, 5, and 6 are Medium Priority; and Priority Groups 2 and 3 are Low Priority. August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Review and Comment: It is important that screening be done in an open and transparent way and that the best available information be used. When screening for thousands of chemicals, EPA may not have access to all available information. The process should provide an opportunity for review and comment on initial rankings and an opportunity to submit additional relevant data and information to update proposed rankings with improved information. III. Second Tier Considerations: After the initial screening, some substances within individual priority groupings may require further rank ordering, particularly where a large number of chemicals are in the same priority group. Listed below are the types of information that will be useful to consider in this Second Tier rank ordering: Biomonitoring/Environmental Monitoring Data: Mere detection of chemicals in humans or the environment, i.e., "found in biomonitoring (CDC), found in water (NCOD), and found in air", while providing an indication of exposure, does not provide a useful criterion for exposure potential because almost any industrial or commercial chemical could be detected at trace levels, given increasingly sensitive analytical methods. Therefore, detection alone primarily reflects only the fact that a specific chemical was included in a measurement program. This criterion will also tend to bias the prioritization of chemicals for which well-established analytical methods are available. Consequently, this criterion is not used in the initial prioritization scheme. However, within a particular priority grouping, reliable monitoring information should be considered for Second Tier rank ordering within a quantitative process that assesses if the data is above a level of concern (i.e., places it in a risk context). Use in Children's Products: Protection of childrens' health is a top priority and, in the initial ranking, child-specific products are captured under general consumer products and all consumer products are weighted equally. The specific IUR reporting of information on chemical use in products intended for children would be considered further within a particular priority grouping for Second Tier rank ordering, noting the following points: the IUR definition is based upon use in a child specific product rather than child specific exposure potential¹ (see below). Without knowing a specific product type, it is difficult to understand if 1 IUR definition (Federal Register Volume 75, Number 156, Friday August 30, 2010, p. 49686): Intended for use by children means the chemical substance or mixture is used in or on a product that is specifically intended for use by children age 14 or younger. A chemical substance or mixture is intended for use by children when the submitter answers "yes" to at least on of the following questions for the product into which the submitter's chemical substance or mixture is incorporated: (1) Is the product commonly recognized (i.e., by a reasonable person) as being intended for children age 14 or younger? (2) Does the manufacturer of the product state through product labeling or other written materials that the product is intended for or will be used by children age 14 or younger? (3) Is the advertising, promotion, or marketing of the product aimed at children age 14 or younger? August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 potential child exposure is greater than for a non-child specific product. For example, how does child exposure to a general use cleaner compare to exposure from use in a child's raincoat. In the VCCEP assessments, there are examples for inhalation exposures where estimates of passive child exposure during adult product use exceeded conservative estimates of child exposure during active use of a child-specific product (such as a hobby product) - differences were related to the amount of product used and substance concentration within the product (MEK VCCEP Submission). the IUR definition targets children age 14 and younger. Younger children may be exposed to a variety of non-child specific products that are in general household use. Older children may be exposed to a variety of additional products. the IUR information request is targeted to manufacturers, which may not have direct knowledge of all uses, particularly the presence in products for specific subpopulations, such as children. Therefore, it is not clear that the information requested for the IUR information would be consistently available across all substances being screened. Ideally, this information should be requested from formulators of child-specific products. Therefore, for the initial prioritization approach, which represents a broad, unrefined categorization, child specific products are captured under general consumer products and all consumer products are weighted equally. The IUR information on child specific use would be utilized within a particular priority grouping for Second Tier rank ordering. If the IUR information is utilized, it is important that the limitations above be considered in its application. Emissions Data: Production volume, which is readily available for substances, is used in this proposed approach, but only serves as a surrogate for environmental emissions. For further prioritization, data or estimates of environmental emissions can be used to refine prioritization. Estimates of environmental emissions will be available for some substances (e.g., TRI data). When TRI data are utilized it should be recognized that it addresses only emissions that result from industrial and not wide dispersive uses. In other cases, emissions estimates can be developed as a percentage of production volume based upon consideration of use categories. Within a particular priority grouping, available emissions information can be considered for Second Tier rank ordering, with the understanding that emissions information is not an indicator of actual exposure. Similarly, non-isolated system intermediates, by definition, would have de minimis exposure potential. Therefore, this IUR information could be considered within a particular priority grouping for Second Tier rank ordering. International Risk Management Actions: An initial screening approach for chemical prioritization should be based upon consistent application of specific hazard and exposure science elements that define risk potential. The hazard and exposure elements should be applicable across all substances being evaluated. For initial screening, existence of international risk management action plans should not be a factor that determines priority grouping. Risk management plans may be based upon many factors, including political drivers. It is unclear how factors, their relative weighting, and the rigor of the evaluation may vary across agencies and substances. For initial screening August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 purposes, the same science-based criteria should be used to rank all substances. Consideration of existing international risk management plans could be utilized to check the functioning of the approach and could be considered within a particular priority grouping for Second Tier rank ordering with the possible effect of moving a chemical up in a grouping if actions are being taken internationally. IV. Summary ACC's prioritization approach is an example of a risk-based screening prioritization process that implements the general principles outlined at the outset of this document. It is based upon widely available information that can be utilized to understand the relative priority of chemicals for further evaluation from a risk perspective, i.e., integrating both hazard and exposure elements. Implementation of the screening framework will be most effective when utilizing the best available information. When conducting screening for thousands of chemicals, EPA may not have access to all available information. An open and iterative process that includes an opportunity for review and comment on initial rankings, together with the information that led to the result, and an opportunity to update the ranking with improved information will create a transparent and scientifically sound process. V. References Arnot, J.A., D. Mackay, T. F. Parkerton, R. T. Zaleski, C.S. Warren (2010), Multimedia modeling of human exposure to chemical substances: The roles of food web biomagnification and biotransformation, Environmental Toxicology and Chemistry 29(1):45-55. Boethling, R., K. Fenner, P. Howard, G. Klecka, T. Madsen, J.R. Snape, M.J. Whelan (2009). Environmental persistence of organic pollutants: guidance for development and review of POP risk profiles. Integrated Environmental Assessment and Management 5(4): 539 - 556. Gobas, F.A.P.C, W. de Wolf, L. P Burkhard, E. Verbruggen, K. Plotzke (2009). Revisiting Bioaccumulation Criteria for POPs and PBT Assessments Integrated Environmental Assessment and Management, 5(4):624-637. MacLeod, M., T. E. McKone (2004). Multimedia persistence as an indicator of potential for population-level intake of environmental contaminants, Environmental Toxicology and Chemistry 23(10):2465-2472. van Wijk,D., R. Chénier, T. Henry, M. D Hernando, C. Schulte (2009). Integrated Approach to PBT and POP Prioritization and Risk Assessment' Integrated Environmental Assessment and Management, 5(4):697-711. August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Proposed Prioritization Approach DRAFT May & 2011 Exposure Elements nat commental consumer 20 2 3 a 33 3 not 8 or Persuntence S not 3 mai 35 a & not 3 Pas $ 3 S the iss = the Tormages RUN $ 3 3 SUM - P8 - Tavamage ranow 3 -13 Expesure Ramking $5 Based os Sum (UN# + pa * Townage PRIORITY GROUPING - Hazard * Expasure Ramkings - 1-8 3-10 11-13 mad Jow Hazard - Highter and Human $ 3 3 & $ Human Mazard Not on Dase 3 low mai * anou % 1000 numour 3 1.8 (duet Nume " 3 & 3 8 Not 100 Acure mi os : 3 A 2000 and not data) 280 v 1000 (pas 1.0 8.0 nomour 8.3 miss Nome 3 & % x CMR Cat 2, on Dawe Call 3: 10 - 3 is # 200 50 ase Igas 0.3 1.0 0.0% - 0.2 mis forme * # $ y GMS CMR Can on OHS Clowe Clat % Repeat Close 10 § on 8 on insurticient 20 information to - - - 0.3 wis 0,00 mist on information to $ 3 a $ August 29, 2011 Source: :https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Hazard and Exposure Criteria for Prioritization Approach HAZARD EXPOSURE Environment and Human Health Classifications based upon GHS Use Elements - based upon IUR Intermediate consumed during industrial processing Envirommental: industrial (not intermediate) - used in an industrial setting From GHS classification guidance document: commercial occupational use in nonindustrial setting Table 4.1.2: scheme for substances hazardous so the aquatic environment. consumer general population residential use Clacufication Persistence: Loag-term Votalile substance (VPS 1000 Pax: Not Persistent if air half life <2 days a (Nate 2) Nonvolatile (VP < 1000 Pa): Not Persistent if: Adequate dass Adequnte voriciny dasa aux a) ready biodegradability (OBCD 301) Rapidly 3 b) inherent biodegradability (OBCD 301, 302, 306) degredable 0) read across from measured data on a related substance. 28 (Note. 3) d) equivalent degree of degradation (i.e. >20% in 28 days) via an abjotic Arute 3 Categorys Chronic 1 Categury: 1 Categasy: I degradation mechanism such as photolysis (OBCD 316) or hydrolysis (OBCD NOEC ar ECA 0.1 NOE - EC cass L 1.00 md of maid 111) and/ar BCF a 200 OR, a substance is Not Persistent if: if e) evaluation of simulation data from transformation in soil, marine water/sediment, Caregusy: Acore 2 Category: Chronic 2 Caregury: Chrumin 2 Caregusy: Chruaic 2 brackish water/sediment, surface water/sediment, oceanic water die away (e.g., OECD 3.00 s: s 10.9 0.1 - NOEC er EC. 13 0.00 <: NOEC - EC, 502 3.00 L(EXC) 10.8 and of andies 308/309) have half lives below 180 days. BCF = 500 as if K. 2 4 OR, if data are lacking: Caregusy: Arnie 3 Caregury: 3 Chrinia 3 f) evaluation via BIOWIN model (EPIWEB 4) 01 EC. : 30,00 1- 100 and fack of Bioaccomulation: stapoid andier BOF: Re 300 if absent log x 3 4 A substance is not bioaccumulative if: 4 4) a) measured TMF < 1 (field study) 3) b) measured fish BMF <1 (lab study) Ne tericity and lack of and BCF 2 500 ase, lag E 4, c) measured fish BCF < 5000 (lab study) MOECA 1 mal d) predicted BCP< 5000 using the BCFBAF model included in EPIWIN 4 The above order reflects the preference for use in decision- making NOTE -- P&B CRITERIA ARB FOR ORGANICS Tonnage - based upon JUR reporting ranges <. 25,000 lbs (below IUR site reporting limit) Human Health: 25.000 - <1 MM lbs national aggregate As above, based upon GHS 1MM - <100 MM lbs national aggregate >100 MM lbs national aggregate August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Risk-Based Prioritization Matrix Ancreasing Exposure Two-Step towest Prionies Prioritization Process Incregaling Second Tier Rank Ordering within Priority Groups Biomonitoring / Environmental Monitoring Use in Children's Products Emissions (e.g. TRI) International Risk Management Actions Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226

what is the use of fire retardant plastics?

qrbn0226

qrbn0226_p0, qrbn0226_p1, qrbn0226_p2, qrbn0226_p3, qrbn0226_p4

Fire Retardant (FR) plastics are used in many products(toys, chairs, electronics, etc.) to reduce the risk of fire and burn hazards.

189 From: White, Kimberly To: Admon. Smadar: Anderson Steven; Batoon, Audrey; Bradley, Kevin; de Lacy Catharine; Blkan, llan; Erraguntia. Neeraja: Goodman. Bryan; Hochschwender, Lane: Jacobi. Sylvia.B. Kannah. Kasturirangan; Levan Steve; Levchik. Sergei; Little Barbara: Manor. Orit: Prero. Judab; Rothenbacher, Klaus; Saunders. Eric L Scherrer. Steve; Simon Robert: Tavior. Jennifer; Tenney, Joel: Thorn Amelia: West Jay; White Kimberly; Haves, A Wallace; Rein. Guillermo; [email protected] Troitzsch. Jurgen; Blais. Matthew; Dourson. Michael (doursoml); Kacew Sam; Osimitz. Thomas Subject: Request to Schedule a Call on Baby Monitor Combustion Project Date: Thursday, May 18, 2017 10:32:45 AM Attachments: Baby Monitor Plastic Flammability Proposal finalpdi Dear NAFRA Science Workgroup Members and Science Advisory Council Members: In follow-up to this week's discussion regarding the current status and next steps for the Baby Monit or Combustion Project, we'd like to schedule a call with members and the researchers. Please access the poll below by 5pm (ET) Monday, May 22nd Note all times in the poll are in Eastern Daylight Time. Poll: http://doodle.com/poll/2piythmxu23tugsd. As well below is a summary of the May meeting discussion as provided by Drs. Ezekoye and Marr and attached or in links below are relevant documents. Please review this information and provide any initial additional thoughts you may have regarding the project next steps. Relevant Documents Baby Monitor Combustion Project Proposal (attached) Link to Baby Monitor Combustion Project Update Summary Report in PDF-March 2017 Link to Baby Monitor Combustion PowerPoint Project Update Presented on May 16, 2017 Summary of Discussion by Drs. Ezekoye and Marr Here are some of the commentsf from our conference call. There were two threads: better characterization of the baby monitor cases and developing more representative failure scenarios. The suggestions related to characterizing the baby monitor cases included: - Use X-Ray Photoelectron Spectroscopy (XPS) to look for bromine in the OEM baby monitor cases - Measure the critical heat flux of the OEM and surrogate baby monitor plastics - Create our own FRtreated cases using FR ABS The suggestions related to developing more representative (lower HRR) failures included: - Explore scaling down the failure mode of the existing batteries - Use a cartridge heater as the heat source After the call, Drs. Ezekoye and Marr also discussed another alternative of scaling down the battery size to get different effective failure energies and HRRs. Kind Regards, Kimberly Wise White, Ph. D. | American Chemistry Council Senior Director, Chemical Products & Technology Division Kimberly [email protected] 700 2nd Street NE Washington, DC | 20002 O: (202) 249-6707 C: (202) 341-7602 www.americanchemistry.com This message may contain confidential information and is intended only for the individual named. If you are not the named addressee do not disseminate, distribute or copy this email. Please notify the sender immediately by email if you have received this email by mistake and delete this email from your system. E-mail Source: https://www.industrydocuments.ucsf.edu/docs/qrbn0226 COCKRELL SCHOOL OF ENGINEERING THE UNIVERSITY OF TEXAS AT AUSTIN the 5 Department of Mechanical Engineering . ETC II 5.160 . http://www.me.utexas.edu 1 University Station C2200 . Austin, Texas . 78712-0292 . (512)471-1131 . Fax (512)471-8727 August 3, 2016 Joel Tenney Director of Advocacy ICL-IP America Subject: Baby Monitor Thermal and Flammability Testing Dear Mr. Tenney, Thank you for your interest in working with UT Fire Research Group (UTFRG) to characterize the thermal stability and fire hazards posed by baby monitors. The appended project whitepaper presents our current understanding of the scope of services sought and terms of the engagement. Once you've reviewed this statement of work, please let me know how you would like to proceed. Sincerely, O.A. ('DK') Ezekoye, Ph.D., P.E. W.R. Woolrich Professor Department of Mechanical Engineering & Department of Civil, Arch. and Environ. Engineering Program Director, Online M.S. in Mechanical Engineering Source: https://www.industrydocuments.ucsf.edu/docs/qrbn0226 UTFRG Recall Testing Whitepaper August 3, 2016 Thermal and Flammability Testing of a Recalled Baby Monitor University of Texas Fire Research Group Summary The proposed scope of work is to conduct experimental testing to investigate the thermal characteristics and flammability of baby monitors. Currently, fire retardant (FR) plastics are used in many products (toys, chairs, electronics, etc.) to reduce the risk of fire and burn hazards. Flame retardants are considered by fire scientists to be an integral part of the management and mitigation of fire and burn hazards. It is understood in fire science that addition of flame retardants in polymeric materials can reduce the ignitability and flame spread characteristics of the material. Some detractors of FRs argue that the environmental and public health impact of flame retardants outweigh their potential fire mitigation capability. For portable electronics accessories such as baby monitors that are powered by lithium-ion batteries the fire risk is greater than passive (i.e., unpowered) baby products. Recently several baby monitors branded by Lorex were recalled due to potential burn hazards related to battery failures. Figure 1 shows images of the Lorex baby monitor and battery, and Figure 2 shows images of a failed battery from the Lorex baby monitor. The swollen battery shown in Figure 2 is the result of the battery overheating and producing flammable gas. Although in this case, there were no reports of fires, if enough flammable gas is produced, the battery casing can fail releasing the gas, which can potentially ignited surrounding materials and cause a fire. In the event of a battery thermal failure, FR is likely to reduce the risk of ignition and fire of the baby monitor plastic. - - - Figure 1. Images of the recalled Lorex baby monitor and the lithium-ion battery. Source: https://www.industrydocuments.ucsf.edu/docs/qrbn0226 UTFRG Recall Testing Whitepaper August 3, 2016 Figure 2. Images of swollen battery from a Lorex baby monitor that had failed. The purpose of the proposed work is to investigate the effectiveness of FR on a representative electronic baby accessory. In this study a baby monitor will be used as the representative exemplar. UTFRG proposes that our services be divided into the following tasks: Task A-Fabricate Replica Baby Monitors $10,000.00 ($15,600 w/ overhead) The scope of Task A is to design and fabricate three replicas of a baby monitor. It is UTFRG's understanding that one possible model of interest is manufactured by Lorex (Model No. WL3520, WL4320, and WL3401). As discussed above, these models have been recalled and are currently unavailable from United States retailers. However, it may be possible to obtain exemplar units from international retailers or third-party resellers. If available, UTFRG will procure exemplar baby monitors. If the make and model is commercially unavailable, an alternative make and model may be used. Any alternative model will be agreed upon in discussions with the sponsor prior to procurement. An exemplar baby monitor housing will be laser scanned and three replicas will be fabricated using a 3-D printer. The replica housings will be constructed of material that does not contain fire retardants. One filament system available for testing for the Makerbot systems is PLA 3D Printer Filament/ MakerBot PLA. Makerbot has information on their website about the flammability concerns of their products Figure 3. Makerbot flammability warning video at http://www.makerbot.com/blog/2010/11/29/makerbot-psa-fire-and-abs-pla-dont-mix Source: https://www.industrydocuments.ucsf.edu/docs/qrbn0226 UTFRG Recall Testing Whitepaper August 3, 2016 UTFRG will evaluate the housing material, and replica housings will be printed using the same material type. Components including the LCD, electronics and battery will be extracted from exemplar units and re-installed in the replica housings. Upon completion of this task, UTFRG will provide the sponsor with a report detailing the procurement process, CAD design details, and photographs of the reassembled baby monitors. Electronic CAD files can also be provided upon request. Task A is expected to take five (5) weeks to complete. The cost estimate for this task includes salary for students and research engineer, student tuition and fees, fringe benefits, and supplies. The cost of procuring exemplar monitors is also included. If the work is routed through the University as a contract as compared to a gift, a 1.56 overhead multiplier takes the nominal cost from $10K to $15.6K. Task B-Thermal & Flammability Testing $20,000.00 ($31,200 w/ overhead) Upon completion of Task A, UTFRG will develop and implement a test program to assess the effectiveness of FR on electronic baby products. The testing will include small scale ignition tests on the base plastics and full system flammability experiments on six (6) baby monitors: three (3) exemplar monitors and three (3) replica monitors. In the full system experiments, fire will be induced by thermally failing the battery. The battery will be charged to 100% state-of- charge (SOC) prior to thermal failure. In actual use scenarios, batteries often fail due to internal shorts from manufacturing defects, mechanical damage overcharging. Because of the stochastic nature of thermal failures, simulating an internal short in a lab setting can be challenging. The most reliable method to thermally fail a battery is to apply external heat; however, external heat may lead to heat damage or potentially ignition of the housing prior to the battery thermal failure. UTFRG will investigate and develop a reliable failure method to fail the battery while minimizing collateral damage during said failure. Testing will be photo-documented and video recorded. Additional measurements will also made. These measurements include, but are not limited to, surface temperature of the baby monitor housing, battery and electronic circuit board, heat release from the induced fire, and thermal imaging of the induced fire. Upon completion of this Task, UTFRG will provide a report and presentation-style report. Raw data and videos will be provided upon request. Task B is expected to take ten (10) weeks to complete. The cost estimate for this task includes salary for students and research engineer, student tuition and fees, fringe benefits, and supplies. The cost of procuring exemplar monitors is also included. If the work is routed through the University as a contract as compared to a gift, a 1.56 overhead multiplier takes the nominal cost from $20K to $31.2K. Source: https://www.industrydocuments.ucsf.edu/docs/qrbn0226

which priority groups are deemed as low priority groups ?

jzbn0226

jzbn0226_p28, jzbn0226_p29, jzbn0226_p30, jzbn0226_p31, jzbn0226_p32, jzbn0226_p33, jzbn0226_p34, jzbn0226_p35, jzbn0226_p36, jzbn0226_p37, jzbn0226_p38, jzbn0226_p39

Priority groups 2 and 3

endpoints, criteria are similarly available for both acute and chronic classification. The use of one common system allows for appropriate assessment of all substances. GHS classification information is readily available for all substances, as U.S. manufacturers have developed GHS classifications for their products to meet international requirements. ACC's support of the GHS criteria for purposes of this prioritization tool is not a categorical endorsement of the GHS criteria for any other purpose. ACC has been an active participant in the development of GHS and supports the system in principle. The GHS has not been broadly implemented to date in the U.S., although the Occupational Safety and Health Administration (OSHA) has indicated an intent to publish a regulation applying GHS in the workplace. ACC's December 29, 2009, comments on OSHA's proposed rule to modify the existing Hazard Communication Standard (HCS) to reflect the GHS urged that implementation of the GHS adhere to certain principles (e.g., continued application of the "Building Block Approach" of the Purple Book). ACC made specific recommendations concerning details of the Hazard Classification definitions, cut-off values, among others. ACC stands behind those comments. In ACC's view, the use of GHS criteria in a screening-level prioritization of chemicals can materially assist in determining which chemicals receive additional evaluation by the Environmental Protection Agency, but does not necessarily preclude the use of other appropriate, applicable criteria developed under other systems. To classify a chemical in a hazard based priority ranking where there is not direct data on the chemical, EPA can employ the full range of approaches, such as QSAR, SAR, read- across and other modeling tools in which EPA has confidence based on molecular structure. In those situations where there still remains insufficient information on either environmental or human health hazards, the chemical would be classified as "high" for its environmental or health ranking. 1. Environmental Ranking Table 1 provides a summary of how GHS criteria could be logically used for chemical management prioritization. Table 1. Environmental Safety - Hazard Ranking GHS Classification - Ranking Environmental Rank Environmental Score Acute I or Chronic I or Insufficient Information to High 4 Classify Acute II or Chronic II Medium High 3 Acute III or Chronic III/IV or Medium 2 none Not classified Low 1 August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 2. Human Health Ranking Table 2. Human Health - Hazard Ranking Health Rank GHS Classification - Human Health Ranking Score GHS CMR Cat 1a, 1b; OR Repeat Dose </= 10 mg/kg/day (oral); </= 20 mg/kg/day (dermal); </= 50 ppm/6hr/day (gas inhalation); High 4 <<= 0.2 mg/1/6h/day (vapour inhalation); </= 0.02 mg/l/6h/day (dust mist fume inhal). OR insufficient information to classify GHS CMR Cat 2; OR Repeat Dose 10 - 100 mg/kg/day (oral); 20 - 200 mg/kg/day (dermal); Medium High 50 - 250 ppm/6hr/day (gas inhalation); 3 0.2 - 1.0 mg/l/6h/day (vapour inhalation); 0.02 - 0.2 mg/l/6h/day (dust mist fume inhal). Not carcinogen/mutagen/repro/develop;OR Repeat Dose 100 - 1000 mg/kg/day (oral); 200 - 2000 mg/kg/day (dermal); Medium 250 - 1000 ppm/6hr/day (gas inhalation); 2 1.0 - 5.0 mg/l/6h/day (vapour inhalation); 0.2 - 1.0 mg/l/6h/day (dust mist fume inhal). Not carcinogen/mutagen/repro/develop; OR Repeat Dose >1000 mg/kg/day (oral); > 2000 mg/kg/day (dermal); Low > 1000 ppm/6hr/day (gas inhalation); 1 >5.0 mg/l/6h/day (vapour inhalation); > 1.0 mg/l/6h/day (dust mist fume inhal). It is important to note that specific concerns about children's health (specifically potential hazards and adverse effects on the nervous system) and those caused by endocrine disruption mechanisms are addressed in this prioritization process: The GHS CMR "R" classification includes specific evaluation of effects on development in utero and upon growth, maturation and reproduction. ("R" stands for reproductive toxicity and includes adverse effects on sexual function and fertility, as well as developmental toxicity in offspring). Endocrine activity is not a distinct toxicological hazard per se, but rather a measure of a compound's ability to interact with components of the endocrine system. The prioritization process evaluates data and information on relevant apical tests, including tests for reproduction and developmental toxicity (potential endocrine pathways). Thus, even if specific August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 screening for potential endocrine activity has not yet been conducted on certain compounds, hazard identification based on observable outcomes from apical toxicity tests (e.g., outcomes such as pathologic states indicative of disease conditions) covers all modes of action, including endocrine pathways. The toxicity information evaluated (CMR and repeat dose toxicity) is directly relevant to evaluating potential hazards to all individuals, including children. Such data typically includes: 1) identification and definition of possible hazards upon all major organ systems from both acute and repeated exposures, including the nervous system; 2) detection of potential hazards arising from in utero exposures, including possible effects on the nervous system; 3) evaluation of potential of a substance to affect reproduction; and 4) evaluation of the potential of a substance to damage DNA. Integration of Hazard Elements: Each of the environmental and human health classifications is assigned a numeric value based upon its ranking, with 1 being the lowest value and 4 the highest. The greatest ranking (highest hazard potential score) of either Environmental or Human Health is used in a substance- specific priority ranking. The numeric value does not imply relative weighting, but rather a numerical order of priority. B. Exposure Potential Ranking The screening method allows for an initial indication of the extent of exposure potential by considering: 1. The chemical's uses and use pattern(s) 2. Production volume as a first pass indicator of relative emission/release potential since magnitude and route (i.e. air, water, soil) of emissions is not available for all substances. 3. Persistence and bioaccumulation characteristics of the substance. Together the 3 elements are used to rank exposure potential. 1. Use Patterns The proposed approach applies the most current 2006 TSCA Inventory Update Reporting rule (IUR, now called the Chemical Data Reporting rule (CDR) data. To keep the initial prioritization simple and transparent, the approach "bins" different use patterns to align with general exposure potential - intermediates, industrial use, commercial use and consumer use. These patterns are the same as those reported in the IUR and are consistent with REACH exposure categories (intermediates, worker, professional, consumer). Chemicals with consumer product use are likely to have widespread potential for general population exposures and are given high priority ranking within the approach. For the initial prioritization approach, child specific products are captured under general consumer products and all consumer products are weighted equally (see additional discussion below under Second Tier Considerations). Intermediates will have low general population exposures, since these substances are consumed, by definition, within the workplace. Therefore, they are given the lowest priority ranking within the approach. In the context of the proposed approach, the intermediates category includes both intermediates and non-isolated intermediates. A chemical used in multiple use patterns is August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 assigned the priority of the highest use, e.g., a chemical in both industrial and commercial uses would be assigned the commercial Medium-High rank. Table 3. Use Patterns - Exposure Ranking Use Pattern Ranking Use Pattern Score Consumer High 4 Commercial Medium-High 3 Industrial Medium 2 Intermediates Low 1 The IUR Definitions of these terms are (40 CFR 710.3, 710.43): "consumer use" means the use of a chemical substance or a mixture containing a chemical substance (including as part of article) when sold to or made available to consumers for their use. "commercial use" means the use of a chemical substance or a mixture containing a chemical substance (including as part of an article) in a commercial enterprise providing saleable goods or services. "industrial use" means use at a site at which one or more chemical substances or mixtures are manufactured (including imported). "intermediate" means any chemical substance: which is intentionally removed from the equipment in which it is manufactured, and which either is consumed in whole or in part in chemical reaction(s) used for the intentional manufacture of other chemical substance(s) or mixture(s), or is intentionally present for the purpose of altering the rate of such chemical reaction(s) "non-isolated intermediate" means any intermediate that is not intentionally removed from the equipment in which is it manufactured, including the reaction vessel in which it is manufactured, equipment which is ancillary to the reaction vessel, and any equipment through which the substance passes during a continuous flow process, but not including tanks or other vessels in which the substance is stored after its manufacture. 2. Production Volume Recognizing that detailed exposure information will not be available for all substances to be screened, the proposed approach uses production volume as an indicator of exposure, which is widely used in many prioritization schemes. As production volume is just a rough surrogate of emissions, ACC suggests only very broad categories, covering about two orders of magnitude each. It may be useful to consider how additional exposure estimates may be applied in the second tier assessment. Table 4. Production Volume as Emission Surrogate - Exposure Ranking Production Volume as Emission Surrogate Ranking Volume Score >= 100,000,000 lbs national aggregate High 4 1,000,000 lbs to < 100,000,000 lbs national Medium - High 3 aggregate August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 >= 25,000 lbs to < 1,000,000 lbs national Medium 2 aggregate < 25,000 lbs (below IUR site reporting limit) Low 1 3. Persistence and Bioaccumulation Persistence and bioaccumulation are viewed as indicators of exposure, and therefore are considered under the exposure axis of the approach. A persistent substance that is emitted to the environment at the same rate as a non-persistent substance with similar partitioning properties will result in higher exposure to humans and the environment. In fact, multimedia modeling clearly indicates that environmental persistence in the compartment to which a substance partitions is a good indicator of human exposure potential (MacLeod & McKone et al. 2004). Similarly, substances that are not subject to biotransformation by higher organisms will exhibit a high bioaccumulation potential that results in higher exposures via the food chain (Arnot et al. 2010). Therefore, it is recommended to apply the proposed persistence and bioaccumulation criteria in assessment of exposure potential as described below. The persistent and bioaccumulative (P&B) criteria of the proposed approach are targeted toward organic chemicals. Separate assessment criteria are likely needed for P&B evaluation for inorganics/metals, as in the approach taken by Canada's Chemical Management Program (CMP). For assessing persistence, based upon recent expert consensus (Boethling et al., 2009) it is recommended to distinguish persistent from non-persistent chemicals using the following criteria: Volatile chemicals can be defined using a vapor pressure cut-off (i.e., > 1000 Pa) For volatile chemicals, persistent versus non-persistent chemicals are differentiated using a half-life cut-off in air (e.g., a substance is not persistent if air half life is < 2 days). For non-volatile chemicals, non-persistent substances can be defined as substances that are deemed: readily or inherently biodegradable using standard biodegradation tests (OECD 301, 302, 306 test guidelines) or SAR or read across from measured data on a related substance, show an equivalent degree of degradation (i.e. >20% in 28 days) via an abiotic degradation mechanism such as photolysis (OECD 316) or hydrolysi (OECD 111), evaluation of simulation data from transformation in soil, marine water/sediment, brackish water/sediment, surface water/sediment, oceanic water die away (e.g. OECD 308/309) have half lives below 180 days, OR if data are lacking, evaluation via BIOWIN model (EPIWEB 4) Non-volatile substances that are not biodegradable or subject to abiotic losses based on the above criteria would be considered persistent. For assessing bioaccumulation, the key question for screening is the potential for biomagnification based on recent expert consensus (Gobas et al. 2009). To determine if a substance has the potential to biomagnify the following metrics have been agreed: Trophic Magnification Factor (TMF)>1, fish Biomagnification Factor (BMF)>1 fish Bioaccumulation Factor (BAF)/Bioconcentration Factor (BCF) > 5000. These metrics can be August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 derived using lab or field measurements (where available) or recently improved computational models that are included in EPA's EPIWEB model that can be freely downloaded at www.epa.gov/oppt/exposure/pubs/episuite.htm. This approach allows all organics to be addressed and is a scientifically updated version of the approach used in Canada's CMP. Based on the above recommendations, substances can be grouped with regard to persistence and bioaccumulation as follows: Table 5. Persistence and Bioaccumulation - Exposure Ranking Persistence and P&B Ranking P&B Score Bioaccumulation Persistent and High 5 Bioaccumulative Persistent and Not Medium 3 Bioaccumulative OR Not Persistent and Bioaccumulative Not Persistent and Not Low 1 Bioaccumulative Integration of Exposure Elements: As demonstrated in the tables, each factor (use pattern, P&B, and production volume) would be assigned a numeric score based upon its ranking. All 3 factors are added to arrive at an overall value. These values are then separated into categories from low to high exposure potential. A proposed "banding" approach is illustrated in Table 6. Table 6. Integration of Exposure Rankings Combined Score - All 3 Exposure Rank Exposure Ranking elements Score 11 13 High 5 9 10 Medium High 4 7 8 Medium 3 5 6 Medium Low 2 3 4 Low 1 Overall Priority Grouping: In the overall approach, both hazard and exposure elements are considered when placing a substance in a risk-based prioritization ranking. The overall prioritization score for priority grouping and risk evaluation is based on the combined consideration of the hazard and exposure rankings. Priority Groups 7, 8, and 9 are deemed High Priority; Priority Groups 4, 5, and 6 are Medium Priority; and Priority Groups 2 and 3 are Low Priority. August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Review and Comment: It is important that screening be done in an open and transparent way and that the best available information be used. When screening for thousands of chemicals, EPA may not have access to all available information. The process should provide an opportunity for review and comment on initial rankings and an opportunity to submit additional relevant data and information to update proposed rankings with improved information. III. Second Tier Considerations: After the initial screening, some substances within individual priority groupings may require further rank ordering, particularly where a large number of chemicals are in the same priority group. Listed below are the types of information that will be useful to consider in this Second Tier rank ordering: Biomonitoring/Environmental Monitoring Data: Mere detection of chemicals in humans or the environment, i.e., "found in biomonitoring (CDC), found in water (NCOD), and found in air", while providing an indication of exposure, does not provide a useful criterion for exposure potential because almost any industrial or commercial chemical could be detected at trace levels, given increasingly sensitive analytical methods. Therefore, detection alone primarily reflects only the fact that a specific chemical was included in a measurement program. This criterion will also tend to bias the prioritization of chemicals for which well-established analytical methods are available. Consequently, this criterion is not used in the initial prioritization scheme. However, within a particular priority grouping, reliable monitoring information should be considered for Second Tier rank ordering within a quantitative process that assesses if the data is above a level of concern (i.e., places it in a risk context). Use in Children's Products: Protection of childrens' health is a top priority and, in the initial ranking, child-specific products are captured under general consumer products and all consumer products are weighted equally. The specific IUR reporting of information on chemical use in products intended for children would be considered further within a particular priority grouping for Second Tier rank ordering, noting the following points: the IUR definition is based upon use in a child specific product rather than child specific exposure potential¹ (see below). Without knowing a specific product type, it is difficult to understand if 1 IUR definition (Federal Register Volume 75, Number 156, Friday August 30, 2010, p. 49686): Intended for use by children means the chemical substance or mixture is used in or on a product that is specifically intended for use by children age 14 or younger. A chemical substance or mixture is intended for use by children when the submitter answers "yes" to at least on of the following questions for the product into which the submitter's chemical substance or mixture is incorporated: (1) Is the product commonly recognized (i.e., by a reasonable person) as being intended for children age 14 or younger? (2) Does the manufacturer of the product state through product labeling or other written materials that the product is intended for or will be used by children age 14 or younger? (3) Is the advertising, promotion, or marketing of the product aimed at children age 14 or younger? August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 potential child exposure is greater than for a non-child specific product. For example, how does child exposure to a general use cleaner compare to exposure from use in a child's raincoat. In the VCCEP assessments, there are examples for inhalation exposures where estimates of passive child exposure during adult product use exceeded conservative estimates of child exposure during active use of a child-specific product (such as a hobby product) - differences were related to the amount of product used and substance concentration within the product (MEK VCCEP Submission). the IUR definition targets children age 14 and younger. Younger children may be exposed to a variety of non-child specific products that are in general household use. Older children may be exposed to a variety of additional products. the IUR information request is targeted to manufacturers, which may not have direct knowledge of all uses, particularly the presence in products for specific subpopulations, such as children. Therefore, it is not clear that the information requested for the IUR information would be consistently available across all substances being screened. Ideally, this information should be requested from formulators of child-specific products. Therefore, for the initial prioritization approach, which represents a broad, unrefined categorization, child specific products are captured under general consumer products and all consumer products are weighted equally. The IUR information on child specific use would be utilized within a particular priority grouping for Second Tier rank ordering. If the IUR information is utilized, it is important that the limitations above be considered in its application. Emissions Data: Production volume, which is readily available for substances, is used in this proposed approach, but only serves as a surrogate for environmental emissions. For further prioritization, data or estimates of environmental emissions can be used to refine prioritization. Estimates of environmental emissions will be available for some substances (e.g., TRI data). When TRI data are utilized it should be recognized that it addresses only emissions that result from industrial and not wide dispersive uses. In other cases, emissions estimates can be developed as a percentage of production volume based upon consideration of use categories. Within a particular priority grouping, available emissions information can be considered for Second Tier rank ordering, with the understanding that emissions information is not an indicator of actual exposure. Similarly, non-isolated system intermediates, by definition, would have de minimis exposure potential. Therefore, this IUR information could be considered within a particular priority grouping for Second Tier rank ordering. International Risk Management Actions: An initial screening approach for chemical prioritization should be based upon consistent application of specific hazard and exposure science elements that define risk potential. The hazard and exposure elements should be applicable across all substances being evaluated. For initial screening, existence of international risk management action plans should not be a factor that determines priority grouping. Risk management plans may be based upon many factors, including political drivers. It is unclear how factors, their relative weighting, and the rigor of the evaluation may vary across agencies and substances. For initial screening August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 purposes, the same science-based criteria should be used to rank all substances. Consideration of existing international risk management plans could be utilized to check the functioning of the approach and could be considered within a particular priority grouping for Second Tier rank ordering with the possible effect of moving a chemical up in a grouping if actions are being taken internationally. IV. Summary ACC's prioritization approach is an example of a risk-based screening prioritization process that implements the general principles outlined at the outset of this document. It is based upon widely available information that can be utilized to understand the relative priority of chemicals for further evaluation from a risk perspective, i.e., integrating both hazard and exposure elements. Implementation of the screening framework will be most effective when utilizing the best available information. When conducting screening for thousands of chemicals, EPA may not have access to all available information. An open and iterative process that includes an opportunity for review and comment on initial rankings, together with the information that led to the result, and an opportunity to update the ranking with improved information will create a transparent and scientifically sound process. V. References Arnot, J.A., D. Mackay, T. F. Parkerton, R. T. Zaleski, C.S. Warren (2010), Multimedia modeling of human exposure to chemical substances: The roles of food web biomagnification and biotransformation, Environmental Toxicology and Chemistry 29(1):45-55. Boethling, R., K. Fenner, P. Howard, G. Klecka, T. Madsen, J.R. Snape, M.J. Whelan (2009). Environmental persistence of organic pollutants: guidance for development and review of POP risk profiles. Integrated Environmental Assessment and Management 5(4): 539 - 556. Gobas, F.A.P.C, W. de Wolf, L. P Burkhard, E. Verbruggen, K. Plotzke (2009). Revisiting Bioaccumulation Criteria for POPs and PBT Assessments Integrated Environmental Assessment and Management, 5(4):624-637. MacLeod, M., T. E. McKone (2004). Multimedia persistence as an indicator of potential for population-level intake of environmental contaminants, Environmental Toxicology and Chemistry 23(10):2465-2472. van Wijk,D., R. Chénier, T. Henry, M. D Hernando, C. Schulte (2009). Integrated Approach to PBT and POP Prioritization and Risk Assessment' Integrated Environmental Assessment and Management, 5(4):697-711. August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Proposed Prioritization Approach DRAFT May & 2011 Exposure Elements nat commental consumer 20 2 3 a 33 3 not 8 or Persuntence S not 3 mai 35 a & not 3 Pas $ 3 S the iss = the Tormages RUN $ 3 3 SUM - P8 - Tavamage ranow 3 -13 Expesure Ramking $5 Based os Sum (UN# + pa * Townage PRIORITY GROUPING - Hazard * Expasure Ramkings - 1-8 3-10 11-13 mad Jow Hazard - Highter and Human $ 3 3 & $ Human Mazard Not on Dase 3 low mai * anou % 1000 numour 3 1.8 (duet Nume " 3 & 3 8 Not 100 Acure mi os : 3 A 2000 and not data) 280 v 1000 (pas 1.0 8.0 nomour 8.3 miss Nome 3 & % x CMR Cat 2, on Dawe Call 3: 10 - 3 is # 200 50 ase Igas 0.3 1.0 0.0% - 0.2 mis forme * # $ y GMS CMR Can on OHS Clowe Clat % Repeat Close 10 § on 8 on insurticient 20 information to - - - 0.3 wis 0,00 mist on information to $ 3 a $ August 29, 2011 Source: :https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Hazard and Exposure Criteria for Prioritization Approach HAZARD EXPOSURE Environment and Human Health Classifications based upon GHS Use Elements - based upon IUR Intermediate consumed during industrial processing Envirommental: industrial (not intermediate) - used in an industrial setting From GHS classification guidance document: commercial occupational use in nonindustrial setting Table 4.1.2: scheme for substances hazardous so the aquatic environment. consumer general population residential use Clacufication Persistence: Loag-term Votalile substance (VPS 1000 Pax: Not Persistent if air half life <2 days a (Nate 2) Nonvolatile (VP < 1000 Pa): Not Persistent if: Adequate dass Adequnte voriciny dasa aux a) ready biodegradability (OBCD 301) Rapidly 3 b) inherent biodegradability (OBCD 301, 302, 306) degredable 0) read across from measured data on a related substance. 28 (Note. 3) d) equivalent degree of degradation (i.e. >20% in 28 days) via an abjotic Arute 3 Categorys Chronic 1 Categury: 1 Categasy: I degradation mechanism such as photolysis (OBCD 316) or hydrolysis (OBCD NOEC ar ECA 0.1 NOE - EC cass L 1.00 md of maid 111) and/ar BCF a 200 OR, a substance is Not Persistent if: if e) evaluation of simulation data from transformation in soil, marine water/sediment, Caregusy: Acore 2 Category: Chronic 2 Caregury: Chrumin 2 Caregusy: Chruaic 2 brackish water/sediment, surface water/sediment, oceanic water die away (e.g., OECD 3.00 s: s 10.9 0.1 - NOEC er EC. 13 0.00 <: NOEC - EC, 502 3.00 L(EXC) 10.8 and of andies 308/309) have half lives below 180 days. BCF = 500 as if K. 2 4 OR, if data are lacking: Caregusy: Arnie 3 Caregury: 3 Chrinia 3 f) evaluation via BIOWIN model (EPIWEB 4) 01 EC. : 30,00 1- 100 and fack of Bioaccomulation: stapoid andier BOF: Re 300 if absent log x 3 4 A substance is not bioaccumulative if: 4 4) a) measured TMF < 1 (field study) 3) b) measured fish BMF <1 (lab study) Ne tericity and lack of and BCF 2 500 ase, lag E 4, c) measured fish BCF < 5000 (lab study) MOECA 1 mal d) predicted BCP< 5000 using the BCFBAF model included in EPIWIN 4 The above order reflects the preference for use in decision- making NOTE -- P&B CRITERIA ARB FOR ORGANICS Tonnage - based upon JUR reporting ranges <. 25,000 lbs (below IUR site reporting limit) Human Health: 25.000 - <1 MM lbs national aggregate As above, based upon GHS 1MM - <100 MM lbs national aggregate >100 MM lbs national aggregate August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Risk-Based Prioritization Matrix Ancreasing Exposure Two-Step towest Prionies Prioritization Process Incregaling Second Tier Rank Ordering within Priority Groups Biomonitoring / Environmental Monitoring Use in Children's Products Emissions (e.g. TRI) International Risk Management Actions Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226

in which year this data was published ?

jzbn0226

jzbn0226_p28, jzbn0226_p29, jzbn0226_p30, jzbn0226_p31, jzbn0226_p32, jzbn0226_p33, jzbn0226_p34, jzbn0226_p35, jzbn0226_p36, jzbn0226_p37, jzbn0226_p38, jzbn0226_p39

2011

endpoints, criteria are similarly available for both acute and chronic classification. The use of one common system allows for appropriate assessment of all substances. GHS classification information is readily available for all substances, as U.S. manufacturers have developed GHS classifications for their products to meet international requirements. ACC's support of the GHS criteria for purposes of this prioritization tool is not a categorical endorsement of the GHS criteria for any other purpose. ACC has been an active participant in the development of GHS and supports the system in principle. The GHS has not been broadly implemented to date in the U.S., although the Occupational Safety and Health Administration (OSHA) has indicated an intent to publish a regulation applying GHS in the workplace. ACC's December 29, 2009, comments on OSHA's proposed rule to modify the existing Hazard Communication Standard (HCS) to reflect the GHS urged that implementation of the GHS adhere to certain principles (e.g., continued application of the "Building Block Approach" of the Purple Book). ACC made specific recommendations concerning details of the Hazard Classification definitions, cut-off values, among others. ACC stands behind those comments. In ACC's view, the use of GHS criteria in a screening-level prioritization of chemicals can materially assist in determining which chemicals receive additional evaluation by the Environmental Protection Agency, but does not necessarily preclude the use of other appropriate, applicable criteria developed under other systems. To classify a chemical in a hazard based priority ranking where there is not direct data on the chemical, EPA can employ the full range of approaches, such as QSAR, SAR, read- across and other modeling tools in which EPA has confidence based on molecular structure. In those situations where there still remains insufficient information on either environmental or human health hazards, the chemical would be classified as "high" for its environmental or health ranking. 1. Environmental Ranking Table 1 provides a summary of how GHS criteria could be logically used for chemical management prioritization. Table 1. Environmental Safety - Hazard Ranking GHS Classification - Ranking Environmental Rank Environmental Score Acute I or Chronic I or Insufficient Information to High 4 Classify Acute II or Chronic II Medium High 3 Acute III or Chronic III/IV or Medium 2 none Not classified Low 1 August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 2. Human Health Ranking Table 2. Human Health - Hazard Ranking Health Rank GHS Classification - Human Health Ranking Score GHS CMR Cat 1a, 1b; OR Repeat Dose </= 10 mg/kg/day (oral); </= 20 mg/kg/day (dermal); </= 50 ppm/6hr/day (gas inhalation); High 4 <<= 0.2 mg/1/6h/day (vapour inhalation); </= 0.02 mg/l/6h/day (dust mist fume inhal). OR insufficient information to classify GHS CMR Cat 2; OR Repeat Dose 10 - 100 mg/kg/day (oral); 20 - 200 mg/kg/day (dermal); Medium High 50 - 250 ppm/6hr/day (gas inhalation); 3 0.2 - 1.0 mg/l/6h/day (vapour inhalation); 0.02 - 0.2 mg/l/6h/day (dust mist fume inhal). Not carcinogen/mutagen/repro/develop;OR Repeat Dose 100 - 1000 mg/kg/day (oral); 200 - 2000 mg/kg/day (dermal); Medium 250 - 1000 ppm/6hr/day (gas inhalation); 2 1.0 - 5.0 mg/l/6h/day (vapour inhalation); 0.2 - 1.0 mg/l/6h/day (dust mist fume inhal). Not carcinogen/mutagen/repro/develop; OR Repeat Dose >1000 mg/kg/day (oral); > 2000 mg/kg/day (dermal); Low > 1000 ppm/6hr/day (gas inhalation); 1 >5.0 mg/l/6h/day (vapour inhalation); > 1.0 mg/l/6h/day (dust mist fume inhal). It is important to note that specific concerns about children's health (specifically potential hazards and adverse effects on the nervous system) and those caused by endocrine disruption mechanisms are addressed in this prioritization process: The GHS CMR "R" classification includes specific evaluation of effects on development in utero and upon growth, maturation and reproduction. ("R" stands for reproductive toxicity and includes adverse effects on sexual function and fertility, as well as developmental toxicity in offspring). Endocrine activity is not a distinct toxicological hazard per se, but rather a measure of a compound's ability to interact with components of the endocrine system. The prioritization process evaluates data and information on relevant apical tests, including tests for reproduction and developmental toxicity (potential endocrine pathways). Thus, even if specific August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 screening for potential endocrine activity has not yet been conducted on certain compounds, hazard identification based on observable outcomes from apical toxicity tests (e.g., outcomes such as pathologic states indicative of disease conditions) covers all modes of action, including endocrine pathways. The toxicity information evaluated (CMR and repeat dose toxicity) is directly relevant to evaluating potential hazards to all individuals, including children. Such data typically includes: 1) identification and definition of possible hazards upon all major organ systems from both acute and repeated exposures, including the nervous system; 2) detection of potential hazards arising from in utero exposures, including possible effects on the nervous system; 3) evaluation of potential of a substance to affect reproduction; and 4) evaluation of the potential of a substance to damage DNA. Integration of Hazard Elements: Each of the environmental and human health classifications is assigned a numeric value based upon its ranking, with 1 being the lowest value and 4 the highest. The greatest ranking (highest hazard potential score) of either Environmental or Human Health is used in a substance- specific priority ranking. The numeric value does not imply relative weighting, but rather a numerical order of priority. B. Exposure Potential Ranking The screening method allows for an initial indication of the extent of exposure potential by considering: 1. The chemical's uses and use pattern(s) 2. Production volume as a first pass indicator of relative emission/release potential since magnitude and route (i.e. air, water, soil) of emissions is not available for all substances. 3. Persistence and bioaccumulation characteristics of the substance. Together the 3 elements are used to rank exposure potential. 1. Use Patterns The proposed approach applies the most current 2006 TSCA Inventory Update Reporting rule (IUR, now called the Chemical Data Reporting rule (CDR) data. To keep the initial prioritization simple and transparent, the approach "bins" different use patterns to align with general exposure potential - intermediates, industrial use, commercial use and consumer use. These patterns are the same as those reported in the IUR and are consistent with REACH exposure categories (intermediates, worker, professional, consumer). Chemicals with consumer product use are likely to have widespread potential for general population exposures and are given high priority ranking within the approach. For the initial prioritization approach, child specific products are captured under general consumer products and all consumer products are weighted equally (see additional discussion below under Second Tier Considerations). Intermediates will have low general population exposures, since these substances are consumed, by definition, within the workplace. Therefore, they are given the lowest priority ranking within the approach. In the context of the proposed approach, the intermediates category includes both intermediates and non-isolated intermediates. A chemical used in multiple use patterns is August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 assigned the priority of the highest use, e.g., a chemical in both industrial and commercial uses would be assigned the commercial Medium-High rank. Table 3. Use Patterns - Exposure Ranking Use Pattern Ranking Use Pattern Score Consumer High 4 Commercial Medium-High 3 Industrial Medium 2 Intermediates Low 1 The IUR Definitions of these terms are (40 CFR 710.3, 710.43): "consumer use" means the use of a chemical substance or a mixture containing a chemical substance (including as part of article) when sold to or made available to consumers for their use. "commercial use" means the use of a chemical substance or a mixture containing a chemical substance (including as part of an article) in a commercial enterprise providing saleable goods or services. "industrial use" means use at a site at which one or more chemical substances or mixtures are manufactured (including imported). "intermediate" means any chemical substance: which is intentionally removed from the equipment in which it is manufactured, and which either is consumed in whole or in part in chemical reaction(s) used for the intentional manufacture of other chemical substance(s) or mixture(s), or is intentionally present for the purpose of altering the rate of such chemical reaction(s) "non-isolated intermediate" means any intermediate that is not intentionally removed from the equipment in which is it manufactured, including the reaction vessel in which it is manufactured, equipment which is ancillary to the reaction vessel, and any equipment through which the substance passes during a continuous flow process, but not including tanks or other vessels in which the substance is stored after its manufacture. 2. Production Volume Recognizing that detailed exposure information will not be available for all substances to be screened, the proposed approach uses production volume as an indicator of exposure, which is widely used in many prioritization schemes. As production volume is just a rough surrogate of emissions, ACC suggests only very broad categories, covering about two orders of magnitude each. It may be useful to consider how additional exposure estimates may be applied in the second tier assessment. Table 4. Production Volume as Emission Surrogate - Exposure Ranking Production Volume as Emission Surrogate Ranking Volume Score >= 100,000,000 lbs national aggregate High 4 1,000,000 lbs to < 100,000,000 lbs national Medium - High 3 aggregate August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 >= 25,000 lbs to < 1,000,000 lbs national Medium 2 aggregate < 25,000 lbs (below IUR site reporting limit) Low 1 3. Persistence and Bioaccumulation Persistence and bioaccumulation are viewed as indicators of exposure, and therefore are considered under the exposure axis of the approach. A persistent substance that is emitted to the environment at the same rate as a non-persistent substance with similar partitioning properties will result in higher exposure to humans and the environment. In fact, multimedia modeling clearly indicates that environmental persistence in the compartment to which a substance partitions is a good indicator of human exposure potential (MacLeod & McKone et al. 2004). Similarly, substances that are not subject to biotransformation by higher organisms will exhibit a high bioaccumulation potential that results in higher exposures via the food chain (Arnot et al. 2010). Therefore, it is recommended to apply the proposed persistence and bioaccumulation criteria in assessment of exposure potential as described below. The persistent and bioaccumulative (P&B) criteria of the proposed approach are targeted toward organic chemicals. Separate assessment criteria are likely needed for P&B evaluation for inorganics/metals, as in the approach taken by Canada's Chemical Management Program (CMP). For assessing persistence, based upon recent expert consensus (Boethling et al., 2009) it is recommended to distinguish persistent from non-persistent chemicals using the following criteria: Volatile chemicals can be defined using a vapor pressure cut-off (i.e., > 1000 Pa) For volatile chemicals, persistent versus non-persistent chemicals are differentiated using a half-life cut-off in air (e.g., a substance is not persistent if air half life is < 2 days). For non-volatile chemicals, non-persistent substances can be defined as substances that are deemed: readily or inherently biodegradable using standard biodegradation tests (OECD 301, 302, 306 test guidelines) or SAR or read across from measured data on a related substance, show an equivalent degree of degradation (i.e. >20% in 28 days) via an abiotic degradation mechanism such as photolysis (OECD 316) or hydrolysi (OECD 111), evaluation of simulation data from transformation in soil, marine water/sediment, brackish water/sediment, surface water/sediment, oceanic water die away (e.g. OECD 308/309) have half lives below 180 days, OR if data are lacking, evaluation via BIOWIN model (EPIWEB 4) Non-volatile substances that are not biodegradable or subject to abiotic losses based on the above criteria would be considered persistent. For assessing bioaccumulation, the key question for screening is the potential for biomagnification based on recent expert consensus (Gobas et al. 2009). To determine if a substance has the potential to biomagnify the following metrics have been agreed: Trophic Magnification Factor (TMF)>1, fish Biomagnification Factor (BMF)>1 fish Bioaccumulation Factor (BAF)/Bioconcentration Factor (BCF) > 5000. These metrics can be August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 derived using lab or field measurements (where available) or recently improved computational models that are included in EPA's EPIWEB model that can be freely downloaded at www.epa.gov/oppt/exposure/pubs/episuite.htm. This approach allows all organics to be addressed and is a scientifically updated version of the approach used in Canada's CMP. Based on the above recommendations, substances can be grouped with regard to persistence and bioaccumulation as follows: Table 5. Persistence and Bioaccumulation - Exposure Ranking Persistence and P&B Ranking P&B Score Bioaccumulation Persistent and High 5 Bioaccumulative Persistent and Not Medium 3 Bioaccumulative OR Not Persistent and Bioaccumulative Not Persistent and Not Low 1 Bioaccumulative Integration of Exposure Elements: As demonstrated in the tables, each factor (use pattern, P&B, and production volume) would be assigned a numeric score based upon its ranking. All 3 factors are added to arrive at an overall value. These values are then separated into categories from low to high exposure potential. A proposed "banding" approach is illustrated in Table 6. Table 6. Integration of Exposure Rankings Combined Score - All 3 Exposure Rank Exposure Ranking elements Score 11 13 High 5 9 10 Medium High 4 7 8 Medium 3 5 6 Medium Low 2 3 4 Low 1 Overall Priority Grouping: In the overall approach, both hazard and exposure elements are considered when placing a substance in a risk-based prioritization ranking. The overall prioritization score for priority grouping and risk evaluation is based on the combined consideration of the hazard and exposure rankings. Priority Groups 7, 8, and 9 are deemed High Priority; Priority Groups 4, 5, and 6 are Medium Priority; and Priority Groups 2 and 3 are Low Priority. August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Review and Comment: It is important that screening be done in an open and transparent way and that the best available information be used. When screening for thousands of chemicals, EPA may not have access to all available information. The process should provide an opportunity for review and comment on initial rankings and an opportunity to submit additional relevant data and information to update proposed rankings with improved information. III. Second Tier Considerations: After the initial screening, some substances within individual priority groupings may require further rank ordering, particularly where a large number of chemicals are in the same priority group. Listed below are the types of information that will be useful to consider in this Second Tier rank ordering: Biomonitoring/Environmental Monitoring Data: Mere detection of chemicals in humans or the environment, i.e., "found in biomonitoring (CDC), found in water (NCOD), and found in air", while providing an indication of exposure, does not provide a useful criterion for exposure potential because almost any industrial or commercial chemical could be detected at trace levels, given increasingly sensitive analytical methods. Therefore, detection alone primarily reflects only the fact that a specific chemical was included in a measurement program. This criterion will also tend to bias the prioritization of chemicals for which well-established analytical methods are available. Consequently, this criterion is not used in the initial prioritization scheme. However, within a particular priority grouping, reliable monitoring information should be considered for Second Tier rank ordering within a quantitative process that assesses if the data is above a level of concern (i.e., places it in a risk context). Use in Children's Products: Protection of childrens' health is a top priority and, in the initial ranking, child-specific products are captured under general consumer products and all consumer products are weighted equally. The specific IUR reporting of information on chemical use in products intended for children would be considered further within a particular priority grouping for Second Tier rank ordering, noting the following points: the IUR definition is based upon use in a child specific product rather than child specific exposure potential¹ (see below). Without knowing a specific product type, it is difficult to understand if 1 IUR definition (Federal Register Volume 75, Number 156, Friday August 30, 2010, p. 49686): Intended for use by children means the chemical substance or mixture is used in or on a product that is specifically intended for use by children age 14 or younger. A chemical substance or mixture is intended for use by children when the submitter answers "yes" to at least on of the following questions for the product into which the submitter's chemical substance or mixture is incorporated: (1) Is the product commonly recognized (i.e., by a reasonable person) as being intended for children age 14 or younger? (2) Does the manufacturer of the product state through product labeling or other written materials that the product is intended for or will be used by children age 14 or younger? (3) Is the advertising, promotion, or marketing of the product aimed at children age 14 or younger? August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 potential child exposure is greater than for a non-child specific product. For example, how does child exposure to a general use cleaner compare to exposure from use in a child's raincoat. In the VCCEP assessments, there are examples for inhalation exposures where estimates of passive child exposure during adult product use exceeded conservative estimates of child exposure during active use of a child-specific product (such as a hobby product) - differences were related to the amount of product used and substance concentration within the product (MEK VCCEP Submission). the IUR definition targets children age 14 and younger. Younger children may be exposed to a variety of non-child specific products that are in general household use. Older children may be exposed to a variety of additional products. the IUR information request is targeted to manufacturers, which may not have direct knowledge of all uses, particularly the presence in products for specific subpopulations, such as children. Therefore, it is not clear that the information requested for the IUR information would be consistently available across all substances being screened. Ideally, this information should be requested from formulators of child-specific products. Therefore, for the initial prioritization approach, which represents a broad, unrefined categorization, child specific products are captured under general consumer products and all consumer products are weighted equally. The IUR information on child specific use would be utilized within a particular priority grouping for Second Tier rank ordering. If the IUR information is utilized, it is important that the limitations above be considered in its application. Emissions Data: Production volume, which is readily available for substances, is used in this proposed approach, but only serves as a surrogate for environmental emissions. For further prioritization, data or estimates of environmental emissions can be used to refine prioritization. Estimates of environmental emissions will be available for some substances (e.g., TRI data). When TRI data are utilized it should be recognized that it addresses only emissions that result from industrial and not wide dispersive uses. In other cases, emissions estimates can be developed as a percentage of production volume based upon consideration of use categories. Within a particular priority grouping, available emissions information can be considered for Second Tier rank ordering, with the understanding that emissions information is not an indicator of actual exposure. Similarly, non-isolated system intermediates, by definition, would have de minimis exposure potential. Therefore, this IUR information could be considered within a particular priority grouping for Second Tier rank ordering. International Risk Management Actions: An initial screening approach for chemical prioritization should be based upon consistent application of specific hazard and exposure science elements that define risk potential. The hazard and exposure elements should be applicable across all substances being evaluated. For initial screening, existence of international risk management action plans should not be a factor that determines priority grouping. Risk management plans may be based upon many factors, including political drivers. It is unclear how factors, their relative weighting, and the rigor of the evaluation may vary across agencies and substances. For initial screening August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 purposes, the same science-based criteria should be used to rank all substances. Consideration of existing international risk management plans could be utilized to check the functioning of the approach and could be considered within a particular priority grouping for Second Tier rank ordering with the possible effect of moving a chemical up in a grouping if actions are being taken internationally. IV. Summary ACC's prioritization approach is an example of a risk-based screening prioritization process that implements the general principles outlined at the outset of this document. It is based upon widely available information that can be utilized to understand the relative priority of chemicals for further evaluation from a risk perspective, i.e., integrating both hazard and exposure elements. Implementation of the screening framework will be most effective when utilizing the best available information. When conducting screening for thousands of chemicals, EPA may not have access to all available information. An open and iterative process that includes an opportunity for review and comment on initial rankings, together with the information that led to the result, and an opportunity to update the ranking with improved information will create a transparent and scientifically sound process. V. References Arnot, J.A., D. Mackay, T. F. Parkerton, R. T. Zaleski, C.S. Warren (2010), Multimedia modeling of human exposure to chemical substances: The roles of food web biomagnification and biotransformation, Environmental Toxicology and Chemistry 29(1):45-55. Boethling, R., K. Fenner, P. Howard, G. Klecka, T. Madsen, J.R. Snape, M.J. Whelan (2009). Environmental persistence of organic pollutants: guidance for development and review of POP risk profiles. Integrated Environmental Assessment and Management 5(4): 539 - 556. Gobas, F.A.P.C, W. de Wolf, L. P Burkhard, E. Verbruggen, K. Plotzke (2009). Revisiting Bioaccumulation Criteria for POPs and PBT Assessments Integrated Environmental Assessment and Management, 5(4):624-637. MacLeod, M., T. E. McKone (2004). Multimedia persistence as an indicator of potential for population-level intake of environmental contaminants, Environmental Toxicology and Chemistry 23(10):2465-2472. van Wijk,D., R. Chénier, T. Henry, M. D Hernando, C. Schulte (2009). Integrated Approach to PBT and POP Prioritization and Risk Assessment' Integrated Environmental Assessment and Management, 5(4):697-711. August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Proposed Prioritization Approach DRAFT May & 2011 Exposure Elements nat commental consumer 20 2 3 a 33 3 not 8 or Persuntence S not 3 mai 35 a & not 3 Pas $ 3 S the iss = the Tormages RUN $ 3 3 SUM - P8 - Tavamage ranow 3 -13 Expesure Ramking $5 Based os Sum (UN# + pa * Townage PRIORITY GROUPING - Hazard * Expasure Ramkings - 1-8 3-10 11-13 mad Jow Hazard - Highter and Human $ 3 3 & $ Human Mazard Not on Dase 3 low mai * anou % 1000 numour 3 1.8 (duet Nume " 3 & 3 8 Not 100 Acure mi os : 3 A 2000 and not data) 280 v 1000 (pas 1.0 8.0 nomour 8.3 miss Nome 3 & % x CMR Cat 2, on Dawe Call 3: 10 - 3 is # 200 50 ase Igas 0.3 1.0 0.0% - 0.2 mis forme * # $ y GMS CMR Can on OHS Clowe Clat % Repeat Close 10 § on 8 on insurticient 20 information to - - - 0.3 wis 0,00 mist on information to $ 3 a $ August 29, 2011 Source: :https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Hazard and Exposure Criteria for Prioritization Approach HAZARD EXPOSURE Environment and Human Health Classifications based upon GHS Use Elements - based upon IUR Intermediate consumed during industrial processing Envirommental: industrial (not intermediate) - used in an industrial setting From GHS classification guidance document: commercial occupational use in nonindustrial setting Table 4.1.2: scheme for substances hazardous so the aquatic environment. consumer general population residential use Clacufication Persistence: Loag-term Votalile substance (VPS 1000 Pax: Not Persistent if air half life <2 days a (Nate 2) Nonvolatile (VP < 1000 Pa): Not Persistent if: Adequate dass Adequnte voriciny dasa aux a) ready biodegradability (OBCD 301) Rapidly 3 b) inherent biodegradability (OBCD 301, 302, 306) degredable 0) read across from measured data on a related substance. 28 (Note. 3) d) equivalent degree of degradation (i.e. >20% in 28 days) via an abjotic Arute 3 Categorys Chronic 1 Categury: 1 Categasy: I degradation mechanism such as photolysis (OBCD 316) or hydrolysis (OBCD NOEC ar ECA 0.1 NOE - EC cass L 1.00 md of maid 111) and/ar BCF a 200 OR, a substance is Not Persistent if: if e) evaluation of simulation data from transformation in soil, marine water/sediment, Caregusy: Acore 2 Category: Chronic 2 Caregury: Chrumin 2 Caregusy: Chruaic 2 brackish water/sediment, surface water/sediment, oceanic water die away (e.g., OECD 3.00 s: s 10.9 0.1 - NOEC er EC. 13 0.00 <: NOEC - EC, 502 3.00 L(EXC) 10.8 and of andies 308/309) have half lives below 180 days. BCF = 500 as if K. 2 4 OR, if data are lacking: Caregusy: Arnie 3 Caregury: 3 Chrinia 3 f) evaluation via BIOWIN model (EPIWEB 4) 01 EC. : 30,00 1- 100 and fack of Bioaccomulation: stapoid andier BOF: Re 300 if absent log x 3 4 A substance is not bioaccumulative if: 4 4) a) measured TMF < 1 (field study) 3) b) measured fish BMF <1 (lab study) Ne tericity and lack of and BCF 2 500 ase, lag E 4, c) measured fish BCF < 5000 (lab study) MOECA 1 mal d) predicted BCP< 5000 using the BCFBAF model included in EPIWIN 4 The above order reflects the preference for use in decision- making NOTE -- P&B CRITERIA ARB FOR ORGANICS Tonnage - based upon JUR reporting ranges <. 25,000 lbs (below IUR site reporting limit) Human Health: 25.000 - <1 MM lbs national aggregate As above, based upon GHS 1MM - <100 MM lbs national aggregate >100 MM lbs national aggregate August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Risk-Based Prioritization Matrix Ancreasing Exposure Two-Step towest Prionies Prioritization Process Incregaling Second Tier Rank Ordering within Priority Groups Biomonitoring / Environmental Monitoring Use in Children's Products Emissions (e.g. TRI) International Risk Management Actions Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226

Who is the Louisiana Commissioner of Agriculture & Forestry?

fgcn0226

fgcn0226_p0, fgcn0226_p1, fgcn0226_p2, fgcn0226_p3, fgcn0226_p4, fgcn0226_p5, fgcn0226_p6, fgcn0226_p7, fgcn0226_p8

Dr. Mike Strain

To: Nitsch, lad[[email protected]] Cc: Wagner, Kenneth[[email protected]]; Bangerter, Layne[[email protected]] From: Davis, Patrick Sent: Thur 3/30/2017 11:52:54 AM Subject: Re: NASDA Commends EPA Decision on Chlorpyrifos Petition [WARNING: SPF validation failed] Thank you Sent from my iPhone On Mar 30, 2017, at 7:41 AM, Nitsch, Chad <[email protected]> wrote: Patrick, Ken, and Layne, Please see attached statement on chlorpyrifos from NASDA. Thank you, Chad Nitsch State and Regional Partnerships | Office of the Administrator Environmental Protection Agency 202-564-4714 From: Dudley Hoskins [mailto:[email protected]] Sent: Wednesday, March 29, 2017 9:06 PM To: Nitsch, Chad <[email protected]>, Osinski, Michael <[email protected]>;! Dexter, Michael <[email protected]>; Bowles, Jack <[email protected]>; Barbery, Andrea <[email protected]> Cc: Nathan Bowen <[email protected]> Britt Aasmundstad <[email protected]> Subject: Fwd: NASDA Commends EPA Decision on Chlorpyrifos Petition [WARNING: SPF validation failed] Source: https://www.industrydocuments.ucsf.edu/docs/fgcn0226_001225_00000021-00001 Chad -- wanted to thank you again for today's meeting (more soon from our end on that front). In the interim, we wanted to share the below NASDA press release supporting EPA's science-based decision to deny petitioner's request to revoke chlorpyrifos tolerances (please share with Layne, Patrick, Ken and others from today's meeting who I may have inadvertently left off or not have email contact in front of me). Please let us know if you all have any questions or would like to discuss further at any points. Many thanks for all that you do! - dudley Sent from my iPhone Begin forwarded message: From: Amanda Culp <[email protected]> Date: March 29, 2017 at 8:06:20 PM EDT Subject: NASDA Commends EPA Decision on Chlorpyrifos Petition FOR IMMEDIATE RELEASE: March 29, 2017 Contact: Amanda Culp Director, Communications (202)296-9680 [email protected] NASDA Commends EPA Decision on Chlorpyrifos Petition The National Association of State Departments of Agriculture (NASDA) today applauded the U.S. Environmental Protection Agency's (EPA) decision to decline a petition to revoke tolerances for chlorpyrifos, which is integral for crop protection, Source: https://www.industrydocuments.ucsf.edu/docs/fgcn0226 001225 00000021-00002 including resistance management and integrated pest management (IPM) in more than 100 countries. NASDA President and Louisiana Commissioner of Agriculture & Forestry Dr. Mike Strain praised the EPA for sticking to its rigorous, scientific risk assessment and registration review process for crop protection tools. "We commend the EPA for its decision today that keeps an important insecticide available for farmers. By maintaining the Maximum Residue Limits (MRLs) for chlorpyrifos, agricultural use of this important tool will continue, significant disruption of international trade is avoided, and harmonization efforts may continue globally. As state regulatory partners with EPA, we look forward to continuing to work with the Agency to ensure current and future tools are reviewed in a rigorous, scientifically sound, and transparent manner." NASDA submitted comments to EPA in January 2016 requesting the Agency reevaluate its proposed tolerance revocations in compliance with the law and regulations that mandate a science-based review. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. NASDA grows and enhances agriculture by forging partnerships and creating consensus to achieve sound policy outcomes between state departments of agriculture, the federal government, and stakeholders. Learn more about NASDA at www.nasda.org. ### <Chlorpyrifos_EPA_03292017.pdf> Source: https://www.industrydocuments.ucsf.edu/docs/fgcn0226 001225_00000021-00003 To: Davis, Patrick[[email protected]]; Wagner, Kenneth[[email protected]] Bangerter, Layne[[email protected]] From: Nitsch, Chad Sent: Thur 3/30/2017 11:41:48 AM Subject: FW: NASDA Commends EPA Decision on Chlorpyrifos Petition [WARNING: SPF validation failed] Chlorpyrifos EPA 03292017.pd Patrick, Ken, and Layne, Please see attached statement on chlorpyrifos from NASDA. Thank you, Chad Nitsch State and Regional Partnerships I Office of the Administrator Environmental Protection Agency 202-564-4714 From: Dudley Hoskins [mailto:[email protected]] Sent: Wednesday, March 29, 2017 9:06 PM To: Nitsch, Chad <[email protected]>; Osinski, Michael <[email protected]>; Dexter, Michael <[email protected]>; Bowles, Jack <[email protected]>; Barbery, Andrea <Barbery [email protected]> Cc: Nathan Bowen <[email protected]>: Britt Aasmundstad <[email protected]> Subject: Fwd: NASDA Commends EPA Decision on Chlorpyrifos Petition [WARNING: SPF validation failed] Chad -- wanted to thank you again for today's meeting (more soon from our end on that front). In the interim, we wanted to share the below NASDA press release supporting EPA's science- based decision to deny petitioner's request to revoke chlorpyrifos tolerances (please share with Source: https://www.industrydocuments.ucsf.edu/docs/fgcn0226 001225 00000022-00001 Layne, Patrick, Ken and others from today's meeting who I may have inadvertently left off or not have email contact in front of me). Please let us know if you all have any questions or would like to discuss further at any points. Many thanks for all that you do! - dudley Sent from my iPhone Begin forwarded message: From: Amanda Culp <[email protected]> Date: March 29, 2017 at 8:06:20 PM EDT Subject: NASDA Commends EPA Decision on Chlorpyrifos Petition FOR IMMEDIATE RELEASE: March 29, 2017 Contact: Amanda Culp Director, Communications (202)296-9680 [email protected] NASDA Commends EPA Decision on Chlorpyrifos Petition The National Association of State Departments of Agriculture (NASDA) today applauded the U.S. Environmental Protection Agency's (EPA) decision to decline a petition to revoke tolerances for chlorpyrifos, which is integral for crop protection, including resistance management and integrated pest management (IPM) in more than 100 countries. NASDA President and Louisiana Commissioner of Agriculture & Forestry Dr. Mike Strain praised the EPA for sticking to its rigorous, scientific risk assessment and registration review process for crop protection tools. Source: https://www.industrydocuments.ucsf.edu/docs/fgcn0226 001225 00000022-00002 "We commend the EPA for its decision today that keeps an important insecticide available for farmers. By maintaining the Maximum Residue Limits (MRLs) for chlorpyrifos, agricultural use of this important tool will continue, significant disruption of international trade is avoided, and harmonization efforts may continue globally. As state regulatory partners with EPA, we look forward to continuing to work with the Agency to ensure current and future tools are reviewed in a rigorous, scientifically sound, and transparent manner. NASDA submitted comments to EPA in January 2016 requesting the Agency reevaluate its proposed tolerance revocations in compliance with the law and regulations that mandate a science-based review. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. NASDA grows and enhances agriculture by forging partnerships and creating consensus to achieve sound policy outcomes between state departments of agriculture, the federal government, and stakeholders. Learn more about NASDA at www.nasda.org. ### Source: https://www.industrydocuments.ucsf.edu/docs/fgcn0226 001225 00000022-00003 Contact: FOR IMMEDIATE RELEASE Amanda Culp March 29, 2017 Director, Communications (202) 296-9680 [email protected] NASDA Commends EPA Decision on Chlorpyrifos Petition The National Association of State Departments of Agriculture (NASDA) today applauded the U.S. Environmental Protection Agency's (EPA) decision to decline a petition to revoke tolerances for chlorpyrifos, which is integral for crop protection, including resistance management and integrated pest management (IPM) in more than 100 countries. NASDA President and Louisiana Commissioner of Agriculture & Forestry Dr. Mike Strain praised the EPA for sticking to its rigorous, scientific risk assessment and registration review process for crop protection tools. "We commend the EPA for its decision today that keeps an important insecticide available for farmers. By maintaining the Maximum Residue L imits (MRLs) for chlorpyrifos, agricultural use of this important tool will continue, significant disruption of international trade is avoided, and harmonization efforts may continue globally. As state regulatory partners with EPA, we look forward to continuing to work with the Agency to ensure current and future tools are review ed in a rigorous, scientifically sound , and transparent manner." - NASDA submitted comments to EPA in January 2016 requesting the Agency reevaluate its proposed tolerance revocations in compliance with the law and regulations that mandate a science-based review. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. NASDA grows and enhances agriculture by forging partnerships and creating consensus to achieve sound policy outcomes between state departments of agriculture, the federal government, and stakeholders. Learn more about NASDA at www.nasda.org. ### National Association of State Departments of Agriculture NASDA 4350 North Fairfax Drive #910 Arlington, VA 22203 Tel: 202-296-9680 www.nasda.org Source: https://www.industrydocuments.ucsf.edu/docs/fgcn0226 001225 00000023-00001 To: Bangerter, , Layne[[email protected]] From: U.S. EPA Media Relations Sent: Wed 3/29/2017 10:35:49 PM Subject: EPA Administrator Pruitt Denies Petition to Ban Widely Used Pesticide CONTACT: [email protected] FOR IMMEDIATE RELEASE March 29, 2017 EPA Administrator Pruitt Denies Petition to Ban Widely Used Pesticide Today, U.S. Environmental Protection Agency (EPA) Administrator Scott Pruitt signed an order denying a petition that sought to ban chlorpyrifos, a pesticide crucial to U.S. agriculture. "We need to provide regulatory certainty to the thousands of American farms that rely on chlorpyrifos, while still protecting human health and the environment," said EPA Administrator Pruitt. "By reversing the previous Administration's steps to ban one of the most widely used pesticides in the world, we are returning to using sound science in decision-making - rather than predetermined results.' "This is a welcome decision grounded in evidence and science," said Sheryl Kunickis, director of the Office of Pest Management Policy at the U.S. Department of Agriculture (USDA). "It means that this important pest management tool will remain available to growers, helping to ensure an abundant and affordable food supply for this nation and the world. This frees American farmers from significant trade disruptions that could have been caused by an unnecessary, unilateral revocation of chlorpyrifos tolerances in the United States. It is also great news for consumers, who will continue to have access to a full range of both domestic and imported fruits and vegetables. We thank our colleagues at EPA for their hard work." In October 2015, under the previous Administration, EPA proposed to revoke all food residue tolerances for chlorpyrifos, an active ingredient in insecticides. This proposal was issued in response to a petition from the Natural Resources Defense Council and Pesticide Action Network North America. The October 2015 proposal largely relied on certain epidemiological study outcomes, whose application is novel and uncertain, to reach its conclusions. The public record lays out serious scientific concerns and substantive process gaps in the proposal. Reliable data, overwhelming in both quantity and quality, contradicts the reliance on - and misapplication of - studies to establish the end points and conclusions used to rationalize the proposal. The USDA disagrees with the methodology used by the previous Administration. Similarly, the National Association of State Departments of Agriculture also objected to EPA's methodology. The Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA) Scientific Advisory Panel (SAP) also expressed concerns with regard to EPA's previous reliance on certain data the Agency had used to support its proposal to ban the pesticide. The FIFRA SAP is a federal advisory committee operating in accordance with the Federal Advisory Committee Act and established under the provisions of FIFRA, as amended by the Food Quality Protection Act of 1996. It provides scientific advice, information and recommendations to the EPA Administrator on pesticides and pesticide-related issues regarding the impact of regulatory decisions on health and the environment. Source: https://www.industrydocuments.ucsf.edu/docs/fgcn0226 001225 00000024-00001 To view the petition: https://www.epa.gov/pesticides R044 If you would rather not receive future communications from Environmental Protection Agency, let us know by clicking here. Environmental Protection Agency, 1200 Pennsylvania Avenue NW, Washington, DC 20460 United States Source: https://www.industrydocuments.ucsf.edu/docs/fgcn0226 001225_00000024-00002

Who is mentioned in the CC:?

pfcn0226

pfcn0226_p0, pfcn0226_p1

OCSPP senior staff Justina Fugh, Senior Counsel for Ethics

STATES UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460 s June 9, 2017 OFFICE OF CHEMICAL SAFETY AND POLLUTION PREVENTION MEMORANDUM SUBJECT: Recusal Statement FROM: Nancy B. Beck, Ph.D., DABT Deputy Assistant Administrator TO: Wendy Cleland-Hamnett Acting Assistant Administrator Because I am in an Administratively Determined position, I have been advised by the Office of General Counsel/Ethics (OGC/Ethics) that I am not subject to Executive Order 13770 and therefore not required to sign the Trump ethics pledge. But as an executive branch employee, I have always understood that I am subject to the conflict of interest statutes codified at Title 18 of the United States Code and the Standards of Ethical Conduct for Employees of the Executive Branch, 5 C.F.R. Part 2635. Pursuant to the federal impartiality standards, I have understood that I have a "covered relationship" with my former employer, the American Chemistry Council (ACC), and have recused myself from participating personally and substantially in any particular matter involving specific parties in which ACC is a party or represents a party. I was advised by OGC/Ethics that my recusal period commenced the day that I left ACC and would remain in effect for one year unless I was authorized by the Office of General Counsel/Ethics (OGC/Ethics) to participate pursuant to 5 C.F.R. 2635.502(d). I have sought and obtained confirmation from OGC/Ethics that I can participate in particular matters of general applicability, such as rulemaking, even if my former employer has an interest, and that I can participate personally and substantially in any discussions or consideration of comments that ACC submitted with regard to rulemaking or other matters of general applicability. See attached. I am also now authorized to attend meetings at which ACC is present or represented, provided that the subject matter of the meeting is a matter of general applicability, if other interested non-federal parties are present, and other EPA personnel attend. For the remainder of my cooling off period, until April 21, 2018, however, I understand that I cannot otherwise participate in any specific party matter involving ACC unless I first seek approval from OGC/Ethics. Source: https://www.industrydocuments.ucsf.edu/docs/pfcn0226 I am issuing this recusal statement to ensure that our staff assist me by directing any ACC specific party matter to you instead of me, without my knowledge or involvement, until after April 21, 2018. In consultation with OGC/Ethics, I will revise and update my recusal statement whenever warranted by changed circumstances, including changes in my financial interests or in my personal or business relationships. cc: OCSPP senior staff Justina Fugh, Senior Counsel for Ethics Source: https://www.industrydocuments.ucsf.edu/docs/pfcn0226

who is the CEO of National Association of Wheat Growers?

ffcn0226

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Chandler Goule

To: Greenwalt, Sarah[[email protected]]; Dravis, Samantha[[email protected]] Brown, Byron[[email protected]];Wagner, Kenneth[[email protected]] From: Hupp, Sydney Sent: Thur 3/30/2017 5:11:34 PM Subject: FW: FINAL Meeting Agenda and Materials Pruitt Meeting Materials.pd FYI. Sydney Hupp Office of the Administrator- Scheduling 202.816.1659 From: Mary Jo Tomalewski [mailto:[email protected]] Sent: Thursday, March 30, 2017 11:22 AM To: Hupp, Sydney <[email protected]> Cc: Jay Vroom <[email protected]> Subject: FINAL Meeting Agenda and Materials Sydney, We have refined our proposed topics for today's CEO Council meeting with the administrator. Attached, please find: Revised "Final Proposed Agenda Topics," which includes the list of those CEO Council members who will attend our meeting today, and their short bios Introduction / Mission Overview of the CEO Council CEO Council Letter to President Trump, dated February 9, 2017 We assume we can skip a formal "round table of introductions" at the beginning of the meeting as our time is short and we want to maximize time spent talking about issues. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000061-00001 MJ Mary Jo Tomalewski Executive Assistant to the President & CEO CropLife America 1156 15th Street, NW Suite 400 Washington, DC 20005 Direct Dial (202) 872-3849 Main Switchboard (202) 296-1585 Mobile Ex. 6 Personal Privacy Fax (202)466-5832 Email [email protected] Web www.croplifeamerica.org How can I serve you today? Future Meetings 2017 Spring Regulator Conference - April 6-7, Arlington, VA 2017 Annual Meeting - September 22-27, Dana Point, CA 2018 Winter Board of Directors Meeting - March 5-7, Washington, DC 2018 Annual Meeting - September 21-26, The Ritz-Carlton Amelia Island Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000061-00002 FINAL PROPOSED AGENDA TOPICS Meeting Information: Office of EPA Administrator Scott Pruitt 1200 Pennsylvania Avenue, NW Washington, DC Thursday, March 30, 2017 3:45-4:30 PM Topic 1. Thanks to Trump Administration and Administrator Pruitt for early decisive actions: a. WOTUS b. Chlorpyrifos Petition 2. Top Priority Issues a. Ag Advisor Position - We recommend adding additional title of "Assistant Deputy Administrator" as a title b. Water i. Next steps to refine / clarify beyond WOTUS ii. NPDES permits (CAFO Program needs work; legislation to fix water permits NOT needed for lawful use of pesticides) c. Pesticides Policy i. Endangered Species Act conflicts with Pesticide Regulation and Biotech Regulation ii. Epidemiology Study Policy (as aftermath from Chlorpyrifos matter) iii. Reform Certification & Training and Worker Protection Rules - Suspend implementation and revise d. Renewable Fuels Standard - current program kept consistent e. Communication / Messaging / Opinion Polling - vital to all parties' ability to advance sound policy f. EPA and USDA Cooperation and Coordination - Already vast progress; more can be done! g. Environmental Justice, Research & Development, and Children's Health Offices - Better integration with and reform of EPA program offices; sound science h. Regulation of Manufacturing & Mining Facilities for Ag Inputs - Restore science and process i. Public and Science Advisory Panels at EPA - Balance, strategic agendas j. "Air Emissions" from farming operations CEO Attendees American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Corn Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Barb Glenn, CEO, ex-officio Departments of Agriculture Others American Farm Bureau Federation Dale Moore, Deputy Executive Director Corn Refiners Association John Bode, President & CEO National Farmers Union Rob Larew, Senior VP Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00001 Production Agriculture's CEO Council Introduction/Mission Statement: The production agriculture "CEO Council" coordinates alignment on core issues of modern agricultural systems through telling our story, sharing information and leveraging our strengths, while serving as a resource for government decision makers and others interested in USA food, fiber and renewable fuels. Core Focus of Interest Research and innovation Technology access Science and risk-based regulation Sustainability, environment, and weather Marketability, trade, and economic prosperity Government leadership and partnership with private sector Food access and food safety Plant and animal health Ag labor The Council supports principles/themes): Accelerating rural economic growth and improving productivity through innovation and technology Promoting research and innovation that enables development oftools and techniques necessary for discovering new products that hold tremendous potential for farmers and society at large Enabling a regulatory and commercial environment in which agricultural products are marketable, both domestically and internationally Appropriate balance between Federal and State Governments and a cooperative regulatory approach Access to essential labor in balance with an effective Federal immigration policy and adequate worker safety protections Support for all methods of agricultural production Transparency and dialogue with consumers Members of the CEO Council (see reversed) March 30, 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00002 CEO Council Members American Farm Bureau Vincent "Zippy" Duvall, President American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Cattlemen's Beef Association Kendal Frazier, CEO National Chicken Council Michael Brown, President National Com Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Farmers Union Roger Johnson, President National Milk Producers Federation Jim Mulhern, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Departments of Barb Glenn, CEO, ex-officio Agriculture March 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00003 February 9, 2017 The President The White House Washington, D.C. 20500 Dear Mr. President, We, the CEO Council (undersigned herein), representing the production agricultural value chain, including many agricultural producers and farm input developers and suppliers, look forward to working with you and your Administration on matters of importance to American agriculture. The challenges we face in agriculture are significant. Many experts emphasize that producers must grow as much food in the next 50 years as was produced over all previous history to meet the demands of our expanding global population. A firm commitment by the U.S. government to aggressively support agricultural innovation and science-based regulatory decisions will be necessary to ensure farmers have the tools they need to produce a safe and abundant supply of nutritious food, in addition to feed, fuel and fiber, in an environmentally sound and sustainable manner. The policy and regulatory environment your Administration establishes can ensure that agricultural innovation flourishes and American farmers are able to meet the food production goals necessary to feed billions more people. We are ready to provide the White House and the Executive Branch Departments and Agencies, as well as Congress, with policy concepts that foster stability in the U.S. agriculture economy with a strong and predictable farm safety net and promotes American competitiveness through research; marketability and trade of agricultural commodities; rural economic growth; and plant, animal, and environmental health, among many other things. We appreciate your attention to these and other issues of value to American production agriculture and food consumers everywhere. Sincerely, American Farm Bureau Foundation, Zippy Duvall American Seed Trade Association, Andy LaVigne American Soybean Association, Steve Censky Biotechnology Innovation Organization, Dana O'Brien CropLife America, Jay Vroom The Fertilizer Institute, Chris Jahn National Association of Wheat Growers, Chandler Goule National Cattlemen's Beef Association, Kendal Frazier National Corn Growers Association, Chris Novak National Cotton Council, Gary Adams National Council of Farmer Cooperatives, Chuck Conner National Farmers Union, Roger Johnson National Milk Producers Federation, Jim Mulhern National Pork Producers Council, Neil Dierks United Fresh Produce Association, Tom Stenzel USA Rice Federation, Betsy Ward Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00004 National Gotton Council OF MERTOA Gary M. Adams President and Chief Executive Officer National Cotton Council of America Gary Adams assumed the position of President and Chief Executive Officer of the National Cotton Council in February 2015. He plays a key role in guiding the industry's seven segments to reach consensus on critical policies affecting U.S. cotton, with the mission of helping all U.S. cotton industry segments compete effectively and profitably in global markets. Prior to that, Gary served the Council for 13 years as the Vice President of Economic and Policy Analysis. As the Council's chief economist, he provided economic outlooks for global cotton markets, as well as analyzing the impacts of farm and trade policies. Gary also represents the U.S. cotton industry as a member of USDA's Agricultural Policy Advisory Committee. Previously, Gary served on USDA's Advisory Committee on Trade from 2005 through 2011 and the NASS Advisory Committee on Agricultural Statistics from 2003 through 2009. Prior to joining the Council, Gary was a Research Assistant Professor in the Department of Agricultural Economics at the University of Missouri. During his 13-year tenure at the university, Gary's primary responsibilities included policy analysis and market outlook for the Food and Agricultural Policy Research Institute, also known as FAPRI. While at FAPRI, Gary and his colleagues were recognized by the American Agricultural Economics Association for their distinguished policy contributions. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00005 Gary has B.S. and M.A. degrees in Applied Mathematics from the University of Alabama and a Ph.D. in Agricultural Economics from the University of Missouri. Gary and his wife, Ex. 6 Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00006 FASA American Soybean Associatión & Stephen L Censky Chief Executive Officer Stephen L. Censky is the American Soybean Association's (ASA) C hief Executive Officer, a staff position he accepted in April 1996. As ASA's top executive, Ce nsky is in charge of managing ASA's legislative, trade policy, membership and education and training programs. The American Soybean Association is a national, not-for-profit commodity organization with over 22,000 members. ASA works as the domestic and international policy advocate for soybean producer members. Prior to joining ASA, Censky worked in Washington, D.C. for ove a decade. He began his career on Capitol Hill as a legislative assistant for agricultural and transportation matters to Senator Jim Abdnor (R-SD). Later he served in both the Reagan and Bush Administrations at the U.S. Department of Agriculture, helping to craft the 1990 Farm Bill and eventually serving as Administrator of the Foreign Agricultural Service where he was involved in global trade negotiations and running our nation's export programs. Censky received his Bachelor's of Science degree of Agriculture from South Dakota State University and his Master's Diploma in Agriculture St of Melbourne, Australia. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00007 NCFC. National Council of Farmer Cooperatives Charles F. (Chuck) Conner President and CEO National Council of Farmer Cooperatives Charles F. (Chuck) Conner became president & CEO of the National Council of Farmer Cooperatives (NCFC) on January 22, 2009. As president of NCFC, Conner will oversee the organization's work to promote and protect the business and public policy interests of America's farmer-owned cooperatives. He will also provide the strategic vision for the trade association as it continues to seek new ways in which to add value for its membership. Prior to joining NCFC, Conner had served as the Deputy Secretary at the U.S. Department of Agriculture since mid-2005. In this capacity, he was the Chief Operating Officer (COO) overseeing day-to-day operations of the department. Conner interacted directly with President George W. Bush and his senior staff to formulate domestic and international food, trade, security and energy policy. He led development of the Bush Administration's $300 billion Farm Bill proposal and the strategy to educate and inform industry, constituents and Congress. From August 2007 to January 2008, Conner served as both USDA Secretary and Deputy Secretary. He played a key role in developing the Administration's immigration policy including important changes to the H2A program. Conner's experience also includes the assignment of Special Assistant to the President, Executive Office of the President, from October 2001 to May 2005, working on the 2001/2 Farm Bill to develop the strategy behind the transfer of several USDA agency functions to the newly formed Department of Homeland Security. From May 1997 to October 2001 Conner served as President of the Corn Refiners Association. He also served for 17 years as an advisor to U.S. Senator Richard Lugar of Indiana. Conner is a graduate of Purdue University, with a Bachelor's of Science degree and is the recipient of Purdue's Distinguished Alumni Award. He and his wife Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00008 NATIONAL PORK PRODUCERS COUNCIL Neil Dierks, Chief Executive Officer Neil Dierks is Chief Executive Officer of the National Pork Producers Council (NPPC). In this position, he is responsible for the overall implementation of all NPPC programs. Dierks' position requires him to spend time in both Des Moines, Iowa, the national office of NPPC, and Washington, D.C. Beginning in 1990, Dierks served NPPC in a series of senior executive positions, including Executive Director of Operations, Vice President for Research and Education and Senior Vice President for Programs. Prior to his service with NPPC, Dierks was the Special Activities Director for the Iowa Pork Producers Association and Marketing Director for the Iowa Corn Promotion Board. Neil grew up on a livestock farm in eastern lowa and remains involved in a family farming operation. He is a graduate of Iowa State University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00009 NASDA Dr. Barbara Glenn recently joined the National Association of State Departments of Agriculture (NASDA) as CEO on August 18, 2014. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. Dr. Glenn is a scientist with decades of experience as a policy researcher and advocate for agriculture. She previously served as Senior Vice President of Science and Regulatory Affairs for CropLife America, where she was responsible for developing policies and regulations to support agriculture through crop protection. Prior to joining CropLife America, Dr. Glenn served as Managing Director of the Animal Bi otechnology, Food and Agriculture Section of the Biotechnology Industry Association in Washington, DC. Dr. Glenn holds a B.S. in animal science and a Ph.D. in ruminan t nutrition from the University of Kentucky. She previously worked for the U.S. Department of Agriculture, Agric ultural Research Service and the Federation of Animal Science Societies. Born in Lincoln, Nebraska and raised in Centerville, Ohio, Dr. Glenn developed a passion for agriculture from her parents and her involvement in 4-H. She lives Ex. 6 - Personal Privacy and serves on various boards for farm bureau and 4-H. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00010 National Association of Wheat Growers Chandler Goule CEO Chandler Goule assumed his responsibilities as CEO of the National Association of Wheat Growers on July 5, 2016. In addition, he also serves as the executive director of the National Wheat Foundation. Most recently, Goule served as senior vice president of programs at the National Farmers Union (NFU) where he was heavily involved in farm bill legislation. Originally from Texas, Goule holds degrees from Texas A&M and George Washington University and served as a subcommittee staff director for the House Agriculture Committee before moving to the National Farmers Union in 2009 as vice president of government relations. He was appointed senior vice president of NFU programs in 2014. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00011 The Fertilizer Institute Nourish, Replenish, Grow BIOGRAPHY OF CHRISTOPHER JAHN President The Fertilizer Institute and the Nutrients for Life Foundation Christopher L. Jahn is president of The Fertilizer Institute (TFI), the fertilizer industry's national trade association. As TFI president, Jahn works to represent, promote and protect a sound fertilizer industry through legislative and regulatory activities and to promote a favorable public image of the fertilizer industry and agriculture. Jahn also serves as president of the Nutrients for Life Foundation (NFL). Jahn comes to TFI having served as president of the National Association of Chemical Distributors (NACD) since 2006. Prior to leading NACD, Jahn served as president of the Contract Services Association (CSA). Before joining CSA, Jahn had an active role in the United States Senate working for nearly 10 years for U.S. Senator Craig Thomas (R-Wyo.) in a variety of roles, including legislative assistant, legislative director and Chief of Staff. After graduating from Columbia University with a B.A. in Political Science, Jahn co-founded a book distribution business. He also earned an MBA from the University of Maryland. A native of Wyoming, Chris and his wife, Ex. 6 - Personal Privacy Ex. Personal Privacy Capitol View 202.962.0490 425 Third Street, S.W., Suite 950 202.962.0577 fax Washington, DC 20024 www.tfi.org Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00012 National Farmers Union Roger Johnson President Roger Johnson is president of the National Farmers Union (NFU), a grassroots organization that represents more than 200,000 family farmers, ranchers, fisherman and rural communities across the Unites States. Johnson was elected to lead the family farm organization at NFU's 107th anniversary convention in 2009. He has since expanded the education department by providing more programs for beginning, college-aged and women farmers, increased the number of Farmers Union state divisions, and developed a strategic plan for the organization. Johnson has also overseen a number of important policy initiatives important to family farmers including: passage of the 2014 Farm Bill; maintaining a strong Renewable Fuel Standard and Country-of-Origir Labeling, promoting policies that allow farmers to address the growing threat of climate change; and renewing the nation's focus on eliminating an overwhelming trade deficit that results in lost jobs and prosperity for rural America. Prior to leading National Farmers Union, Johnson, a third-generation family farmer from Turtle Lake, N.D., served as North Dakota Agriculture Commissioner, a position he was first elected to in 1996. While Agriculture Commissioner, Johnson served on the State Industrial Commission, the North Dakota Trade Office Advisory Board, and the State Board of Agricultural Research and Education, among many other boards and commissions. From 2007-2008, Johnson served as president of the National Association of State Departments of Agriculture (NASDA). He is a past president of the Midwestern Association of State Departments of Agriculture (MASDA), past president of the Food Export Association of the Midwest and a former chairman of the Interstate Pest Control Compact. Johnson graduated from North Dakota State University with a degree in agricultural economics. Johnson and his wife Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00013 AMERICAN SEED TRADE ASSOCIATION asta first-the - seed R Andrew W. "Andy" LaVigne President & CEO Andrew W. LaVigne is currently the President and CEO of the Ame rican Seed Trade Association. He joined ASTA in February, 2006. Andy has had a 30-year career i n government relations, industry representation, public affairs advocacy, and management. His C ore areas of expertise include agriculture, food policy and international trade. Prior to joining ASTA, Andy was Executive Vice President/CEC of Florida Citrus Mutual, representing citrus growers on issues affecting their business. Prejaiming tFdorida Citrus Mutual, Andy spent four years as Florida Fertilizer and Agrichemical Association's (FFAA) President and Executive Director. FFAA is a non-profit, agricultural trade organization representing companies that specialize in crop protection and plant nutrition products. Before his position at FFAA, Andy spent eight years in Washingt on, D.C. working in the U.S. Congress and the U.S. Department of Agriculture. He served as Legislative Director for Congressman Charles Canady, Agriculture Committee staffer for Congressman Tom Lewis , and on the staff of USDA Secretary Ed Madigan. Andy is a native of Florida with a BA degree in Political Scien ce, with a minor in economics, from the University of Florida. 1701 Duke Street Suite 275 Alexandria, VA 22314 Phone: (703)837-8140 Fax: (703)837-9365 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00014 Biotechnology Innovation Organization Dana O'Brien Executive Vice President, Food & Agriculture Dana O'Brien is Executive Vice President for Food and Agriculture and is responsible for the development of public policy and strategic advocacy, public affairo, and legal strategies that advance industry and stakeholder objectives in the United States. Prior to becoming EVP, Dana served bs BIO Food and Agriculture's chief legislative advocate as Senior Director of Federal Government Relations aince March 2011. Before BIO, Dana worked in Congress for the late Representative lke Skelton (D-MO) managing his legislative team and concentrating on a variety of agricultural, energy, and trade matters. A native of Sedalia, Missouri, and a graduate of Missouri University with a bachelor's degree in psychology, Dana joined the Skelton team immediately out of college and served there for nearly 14 years Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00015 UNITED FRESH is PRODUCE ASSOCIATION Tom Stenzel President and CEO United Fresh Produce Association 1901 Pennsylvania Avenue NW, Suite 1100 Washington, DC 20006 202/303-3400 [email protected] Tom Stenzel is President and CEO of the United Fresh Produce Association, a position he has held since 1993. United Fresh is the pre-eminent trade association for the produce industry in shaping legislative and regulatory policies; providing scientific and technical leadership in food safety and nutrition; and developing educational programs for its members. Founded in 1904, United Fresh represents the interests of companies from small family businesses to the largest international corporations throughout the global fresh produce supply chain. United Fresh is widely known for its work in government affairs, agricultural policy, food safety and nutrition, working to promote political and environmental change to help the next generation of children double their consumption of fresh produce. The United Fresh Start Foundation is committed to increasing children's access to fresh fruits and vegetables, and is a founding partner of the Let's Move Salad Bars to Schools campaign. The campaign has donated salad bars to more than 6,000 schools across the country. Tom is a frequent speaker on industry issues and has been recognized often by the produce industry throughout his career. He was honored as the 2002 Produce Man of the Year by The Packer newspaper, and is the past Chairman of the International Federation for Produce Standards, a global body representing national produce associations around the world. He is a member of the U.S. Chamber of Commerce Committee of 100 leading association executives, the Advisory Board of the International Food Protection Training Institute, and the Key Industry Associations Committee of the American Society of Association Executives, from which he achieved the Certified Association Executive (CAE) designation in 1990. He has served in many government and industry leadership positions, including the first U.S. Department of Agriculture Fruit and Vegetable Industry Advisory Committee, President George W. Bush's Transition Advisory Team for Agriculture, and as an advisor on the U.S. Agricultural Policy Advisory Committee for Trade. Tom was the founding President of the International Food Information Council (IFIC) in 1986, and was previously director of public affairs for the National Soft Drink Association. Tom is a 1977 graduate of the University of Richmond. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00016 as of January 17, 2017 Jay Vroom has served as President and CEO of the trade association known as CropLife America (CLA) since 1989. CLA is the leading U.S. trade group for the crop protection industry in the U.S. Vroom is a founding member of the CropLife Foundation, serving as chairman since its inception in 2001, and now serves as the Foundation's Vice-Chair, since 2015. His sits of the Board of Directors for the Agricultural Retailers Association, Asmark, National Wheat Foundation, the National Association of Manufacturers Council of Manufacturing Associations, and the Soil Health Institute. He is also a member of the Farm Foundation Roundtable Steering Committee, and the North American Climate Smart Ag Alliance Steering Committee. Vroom was a member of the youth organization, Future Farmers of America, and served as an elected state officer in Illinois. Today, he is a member of the FFA Foundation's Individual Giving Council and Board of Trustees. Vroom co-chairs the Coalition for the Advancement of Precision Agriculture and the CEO Council. He is a member of the Friends of the National Arboretum (FONA) FONA Council. He graduated with honors from the College of Agriculture, Consumer and Environmental Sciences at the University of Illinois Urbana-Champaign. Vroom was raised on a grain and livestock farm in north-central Illinois and continues to own the farming operation. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00017 Elizabeth Ward Betsy Ward was appointed President & CEO of the USA Rice Federation in 2007. From 2003- 2005, Ward was the Vice President of International and Domestic Promotion at USA Rice where she was in charge of developing and implementing domestic and international promotion, and food aid programs. From 2005-2007, Ward served as the chief executive for the Hardwood Federation, a trade association representing over 15,000 hardwood producers across the United States. From 1995 to 2003, she ran the Wood Products International Group at the American Forest & Paper Association, directing the wood trade policy and global forestry agenda for the industry. In 2011, Ward was elected Chairman of the U.S. Agricultural Export Development Council (USAEDC) which represents the interests of more than 80 commodity organizations who grow and process a wide variety of U.S. agricultural products. She currently serves as Past Chair. Since 2011, Ward has also served on the Board of Directors of the Sustainable Fisheries Partnership, an independent non-governmental organization (NGO) working to ensure healthy marine and aquatic tecosystems; secure seafood supplies; and a thriving, responsible seafood economy. Ward served for six years as a cleared advisor on the Industry Trade Advisory Committee for forest and paper products (ITAC-7) and was appointed forest products representative to USDA's Agricultural Policy Advisory Committee (APAC) in 2001. Ward holds a Bachelor's degree in History and Political Science from the University of New Hampshire and a Master's degree in International Security Affairs from the School of International Affairs at Columbia University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00018 To: Brown, Byron[[email protected]]; Jackson, Ryan[[email protected]] From: Rebeckah Adcock Sent: Thur 3/30/2017 4:10:52 PM Subject: FW: FINAL CEO Council Meeting Agenda and Materials Pruitt Meeting Materials.pdf ATT00001.htm FYI - final materials for today's meeting. Reb From: "Mary Jo Tomalewski" <[email protected]> To: "Hupp, Sydney" <[email protected]> Cc: "Jay Vroom" <[email protected]> Subject: FINAL Meeting Agenda and Materials Sydney, We have refined our proposed topics for today's CEO Council meeting with the administrator. Attached, please find: Revised "Final Proposed Agenda Topics," which includes the list of those CEO Council members who will attend our meeting today, and their short bios Introduction / Mission Overview of the CEO Council CEO Council Letter to President Trump, dated February 9, 2017 We assume we can skip a formal "round table of introductions" at the beginning of the meeting as our time is short and we want to maximize time spent talking about issues. MJ Mary Jo Tomalewski Executive Assistant to the President & CEO CropLife America Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000063-00001 1156 15th Street, NW Suite 400 Washington, DC 20005 Direct Dial (202) 872-3849 Main Switchboard (202) 296-1585 Mobilé Ex. 6 Personal Privacy Fax (202) 466-5832 Email [email protected] Web www.croplifeamerica.org How can I serve you today? Future Meetings 2017 Spring Regulator Conference - April 6-7, Arlington, VA 2017 Annual Meeting - September 22-27, Dana Point, CA 2018 Winter Board of Directors Meeting - March 5-7, Washington, DC 2018 Annual Meeting - September 21-26, The Ritz-Carlton Amelia Island Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000063-00002 FINAL PROPOSED AGENDA TOPICS Meeting Information: Office of EPA Administrator Scott Pruitt 1200 Pennsylvania Avenue, NW Washington, DC Thursday, March 30, 2017 3:45-4:30 PM Topic 1. Thanks to Trump Administration and Administrator Pruitt for early decisive actions: a. WOTUS b. Chlorpyrifos Petition 2. Top Priority Issues a. Ag Advisor Position - We recommend adding additional title of "Assistant Deputy Administrator" as a title b. Water i. Next steps to refine / clarify beyond WOTUS ii. NPDES permits (CAFO Program needs work; legislation to fix water permits NOT needed for lawful use of pesticides) c. Pesticides Policy i. Endangered Species Act conflicts with Pesticide Regulation and Biotech Regulation ii. Epidemiology Study Policy (as aftermath from Chlorpyrifos matter) iii. Reform Certification & Training and Worker Protection Rules - Suspend implementation and revise d. Renewable Fuels Standard - current program kept consistent e. Communication / Messaging / Opinion Polling - vital to all parties' ability to advance sound policy f. EPA and USDA Cooperation and Coordination - Already vast progress; more can be done! g. Environmental Justice, Research & Development, and Children's Health Offices - Better integration with and reform of EPA program offices; sound science h. Regulation of Manufacturing & Mining Facilities for Ag Inputs - Restore science and process i. Public and Science Advisory Panels at EPA - Balance, strategic agendas j. "Air Emissions" from farming operations CEO Attendees American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Corn Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Barb Glenn, CEO, ex-officio Departments of Agriculture Others American Farm Bureau Federation Dale Moore, Deputy Executive Director Corn Refiners Association John Bode, President & CEO National Farmers Union Rob Larew, Senior VP Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00001 Production Agriculture's CEO Council Introduction/Mission Statement: The production agriculture "CEO Council" coordinates alignment on core issues of modern agricultural systems through telling our story, sharing information and leveraging our strengths, while serving as a resource for government decision makers and others interested in USA food, fiber and renewable fuels. Core Focus of Interest Research and innovation Technology access Science and risk-based regulation Sustainability, environment, and weather Marketability, trade, and economic prosperity Government leadership and partnership with private sector Food access and food safety Plant and animal health Ag labor The Council supports principles/themes): Accelerating rural economic growth and improving productivity through innovation and technology Promoting research and innovation that enables development oftools and techniques necessary for discovering new products that hold tremendous potential for farmers and society at large Enabling a regulatory and commercial environment in which agricultural products are marketable, both domestically and internationally Appropriate balance between Federal and State Governments and a cooperative regulatory approach Access to essential labor in balance with an effective Federal immigration policy and adequate worker safety protections Support for all methods of agricultural production Transparency and dialogue with consumers Members of the CEO Council (see reversed) March 30, 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00002 CEO Council Members American Farm Bureau Vincent "Zippy" Duvall, President American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Cattlemen's Beef Association Kendal Frazier, CEO National Chicken Council Michael Brown, President National Com Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Farmers Union Roger Johnson, President National Milk Producers Federation Jim Mulhern, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Departments of Barb Glenn, CEO, ex-officio Agriculture March 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00003 February 9, 2017 The President The White House Washington, D.C. 20500 Dear Mr. President, We, the CEO Council (undersigned herein), representing the production agricultural value chain, including many agricultural producers and farm input developers and suppliers, look forward to working with you and your Administration on matters of importance to American agriculture. The challenges we face in agriculture are significant. Many experts emphasize that producers must grow as much food in the next 50 years as was produced over all previous history to meet the demands of our expanding global population. A firm commitment by the U.S. government to aggressively support agricultural innovation and science-based regulatory decisions will be necessary to ensure farmers have the tools they need to produce a safe and abundant supply of nutritious food, in addition to feed, fuel and fiber, in an environmentally sound and sustainable manner. The policy and regulatory environment your Administration establishes can ensure that agricultural innovation flourishes and American farmers are able to meet the food production goals necessary to feed billions more people. We are ready to provide the White House and the Executive Branch Departments and Agencies, as well as Congress, with policy concepts that foster stability in the U.S. agriculture economy with a strong and predictable farm safety net and promotes American competitiveness through research; marketability and trade of agricultural commodities; rural economic growth; and plant, animal, and environmental health, among many other things. We appreciate your attention to these and other issues of value to American production agriculture and food consumers everywhere. Sincerely, American Farm Bureau Foundation, Zippy Duvall American Seed Trade Association, Andy LaVigne American Soybean Association, Steve Censky Biotechnology Innovation Organization, Dana O'Brien CropLife America, Jay Vroom The Fertilizer Institute, Chris Jahn National Association of Wheat Growers, Chandler Goule National Cattlemen's Beef Association, Kendal Frazier National Corn Growers Association, Chris Novak National Cotton Council, Gary Adams National Council of Farmer Cooperatives, Chuck Conner National Farmers Union, Roger Johnson National Milk Producers Federation, Jim Mulhern National Pork Producers Council, Neil Dierks United Fresh Produce Association, Tom Stenzel USA Rice Federation, Betsy Ward Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00004 National Gotton Council OF MERTOA Gary M. Adams President and Chief Executive Officer National Cotton Council of America Gary Adams assumed the position of President and Chief Executive Officer of the National Cotton Council in February 2015. He plays a key role in guiding the industry's seven segments to reach consensus on critical policies affecting U.S. cotton, with the mission of helping all U.S. cotton industry segments compete effectively and profitably in global markets. Prior to that, Gary served the Council for 13 years as the Vice President of Economic and Policy Analysis. As the Council's chief economist, he provided economic outlooks for global cotton markets, as well as analyzing the impacts of farm and trade policies. Gary also represents the U.S. cotton industry as a member of USDA's Agricultural Policy Advisory Committee. Previously, Gary served on USDA's Advisory Committee on Trade from 2005 through 2011 and the NASS Advisory Committee on Agricultural Statistics from 2003 through 2009. Prior to joining the Council, Gary was a Research Assistant Professor in the Department of Agricultural Economics at the University of Missouri. During his 13-year tenure at the university, Gary's primary responsibilities included policy analysis and market outlook for the Food and Agricultural Policy Research Institute, also known as FAPRI. While at FAPRI, Gary and his colleagues were recognized by the American Agricultural Economics Association for their distinguished policy contributions. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00005 Gary has B.S. and M.A. degrees in Applied Mathematics from the University of Alabama. and a Ph.D. in Agricultural Economics from the University of Missouri. Gary and his wife, Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00006 FASA American Soybean Associatión & Stephen L Censky Chief Executive Officer Stephen L. Censky is the American Soybean Association's (ASA) C hief Executive Officer, a staff position he accepted in April 1996. As ASA's top executive, Ce nsky is in charge of managing ASA's legislative, trade policy, membership and education and training programs. The American Soybean Association is a national, not-for-profit commodity organization with over 22,000 members. ASA works as the domestic and international policy advocate for soybean producer members. Prior to joining ASA, Censky worked in Washington, D.C. for ove a decade. He began his career on Capitol Hill as a legislative assistant for agricultural and transportation matters to Senator Jim Abdnor (R-SD). Later he served in both the Reagan and Bush Administrations at the U.S. Department of Agriculture, helping to craft the 1990 Farm Bill and eventually serving as Administrator of the Foreign Agricultural Service where he was involved in global trade negotiations and running our nation's export programs. Censky received his Bachelor's of Science degree of Agriculture from South Dakota State University and his Master's Diploma in Agriculture St of Melbourne, Australia. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00007 NCFC. National Council of Farmer Cooperatives Charles F. (Chuck) Conner President and CEO National Council of Farmer Cooperatives Charles F. (Chuck) Conner became president & CEO of the National Council of Farmer Cooperatives (NCFC) on January 22, 2009. As president of NCFC, Conner will oversee the organization's work to promote and protect the business and public policy interests of America's farmer-owned cooperatives. He will also provide the strategic vision for the trade association as it continues to seek new ways in which to add value for its membership. Prior to joining NCFC, Conner had served as the Deputy Secretary at the U.S. Department of Agriculture since mid-2005. In this capacity, he was the Chief Operating Officer (COO) overseeing day-to-day operations of the department. Conner interacted directly with President George W. Bush and his senior staff to formulate domestic and international food, trade, security and energy policy. He led development of the Bush Administration's $300 billion Farm Bill proposal and the strategy to educate and inform industry, constituents and Congress. From August 2007 to January 2008, Conner served as both USDA Secretary and Deputy Secretary. He played a key role in developing the Administration's immigration policy including important changes to the H2A program. Conner's experience also includes the assignment of Special Assistant to the President, Executive Office of the President, from October 2001 to May 2005, working on the 2001/2 Farm Bill to develop the strategy behind the transfer of several USDA agency functions to the newly formed Department of Homeland Security. From May 1997 to October 2001 Conner served as President of the Corn Refiners Association. He also served for 17 years as an advisor to U.S. Senator Richard Lugar of Indiana. Conner is a graduate of Purdue University, with a Bachelor's of Science degree and is the recipient of Purdue's Distinguished Alumni Award. He and his wife Ex. 6 - Personal Privacy Source: :https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00008 NATIONAL PORK PRODUCERS COUNCIL Neil Dierks, Chief Executive Officer Neil Dierks is Chief Executive Officer of the National Pork Producers Council (NPPC). In this position, he is responsible for the overall implementation of all NPPC programs. Dierks' position requires him to spend time in both Des Moines, Iowa, the national office of NPPC, and Washington, D.C. Beginning in 1990, Dierks served NPPC in a series of senior executive positions, including Executive Director of Operations, Vice President for Research and Education and Senior Vice President for Programs. Prior to his service with NPPC, Dierks was the Special Activities Director for the Iowa Pork Producers Association and Marketing Director for the Iowa Corn Promotion Board. Neil grew up on a livestock farm in eastern lowa and remains involved in a family farming operation. He is a graduate of Iowa State University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00009 NASDA Dr. Barbara Glenn recently joined the National Association of State Departments of Agriculture (NASDA) as CEO on August 18, 2014. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. Dr. Glenn is a scientist with decades of experience as a policy researcher and advocate for agriculture. She previously served as Senior Vice President of Science and Regulatory Affairs for CropLife America, where she was responsible for developing policies and regulations to support agriculture through crop protection. Prior to joining CropLife America, Dr. Glenn served as Managing Director of the Animal Bi otechnology, Food and Agriculture Section of the Biotechnology Industry Association in Washington, DC. Dr. Glenn holds a B.S. in animal science and a Ph.D. in ruminan t nutrition from the University of Kentucky. She previously worked for the U.S. Department of Agriculture, Agric ultural Research Service and the Federation of Animal Science Societies. Born in Lincoln, Nebraska and raised in Centerville, Ohio, Dr. Glenn developed a passion for agriculture from her parents and her involvement in 4-H. She lives on a small farm in Maryland with her husband: Ex. 6 - Personal Privacy and serves on various boards for farm bureau and 4-H. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00010

When did Chandler Goule assume his responsibilities as CEO?

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on July 5, 2016., July 5, 2016

To: Greenwalt, Sarah[[email protected]]; Dravis, Samantha[[email protected]] Brown, Byron[[email protected]];Wagner, Kenneth[[email protected]] From: Hupp, Sydney Sent: Thur 3/30/2017 5:11:34 PM Subject: FW: FINAL Meeting Agenda and Materials Pruitt Meeting Materials.pd FYI. Sydney Hupp Office of the Administrator- Scheduling 202.816.1659 From: Mary Jo Tomalewski [mailto:[email protected]] Sent: Thursday, March 30, 2017 11:22 AM To: Hupp, Sydney <[email protected]> Cc: Jay Vroom <[email protected]> Subject: FINAL Meeting Agenda and Materials Sydney, We have refined our proposed topics for today's CEO Council meeting with the administrator. Attached, please find: Revised "Final Proposed Agenda Topics," which includes the list of those CEO Council members who will attend our meeting today, and their short bios Introduction / Mission Overview of the CEO Council CEO Council Letter to President Trump, dated February 9, 2017 We assume we can skip a formal "round table of introductions" at the beginning of the meeting as our time is short and we want to maximize time spent talking about issues. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000061-00001 MJ Mary Jo Tomalewski Executive Assistant to the President & CEO CropLife America 1156 15th Street, NW Suite 400 Washington, DC 20005 Direct Dial (202) 872-3849 Main Switchboard (202) 296-1585 Mobile Ex. 6 Personal Privacy Fax (202)466-5832 Email [email protected] Web www.croplifeamerica.org How can I serve you today? Future Meetings 2017 Spring Regulator Conference - April 6-7, Arlington, VA 2017 Annual Meeting - September 22-27, Dana Point, CA 2018 Winter Board of Directors Meeting - March 5-7, Washington, DC 2018 Annual Meeting - September 21-26, The Ritz-Carlton Amelia Island Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000061-00002 FINAL PROPOSED AGENDA TOPICS Meeting Information: Office of EPA Administrator Scott Pruitt 1200 Pennsylvania Avenue, NW Washington, DC Thursday, March 30, 2017 3:45-4:30 PM Topic 1. Thanks to Trump Administration and Administrator Pruitt for early decisive actions: a. WOTUS b. Chlorpyrifos Petition 2. Top Priority Issues a. Ag Advisor Position - We recommend adding additional title of "Assistant Deputy Administrator" as a title b. Water i. Next steps to refine / clarify beyond WOTUS ii. NPDES permits (CAFO Program needs work; legislation to fix water permits NOT needed for lawful use of pesticides) c. Pesticides Policy i. Endangered Species Act conflicts with Pesticide Regulation and Biotech Regulation ii. Epidemiology Study Policy (as aftermath from Chlorpyrifos matter) iii. Reform Certification & Training and Worker Protection Rules - Suspend implementation and revise d. Renewable Fuels Standard - current program kept consistent e. Communication / Messaging / Opinion Polling - vital to all parties' ability to advance sound policy f. EPA and USDA Cooperation and Coordination - Already vast progress; more can be done! g. Environmental Justice, Research & Development, and Children's Health Offices - Better integration with and reform of EPA program offices; sound science h. Regulation of Manufacturing & Mining Facilities for Ag Inputs - Restore science and process i. Public and Science Advisory Panels at EPA - Balance, strategic agendas j. "Air Emissions" from farming operations CEO Attendees American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Corn Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Barb Glenn, CEO, ex-officio Departments of Agriculture Others American Farm Bureau Federation Dale Moore, Deputy Executive Director Corn Refiners Association John Bode, President & CEO National Farmers Union Rob Larew, Senior VP Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00001 Production Agriculture's CEO Council Introduction/Mission Statement: The production agriculture "CEO Council" coordinates alignment on core issues of modern agricultural systems through telling our story, sharing information and leveraging our strengths, while serving as a resource for government decision makers and others interested in USA food, fiber and renewable fuels. Core Focus of Interest Research and innovation Technology access Science and risk-based regulation Sustainability, environment, and weather Marketability, trade, and economic prosperity Government leadership and partnership with private sector Food access and food safety Plant and animal health Ag labor The Council supports principles/themes): Accelerating rural economic growth and improving productivity through innovation and technology Promoting research and innovation that enables development oftools and techniques necessary for discovering new products that hold tremendous potential for farmers and society at large Enabling a regulatory and commercial environment in which agricultural products are marketable, both domestically and internationally Appropriate balance between Federal and State Governments and a cooperative regulatory approach Access to essential labor in balance with an effective Federal immigration policy and adequate worker safety protections Support for all methods of agricultural production Transparency and dialogue with consumers Members of the CEO Council (see reversed) March 30, 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00002 CEO Council Members American Farm Bureau Vincent "Zippy" Duvall, President American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Cattlemen's Beef Association Kendal Frazier, CEO National Chicken Council Michael Brown, President National Com Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Farmers Union Roger Johnson, President National Milk Producers Federation Jim Mulhern, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Departments of Barb Glenn, CEO, ex-officio Agriculture March 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00003 February 9, 2017 The President The White House Washington, D.C. 20500 Dear Mr. President, We, the CEO Council (undersigned herein), representing the production agricultural value chain, including many agricultural producers and farm input developers and suppliers, look forward to working with you and your Administration on matters of importance to American agriculture. The challenges we face in agriculture are significant. Many experts emphasize that producers must grow as much food in the next 50 years as was produced over all previous history to meet the demands of our expanding global population. A firm commitment by the U.S. government to aggressively support agricultural innovation and science-based regulatory decisions will be necessary to ensure farmers have the tools they need to produce a safe and abundant supply of nutritious food, in addition to feed, fuel and fiber, in an environmentally sound and sustainable manner. The policy and regulatory environment your Administration establishes can ensure that agricultural innovation flourishes and American farmers are able to meet the food production goals necessary to feed billions more people. We are ready to provide the White House and the Executive Branch Departments and Agencies, as well as Congress, with policy concepts that foster stability in the U.S. agriculture economy with a strong and predictable farm safety net and promotes American competitiveness through research; marketability and trade of agricultural commodities; rural economic growth; and plant, animal, and environmental health, among many other things. We appreciate your attention to these and other issues of value to American production agriculture and food consumers everywhere. Sincerely, American Farm Bureau Foundation, Zippy Duvall American Seed Trade Association, Andy LaVigne American Soybean Association, Steve Censky Biotechnology Innovation Organization, Dana O'Brien CropLife America, Jay Vroom The Fertilizer Institute, Chris Jahn National Association of Wheat Growers, Chandler Goule National Cattlemen's Beef Association, Kendal Frazier National Corn Growers Association, Chris Novak National Cotton Council, Gary Adams National Council of Farmer Cooperatives, Chuck Conner National Farmers Union, Roger Johnson National Milk Producers Federation, Jim Mulhern National Pork Producers Council, Neil Dierks United Fresh Produce Association, Tom Stenzel USA Rice Federation, Betsy Ward Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00004 National Gotton Council OF MERTOA Gary M. Adams President and Chief Executive Officer National Cotton Council of America Gary Adams assumed the position of President and Chief Executive Officer of the National Cotton Council in February 2015. He plays a key role in guiding the industry's seven segments to reach consensus on critical policies affecting U.S. cotton, with the mission of helping all U.S. cotton industry segments compete effectively and profitably in global markets. Prior to that, Gary served the Council for 13 years as the Vice President of Economic and Policy Analysis. As the Council's chief economist, he provided economic outlooks for global cotton markets, as well as analyzing the impacts of farm and trade policies. Gary also represents the U.S. cotton industry as a member of USDA's Agricultural Policy Advisory Committee. Previously, Gary served on USDA's Advisory Committee on Trade from 2005 through 2011 and the NASS Advisory Committee on Agricultural Statistics from 2003 through 2009. Prior to joining the Council, Gary was a Research Assistant Professor in the Department of Agricultural Economics at the University of Missouri. During his 13-year tenure at the university, Gary's primary responsibilities included policy analysis and market outlook for the Food and Agricultural Policy Research Institute, also known as FAPRI. While at FAPRI, Gary and his colleagues were recognized by the American Agricultural Economics Association for their distinguished policy contributions. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00005 Gary has B.S. and M.A. degrees in Applied Mathematics from the University of Alabama and a Ph.D. in Agricultural Economics from the University of Missouri. Gary and his wife, Ex. 6 Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00006 FASA American Soybean Associatión & Stephen L Censky Chief Executive Officer Stephen L. Censky is the American Soybean Association's (ASA) C hief Executive Officer, a staff position he accepted in April 1996. As ASA's top executive, Ce nsky is in charge of managing ASA's legislative, trade policy, membership and education and training programs. The American Soybean Association is a national, not-for-profit commodity organization with over 22,000 members. ASA works as the domestic and international policy advocate for soybean producer members. Prior to joining ASA, Censky worked in Washington, D.C. for ove a decade. He began his career on Capitol Hill as a legislative assistant for agricultural and transportation matters to Senator Jim Abdnor (R-SD). Later he served in both the Reagan and Bush Administrations at the U.S. Department of Agriculture, helping to craft the 1990 Farm Bill and eventually serving as Administrator of the Foreign Agricultural Service where he was involved in global trade negotiations and running our nation's export programs. Censky received his Bachelor's of Science degree of Agriculture from South Dakota State University and his Master's Diploma in Agriculture St of Melbourne, Australia. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00007 NCFC. National Council of Farmer Cooperatives Charles F. (Chuck) Conner President and CEO National Council of Farmer Cooperatives Charles F. (Chuck) Conner became president & CEO of the National Council of Farmer Cooperatives (NCFC) on January 22, 2009. As president of NCFC, Conner will oversee the organization's work to promote and protect the business and public policy interests of America's farmer-owned cooperatives. He will also provide the strategic vision for the trade association as it continues to seek new ways in which to add value for its membership. Prior to joining NCFC, Conner had served as the Deputy Secretary at the U.S. Department of Agriculture since mid-2005. In this capacity, he was the Chief Operating Officer (COO) overseeing day-to-day operations of the department. Conner interacted directly with President George W. Bush and his senior staff to formulate domestic and international food, trade, security and energy policy. He led development of the Bush Administration's $300 billion Farm Bill proposal and the strategy to educate and inform industry, constituents and Congress. From August 2007 to January 2008, Conner served as both USDA Secretary and Deputy Secretary. He played a key role in developing the Administration's immigration policy including important changes to the H2A program. Conner's experience also includes the assignment of Special Assistant to the President, Executive Office of the President, from October 2001 to May 2005, working on the 2001/2 Farm Bill to develop the strategy behind the transfer of several USDA agency functions to the newly formed Department of Homeland Security. From May 1997 to October 2001 Conner served as President of the Corn Refiners Association. He also served for 17 years as an advisor to U.S. Senator Richard Lugar of Indiana. Conner is a graduate of Purdue University, with a Bachelor's of Science degree and is the recipient of Purdue's Distinguished Alumni Award. He and his wife Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00008 NATIONAL PORK PRODUCERS COUNCIL Neil Dierks, Chief Executive Officer Neil Dierks is Chief Executive Officer of the National Pork Producers Council (NPPC). In this position, he is responsible for the overall implementation of all NPPC programs. Dierks' position requires him to spend time in both Des Moines, Iowa, the national office of NPPC, and Washington, D.C. Beginning in 1990, Dierks served NPPC in a series of senior executive positions, including Executive Director of Operations, Vice President for Research and Education and Senior Vice President for Programs. Prior to his service with NPPC, Dierks was the Special Activities Director for the Iowa Pork Producers Association and Marketing Director for the Iowa Corn Promotion Board. Neil grew up on a livestock farm in eastern lowa and remains involved in a family farming operation. He is a graduate of Iowa State University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00009 NASDA Dr. Barbara Glenn recently joined the National Association of State Departments of Agriculture (NASDA) as CEO on August 18, 2014. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. Dr. Glenn is a scientist with decades of experience as a policy researcher and advocate for agriculture. She previously served as Senior Vice President of Science and Regulatory Affairs for CropLife America, where she was responsible for developing policies and regulations to support agriculture through crop protection. Prior to joining CropLife America, Dr. Glenn served as Managing Director of the Animal Bi otechnology, Food and Agriculture Section of the Biotechnology Industry Association in Washington, DC. Dr. Glenn holds a B.S. in animal science and a Ph.D. in ruminan t nutrition from the University of Kentucky. She previously worked for the U.S. Department of Agriculture, Agric ultural Research Service and the Federation of Animal Science Societies. Born in Lincoln, Nebraska and raised in Centerville, Ohio, Dr. Glenn developed a passion for agriculture from her parents and her involvement in 4-H. She lives Ex. 6 - Personal Privacy and serves on various boards for farm bureau and 4-H. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00010 National Association of Wheat Growers Chandler Goule CEO Chandler Goule assumed his responsibilities as CEO of the National Association of Wheat Growers on July 5, 2016. In addition, he also serves as the executive director of the National Wheat Foundation. Most recently, Goule served as senior vice president of programs at the National Farmers Union (NFU) where he was heavily involved in farm bill legislation. Originally from Texas, Goule holds degrees from Texas A&M and George Washington University and served as a subcommittee staff director for the House Agriculture Committee before moving to the National Farmers Union in 2009 as vice president of government relations. He was appointed senior vice president of NFU programs in 2014. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00011 The Fertilizer Institute Nourish, Replenish, Grow BIOGRAPHY OF CHRISTOPHER JAHN President The Fertilizer Institute and the Nutrients for Life Foundation Christopher L. Jahn is president of The Fertilizer Institute (TFI), the fertilizer industry's national trade association. As TFI president, Jahn works to represent, promote and protect a sound fertilizer industry through legislative and regulatory activities and to promote a favorable public image of the fertilizer industry and agriculture. Jahn also serves as president of the Nutrients for Life Foundation (NFL). Jahn comes to TFI having served as president of the National Association of Chemical Distributors (NACD) since 2006. Prior to leading NACD, Jahn served as president of the Contract Services Association (CSA). Before joining CSA, Jahn had an active role in the United States Senate working for nearly 10 years for U.S. Senator Craig Thomas (R-Wyo.) in a variety of roles, including legislative assistant, legislative director and Chief of Staff. After graduating from Columbia University with a B.A. in Political Science, Jahn co-founded a book distribution business. He also earned an MBA from the University of Maryland. A native of Wyoming, Chris and his wife, Ex. 6 - Personal Privacy Ex. Personal Privacy Capitol View 202.962.0490 425 Third Street, S.W., Suite 950 202.962.0577 fax Washington, DC 20024 www.tfi.org Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00012 National Farmers Union Roger Johnson President Roger Johnson is president of the National Farmers Union (NFU), a grassroots organization that represents more than 200,000 family farmers, ranchers, fisherman and rural communities across the Unites States. Johnson was elected to lead the family farm organization at NFU's 107th anniversary convention in 2009. He has since expanded the education department by providing more programs for beginning, college-aged and women farmers, increased the number of Farmers Union state divisions, and developed a strategic plan for the organization. Johnson has also overseen a number of important policy initiatives important to family farmers including: passage of the 2014 Farm Bill; maintaining a strong Renewable Fuel Standard and Country-of-Origir Labeling, promoting policies that allow farmers to address the growing threat of climate change; and renewing the nation's focus on eliminating an overwhelming trade deficit that results in lost jobs and prosperity for rural America. Prior to leading National Farmers Union, Johnson, a third-generation family farmer from Turtle Lake, N.D., served as North Dakota Agriculture Commissioner, a position he was first elected to in 1996. While Agriculture Commissioner, Johnson served on the State Industrial Commission, the North Dakota Trade Office Advisory Board, and the State Board of Agricultural Research and Education, among many other boards and commissions. From 2007-2008, Johnson served as president of the National Association of State Departments of Agriculture (NASDA). He is a past president of the Midwestern Association of State Departments of Agriculture (MASDA), past president of the Food Export Association of the Midwest and a former chairman of the Interstate Pest Control Compact. Johnson graduated from North Dakota State University with a degree in agricultural economics. Johnson and his wife Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00013 AMERICAN SEED TRADE ASSOCIATION asta first-the - seed R Andrew W. "Andy" LaVigne President & CEO Andrew W. LaVigne is currently the President and CEO of the Ame rican Seed Trade Association. He joined ASTA in February, 2006. Andy has had a 30-year career i n government relations, industry representation, public affairs advocacy, and management. His C ore areas of expertise include agriculture, food policy and international trade. Prior to joining ASTA, Andy was Executive Vice President/CEC of Florida Citrus Mutual, representing citrus growers on issues affecting their business. Prejaiming tFdorida Citrus Mutual, Andy spent four years as Florida Fertilizer and Agrichemical Association's (FFAA) President and Executive Director. FFAA is a non-profit, agricultural trade organization representing companies that specialize in crop protection and plant nutrition products. Before his position at FFAA, Andy spent eight years in Washingt on, D.C. working in the U.S. Congress and the U.S. Department of Agriculture. He served as Legislative Director for Congressman Charles Canady, Agriculture Committee staffer for Congressman Tom Lewis , and on the staff of USDA Secretary Ed Madigan. Andy is a native of Florida with a BA degree in Political Scien ce, with a minor in economics, from the University of Florida. 1701 Duke Street Suite 275 Alexandria, VA 22314 Phone: (703)837-8140 Fax: (703)837-9365 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00014 Biotechnology Innovation Organization Dana O'Brien Executive Vice President, Food & Agriculture Dana O'Brien is Executive Vice President for Food and Agriculture and is responsible for the development of public policy and strategic advocacy, public affairo, and legal strategies that advance industry and stakeholder objectives in the United States. Prior to becoming EVP, Dana served bs BIO Food and Agriculture's chief legislative advocate as Senior Director of Federal Government Relations aince March 2011. Before BIO, Dana worked in Congress for the late Representative lke Skelton (D-MO) managing his legislative team and concentrating on a variety of agricultural, energy, and trade matters. A native of Sedalia, Missouri, and a graduate of Missouri University with a bachelor's degree in psychology, Dana joined the Skelton team immediately out of college and served there for nearly 14 years Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00015 UNITED FRESH is PRODUCE ASSOCIATION Tom Stenzel President and CEO United Fresh Produce Association 1901 Pennsylvania Avenue NW, Suite 1100 Washington, DC 20006 202/303-3400 [email protected] Tom Stenzel is President and CEO of the United Fresh Produce Association, a position he has held since 1993. United Fresh is the pre-eminent trade association for the produce industry in shaping legislative and regulatory policies; providing scientific and technical leadership in food safety and nutrition; and developing educational programs for its members. Founded in 1904, United Fresh represents the interests of companies from small family businesses to the largest international corporations throughout the global fresh produce supply chain. United Fresh is widely known for its work in government affairs, agricultural policy, food safety and nutrition, working to promote political and environmental change to help the next generation of children double their consumption of fresh produce. The United Fresh Start Foundation is committed to increasing children's access to fresh fruits and vegetables, and is a founding partner of the Let's Move Salad Bars to Schools campaign. The campaign has donated salad bars to more than 6,000 schools across the country. Tom is a frequent speaker on industry issues and has been recognized often by the produce industry throughout his career. He was honored as the 2002 Produce Man of the Year by The Packer newspaper, and is the past Chairman of the International Federation for Produce Standards, a global body representing national produce associations around the world. He is a member of the U.S. Chamber of Commerce Committee of 100 leading association executives, the Advisory Board of the International Food Protection Training Institute, and the Key Industry Associations Committee of the American Society of Association Executives, from which he achieved the Certified Association Executive (CAE) designation in 1990. He has served in many government and industry leadership positions, including the first U.S. Department of Agriculture Fruit and Vegetable Industry Advisory Committee, President George W. Bush's Transition Advisory Team for Agriculture, and as an advisor on the U.S. Agricultural Policy Advisory Committee for Trade. Tom was the founding President of the International Food Information Council (IFIC) in 1986, and was previously director of public affairs for the National Soft Drink Association. Tom is a 1977 graduate of the University of Richmond. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00016 as of January 17, 2017 Jay Vroom has served as President and CEO of the trade association known as CropLife America (CLA) since 1989. CLA is the leading U.S. trade group for the crop protection industry in the U.S. Vroom is a founding member of the CropLife Foundation, serving as chairman since its inception in 2001, and now serves as the Foundation's Vice-Chair, since 2015. His sits of the Board of Directors for the Agricultural Retailers Association, Asmark, National Wheat Foundation, the National Association of Manufacturers Council of Manufacturing Associations, and the Soil Health Institute. He is also a member of the Farm Foundation Roundtable Steering Committee, and the North American Climate Smart Ag Alliance Steering Committee. Vroom was a member of the youth organization, Future Farmers of America, and served as an elected state officer in Illinois. Today, he is a member of the FFA Foundation's Individual Giving Council and Board of Trustees. Vroom co-chairs the Coalition for the Advancement of Precision Agriculture and the CEO Council. He is a member of the Friends of the National Arboretum (FONA) FONA Council. He graduated with honors from the College of Agriculture, Consumer and Environmental Sciences at the University of Illinois Urbana-Champaign. Vroom was raised on a grain and livestock farm in north-central Illinois and continues to own the farming operation. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00017 Elizabeth Ward Betsy Ward was appointed President & CEO of the USA Rice Federation in 2007. From 2003- 2005, Ward was the Vice President of International and Domestic Promotion at USA Rice where she was in charge of developing and implementing domestic and international promotion, and food aid programs. From 2005-2007, Ward served as the chief executive for the Hardwood Federation, a trade association representing over 15,000 hardwood producers across the United States. From 1995 to 2003, she ran the Wood Products International Group at the American Forest & Paper Association, directing the wood trade policy and global forestry agenda for the industry. In 2011, Ward was elected Chairman of the U.S. Agricultural Export Development Council (USAEDC) which represents the interests of more than 80 commodity organizations who grow and process a wide variety of U.S. agricultural products. She currently serves as Past Chair. Since 2011, Ward has also served on the Board of Directors of the Sustainable Fisheries Partnership, an independent non-governmental organization (NGO) working to ensure healthy marine and aquatic tecosystems; secure seafood supplies; and a thriving, responsible seafood economy. Ward served for six years as a cleared advisor on the Industry Trade Advisory Committee for forest and paper products (ITAC-7) and was appointed forest products representative to USDA's Agricultural Policy Advisory Committee (APAC) in 2001. Ward holds a Bachelor's degree in History and Political Science from the University of New Hampshire and a Master's degree in International Security Affairs from the School of International Affairs at Columbia University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00018 To: Brown, Byron[[email protected]]; Jackson, Ryan[[email protected]] From: Rebeckah Adcock Sent: Thur 3/30/2017 4:10:52 PM Subject: FW: FINAL CEO Council Meeting Agenda and Materials Pruitt Meeting Materials.pdf ATT00001.htm FYI - final materials for today's meeting. Reb From: "Mary Jo Tomalewski" <[email protected]> To: "Hupp, Sydney" <[email protected]> Cc: "Jay Vroom" <[email protected]> Subject: FINAL Meeting Agenda and Materials Sydney, We have refined our proposed topics for today's CEO Council meeting with the administrator. Attached, please find: Revised "Final Proposed Agenda Topics," which includes the list of those CEO Council members who will attend our meeting today, and their short bios Introduction / Mission Overview of the CEO Council CEO Council Letter to President Trump, dated February 9, 2017 We assume we can skip a formal "round table of introductions" at the beginning of the meeting as our time is short and we want to maximize time spent talking about issues. MJ Mary Jo Tomalewski Executive Assistant to the President & CEO CropLife America Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000063-00001 1156 15th Street, NW Suite 400 Washington, DC 20005 Direct Dial (202) 872-3849 Main Switchboard (202) 296-1585 Mobilé Ex. 6 Personal Privacy Fax (202) 466-5832 Email [email protected] Web www.croplifeamerica.org How can I serve you today? Future Meetings 2017 Spring Regulator Conference - April 6-7, Arlington, VA 2017 Annual Meeting - September 22-27, Dana Point, CA 2018 Winter Board of Directors Meeting - March 5-7, Washington, DC 2018 Annual Meeting - September 21-26, The Ritz-Carlton Amelia Island Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000063-00002 FINAL PROPOSED AGENDA TOPICS Meeting Information: Office of EPA Administrator Scott Pruitt 1200 Pennsylvania Avenue, NW Washington, DC Thursday, March 30, 2017 3:45-4:30 PM Topic 1. Thanks to Trump Administration and Administrator Pruitt for early decisive actions: a. WOTUS b. Chlorpyrifos Petition 2. Top Priority Issues a. Ag Advisor Position - We recommend adding additional title of "Assistant Deputy Administrator" as a title b. Water i. Next steps to refine / clarify beyond WOTUS ii. NPDES permits (CAFO Program needs work; legislation to fix water permits NOT needed for lawful use of pesticides) c. Pesticides Policy i. Endangered Species Act conflicts with Pesticide Regulation and Biotech Regulation ii. Epidemiology Study Policy (as aftermath from Chlorpyrifos matter) iii. Reform Certification & Training and Worker Protection Rules - Suspend implementation and revise d. Renewable Fuels Standard - current program kept consistent e. Communication / Messaging / Opinion Polling - vital to all parties' ability to advance sound policy f. EPA and USDA Cooperation and Coordination - Already vast progress; more can be done! g. Environmental Justice, Research & Development, and Children's Health Offices - Better integration with and reform of EPA program offices; sound science h. Regulation of Manufacturing & Mining Facilities for Ag Inputs - Restore science and process i. Public and Science Advisory Panels at EPA - Balance, strategic agendas j. "Air Emissions" from farming operations CEO Attendees American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Corn Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Barb Glenn, CEO, ex-officio Departments of Agriculture Others American Farm Bureau Federation Dale Moore, Deputy Executive Director Corn Refiners Association John Bode, President & CEO National Farmers Union Rob Larew, Senior VP Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00001 Production Agriculture's CEO Council Introduction/Mission Statement: The production agriculture "CEO Council" coordinates alignment on core issues of modern agricultural systems through telling our story, sharing information and leveraging our strengths, while serving as a resource for government decision makers and others interested in USA food, fiber and renewable fuels. Core Focus of Interest Research and innovation Technology access Science and risk-based regulation Sustainability, environment, and weather Marketability, trade, and economic prosperity Government leadership and partnership with private sector Food access and food safety Plant and animal health Ag labor The Council supports principles/themes): Accelerating rural economic growth and improving productivity through innovation and technology Promoting research and innovation that enables development oftools and techniques necessary for discovering new products that hold tremendous potential for farmers and society at large Enabling a regulatory and commercial environment in which agricultural products are marketable, both domestically and internationally Appropriate balance between Federal and State Governments and a cooperative regulatory approach Access to essential labor in balance with an effective Federal immigration policy and adequate worker safety protections Support for all methods of agricultural production Transparency and dialogue with consumers Members of the CEO Council (see reversed) March 30, 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00002 CEO Council Members American Farm Bureau Vincent "Zippy" Duvall, President American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Cattlemen's Beef Association Kendal Frazier, CEO National Chicken Council Michael Brown, President National Com Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Farmers Union Roger Johnson, President National Milk Producers Federation Jim Mulhern, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Departments of Barb Glenn, CEO, ex-officio Agriculture March 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00003 February 9, 2017 The President The White House Washington, D.C. 20500 Dear Mr. President, We, the CEO Council (undersigned herein), representing the production agricultural value chain, including many agricultural producers and farm input developers and suppliers, look forward to working with you and your Administration on matters of importance to American agriculture. The challenges we face in agriculture are significant. Many experts emphasize that producers must grow as much food in the next 50 years as was produced over all previous history to meet the demands of our expanding global population. A firm commitment by the U.S. government to aggressively support agricultural innovation and science-based regulatory decisions will be necessary to ensure farmers have the tools they need to produce a safe and abundant supply of nutritious food, in addition to feed, fuel and fiber, in an environmentally sound and sustainable manner. The policy and regulatory environment your Administration establishes can ensure that agricultural innovation flourishes and American farmers are able to meet the food production goals necessary to feed billions more people. We are ready to provide the White House and the Executive Branch Departments and Agencies, as well as Congress, with policy concepts that foster stability in the U.S. agriculture economy with a strong and predictable farm safety net and promotes American competitiveness through research; marketability and trade of agricultural commodities; rural economic growth; and plant, animal, and environmental health, among many other things. We appreciate your attention to these and other issues of value to American production agriculture and food consumers everywhere. Sincerely, American Farm Bureau Foundation, Zippy Duvall American Seed Trade Association, Andy LaVigne American Soybean Association, Steve Censky Biotechnology Innovation Organization, Dana O'Brien CropLife America, Jay Vroom The Fertilizer Institute, Chris Jahn National Association of Wheat Growers, Chandler Goule National Cattlemen's Beef Association, Kendal Frazier National Corn Growers Association, Chris Novak National Cotton Council, Gary Adams National Council of Farmer Cooperatives, Chuck Conner National Farmers Union, Roger Johnson National Milk Producers Federation, Jim Mulhern National Pork Producers Council, Neil Dierks United Fresh Produce Association, Tom Stenzel USA Rice Federation, Betsy Ward Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00004 National Gotton Council OF MERTOA Gary M. Adams President and Chief Executive Officer National Cotton Council of America Gary Adams assumed the position of President and Chief Executive Officer of the National Cotton Council in February 2015. He plays a key role in guiding the industry's seven segments to reach consensus on critical policies affecting U.S. cotton, with the mission of helping all U.S. cotton industry segments compete effectively and profitably in global markets. Prior to that, Gary served the Council for 13 years as the Vice President of Economic and Policy Analysis. As the Council's chief economist, he provided economic outlooks for global cotton markets, as well as analyzing the impacts of farm and trade policies. Gary also represents the U.S. cotton industry as a member of USDA's Agricultural Policy Advisory Committee. Previously, Gary served on USDA's Advisory Committee on Trade from 2005 through 2011 and the NASS Advisory Committee on Agricultural Statistics from 2003 through 2009. Prior to joining the Council, Gary was a Research Assistant Professor in the Department of Agricultural Economics at the University of Missouri. During his 13-year tenure at the university, Gary's primary responsibilities included policy analysis and market outlook for the Food and Agricultural Policy Research Institute, also known as FAPRI. While at FAPRI, Gary and his colleagues were recognized by the American Agricultural Economics Association for their distinguished policy contributions. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00005 Gary has B.S. and M.A. degrees in Applied Mathematics from the University of Alabama. and a Ph.D. in Agricultural Economics from the University of Missouri. Gary and his wife, Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00006 FASA American Soybean Associatión & Stephen L Censky Chief Executive Officer Stephen L. Censky is the American Soybean Association's (ASA) C hief Executive Officer, a staff position he accepted in April 1996. As ASA's top executive, Ce nsky is in charge of managing ASA's legislative, trade policy, membership and education and training programs. The American Soybean Association is a national, not-for-profit commodity organization with over 22,000 members. ASA works as the domestic and international policy advocate for soybean producer members. Prior to joining ASA, Censky worked in Washington, D.C. for ove a decade. He began his career on Capitol Hill as a legislative assistant for agricultural and transportation matters to Senator Jim Abdnor (R-SD). Later he served in both the Reagan and Bush Administrations at the U.S. Department of Agriculture, helping to craft the 1990 Farm Bill and eventually serving as Administrator of the Foreign Agricultural Service where he was involved in global trade negotiations and running our nation's export programs. Censky received his Bachelor's of Science degree of Agriculture from South Dakota State University and his Master's Diploma in Agriculture St of Melbourne, Australia. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00007 NCFC. National Council of Farmer Cooperatives Charles F. (Chuck) Conner President and CEO National Council of Farmer Cooperatives Charles F. (Chuck) Conner became president & CEO of the National Council of Farmer Cooperatives (NCFC) on January 22, 2009. As president of NCFC, Conner will oversee the organization's work to promote and protect the business and public policy interests of America's farmer-owned cooperatives. He will also provide the strategic vision for the trade association as it continues to seek new ways in which to add value for its membership. Prior to joining NCFC, Conner had served as the Deputy Secretary at the U.S. Department of Agriculture since mid-2005. In this capacity, he was the Chief Operating Officer (COO) overseeing day-to-day operations of the department. Conner interacted directly with President George W. Bush and his senior staff to formulate domestic and international food, trade, security and energy policy. He led development of the Bush Administration's $300 billion Farm Bill proposal and the strategy to educate and inform industry, constituents and Congress. From August 2007 to January 2008, Conner served as both USDA Secretary and Deputy Secretary. He played a key role in developing the Administration's immigration policy including important changes to the H2A program. Conner's experience also includes the assignment of Special Assistant to the President, Executive Office of the President, from October 2001 to May 2005, working on the 2001/2 Farm Bill to develop the strategy behind the transfer of several USDA agency functions to the newly formed Department of Homeland Security. From May 1997 to October 2001 Conner served as President of the Corn Refiners Association. He also served for 17 years as an advisor to U.S. Senator Richard Lugar of Indiana. Conner is a graduate of Purdue University, with a Bachelor's of Science degree and is the recipient of Purdue's Distinguished Alumni Award. He and his wife Ex. 6 - Personal Privacy Source: :https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00008 NATIONAL PORK PRODUCERS COUNCIL Neil Dierks, Chief Executive Officer Neil Dierks is Chief Executive Officer of the National Pork Producers Council (NPPC). In this position, he is responsible for the overall implementation of all NPPC programs. Dierks' position requires him to spend time in both Des Moines, Iowa, the national office of NPPC, and Washington, D.C. Beginning in 1990, Dierks served NPPC in a series of senior executive positions, including Executive Director of Operations, Vice President for Research and Education and Senior Vice President for Programs. Prior to his service with NPPC, Dierks was the Special Activities Director for the Iowa Pork Producers Association and Marketing Director for the Iowa Corn Promotion Board. Neil grew up on a livestock farm in eastern lowa and remains involved in a family farming operation. He is a graduate of Iowa State University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00009 NASDA Dr. Barbara Glenn recently joined the National Association of State Departments of Agriculture (NASDA) as CEO on August 18, 2014. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. Dr. Glenn is a scientist with decades of experience as a policy researcher and advocate for agriculture. She previously served as Senior Vice President of Science and Regulatory Affairs for CropLife America, where she was responsible for developing policies and regulations to support agriculture through crop protection. Prior to joining CropLife America, Dr. Glenn served as Managing Director of the Animal Bi otechnology, Food and Agriculture Section of the Biotechnology Industry Association in Washington, DC. Dr. Glenn holds a B.S. in animal science and a Ph.D. in ruminan t nutrition from the University of Kentucky. She previously worked for the U.S. Department of Agriculture, Agric ultural Research Service and the Federation of Animal Science Societies. Born in Lincoln, Nebraska and raised in Centerville, Ohio, Dr. Glenn developed a passion for agriculture from her parents and her involvement in 4-H. She lives on a small farm in Maryland with her husband: Ex. 6 - Personal Privacy and serves on various boards for farm bureau and 4-H. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00010

What happens if enough flammable gas is produced ?

qrbn0226

qrbn0226_p0, qrbn0226_p1, qrbn0226_p2, qrbn0226_p3, qrbn0226_p4

the battery casing can fail releasing the gas, which can potentially ignited surrounding materials and cause a fire.

189 From: White, Kimberly To: Admon. Smadar: Anderson Steven; Batoon, Audrey; Bradley, Kevin; de Lacy Catharine; Blkan, llan; Erraguntia. Neeraja: Goodman. Bryan; Hochschwender, Lane: Jacobi. Sylvia.B. Kannah. Kasturirangan; Levan Steve; Levchik. Sergei; Little Barbara: Manor. Orit: Prero. Judab; Rothenbacher, Klaus; Saunders. Eric L Scherrer. Steve; Simon Robert: Tavior. Jennifer; Tenney, Joel: Thorn Amelia: West Jay; White Kimberly; Haves, A Wallace; Rein. Guillermo; [email protected] Troitzsch. Jurgen; Blais. Matthew; Dourson. Michael (doursoml); Kacew Sam; Osimitz. Thomas Subject: Request to Schedule a Call on Baby Monitor Combustion Project Date: Thursday, May 18, 2017 10:32:45 AM Attachments: Baby Monitor Plastic Flammability Proposal finalpdi Dear NAFRA Science Workgroup Members and Science Advisory Council Members: In follow-up to this week's discussion regarding the current status and next steps for the Baby Monit or Combustion Project, we'd like to schedule a call with members and the researchers. Please access the poll below by 5pm (ET) Monday, May 22nd Note all times in the poll are in Eastern Daylight Time. Poll: http://doodle.com/poll/2piythmxu23tugsd. As well below is a summary of the May meeting discussion as provided by Drs. Ezekoye and Marr and attached or in links below are relevant documents. Please review this information and provide any initial additional thoughts you may have regarding the project next steps. Relevant Documents Baby Monitor Combustion Project Proposal (attached) Link to Baby Monitor Combustion Project Update Summary Report in PDF-March 2017 Link to Baby Monitor Combustion PowerPoint Project Update Presented on May 16, 2017 Summary of Discussion by Drs. Ezekoye and Marr Here are some of the commentsf from our conference call. There were two threads: better characterization of the baby monitor cases and developing more representative failure scenarios. The suggestions related to characterizing the baby monitor cases included: - Use X-Ray Photoelectron Spectroscopy (XPS) to look for bromine in the OEM baby monitor cases - Measure the critical heat flux of the OEM and surrogate baby monitor plastics - Create our own FRtreated cases using FR ABS The suggestions related to developing more representative (lower HRR) failures included: - Explore scaling down the failure mode of the existing batteries - Use a cartridge heater as the heat source After the call, Drs. Ezekoye and Marr also discussed another alternative of scaling down the battery size to get different effective failure energies and HRRs. Kind Regards, Kimberly Wise White, Ph. D. | American Chemistry Council Senior Director, Chemical Products & Technology Division Kimberly [email protected] 700 2nd Street NE Washington, DC | 20002 O: (202) 249-6707 C: (202) 341-7602 www.americanchemistry.com This message may contain confidential information and is intended only for the individual named. If you are not the named addressee do not disseminate, distribute or copy this email. Please notify the sender immediately by email if you have received this email by mistake and delete this email from your system. E-mail Source: https://www.industrydocuments.ucsf.edu/docs/qrbn0226 COCKRELL SCHOOL OF ENGINEERING THE UNIVERSITY OF TEXAS AT AUSTIN the 5 Department of Mechanical Engineering . ETC II 5.160 . http://www.me.utexas.edu 1 University Station C2200 . Austin, Texas . 78712-0292 . (512)471-1131 . Fax (512)471-8727 August 3, 2016 Joel Tenney Director of Advocacy ICL-IP America Subject: Baby Monitor Thermal and Flammability Testing Dear Mr. Tenney, Thank you for your interest in working with UT Fire Research Group (UTFRG) to characterize the thermal stability and fire hazards posed by baby monitors. The appended project whitepaper presents our current understanding of the scope of services sought and terms of the engagement. Once you've reviewed this statement of work, please let me know how you would like to proceed. Sincerely, O.A. ('DK') Ezekoye, Ph.D., P.E. W.R. Woolrich Professor Department of Mechanical Engineering & Department of Civil, Arch. and Environ. Engineering Program Director, Online M.S. in Mechanical Engineering Source: https://www.industrydocuments.ucsf.edu/docs/qrbn0226 UTFRG Recall Testing Whitepaper August 3, 2016 Thermal and Flammability Testing of a Recalled Baby Monitor University of Texas Fire Research Group Summary The proposed scope of work is to conduct experimental testing to investigate the thermal characteristics and flammability of baby monitors. Currently, fire retardant (FR) plastics are used in many products (toys, chairs, electronics, etc.) to reduce the risk of fire and burn hazards. Flame retardants are considered by fire scientists to be an integral part of the management and mitigation of fire and burn hazards. It is understood in fire science that addition of flame retardants in polymeric materials can reduce the ignitability and flame spread characteristics of the material. Some detractors of FRs argue that the environmental and public health impact of flame retardants outweigh their potential fire mitigation capability. For portable electronics accessories such as baby monitors that are powered by lithium-ion batteries the fire risk is greater than passive (i.e., unpowered) baby products. Recently several baby monitors branded by Lorex were recalled due to potential burn hazards related to battery failures. Figure 1 shows images of the Lorex baby monitor and battery, and Figure 2 shows images of a failed battery from the Lorex baby monitor. The swollen battery shown in Figure 2 is the result of the battery overheating and producing flammable gas. Although in this case, there were no reports of fires, if enough flammable gas is produced, the battery casing can fail releasing the gas, which can potentially ignited surrounding materials and cause a fire. In the event of a battery thermal failure, FR is likely to reduce the risk of ignition and fire of the baby monitor plastic. - - - Figure 1. Images of the recalled Lorex baby monitor and the lithium-ion battery. Source: https://www.industrydocuments.ucsf.edu/docs/qrbn0226 UTFRG Recall Testing Whitepaper August 3, 2016 Figure 2. Images of swollen battery from a Lorex baby monitor that had failed. The purpose of the proposed work is to investigate the effectiveness of FR on a representative electronic baby accessory. In this study a baby monitor will be used as the representative exemplar. UTFRG proposes that our services be divided into the following tasks: Task A-Fabricate Replica Baby Monitors $10,000.00 ($15,600 w/ overhead) The scope of Task A is to design and fabricate three replicas of a baby monitor. It is UTFRG's understanding that one possible model of interest is manufactured by Lorex (Model No. WL3520, WL4320, and WL3401). As discussed above, these models have been recalled and are currently unavailable from United States retailers. However, it may be possible to obtain exemplar units from international retailers or third-party resellers. If available, UTFRG will procure exemplar baby monitors. If the make and model is commercially unavailable, an alternative make and model may be used. Any alternative model will be agreed upon in discussions with the sponsor prior to procurement. An exemplar baby monitor housing will be laser scanned and three replicas will be fabricated using a 3-D printer. The replica housings will be constructed of material that does not contain fire retardants. One filament system available for testing for the Makerbot systems is PLA 3D Printer Filament/ MakerBot PLA. Makerbot has information on their website about the flammability concerns of their products Figure 3. Makerbot flammability warning video at http://www.makerbot.com/blog/2010/11/29/makerbot-psa-fire-and-abs-pla-dont-mix Source: https://www.industrydocuments.ucsf.edu/docs/qrbn0226 UTFRG Recall Testing Whitepaper August 3, 2016 UTFRG will evaluate the housing material, and replica housings will be printed using the same material type. Components including the LCD, electronics and battery will be extracted from exemplar units and re-installed in the replica housings. Upon completion of this task, UTFRG will provide the sponsor with a report detailing the procurement process, CAD design details, and photographs of the reassembled baby monitors. Electronic CAD files can also be provided upon request. Task A is expected to take five (5) weeks to complete. The cost estimate for this task includes salary for students and research engineer, student tuition and fees, fringe benefits, and supplies. The cost of procuring exemplar monitors is also included. If the work is routed through the University as a contract as compared to a gift, a 1.56 overhead multiplier takes the nominal cost from $10K to $15.6K. Task B-Thermal & Flammability Testing $20,000.00 ($31,200 w/ overhead) Upon completion of Task A, UTFRG will develop and implement a test program to assess the effectiveness of FR on electronic baby products. The testing will include small scale ignition tests on the base plastics and full system flammability experiments on six (6) baby monitors: three (3) exemplar monitors and three (3) replica monitors. In the full system experiments, fire will be induced by thermally failing the battery. The battery will be charged to 100% state-of- charge (SOC) prior to thermal failure. In actual use scenarios, batteries often fail due to internal shorts from manufacturing defects, mechanical damage overcharging. Because of the stochastic nature of thermal failures, simulating an internal short in a lab setting can be challenging. The most reliable method to thermally fail a battery is to apply external heat; however, external heat may lead to heat damage or potentially ignition of the housing prior to the battery thermal failure. UTFRG will investigate and develop a reliable failure method to fail the battery while minimizing collateral damage during said failure. Testing will be photo-documented and video recorded. Additional measurements will also made. These measurements include, but are not limited to, surface temperature of the baby monitor housing, battery and electronic circuit board, heat release from the induced fire, and thermal imaging of the induced fire. Upon completion of this Task, UTFRG will provide a report and presentation-style report. Raw data and videos will be provided upon request. Task B is expected to take ten (10) weeks to complete. The cost estimate for this task includes salary for students and research engineer, student tuition and fees, fringe benefits, and supplies. The cost of procuring exemplar monitors is also included. If the work is routed through the University as a contract as compared to a gift, a 1.56 overhead multiplier takes the nominal cost from $20K to $31.2K. Source: https://www.industrydocuments.ucsf.edu/docs/qrbn0226

What was Chandler Goule's position in national wheat foundation?

ffcn0226

ffcn0226_p0, ffcn0226_p1, ffcn0226_p2, ffcn0226_p3, ffcn0226_p4, ffcn0226_p5, ffcn0226_p6, ffcn0226_p7, ffcn0226_p8, ffcn0226_p9, ffcn0226_p10, ffcn0226_p11, ffcn0226_p12, ffcn0226_p13, ffcn0226_p14, ffcn0226_p15, ffcn0226_p16, ffcn0226_p17, ffcn0226_p18, ffcn0226_p19, ffcn0226_p20, ffcn0226_p21, ffcn0226_p22, ffcn0226_p23, ffcn0226_p24, ffcn0226_p25, ffcn0226_p26, ffcn0226_p27, ffcn0226_p28, ffcn0226_p29, ffcn0226_p30, ffcn0226_p31

Executive Director, CEO

To: Greenwalt, Sarah[[email protected]]; Dravis, Samantha[[email protected]] Brown, Byron[[email protected]];Wagner, Kenneth[[email protected]] From: Hupp, Sydney Sent: Thur 3/30/2017 5:11:34 PM Subject: FW: FINAL Meeting Agenda and Materials Pruitt Meeting Materials.pd FYI. Sydney Hupp Office of the Administrator- Scheduling 202.816.1659 From: Mary Jo Tomalewski [mailto:[email protected]] Sent: Thursday, March 30, 2017 11:22 AM To: Hupp, Sydney <[email protected]> Cc: Jay Vroom <[email protected]> Subject: FINAL Meeting Agenda and Materials Sydney, We have refined our proposed topics for today's CEO Council meeting with the administrator. Attached, please find: Revised "Final Proposed Agenda Topics," which includes the list of those CEO Council members who will attend our meeting today, and their short bios Introduction / Mission Overview of the CEO Council CEO Council Letter to President Trump, dated February 9, 2017 We assume we can skip a formal "round table of introductions" at the beginning of the meeting as our time is short and we want to maximize time spent talking about issues. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000061-00001 MJ Mary Jo Tomalewski Executive Assistant to the President & CEO CropLife America 1156 15th Street, NW Suite 400 Washington, DC 20005 Direct Dial (202) 872-3849 Main Switchboard (202) 296-1585 Mobile Ex. 6 Personal Privacy Fax (202)466-5832 Email [email protected] Web www.croplifeamerica.org How can I serve you today? Future Meetings 2017 Spring Regulator Conference - April 6-7, Arlington, VA 2017 Annual Meeting - September 22-27, Dana Point, CA 2018 Winter Board of Directors Meeting - March 5-7, Washington, DC 2018 Annual Meeting - September 21-26, The Ritz-Carlton Amelia Island Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000061-00002 FINAL PROPOSED AGENDA TOPICS Meeting Information: Office of EPA Administrator Scott Pruitt 1200 Pennsylvania Avenue, NW Washington, DC Thursday, March 30, 2017 3:45-4:30 PM Topic 1. Thanks to Trump Administration and Administrator Pruitt for early decisive actions: a. WOTUS b. Chlorpyrifos Petition 2. Top Priority Issues a. Ag Advisor Position - We recommend adding additional title of "Assistant Deputy Administrator" as a title b. Water i. Next steps to refine / clarify beyond WOTUS ii. NPDES permits (CAFO Program needs work; legislation to fix water permits NOT needed for lawful use of pesticides) c. Pesticides Policy i. Endangered Species Act conflicts with Pesticide Regulation and Biotech Regulation ii. Epidemiology Study Policy (as aftermath from Chlorpyrifos matter) iii. Reform Certification & Training and Worker Protection Rules - Suspend implementation and revise d. Renewable Fuels Standard - current program kept consistent e. Communication / Messaging / Opinion Polling - vital to all parties' ability to advance sound policy f. EPA and USDA Cooperation and Coordination - Already vast progress; more can be done! g. Environmental Justice, Research & Development, and Children's Health Offices - Better integration with and reform of EPA program offices; sound science h. Regulation of Manufacturing & Mining Facilities for Ag Inputs - Restore science and process i. Public and Science Advisory Panels at EPA - Balance, strategic agendas j. "Air Emissions" from farming operations CEO Attendees American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Corn Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Barb Glenn, CEO, ex-officio Departments of Agriculture Others American Farm Bureau Federation Dale Moore, Deputy Executive Director Corn Refiners Association John Bode, President & CEO National Farmers Union Rob Larew, Senior VP Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00001 Production Agriculture's CEO Council Introduction/Mission Statement: The production agriculture "CEO Council" coordinates alignment on core issues of modern agricultural systems through telling our story, sharing information and leveraging our strengths, while serving as a resource for government decision makers and others interested in USA food, fiber and renewable fuels. Core Focus of Interest Research and innovation Technology access Science and risk-based regulation Sustainability, environment, and weather Marketability, trade, and economic prosperity Government leadership and partnership with private sector Food access and food safety Plant and animal health Ag labor The Council supports principles/themes): Accelerating rural economic growth and improving productivity through innovation and technology Promoting research and innovation that enables development oftools and techniques necessary for discovering new products that hold tremendous potential for farmers and society at large Enabling a regulatory and commercial environment in which agricultural products are marketable, both domestically and internationally Appropriate balance between Federal and State Governments and a cooperative regulatory approach Access to essential labor in balance with an effective Federal immigration policy and adequate worker safety protections Support for all methods of agricultural production Transparency and dialogue with consumers Members of the CEO Council (see reversed) March 30, 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00002 CEO Council Members American Farm Bureau Vincent "Zippy" Duvall, President American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Cattlemen's Beef Association Kendal Frazier, CEO National Chicken Council Michael Brown, President National Com Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Farmers Union Roger Johnson, President National Milk Producers Federation Jim Mulhern, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Departments of Barb Glenn, CEO, ex-officio Agriculture March 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00003 February 9, 2017 The President The White House Washington, D.C. 20500 Dear Mr. President, We, the CEO Council (undersigned herein), representing the production agricultural value chain, including many agricultural producers and farm input developers and suppliers, look forward to working with you and your Administration on matters of importance to American agriculture. The challenges we face in agriculture are significant. Many experts emphasize that producers must grow as much food in the next 50 years as was produced over all previous history to meet the demands of our expanding global population. A firm commitment by the U.S. government to aggressively support agricultural innovation and science-based regulatory decisions will be necessary to ensure farmers have the tools they need to produce a safe and abundant supply of nutritious food, in addition to feed, fuel and fiber, in an environmentally sound and sustainable manner. The policy and regulatory environment your Administration establishes can ensure that agricultural innovation flourishes and American farmers are able to meet the food production goals necessary to feed billions more people. We are ready to provide the White House and the Executive Branch Departments and Agencies, as well as Congress, with policy concepts that foster stability in the U.S. agriculture economy with a strong and predictable farm safety net and promotes American competitiveness through research; marketability and trade of agricultural commodities; rural economic growth; and plant, animal, and environmental health, among many other things. We appreciate your attention to these and other issues of value to American production agriculture and food consumers everywhere. Sincerely, American Farm Bureau Foundation, Zippy Duvall American Seed Trade Association, Andy LaVigne American Soybean Association, Steve Censky Biotechnology Innovation Organization, Dana O'Brien CropLife America, Jay Vroom The Fertilizer Institute, Chris Jahn National Association of Wheat Growers, Chandler Goule National Cattlemen's Beef Association, Kendal Frazier National Corn Growers Association, Chris Novak National Cotton Council, Gary Adams National Council of Farmer Cooperatives, Chuck Conner National Farmers Union, Roger Johnson National Milk Producers Federation, Jim Mulhern National Pork Producers Council, Neil Dierks United Fresh Produce Association, Tom Stenzel USA Rice Federation, Betsy Ward Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00004 National Gotton Council OF MERTOA Gary M. Adams President and Chief Executive Officer National Cotton Council of America Gary Adams assumed the position of President and Chief Executive Officer of the National Cotton Council in February 2015. He plays a key role in guiding the industry's seven segments to reach consensus on critical policies affecting U.S. cotton, with the mission of helping all U.S. cotton industry segments compete effectively and profitably in global markets. Prior to that, Gary served the Council for 13 years as the Vice President of Economic and Policy Analysis. As the Council's chief economist, he provided economic outlooks for global cotton markets, as well as analyzing the impacts of farm and trade policies. Gary also represents the U.S. cotton industry as a member of USDA's Agricultural Policy Advisory Committee. Previously, Gary served on USDA's Advisory Committee on Trade from 2005 through 2011 and the NASS Advisory Committee on Agricultural Statistics from 2003 through 2009. Prior to joining the Council, Gary was a Research Assistant Professor in the Department of Agricultural Economics at the University of Missouri. During his 13-year tenure at the university, Gary's primary responsibilities included policy analysis and market outlook for the Food and Agricultural Policy Research Institute, also known as FAPRI. While at FAPRI, Gary and his colleagues were recognized by the American Agricultural Economics Association for their distinguished policy contributions. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00005 Gary has B.S. and M.A. degrees in Applied Mathematics from the University of Alabama and a Ph.D. in Agricultural Economics from the University of Missouri. Gary and his wife, Ex. 6 Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00006 FASA American Soybean Associatión & Stephen L Censky Chief Executive Officer Stephen L. Censky is the American Soybean Association's (ASA) C hief Executive Officer, a staff position he accepted in April 1996. As ASA's top executive, Ce nsky is in charge of managing ASA's legislative, trade policy, membership and education and training programs. The American Soybean Association is a national, not-for-profit commodity organization with over 22,000 members. ASA works as the domestic and international policy advocate for soybean producer members. Prior to joining ASA, Censky worked in Washington, D.C. for ove a decade. He began his career on Capitol Hill as a legislative assistant for agricultural and transportation matters to Senator Jim Abdnor (R-SD). Later he served in both the Reagan and Bush Administrations at the U.S. Department of Agriculture, helping to craft the 1990 Farm Bill and eventually serving as Administrator of the Foreign Agricultural Service where he was involved in global trade negotiations and running our nation's export programs. Censky received his Bachelor's of Science degree of Agriculture from South Dakota State University and his Master's Diploma in Agriculture St of Melbourne, Australia. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00007 NCFC. National Council of Farmer Cooperatives Charles F. (Chuck) Conner President and CEO National Council of Farmer Cooperatives Charles F. (Chuck) Conner became president & CEO of the National Council of Farmer Cooperatives (NCFC) on January 22, 2009. As president of NCFC, Conner will oversee the organization's work to promote and protect the business and public policy interests of America's farmer-owned cooperatives. He will also provide the strategic vision for the trade association as it continues to seek new ways in which to add value for its membership. Prior to joining NCFC, Conner had served as the Deputy Secretary at the U.S. Department of Agriculture since mid-2005. In this capacity, he was the Chief Operating Officer (COO) overseeing day-to-day operations of the department. Conner interacted directly with President George W. Bush and his senior staff to formulate domestic and international food, trade, security and energy policy. He led development of the Bush Administration's $300 billion Farm Bill proposal and the strategy to educate and inform industry, constituents and Congress. From August 2007 to January 2008, Conner served as both USDA Secretary and Deputy Secretary. He played a key role in developing the Administration's immigration policy including important changes to the H2A program. Conner's experience also includes the assignment of Special Assistant to the President, Executive Office of the President, from October 2001 to May 2005, working on the 2001/2 Farm Bill to develop the strategy behind the transfer of several USDA agency functions to the newly formed Department of Homeland Security. From May 1997 to October 2001 Conner served as President of the Corn Refiners Association. He also served for 17 years as an advisor to U.S. Senator Richard Lugar of Indiana. Conner is a graduate of Purdue University, with a Bachelor's of Science degree and is the recipient of Purdue's Distinguished Alumni Award. He and his wife Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00008 NATIONAL PORK PRODUCERS COUNCIL Neil Dierks, Chief Executive Officer Neil Dierks is Chief Executive Officer of the National Pork Producers Council (NPPC). In this position, he is responsible for the overall implementation of all NPPC programs. Dierks' position requires him to spend time in both Des Moines, Iowa, the national office of NPPC, and Washington, D.C. Beginning in 1990, Dierks served NPPC in a series of senior executive positions, including Executive Director of Operations, Vice President for Research and Education and Senior Vice President for Programs. Prior to his service with NPPC, Dierks was the Special Activities Director for the Iowa Pork Producers Association and Marketing Director for the Iowa Corn Promotion Board. Neil grew up on a livestock farm in eastern lowa and remains involved in a family farming operation. He is a graduate of Iowa State University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00009 NASDA Dr. Barbara Glenn recently joined the National Association of State Departments of Agriculture (NASDA) as CEO on August 18, 2014. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. Dr. Glenn is a scientist with decades of experience as a policy researcher and advocate for agriculture. She previously served as Senior Vice President of Science and Regulatory Affairs for CropLife America, where she was responsible for developing policies and regulations to support agriculture through crop protection. Prior to joining CropLife America, Dr. Glenn served as Managing Director of the Animal Bi otechnology, Food and Agriculture Section of the Biotechnology Industry Association in Washington, DC. Dr. Glenn holds a B.S. in animal science and a Ph.D. in ruminan t nutrition from the University of Kentucky. She previously worked for the U.S. Department of Agriculture, Agric ultural Research Service and the Federation of Animal Science Societies. Born in Lincoln, Nebraska and raised in Centerville, Ohio, Dr. Glenn developed a passion for agriculture from her parents and her involvement in 4-H. She lives Ex. 6 - Personal Privacy and serves on various boards for farm bureau and 4-H. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00010 National Association of Wheat Growers Chandler Goule CEO Chandler Goule assumed his responsibilities as CEO of the National Association of Wheat Growers on July 5, 2016. In addition, he also serves as the executive director of the National Wheat Foundation. Most recently, Goule served as senior vice president of programs at the National Farmers Union (NFU) where he was heavily involved in farm bill legislation. Originally from Texas, Goule holds degrees from Texas A&M and George Washington University and served as a subcommittee staff director for the House Agriculture Committee before moving to the National Farmers Union in 2009 as vice president of government relations. He was appointed senior vice president of NFU programs in 2014. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00011 The Fertilizer Institute Nourish, Replenish, Grow BIOGRAPHY OF CHRISTOPHER JAHN President The Fertilizer Institute and the Nutrients for Life Foundation Christopher L. Jahn is president of The Fertilizer Institute (TFI), the fertilizer industry's national trade association. As TFI president, Jahn works to represent, promote and protect a sound fertilizer industry through legislative and regulatory activities and to promote a favorable public image of the fertilizer industry and agriculture. Jahn also serves as president of the Nutrients for Life Foundation (NFL). Jahn comes to TFI having served as president of the National Association of Chemical Distributors (NACD) since 2006. Prior to leading NACD, Jahn served as president of the Contract Services Association (CSA). Before joining CSA, Jahn had an active role in the United States Senate working for nearly 10 years for U.S. Senator Craig Thomas (R-Wyo.) in a variety of roles, including legislative assistant, legislative director and Chief of Staff. After graduating from Columbia University with a B.A. in Political Science, Jahn co-founded a book distribution business. He also earned an MBA from the University of Maryland. A native of Wyoming, Chris and his wife, Ex. 6 - Personal Privacy Ex. Personal Privacy Capitol View 202.962.0490 425 Third Street, S.W., Suite 950 202.962.0577 fax Washington, DC 20024 www.tfi.org Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00012 National Farmers Union Roger Johnson President Roger Johnson is president of the National Farmers Union (NFU), a grassroots organization that represents more than 200,000 family farmers, ranchers, fisherman and rural communities across the Unites States. Johnson was elected to lead the family farm organization at NFU's 107th anniversary convention in 2009. He has since expanded the education department by providing more programs for beginning, college-aged and women farmers, increased the number of Farmers Union state divisions, and developed a strategic plan for the organization. Johnson has also overseen a number of important policy initiatives important to family farmers including: passage of the 2014 Farm Bill; maintaining a strong Renewable Fuel Standard and Country-of-Origir Labeling, promoting policies that allow farmers to address the growing threat of climate change; and renewing the nation's focus on eliminating an overwhelming trade deficit that results in lost jobs and prosperity for rural America. Prior to leading National Farmers Union, Johnson, a third-generation family farmer from Turtle Lake, N.D., served as North Dakota Agriculture Commissioner, a position he was first elected to in 1996. While Agriculture Commissioner, Johnson served on the State Industrial Commission, the North Dakota Trade Office Advisory Board, and the State Board of Agricultural Research and Education, among many other boards and commissions. From 2007-2008, Johnson served as president of the National Association of State Departments of Agriculture (NASDA). He is a past president of the Midwestern Association of State Departments of Agriculture (MASDA), past president of the Food Export Association of the Midwest and a former chairman of the Interstate Pest Control Compact. Johnson graduated from North Dakota State University with a degree in agricultural economics. Johnson and his wife Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00013 AMERICAN SEED TRADE ASSOCIATION asta first-the - seed R Andrew W. "Andy" LaVigne President & CEO Andrew W. LaVigne is currently the President and CEO of the Ame rican Seed Trade Association. He joined ASTA in February, 2006. Andy has had a 30-year career i n government relations, industry representation, public affairs advocacy, and management. His C ore areas of expertise include agriculture, food policy and international trade. Prior to joining ASTA, Andy was Executive Vice President/CEC of Florida Citrus Mutual, representing citrus growers on issues affecting their business. Prejaiming tFdorida Citrus Mutual, Andy spent four years as Florida Fertilizer and Agrichemical Association's (FFAA) President and Executive Director. FFAA is a non-profit, agricultural trade organization representing companies that specialize in crop protection and plant nutrition products. Before his position at FFAA, Andy spent eight years in Washingt on, D.C. working in the U.S. Congress and the U.S. Department of Agriculture. He served as Legislative Director for Congressman Charles Canady, Agriculture Committee staffer for Congressman Tom Lewis , and on the staff of USDA Secretary Ed Madigan. Andy is a native of Florida with a BA degree in Political Scien ce, with a minor in economics, from the University of Florida. 1701 Duke Street Suite 275 Alexandria, VA 22314 Phone: (703)837-8140 Fax: (703)837-9365 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00014 Biotechnology Innovation Organization Dana O'Brien Executive Vice President, Food & Agriculture Dana O'Brien is Executive Vice President for Food and Agriculture and is responsible for the development of public policy and strategic advocacy, public affairo, and legal strategies that advance industry and stakeholder objectives in the United States. Prior to becoming EVP, Dana served bs BIO Food and Agriculture's chief legislative advocate as Senior Director of Federal Government Relations aince March 2011. Before BIO, Dana worked in Congress for the late Representative lke Skelton (D-MO) managing his legislative team and concentrating on a variety of agricultural, energy, and trade matters. A native of Sedalia, Missouri, and a graduate of Missouri University with a bachelor's degree in psychology, Dana joined the Skelton team immediately out of college and served there for nearly 14 years Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00015 UNITED FRESH is PRODUCE ASSOCIATION Tom Stenzel President and CEO United Fresh Produce Association 1901 Pennsylvania Avenue NW, Suite 1100 Washington, DC 20006 202/303-3400 [email protected] Tom Stenzel is President and CEO of the United Fresh Produce Association, a position he has held since 1993. United Fresh is the pre-eminent trade association for the produce industry in shaping legislative and regulatory policies; providing scientific and technical leadership in food safety and nutrition; and developing educational programs for its members. Founded in 1904, United Fresh represents the interests of companies from small family businesses to the largest international corporations throughout the global fresh produce supply chain. United Fresh is widely known for its work in government affairs, agricultural policy, food safety and nutrition, working to promote political and environmental change to help the next generation of children double their consumption of fresh produce. The United Fresh Start Foundation is committed to increasing children's access to fresh fruits and vegetables, and is a founding partner of the Let's Move Salad Bars to Schools campaign. The campaign has donated salad bars to more than 6,000 schools across the country. Tom is a frequent speaker on industry issues and has been recognized often by the produce industry throughout his career. He was honored as the 2002 Produce Man of the Year by The Packer newspaper, and is the past Chairman of the International Federation for Produce Standards, a global body representing national produce associations around the world. He is a member of the U.S. Chamber of Commerce Committee of 100 leading association executives, the Advisory Board of the International Food Protection Training Institute, and the Key Industry Associations Committee of the American Society of Association Executives, from which he achieved the Certified Association Executive (CAE) designation in 1990. He has served in many government and industry leadership positions, including the first U.S. Department of Agriculture Fruit and Vegetable Industry Advisory Committee, President George W. Bush's Transition Advisory Team for Agriculture, and as an advisor on the U.S. Agricultural Policy Advisory Committee for Trade. Tom was the founding President of the International Food Information Council (IFIC) in 1986, and was previously director of public affairs for the National Soft Drink Association. Tom is a 1977 graduate of the University of Richmond. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00016 as of January 17, 2017 Jay Vroom has served as President and CEO of the trade association known as CropLife America (CLA) since 1989. CLA is the leading U.S. trade group for the crop protection industry in the U.S. Vroom is a founding member of the CropLife Foundation, serving as chairman since its inception in 2001, and now serves as the Foundation's Vice-Chair, since 2015. His sits of the Board of Directors for the Agricultural Retailers Association, Asmark, National Wheat Foundation, the National Association of Manufacturers Council of Manufacturing Associations, and the Soil Health Institute. He is also a member of the Farm Foundation Roundtable Steering Committee, and the North American Climate Smart Ag Alliance Steering Committee. Vroom was a member of the youth organization, Future Farmers of America, and served as an elected state officer in Illinois. Today, he is a member of the FFA Foundation's Individual Giving Council and Board of Trustees. Vroom co-chairs the Coalition for the Advancement of Precision Agriculture and the CEO Council. He is a member of the Friends of the National Arboretum (FONA) FONA Council. He graduated with honors from the College of Agriculture, Consumer and Environmental Sciences at the University of Illinois Urbana-Champaign. Vroom was raised on a grain and livestock farm in north-central Illinois and continues to own the farming operation. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00017 Elizabeth Ward Betsy Ward was appointed President & CEO of the USA Rice Federation in 2007. From 2003- 2005, Ward was the Vice President of International and Domestic Promotion at USA Rice where she was in charge of developing and implementing domestic and international promotion, and food aid programs. From 2005-2007, Ward served as the chief executive for the Hardwood Federation, a trade association representing over 15,000 hardwood producers across the United States. From 1995 to 2003, she ran the Wood Products International Group at the American Forest & Paper Association, directing the wood trade policy and global forestry agenda for the industry. In 2011, Ward was elected Chairman of the U.S. Agricultural Export Development Council (USAEDC) which represents the interests of more than 80 commodity organizations who grow and process a wide variety of U.S. agricultural products. She currently serves as Past Chair. Since 2011, Ward has also served on the Board of Directors of the Sustainable Fisheries Partnership, an independent non-governmental organization (NGO) working to ensure healthy marine and aquatic tecosystems; secure seafood supplies; and a thriving, responsible seafood economy. Ward served for six years as a cleared advisor on the Industry Trade Advisory Committee for forest and paper products (ITAC-7) and was appointed forest products representative to USDA's Agricultural Policy Advisory Committee (APAC) in 2001. Ward holds a Bachelor's degree in History and Political Science from the University of New Hampshire and a Master's degree in International Security Affairs from the School of International Affairs at Columbia University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00018 To: Brown, Byron[[email protected]]; Jackson, Ryan[[email protected]] From: Rebeckah Adcock Sent: Thur 3/30/2017 4:10:52 PM Subject: FW: FINAL CEO Council Meeting Agenda and Materials Pruitt Meeting Materials.pdf ATT00001.htm FYI - final materials for today's meeting. Reb From: "Mary Jo Tomalewski" <[email protected]> To: "Hupp, Sydney" <[email protected]> Cc: "Jay Vroom" <[email protected]> Subject: FINAL Meeting Agenda and Materials Sydney, We have refined our proposed topics for today's CEO Council meeting with the administrator. Attached, please find: Revised "Final Proposed Agenda Topics," which includes the list of those CEO Council members who will attend our meeting today, and their short bios Introduction / Mission Overview of the CEO Council CEO Council Letter to President Trump, dated February 9, 2017 We assume we can skip a formal "round table of introductions" at the beginning of the meeting as our time is short and we want to maximize time spent talking about issues. MJ Mary Jo Tomalewski Executive Assistant to the President & CEO CropLife America Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000063-00001 1156 15th Street, NW Suite 400 Washington, DC 20005 Direct Dial (202) 872-3849 Main Switchboard (202) 296-1585 Mobilé Ex. 6 Personal Privacy Fax (202) 466-5832 Email [email protected] Web www.croplifeamerica.org How can I serve you today? Future Meetings 2017 Spring Regulator Conference - April 6-7, Arlington, VA 2017 Annual Meeting - September 22-27, Dana Point, CA 2018 Winter Board of Directors Meeting - March 5-7, Washington, DC 2018 Annual Meeting - September 21-26, The Ritz-Carlton Amelia Island Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000063-00002 FINAL PROPOSED AGENDA TOPICS Meeting Information: Office of EPA Administrator Scott Pruitt 1200 Pennsylvania Avenue, NW Washington, DC Thursday, March 30, 2017 3:45-4:30 PM Topic 1. Thanks to Trump Administration and Administrator Pruitt for early decisive actions: a. WOTUS b. Chlorpyrifos Petition 2. Top Priority Issues a. Ag Advisor Position - We recommend adding additional title of "Assistant Deputy Administrator" as a title b. Water i. Next steps to refine / clarify beyond WOTUS ii. NPDES permits (CAFO Program needs work; legislation to fix water permits NOT needed for lawful use of pesticides) c. Pesticides Policy i. Endangered Species Act conflicts with Pesticide Regulation and Biotech Regulation ii. Epidemiology Study Policy (as aftermath from Chlorpyrifos matter) iii. Reform Certification & Training and Worker Protection Rules - Suspend implementation and revise d. Renewable Fuels Standard - current program kept consistent e. Communication / Messaging / Opinion Polling - vital to all parties' ability to advance sound policy f. EPA and USDA Cooperation and Coordination - Already vast progress; more can be done! g. Environmental Justice, Research & Development, and Children's Health Offices - Better integration with and reform of EPA program offices; sound science h. Regulation of Manufacturing & Mining Facilities for Ag Inputs - Restore science and process i. Public and Science Advisory Panels at EPA - Balance, strategic agendas j. "Air Emissions" from farming operations CEO Attendees American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Corn Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Barb Glenn, CEO, ex-officio Departments of Agriculture Others American Farm Bureau Federation Dale Moore, Deputy Executive Director Corn Refiners Association John Bode, President & CEO National Farmers Union Rob Larew, Senior VP Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00001 Production Agriculture's CEO Council Introduction/Mission Statement: The production agriculture "CEO Council" coordinates alignment on core issues of modern agricultural systems through telling our story, sharing information and leveraging our strengths, while serving as a resource for government decision makers and others interested in USA food, fiber and renewable fuels. Core Focus of Interest Research and innovation Technology access Science and risk-based regulation Sustainability, environment, and weather Marketability, trade, and economic prosperity Government leadership and partnership with private sector Food access and food safety Plant and animal health Ag labor The Council supports principles/themes): Accelerating rural economic growth and improving productivity through innovation and technology Promoting research and innovation that enables development oftools and techniques necessary for discovering new products that hold tremendous potential for farmers and society at large Enabling a regulatory and commercial environment in which agricultural products are marketable, both domestically and internationally Appropriate balance between Federal and State Governments and a cooperative regulatory approach Access to essential labor in balance with an effective Federal immigration policy and adequate worker safety protections Support for all methods of agricultural production Transparency and dialogue with consumers Members of the CEO Council (see reversed) March 30, 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00002 CEO Council Members American Farm Bureau Vincent "Zippy" Duvall, President American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Cattlemen's Beef Association Kendal Frazier, CEO National Chicken Council Michael Brown, President National Com Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Farmers Union Roger Johnson, President National Milk Producers Federation Jim Mulhern, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Departments of Barb Glenn, CEO, ex-officio Agriculture March 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00003 February 9, 2017 The President The White House Washington, D.C. 20500 Dear Mr. President, We, the CEO Council (undersigned herein), representing the production agricultural value chain, including many agricultural producers and farm input developers and suppliers, look forward to working with you and your Administration on matters of importance to American agriculture. The challenges we face in agriculture are significant. Many experts emphasize that producers must grow as much food in the next 50 years as was produced over all previous history to meet the demands of our expanding global population. A firm commitment by the U.S. government to aggressively support agricultural innovation and science-based regulatory decisions will be necessary to ensure farmers have the tools they need to produce a safe and abundant supply of nutritious food, in addition to feed, fuel and fiber, in an environmentally sound and sustainable manner. The policy and regulatory environment your Administration establishes can ensure that agricultural innovation flourishes and American farmers are able to meet the food production goals necessary to feed billions more people. We are ready to provide the White House and the Executive Branch Departments and Agencies, as well as Congress, with policy concepts that foster stability in the U.S. agriculture economy with a strong and predictable farm safety net and promotes American competitiveness through research; marketability and trade of agricultural commodities; rural economic growth; and plant, animal, and environmental health, among many other things. We appreciate your attention to these and other issues of value to American production agriculture and food consumers everywhere. Sincerely, American Farm Bureau Foundation, Zippy Duvall American Seed Trade Association, Andy LaVigne American Soybean Association, Steve Censky Biotechnology Innovation Organization, Dana O'Brien CropLife America, Jay Vroom The Fertilizer Institute, Chris Jahn National Association of Wheat Growers, Chandler Goule National Cattlemen's Beef Association, Kendal Frazier National Corn Growers Association, Chris Novak National Cotton Council, Gary Adams National Council of Farmer Cooperatives, Chuck Conner National Farmers Union, Roger Johnson National Milk Producers Federation, Jim Mulhern National Pork Producers Council, Neil Dierks United Fresh Produce Association, Tom Stenzel USA Rice Federation, Betsy Ward Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00004 National Gotton Council OF MERTOA Gary M. Adams President and Chief Executive Officer National Cotton Council of America Gary Adams assumed the position of President and Chief Executive Officer of the National Cotton Council in February 2015. He plays a key role in guiding the industry's seven segments to reach consensus on critical policies affecting U.S. cotton, with the mission of helping all U.S. cotton industry segments compete effectively and profitably in global markets. Prior to that, Gary served the Council for 13 years as the Vice President of Economic and Policy Analysis. As the Council's chief economist, he provided economic outlooks for global cotton markets, as well as analyzing the impacts of farm and trade policies. Gary also represents the U.S. cotton industry as a member of USDA's Agricultural Policy Advisory Committee. Previously, Gary served on USDA's Advisory Committee on Trade from 2005 through 2011 and the NASS Advisory Committee on Agricultural Statistics from 2003 through 2009. Prior to joining the Council, Gary was a Research Assistant Professor in the Department of Agricultural Economics at the University of Missouri. During his 13-year tenure at the university, Gary's primary responsibilities included policy analysis and market outlook for the Food and Agricultural Policy Research Institute, also known as FAPRI. While at FAPRI, Gary and his colleagues were recognized by the American Agricultural Economics Association for their distinguished policy contributions. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00005 Gary has B.S. and M.A. degrees in Applied Mathematics from the University of Alabama. and a Ph.D. in Agricultural Economics from the University of Missouri. Gary and his wife, Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00006 FASA American Soybean Associatión & Stephen L Censky Chief Executive Officer Stephen L. Censky is the American Soybean Association's (ASA) C hief Executive Officer, a staff position he accepted in April 1996. As ASA's top executive, Ce nsky is in charge of managing ASA's legislative, trade policy, membership and education and training programs. The American Soybean Association is a national, not-for-profit commodity organization with over 22,000 members. ASA works as the domestic and international policy advocate for soybean producer members. Prior to joining ASA, Censky worked in Washington, D.C. for ove a decade. He began his career on Capitol Hill as a legislative assistant for agricultural and transportation matters to Senator Jim Abdnor (R-SD). Later he served in both the Reagan and Bush Administrations at the U.S. Department of Agriculture, helping to craft the 1990 Farm Bill and eventually serving as Administrator of the Foreign Agricultural Service where he was involved in global trade negotiations and running our nation's export programs. Censky received his Bachelor's of Science degree of Agriculture from South Dakota State University and his Master's Diploma in Agriculture St of Melbourne, Australia. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00007 NCFC. National Council of Farmer Cooperatives Charles F. (Chuck) Conner President and CEO National Council of Farmer Cooperatives Charles F. (Chuck) Conner became president & CEO of the National Council of Farmer Cooperatives (NCFC) on January 22, 2009. As president of NCFC, Conner will oversee the organization's work to promote and protect the business and public policy interests of America's farmer-owned cooperatives. He will also provide the strategic vision for the trade association as it continues to seek new ways in which to add value for its membership. Prior to joining NCFC, Conner had served as the Deputy Secretary at the U.S. Department of Agriculture since mid-2005. In this capacity, he was the Chief Operating Officer (COO) overseeing day-to-day operations of the department. Conner interacted directly with President George W. Bush and his senior staff to formulate domestic and international food, trade, security and energy policy. He led development of the Bush Administration's $300 billion Farm Bill proposal and the strategy to educate and inform industry, constituents and Congress. From August 2007 to January 2008, Conner served as both USDA Secretary and Deputy Secretary. He played a key role in developing the Administration's immigration policy including important changes to the H2A program. Conner's experience also includes the assignment of Special Assistant to the President, Executive Office of the President, from October 2001 to May 2005, working on the 2001/2 Farm Bill to develop the strategy behind the transfer of several USDA agency functions to the newly formed Department of Homeland Security. From May 1997 to October 2001 Conner served as President of the Corn Refiners Association. He also served for 17 years as an advisor to U.S. Senator Richard Lugar of Indiana. Conner is a graduate of Purdue University, with a Bachelor's of Science degree and is the recipient of Purdue's Distinguished Alumni Award. He and his wife Ex. 6 - Personal Privacy Source: :https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00008 NATIONAL PORK PRODUCERS COUNCIL Neil Dierks, Chief Executive Officer Neil Dierks is Chief Executive Officer of the National Pork Producers Council (NPPC). In this position, he is responsible for the overall implementation of all NPPC programs. Dierks' position requires him to spend time in both Des Moines, Iowa, the national office of NPPC, and Washington, D.C. Beginning in 1990, Dierks served NPPC in a series of senior executive positions, including Executive Director of Operations, Vice President for Research and Education and Senior Vice President for Programs. Prior to his service with NPPC, Dierks was the Special Activities Director for the Iowa Pork Producers Association and Marketing Director for the Iowa Corn Promotion Board. Neil grew up on a livestock farm in eastern lowa and remains involved in a family farming operation. He is a graduate of Iowa State University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00009 NASDA Dr. Barbara Glenn recently joined the National Association of State Departments of Agriculture (NASDA) as CEO on August 18, 2014. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. Dr. Glenn is a scientist with decades of experience as a policy researcher and advocate for agriculture. She previously served as Senior Vice President of Science and Regulatory Affairs for CropLife America, where she was responsible for developing policies and regulations to support agriculture through crop protection. Prior to joining CropLife America, Dr. Glenn served as Managing Director of the Animal Bi otechnology, Food and Agriculture Section of the Biotechnology Industry Association in Washington, DC. Dr. Glenn holds a B.S. in animal science and a Ph.D. in ruminan t nutrition from the University of Kentucky. She previously worked for the U.S. Department of Agriculture, Agric ultural Research Service and the Federation of Animal Science Societies. Born in Lincoln, Nebraska and raised in Centerville, Ohio, Dr. Glenn developed a passion for agriculture from her parents and her involvement in 4-H. She lives on a small farm in Maryland with her husband: Ex. 6 - Personal Privacy and serves on various boards for farm bureau and 4-H. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00010

under which safety act this is performed ?

ylcn0226

ylcn0226_p0, ylcn0226_p1, ylcn0226_p2, ylcn0226_p3, ylcn0226_p4, ylcn0226_p5, ylcn0226_p6, ylcn0226_p7, ylcn0226_p8, ylcn0226_p9

Launtenberg Chemical Safety Act

Search 1/19/17 snapshot Assessing and Managing Chemicals under TSCA Contact Us Share Assessing and Managing Chemicals under The Frank R. Lautenberg TSCA Home Chemical Safety for the How EPA Assesses Chemical Safety 2 1st Century Act Assessments for TSCA Work Plan Chemicals On June 22, 2016, President Obama signed into law the Frank R. Lautenberg Chemical Safety for Sign up for Current Chemical the 21st Century Act which amends the Toxic TSCA and Risk Reduction Activities Other Substances Control Act (ISCA), the Nation's Chemical ChemView primary chemicals management law. Safety News Chemical Data Reporting The new law, which received bipartisan support in both the U.S. House of Representatives and Getemail alerts the Senate, includes much needed improvements such as: Enter email address sign up Mandatory requirement for EPA to evaluate existing chemicals with clear and enforceable deadlines; New risk-based safety standard; Increased public transparency for chemical information; and Recent Consistent source of funding for EPA to carry additions out the responsibilities under the new law. Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226 American" Chemistry Council August 24, 2016 Wendy Cleland-Hamnett Director, Office of Pollution Prevention and Toxics Environmental Protection Agency 1200 Pennsylvania Ave. NW Washington, DC 20460-0001 Sent electronically to www.regulations.gov docket # EPA-HQ-OPPT-2016-0400 Re: ACC Comments to Inform EPA's Rulemaking on the Conduct of Risk Evaluations under the Lautenberg Chemical Safety Act Dear Ms. Cleland-Hamnett: The American Chemistry Council (ACC¹ appreciates the opportunity to provide input to the Office of Pollution Prevention and Toxics to inform the Agency's development of a risk evaluation rulemaking under the Frank R. Lautenberg Chemical Safety for the 21st Century Act (LCSA). ACC has a long-standing commitment to a robust, science-based approach to evaluation of human and environmental risk. ACC is committed to the effective implementation of the LCSA and supports a workable, rigorous process that allows for timely, high quality reviews. Given the strong emphasis on a risk-based approach in the LCSA, the Section 6(b)(4) rulemaking is particularly important because it will guide the conduct of future risk evaluations that will then inform risk management activities. ACC is committed to being a constructive stakeholder throughout the implementation of LCSA. We will continue to draw from the breadth and depth of our member companies' expertise to ensure that our recommendations are not only science-based, but also allow for the efficient and effective implementation of the LCSA. In doing so, ACC will continue to consider the high quality science standards in the LCSA as well as the timeframes and deadlines imposed therein. The enclosed recommendations were developed with these important considerations in mind. If EPA has any questions, please contact me at nancy [email protected] or 202-249-6417. Sincerely, Nancy B. Beck, PhD, DABT Senior Director, Regulatory and Technical Affairs Cc: Jim Jones, OCSPP Assistant Administrator Louise Wise, Deputy Assistant Administrator Jeffery Morris, Deputy Director for Programs, OPPT Tala Henry, Director, Risk Assessment Division, OPPT 1 The American Chemistry Council (ACC) represents the leading companies engaged in the business of chemistry. More information about ACC is presented in the body of our comments. 1 IPage Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226 American Chemistry Council Initial Input to U.S. Environmental Protection Agency In Regard to the Risk Evaluation Rule under the Lautenberg Chemical Safety Act Table of Contents I. Introduction and Executive Summary 4 II. The Risk Evaluation Rulemaking Must Include both Procedural And Substantive Elements to Effect the Purposes of the Statute 5 III. The Proposed Rule Should Include a Tiered Approach to Risk Evaluation 6 IV. The Rule Should Clarify the Process for Preparation and Contents of the Scope 8 V. The Proposed Rule Should Include a Detailed Description of Substantive Elements of Risk Evaluation 8 VI. Proposed Rule Should Ensure Consistency with Section 6(b)(4)(F) 9 a. Integration and Assessment of Information Relevant to Risks and Information on Potentially Exposed and Susceptible Populations 10 i. Conditions of Use That are Relevant 10 ii. Potentially Exposed or Susceptible Subpopulations 10 b. Aggregate and Sentinel Exposures 12 i. Aggregate Exposures 12 ii. Sentinel Exposures 12 c. Exposure Assessment 13 d. Weight of the Evidence 14 VII. The Proposed Rule Should Incorporate Section 26(h) Scientific Standards 14 a. Fit-for-Purpose Approach 15 b. Consideration of Relevant Information 16 i. Improving Hazard Assessment 16 ii. Improving Dose Response Assessment 17 iii. Reliance on Guidance 17 c. Importance of High Quality Risk Characterization 18 d. Clearly Addressing Variability and Uncertainty 18 e. Ensuring Appropriate Peer Review and Forming a Science Advisory Committee on Chemicals 19 21 Page Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226 VIII. The Proposed Rule Should Implement a Weight of the Scientific Evidence (WoE) Approach 20 a. Systematic Review is Required 20 i. Development of a Protocol 21 ii. Search Strategy 21 iii. Transparency 21 b. A Systematic Review is Not Automatically a WoE Assessment 21 c. WoE and Systematic Review for Screening Level Risk Evaluations 22 d. WoE and Systematic Review for Refined Risk Evaluations 22 e. Strength of Evidence is Not the Same as WoE 23 IX. EPA Should Make Information Available Consistent with Section 26(j) 24 X. EPA Should Use Reasonably Available Information and CBI Consistent with Section 26(k) 24 XI. EPA Should Utilize Fit-for-Purpose Exposure Evaluation Tools 25 XII. The Requirements of Sections 6 and 26 Apply to Environmental Risk Evaluations 26 a. Advancing Models for Environmental Risks 27 b. Improving Data Sourcing, Generation, and Evaluation 27 c. Persistent, Bioaccumulative and Toxic (PBT) Substances 28 XIII. EPA Should Leverage International and Inter-Agency Cooperation 28 XIV. Incorporating High Throughput Tools and Alternative Methods 29 XV. Stakeholders and EPA Must Be Held to the Same High Standard 30 APPENDIX A: ACC's Principles for Improving Chemical Hazard and Risk Assessment 31 APPENDIX B: Improving Hazard Assessment 32 APPENDIX C: Improving Does Response Assessment 33 APPRNDIX D: Improving Risk Characterization 35 APPENDIX E: Ensuring Robust Peer Review 37 APPENDIX F: Exposure Modeling Tools 39 APPENDIX G: Additional Information on the ECETOC TRA 41 3 I P a 3 e Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226 I. Introduction and Executive Summary The American Chemistry Council (ACC)2 is pleased to provide the U.S. Environmental Protection Agency (EPA) this initial input on the Lautenberg Chemical Safety Act's (LCSA) requirement for the Agency to establish, by rule, the process for conducting risk evaluations. ACC appreciates EPA's early efforts to obtain input from stakeholders at its August 9, 2016, public meeting. We also appreciate EPA's solicitation of written comments to be entered into the docket, well in advance of publication of the proposed rule. Our comments both clarify, as well as supplement and expand upon, the oral comments we presented at the August 9 meeting. ACC strongly supported Congress' efforts to update and reform the Toxic Substances Control Act (TSCA). We believe that high quality risk evaluation, using best available science and weight of the evidence (WoE), is at the very heart of the LCSA. Effective and efficient risk evaluations will help deliver the results intended by Congress. Section 6(b)(4)(B) of the statute requires EPA to establish, by rule, "a process to conduct risk evaluations.' This certainly should include a description of the sequence of events, timelines, opportunities for public comments and peer review. Both Sections 6 and 26 of the LCSA outline various substantive elements that apply to and inform risk evaluation. A risk evaluation must: Be conducted in a manner designed to determine "whether a chemical substance presents an unreasonable risk of injury to health or the environment;" as set out in Section 6(b)(4)(A); Identify whether there exists "an unreasonable risk to a potentially exposed or susceptible subpopulation." EPA must identify potentially exposed or susceptible subpopulations relevant to the risk evaluation under conditions of use; Address the specific elements set out in Section 6(b)(4)(F); and Comply with the specific requirements of Section 26, including the best available science, weight of the evidence, and transparency requirements. Because these elements are at the core of the risk evaluation process, and affect risk management measures, they are substantive and should be described in adequate detail in the regulation. In general, where risk evaluation elements are now required by statute, EPA should apply them uniformly and universally reflecting them in the body of the regulation. The recommendations provided by ACC in these comments address screening and refined risk evaluations and are meant to apply to both human health and environmental risks. Specific tools, testing methods, databases, and the like may develop over time, or course, and can be updated as necessary in policies, 2 The American Chemistry Council (ACC) represents the leading companies engaged in the business of chemistry. ACC members apply the science of chemistry to make innovative products and services that make people's lives better, healthier and safer. ACC is committed to improved environmental, health and safety performance through Responsible Care common sense advocacy designed to address major public policy issues, and health and environmental research and product testing. The business of chemistry is a $797 billion enterprise and a key element of the nation's economy. It is the nation's largest exporter, accounting for fourteen percent of all U.S. exports. Chemistry companies are among the largest investors in research and development. Safety and security have always been primary concerns of ACC members, and they have intensified their efforts, working closely with government agencies to improve security and to defend against any threat to the nation's critical infrastructure. 4 Page Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226 procedures and guidance. Our comments strive to make these differentiations and explain where particular elements of risk evaluation should be included in the rule proper. Specifically, our recommendations suggest definitions, and procedural steps and elements that will allow EPA to ensure that risk evaluations are consistent with the statutory requirements for EPA to use the best available science and WoE approaches. The recommendations also include definitions and procedural steps are not expected to change over time. ACC has referenced each of our suggestions to an existing EPA guidance, a National Academies (NAS) report, or another authoritative body or peer reviewed report. For instance, the recommendations in EPA's 2000 Risk Characterization Handbook still represent best practices today. Adding adequate definitions and explanation to the rule is particularly important to achieving incorporation of statutory requirements. We also note that in addition to Section 6, Sections 26(h), 26(i), 26(j), and 26(k) of the LCSA each present legal requirements that are applicable to the risk evaluation. EPA will now need to provide a level of transparency regarding not only the inputs, but also the methods of the analysis, including clear descriptions of uncertainties and variability. EPA should leverage information from other jurisdictions where data and information is applicable and of sufficient quality to meet the science standards in the LCSA. Incorporating these elements into the rulemaking creates a better platform for clear and consistent articulation of the Agency's understanding of statutory requirements, and will better support consistent and uniform application of the elements of risk evaluation. It is critically important that EPA engage the public as EPA plans, scopes, and conducts risk evaluations. Industry scientists often have unique insight and experience with their companies' chemistries and collectively have a large body of knowledge of risk assessment processes globally, including an understanding of potential human health and environmental impacts. ACC encourages EPA to leverage this knowledge and engage early (well before draft risk evaluations are released) and frequently with industry throughout the risk evaluation process. II. The Risk Evaluation Rulemaking Must Include both Procedural and Substantive Elements to Effect the Purposes of the Statute Congress included a specific mandate to EPA to establish a risk evaluation rulemaking. There is little question that the rule must describe the process by which risk evaluations will be conducted. However, to 3 effect the purposes of the statute, the process described in the rule cannot merely set out timelines or the sequence of the risk evaluation. It must include a clear articulation of the substantive elements of risk evaluation, and more particularly, it must explain how it will apply the principles set out in Section 6(b)(4)(F), Section 26, and other parts of the statute. If Congress had intended the scientific standard of "best available science" or "weight of the scientific evidence" to be incorporated into guidance alone, it would have included them only in Section 26(1) on "policies, procedures and guidance." 3 "[T]he Administrator shall establish, by rule, a process to conduct risk evaluations in accordance with subparagraph (A) " Section 6(b)(4)(A). 5 I Page Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226 The very purpose of the risk evaluation is to develop the evidentiary and scientific basis to enable EPA to complete the risk determination required by statute. That risk determination has substantive impact - it significantly affects conduct, activity or a substantive interest that is the subject of agency regulation. The determination following risk evaluation is a necessary prerequisite for a chemical to proceed to risk management, if warranted. The rule should thus include a clear description of how EPA will undertake risk evaluations in order to meet the new statutory requirements of the LCSA. This includes a description of the scoping process and requirements for a published scope as well as the elements of the risk evaluation itself and the mechanism for gauging adequacy as measured against statutory criteria. III. The Proposed Rule Should Include a Tiered Approach to Risk Evaluation We believe the statute contemplates a tiered approach to risk evaluation and recommend that EPA include a tiered approach in the rule. Under the LCSA, EPA must initiate the risk evaluation "upon designating" a chemical as a high-priority substance. The scope, however, is not required to be published "upon initiation" -- EPA has up to six months following the initiation of the risk evaluation to prepare and publish the scope. Congress intended this six month period to be used for a scoping exercise, where EPA identifies "the hazards, exposures, conditions of use, and the potentially exposed or susceptible subpopulations the Administrator expects to consider in the risk evaluation." This six month period is a "step" between the high priority designation and the publication of the scope. In order for EPA to conduct risk evaluations consistent with the quality required by the LCSA and within the timeframes required, EPA should conduct a screening level evaluation during the scoping phase. During the scoping phase of risk evaluations, tools exist to allow EPA to conduct quantitative screening level analyses of multiple exposure scenarios, as appropriate for consumers, sensitive subpopulations, and the environment. This will allow EPA to have a more tailored focus on those populations and exposures of greatest concern during a refined risk evaluation process. Figure 1 below depicts ACC's recommended approach. 6 I Page Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226 - y 10 Worknlan High-Duality Refined Risk Evaluation High Pricrity Chemicats & DRAFT Chemicals Manufacturer Risk Evaluation Requested EXPOSSURES HAZARD Evaluation incorporating Sections 6 and 26 of the Lautenberg Chemicel Safety Act (LCSA): Scope/Screening Level Risk Evatuation Scientific Standards FINAL Susceprible Weight of Scientific Evidence Evaluations Risk Evaluation Exposures Pupulations or use Certain Conditions of Use Present Do not present an anreasonable risk an unreasonable risk Refined No further risk evaluation risk avaluation No further action; needed RUREMAKING PROCESS COMPLETE the Figure 1. A Two-Step Process for Conducting Risk Evaluations Note: This is a simplified version of the process. A tiered approach, where EPA uses the scoping step (step 1) to conduct a quantitative screening level analysis, will allow EPA to focus its limited resources on more robust refined risk evaluations for only those conditions of use where unreasonable risks cannot be ruled out. Screening-level assessments require less data and information, and are typically deterministic and based on conservative, health protective assumptions and methods. When a screening assessment indicates low risk for a particular condition of use, the Agency should have a high degree of confidence that the potential risks are much lower than the calculation and, therefore, the actual risks are lower and/or perhaps non-existent. However, when a screening-level risk assessment indicates a potential concern for an adverse effect, this does not mean that the actual risks are significant and warrant action. Rather, it indicates the Agency should take a second step in the risk evaluation process to refine the evaluation to more accurately quantify potential risks. The refined risk evaluation (step 2) will require realistic and representative data, higher tier modeling approaches, including probabilistic exposure modeling, and a more comprehensive consideration of human relevance and dose-response relationships. In a refined evaluation, EPA should also consider targeted exposure studies, as well as biomonitoring and environmental monitoring data, to the extent that this information is available and relevant. This approach is consistent with EPA's 2014 Framework for Human Health Risk Assessment to Inform Decision Making (HHRA Framework)4. which also emphasizes the importance of a fit-for-purpose approach to risk evaluation. This approach is also consistent with EPA's exposure assessment guidelines and practices. The concept of a tiered approach and a fit-for-purpose 5 evaluation are woven throughout ACC's recommendations. 4 See tps://www.epa.gov/sites/production/files/2014-12/documents/hhra-framework-final-2014.pdf. 5 See: tps://www.epa.gov/expobox/exposure-assessment-tools-tiers-and-types-screening-level-and-refined. 7 Page Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226 The tiered approach ACC recommends is consistent with the approach EPA took in the problem formulation and initial assessment document for tetrabromobisphenol A (TBBPA.6 In that document, EPA conducted an initial screening level evaluation to support its conceptual model and analysis plan. EPA appropriately used high-end exposure values coupled with the lowest toxicity values to evaluate uses and exposure pathways of potential concern. While EPA did not share the relevant risk evaluation calculations in its public document, the general approach is consistent with that of a screening level risk evaluation. ACC encourages EPA to continue with this approach and to transparently and clearly present quantitative screening level analyses for the conditions of use and exposure scenarios that are part of the conceptual model EPA develops as part of the scoping phase. IV. The Rule Should Clarify the Process for Preparation and Contents of the Scope As noted above, Congress allowed a six month period for preparation of the scope of the risk evaluation, contemplating that time and effort would be needed to move from prioritization to a published scope. The six month period is to enable EPA to identify "the hazards, exposures, conditions of use, and the potentially exposed or susceptible subpopulations the Administrator expects to consider in the risk evaluation." Two things are evident from this language and the time frame afforded: 1) EPA should use this period to evaluate and decide which, if any, potentially exposed or susceptible subpopulations should be included in the risk evaluation (in other words, it need not include all such subpopulations, regardless of size, impact, or relevance); and 2) tEPA has flexibility to actually conduct a full risk evaluation of some or all the potential scenarios set out in the scope. In short, EPA need not include every conceivable condition of use in a risk evaluation. This view is further buttressed by the definition of "conditions of use" in Section 3 of the LCSA, which points to the need for EPA to determine the relevant conditions of use: "the circumstances, as determined by the Administrator, under which a chemical substance is intended, known, or reasonably foreseen to be manufactured, processed, distributed in commerce, used, or disposed of." (Emphasis added). V. The Proposed Rule Should Include a Detailed Description of Substantive Elements of Risk Evaluation The term, "risk evaluation" is not expressly defined in the LCSA. While the term "risk assessment" has been widely used in EPA programs and operationally has clear meaning derived from years of guidance, policies and practices, that term was not used in the statute. Therefore even though it may be reasonable to assume "risk evaluation" may fully equate with the term "risk assessment," given the context of its use (integrating hazard with exposure) in the LCSA, EPA is encouraged to explicitly define and operationalize this term as part of its rulemaking. The term will not have clear meaning until an interpretation is assigned by EPA. We believe the essential elements of a Section 6 and 26 risk evaluation must be articulated in a clear regulatory definition as we discuss below. 6 EPA, Problem Formulation and Initial Assessment Tetrabromobisphenol A and Related Chemicals Cluster Flame Retardants, 2015, available at: https://www.epa.gov/assessing-and-managing-chemicals-under-tsca/tsca-work-plan-chemical-problem- formulation-and-2. 8 IPage Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226 Section 6(b)(4)(B) of the statute requires EPA to establish, by rule, "a process to conduct risk evaluations." This process is itself required to meet a number of substantive elements described in the LCSA; a risk evaluation must: Be conducted in a manner designed to help the agency determine "whether a chemical substance presents an unreasonable risk of injury to health or the environment;" as set out in Section 6(b)(4)(A). Include consideration of "an unreasonable risk to a potentially exposed or susceptible subpopulation." EPA must identify relevant potentially exposed or susceptible subpopulations relevant to the risk evaluation under conditions of use; Address the specific elements set out in Section 6(b)(4)(F); and Comply with the specific requirements of Section 26, including the best available science, weight of the evidence, and transparency requirements. The very purpose of the risk evaluation is to develop the evidentiary and scientific basis to enable EPA to complete the risk determination required by statute. That risk determination has substantive impact - it significantly affects conduct, activity or a substantive interest that is the subject of agency regulation. The basis for the risk determination thus should be adequately described in the rule itself to offer sufficient notice to the regulated community. This is particularly important for decisions that inform safety and safety determinations. Likewise, decisions that have broad reaching impact should be supported in regulations, not merely through guidance or agency policy. 8 While EPA cannot substitute policy or guidance for a regulatory description of what will constitute a complete and robust risk evaluation, we believe the necessary elements can be developed in this rulemaking in a timely manner. VI. The Proposed Rule Should Ensure Consistency with Section 6(b)(4)(F) As discussed below, Section 6(b)(4)(F) of the LCSA describes five requirements for risk evaluations that shall be considered by the Administrator and must be incorporated into the risk evaluation rulemaking. 7 See, e.g., MST Express v. U.S. Department of Transportation, 108 F.3d 401 (D.C. Cir. 1997). DOT was directed under the Motor Carrier Safety Act (MCSA) to "prescribe regulations establishing a procedure to decide on the safety fitness of owners and operators of commercial motor vehicles." [Emphasis added]. The MCSA stated that implementing regulations would include "a means of deciding whether the owners, operators, and persons meet the safety fitness requirements." DOT promulgated regulations that set out a process for decision making but used guidance to articulate the tests by which the agency would determine whether vehicles met the safety fitness requirements. The court rejected DOT's reliance on guidance because it "failed to carry out its statutory obligation to establish by regulation a means of determining whether a carrier has complied with the safety fitness requirements." 8 As a general matter, "...it seems to be established that "regulations,' 'substantive rules' or 'legislative rules' are those which create law, usually implementary to an existing law." Gibson Wine Co. v. Snyder, 194 F.2d 329, 331 (D.C. Cir. 1952), cited by Brown Express, Inc. v. U.S., 607 F.2d 695, 700 (5th Cir. 1979). A "rule" is defined under Section 2 of the Administrative Procedure Act, in relevant part, as: "the whole or part of an agency statement of general or particular applicability and future effect designed to implement, interpret, or prescribe law or policy or describing the organization, procedure, or practice requirements of an agency." 5 U.S.C. § 551(4). 9 I Page Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226

what is the date mentioned in the given invoice ?

hpbn0226

hpbn0226_p0, hpbn0226_p1

may 12,2017, May 12, 2017

368 From: Ehrhardt. Clinton (ehrharon) To: Chilli AP Invoices Cc: Burleigh-Flaver, Heather; Dourson. Michael (doursomi); Maier Michael (maierma); Avers, Valerie (aversvi) Subject: Invoice for UC - PPG PO F2D71625 Date: Friday, May 12, 2017 12:05:55 PM Attachments: PPG2Mav17.pp Attached you will find an invoice for work on PO F2D71625. Please let me know if you have any questions. Thank you, Clinton Ehrhardt Grant Administrator University of Cincinnati, College of Medicine Department of Environmental Health 3223 Eden Ave PO Box 670056 Cincinnati, OH 45267-0056 (513)558-5067 [email protected] Source: https://www.industrydocuments.ucsf.edu/docs/hpbn0226 University of Cincinnati INVOICE Physicians Company University Environmental Health Foundation Invoice# PPGMay17 Date: May 12, 2017 To: For: Heather Burleigh-Flayer, Ph.D., DABT Project: Support for Packaging SBU Global Manager of Toxicology Corporate EHS, PPG 440 College Park Drive Monroeville, PA 15146 DESCRIPTION RATE HOURS AMOUNT Support for Packaging SBU for the period of 4/1/17 - 4/30/17 PO F2D71625 For the following tasks: Reviewed the text entitled "Buyer Beware Report" Revised a 1 page description of TMBFstudies testing potential endocrine disruption based on sponsor review Attended a 1 day meeting with sponsors at their facility; discussed briefly with Rsik Science Center staff the likely work flow from this meeting Michael Dourson. PhD $ 299.00 13.5 $ 4,036.50 Jacqueline Patterson M En $ 288.00 5 $ 1,440.00 TOTAL $5,476.50 Please make Checks payable to: University Environmental Health Foundation Mail Checks to: Department of Environmental Health University of Cincinnati PO Box 670056 Cincinnati, OH 45267-0056 Source: https://www.industrydocuments.ucsf.edu/docs/hpbn0226

what is the name of the foundation?

hpbn0226

hpbn0226_p0, hpbn0226_p1

University Environmental Health Foundation, university environmental health foundation

368 From: Ehrhardt. Clinton (ehrharon) To: Chilli AP Invoices Cc: Burleigh-Flaver, Heather; Dourson. Michael (doursomi); Maier Michael (maierma); Avers, Valerie (aversvi) Subject: Invoice for UC - PPG PO F2D71625 Date: Friday, May 12, 2017 12:05:55 PM Attachments: PPG2Mav17.pp Attached you will find an invoice for work on PO F2D71625. Please let me know if you have any questions. Thank you, Clinton Ehrhardt Grant Administrator University of Cincinnati, College of Medicine Department of Environmental Health 3223 Eden Ave PO Box 670056 Cincinnati, OH 45267-0056 (513)558-5067 [email protected] Source: https://www.industrydocuments.ucsf.edu/docs/hpbn0226 University of Cincinnati INVOICE Physicians Company University Environmental Health Foundation Invoice# PPGMay17 Date: May 12, 2017 To: For: Heather Burleigh-Flayer, Ph.D., DABT Project: Support for Packaging SBU Global Manager of Toxicology Corporate EHS, PPG 440 College Park Drive Monroeville, PA 15146 DESCRIPTION RATE HOURS AMOUNT Support for Packaging SBU for the period of 4/1/17 - 4/30/17 PO F2D71625 For the following tasks: Reviewed the text entitled "Buyer Beware Report" Revised a 1 page description of TMBFstudies testing potential endocrine disruption based on sponsor review Attended a 1 day meeting with sponsors at their facility; discussed briefly with Rsik Science Center staff the likely work flow from this meeting Michael Dourson. PhD $ 299.00 13.5 $ 4,036.50 Jacqueline Patterson M En $ 288.00 5 $ 1,440.00 TOTAL $5,476.50 Please make Checks payable to: University Environmental Health Foundation Mail Checks to: Department of Environmental Health University of Cincinnati PO Box 670056 Cincinnati, OH 45267-0056 Source: https://www.industrydocuments.ucsf.edu/docs/hpbn0226

what is the name of the university ?

hpbn0226

hpbn0226_p0, hpbn0226_p1

University of Cincinnati, university of cincinnati

368 From: Ehrhardt. Clinton (ehrharon) To: Chilli AP Invoices Cc: Burleigh-Flaver, Heather; Dourson. Michael (doursomi); Maier Michael (maierma); Avers, Valerie (aversvi) Subject: Invoice for UC - PPG PO F2D71625 Date: Friday, May 12, 2017 12:05:55 PM Attachments: PPG2Mav17.pp Attached you will find an invoice for work on PO F2D71625. Please let me know if you have any questions. Thank you, Clinton Ehrhardt Grant Administrator University of Cincinnati, College of Medicine Department of Environmental Health 3223 Eden Ave PO Box 670056 Cincinnati, OH 45267-0056 (513)558-5067 [email protected] Source: https://www.industrydocuments.ucsf.edu/docs/hpbn0226 University of Cincinnati INVOICE Physicians Company University Environmental Health Foundation Invoice# PPGMay17 Date: May 12, 2017 To: For: Heather Burleigh-Flayer, Ph.D., DABT Project: Support for Packaging SBU Global Manager of Toxicology Corporate EHS, PPG 440 College Park Drive Monroeville, PA 15146 DESCRIPTION RATE HOURS AMOUNT Support for Packaging SBU for the period of 4/1/17 - 4/30/17 PO F2D71625 For the following tasks: Reviewed the text entitled "Buyer Beware Report" Revised a 1 page description of TMBFstudies testing potential endocrine disruption based on sponsor review Attended a 1 day meeting with sponsors at their facility; discussed briefly with Rsik Science Center staff the likely work flow from this meeting Michael Dourson. PhD $ 299.00 13.5 $ 4,036.50 Jacqueline Patterson M En $ 288.00 5 $ 1,440.00 TOTAL $5,476.50 Please make Checks payable to: University Environmental Health Foundation Mail Checks to: Department of Environmental Health University of Cincinnati PO Box 670056 Cincinnati, OH 45267-0056 Source: https://www.industrydocuments.ucsf.edu/docs/hpbn0226

Earlier where did Goule worked as senior vice president of programs?

ffcn0226

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National Farmers Union, At National Farmers Union., NFU

To: Greenwalt, Sarah[[email protected]]; Dravis, Samantha[[email protected]] Brown, Byron[[email protected]];Wagner, Kenneth[[email protected]] From: Hupp, Sydney Sent: Thur 3/30/2017 5:11:34 PM Subject: FW: FINAL Meeting Agenda and Materials Pruitt Meeting Materials.pd FYI. Sydney Hupp Office of the Administrator- Scheduling 202.816.1659 From: Mary Jo Tomalewski [mailto:[email protected]] Sent: Thursday, March 30, 2017 11:22 AM To: Hupp, Sydney <[email protected]> Cc: Jay Vroom <[email protected]> Subject: FINAL Meeting Agenda and Materials Sydney, We have refined our proposed topics for today's CEO Council meeting with the administrator. Attached, please find: Revised "Final Proposed Agenda Topics," which includes the list of those CEO Council members who will attend our meeting today, and their short bios Introduction / Mission Overview of the CEO Council CEO Council Letter to President Trump, dated February 9, 2017 We assume we can skip a formal "round table of introductions" at the beginning of the meeting as our time is short and we want to maximize time spent talking about issues. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000061-00001 MJ Mary Jo Tomalewski Executive Assistant to the President & CEO CropLife America 1156 15th Street, NW Suite 400 Washington, DC 20005 Direct Dial (202) 872-3849 Main Switchboard (202) 296-1585 Mobile Ex. 6 Personal Privacy Fax (202)466-5832 Email [email protected] Web www.croplifeamerica.org How can I serve you today? Future Meetings 2017 Spring Regulator Conference - April 6-7, Arlington, VA 2017 Annual Meeting - September 22-27, Dana Point, CA 2018 Winter Board of Directors Meeting - March 5-7, Washington, DC 2018 Annual Meeting - September 21-26, The Ritz-Carlton Amelia Island Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000061-00002 FINAL PROPOSED AGENDA TOPICS Meeting Information: Office of EPA Administrator Scott Pruitt 1200 Pennsylvania Avenue, NW Washington, DC Thursday, March 30, 2017 3:45-4:30 PM Topic 1. Thanks to Trump Administration and Administrator Pruitt for early decisive actions: a. WOTUS b. Chlorpyrifos Petition 2. Top Priority Issues a. Ag Advisor Position - We recommend adding additional title of "Assistant Deputy Administrator" as a title b. Water i. Next steps to refine / clarify beyond WOTUS ii. NPDES permits (CAFO Program needs work; legislation to fix water permits NOT needed for lawful use of pesticides) c. Pesticides Policy i. Endangered Species Act conflicts with Pesticide Regulation and Biotech Regulation ii. Epidemiology Study Policy (as aftermath from Chlorpyrifos matter) iii. Reform Certification & Training and Worker Protection Rules - Suspend implementation and revise d. Renewable Fuels Standard - current program kept consistent e. Communication / Messaging / Opinion Polling - vital to all parties' ability to advance sound policy f. EPA and USDA Cooperation and Coordination - Already vast progress; more can be done! g. Environmental Justice, Research & Development, and Children's Health Offices - Better integration with and reform of EPA program offices; sound science h. Regulation of Manufacturing & Mining Facilities for Ag Inputs - Restore science and process i. Public and Science Advisory Panels at EPA - Balance, strategic agendas j. "Air Emissions" from farming operations CEO Attendees American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Corn Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Barb Glenn, CEO, ex-officio Departments of Agriculture Others American Farm Bureau Federation Dale Moore, Deputy Executive Director Corn Refiners Association John Bode, President & CEO National Farmers Union Rob Larew, Senior VP Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00001 Production Agriculture's CEO Council Introduction/Mission Statement: The production agriculture "CEO Council" coordinates alignment on core issues of modern agricultural systems through telling our story, sharing information and leveraging our strengths, while serving as a resource for government decision makers and others interested in USA food, fiber and renewable fuels. Core Focus of Interest Research and innovation Technology access Science and risk-based regulation Sustainability, environment, and weather Marketability, trade, and economic prosperity Government leadership and partnership with private sector Food access and food safety Plant and animal health Ag labor The Council supports principles/themes): Accelerating rural economic growth and improving productivity through innovation and technology Promoting research and innovation that enables development oftools and techniques necessary for discovering new products that hold tremendous potential for farmers and society at large Enabling a regulatory and commercial environment in which agricultural products are marketable, both domestically and internationally Appropriate balance between Federal and State Governments and a cooperative regulatory approach Access to essential labor in balance with an effective Federal immigration policy and adequate worker safety protections Support for all methods of agricultural production Transparency and dialogue with consumers Members of the CEO Council (see reversed) March 30, 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00002 CEO Council Members American Farm Bureau Vincent "Zippy" Duvall, President American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Cattlemen's Beef Association Kendal Frazier, CEO National Chicken Council Michael Brown, President National Com Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Farmers Union Roger Johnson, President National Milk Producers Federation Jim Mulhern, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Departments of Barb Glenn, CEO, ex-officio Agriculture March 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00003 February 9, 2017 The President The White House Washington, D.C. 20500 Dear Mr. President, We, the CEO Council (undersigned herein), representing the production agricultural value chain, including many agricultural producers and farm input developers and suppliers, look forward to working with you and your Administration on matters of importance to American agriculture. The challenges we face in agriculture are significant. Many experts emphasize that producers must grow as much food in the next 50 years as was produced over all previous history to meet the demands of our expanding global population. A firm commitment by the U.S. government to aggressively support agricultural innovation and science-based regulatory decisions will be necessary to ensure farmers have the tools they need to produce a safe and abundant supply of nutritious food, in addition to feed, fuel and fiber, in an environmentally sound and sustainable manner. The policy and regulatory environment your Administration establishes can ensure that agricultural innovation flourishes and American farmers are able to meet the food production goals necessary to feed billions more people. We are ready to provide the White House and the Executive Branch Departments and Agencies, as well as Congress, with policy concepts that foster stability in the U.S. agriculture economy with a strong and predictable farm safety net and promotes American competitiveness through research; marketability and trade of agricultural commodities; rural economic growth; and plant, animal, and environmental health, among many other things. We appreciate your attention to these and other issues of value to American production agriculture and food consumers everywhere. Sincerely, American Farm Bureau Foundation, Zippy Duvall American Seed Trade Association, Andy LaVigne American Soybean Association, Steve Censky Biotechnology Innovation Organization, Dana O'Brien CropLife America, Jay Vroom The Fertilizer Institute, Chris Jahn National Association of Wheat Growers, Chandler Goule National Cattlemen's Beef Association, Kendal Frazier National Corn Growers Association, Chris Novak National Cotton Council, Gary Adams National Council of Farmer Cooperatives, Chuck Conner National Farmers Union, Roger Johnson National Milk Producers Federation, Jim Mulhern National Pork Producers Council, Neil Dierks United Fresh Produce Association, Tom Stenzel USA Rice Federation, Betsy Ward Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00004 National Gotton Council OF MERTOA Gary M. Adams President and Chief Executive Officer National Cotton Council of America Gary Adams assumed the position of President and Chief Executive Officer of the National Cotton Council in February 2015. He plays a key role in guiding the industry's seven segments to reach consensus on critical policies affecting U.S. cotton, with the mission of helping all U.S. cotton industry segments compete effectively and profitably in global markets. Prior to that, Gary served the Council for 13 years as the Vice President of Economic and Policy Analysis. As the Council's chief economist, he provided economic outlooks for global cotton markets, as well as analyzing the impacts of farm and trade policies. Gary also represents the U.S. cotton industry as a member of USDA's Agricultural Policy Advisory Committee. Previously, Gary served on USDA's Advisory Committee on Trade from 2005 through 2011 and the NASS Advisory Committee on Agricultural Statistics from 2003 through 2009. Prior to joining the Council, Gary was a Research Assistant Professor in the Department of Agricultural Economics at the University of Missouri. During his 13-year tenure at the university, Gary's primary responsibilities included policy analysis and market outlook for the Food and Agricultural Policy Research Institute, also known as FAPRI. While at FAPRI, Gary and his colleagues were recognized by the American Agricultural Economics Association for their distinguished policy contributions. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00005 Gary has B.S. and M.A. degrees in Applied Mathematics from the University of Alabama and a Ph.D. in Agricultural Economics from the University of Missouri. Gary and his wife, Ex. 6 Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00006 FASA American Soybean Associatión & Stephen L Censky Chief Executive Officer Stephen L. Censky is the American Soybean Association's (ASA) C hief Executive Officer, a staff position he accepted in April 1996. As ASA's top executive, Ce nsky is in charge of managing ASA's legislative, trade policy, membership and education and training programs. The American Soybean Association is a national, not-for-profit commodity organization with over 22,000 members. ASA works as the domestic and international policy advocate for soybean producer members. Prior to joining ASA, Censky worked in Washington, D.C. for ove a decade. He began his career on Capitol Hill as a legislative assistant for agricultural and transportation matters to Senator Jim Abdnor (R-SD). Later he served in both the Reagan and Bush Administrations at the U.S. Department of Agriculture, helping to craft the 1990 Farm Bill and eventually serving as Administrator of the Foreign Agricultural Service where he was involved in global trade negotiations and running our nation's export programs. Censky received his Bachelor's of Science degree of Agriculture from South Dakota State University and his Master's Diploma in Agriculture St of Melbourne, Australia. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00007 NCFC. National Council of Farmer Cooperatives Charles F. (Chuck) Conner President and CEO National Council of Farmer Cooperatives Charles F. (Chuck) Conner became president & CEO of the National Council of Farmer Cooperatives (NCFC) on January 22, 2009. As president of NCFC, Conner will oversee the organization's work to promote and protect the business and public policy interests of America's farmer-owned cooperatives. He will also provide the strategic vision for the trade association as it continues to seek new ways in which to add value for its membership. Prior to joining NCFC, Conner had served as the Deputy Secretary at the U.S. Department of Agriculture since mid-2005. In this capacity, he was the Chief Operating Officer (COO) overseeing day-to-day operations of the department. Conner interacted directly with President George W. Bush and his senior staff to formulate domestic and international food, trade, security and energy policy. He led development of the Bush Administration's $300 billion Farm Bill proposal and the strategy to educate and inform industry, constituents and Congress. From August 2007 to January 2008, Conner served as both USDA Secretary and Deputy Secretary. He played a key role in developing the Administration's immigration policy including important changes to the H2A program. Conner's experience also includes the assignment of Special Assistant to the President, Executive Office of the President, from October 2001 to May 2005, working on the 2001/2 Farm Bill to develop the strategy behind the transfer of several USDA agency functions to the newly formed Department of Homeland Security. From May 1997 to October 2001 Conner served as President of the Corn Refiners Association. He also served for 17 years as an advisor to U.S. Senator Richard Lugar of Indiana. Conner is a graduate of Purdue University, with a Bachelor's of Science degree and is the recipient of Purdue's Distinguished Alumni Award. He and his wife Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00008 NATIONAL PORK PRODUCERS COUNCIL Neil Dierks, Chief Executive Officer Neil Dierks is Chief Executive Officer of the National Pork Producers Council (NPPC). In this position, he is responsible for the overall implementation of all NPPC programs. Dierks' position requires him to spend time in both Des Moines, Iowa, the national office of NPPC, and Washington, D.C. Beginning in 1990, Dierks served NPPC in a series of senior executive positions, including Executive Director of Operations, Vice President for Research and Education and Senior Vice President for Programs. Prior to his service with NPPC, Dierks was the Special Activities Director for the Iowa Pork Producers Association and Marketing Director for the Iowa Corn Promotion Board. Neil grew up on a livestock farm in eastern lowa and remains involved in a family farming operation. He is a graduate of Iowa State University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00009 NASDA Dr. Barbara Glenn recently joined the National Association of State Departments of Agriculture (NASDA) as CEO on August 18, 2014. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. Dr. Glenn is a scientist with decades of experience as a policy researcher and advocate for agriculture. She previously served as Senior Vice President of Science and Regulatory Affairs for CropLife America, where she was responsible for developing policies and regulations to support agriculture through crop protection. Prior to joining CropLife America, Dr. Glenn served as Managing Director of the Animal Bi otechnology, Food and Agriculture Section of the Biotechnology Industry Association in Washington, DC. Dr. Glenn holds a B.S. in animal science and a Ph.D. in ruminan t nutrition from the University of Kentucky. She previously worked for the U.S. Department of Agriculture, Agric ultural Research Service and the Federation of Animal Science Societies. Born in Lincoln, Nebraska and raised in Centerville, Ohio, Dr. Glenn developed a passion for agriculture from her parents and her involvement in 4-H. She lives Ex. 6 - Personal Privacy and serves on various boards for farm bureau and 4-H. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00010 National Association of Wheat Growers Chandler Goule CEO Chandler Goule assumed his responsibilities as CEO of the National Association of Wheat Growers on July 5, 2016. In addition, he also serves as the executive director of the National Wheat Foundation. Most recently, Goule served as senior vice president of programs at the National Farmers Union (NFU) where he was heavily involved in farm bill legislation. Originally from Texas, Goule holds degrees from Texas A&M and George Washington University and served as a subcommittee staff director for the House Agriculture Committee before moving to the National Farmers Union in 2009 as vice president of government relations. He was appointed senior vice president of NFU programs in 2014. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00011 The Fertilizer Institute Nourish, Replenish, Grow BIOGRAPHY OF CHRISTOPHER JAHN President The Fertilizer Institute and the Nutrients for Life Foundation Christopher L. Jahn is president of The Fertilizer Institute (TFI), the fertilizer industry's national trade association. As TFI president, Jahn works to represent, promote and protect a sound fertilizer industry through legislative and regulatory activities and to promote a favorable public image of the fertilizer industry and agriculture. Jahn also serves as president of the Nutrients for Life Foundation (NFL). Jahn comes to TFI having served as president of the National Association of Chemical Distributors (NACD) since 2006. Prior to leading NACD, Jahn served as president of the Contract Services Association (CSA). Before joining CSA, Jahn had an active role in the United States Senate working for nearly 10 years for U.S. Senator Craig Thomas (R-Wyo.) in a variety of roles, including legislative assistant, legislative director and Chief of Staff. After graduating from Columbia University with a B.A. in Political Science, Jahn co-founded a book distribution business. He also earned an MBA from the University of Maryland. A native of Wyoming, Chris and his wife, Ex. 6 - Personal Privacy Ex. Personal Privacy Capitol View 202.962.0490 425 Third Street, S.W., Suite 950 202.962.0577 fax Washington, DC 20024 www.tfi.org Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00012 National Farmers Union Roger Johnson President Roger Johnson is president of the National Farmers Union (NFU), a grassroots organization that represents more than 200,000 family farmers, ranchers, fisherman and rural communities across the Unites States. Johnson was elected to lead the family farm organization at NFU's 107th anniversary convention in 2009. He has since expanded the education department by providing more programs for beginning, college-aged and women farmers, increased the number of Farmers Union state divisions, and developed a strategic plan for the organization. Johnson has also overseen a number of important policy initiatives important to family farmers including: passage of the 2014 Farm Bill; maintaining a strong Renewable Fuel Standard and Country-of-Origir Labeling, promoting policies that allow farmers to address the growing threat of climate change; and renewing the nation's focus on eliminating an overwhelming trade deficit that results in lost jobs and prosperity for rural America. Prior to leading National Farmers Union, Johnson, a third-generation family farmer from Turtle Lake, N.D., served as North Dakota Agriculture Commissioner, a position he was first elected to in 1996. While Agriculture Commissioner, Johnson served on the State Industrial Commission, the North Dakota Trade Office Advisory Board, and the State Board of Agricultural Research and Education, among many other boards and commissions. From 2007-2008, Johnson served as president of the National Association of State Departments of Agriculture (NASDA). He is a past president of the Midwestern Association of State Departments of Agriculture (MASDA), past president of the Food Export Association of the Midwest and a former chairman of the Interstate Pest Control Compact. Johnson graduated from North Dakota State University with a degree in agricultural economics. Johnson and his wife Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00013 AMERICAN SEED TRADE ASSOCIATION asta first-the - seed R Andrew W. "Andy" LaVigne President & CEO Andrew W. LaVigne is currently the President and CEO of the Ame rican Seed Trade Association. He joined ASTA in February, 2006. Andy has had a 30-year career i n government relations, industry representation, public affairs advocacy, and management. His C ore areas of expertise include agriculture, food policy and international trade. Prior to joining ASTA, Andy was Executive Vice President/CEC of Florida Citrus Mutual, representing citrus growers on issues affecting their business. Prejaiming tFdorida Citrus Mutual, Andy spent four years as Florida Fertilizer and Agrichemical Association's (FFAA) President and Executive Director. FFAA is a non-profit, agricultural trade organization representing companies that specialize in crop protection and plant nutrition products. Before his position at FFAA, Andy spent eight years in Washingt on, D.C. working in the U.S. Congress and the U.S. Department of Agriculture. He served as Legislative Director for Congressman Charles Canady, Agriculture Committee staffer for Congressman Tom Lewis , and on the staff of USDA Secretary Ed Madigan. Andy is a native of Florida with a BA degree in Political Scien ce, with a minor in economics, from the University of Florida. 1701 Duke Street Suite 275 Alexandria, VA 22314 Phone: (703)837-8140 Fax: (703)837-9365 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00014 Biotechnology Innovation Organization Dana O'Brien Executive Vice President, Food & Agriculture Dana O'Brien is Executive Vice President for Food and Agriculture and is responsible for the development of public policy and strategic advocacy, public affairo, and legal strategies that advance industry and stakeholder objectives in the United States. Prior to becoming EVP, Dana served bs BIO Food and Agriculture's chief legislative advocate as Senior Director of Federal Government Relations aince March 2011. Before BIO, Dana worked in Congress for the late Representative lke Skelton (D-MO) managing his legislative team and concentrating on a variety of agricultural, energy, and trade matters. A native of Sedalia, Missouri, and a graduate of Missouri University with a bachelor's degree in psychology, Dana joined the Skelton team immediately out of college and served there for nearly 14 years Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00015 UNITED FRESH is PRODUCE ASSOCIATION Tom Stenzel President and CEO United Fresh Produce Association 1901 Pennsylvania Avenue NW, Suite 1100 Washington, DC 20006 202/303-3400 [email protected] Tom Stenzel is President and CEO of the United Fresh Produce Association, a position he has held since 1993. United Fresh is the pre-eminent trade association for the produce industry in shaping legislative and regulatory policies; providing scientific and technical leadership in food safety and nutrition; and developing educational programs for its members. Founded in 1904, United Fresh represents the interests of companies from small family businesses to the largest international corporations throughout the global fresh produce supply chain. United Fresh is widely known for its work in government affairs, agricultural policy, food safety and nutrition, working to promote political and environmental change to help the next generation of children double their consumption of fresh produce. The United Fresh Start Foundation is committed to increasing children's access to fresh fruits and vegetables, and is a founding partner of the Let's Move Salad Bars to Schools campaign. The campaign has donated salad bars to more than 6,000 schools across the country. Tom is a frequent speaker on industry issues and has been recognized often by the produce industry throughout his career. He was honored as the 2002 Produce Man of the Year by The Packer newspaper, and is the past Chairman of the International Federation for Produce Standards, a global body representing national produce associations around the world. He is a member of the U.S. Chamber of Commerce Committee of 100 leading association executives, the Advisory Board of the International Food Protection Training Institute, and the Key Industry Associations Committee of the American Society of Association Executives, from which he achieved the Certified Association Executive (CAE) designation in 1990. He has served in many government and industry leadership positions, including the first U.S. Department of Agriculture Fruit and Vegetable Industry Advisory Committee, President George W. Bush's Transition Advisory Team for Agriculture, and as an advisor on the U.S. Agricultural Policy Advisory Committee for Trade. Tom was the founding President of the International Food Information Council (IFIC) in 1986, and was previously director of public affairs for the National Soft Drink Association. Tom is a 1977 graduate of the University of Richmond. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00016 as of January 17, 2017 Jay Vroom has served as President and CEO of the trade association known as CropLife America (CLA) since 1989. CLA is the leading U.S. trade group for the crop protection industry in the U.S. Vroom is a founding member of the CropLife Foundation, serving as chairman since its inception in 2001, and now serves as the Foundation's Vice-Chair, since 2015. His sits of the Board of Directors for the Agricultural Retailers Association, Asmark, National Wheat Foundation, the National Association of Manufacturers Council of Manufacturing Associations, and the Soil Health Institute. He is also a member of the Farm Foundation Roundtable Steering Committee, and the North American Climate Smart Ag Alliance Steering Committee. Vroom was a member of the youth organization, Future Farmers of America, and served as an elected state officer in Illinois. Today, he is a member of the FFA Foundation's Individual Giving Council and Board of Trustees. Vroom co-chairs the Coalition for the Advancement of Precision Agriculture and the CEO Council. He is a member of the Friends of the National Arboretum (FONA) FONA Council. He graduated with honors from the College of Agriculture, Consumer and Environmental Sciences at the University of Illinois Urbana-Champaign. Vroom was raised on a grain and livestock farm in north-central Illinois and continues to own the farming operation. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00017 Elizabeth Ward Betsy Ward was appointed President & CEO of the USA Rice Federation in 2007. From 2003- 2005, Ward was the Vice President of International and Domestic Promotion at USA Rice where she was in charge of developing and implementing domestic and international promotion, and food aid programs. From 2005-2007, Ward served as the chief executive for the Hardwood Federation, a trade association representing over 15,000 hardwood producers across the United States. From 1995 to 2003, she ran the Wood Products International Group at the American Forest & Paper Association, directing the wood trade policy and global forestry agenda for the industry. In 2011, Ward was elected Chairman of the U.S. Agricultural Export Development Council (USAEDC) which represents the interests of more than 80 commodity organizations who grow and process a wide variety of U.S. agricultural products. She currently serves as Past Chair. Since 2011, Ward has also served on the Board of Directors of the Sustainable Fisheries Partnership, an independent non-governmental organization (NGO) working to ensure healthy marine and aquatic tecosystems; secure seafood supplies; and a thriving, responsible seafood economy. Ward served for six years as a cleared advisor on the Industry Trade Advisory Committee for forest and paper products (ITAC-7) and was appointed forest products representative to USDA's Agricultural Policy Advisory Committee (APAC) in 2001. Ward holds a Bachelor's degree in History and Political Science from the University of New Hampshire and a Master's degree in International Security Affairs from the School of International Affairs at Columbia University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00018 To: Brown, Byron[[email protected]]; Jackson, Ryan[[email protected]] From: Rebeckah Adcock Sent: Thur 3/30/2017 4:10:52 PM Subject: FW: FINAL CEO Council Meeting Agenda and Materials Pruitt Meeting Materials.pdf ATT00001.htm FYI - final materials for today's meeting. Reb From: "Mary Jo Tomalewski" <[email protected]> To: "Hupp, Sydney" <[email protected]> Cc: "Jay Vroom" <[email protected]> Subject: FINAL Meeting Agenda and Materials Sydney, We have refined our proposed topics for today's CEO Council meeting with the administrator. Attached, please find: Revised "Final Proposed Agenda Topics," which includes the list of those CEO Council members who will attend our meeting today, and their short bios Introduction / Mission Overview of the CEO Council CEO Council Letter to President Trump, dated February 9, 2017 We assume we can skip a formal "round table of introductions" at the beginning of the meeting as our time is short and we want to maximize time spent talking about issues. MJ Mary Jo Tomalewski Executive Assistant to the President & CEO CropLife America Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000063-00001 1156 15th Street, NW Suite 400 Washington, DC 20005 Direct Dial (202) 872-3849 Main Switchboard (202) 296-1585 Mobilé Ex. 6 Personal Privacy Fax (202) 466-5832 Email [email protected] Web www.croplifeamerica.org How can I serve you today? Future Meetings 2017 Spring Regulator Conference - April 6-7, Arlington, VA 2017 Annual Meeting - September 22-27, Dana Point, CA 2018 Winter Board of Directors Meeting - March 5-7, Washington, DC 2018 Annual Meeting - September 21-26, The Ritz-Carlton Amelia Island Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000063-00002 FINAL PROPOSED AGENDA TOPICS Meeting Information: Office of EPA Administrator Scott Pruitt 1200 Pennsylvania Avenue, NW Washington, DC Thursday, March 30, 2017 3:45-4:30 PM Topic 1. Thanks to Trump Administration and Administrator Pruitt for early decisive actions: a. WOTUS b. Chlorpyrifos Petition 2. Top Priority Issues a. Ag Advisor Position - We recommend adding additional title of "Assistant Deputy Administrator" as a title b. Water i. Next steps to refine / clarify beyond WOTUS ii. NPDES permits (CAFO Program needs work; legislation to fix water permits NOT needed for lawful use of pesticides) c. Pesticides Policy i. Endangered Species Act conflicts with Pesticide Regulation and Biotech Regulation ii. Epidemiology Study Policy (as aftermath from Chlorpyrifos matter) iii. Reform Certification & Training and Worker Protection Rules - Suspend implementation and revise d. Renewable Fuels Standard - current program kept consistent e. Communication / Messaging / Opinion Polling - vital to all parties' ability to advance sound policy f. EPA and USDA Cooperation and Coordination - Already vast progress; more can be done! g. Environmental Justice, Research & Development, and Children's Health Offices - Better integration with and reform of EPA program offices; sound science h. Regulation of Manufacturing & Mining Facilities for Ag Inputs - Restore science and process i. Public and Science Advisory Panels at EPA - Balance, strategic agendas j. "Air Emissions" from farming operations CEO Attendees American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Corn Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Barb Glenn, CEO, ex-officio Departments of Agriculture Others American Farm Bureau Federation Dale Moore, Deputy Executive Director Corn Refiners Association John Bode, President & CEO National Farmers Union Rob Larew, Senior VP Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00001 Production Agriculture's CEO Council Introduction/Mission Statement: The production agriculture "CEO Council" coordinates alignment on core issues of modern agricultural systems through telling our story, sharing information and leveraging our strengths, while serving as a resource for government decision makers and others interested in USA food, fiber and renewable fuels. Core Focus of Interest Research and innovation Technology access Science and risk-based regulation Sustainability, environment, and weather Marketability, trade, and economic prosperity Government leadership and partnership with private sector Food access and food safety Plant and animal health Ag labor The Council supports principles/themes): Accelerating rural economic growth and improving productivity through innovation and technology Promoting research and innovation that enables development oftools and techniques necessary for discovering new products that hold tremendous potential for farmers and society at large Enabling a regulatory and commercial environment in which agricultural products are marketable, both domestically and internationally Appropriate balance between Federal and State Governments and a cooperative regulatory approach Access to essential labor in balance with an effective Federal immigration policy and adequate worker safety protections Support for all methods of agricultural production Transparency and dialogue with consumers Members of the CEO Council (see reversed) March 30, 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00002 CEO Council Members American Farm Bureau Vincent "Zippy" Duvall, President American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Cattlemen's Beef Association Kendal Frazier, CEO National Chicken Council Michael Brown, President National Com Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Farmers Union Roger Johnson, President National Milk Producers Federation Jim Mulhern, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Departments of Barb Glenn, CEO, ex-officio Agriculture March 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00003 February 9, 2017 The President The White House Washington, D.C. 20500 Dear Mr. President, We, the CEO Council (undersigned herein), representing the production agricultural value chain, including many agricultural producers and farm input developers and suppliers, look forward to working with you and your Administration on matters of importance to American agriculture. The challenges we face in agriculture are significant. Many experts emphasize that producers must grow as much food in the next 50 years as was produced over all previous history to meet the demands of our expanding global population. A firm commitment by the U.S. government to aggressively support agricultural innovation and science-based regulatory decisions will be necessary to ensure farmers have the tools they need to produce a safe and abundant supply of nutritious food, in addition to feed, fuel and fiber, in an environmentally sound and sustainable manner. The policy and regulatory environment your Administration establishes can ensure that agricultural innovation flourishes and American farmers are able to meet the food production goals necessary to feed billions more people. We are ready to provide the White House and the Executive Branch Departments and Agencies, as well as Congress, with policy concepts that foster stability in the U.S. agriculture economy with a strong and predictable farm safety net and promotes American competitiveness through research; marketability and trade of agricultural commodities; rural economic growth; and plant, animal, and environmental health, among many other things. We appreciate your attention to these and other issues of value to American production agriculture and food consumers everywhere. Sincerely, American Farm Bureau Foundation, Zippy Duvall American Seed Trade Association, Andy LaVigne American Soybean Association, Steve Censky Biotechnology Innovation Organization, Dana O'Brien CropLife America, Jay Vroom The Fertilizer Institute, Chris Jahn National Association of Wheat Growers, Chandler Goule National Cattlemen's Beef Association, Kendal Frazier National Corn Growers Association, Chris Novak National Cotton Council, Gary Adams National Council of Farmer Cooperatives, Chuck Conner National Farmers Union, Roger Johnson National Milk Producers Federation, Jim Mulhern National Pork Producers Council, Neil Dierks United Fresh Produce Association, Tom Stenzel USA Rice Federation, Betsy Ward Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00004 National Gotton Council OF MERTOA Gary M. Adams President and Chief Executive Officer National Cotton Council of America Gary Adams assumed the position of President and Chief Executive Officer of the National Cotton Council in February 2015. He plays a key role in guiding the industry's seven segments to reach consensus on critical policies affecting U.S. cotton, with the mission of helping all U.S. cotton industry segments compete effectively and profitably in global markets. Prior to that, Gary served the Council for 13 years as the Vice President of Economic and Policy Analysis. As the Council's chief economist, he provided economic outlooks for global cotton markets, as well as analyzing the impacts of farm and trade policies. Gary also represents the U.S. cotton industry as a member of USDA's Agricultural Policy Advisory Committee. Previously, Gary served on USDA's Advisory Committee on Trade from 2005 through 2011 and the NASS Advisory Committee on Agricultural Statistics from 2003 through 2009. Prior to joining the Council, Gary was a Research Assistant Professor in the Department of Agricultural Economics at the University of Missouri. During his 13-year tenure at the university, Gary's primary responsibilities included policy analysis and market outlook for the Food and Agricultural Policy Research Institute, also known as FAPRI. While at FAPRI, Gary and his colleagues were recognized by the American Agricultural Economics Association for their distinguished policy contributions. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00005 Gary has B.S. and M.A. degrees in Applied Mathematics from the University of Alabama. and a Ph.D. in Agricultural Economics from the University of Missouri. Gary and his wife, Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00006 FASA American Soybean Associatión & Stephen L Censky Chief Executive Officer Stephen L. Censky is the American Soybean Association's (ASA) C hief Executive Officer, a staff position he accepted in April 1996. As ASA's top executive, Ce nsky is in charge of managing ASA's legislative, trade policy, membership and education and training programs. The American Soybean Association is a national, not-for-profit commodity organization with over 22,000 members. ASA works as the domestic and international policy advocate for soybean producer members. Prior to joining ASA, Censky worked in Washington, D.C. for ove a decade. He began his career on Capitol Hill as a legislative assistant for agricultural and transportation matters to Senator Jim Abdnor (R-SD). Later he served in both the Reagan and Bush Administrations at the U.S. Department of Agriculture, helping to craft the 1990 Farm Bill and eventually serving as Administrator of the Foreign Agricultural Service where he was involved in global trade negotiations and running our nation's export programs. Censky received his Bachelor's of Science degree of Agriculture from South Dakota State University and his Master's Diploma in Agriculture St of Melbourne, Australia. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00007 NCFC. National Council of Farmer Cooperatives Charles F. (Chuck) Conner President and CEO National Council of Farmer Cooperatives Charles F. (Chuck) Conner became president & CEO of the National Council of Farmer Cooperatives (NCFC) on January 22, 2009. As president of NCFC, Conner will oversee the organization's work to promote and protect the business and public policy interests of America's farmer-owned cooperatives. He will also provide the strategic vision for the trade association as it continues to seek new ways in which to add value for its membership. Prior to joining NCFC, Conner had served as the Deputy Secretary at the U.S. Department of Agriculture since mid-2005. In this capacity, he was the Chief Operating Officer (COO) overseeing day-to-day operations of the department. Conner interacted directly with President George W. Bush and his senior staff to formulate domestic and international food, trade, security and energy policy. He led development of the Bush Administration's $300 billion Farm Bill proposal and the strategy to educate and inform industry, constituents and Congress. From August 2007 to January 2008, Conner served as both USDA Secretary and Deputy Secretary. He played a key role in developing the Administration's immigration policy including important changes to the H2A program. Conner's experience also includes the assignment of Special Assistant to the President, Executive Office of the President, from October 2001 to May 2005, working on the 2001/2 Farm Bill to develop the strategy behind the transfer of several USDA agency functions to the newly formed Department of Homeland Security. From May 1997 to October 2001 Conner served as President of the Corn Refiners Association. He also served for 17 years as an advisor to U.S. Senator Richard Lugar of Indiana. Conner is a graduate of Purdue University, with a Bachelor's of Science degree and is the recipient of Purdue's Distinguished Alumni Award. He and his wife Ex. 6 - Personal Privacy Source: :https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00008 NATIONAL PORK PRODUCERS COUNCIL Neil Dierks, Chief Executive Officer Neil Dierks is Chief Executive Officer of the National Pork Producers Council (NPPC). In this position, he is responsible for the overall implementation of all NPPC programs. Dierks' position requires him to spend time in both Des Moines, Iowa, the national office of NPPC, and Washington, D.C. Beginning in 1990, Dierks served NPPC in a series of senior executive positions, including Executive Director of Operations, Vice President for Research and Education and Senior Vice President for Programs. Prior to his service with NPPC, Dierks was the Special Activities Director for the Iowa Pork Producers Association and Marketing Director for the Iowa Corn Promotion Board. Neil grew up on a livestock farm in eastern lowa and remains involved in a family farming operation. He is a graduate of Iowa State University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00009 NASDA Dr. Barbara Glenn recently joined the National Association of State Departments of Agriculture (NASDA) as CEO on August 18, 2014. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. Dr. Glenn is a scientist with decades of experience as a policy researcher and advocate for agriculture. She previously served as Senior Vice President of Science and Regulatory Affairs for CropLife America, where she was responsible for developing policies and regulations to support agriculture through crop protection. Prior to joining CropLife America, Dr. Glenn served as Managing Director of the Animal Bi otechnology, Food and Agriculture Section of the Biotechnology Industry Association in Washington, DC. Dr. Glenn holds a B.S. in animal science and a Ph.D. in ruminan t nutrition from the University of Kentucky. She previously worked for the U.S. Department of Agriculture, Agric ultural Research Service and the Federation of Animal Science Societies. Born in Lincoln, Nebraska and raised in Centerville, Ohio, Dr. Glenn developed a passion for agriculture from her parents and her involvement in 4-H. She lives on a small farm in Maryland with her husband: Ex. 6 - Personal Privacy and serves on various boards for farm bureau and 4-H. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00010

What is NFU?

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National Farmers Union, National Farmers Union.

To: Greenwalt, Sarah[[email protected]]; Dravis, Samantha[[email protected]] Brown, Byron[[email protected]];Wagner, Kenneth[[email protected]] From: Hupp, Sydney Sent: Thur 3/30/2017 5:11:34 PM Subject: FW: FINAL Meeting Agenda and Materials Pruitt Meeting Materials.pd FYI. Sydney Hupp Office of the Administrator- Scheduling 202.816.1659 From: Mary Jo Tomalewski [mailto:[email protected]] Sent: Thursday, March 30, 2017 11:22 AM To: Hupp, Sydney <[email protected]> Cc: Jay Vroom <[email protected]> Subject: FINAL Meeting Agenda and Materials Sydney, We have refined our proposed topics for today's CEO Council meeting with the administrator. Attached, please find: Revised "Final Proposed Agenda Topics," which includes the list of those CEO Council members who will attend our meeting today, and their short bios Introduction / Mission Overview of the CEO Council CEO Council Letter to President Trump, dated February 9, 2017 We assume we can skip a formal "round table of introductions" at the beginning of the meeting as our time is short and we want to maximize time spent talking about issues. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000061-00001 MJ Mary Jo Tomalewski Executive Assistant to the President & CEO CropLife America 1156 15th Street, NW Suite 400 Washington, DC 20005 Direct Dial (202) 872-3849 Main Switchboard (202) 296-1585 Mobile Ex. 6 Personal Privacy Fax (202)466-5832 Email [email protected] Web www.croplifeamerica.org How can I serve you today? Future Meetings 2017 Spring Regulator Conference - April 6-7, Arlington, VA 2017 Annual Meeting - September 22-27, Dana Point, CA 2018 Winter Board of Directors Meeting - March 5-7, Washington, DC 2018 Annual Meeting - September 21-26, The Ritz-Carlton Amelia Island Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000061-00002 FINAL PROPOSED AGENDA TOPICS Meeting Information: Office of EPA Administrator Scott Pruitt 1200 Pennsylvania Avenue, NW Washington, DC Thursday, March 30, 2017 3:45-4:30 PM Topic 1. Thanks to Trump Administration and Administrator Pruitt for early decisive actions: a. WOTUS b. Chlorpyrifos Petition 2. Top Priority Issues a. Ag Advisor Position - We recommend adding additional title of "Assistant Deputy Administrator" as a title b. Water i. Next steps to refine / clarify beyond WOTUS ii. NPDES permits (CAFO Program needs work; legislation to fix water permits NOT needed for lawful use of pesticides) c. Pesticides Policy i. Endangered Species Act conflicts with Pesticide Regulation and Biotech Regulation ii. Epidemiology Study Policy (as aftermath from Chlorpyrifos matter) iii. Reform Certification & Training and Worker Protection Rules - Suspend implementation and revise d. Renewable Fuels Standard - current program kept consistent e. Communication / Messaging / Opinion Polling - vital to all parties' ability to advance sound policy f. EPA and USDA Cooperation and Coordination - Already vast progress; more can be done! g. Environmental Justice, Research & Development, and Children's Health Offices - Better integration with and reform of EPA program offices; sound science h. Regulation of Manufacturing & Mining Facilities for Ag Inputs - Restore science and process i. Public and Science Advisory Panels at EPA - Balance, strategic agendas j. "Air Emissions" from farming operations CEO Attendees American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Corn Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Barb Glenn, CEO, ex-officio Departments of Agriculture Others American Farm Bureau Federation Dale Moore, Deputy Executive Director Corn Refiners Association John Bode, President & CEO National Farmers Union Rob Larew, Senior VP Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00001 Production Agriculture's CEO Council Introduction/Mission Statement: The production agriculture "CEO Council" coordinates alignment on core issues of modern agricultural systems through telling our story, sharing information and leveraging our strengths, while serving as a resource for government decision makers and others interested in USA food, fiber and renewable fuels. Core Focus of Interest Research and innovation Technology access Science and risk-based regulation Sustainability, environment, and weather Marketability, trade, and economic prosperity Government leadership and partnership with private sector Food access and food safety Plant and animal health Ag labor The Council supports principles/themes): Accelerating rural economic growth and improving productivity through innovation and technology Promoting research and innovation that enables development oftools and techniques necessary for discovering new products that hold tremendous potential for farmers and society at large Enabling a regulatory and commercial environment in which agricultural products are marketable, both domestically and internationally Appropriate balance between Federal and State Governments and a cooperative regulatory approach Access to essential labor in balance with an effective Federal immigration policy and adequate worker safety protections Support for all methods of agricultural production Transparency and dialogue with consumers Members of the CEO Council (see reversed) March 30, 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00002 CEO Council Members American Farm Bureau Vincent "Zippy" Duvall, President American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Cattlemen's Beef Association Kendal Frazier, CEO National Chicken Council Michael Brown, President National Com Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Farmers Union Roger Johnson, President National Milk Producers Federation Jim Mulhern, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Departments of Barb Glenn, CEO, ex-officio Agriculture March 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00003 February 9, 2017 The President The White House Washington, D.C. 20500 Dear Mr. President, We, the CEO Council (undersigned herein), representing the production agricultural value chain, including many agricultural producers and farm input developers and suppliers, look forward to working with you and your Administration on matters of importance to American agriculture. The challenges we face in agriculture are significant. Many experts emphasize that producers must grow as much food in the next 50 years as was produced over all previous history to meet the demands of our expanding global population. A firm commitment by the U.S. government to aggressively support agricultural innovation and science-based regulatory decisions will be necessary to ensure farmers have the tools they need to produce a safe and abundant supply of nutritious food, in addition to feed, fuel and fiber, in an environmentally sound and sustainable manner. The policy and regulatory environment your Administration establishes can ensure that agricultural innovation flourishes and American farmers are able to meet the food production goals necessary to feed billions more people. We are ready to provide the White House and the Executive Branch Departments and Agencies, as well as Congress, with policy concepts that foster stability in the U.S. agriculture economy with a strong and predictable farm safety net and promotes American competitiveness through research; marketability and trade of agricultural commodities; rural economic growth; and plant, animal, and environmental health, among many other things. We appreciate your attention to these and other issues of value to American production agriculture and food consumers everywhere. Sincerely, American Farm Bureau Foundation, Zippy Duvall American Seed Trade Association, Andy LaVigne American Soybean Association, Steve Censky Biotechnology Innovation Organization, Dana O'Brien CropLife America, Jay Vroom The Fertilizer Institute, Chris Jahn National Association of Wheat Growers, Chandler Goule National Cattlemen's Beef Association, Kendal Frazier National Corn Growers Association, Chris Novak National Cotton Council, Gary Adams National Council of Farmer Cooperatives, Chuck Conner National Farmers Union, Roger Johnson National Milk Producers Federation, Jim Mulhern National Pork Producers Council, Neil Dierks United Fresh Produce Association, Tom Stenzel USA Rice Federation, Betsy Ward Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00004 National Gotton Council OF MERTOA Gary M. Adams President and Chief Executive Officer National Cotton Council of America Gary Adams assumed the position of President and Chief Executive Officer of the National Cotton Council in February 2015. He plays a key role in guiding the industry's seven segments to reach consensus on critical policies affecting U.S. cotton, with the mission of helping all U.S. cotton industry segments compete effectively and profitably in global markets. Prior to that, Gary served the Council for 13 years as the Vice President of Economic and Policy Analysis. As the Council's chief economist, he provided economic outlooks for global cotton markets, as well as analyzing the impacts of farm and trade policies. Gary also represents the U.S. cotton industry as a member of USDA's Agricultural Policy Advisory Committee. Previously, Gary served on USDA's Advisory Committee on Trade from 2005 through 2011 and the NASS Advisory Committee on Agricultural Statistics from 2003 through 2009. Prior to joining the Council, Gary was a Research Assistant Professor in the Department of Agricultural Economics at the University of Missouri. During his 13-year tenure at the university, Gary's primary responsibilities included policy analysis and market outlook for the Food and Agricultural Policy Research Institute, also known as FAPRI. While at FAPRI, Gary and his colleagues were recognized by the American Agricultural Economics Association for their distinguished policy contributions. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00005 Gary has B.S. and M.A. degrees in Applied Mathematics from the University of Alabama and a Ph.D. in Agricultural Economics from the University of Missouri. Gary and his wife, Ex. 6 Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00006 FASA American Soybean Associatión & Stephen L Censky Chief Executive Officer Stephen L. Censky is the American Soybean Association's (ASA) C hief Executive Officer, a staff position he accepted in April 1996. As ASA's top executive, Ce nsky is in charge of managing ASA's legislative, trade policy, membership and education and training programs. The American Soybean Association is a national, not-for-profit commodity organization with over 22,000 members. ASA works as the domestic and international policy advocate for soybean producer members. Prior to joining ASA, Censky worked in Washington, D.C. for ove a decade. He began his career on Capitol Hill as a legislative assistant for agricultural and transportation matters to Senator Jim Abdnor (R-SD). Later he served in both the Reagan and Bush Administrations at the U.S. Department of Agriculture, helping to craft the 1990 Farm Bill and eventually serving as Administrator of the Foreign Agricultural Service where he was involved in global trade negotiations and running our nation's export programs. Censky received his Bachelor's of Science degree of Agriculture from South Dakota State University and his Master's Diploma in Agriculture St of Melbourne, Australia. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00007 NCFC. National Council of Farmer Cooperatives Charles F. (Chuck) Conner President and CEO National Council of Farmer Cooperatives Charles F. (Chuck) Conner became president & CEO of the National Council of Farmer Cooperatives (NCFC) on January 22, 2009. As president of NCFC, Conner will oversee the organization's work to promote and protect the business and public policy interests of America's farmer-owned cooperatives. He will also provide the strategic vision for the trade association as it continues to seek new ways in which to add value for its membership. Prior to joining NCFC, Conner had served as the Deputy Secretary at the U.S. Department of Agriculture since mid-2005. In this capacity, he was the Chief Operating Officer (COO) overseeing day-to-day operations of the department. Conner interacted directly with President George W. Bush and his senior staff to formulate domestic and international food, trade, security and energy policy. He led development of the Bush Administration's $300 billion Farm Bill proposal and the strategy to educate and inform industry, constituents and Congress. From August 2007 to January 2008, Conner served as both USDA Secretary and Deputy Secretary. He played a key role in developing the Administration's immigration policy including important changes to the H2A program. Conner's experience also includes the assignment of Special Assistant to the President, Executive Office of the President, from October 2001 to May 2005, working on the 2001/2 Farm Bill to develop the strategy behind the transfer of several USDA agency functions to the newly formed Department of Homeland Security. From May 1997 to October 2001 Conner served as President of the Corn Refiners Association. He also served for 17 years as an advisor to U.S. Senator Richard Lugar of Indiana. Conner is a graduate of Purdue University, with a Bachelor's of Science degree and is the recipient of Purdue's Distinguished Alumni Award. He and his wife Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00008 NATIONAL PORK PRODUCERS COUNCIL Neil Dierks, Chief Executive Officer Neil Dierks is Chief Executive Officer of the National Pork Producers Council (NPPC). In this position, he is responsible for the overall implementation of all NPPC programs. Dierks' position requires him to spend time in both Des Moines, Iowa, the national office of NPPC, and Washington, D.C. Beginning in 1990, Dierks served NPPC in a series of senior executive positions, including Executive Director of Operations, Vice President for Research and Education and Senior Vice President for Programs. Prior to his service with NPPC, Dierks was the Special Activities Director for the Iowa Pork Producers Association and Marketing Director for the Iowa Corn Promotion Board. Neil grew up on a livestock farm in eastern lowa and remains involved in a family farming operation. He is a graduate of Iowa State University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00009 NASDA Dr. Barbara Glenn recently joined the National Association of State Departments of Agriculture (NASDA) as CEO on August 18, 2014. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. Dr. Glenn is a scientist with decades of experience as a policy researcher and advocate for agriculture. She previously served as Senior Vice President of Science and Regulatory Affairs for CropLife America, where she was responsible for developing policies and regulations to support agriculture through crop protection. Prior to joining CropLife America, Dr. Glenn served as Managing Director of the Animal Bi otechnology, Food and Agriculture Section of the Biotechnology Industry Association in Washington, DC. Dr. Glenn holds a B.S. in animal science and a Ph.D. in ruminan t nutrition from the University of Kentucky. She previously worked for the U.S. Department of Agriculture, Agric ultural Research Service and the Federation of Animal Science Societies. Born in Lincoln, Nebraska and raised in Centerville, Ohio, Dr. Glenn developed a passion for agriculture from her parents and her involvement in 4-H. She lives Ex. 6 - Personal Privacy and serves on various boards for farm bureau and 4-H. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00010 National Association of Wheat Growers Chandler Goule CEO Chandler Goule assumed his responsibilities as CEO of the National Association of Wheat Growers on July 5, 2016. In addition, he also serves as the executive director of the National Wheat Foundation. Most recently, Goule served as senior vice president of programs at the National Farmers Union (NFU) where he was heavily involved in farm bill legislation. Originally from Texas, Goule holds degrees from Texas A&M and George Washington University and served as a subcommittee staff director for the House Agriculture Committee before moving to the National Farmers Union in 2009 as vice president of government relations. He was appointed senior vice president of NFU programs in 2014. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00011 The Fertilizer Institute Nourish, Replenish, Grow BIOGRAPHY OF CHRISTOPHER JAHN President The Fertilizer Institute and the Nutrients for Life Foundation Christopher L. Jahn is president of The Fertilizer Institute (TFI), the fertilizer industry's national trade association. As TFI president, Jahn works to represent, promote and protect a sound fertilizer industry through legislative and regulatory activities and to promote a favorable public image of the fertilizer industry and agriculture. Jahn also serves as president of the Nutrients for Life Foundation (NFL). Jahn comes to TFI having served as president of the National Association of Chemical Distributors (NACD) since 2006. Prior to leading NACD, Jahn served as president of the Contract Services Association (CSA). Before joining CSA, Jahn had an active role in the United States Senate working for nearly 10 years for U.S. Senator Craig Thomas (R-Wyo.) in a variety of roles, including legislative assistant, legislative director and Chief of Staff. After graduating from Columbia University with a B.A. in Political Science, Jahn co-founded a book distribution business. He also earned an MBA from the University of Maryland. A native of Wyoming, Chris and his wife, Ex. 6 - Personal Privacy Ex. Personal Privacy Capitol View 202.962.0490 425 Third Street, S.W., Suite 950 202.962.0577 fax Washington, DC 20024 www.tfi.org Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00012 National Farmers Union Roger Johnson President Roger Johnson is president of the National Farmers Union (NFU), a grassroots organization that represents more than 200,000 family farmers, ranchers, fisherman and rural communities across the Unites States. Johnson was elected to lead the family farm organization at NFU's 107th anniversary convention in 2009. He has since expanded the education department by providing more programs for beginning, college-aged and women farmers, increased the number of Farmers Union state divisions, and developed a strategic plan for the organization. Johnson has also overseen a number of important policy initiatives important to family farmers including: passage of the 2014 Farm Bill; maintaining a strong Renewable Fuel Standard and Country-of-Origir Labeling, promoting policies that allow farmers to address the growing threat of climate change; and renewing the nation's focus on eliminating an overwhelming trade deficit that results in lost jobs and prosperity for rural America. Prior to leading National Farmers Union, Johnson, a third-generation family farmer from Turtle Lake, N.D., served as North Dakota Agriculture Commissioner, a position he was first elected to in 1996. While Agriculture Commissioner, Johnson served on the State Industrial Commission, the North Dakota Trade Office Advisory Board, and the State Board of Agricultural Research and Education, among many other boards and commissions. From 2007-2008, Johnson served as president of the National Association of State Departments of Agriculture (NASDA). He is a past president of the Midwestern Association of State Departments of Agriculture (MASDA), past president of the Food Export Association of the Midwest and a former chairman of the Interstate Pest Control Compact. Johnson graduated from North Dakota State University with a degree in agricultural economics. Johnson and his wife Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00013 AMERICAN SEED TRADE ASSOCIATION asta first-the - seed R Andrew W. "Andy" LaVigne President & CEO Andrew W. LaVigne is currently the President and CEO of the Ame rican Seed Trade Association. He joined ASTA in February, 2006. Andy has had a 30-year career i n government relations, industry representation, public affairs advocacy, and management. His C ore areas of expertise include agriculture, food policy and international trade. Prior to joining ASTA, Andy was Executive Vice President/CEC of Florida Citrus Mutual, representing citrus growers on issues affecting their business. Prejaiming tFdorida Citrus Mutual, Andy spent four years as Florida Fertilizer and Agrichemical Association's (FFAA) President and Executive Director. FFAA is a non-profit, agricultural trade organization representing companies that specialize in crop protection and plant nutrition products. Before his position at FFAA, Andy spent eight years in Washingt on, D.C. working in the U.S. Congress and the U.S. Department of Agriculture. He served as Legislative Director for Congressman Charles Canady, Agriculture Committee staffer for Congressman Tom Lewis , and on the staff of USDA Secretary Ed Madigan. Andy is a native of Florida with a BA degree in Political Scien ce, with a minor in economics, from the University of Florida. 1701 Duke Street Suite 275 Alexandria, VA 22314 Phone: (703)837-8140 Fax: (703)837-9365 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00014 Biotechnology Innovation Organization Dana O'Brien Executive Vice President, Food & Agriculture Dana O'Brien is Executive Vice President for Food and Agriculture and is responsible for the development of public policy and strategic advocacy, public affairo, and legal strategies that advance industry and stakeholder objectives in the United States. Prior to becoming EVP, Dana served bs BIO Food and Agriculture's chief legislative advocate as Senior Director of Federal Government Relations aince March 2011. Before BIO, Dana worked in Congress for the late Representative lke Skelton (D-MO) managing his legislative team and concentrating on a variety of agricultural, energy, and trade matters. A native of Sedalia, Missouri, and a graduate of Missouri University with a bachelor's degree in psychology, Dana joined the Skelton team immediately out of college and served there for nearly 14 years Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00015 UNITED FRESH is PRODUCE ASSOCIATION Tom Stenzel President and CEO United Fresh Produce Association 1901 Pennsylvania Avenue NW, Suite 1100 Washington, DC 20006 202/303-3400 [email protected] Tom Stenzel is President and CEO of the United Fresh Produce Association, a position he has held since 1993. United Fresh is the pre-eminent trade association for the produce industry in shaping legislative and regulatory policies; providing scientific and technical leadership in food safety and nutrition; and developing educational programs for its members. Founded in 1904, United Fresh represents the interests of companies from small family businesses to the largest international corporations throughout the global fresh produce supply chain. United Fresh is widely known for its work in government affairs, agricultural policy, food safety and nutrition, working to promote political and environmental change to help the next generation of children double their consumption of fresh produce. The United Fresh Start Foundation is committed to increasing children's access to fresh fruits and vegetables, and is a founding partner of the Let's Move Salad Bars to Schools campaign. The campaign has donated salad bars to more than 6,000 schools across the country. Tom is a frequent speaker on industry issues and has been recognized often by the produce industry throughout his career. He was honored as the 2002 Produce Man of the Year by The Packer newspaper, and is the past Chairman of the International Federation for Produce Standards, a global body representing national produce associations around the world. He is a member of the U.S. Chamber of Commerce Committee of 100 leading association executives, the Advisory Board of the International Food Protection Training Institute, and the Key Industry Associations Committee of the American Society of Association Executives, from which he achieved the Certified Association Executive (CAE) designation in 1990. He has served in many government and industry leadership positions, including the first U.S. Department of Agriculture Fruit and Vegetable Industry Advisory Committee, President George W. Bush's Transition Advisory Team for Agriculture, and as an advisor on the U.S. Agricultural Policy Advisory Committee for Trade. Tom was the founding President of the International Food Information Council (IFIC) in 1986, and was previously director of public affairs for the National Soft Drink Association. Tom is a 1977 graduate of the University of Richmond. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00016 as of January 17, 2017 Jay Vroom has served as President and CEO of the trade association known as CropLife America (CLA) since 1989. CLA is the leading U.S. trade group for the crop protection industry in the U.S. Vroom is a founding member of the CropLife Foundation, serving as chairman since its inception in 2001, and now serves as the Foundation's Vice-Chair, since 2015. His sits of the Board of Directors for the Agricultural Retailers Association, Asmark, National Wheat Foundation, the National Association of Manufacturers Council of Manufacturing Associations, and the Soil Health Institute. He is also a member of the Farm Foundation Roundtable Steering Committee, and the North American Climate Smart Ag Alliance Steering Committee. Vroom was a member of the youth organization, Future Farmers of America, and served as an elected state officer in Illinois. Today, he is a member of the FFA Foundation's Individual Giving Council and Board of Trustees. Vroom co-chairs the Coalition for the Advancement of Precision Agriculture and the CEO Council. He is a member of the Friends of the National Arboretum (FONA) FONA Council. He graduated with honors from the College of Agriculture, Consumer and Environmental Sciences at the University of Illinois Urbana-Champaign. Vroom was raised on a grain and livestock farm in north-central Illinois and continues to own the farming operation. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00017 Elizabeth Ward Betsy Ward was appointed President & CEO of the USA Rice Federation in 2007. From 2003- 2005, Ward was the Vice President of International and Domestic Promotion at USA Rice where she was in charge of developing and implementing domestic and international promotion, and food aid programs. From 2005-2007, Ward served as the chief executive for the Hardwood Federation, a trade association representing over 15,000 hardwood producers across the United States. From 1995 to 2003, she ran the Wood Products International Group at the American Forest & Paper Association, directing the wood trade policy and global forestry agenda for the industry. In 2011, Ward was elected Chairman of the U.S. Agricultural Export Development Council (USAEDC) which represents the interests of more than 80 commodity organizations who grow and process a wide variety of U.S. agricultural products. She currently serves as Past Chair. Since 2011, Ward has also served on the Board of Directors of the Sustainable Fisheries Partnership, an independent non-governmental organization (NGO) working to ensure healthy marine and aquatic tecosystems; secure seafood supplies; and a thriving, responsible seafood economy. Ward served for six years as a cleared advisor on the Industry Trade Advisory Committee for forest and paper products (ITAC-7) and was appointed forest products representative to USDA's Agricultural Policy Advisory Committee (APAC) in 2001. Ward holds a Bachelor's degree in History and Political Science from the University of New Hampshire and a Master's degree in International Security Affairs from the School of International Affairs at Columbia University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00018 To: Brown, Byron[[email protected]]; Jackson, Ryan[[email protected]] From: Rebeckah Adcock Sent: Thur 3/30/2017 4:10:52 PM Subject: FW: FINAL CEO Council Meeting Agenda and Materials Pruitt Meeting Materials.pdf ATT00001.htm FYI - final materials for today's meeting. Reb From: "Mary Jo Tomalewski" <[email protected]> To: "Hupp, Sydney" <[email protected]> Cc: "Jay Vroom" <[email protected]> Subject: FINAL Meeting Agenda and Materials Sydney, We have refined our proposed topics for today's CEO Council meeting with the administrator. Attached, please find: Revised "Final Proposed Agenda Topics," which includes the list of those CEO Council members who will attend our meeting today, and their short bios Introduction / Mission Overview of the CEO Council CEO Council Letter to President Trump, dated February 9, 2017 We assume we can skip a formal "round table of introductions" at the beginning of the meeting as our time is short and we want to maximize time spent talking about issues. MJ Mary Jo Tomalewski Executive Assistant to the President & CEO CropLife America Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000063-00001 1156 15th Street, NW Suite 400 Washington, DC 20005 Direct Dial (202) 872-3849 Main Switchboard (202) 296-1585 Mobilé Ex. 6 Personal Privacy Fax (202) 466-5832 Email [email protected] Web www.croplifeamerica.org How can I serve you today? Future Meetings 2017 Spring Regulator Conference - April 6-7, Arlington, VA 2017 Annual Meeting - September 22-27, Dana Point, CA 2018 Winter Board of Directors Meeting - March 5-7, Washington, DC 2018 Annual Meeting - September 21-26, The Ritz-Carlton Amelia Island Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000063-00002 FINAL PROPOSED AGENDA TOPICS Meeting Information: Office of EPA Administrator Scott Pruitt 1200 Pennsylvania Avenue, NW Washington, DC Thursday, March 30, 2017 3:45-4:30 PM Topic 1. Thanks to Trump Administration and Administrator Pruitt for early decisive actions: a. WOTUS b. Chlorpyrifos Petition 2. Top Priority Issues a. Ag Advisor Position - We recommend adding additional title of "Assistant Deputy Administrator" as a title b. Water i. Next steps to refine / clarify beyond WOTUS ii. NPDES permits (CAFO Program needs work; legislation to fix water permits NOT needed for lawful use of pesticides) c. Pesticides Policy i. Endangered Species Act conflicts with Pesticide Regulation and Biotech Regulation ii. Epidemiology Study Policy (as aftermath from Chlorpyrifos matter) iii. Reform Certification & Training and Worker Protection Rules - Suspend implementation and revise d. Renewable Fuels Standard - current program kept consistent e. Communication / Messaging / Opinion Polling - vital to all parties' ability to advance sound policy f. EPA and USDA Cooperation and Coordination - Already vast progress; more can be done! g. Environmental Justice, Research & Development, and Children's Health Offices - Better integration with and reform of EPA program offices; sound science h. Regulation of Manufacturing & Mining Facilities for Ag Inputs - Restore science and process i. Public and Science Advisory Panels at EPA - Balance, strategic agendas j. "Air Emissions" from farming operations CEO Attendees American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Corn Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Barb Glenn, CEO, ex-officio Departments of Agriculture Others American Farm Bureau Federation Dale Moore, Deputy Executive Director Corn Refiners Association John Bode, President & CEO National Farmers Union Rob Larew, Senior VP Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00001 Production Agriculture's CEO Council Introduction/Mission Statement: The production agriculture "CEO Council" coordinates alignment on core issues of modern agricultural systems through telling our story, sharing information and leveraging our strengths, while serving as a resource for government decision makers and others interested in USA food, fiber and renewable fuels. Core Focus of Interest Research and innovation Technology access Science and risk-based regulation Sustainability, environment, and weather Marketability, trade, and economic prosperity Government leadership and partnership with private sector Food access and food safety Plant and animal health Ag labor The Council supports principles/themes): Accelerating rural economic growth and improving productivity through innovation and technology Promoting research and innovation that enables development oftools and techniques necessary for discovering new products that hold tremendous potential for farmers and society at large Enabling a regulatory and commercial environment in which agricultural products are marketable, both domestically and internationally Appropriate balance between Federal and State Governments and a cooperative regulatory approach Access to essential labor in balance with an effective Federal immigration policy and adequate worker safety protections Support for all methods of agricultural production Transparency and dialogue with consumers Members of the CEO Council (see reversed) March 30, 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00002 CEO Council Members American Farm Bureau Vincent "Zippy" Duvall, President American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Cattlemen's Beef Association Kendal Frazier, CEO National Chicken Council Michael Brown, President National Com Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Farmers Union Roger Johnson, President National Milk Producers Federation Jim Mulhern, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Departments of Barb Glenn, CEO, ex-officio Agriculture March 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00003 February 9, 2017 The President The White House Washington, D.C. 20500 Dear Mr. President, We, the CEO Council (undersigned herein), representing the production agricultural value chain, including many agricultural producers and farm input developers and suppliers, look forward to working with you and your Administration on matters of importance to American agriculture. The challenges we face in agriculture are significant. Many experts emphasize that producers must grow as much food in the next 50 years as was produced over all previous history to meet the demands of our expanding global population. A firm commitment by the U.S. government to aggressively support agricultural innovation and science-based regulatory decisions will be necessary to ensure farmers have the tools they need to produce a safe and abundant supply of nutritious food, in addition to feed, fuel and fiber, in an environmentally sound and sustainable manner. The policy and regulatory environment your Administration establishes can ensure that agricultural innovation flourishes and American farmers are able to meet the food production goals necessary to feed billions more people. We are ready to provide the White House and the Executive Branch Departments and Agencies, as well as Congress, with policy concepts that foster stability in the U.S. agriculture economy with a strong and predictable farm safety net and promotes American competitiveness through research; marketability and trade of agricultural commodities; rural economic growth; and plant, animal, and environmental health, among many other things. We appreciate your attention to these and other issues of value to American production agriculture and food consumers everywhere. Sincerely, American Farm Bureau Foundation, Zippy Duvall American Seed Trade Association, Andy LaVigne American Soybean Association, Steve Censky Biotechnology Innovation Organization, Dana O'Brien CropLife America, Jay Vroom The Fertilizer Institute, Chris Jahn National Association of Wheat Growers, Chandler Goule National Cattlemen's Beef Association, Kendal Frazier National Corn Growers Association, Chris Novak National Cotton Council, Gary Adams National Council of Farmer Cooperatives, Chuck Conner National Farmers Union, Roger Johnson National Milk Producers Federation, Jim Mulhern National Pork Producers Council, Neil Dierks United Fresh Produce Association, Tom Stenzel USA Rice Federation, Betsy Ward Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00004 National Gotton Council OF MERTOA Gary M. Adams President and Chief Executive Officer National Cotton Council of America Gary Adams assumed the position of President and Chief Executive Officer of the National Cotton Council in February 2015. He plays a key role in guiding the industry's seven segments to reach consensus on critical policies affecting U.S. cotton, with the mission of helping all U.S. cotton industry segments compete effectively and profitably in global markets. Prior to that, Gary served the Council for 13 years as the Vice President of Economic and Policy Analysis. As the Council's chief economist, he provided economic outlooks for global cotton markets, as well as analyzing the impacts of farm and trade policies. Gary also represents the U.S. cotton industry as a member of USDA's Agricultural Policy Advisory Committee. Previously, Gary served on USDA's Advisory Committee on Trade from 2005 through 2011 and the NASS Advisory Committee on Agricultural Statistics from 2003 through 2009. Prior to joining the Council, Gary was a Research Assistant Professor in the Department of Agricultural Economics at the University of Missouri. During his 13-year tenure at the university, Gary's primary responsibilities included policy analysis and market outlook for the Food and Agricultural Policy Research Institute, also known as FAPRI. While at FAPRI, Gary and his colleagues were recognized by the American Agricultural Economics Association for their distinguished policy contributions. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00005 Gary has B.S. and M.A. degrees in Applied Mathematics from the University of Alabama. and a Ph.D. in Agricultural Economics from the University of Missouri. Gary and his wife, Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00006 FASA American Soybean Associatión & Stephen L Censky Chief Executive Officer Stephen L. Censky is the American Soybean Association's (ASA) C hief Executive Officer, a staff position he accepted in April 1996. As ASA's top executive, Ce nsky is in charge of managing ASA's legislative, trade policy, membership and education and training programs. The American Soybean Association is a national, not-for-profit commodity organization with over 22,000 members. ASA works as the domestic and international policy advocate for soybean producer members. Prior to joining ASA, Censky worked in Washington, D.C. for ove a decade. He began his career on Capitol Hill as a legislative assistant for agricultural and transportation matters to Senator Jim Abdnor (R-SD). Later he served in both the Reagan and Bush Administrations at the U.S. Department of Agriculture, helping to craft the 1990 Farm Bill and eventually serving as Administrator of the Foreign Agricultural Service where he was involved in global trade negotiations and running our nation's export programs. Censky received his Bachelor's of Science degree of Agriculture from South Dakota State University and his Master's Diploma in Agriculture St of Melbourne, Australia. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00007 NCFC. National Council of Farmer Cooperatives Charles F. (Chuck) Conner President and CEO National Council of Farmer Cooperatives Charles F. (Chuck) Conner became president & CEO of the National Council of Farmer Cooperatives (NCFC) on January 22, 2009. As president of NCFC, Conner will oversee the organization's work to promote and protect the business and public policy interests of America's farmer-owned cooperatives. He will also provide the strategic vision for the trade association as it continues to seek new ways in which to add value for its membership. Prior to joining NCFC, Conner had served as the Deputy Secretary at the U.S. Department of Agriculture since mid-2005. In this capacity, he was the Chief Operating Officer (COO) overseeing day-to-day operations of the department. Conner interacted directly with President George W. Bush and his senior staff to formulate domestic and international food, trade, security and energy policy. He led development of the Bush Administration's $300 billion Farm Bill proposal and the strategy to educate and inform industry, constituents and Congress. From August 2007 to January 2008, Conner served as both USDA Secretary and Deputy Secretary. He played a key role in developing the Administration's immigration policy including important changes to the H2A program. Conner's experience also includes the assignment of Special Assistant to the President, Executive Office of the President, from October 2001 to May 2005, working on the 2001/2 Farm Bill to develop the strategy behind the transfer of several USDA agency functions to the newly formed Department of Homeland Security. From May 1997 to October 2001 Conner served as President of the Corn Refiners Association. He also served for 17 years as an advisor to U.S. Senator Richard Lugar of Indiana. Conner is a graduate of Purdue University, with a Bachelor's of Science degree and is the recipient of Purdue's Distinguished Alumni Award. He and his wife Ex. 6 - Personal Privacy Source: :https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00008 NATIONAL PORK PRODUCERS COUNCIL Neil Dierks, Chief Executive Officer Neil Dierks is Chief Executive Officer of the National Pork Producers Council (NPPC). In this position, he is responsible for the overall implementation of all NPPC programs. Dierks' position requires him to spend time in both Des Moines, Iowa, the national office of NPPC, and Washington, D.C. Beginning in 1990, Dierks served NPPC in a series of senior executive positions, including Executive Director of Operations, Vice President for Research and Education and Senior Vice President for Programs. Prior to his service with NPPC, Dierks was the Special Activities Director for the Iowa Pork Producers Association and Marketing Director for the Iowa Corn Promotion Board. Neil grew up on a livestock farm in eastern lowa and remains involved in a family farming operation. He is a graduate of Iowa State University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00009 NASDA Dr. Barbara Glenn recently joined the National Association of State Departments of Agriculture (NASDA) as CEO on August 18, 2014. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. Dr. Glenn is a scientist with decades of experience as a policy researcher and advocate for agriculture. She previously served as Senior Vice President of Science and Regulatory Affairs for CropLife America, where she was responsible for developing policies and regulations to support agriculture through crop protection. Prior to joining CropLife America, Dr. Glenn served as Managing Director of the Animal Bi otechnology, Food and Agriculture Section of the Biotechnology Industry Association in Washington, DC. Dr. Glenn holds a B.S. in animal science and a Ph.D. in ruminan t nutrition from the University of Kentucky. She previously worked for the U.S. Department of Agriculture, Agric ultural Research Service and the Federation of Animal Science Societies. Born in Lincoln, Nebraska and raised in Centerville, Ohio, Dr. Glenn developed a passion for agriculture from her parents and her involvement in 4-H. She lives on a small farm in Maryland with her husband: Ex. 6 - Personal Privacy and serves on various boards for farm bureau and 4-H. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00010

under which country initial input to environmental protection agency is performed ?

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U.S., U.S

Search 1/19/17 snapshot Assessing and Managing Chemicals under TSCA Contact Us Share Assessing and Managing Chemicals under The Frank R. Lautenberg TSCA Home Chemical Safety for the How EPA Assesses Chemical Safety 2 1st Century Act Assessments for TSCA Work Plan Chemicals On June 22, 2016, President Obama signed into law the Frank R. Lautenberg Chemical Safety for Sign up for Current Chemical the 21st Century Act which amends the Toxic TSCA and Risk Reduction Activities Other Substances Control Act (ISCA), the Nation's Chemical ChemView primary chemicals management law. Safety News Chemical Data Reporting The new law, which received bipartisan support in both the U.S. House of Representatives and Getemail alerts the Senate, includes much needed improvements such as: Enter email address sign up Mandatory requirement for EPA to evaluate existing chemicals with clear and enforceable deadlines; New risk-based safety standard; Increased public transparency for chemical information; and Recent Consistent source of funding for EPA to carry additions out the responsibilities under the new law. Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226 American" Chemistry Council August 24, 2016 Wendy Cleland-Hamnett Director, Office of Pollution Prevention and Toxics Environmental Protection Agency 1200 Pennsylvania Ave. NW Washington, DC 20460-0001 Sent electronically to www.regulations.gov docket # EPA-HQ-OPPT-2016-0400 Re: ACC Comments to Inform EPA's Rulemaking on the Conduct of Risk Evaluations under the Lautenberg Chemical Safety Act Dear Ms. Cleland-Hamnett: The American Chemistry Council (ACC¹ appreciates the opportunity to provide input to the Office of Pollution Prevention and Toxics to inform the Agency's development of a risk evaluation rulemaking under the Frank R. Lautenberg Chemical Safety for the 21st Century Act (LCSA). ACC has a long-standing commitment to a robust, science-based approach to evaluation of human and environmental risk. ACC is committed to the effective implementation of the LCSA and supports a workable, rigorous process that allows for timely, high quality reviews. Given the strong emphasis on a risk-based approach in the LCSA, the Section 6(b)(4) rulemaking is particularly important because it will guide the conduct of future risk evaluations that will then inform risk management activities. ACC is committed to being a constructive stakeholder throughout the implementation of LCSA. We will continue to draw from the breadth and depth of our member companies' expertise to ensure that our recommendations are not only science-based, but also allow for the efficient and effective implementation of the LCSA. In doing so, ACC will continue to consider the high quality science standards in the LCSA as well as the timeframes and deadlines imposed therein. The enclosed recommendations were developed with these important considerations in mind. If EPA has any questions, please contact me at nancy [email protected] or 202-249-6417. Sincerely, Nancy B. Beck, PhD, DABT Senior Director, Regulatory and Technical Affairs Cc: Jim Jones, OCSPP Assistant Administrator Louise Wise, Deputy Assistant Administrator Jeffery Morris, Deputy Director for Programs, OPPT Tala Henry, Director, Risk Assessment Division, OPPT 1 The American Chemistry Council (ACC) represents the leading companies engaged in the business of chemistry. More information about ACC is presented in the body of our comments. 1 IPage Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226 American Chemistry Council Initial Input to U.S. Environmental Protection Agency In Regard to the Risk Evaluation Rule under the Lautenberg Chemical Safety Act Table of Contents I. Introduction and Executive Summary 4 II. The Risk Evaluation Rulemaking Must Include both Procedural And Substantive Elements to Effect the Purposes of the Statute 5 III. The Proposed Rule Should Include a Tiered Approach to Risk Evaluation 6 IV. The Rule Should Clarify the Process for Preparation and Contents of the Scope 8 V. The Proposed Rule Should Include a Detailed Description of Substantive Elements of Risk Evaluation 8 VI. Proposed Rule Should Ensure Consistency with Section 6(b)(4)(F) 9 a. Integration and Assessment of Information Relevant to Risks and Information on Potentially Exposed and Susceptible Populations 10 i. Conditions of Use That are Relevant 10 ii. Potentially Exposed or Susceptible Subpopulations 10 b. Aggregate and Sentinel Exposures 12 i. Aggregate Exposures 12 ii. Sentinel Exposures 12 c. Exposure Assessment 13 d. Weight of the Evidence 14 VII. The Proposed Rule Should Incorporate Section 26(h) Scientific Standards 14 a. Fit-for-Purpose Approach 15 b. Consideration of Relevant Information 16 i. Improving Hazard Assessment 16 ii. Improving Dose Response Assessment 17 iii. Reliance on Guidance 17 c. Importance of High Quality Risk Characterization 18 d. Clearly Addressing Variability and Uncertainty 18 e. Ensuring Appropriate Peer Review and Forming a Science Advisory Committee on Chemicals 19 21 Page Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226 VIII. The Proposed Rule Should Implement a Weight of the Scientific Evidence (WoE) Approach 20 a. Systematic Review is Required 20 i. Development of a Protocol 21 ii. Search Strategy 21 iii. Transparency 21 b. A Systematic Review is Not Automatically a WoE Assessment 21 c. WoE and Systematic Review for Screening Level Risk Evaluations 22 d. WoE and Systematic Review for Refined Risk Evaluations 22 e. Strength of Evidence is Not the Same as WoE 23 IX. EPA Should Make Information Available Consistent with Section 26(j) 24 X. EPA Should Use Reasonably Available Information and CBI Consistent with Section 26(k) 24 XI. EPA Should Utilize Fit-for-Purpose Exposure Evaluation Tools 25 XII. The Requirements of Sections 6 and 26 Apply to Environmental Risk Evaluations 26 a. Advancing Models for Environmental Risks 27 b. Improving Data Sourcing, Generation, and Evaluation 27 c. Persistent, Bioaccumulative and Toxic (PBT) Substances 28 XIII. EPA Should Leverage International and Inter-Agency Cooperation 28 XIV. Incorporating High Throughput Tools and Alternative Methods 29 XV. Stakeholders and EPA Must Be Held to the Same High Standard 30 APPENDIX A: ACC's Principles for Improving Chemical Hazard and Risk Assessment 31 APPENDIX B: Improving Hazard Assessment 32 APPENDIX C: Improving Does Response Assessment 33 APPRNDIX D: Improving Risk Characterization 35 APPENDIX E: Ensuring Robust Peer Review 37 APPENDIX F: Exposure Modeling Tools 39 APPENDIX G: Additional Information on the ECETOC TRA 41 3 I P a 3 e Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226 I. Introduction and Executive Summary The American Chemistry Council (ACC)2 is pleased to provide the U.S. Environmental Protection Agency (EPA) this initial input on the Lautenberg Chemical Safety Act's (LCSA) requirement for the Agency to establish, by rule, the process for conducting risk evaluations. ACC appreciates EPA's early efforts to obtain input from stakeholders at its August 9, 2016, public meeting. We also appreciate EPA's solicitation of written comments to be entered into the docket, well in advance of publication of the proposed rule. Our comments both clarify, as well as supplement and expand upon, the oral comments we presented at the August 9 meeting. ACC strongly supported Congress' efforts to update and reform the Toxic Substances Control Act (TSCA). We believe that high quality risk evaluation, using best available science and weight of the evidence (WoE), is at the very heart of the LCSA. Effective and efficient risk evaluations will help deliver the results intended by Congress. Section 6(b)(4)(B) of the statute requires EPA to establish, by rule, "a process to conduct risk evaluations.' This certainly should include a description of the sequence of events, timelines, opportunities for public comments and peer review. Both Sections 6 and 26 of the LCSA outline various substantive elements that apply to and inform risk evaluation. A risk evaluation must: Be conducted in a manner designed to determine "whether a chemical substance presents an unreasonable risk of injury to health or the environment;" as set out in Section 6(b)(4)(A); Identify whether there exists "an unreasonable risk to a potentially exposed or susceptible subpopulation." EPA must identify potentially exposed or susceptible subpopulations relevant to the risk evaluation under conditions of use; Address the specific elements set out in Section 6(b)(4)(F); and Comply with the specific requirements of Section 26, including the best available science, weight of the evidence, and transparency requirements. Because these elements are at the core of the risk evaluation process, and affect risk management measures, they are substantive and should be described in adequate detail in the regulation. In general, where risk evaluation elements are now required by statute, EPA should apply them uniformly and universally reflecting them in the body of the regulation. The recommendations provided by ACC in these comments address screening and refined risk evaluations and are meant to apply to both human health and environmental risks. Specific tools, testing methods, databases, and the like may develop over time, or course, and can be updated as necessary in policies, 2 The American Chemistry Council (ACC) represents the leading companies engaged in the business of chemistry. ACC members apply the science of chemistry to make innovative products and services that make people's lives better, healthier and safer. ACC is committed to improved environmental, health and safety performance through Responsible Care common sense advocacy designed to address major public policy issues, and health and environmental research and product testing. The business of chemistry is a $797 billion enterprise and a key element of the nation's economy. It is the nation's largest exporter, accounting for fourteen percent of all U.S. exports. Chemistry companies are among the largest investors in research and development. Safety and security have always been primary concerns of ACC members, and they have intensified their efforts, working closely with government agencies to improve security and to defend against any threat to the nation's critical infrastructure. 4 Page Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226 procedures and guidance. Our comments strive to make these differentiations and explain where particular elements of risk evaluation should be included in the rule proper. Specifically, our recommendations suggest definitions, and procedural steps and elements that will allow EPA to ensure that risk evaluations are consistent with the statutory requirements for EPA to use the best available science and WoE approaches. The recommendations also include definitions and procedural steps are not expected to change over time. ACC has referenced each of our suggestions to an existing EPA guidance, a National Academies (NAS) report, or another authoritative body or peer reviewed report. For instance, the recommendations in EPA's 2000 Risk Characterization Handbook still represent best practices today. Adding adequate definitions and explanation to the rule is particularly important to achieving incorporation of statutory requirements. We also note that in addition to Section 6, Sections 26(h), 26(i), 26(j), and 26(k) of the LCSA each present legal requirements that are applicable to the risk evaluation. EPA will now need to provide a level of transparency regarding not only the inputs, but also the methods of the analysis, including clear descriptions of uncertainties and variability. EPA should leverage information from other jurisdictions where data and information is applicable and of sufficient quality to meet the science standards in the LCSA. Incorporating these elements into the rulemaking creates a better platform for clear and consistent articulation of the Agency's understanding of statutory requirements, and will better support consistent and uniform application of the elements of risk evaluation. It is critically important that EPA engage the public as EPA plans, scopes, and conducts risk evaluations. Industry scientists often have unique insight and experience with their companies' chemistries and collectively have a large body of knowledge of risk assessment processes globally, including an understanding of potential human health and environmental impacts. ACC encourages EPA to leverage this knowledge and engage early (well before draft risk evaluations are released) and frequently with industry throughout the risk evaluation process. II. The Risk Evaluation Rulemaking Must Include both Procedural and Substantive Elements to Effect the Purposes of the Statute Congress included a specific mandate to EPA to establish a risk evaluation rulemaking. There is little question that the rule must describe the process by which risk evaluations will be conducted. However, to 3 effect the purposes of the statute, the process described in the rule cannot merely set out timelines or the sequence of the risk evaluation. It must include a clear articulation of the substantive elements of risk evaluation, and more particularly, it must explain how it will apply the principles set out in Section 6(b)(4)(F), Section 26, and other parts of the statute. If Congress had intended the scientific standard of "best available science" or "weight of the scientific evidence" to be incorporated into guidance alone, it would have included them only in Section 26(1) on "policies, procedures and guidance." 3 "[T]he Administrator shall establish, by rule, a process to conduct risk evaluations in accordance with subparagraph (A) " Section 6(b)(4)(A). 5 I Page Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226 The very purpose of the risk evaluation is to develop the evidentiary and scientific basis to enable EPA to complete the risk determination required by statute. That risk determination has substantive impact - it significantly affects conduct, activity or a substantive interest that is the subject of agency regulation. The determination following risk evaluation is a necessary prerequisite for a chemical to proceed to risk management, if warranted. The rule should thus include a clear description of how EPA will undertake risk evaluations in order to meet the new statutory requirements of the LCSA. This includes a description of the scoping process and requirements for a published scope as well as the elements of the risk evaluation itself and the mechanism for gauging adequacy as measured against statutory criteria. III. The Proposed Rule Should Include a Tiered Approach to Risk Evaluation We believe the statute contemplates a tiered approach to risk evaluation and recommend that EPA include a tiered approach in the rule. Under the LCSA, EPA must initiate the risk evaluation "upon designating" a chemical as a high-priority substance. The scope, however, is not required to be published "upon initiation" -- EPA has up to six months following the initiation of the risk evaluation to prepare and publish the scope. Congress intended this six month period to be used for a scoping exercise, where EPA identifies "the hazards, exposures, conditions of use, and the potentially exposed or susceptible subpopulations the Administrator expects to consider in the risk evaluation." This six month period is a "step" between the high priority designation and the publication of the scope. In order for EPA to conduct risk evaluations consistent with the quality required by the LCSA and within the timeframes required, EPA should conduct a screening level evaluation during the scoping phase. During the scoping phase of risk evaluations, tools exist to allow EPA to conduct quantitative screening level analyses of multiple exposure scenarios, as appropriate for consumers, sensitive subpopulations, and the environment. This will allow EPA to have a more tailored focus on those populations and exposures of greatest concern during a refined risk evaluation process. Figure 1 below depicts ACC's recommended approach. 6 I Page Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226 - y 10 Worknlan High-Duality Refined Risk Evaluation High Pricrity Chemicats & DRAFT Chemicals Manufacturer Risk Evaluation Requested EXPOSSURES HAZARD Evaluation incorporating Sections 6 and 26 of the Lautenberg Chemicel Safety Act (LCSA): Scope/Screening Level Risk Evatuation Scientific Standards FINAL Susceprible Weight of Scientific Evidence Evaluations Risk Evaluation Exposures Pupulations or use Certain Conditions of Use Present Do not present an anreasonable risk an unreasonable risk Refined No further risk evaluation risk avaluation No further action; needed RUREMAKING PROCESS COMPLETE the Figure 1. A Two-Step Process for Conducting Risk Evaluations Note: This is a simplified version of the process. A tiered approach, where EPA uses the scoping step (step 1) to conduct a quantitative screening level analysis, will allow EPA to focus its limited resources on more robust refined risk evaluations for only those conditions of use where unreasonable risks cannot be ruled out. Screening-level assessments require less data and information, and are typically deterministic and based on conservative, health protective assumptions and methods. When a screening assessment indicates low risk for a particular condition of use, the Agency should have a high degree of confidence that the potential risks are much lower than the calculation and, therefore, the actual risks are lower and/or perhaps non-existent. However, when a screening-level risk assessment indicates a potential concern for an adverse effect, this does not mean that the actual risks are significant and warrant action. Rather, it indicates the Agency should take a second step in the risk evaluation process to refine the evaluation to more accurately quantify potential risks. The refined risk evaluation (step 2) will require realistic and representative data, higher tier modeling approaches, including probabilistic exposure modeling, and a more comprehensive consideration of human relevance and dose-response relationships. In a refined evaluation, EPA should also consider targeted exposure studies, as well as biomonitoring and environmental monitoring data, to the extent that this information is available and relevant. This approach is consistent with EPA's 2014 Framework for Human Health Risk Assessment to Inform Decision Making (HHRA Framework)4. which also emphasizes the importance of a fit-for-purpose approach to risk evaluation. This approach is also consistent with EPA's exposure assessment guidelines and practices. The concept of a tiered approach and a fit-for-purpose 5 evaluation are woven throughout ACC's recommendations. 4 See tps://www.epa.gov/sites/production/files/2014-12/documents/hhra-framework-final-2014.pdf. 5 See: tps://www.epa.gov/expobox/exposure-assessment-tools-tiers-and-types-screening-level-and-refined. 7 Page Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226 The tiered approach ACC recommends is consistent with the approach EPA took in the problem formulation and initial assessment document for tetrabromobisphenol A (TBBPA.6 In that document, EPA conducted an initial screening level evaluation to support its conceptual model and analysis plan. EPA appropriately used high-end exposure values coupled with the lowest toxicity values to evaluate uses and exposure pathways of potential concern. While EPA did not share the relevant risk evaluation calculations in its public document, the general approach is consistent with that of a screening level risk evaluation. ACC encourages EPA to continue with this approach and to transparently and clearly present quantitative screening level analyses for the conditions of use and exposure scenarios that are part of the conceptual model EPA develops as part of the scoping phase. IV. The Rule Should Clarify the Process for Preparation and Contents of the Scope As noted above, Congress allowed a six month period for preparation of the scope of the risk evaluation, contemplating that time and effort would be needed to move from prioritization to a published scope. The six month period is to enable EPA to identify "the hazards, exposures, conditions of use, and the potentially exposed or susceptible subpopulations the Administrator expects to consider in the risk evaluation." Two things are evident from this language and the time frame afforded: 1) EPA should use this period to evaluate and decide which, if any, potentially exposed or susceptible subpopulations should be included in the risk evaluation (in other words, it need not include all such subpopulations, regardless of size, impact, or relevance); and 2) tEPA has flexibility to actually conduct a full risk evaluation of some or all the potential scenarios set out in the scope. In short, EPA need not include every conceivable condition of use in a risk evaluation. This view is further buttressed by the definition of "conditions of use" in Section 3 of the LCSA, which points to the need for EPA to determine the relevant conditions of use: "the circumstances, as determined by the Administrator, under which a chemical substance is intended, known, or reasonably foreseen to be manufactured, processed, distributed in commerce, used, or disposed of." (Emphasis added). V. The Proposed Rule Should Include a Detailed Description of Substantive Elements of Risk Evaluation The term, "risk evaluation" is not expressly defined in the LCSA. While the term "risk assessment" has been widely used in EPA programs and operationally has clear meaning derived from years of guidance, policies and practices, that term was not used in the statute. Therefore even though it may be reasonable to assume "risk evaluation" may fully equate with the term "risk assessment," given the context of its use (integrating hazard with exposure) in the LCSA, EPA is encouraged to explicitly define and operationalize this term as part of its rulemaking. The term will not have clear meaning until an interpretation is assigned by EPA. We believe the essential elements of a Section 6 and 26 risk evaluation must be articulated in a clear regulatory definition as we discuss below. 6 EPA, Problem Formulation and Initial Assessment Tetrabromobisphenol A and Related Chemicals Cluster Flame Retardants, 2015, available at: https://www.epa.gov/assessing-and-managing-chemicals-under-tsca/tsca-work-plan-chemical-problem- formulation-and-2. 8 IPage Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226 Section 6(b)(4)(B) of the statute requires EPA to establish, by rule, "a process to conduct risk evaluations." This process is itself required to meet a number of substantive elements described in the LCSA; a risk evaluation must: Be conducted in a manner designed to help the agency determine "whether a chemical substance presents an unreasonable risk of injury to health or the environment;" as set out in Section 6(b)(4)(A). Include consideration of "an unreasonable risk to a potentially exposed or susceptible subpopulation." EPA must identify relevant potentially exposed or susceptible subpopulations relevant to the risk evaluation under conditions of use; Address the specific elements set out in Section 6(b)(4)(F); and Comply with the specific requirements of Section 26, including the best available science, weight of the evidence, and transparency requirements. The very purpose of the risk evaluation is to develop the evidentiary and scientific basis to enable EPA to complete the risk determination required by statute. That risk determination has substantive impact - it significantly affects conduct, activity or a substantive interest that is the subject of agency regulation. The basis for the risk determination thus should be adequately described in the rule itself to offer sufficient notice to the regulated community. This is particularly important for decisions that inform safety and safety determinations. Likewise, decisions that have broad reaching impact should be supported in regulations, not merely through guidance or agency policy. 8 While EPA cannot substitute policy or guidance for a regulatory description of what will constitute a complete and robust risk evaluation, we believe the necessary elements can be developed in this rulemaking in a timely manner. VI. The Proposed Rule Should Ensure Consistency with Section 6(b)(4)(F) As discussed below, Section 6(b)(4)(F) of the LCSA describes five requirements for risk evaluations that shall be considered by the Administrator and must be incorporated into the risk evaluation rulemaking. 7 See, e.g., MST Express v. U.S. Department of Transportation, 108 F.3d 401 (D.C. Cir. 1997). DOT was directed under the Motor Carrier Safety Act (MCSA) to "prescribe regulations establishing a procedure to decide on the safety fitness of owners and operators of commercial motor vehicles." [Emphasis added]. The MCSA stated that implementing regulations would include "a means of deciding whether the owners, operators, and persons meet the safety fitness requirements." DOT promulgated regulations that set out a process for decision making but used guidance to articulate the tests by which the agency would determine whether vehicles met the safety fitness requirements. The court rejected DOT's reliance on guidance because it "failed to carry out its statutory obligation to establish by regulation a means of determining whether a carrier has complied with the safety fitness requirements." 8 As a general matter, "...it seems to be established that "regulations,' 'substantive rules' or 'legislative rules' are those which create law, usually implementary to an existing law." Gibson Wine Co. v. Snyder, 194 F.2d 329, 331 (D.C. Cir. 1952), cited by Brown Express, Inc. v. U.S., 607 F.2d 695, 700 (5th Cir. 1979). A "rule" is defined under Section 2 of the Administrative Procedure Act, in relevant part, as: "the whole or part of an agency statement of general or particular applicability and future effect designed to implement, interpret, or prescribe law or policy or describing the organization, procedure, or practice requirements of an agency." 5 U.S.C. § 551(4). 9 I Page Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226

to whom the payment of checks to be done ?

hpbn0226

hpbn0226_p0, hpbn0226_p1

university environmental health foundation

368 From: Ehrhardt. Clinton (ehrharon) To: Chilli AP Invoices Cc: Burleigh-Flaver, Heather; Dourson. Michael (doursomi); Maier Michael (maierma); Avers, Valerie (aversvi) Subject: Invoice for UC - PPG PO F2D71625 Date: Friday, May 12, 2017 12:05:55 PM Attachments: PPG2Mav17.pp Attached you will find an invoice for work on PO F2D71625. Please let me know if you have any questions. Thank you, Clinton Ehrhardt Grant Administrator University of Cincinnati, College of Medicine Department of Environmental Health 3223 Eden Ave PO Box 670056 Cincinnati, OH 45267-0056 (513)558-5067 [email protected] Source: https://www.industrydocuments.ucsf.edu/docs/hpbn0226 University of Cincinnati INVOICE Physicians Company University Environmental Health Foundation Invoice# PPGMay17 Date: May 12, 2017 To: For: Heather Burleigh-Flayer, Ph.D., DABT Project: Support for Packaging SBU Global Manager of Toxicology Corporate EHS, PPG 440 College Park Drive Monroeville, PA 15146 DESCRIPTION RATE HOURS AMOUNT Support for Packaging SBU for the period of 4/1/17 - 4/30/17 PO F2D71625 For the following tasks: Reviewed the text entitled "Buyer Beware Report" Revised a 1 page description of TMBFstudies testing potential endocrine disruption based on sponsor review Attended a 1 day meeting with sponsors at their facility; discussed briefly with Rsik Science Center staff the likely work flow from this meeting Michael Dourson. PhD $ 299.00 13.5 $ 4,036.50 Jacqueline Patterson M En $ 288.00 5 $ 1,440.00 TOTAL $5,476.50 Please make Checks payable to: University Environmental Health Foundation Mail Checks to: Department of Environmental Health University of Cincinnati PO Box 670056 Cincinnati, OH 45267-0056 Source: https://www.industrydocuments.ucsf.edu/docs/hpbn0226

what is mentioned in the table content 1 ?

ylcn0226

ylcn0226_p0, ylcn0226_p1, ylcn0226_p2, ylcn0226_p3, ylcn0226_p4, ylcn0226_p5, ylcn0226_p6, ylcn0226_p7, ylcn0226_p8, ylcn0226_p9

Introduction and Executive Summary

Search 1/19/17 snapshot Assessing and Managing Chemicals under TSCA Contact Us Share Assessing and Managing Chemicals under The Frank R. Lautenberg TSCA Home Chemical Safety for the How EPA Assesses Chemical Safety 2 1st Century Act Assessments for TSCA Work Plan Chemicals On June 22, 2016, President Obama signed into law the Frank R. Lautenberg Chemical Safety for Sign up for Current Chemical the 21st Century Act which amends the Toxic TSCA and Risk Reduction Activities Other Substances Control Act (ISCA), the Nation's Chemical ChemView primary chemicals management law. Safety News Chemical Data Reporting The new law, which received bipartisan support in both the U.S. House of Representatives and Getemail alerts the Senate, includes much needed improvements such as: Enter email address sign up Mandatory requirement for EPA to evaluate existing chemicals with clear and enforceable deadlines; New risk-based safety standard; Increased public transparency for chemical information; and Recent Consistent source of funding for EPA to carry additions out the responsibilities under the new law. Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226 American" Chemistry Council August 24, 2016 Wendy Cleland-Hamnett Director, Office of Pollution Prevention and Toxics Environmental Protection Agency 1200 Pennsylvania Ave. NW Washington, DC 20460-0001 Sent electronically to www.regulations.gov docket # EPA-HQ-OPPT-2016-0400 Re: ACC Comments to Inform EPA's Rulemaking on the Conduct of Risk Evaluations under the Lautenberg Chemical Safety Act Dear Ms. Cleland-Hamnett: The American Chemistry Council (ACC¹ appreciates the opportunity to provide input to the Office of Pollution Prevention and Toxics to inform the Agency's development of a risk evaluation rulemaking under the Frank R. Lautenberg Chemical Safety for the 21st Century Act (LCSA). ACC has a long-standing commitment to a robust, science-based approach to evaluation of human and environmental risk. ACC is committed to the effective implementation of the LCSA and supports a workable, rigorous process that allows for timely, high quality reviews. Given the strong emphasis on a risk-based approach in the LCSA, the Section 6(b)(4) rulemaking is particularly important because it will guide the conduct of future risk evaluations that will then inform risk management activities. ACC is committed to being a constructive stakeholder throughout the implementation of LCSA. We will continue to draw from the breadth and depth of our member companies' expertise to ensure that our recommendations are not only science-based, but also allow for the efficient and effective implementation of the LCSA. In doing so, ACC will continue to consider the high quality science standards in the LCSA as well as the timeframes and deadlines imposed therein. The enclosed recommendations were developed with these important considerations in mind. If EPA has any questions, please contact me at nancy [email protected] or 202-249-6417. Sincerely, Nancy B. Beck, PhD, DABT Senior Director, Regulatory and Technical Affairs Cc: Jim Jones, OCSPP Assistant Administrator Louise Wise, Deputy Assistant Administrator Jeffery Morris, Deputy Director for Programs, OPPT Tala Henry, Director, Risk Assessment Division, OPPT 1 The American Chemistry Council (ACC) represents the leading companies engaged in the business of chemistry. More information about ACC is presented in the body of our comments. 1 IPage Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226 American Chemistry Council Initial Input to U.S. Environmental Protection Agency In Regard to the Risk Evaluation Rule under the Lautenberg Chemical Safety Act Table of Contents I. Introduction and Executive Summary 4 II. The Risk Evaluation Rulemaking Must Include both Procedural And Substantive Elements to Effect the Purposes of the Statute 5 III. The Proposed Rule Should Include a Tiered Approach to Risk Evaluation 6 IV. The Rule Should Clarify the Process for Preparation and Contents of the Scope 8 V. The Proposed Rule Should Include a Detailed Description of Substantive Elements of Risk Evaluation 8 VI. Proposed Rule Should Ensure Consistency with Section 6(b)(4)(F) 9 a. Integration and Assessment of Information Relevant to Risks and Information on Potentially Exposed and Susceptible Populations 10 i. Conditions of Use That are Relevant 10 ii. Potentially Exposed or Susceptible Subpopulations 10 b. Aggregate and Sentinel Exposures 12 i. Aggregate Exposures 12 ii. Sentinel Exposures 12 c. Exposure Assessment 13 d. Weight of the Evidence 14 VII. The Proposed Rule Should Incorporate Section 26(h) Scientific Standards 14 a. Fit-for-Purpose Approach 15 b. Consideration of Relevant Information 16 i. Improving Hazard Assessment 16 ii. Improving Dose Response Assessment 17 iii. Reliance on Guidance 17 c. Importance of High Quality Risk Characterization 18 d. Clearly Addressing Variability and Uncertainty 18 e. Ensuring Appropriate Peer Review and Forming a Science Advisory Committee on Chemicals 19 21 Page Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226 VIII. The Proposed Rule Should Implement a Weight of the Scientific Evidence (WoE) Approach 20 a. Systematic Review is Required 20 i. Development of a Protocol 21 ii. Search Strategy 21 iii. Transparency 21 b. A Systematic Review is Not Automatically a WoE Assessment 21 c. WoE and Systematic Review for Screening Level Risk Evaluations 22 d. WoE and Systematic Review for Refined Risk Evaluations 22 e. Strength of Evidence is Not the Same as WoE 23 IX. EPA Should Make Information Available Consistent with Section 26(j) 24 X. EPA Should Use Reasonably Available Information and CBI Consistent with Section 26(k) 24 XI. EPA Should Utilize Fit-for-Purpose Exposure Evaluation Tools 25 XII. The Requirements of Sections 6 and 26 Apply to Environmental Risk Evaluations 26 a. Advancing Models for Environmental Risks 27 b. Improving Data Sourcing, Generation, and Evaluation 27 c. Persistent, Bioaccumulative and Toxic (PBT) Substances 28 XIII. EPA Should Leverage International and Inter-Agency Cooperation 28 XIV. Incorporating High Throughput Tools and Alternative Methods 29 XV. Stakeholders and EPA Must Be Held to the Same High Standard 30 APPENDIX A: ACC's Principles for Improving Chemical Hazard and Risk Assessment 31 APPENDIX B: Improving Hazard Assessment 32 APPENDIX C: Improving Does Response Assessment 33 APPRNDIX D: Improving Risk Characterization 35 APPENDIX E: Ensuring Robust Peer Review 37 APPENDIX F: Exposure Modeling Tools 39 APPENDIX G: Additional Information on the ECETOC TRA 41 3 I P a 3 e Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226 I. Introduction and Executive Summary The American Chemistry Council (ACC)2 is pleased to provide the U.S. Environmental Protection Agency (EPA) this initial input on the Lautenberg Chemical Safety Act's (LCSA) requirement for the Agency to establish, by rule, the process for conducting risk evaluations. ACC appreciates EPA's early efforts to obtain input from stakeholders at its August 9, 2016, public meeting. We also appreciate EPA's solicitation of written comments to be entered into the docket, well in advance of publication of the proposed rule. Our comments both clarify, as well as supplement and expand upon, the oral comments we presented at the August 9 meeting. ACC strongly supported Congress' efforts to update and reform the Toxic Substances Control Act (TSCA). We believe that high quality risk evaluation, using best available science and weight of the evidence (WoE), is at the very heart of the LCSA. Effective and efficient risk evaluations will help deliver the results intended by Congress. Section 6(b)(4)(B) of the statute requires EPA to establish, by rule, "a process to conduct risk evaluations.' This certainly should include a description of the sequence of events, timelines, opportunities for public comments and peer review. Both Sections 6 and 26 of the LCSA outline various substantive elements that apply to and inform risk evaluation. A risk evaluation must: Be conducted in a manner designed to determine "whether a chemical substance presents an unreasonable risk of injury to health or the environment;" as set out in Section 6(b)(4)(A); Identify whether there exists "an unreasonable risk to a potentially exposed or susceptible subpopulation." EPA must identify potentially exposed or susceptible subpopulations relevant to the risk evaluation under conditions of use; Address the specific elements set out in Section 6(b)(4)(F); and Comply with the specific requirements of Section 26, including the best available science, weight of the evidence, and transparency requirements. Because these elements are at the core of the risk evaluation process, and affect risk management measures, they are substantive and should be described in adequate detail in the regulation. In general, where risk evaluation elements are now required by statute, EPA should apply them uniformly and universally reflecting them in the body of the regulation. The recommendations provided by ACC in these comments address screening and refined risk evaluations and are meant to apply to both human health and environmental risks. Specific tools, testing methods, databases, and the like may develop over time, or course, and can be updated as necessary in policies, 2 The American Chemistry Council (ACC) represents the leading companies engaged in the business of chemistry. ACC members apply the science of chemistry to make innovative products and services that make people's lives better, healthier and safer. ACC is committed to improved environmental, health and safety performance through Responsible Care common sense advocacy designed to address major public policy issues, and health and environmental research and product testing. The business of chemistry is a $797 billion enterprise and a key element of the nation's economy. It is the nation's largest exporter, accounting for fourteen percent of all U.S. exports. Chemistry companies are among the largest investors in research and development. Safety and security have always been primary concerns of ACC members, and they have intensified their efforts, working closely with government agencies to improve security and to defend against any threat to the nation's critical infrastructure. 4 Page Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226 procedures and guidance. Our comments strive to make these differentiations and explain where particular elements of risk evaluation should be included in the rule proper. Specifically, our recommendations suggest definitions, and procedural steps and elements that will allow EPA to ensure that risk evaluations are consistent with the statutory requirements for EPA to use the best available science and WoE approaches. The recommendations also include definitions and procedural steps are not expected to change over time. ACC has referenced each of our suggestions to an existing EPA guidance, a National Academies (NAS) report, or another authoritative body or peer reviewed report. For instance, the recommendations in EPA's 2000 Risk Characterization Handbook still represent best practices today. Adding adequate definitions and explanation to the rule is particularly important to achieving incorporation of statutory requirements. We also note that in addition to Section 6, Sections 26(h), 26(i), 26(j), and 26(k) of the LCSA each present legal requirements that are applicable to the risk evaluation. EPA will now need to provide a level of transparency regarding not only the inputs, but also the methods of the analysis, including clear descriptions of uncertainties and variability. EPA should leverage information from other jurisdictions where data and information is applicable and of sufficient quality to meet the science standards in the LCSA. Incorporating these elements into the rulemaking creates a better platform for clear and consistent articulation of the Agency's understanding of statutory requirements, and will better support consistent and uniform application of the elements of risk evaluation. It is critically important that EPA engage the public as EPA plans, scopes, and conducts risk evaluations. Industry scientists often have unique insight and experience with their companies' chemistries and collectively have a large body of knowledge of risk assessment processes globally, including an understanding of potential human health and environmental impacts. ACC encourages EPA to leverage this knowledge and engage early (well before draft risk evaluations are released) and frequently with industry throughout the risk evaluation process. II. The Risk Evaluation Rulemaking Must Include both Procedural and Substantive Elements to Effect the Purposes of the Statute Congress included a specific mandate to EPA to establish a risk evaluation rulemaking. There is little question that the rule must describe the process by which risk evaluations will be conducted. However, to 3 effect the purposes of the statute, the process described in the rule cannot merely set out timelines or the sequence of the risk evaluation. It must include a clear articulation of the substantive elements of risk evaluation, and more particularly, it must explain how it will apply the principles set out in Section 6(b)(4)(F), Section 26, and other parts of the statute. If Congress had intended the scientific standard of "best available science" or "weight of the scientific evidence" to be incorporated into guidance alone, it would have included them only in Section 26(1) on "policies, procedures and guidance." 3 "[T]he Administrator shall establish, by rule, a process to conduct risk evaluations in accordance with subparagraph (A) " Section 6(b)(4)(A). 5 I Page Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226 The very purpose of the risk evaluation is to develop the evidentiary and scientific basis to enable EPA to complete the risk determination required by statute. That risk determination has substantive impact - it significantly affects conduct, activity or a substantive interest that is the subject of agency regulation. The determination following risk evaluation is a necessary prerequisite for a chemical to proceed to risk management, if warranted. The rule should thus include a clear description of how EPA will undertake risk evaluations in order to meet the new statutory requirements of the LCSA. This includes a description of the scoping process and requirements for a published scope as well as the elements of the risk evaluation itself and the mechanism for gauging adequacy as measured against statutory criteria. III. The Proposed Rule Should Include a Tiered Approach to Risk Evaluation We believe the statute contemplates a tiered approach to risk evaluation and recommend that EPA include a tiered approach in the rule. Under the LCSA, EPA must initiate the risk evaluation "upon designating" a chemical as a high-priority substance. The scope, however, is not required to be published "upon initiation" -- EPA has up to six months following the initiation of the risk evaluation to prepare and publish the scope. Congress intended this six month period to be used for a scoping exercise, where EPA identifies "the hazards, exposures, conditions of use, and the potentially exposed or susceptible subpopulations the Administrator expects to consider in the risk evaluation." This six month period is a "step" between the high priority designation and the publication of the scope. In order for EPA to conduct risk evaluations consistent with the quality required by the LCSA and within the timeframes required, EPA should conduct a screening level evaluation during the scoping phase. During the scoping phase of risk evaluations, tools exist to allow EPA to conduct quantitative screening level analyses of multiple exposure scenarios, as appropriate for consumers, sensitive subpopulations, and the environment. This will allow EPA to have a more tailored focus on those populations and exposures of greatest concern during a refined risk evaluation process. Figure 1 below depicts ACC's recommended approach. 6 I Page Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226 - y 10 Worknlan High-Duality Refined Risk Evaluation High Pricrity Chemicats & DRAFT Chemicals Manufacturer Risk Evaluation Requested EXPOSSURES HAZARD Evaluation incorporating Sections 6 and 26 of the Lautenberg Chemicel Safety Act (LCSA): Scope/Screening Level Risk Evatuation Scientific Standards FINAL Susceprible Weight of Scientific Evidence Evaluations Risk Evaluation Exposures Pupulations or use Certain Conditions of Use Present Do not present an anreasonable risk an unreasonable risk Refined No further risk evaluation risk avaluation No further action; needed RUREMAKING PROCESS COMPLETE the Figure 1. A Two-Step Process for Conducting Risk Evaluations Note: This is a simplified version of the process. A tiered approach, where EPA uses the scoping step (step 1) to conduct a quantitative screening level analysis, will allow EPA to focus its limited resources on more robust refined risk evaluations for only those conditions of use where unreasonable risks cannot be ruled out. Screening-level assessments require less data and information, and are typically deterministic and based on conservative, health protective assumptions and methods. When a screening assessment indicates low risk for a particular condition of use, the Agency should have a high degree of confidence that the potential risks are much lower than the calculation and, therefore, the actual risks are lower and/or perhaps non-existent. However, when a screening-level risk assessment indicates a potential concern for an adverse effect, this does not mean that the actual risks are significant and warrant action. Rather, it indicates the Agency should take a second step in the risk evaluation process to refine the evaluation to more accurately quantify potential risks. The refined risk evaluation (step 2) will require realistic and representative data, higher tier modeling approaches, including probabilistic exposure modeling, and a more comprehensive consideration of human relevance and dose-response relationships. In a refined evaluation, EPA should also consider targeted exposure studies, as well as biomonitoring and environmental monitoring data, to the extent that this information is available and relevant. This approach is consistent with EPA's 2014 Framework for Human Health Risk Assessment to Inform Decision Making (HHRA Framework)4. which also emphasizes the importance of a fit-for-purpose approach to risk evaluation. This approach is also consistent with EPA's exposure assessment guidelines and practices. The concept of a tiered approach and a fit-for-purpose 5 evaluation are woven throughout ACC's recommendations. 4 See tps://www.epa.gov/sites/production/files/2014-12/documents/hhra-framework-final-2014.pdf. 5 See: tps://www.epa.gov/expobox/exposure-assessment-tools-tiers-and-types-screening-level-and-refined. 7 Page Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226 The tiered approach ACC recommends is consistent with the approach EPA took in the problem formulation and initial assessment document for tetrabromobisphenol A (TBBPA.6 In that document, EPA conducted an initial screening level evaluation to support its conceptual model and analysis plan. EPA appropriately used high-end exposure values coupled with the lowest toxicity values to evaluate uses and exposure pathways of potential concern. While EPA did not share the relevant risk evaluation calculations in its public document, the general approach is consistent with that of a screening level risk evaluation. ACC encourages EPA to continue with this approach and to transparently and clearly present quantitative screening level analyses for the conditions of use and exposure scenarios that are part of the conceptual model EPA develops as part of the scoping phase. IV. The Rule Should Clarify the Process for Preparation and Contents of the Scope As noted above, Congress allowed a six month period for preparation of the scope of the risk evaluation, contemplating that time and effort would be needed to move from prioritization to a published scope. The six month period is to enable EPA to identify "the hazards, exposures, conditions of use, and the potentially exposed or susceptible subpopulations the Administrator expects to consider in the risk evaluation." Two things are evident from this language and the time frame afforded: 1) EPA should use this period to evaluate and decide which, if any, potentially exposed or susceptible subpopulations should be included in the risk evaluation (in other words, it need not include all such subpopulations, regardless of size, impact, or relevance); and 2) tEPA has flexibility to actually conduct a full risk evaluation of some or all the potential scenarios set out in the scope. In short, EPA need not include every conceivable condition of use in a risk evaluation. This view is further buttressed by the definition of "conditions of use" in Section 3 of the LCSA, which points to the need for EPA to determine the relevant conditions of use: "the circumstances, as determined by the Administrator, under which a chemical substance is intended, known, or reasonably foreseen to be manufactured, processed, distributed in commerce, used, or disposed of." (Emphasis added). V. The Proposed Rule Should Include a Detailed Description of Substantive Elements of Risk Evaluation The term, "risk evaluation" is not expressly defined in the LCSA. While the term "risk assessment" has been widely used in EPA programs and operationally has clear meaning derived from years of guidance, policies and practices, that term was not used in the statute. Therefore even though it may be reasonable to assume "risk evaluation" may fully equate with the term "risk assessment," given the context of its use (integrating hazard with exposure) in the LCSA, EPA is encouraged to explicitly define and operationalize this term as part of its rulemaking. The term will not have clear meaning until an interpretation is assigned by EPA. We believe the essential elements of a Section 6 and 26 risk evaluation must be articulated in a clear regulatory definition as we discuss below. 6 EPA, Problem Formulation and Initial Assessment Tetrabromobisphenol A and Related Chemicals Cluster Flame Retardants, 2015, available at: https://www.epa.gov/assessing-and-managing-chemicals-under-tsca/tsca-work-plan-chemical-problem- formulation-and-2. 8 IPage Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226 Section 6(b)(4)(B) of the statute requires EPA to establish, by rule, "a process to conduct risk evaluations." This process is itself required to meet a number of substantive elements described in the LCSA; a risk evaluation must: Be conducted in a manner designed to help the agency determine "whether a chemical substance presents an unreasonable risk of injury to health or the environment;" as set out in Section 6(b)(4)(A). Include consideration of "an unreasonable risk to a potentially exposed or susceptible subpopulation." EPA must identify relevant potentially exposed or susceptible subpopulations relevant to the risk evaluation under conditions of use; Address the specific elements set out in Section 6(b)(4)(F); and Comply with the specific requirements of Section 26, including the best available science, weight of the evidence, and transparency requirements. The very purpose of the risk evaluation is to develop the evidentiary and scientific basis to enable EPA to complete the risk determination required by statute. That risk determination has substantive impact - it significantly affects conduct, activity or a substantive interest that is the subject of agency regulation. The basis for the risk determination thus should be adequately described in the rule itself to offer sufficient notice to the regulated community. This is particularly important for decisions that inform safety and safety determinations. Likewise, decisions that have broad reaching impact should be supported in regulations, not merely through guidance or agency policy. 8 While EPA cannot substitute policy or guidance for a regulatory description of what will constitute a complete and robust risk evaluation, we believe the necessary elements can be developed in this rulemaking in a timely manner. VI. The Proposed Rule Should Ensure Consistency with Section 6(b)(4)(F) As discussed below, Section 6(b)(4)(F) of the LCSA describes five requirements for risk evaluations that shall be considered by the Administrator and must be incorporated into the risk evaluation rulemaking. 7 See, e.g., MST Express v. U.S. Department of Transportation, 108 F.3d 401 (D.C. Cir. 1997). DOT was directed under the Motor Carrier Safety Act (MCSA) to "prescribe regulations establishing a procedure to decide on the safety fitness of owners and operators of commercial motor vehicles." [Emphasis added]. The MCSA stated that implementing regulations would include "a means of deciding whether the owners, operators, and persons meet the safety fitness requirements." DOT promulgated regulations that set out a process for decision making but used guidance to articulate the tests by which the agency would determine whether vehicles met the safety fitness requirements. The court rejected DOT's reliance on guidance because it "failed to carry out its statutory obligation to establish by regulation a means of determining whether a carrier has complied with the safety fitness requirements." 8 As a general matter, "...it seems to be established that "regulations,' 'substantive rules' or 'legislative rules' are those which create law, usually implementary to an existing law." Gibson Wine Co. v. Snyder, 194 F.2d 329, 331 (D.C. Cir. 1952), cited by Brown Express, Inc. v. U.S., 607 F.2d 695, 700 (5th Cir. 1979). A "rule" is defined under Section 2 of the Administrative Procedure Act, in relevant part, as: "the whole or part of an agency statement of general or particular applicability and future effect designed to implement, interpret, or prescribe law or policy or describing the organization, procedure, or practice requirements of an agency." 5 U.S.C. § 551(4). 9 I Page Source: https://www.industrydocuments.ucsf.edu/docs/ylcn0226

Where does Goule hail from?

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Texas

To: Greenwalt, Sarah[[email protected]]; Dravis, Samantha[[email protected]] Brown, Byron[[email protected]];Wagner, Kenneth[[email protected]] From: Hupp, Sydney Sent: Thur 3/30/2017 5:11:34 PM Subject: FW: FINAL Meeting Agenda and Materials Pruitt Meeting Materials.pd FYI. Sydney Hupp Office of the Administrator- Scheduling 202.816.1659 From: Mary Jo Tomalewski [mailto:[email protected]] Sent: Thursday, March 30, 2017 11:22 AM To: Hupp, Sydney <[email protected]> Cc: Jay Vroom <[email protected]> Subject: FINAL Meeting Agenda and Materials Sydney, We have refined our proposed topics for today's CEO Council meeting with the administrator. Attached, please find: Revised "Final Proposed Agenda Topics," which includes the list of those CEO Council members who will attend our meeting today, and their short bios Introduction / Mission Overview of the CEO Council CEO Council Letter to President Trump, dated February 9, 2017 We assume we can skip a formal "round table of introductions" at the beginning of the meeting as our time is short and we want to maximize time spent talking about issues. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000061-00001 MJ Mary Jo Tomalewski Executive Assistant to the President & CEO CropLife America 1156 15th Street, NW Suite 400 Washington, DC 20005 Direct Dial (202) 872-3849 Main Switchboard (202) 296-1585 Mobile Ex. 6 Personal Privacy Fax (202)466-5832 Email [email protected] Web www.croplifeamerica.org How can I serve you today? Future Meetings 2017 Spring Regulator Conference - April 6-7, Arlington, VA 2017 Annual Meeting - September 22-27, Dana Point, CA 2018 Winter Board of Directors Meeting - March 5-7, Washington, DC 2018 Annual Meeting - September 21-26, The Ritz-Carlton Amelia Island Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000061-00002 FINAL PROPOSED AGENDA TOPICS Meeting Information: Office of EPA Administrator Scott Pruitt 1200 Pennsylvania Avenue, NW Washington, DC Thursday, March 30, 2017 3:45-4:30 PM Topic 1. Thanks to Trump Administration and Administrator Pruitt for early decisive actions: a. WOTUS b. Chlorpyrifos Petition 2. Top Priority Issues a. Ag Advisor Position - We recommend adding additional title of "Assistant Deputy Administrator" as a title b. Water i. Next steps to refine / clarify beyond WOTUS ii. NPDES permits (CAFO Program needs work; legislation to fix water permits NOT needed for lawful use of pesticides) c. Pesticides Policy i. Endangered Species Act conflicts with Pesticide Regulation and Biotech Regulation ii. Epidemiology Study Policy (as aftermath from Chlorpyrifos matter) iii. Reform Certification & Training and Worker Protection Rules - Suspend implementation and revise d. Renewable Fuels Standard - current program kept consistent e. Communication / Messaging / Opinion Polling - vital to all parties' ability to advance sound policy f. EPA and USDA Cooperation and Coordination - Already vast progress; more can be done! g. Environmental Justice, Research & Development, and Children's Health Offices - Better integration with and reform of EPA program offices; sound science h. Regulation of Manufacturing & Mining Facilities for Ag Inputs - Restore science and process i. Public and Science Advisory Panels at EPA - Balance, strategic agendas j. "Air Emissions" from farming operations CEO Attendees American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Corn Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Barb Glenn, CEO, ex-officio Departments of Agriculture Others American Farm Bureau Federation Dale Moore, Deputy Executive Director Corn Refiners Association John Bode, President & CEO National Farmers Union Rob Larew, Senior VP Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00001 Production Agriculture's CEO Council Introduction/Mission Statement: The production agriculture "CEO Council" coordinates alignment on core issues of modern agricultural systems through telling our story, sharing information and leveraging our strengths, while serving as a resource for government decision makers and others interested in USA food, fiber and renewable fuels. Core Focus of Interest Research and innovation Technology access Science and risk-based regulation Sustainability, environment, and weather Marketability, trade, and economic prosperity Government leadership and partnership with private sector Food access and food safety Plant and animal health Ag labor The Council supports principles/themes): Accelerating rural economic growth and improving productivity through innovation and technology Promoting research and innovation that enables development oftools and techniques necessary for discovering new products that hold tremendous potential for farmers and society at large Enabling a regulatory and commercial environment in which agricultural products are marketable, both domestically and internationally Appropriate balance between Federal and State Governments and a cooperative regulatory approach Access to essential labor in balance with an effective Federal immigration policy and adequate worker safety protections Support for all methods of agricultural production Transparency and dialogue with consumers Members of the CEO Council (see reversed) March 30, 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00002 CEO Council Members American Farm Bureau Vincent "Zippy" Duvall, President American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Cattlemen's Beef Association Kendal Frazier, CEO National Chicken Council Michael Brown, President National Com Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Farmers Union Roger Johnson, President National Milk Producers Federation Jim Mulhern, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Departments of Barb Glenn, CEO, ex-officio Agriculture March 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00003 February 9, 2017 The President The White House Washington, D.C. 20500 Dear Mr. President, We, the CEO Council (undersigned herein), representing the production agricultural value chain, including many agricultural producers and farm input developers and suppliers, look forward to working with you and your Administration on matters of importance to American agriculture. The challenges we face in agriculture are significant. Many experts emphasize that producers must grow as much food in the next 50 years as was produced over all previous history to meet the demands of our expanding global population. A firm commitment by the U.S. government to aggressively support agricultural innovation and science-based regulatory decisions will be necessary to ensure farmers have the tools they need to produce a safe and abundant supply of nutritious food, in addition to feed, fuel and fiber, in an environmentally sound and sustainable manner. The policy and regulatory environment your Administration establishes can ensure that agricultural innovation flourishes and American farmers are able to meet the food production goals necessary to feed billions more people. We are ready to provide the White House and the Executive Branch Departments and Agencies, as well as Congress, with policy concepts that foster stability in the U.S. agriculture economy with a strong and predictable farm safety net and promotes American competitiveness through research; marketability and trade of agricultural commodities; rural economic growth; and plant, animal, and environmental health, among many other things. We appreciate your attention to these and other issues of value to American production agriculture and food consumers everywhere. Sincerely, American Farm Bureau Foundation, Zippy Duvall American Seed Trade Association, Andy LaVigne American Soybean Association, Steve Censky Biotechnology Innovation Organization, Dana O'Brien CropLife America, Jay Vroom The Fertilizer Institute, Chris Jahn National Association of Wheat Growers, Chandler Goule National Cattlemen's Beef Association, Kendal Frazier National Corn Growers Association, Chris Novak National Cotton Council, Gary Adams National Council of Farmer Cooperatives, Chuck Conner National Farmers Union, Roger Johnson National Milk Producers Federation, Jim Mulhern National Pork Producers Council, Neil Dierks United Fresh Produce Association, Tom Stenzel USA Rice Federation, Betsy Ward Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00004 National Gotton Council OF MERTOA Gary M. Adams President and Chief Executive Officer National Cotton Council of America Gary Adams assumed the position of President and Chief Executive Officer of the National Cotton Council in February 2015. He plays a key role in guiding the industry's seven segments to reach consensus on critical policies affecting U.S. cotton, with the mission of helping all U.S. cotton industry segments compete effectively and profitably in global markets. Prior to that, Gary served the Council for 13 years as the Vice President of Economic and Policy Analysis. As the Council's chief economist, he provided economic outlooks for global cotton markets, as well as analyzing the impacts of farm and trade policies. Gary also represents the U.S. cotton industry as a member of USDA's Agricultural Policy Advisory Committee. Previously, Gary served on USDA's Advisory Committee on Trade from 2005 through 2011 and the NASS Advisory Committee on Agricultural Statistics from 2003 through 2009. Prior to joining the Council, Gary was a Research Assistant Professor in the Department of Agricultural Economics at the University of Missouri. During his 13-year tenure at the university, Gary's primary responsibilities included policy analysis and market outlook for the Food and Agricultural Policy Research Institute, also known as FAPRI. While at FAPRI, Gary and his colleagues were recognized by the American Agricultural Economics Association for their distinguished policy contributions. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00005 Gary has B.S. and M.A. degrees in Applied Mathematics from the University of Alabama and a Ph.D. in Agricultural Economics from the University of Missouri. Gary and his wife, Ex. 6 Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00006 FASA American Soybean Associatión & Stephen L Censky Chief Executive Officer Stephen L. Censky is the American Soybean Association's (ASA) C hief Executive Officer, a staff position he accepted in April 1996. As ASA's top executive, Ce nsky is in charge of managing ASA's legislative, trade policy, membership and education and training programs. The American Soybean Association is a national, not-for-profit commodity organization with over 22,000 members. ASA works as the domestic and international policy advocate for soybean producer members. Prior to joining ASA, Censky worked in Washington, D.C. for ove a decade. He began his career on Capitol Hill as a legislative assistant for agricultural and transportation matters to Senator Jim Abdnor (R-SD). Later he served in both the Reagan and Bush Administrations at the U.S. Department of Agriculture, helping to craft the 1990 Farm Bill and eventually serving as Administrator of the Foreign Agricultural Service where he was involved in global trade negotiations and running our nation's export programs. Censky received his Bachelor's of Science degree of Agriculture from South Dakota State University and his Master's Diploma in Agriculture St of Melbourne, Australia. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00007 NCFC. National Council of Farmer Cooperatives Charles F. (Chuck) Conner President and CEO National Council of Farmer Cooperatives Charles F. (Chuck) Conner became president & CEO of the National Council of Farmer Cooperatives (NCFC) on January 22, 2009. As president of NCFC, Conner will oversee the organization's work to promote and protect the business and public policy interests of America's farmer-owned cooperatives. He will also provide the strategic vision for the trade association as it continues to seek new ways in which to add value for its membership. Prior to joining NCFC, Conner had served as the Deputy Secretary at the U.S. Department of Agriculture since mid-2005. In this capacity, he was the Chief Operating Officer (COO) overseeing day-to-day operations of the department. Conner interacted directly with President George W. Bush and his senior staff to formulate domestic and international food, trade, security and energy policy. He led development of the Bush Administration's $300 billion Farm Bill proposal and the strategy to educate and inform industry, constituents and Congress. From August 2007 to January 2008, Conner served as both USDA Secretary and Deputy Secretary. He played a key role in developing the Administration's immigration policy including important changes to the H2A program. Conner's experience also includes the assignment of Special Assistant to the President, Executive Office of the President, from October 2001 to May 2005, working on the 2001/2 Farm Bill to develop the strategy behind the transfer of several USDA agency functions to the newly formed Department of Homeland Security. From May 1997 to October 2001 Conner served as President of the Corn Refiners Association. He also served for 17 years as an advisor to U.S. Senator Richard Lugar of Indiana. Conner is a graduate of Purdue University, with a Bachelor's of Science degree and is the recipient of Purdue's Distinguished Alumni Award. He and his wife Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00008 NATIONAL PORK PRODUCERS COUNCIL Neil Dierks, Chief Executive Officer Neil Dierks is Chief Executive Officer of the National Pork Producers Council (NPPC). In this position, he is responsible for the overall implementation of all NPPC programs. Dierks' position requires him to spend time in both Des Moines, Iowa, the national office of NPPC, and Washington, D.C. Beginning in 1990, Dierks served NPPC in a series of senior executive positions, including Executive Director of Operations, Vice President for Research and Education and Senior Vice President for Programs. Prior to his service with NPPC, Dierks was the Special Activities Director for the Iowa Pork Producers Association and Marketing Director for the Iowa Corn Promotion Board. Neil grew up on a livestock farm in eastern lowa and remains involved in a family farming operation. He is a graduate of Iowa State University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00009 NASDA Dr. Barbara Glenn recently joined the National Association of State Departments of Agriculture (NASDA) as CEO on August 18, 2014. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. Dr. Glenn is a scientist with decades of experience as a policy researcher and advocate for agriculture. She previously served as Senior Vice President of Science and Regulatory Affairs for CropLife America, where she was responsible for developing policies and regulations to support agriculture through crop protection. Prior to joining CropLife America, Dr. Glenn served as Managing Director of the Animal Bi otechnology, Food and Agriculture Section of the Biotechnology Industry Association in Washington, DC. Dr. Glenn holds a B.S. in animal science and a Ph.D. in ruminan t nutrition from the University of Kentucky. She previously worked for the U.S. Department of Agriculture, Agric ultural Research Service and the Federation of Animal Science Societies. Born in Lincoln, Nebraska and raised in Centerville, Ohio, Dr. Glenn developed a passion for agriculture from her parents and her involvement in 4-H. She lives Ex. 6 - Personal Privacy and serves on various boards for farm bureau and 4-H. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00010 National Association of Wheat Growers Chandler Goule CEO Chandler Goule assumed his responsibilities as CEO of the National Association of Wheat Growers on July 5, 2016. In addition, he also serves as the executive director of the National Wheat Foundation. Most recently, Goule served as senior vice president of programs at the National Farmers Union (NFU) where he was heavily involved in farm bill legislation. Originally from Texas, Goule holds degrees from Texas A&M and George Washington University and served as a subcommittee staff director for the House Agriculture Committee before moving to the National Farmers Union in 2009 as vice president of government relations. He was appointed senior vice president of NFU programs in 2014. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00011 The Fertilizer Institute Nourish, Replenish, Grow BIOGRAPHY OF CHRISTOPHER JAHN President The Fertilizer Institute and the Nutrients for Life Foundation Christopher L. Jahn is president of The Fertilizer Institute (TFI), the fertilizer industry's national trade association. As TFI president, Jahn works to represent, promote and protect a sound fertilizer industry through legislative and regulatory activities and to promote a favorable public image of the fertilizer industry and agriculture. Jahn also serves as president of the Nutrients for Life Foundation (NFL). Jahn comes to TFI having served as president of the National Association of Chemical Distributors (NACD) since 2006. Prior to leading NACD, Jahn served as president of the Contract Services Association (CSA). Before joining CSA, Jahn had an active role in the United States Senate working for nearly 10 years for U.S. Senator Craig Thomas (R-Wyo.) in a variety of roles, including legislative assistant, legislative director and Chief of Staff. After graduating from Columbia University with a B.A. in Political Science, Jahn co-founded a book distribution business. He also earned an MBA from the University of Maryland. A native of Wyoming, Chris and his wife, Ex. 6 - Personal Privacy Ex. Personal Privacy Capitol View 202.962.0490 425 Third Street, S.W., Suite 950 202.962.0577 fax Washington, DC 20024 www.tfi.org Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00012 National Farmers Union Roger Johnson President Roger Johnson is president of the National Farmers Union (NFU), a grassroots organization that represents more than 200,000 family farmers, ranchers, fisherman and rural communities across the Unites States. Johnson was elected to lead the family farm organization at NFU's 107th anniversary convention in 2009. He has since expanded the education department by providing more programs for beginning, college-aged and women farmers, increased the number of Farmers Union state divisions, and developed a strategic plan for the organization. Johnson has also overseen a number of important policy initiatives important to family farmers including: passage of the 2014 Farm Bill; maintaining a strong Renewable Fuel Standard and Country-of-Origir Labeling, promoting policies that allow farmers to address the growing threat of climate change; and renewing the nation's focus on eliminating an overwhelming trade deficit that results in lost jobs and prosperity for rural America. Prior to leading National Farmers Union, Johnson, a third-generation family farmer from Turtle Lake, N.D., served as North Dakota Agriculture Commissioner, a position he was first elected to in 1996. While Agriculture Commissioner, Johnson served on the State Industrial Commission, the North Dakota Trade Office Advisory Board, and the State Board of Agricultural Research and Education, among many other boards and commissions. From 2007-2008, Johnson served as president of the National Association of State Departments of Agriculture (NASDA). He is a past president of the Midwestern Association of State Departments of Agriculture (MASDA), past president of the Food Export Association of the Midwest and a former chairman of the Interstate Pest Control Compact. Johnson graduated from North Dakota State University with a degree in agricultural economics. Johnson and his wife Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00013 AMERICAN SEED TRADE ASSOCIATION asta first-the - seed R Andrew W. "Andy" LaVigne President & CEO Andrew W. LaVigne is currently the President and CEO of the Ame rican Seed Trade Association. He joined ASTA in February, 2006. Andy has had a 30-year career i n government relations, industry representation, public affairs advocacy, and management. His C ore areas of expertise include agriculture, food policy and international trade. Prior to joining ASTA, Andy was Executive Vice President/CEC of Florida Citrus Mutual, representing citrus growers on issues affecting their business. Prejaiming tFdorida Citrus Mutual, Andy spent four years as Florida Fertilizer and Agrichemical Association's (FFAA) President and Executive Director. FFAA is a non-profit, agricultural trade organization representing companies that specialize in crop protection and plant nutrition products. Before his position at FFAA, Andy spent eight years in Washingt on, D.C. working in the U.S. Congress and the U.S. Department of Agriculture. He served as Legislative Director for Congressman Charles Canady, Agriculture Committee staffer for Congressman Tom Lewis , and on the staff of USDA Secretary Ed Madigan. Andy is a native of Florida with a BA degree in Political Scien ce, with a minor in economics, from the University of Florida. 1701 Duke Street Suite 275 Alexandria, VA 22314 Phone: (703)837-8140 Fax: (703)837-9365 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00014 Biotechnology Innovation Organization Dana O'Brien Executive Vice President, Food & Agriculture Dana O'Brien is Executive Vice President for Food and Agriculture and is responsible for the development of public policy and strategic advocacy, public affairo, and legal strategies that advance industry and stakeholder objectives in the United States. Prior to becoming EVP, Dana served bs BIO Food and Agriculture's chief legislative advocate as Senior Director of Federal Government Relations aince March 2011. Before BIO, Dana worked in Congress for the late Representative lke Skelton (D-MO) managing his legislative team and concentrating on a variety of agricultural, energy, and trade matters. A native of Sedalia, Missouri, and a graduate of Missouri University with a bachelor's degree in psychology, Dana joined the Skelton team immediately out of college and served there for nearly 14 years Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00015 UNITED FRESH is PRODUCE ASSOCIATION Tom Stenzel President and CEO United Fresh Produce Association 1901 Pennsylvania Avenue NW, Suite 1100 Washington, DC 20006 202/303-3400 [email protected] Tom Stenzel is President and CEO of the United Fresh Produce Association, a position he has held since 1993. United Fresh is the pre-eminent trade association for the produce industry in shaping legislative and regulatory policies; providing scientific and technical leadership in food safety and nutrition; and developing educational programs for its members. Founded in 1904, United Fresh represents the interests of companies from small family businesses to the largest international corporations throughout the global fresh produce supply chain. United Fresh is widely known for its work in government affairs, agricultural policy, food safety and nutrition, working to promote political and environmental change to help the next generation of children double their consumption of fresh produce. The United Fresh Start Foundation is committed to increasing children's access to fresh fruits and vegetables, and is a founding partner of the Let's Move Salad Bars to Schools campaign. The campaign has donated salad bars to more than 6,000 schools across the country. Tom is a frequent speaker on industry issues and has been recognized often by the produce industry throughout his career. He was honored as the 2002 Produce Man of the Year by The Packer newspaper, and is the past Chairman of the International Federation for Produce Standards, a global body representing national produce associations around the world. He is a member of the U.S. Chamber of Commerce Committee of 100 leading association executives, the Advisory Board of the International Food Protection Training Institute, and the Key Industry Associations Committee of the American Society of Association Executives, from which he achieved the Certified Association Executive (CAE) designation in 1990. He has served in many government and industry leadership positions, including the first U.S. Department of Agriculture Fruit and Vegetable Industry Advisory Committee, President George W. Bush's Transition Advisory Team for Agriculture, and as an advisor on the U.S. Agricultural Policy Advisory Committee for Trade. Tom was the founding President of the International Food Information Council (IFIC) in 1986, and was previously director of public affairs for the National Soft Drink Association. Tom is a 1977 graduate of the University of Richmond. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00016 as of January 17, 2017 Jay Vroom has served as President and CEO of the trade association known as CropLife America (CLA) since 1989. CLA is the leading U.S. trade group for the crop protection industry in the U.S. Vroom is a founding member of the CropLife Foundation, serving as chairman since its inception in 2001, and now serves as the Foundation's Vice-Chair, since 2015. His sits of the Board of Directors for the Agricultural Retailers Association, Asmark, National Wheat Foundation, the National Association of Manufacturers Council of Manufacturing Associations, and the Soil Health Institute. He is also a member of the Farm Foundation Roundtable Steering Committee, and the North American Climate Smart Ag Alliance Steering Committee. Vroom was a member of the youth organization, Future Farmers of America, and served as an elected state officer in Illinois. Today, he is a member of the FFA Foundation's Individual Giving Council and Board of Trustees. Vroom co-chairs the Coalition for the Advancement of Precision Agriculture and the CEO Council. He is a member of the Friends of the National Arboretum (FONA) FONA Council. He graduated with honors from the College of Agriculture, Consumer and Environmental Sciences at the University of Illinois Urbana-Champaign. Vroom was raised on a grain and livestock farm in north-central Illinois and continues to own the farming operation. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00017 Elizabeth Ward Betsy Ward was appointed President & CEO of the USA Rice Federation in 2007. From 2003- 2005, Ward was the Vice President of International and Domestic Promotion at USA Rice where she was in charge of developing and implementing domestic and international promotion, and food aid programs. From 2005-2007, Ward served as the chief executive for the Hardwood Federation, a trade association representing over 15,000 hardwood producers across the United States. From 1995 to 2003, she ran the Wood Products International Group at the American Forest & Paper Association, directing the wood trade policy and global forestry agenda for the industry. In 2011, Ward was elected Chairman of the U.S. Agricultural Export Development Council (USAEDC) which represents the interests of more than 80 commodity organizations who grow and process a wide variety of U.S. agricultural products. She currently serves as Past Chair. Since 2011, Ward has also served on the Board of Directors of the Sustainable Fisheries Partnership, an independent non-governmental organization (NGO) working to ensure healthy marine and aquatic tecosystems; secure seafood supplies; and a thriving, responsible seafood economy. Ward served for six years as a cleared advisor on the Industry Trade Advisory Committee for forest and paper products (ITAC-7) and was appointed forest products representative to USDA's Agricultural Policy Advisory Committee (APAC) in 2001. Ward holds a Bachelor's degree in History and Political Science from the University of New Hampshire and a Master's degree in International Security Affairs from the School of International Affairs at Columbia University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00018 To: Brown, Byron[[email protected]]; Jackson, Ryan[[email protected]] From: Rebeckah Adcock Sent: Thur 3/30/2017 4:10:52 PM Subject: FW: FINAL CEO Council Meeting Agenda and Materials Pruitt Meeting Materials.pdf ATT00001.htm FYI - final materials for today's meeting. Reb From: "Mary Jo Tomalewski" <[email protected]> To: "Hupp, Sydney" <[email protected]> Cc: "Jay Vroom" <[email protected]> Subject: FINAL Meeting Agenda and Materials Sydney, We have refined our proposed topics for today's CEO Council meeting with the administrator. Attached, please find: Revised "Final Proposed Agenda Topics," which includes the list of those CEO Council members who will attend our meeting today, and their short bios Introduction / Mission Overview of the CEO Council CEO Council Letter to President Trump, dated February 9, 2017 We assume we can skip a formal "round table of introductions" at the beginning of the meeting as our time is short and we want to maximize time spent talking about issues. MJ Mary Jo Tomalewski Executive Assistant to the President & CEO CropLife America Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000063-00001 1156 15th Street, NW Suite 400 Washington, DC 20005 Direct Dial (202) 872-3849 Main Switchboard (202) 296-1585 Mobilé Ex. 6 Personal Privacy Fax (202) 466-5832 Email [email protected] Web www.croplifeamerica.org How can I serve you today? Future Meetings 2017 Spring Regulator Conference - April 6-7, Arlington, VA 2017 Annual Meeting - September 22-27, Dana Point, CA 2018 Winter Board of Directors Meeting - March 5-7, Washington, DC 2018 Annual Meeting - September 21-26, The Ritz-Carlton Amelia Island Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000063-00002 FINAL PROPOSED AGENDA TOPICS Meeting Information: Office of EPA Administrator Scott Pruitt 1200 Pennsylvania Avenue, NW Washington, DC Thursday, March 30, 2017 3:45-4:30 PM Topic 1. Thanks to Trump Administration and Administrator Pruitt for early decisive actions: a. WOTUS b. Chlorpyrifos Petition 2. Top Priority Issues a. Ag Advisor Position - We recommend adding additional title of "Assistant Deputy Administrator" as a title b. Water i. Next steps to refine / clarify beyond WOTUS ii. NPDES permits (CAFO Program needs work; legislation to fix water permits NOT needed for lawful use of pesticides) c. Pesticides Policy i. Endangered Species Act conflicts with Pesticide Regulation and Biotech Regulation ii. Epidemiology Study Policy (as aftermath from Chlorpyrifos matter) iii. Reform Certification & Training and Worker Protection Rules - Suspend implementation and revise d. Renewable Fuels Standard - current program kept consistent e. Communication / Messaging / Opinion Polling - vital to all parties' ability to advance sound policy f. EPA and USDA Cooperation and Coordination - Already vast progress; more can be done! g. Environmental Justice, Research & Development, and Children's Health Offices - Better integration with and reform of EPA program offices; sound science h. Regulation of Manufacturing & Mining Facilities for Ag Inputs - Restore science and process i. Public and Science Advisory Panels at EPA - Balance, strategic agendas j. "Air Emissions" from farming operations CEO Attendees American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Corn Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Barb Glenn, CEO, ex-officio Departments of Agriculture Others American Farm Bureau Federation Dale Moore, Deputy Executive Director Corn Refiners Association John Bode, President & CEO National Farmers Union Rob Larew, Senior VP Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00001 Production Agriculture's CEO Council Introduction/Mission Statement: The production agriculture "CEO Council" coordinates alignment on core issues of modern agricultural systems through telling our story, sharing information and leveraging our strengths, while serving as a resource for government decision makers and others interested in USA food, fiber and renewable fuels. Core Focus of Interest Research and innovation Technology access Science and risk-based regulation Sustainability, environment, and weather Marketability, trade, and economic prosperity Government leadership and partnership with private sector Food access and food safety Plant and animal health Ag labor The Council supports principles/themes): Accelerating rural economic growth and improving productivity through innovation and technology Promoting research and innovation that enables development oftools and techniques necessary for discovering new products that hold tremendous potential for farmers and society at large Enabling a regulatory and commercial environment in which agricultural products are marketable, both domestically and internationally Appropriate balance between Federal and State Governments and a cooperative regulatory approach Access to essential labor in balance with an effective Federal immigration policy and adequate worker safety protections Support for all methods of agricultural production Transparency and dialogue with consumers Members of the CEO Council (see reversed) March 30, 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00002 CEO Council Members American Farm Bureau Vincent "Zippy" Duvall, President American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Cattlemen's Beef Association Kendal Frazier, CEO National Chicken Council Michael Brown, President National Com Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Farmers Union Roger Johnson, President National Milk Producers Federation Jim Mulhern, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Departments of Barb Glenn, CEO, ex-officio Agriculture March 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00003 February 9, 2017 The President The White House Washington, D.C. 20500 Dear Mr. President, We, the CEO Council (undersigned herein), representing the production agricultural value chain, including many agricultural producers and farm input developers and suppliers, look forward to working with you and your Administration on matters of importance to American agriculture. The challenges we face in agriculture are significant. Many experts emphasize that producers must grow as much food in the next 50 years as was produced over all previous history to meet the demands of our expanding global population. A firm commitment by the U.S. government to aggressively support agricultural innovation and science-based regulatory decisions will be necessary to ensure farmers have the tools they need to produce a safe and abundant supply of nutritious food, in addition to feed, fuel and fiber, in an environmentally sound and sustainable manner. The policy and regulatory environment your Administration establishes can ensure that agricultural innovation flourishes and American farmers are able to meet the food production goals necessary to feed billions more people. We are ready to provide the White House and the Executive Branch Departments and Agencies, as well as Congress, with policy concepts that foster stability in the U.S. agriculture economy with a strong and predictable farm safety net and promotes American competitiveness through research; marketability and trade of agricultural commodities; rural economic growth; and plant, animal, and environmental health, among many other things. We appreciate your attention to these and other issues of value to American production agriculture and food consumers everywhere. Sincerely, American Farm Bureau Foundation, Zippy Duvall American Seed Trade Association, Andy LaVigne American Soybean Association, Steve Censky Biotechnology Innovation Organization, Dana O'Brien CropLife America, Jay Vroom The Fertilizer Institute, Chris Jahn National Association of Wheat Growers, Chandler Goule National Cattlemen's Beef Association, Kendal Frazier National Corn Growers Association, Chris Novak National Cotton Council, Gary Adams National Council of Farmer Cooperatives, Chuck Conner National Farmers Union, Roger Johnson National Milk Producers Federation, Jim Mulhern National Pork Producers Council, Neil Dierks United Fresh Produce Association, Tom Stenzel USA Rice Federation, Betsy Ward Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00004 National Gotton Council OF MERTOA Gary M. Adams President and Chief Executive Officer National Cotton Council of America Gary Adams assumed the position of President and Chief Executive Officer of the National Cotton Council in February 2015. He plays a key role in guiding the industry's seven segments to reach consensus on critical policies affecting U.S. cotton, with the mission of helping all U.S. cotton industry segments compete effectively and profitably in global markets. Prior to that, Gary served the Council for 13 years as the Vice President of Economic and Policy Analysis. As the Council's chief economist, he provided economic outlooks for global cotton markets, as well as analyzing the impacts of farm and trade policies. Gary also represents the U.S. cotton industry as a member of USDA's Agricultural Policy Advisory Committee. Previously, Gary served on USDA's Advisory Committee on Trade from 2005 through 2011 and the NASS Advisory Committee on Agricultural Statistics from 2003 through 2009. Prior to joining the Council, Gary was a Research Assistant Professor in the Department of Agricultural Economics at the University of Missouri. During his 13-year tenure at the university, Gary's primary responsibilities included policy analysis and market outlook for the Food and Agricultural Policy Research Institute, also known as FAPRI. While at FAPRI, Gary and his colleagues were recognized by the American Agricultural Economics Association for their distinguished policy contributions. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00005 Gary has B.S. and M.A. degrees in Applied Mathematics from the University of Alabama. and a Ph.D. in Agricultural Economics from the University of Missouri. Gary and his wife, Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00006 FASA American Soybean Associatión & Stephen L Censky Chief Executive Officer Stephen L. Censky is the American Soybean Association's (ASA) C hief Executive Officer, a staff position he accepted in April 1996. As ASA's top executive, Ce nsky is in charge of managing ASA's legislative, trade policy, membership and education and training programs. The American Soybean Association is a national, not-for-profit commodity organization with over 22,000 members. ASA works as the domestic and international policy advocate for soybean producer members. Prior to joining ASA, Censky worked in Washington, D.C. for ove a decade. He began his career on Capitol Hill as a legislative assistant for agricultural and transportation matters to Senator Jim Abdnor (R-SD). Later he served in both the Reagan and Bush Administrations at the U.S. Department of Agriculture, helping to craft the 1990 Farm Bill and eventually serving as Administrator of the Foreign Agricultural Service where he was involved in global trade negotiations and running our nation's export programs. Censky received his Bachelor's of Science degree of Agriculture from South Dakota State University and his Master's Diploma in Agriculture St of Melbourne, Australia. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00007 NCFC. National Council of Farmer Cooperatives Charles F. (Chuck) Conner President and CEO National Council of Farmer Cooperatives Charles F. (Chuck) Conner became president & CEO of the National Council of Farmer Cooperatives (NCFC) on January 22, 2009. As president of NCFC, Conner will oversee the organization's work to promote and protect the business and public policy interests of America's farmer-owned cooperatives. He will also provide the strategic vision for the trade association as it continues to seek new ways in which to add value for its membership. Prior to joining NCFC, Conner had served as the Deputy Secretary at the U.S. Department of Agriculture since mid-2005. In this capacity, he was the Chief Operating Officer (COO) overseeing day-to-day operations of the department. Conner interacted directly with President George W. Bush and his senior staff to formulate domestic and international food, trade, security and energy policy. He led development of the Bush Administration's $300 billion Farm Bill proposal and the strategy to educate and inform industry, constituents and Congress. From August 2007 to January 2008, Conner served as both USDA Secretary and Deputy Secretary. He played a key role in developing the Administration's immigration policy including important changes to the H2A program. Conner's experience also includes the assignment of Special Assistant to the President, Executive Office of the President, from October 2001 to May 2005, working on the 2001/2 Farm Bill to develop the strategy behind the transfer of several USDA agency functions to the newly formed Department of Homeland Security. From May 1997 to October 2001 Conner served as President of the Corn Refiners Association. He also served for 17 years as an advisor to U.S. Senator Richard Lugar of Indiana. Conner is a graduate of Purdue University, with a Bachelor's of Science degree and is the recipient of Purdue's Distinguished Alumni Award. He and his wife Ex. 6 - Personal Privacy Source: :https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00008 NATIONAL PORK PRODUCERS COUNCIL Neil Dierks, Chief Executive Officer Neil Dierks is Chief Executive Officer of the National Pork Producers Council (NPPC). In this position, he is responsible for the overall implementation of all NPPC programs. Dierks' position requires him to spend time in both Des Moines, Iowa, the national office of NPPC, and Washington, D.C. Beginning in 1990, Dierks served NPPC in a series of senior executive positions, including Executive Director of Operations, Vice President for Research and Education and Senior Vice President for Programs. Prior to his service with NPPC, Dierks was the Special Activities Director for the Iowa Pork Producers Association and Marketing Director for the Iowa Corn Promotion Board. Neil grew up on a livestock farm in eastern lowa and remains involved in a family farming operation. He is a graduate of Iowa State University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00009 NASDA Dr. Barbara Glenn recently joined the National Association of State Departments of Agriculture (NASDA) as CEO on August 18, 2014. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. Dr. Glenn is a scientist with decades of experience as a policy researcher and advocate for agriculture. She previously served as Senior Vice President of Science and Regulatory Affairs for CropLife America, where she was responsible for developing policies and regulations to support agriculture through crop protection. Prior to joining CropLife America, Dr. Glenn served as Managing Director of the Animal Bi otechnology, Food and Agriculture Section of the Biotechnology Industry Association in Washington, DC. Dr. Glenn holds a B.S. in animal science and a Ph.D. in ruminan t nutrition from the University of Kentucky. She previously worked for the U.S. Department of Agriculture, Agric ultural Research Service and the Federation of Animal Science Societies. Born in Lincoln, Nebraska and raised in Centerville, Ohio, Dr. Glenn developed a passion for agriculture from her parents and her involvement in 4-H. She lives on a small farm in Maryland with her husband: Ex. 6 - Personal Privacy and serves on various boards for farm bureau and 4-H. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00010

when was this information published ?

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endpoints, criteria are similarly available for both acute and chronic classification. The use of one common system allows for appropriate assessment of all substances. GHS classification information is readily available for all substances, as U.S. manufacturers have developed GHS classifications for their products to meet international requirements. ACC's support of the GHS criteria for purposes of this prioritization tool is not a categorical endorsement of the GHS criteria for any other purpose. ACC has been an active participant in the development of GHS and supports the system in principle. The GHS has not been broadly implemented to date in the U.S., although the Occupational Safety and Health Administration (OSHA) has indicated an intent to publish a regulation applying GHS in the workplace. ACC's December 29, 2009, comments on OSHA's proposed rule to modify the existing Hazard Communication Standard (HCS) to reflect the GHS urged that implementation of the GHS adhere to certain principles (e.g., continued application of the "Building Block Approach" of the Purple Book). ACC made specific recommendations concerning details of the Hazard Classification definitions, cut-off values, among others. ACC stands behind those comments. In ACC's view, the use of GHS criteria in a screening-level prioritization of chemicals can materially assist in determining which chemicals receive additional evaluation by the Environmental Protection Agency, but does not necessarily preclude the use of other appropriate, applicable criteria developed under other systems. To classify a chemical in a hazard based priority ranking where there is not direct data on the chemical, EPA can employ the full range of approaches, such as QSAR, SAR, read- across and other modeling tools in which EPA has confidence based on molecular structure. In those situations where there still remains insufficient information on either environmental or human health hazards, the chemical would be classified as "high" for its environmental or health ranking. 1. Environmental Ranking Table 1 provides a summary of how GHS criteria could be logically used for chemical management prioritization. Table 1. Environmental Safety - Hazard Ranking GHS Classification - Ranking Environmental Rank Environmental Score Acute I or Chronic I or Insufficient Information to High 4 Classify Acute II or Chronic II Medium High 3 Acute III or Chronic III/IV or Medium 2 none Not classified Low 1 August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 2. Human Health Ranking Table 2. Human Health - Hazard Ranking Health Rank GHS Classification - Human Health Ranking Score GHS CMR Cat 1a, 1b; OR Repeat Dose </= 10 mg/kg/day (oral); </= 20 mg/kg/day (dermal); </= 50 ppm/6hr/day (gas inhalation); High 4 <<= 0.2 mg/1/6h/day (vapour inhalation); </= 0.02 mg/l/6h/day (dust mist fume inhal). OR insufficient information to classify GHS CMR Cat 2; OR Repeat Dose 10 - 100 mg/kg/day (oral); 20 - 200 mg/kg/day (dermal); Medium High 50 - 250 ppm/6hr/day (gas inhalation); 3 0.2 - 1.0 mg/l/6h/day (vapour inhalation); 0.02 - 0.2 mg/l/6h/day (dust mist fume inhal). Not carcinogen/mutagen/repro/develop;OR Repeat Dose 100 - 1000 mg/kg/day (oral); 200 - 2000 mg/kg/day (dermal); Medium 250 - 1000 ppm/6hr/day (gas inhalation); 2 1.0 - 5.0 mg/l/6h/day (vapour inhalation); 0.2 - 1.0 mg/l/6h/day (dust mist fume inhal). Not carcinogen/mutagen/repro/develop; OR Repeat Dose >1000 mg/kg/day (oral); > 2000 mg/kg/day (dermal); Low > 1000 ppm/6hr/day (gas inhalation); 1 >5.0 mg/l/6h/day (vapour inhalation); > 1.0 mg/l/6h/day (dust mist fume inhal). It is important to note that specific concerns about children's health (specifically potential hazards and adverse effects on the nervous system) and those caused by endocrine disruption mechanisms are addressed in this prioritization process: The GHS CMR "R" classification includes specific evaluation of effects on development in utero and upon growth, maturation and reproduction. ("R" stands for reproductive toxicity and includes adverse effects on sexual function and fertility, as well as developmental toxicity in offspring). Endocrine activity is not a distinct toxicological hazard per se, but rather a measure of a compound's ability to interact with components of the endocrine system. The prioritization process evaluates data and information on relevant apical tests, including tests for reproduction and developmental toxicity (potential endocrine pathways). Thus, even if specific August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 screening for potential endocrine activity has not yet been conducted on certain compounds, hazard identification based on observable outcomes from apical toxicity tests (e.g., outcomes such as pathologic states indicative of disease conditions) covers all modes of action, including endocrine pathways. The toxicity information evaluated (CMR and repeat dose toxicity) is directly relevant to evaluating potential hazards to all individuals, including children. Such data typically includes: 1) identification and definition of possible hazards upon all major organ systems from both acute and repeated exposures, including the nervous system; 2) detection of potential hazards arising from in utero exposures, including possible effects on the nervous system; 3) evaluation of potential of a substance to affect reproduction; and 4) evaluation of the potential of a substance to damage DNA. Integration of Hazard Elements: Each of the environmental and human health classifications is assigned a numeric value based upon its ranking, with 1 being the lowest value and 4 the highest. The greatest ranking (highest hazard potential score) of either Environmental or Human Health is used in a substance- specific priority ranking. The numeric value does not imply relative weighting, but rather a numerical order of priority. B. Exposure Potential Ranking The screening method allows for an initial indication of the extent of exposure potential by considering: 1. The chemical's uses and use pattern(s) 2. Production volume as a first pass indicator of relative emission/release potential since magnitude and route (i.e. air, water, soil) of emissions is not available for all substances. 3. Persistence and bioaccumulation characteristics of the substance. Together the 3 elements are used to rank exposure potential. 1. Use Patterns The proposed approach applies the most current 2006 TSCA Inventory Update Reporting rule (IUR, now called the Chemical Data Reporting rule (CDR) data. To keep the initial prioritization simple and transparent, the approach "bins" different use patterns to align with general exposure potential - intermediates, industrial use, commercial use and consumer use. These patterns are the same as those reported in the IUR and are consistent with REACH exposure categories (intermediates, worker, professional, consumer). Chemicals with consumer product use are likely to have widespread potential for general population exposures and are given high priority ranking within the approach. For the initial prioritization approach, child specific products are captured under general consumer products and all consumer products are weighted equally (see additional discussion below under Second Tier Considerations). Intermediates will have low general population exposures, since these substances are consumed, by definition, within the workplace. Therefore, they are given the lowest priority ranking within the approach. In the context of the proposed approach, the intermediates category includes both intermediates and non-isolated intermediates. A chemical used in multiple use patterns is August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 assigned the priority of the highest use, e.g., a chemical in both industrial and commercial uses would be assigned the commercial Medium-High rank. Table 3. Use Patterns - Exposure Ranking Use Pattern Ranking Use Pattern Score Consumer High 4 Commercial Medium-High 3 Industrial Medium 2 Intermediates Low 1 The IUR Definitions of these terms are (40 CFR 710.3, 710.43): "consumer use" means the use of a chemical substance or a mixture containing a chemical substance (including as part of article) when sold to or made available to consumers for their use. "commercial use" means the use of a chemical substance or a mixture containing a chemical substance (including as part of an article) in a commercial enterprise providing saleable goods or services. "industrial use" means use at a site at which one or more chemical substances or mixtures are manufactured (including imported). "intermediate" means any chemical substance: which is intentionally removed from the equipment in which it is manufactured, and which either is consumed in whole or in part in chemical reaction(s) used for the intentional manufacture of other chemical substance(s) or mixture(s), or is intentionally present for the purpose of altering the rate of such chemical reaction(s) "non-isolated intermediate" means any intermediate that is not intentionally removed from the equipment in which is it manufactured, including the reaction vessel in which it is manufactured, equipment which is ancillary to the reaction vessel, and any equipment through which the substance passes during a continuous flow process, but not including tanks or other vessels in which the substance is stored after its manufacture. 2. Production Volume Recognizing that detailed exposure information will not be available for all substances to be screened, the proposed approach uses production volume as an indicator of exposure, which is widely used in many prioritization schemes. As production volume is just a rough surrogate of emissions, ACC suggests only very broad categories, covering about two orders of magnitude each. It may be useful to consider how additional exposure estimates may be applied in the second tier assessment. Table 4. Production Volume as Emission Surrogate - Exposure Ranking Production Volume as Emission Surrogate Ranking Volume Score >= 100,000,000 lbs national aggregate High 4 1,000,000 lbs to < 100,000,000 lbs national Medium - High 3 aggregate August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 >= 25,000 lbs to < 1,000,000 lbs national Medium 2 aggregate < 25,000 lbs (below IUR site reporting limit) Low 1 3. Persistence and Bioaccumulation Persistence and bioaccumulation are viewed as indicators of exposure, and therefore are considered under the exposure axis of the approach. A persistent substance that is emitted to the environment at the same rate as a non-persistent substance with similar partitioning properties will result in higher exposure to humans and the environment. In fact, multimedia modeling clearly indicates that environmental persistence in the compartment to which a substance partitions is a good indicator of human exposure potential (MacLeod & McKone et al. 2004). Similarly, substances that are not subject to biotransformation by higher organisms will exhibit a high bioaccumulation potential that results in higher exposures via the food chain (Arnot et al. 2010). Therefore, it is recommended to apply the proposed persistence and bioaccumulation criteria in assessment of exposure potential as described below. The persistent and bioaccumulative (P&B) criteria of the proposed approach are targeted toward organic chemicals. Separate assessment criteria are likely needed for P&B evaluation for inorganics/metals, as in the approach taken by Canada's Chemical Management Program (CMP). For assessing persistence, based upon recent expert consensus (Boethling et al., 2009) it is recommended to distinguish persistent from non-persistent chemicals using the following criteria: Volatile chemicals can be defined using a vapor pressure cut-off (i.e., > 1000 Pa) For volatile chemicals, persistent versus non-persistent chemicals are differentiated using a half-life cut-off in air (e.g., a substance is not persistent if air half life is < 2 days). For non-volatile chemicals, non-persistent substances can be defined as substances that are deemed: readily or inherently biodegradable using standard biodegradation tests (OECD 301, 302, 306 test guidelines) or SAR or read across from measured data on a related substance, show an equivalent degree of degradation (i.e. >20% in 28 days) via an abiotic degradation mechanism such as photolysis (OECD 316) or hydrolysi (OECD 111), evaluation of simulation data from transformation in soil, marine water/sediment, brackish water/sediment, surface water/sediment, oceanic water die away (e.g. OECD 308/309) have half lives below 180 days, OR if data are lacking, evaluation via BIOWIN model (EPIWEB 4) Non-volatile substances that are not biodegradable or subject to abiotic losses based on the above criteria would be considered persistent. For assessing bioaccumulation, the key question for screening is the potential for biomagnification based on recent expert consensus (Gobas et al. 2009). To determine if a substance has the potential to biomagnify the following metrics have been agreed: Trophic Magnification Factor (TMF)>1, fish Biomagnification Factor (BMF)>1 fish Bioaccumulation Factor (BAF)/Bioconcentration Factor (BCF) > 5000. These metrics can be August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 derived using lab or field measurements (where available) or recently improved computational models that are included in EPA's EPIWEB model that can be freely downloaded at www.epa.gov/oppt/exposure/pubs/episuite.htm. This approach allows all organics to be addressed and is a scientifically updated version of the approach used in Canada's CMP. Based on the above recommendations, substances can be grouped with regard to persistence and bioaccumulation as follows: Table 5. Persistence and Bioaccumulation - Exposure Ranking Persistence and P&B Ranking P&B Score Bioaccumulation Persistent and High 5 Bioaccumulative Persistent and Not Medium 3 Bioaccumulative OR Not Persistent and Bioaccumulative Not Persistent and Not Low 1 Bioaccumulative Integration of Exposure Elements: As demonstrated in the tables, each factor (use pattern, P&B, and production volume) would be assigned a numeric score based upon its ranking. All 3 factors are added to arrive at an overall value. These values are then separated into categories from low to high exposure potential. A proposed "banding" approach is illustrated in Table 6. Table 6. Integration of Exposure Rankings Combined Score - All 3 Exposure Rank Exposure Ranking elements Score 11 13 High 5 9 10 Medium High 4 7 8 Medium 3 5 6 Medium Low 2 3 4 Low 1 Overall Priority Grouping: In the overall approach, both hazard and exposure elements are considered when placing a substance in a risk-based prioritization ranking. The overall prioritization score for priority grouping and risk evaluation is based on the combined consideration of the hazard and exposure rankings. Priority Groups 7, 8, and 9 are deemed High Priority; Priority Groups 4, 5, and 6 are Medium Priority; and Priority Groups 2 and 3 are Low Priority. August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Review and Comment: It is important that screening be done in an open and transparent way and that the best available information be used. When screening for thousands of chemicals, EPA may not have access to all available information. The process should provide an opportunity for review and comment on initial rankings and an opportunity to submit additional relevant data and information to update proposed rankings with improved information. III. Second Tier Considerations: After the initial screening, some substances within individual priority groupings may require further rank ordering, particularly where a large number of chemicals are in the same priority group. Listed below are the types of information that will be useful to consider in this Second Tier rank ordering: Biomonitoring/Environmental Monitoring Data: Mere detection of chemicals in humans or the environment, i.e., "found in biomonitoring (CDC), found in water (NCOD), and found in air", while providing an indication of exposure, does not provide a useful criterion for exposure potential because almost any industrial or commercial chemical could be detected at trace levels, given increasingly sensitive analytical methods. Therefore, detection alone primarily reflects only the fact that a specific chemical was included in a measurement program. This criterion will also tend to bias the prioritization of chemicals for which well-established analytical methods are available. Consequently, this criterion is not used in the initial prioritization scheme. However, within a particular priority grouping, reliable monitoring information should be considered for Second Tier rank ordering within a quantitative process that assesses if the data is above a level of concern (i.e., places it in a risk context). Use in Children's Products: Protection of childrens' health is a top priority and, in the initial ranking, child-specific products are captured under general consumer products and all consumer products are weighted equally. The specific IUR reporting of information on chemical use in products intended for children would be considered further within a particular priority grouping for Second Tier rank ordering, noting the following points: the IUR definition is based upon use in a child specific product rather than child specific exposure potential¹ (see below). Without knowing a specific product type, it is difficult to understand if 1 IUR definition (Federal Register Volume 75, Number 156, Friday August 30, 2010, p. 49686): Intended for use by children means the chemical substance or mixture is used in or on a product that is specifically intended for use by children age 14 or younger. A chemical substance or mixture is intended for use by children when the submitter answers "yes" to at least on of the following questions for the product into which the submitter's chemical substance or mixture is incorporated: (1) Is the product commonly recognized (i.e., by a reasonable person) as being intended for children age 14 or younger? (2) Does the manufacturer of the product state through product labeling or other written materials that the product is intended for or will be used by children age 14 or younger? (3) Is the advertising, promotion, or marketing of the product aimed at children age 14 or younger? August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 potential child exposure is greater than for a non-child specific product. For example, how does child exposure to a general use cleaner compare to exposure from use in a child's raincoat. In the VCCEP assessments, there are examples for inhalation exposures where estimates of passive child exposure during adult product use exceeded conservative estimates of child exposure during active use of a child-specific product (such as a hobby product) - differences were related to the amount of product used and substance concentration within the product (MEK VCCEP Submission). the IUR definition targets children age 14 and younger. Younger children may be exposed to a variety of non-child specific products that are in general household use. Older children may be exposed to a variety of additional products. the IUR information request is targeted to manufacturers, which may not have direct knowledge of all uses, particularly the presence in products for specific subpopulations, such as children. Therefore, it is not clear that the information requested for the IUR information would be consistently available across all substances being screened. Ideally, this information should be requested from formulators of child-specific products. Therefore, for the initial prioritization approach, which represents a broad, unrefined categorization, child specific products are captured under general consumer products and all consumer products are weighted equally. The IUR information on child specific use would be utilized within a particular priority grouping for Second Tier rank ordering. If the IUR information is utilized, it is important that the limitations above be considered in its application. Emissions Data: Production volume, which is readily available for substances, is used in this proposed approach, but only serves as a surrogate for environmental emissions. For further prioritization, data or estimates of environmental emissions can be used to refine prioritization. Estimates of environmental emissions will be available for some substances (e.g., TRI data). When TRI data are utilized it should be recognized that it addresses only emissions that result from industrial and not wide dispersive uses. In other cases, emissions estimates can be developed as a percentage of production volume based upon consideration of use categories. Within a particular priority grouping, available emissions information can be considered for Second Tier rank ordering, with the understanding that emissions information is not an indicator of actual exposure. Similarly, non-isolated system intermediates, by definition, would have de minimis exposure potential. Therefore, this IUR information could be considered within a particular priority grouping for Second Tier rank ordering. International Risk Management Actions: An initial screening approach for chemical prioritization should be based upon consistent application of specific hazard and exposure science elements that define risk potential. The hazard and exposure elements should be applicable across all substances being evaluated. For initial screening, existence of international risk management action plans should not be a factor that determines priority grouping. Risk management plans may be based upon many factors, including political drivers. It is unclear how factors, their relative weighting, and the rigor of the evaluation may vary across agencies and substances. For initial screening August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 purposes, the same science-based criteria should be used to rank all substances. Consideration of existing international risk management plans could be utilized to check the functioning of the approach and could be considered within a particular priority grouping for Second Tier rank ordering with the possible effect of moving a chemical up in a grouping if actions are being taken internationally. IV. Summary ACC's prioritization approach is an example of a risk-based screening prioritization process that implements the general principles outlined at the outset of this document. It is based upon widely available information that can be utilized to understand the relative priority of chemicals for further evaluation from a risk perspective, i.e., integrating both hazard and exposure elements. Implementation of the screening framework will be most effective when utilizing the best available information. When conducting screening for thousands of chemicals, EPA may not have access to all available information. An open and iterative process that includes an opportunity for review and comment on initial rankings, together with the information that led to the result, and an opportunity to update the ranking with improved information will create a transparent and scientifically sound process. V. References Arnot, J.A., D. Mackay, T. F. Parkerton, R. T. Zaleski, C.S. Warren (2010), Multimedia modeling of human exposure to chemical substances: The roles of food web biomagnification and biotransformation, Environmental Toxicology and Chemistry 29(1):45-55. Boethling, R., K. Fenner, P. Howard, G. Klecka, T. Madsen, J.R. Snape, M.J. Whelan (2009). Environmental persistence of organic pollutants: guidance for development and review of POP risk profiles. Integrated Environmental Assessment and Management 5(4): 539 - 556. Gobas, F.A.P.C, W. de Wolf, L. P Burkhard, E. Verbruggen, K. Plotzke (2009). Revisiting Bioaccumulation Criteria for POPs and PBT Assessments Integrated Environmental Assessment and Management, 5(4):624-637. MacLeod, M., T. E. McKone (2004). Multimedia persistence as an indicator of potential for population-level intake of environmental contaminants, Environmental Toxicology and Chemistry 23(10):2465-2472. van Wijk,D., R. Chénier, T. Henry, M. D Hernando, C. Schulte (2009). Integrated Approach to PBT and POP Prioritization and Risk Assessment' Integrated Environmental Assessment and Management, 5(4):697-711. August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Proposed Prioritization Approach DRAFT May & 2011 Exposure Elements nat commental consumer 20 2 3 a 33 3 not 8 or Persuntence S not 3 mai 35 a & not 3 Pas $ 3 S the iss = the Tormages RUN $ 3 3 SUM - P8 - Tavamage ranow 3 -13 Expesure Ramking $5 Based os Sum (UN# + pa * Townage PRIORITY GROUPING - Hazard * Expasure Ramkings - 1-8 3-10 11-13 mad Jow Hazard - Highter and Human $ 3 3 & $ Human Mazard Not on Dase 3 low mai * anou % 1000 numour 3 1.8 (duet Nume " 3 & 3 8 Not 100 Acure mi os : 3 A 2000 and not data) 280 v 1000 (pas 1.0 8.0 nomour 8.3 miss Nome 3 & % x CMR Cat 2, on Dawe Call 3: 10 - 3 is # 200 50 ase Igas 0.3 1.0 0.0% - 0.2 mis forme * # $ y GMS CMR Can on OHS Clowe Clat % Repeat Close 10 § on 8 on insurticient 20 information to - - - 0.3 wis 0,00 mist on information to $ 3 a $ August 29, 2011 Source: :https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Hazard and Exposure Criteria for Prioritization Approach HAZARD EXPOSURE Environment and Human Health Classifications based upon GHS Use Elements - based upon IUR Intermediate consumed during industrial processing Envirommental: industrial (not intermediate) - used in an industrial setting From GHS classification guidance document: commercial occupational use in nonindustrial setting Table 4.1.2: scheme for substances hazardous so the aquatic environment. consumer general population residential use Clacufication Persistence: Loag-term Votalile substance (VPS 1000 Pax: Not Persistent if air half life <2 days a (Nate 2) Nonvolatile (VP < 1000 Pa): Not Persistent if: Adequate dass Adequnte voriciny dasa aux a) ready biodegradability (OBCD 301) Rapidly 3 b) inherent biodegradability (OBCD 301, 302, 306) degredable 0) read across from measured data on a related substance. 28 (Note. 3) d) equivalent degree of degradation (i.e. >20% in 28 days) via an abjotic Arute 3 Categorys Chronic 1 Categury: 1 Categasy: I degradation mechanism such as photolysis (OBCD 316) or hydrolysis (OBCD NOEC ar ECA 0.1 NOE - EC cass L 1.00 md of maid 111) and/ar BCF a 200 OR, a substance is Not Persistent if: if e) evaluation of simulation data from transformation in soil, marine water/sediment, Caregusy: Acore 2 Category: Chronic 2 Caregury: Chrumin 2 Caregusy: Chruaic 2 brackish water/sediment, surface water/sediment, oceanic water die away (e.g., OECD 3.00 s: s 10.9 0.1 - NOEC er EC. 13 0.00 <: NOEC - EC, 502 3.00 L(EXC) 10.8 and of andies 308/309) have half lives below 180 days. BCF = 500 as if K. 2 4 OR, if data are lacking: Caregusy: Arnie 3 Caregury: 3 Chrinia 3 f) evaluation via BIOWIN model (EPIWEB 4) 01 EC. : 30,00 1- 100 and fack of Bioaccomulation: stapoid andier BOF: Re 300 if absent log x 3 4 A substance is not bioaccumulative if: 4 4) a) measured TMF < 1 (field study) 3) b) measured fish BMF <1 (lab study) Ne tericity and lack of and BCF 2 500 ase, lag E 4, c) measured fish BCF < 5000 (lab study) MOECA 1 mal d) predicted BCP< 5000 using the BCFBAF model included in EPIWIN 4 The above order reflects the preference for use in decision- making NOTE -- P&B CRITERIA ARB FOR ORGANICS Tonnage - based upon JUR reporting ranges <. 25,000 lbs (below IUR site reporting limit) Human Health: 25.000 - <1 MM lbs national aggregate As above, based upon GHS 1MM - <100 MM lbs national aggregate >100 MM lbs national aggregate August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Risk-Based Prioritization Matrix Ancreasing Exposure Two-Step towest Prionies Prioritization Process Incregaling Second Tier Rank Ordering within Priority Groups Biomonitoring / Environmental Monitoring Use in Children's Products Emissions (e.g. TRI) International Risk Management Actions Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226

Where does Goule holds degree from?

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Texas A&M and George Washington University

To: Greenwalt, Sarah[[email protected]]; Dravis, Samantha[[email protected]] Brown, Byron[[email protected]];Wagner, Kenneth[[email protected]] From: Hupp, Sydney Sent: Thur 3/30/2017 5:11:34 PM Subject: FW: FINAL Meeting Agenda and Materials Pruitt Meeting Materials.pd FYI. Sydney Hupp Office of the Administrator- Scheduling 202.816.1659 From: Mary Jo Tomalewski [mailto:[email protected]] Sent: Thursday, March 30, 2017 11:22 AM To: Hupp, Sydney <[email protected]> Cc: Jay Vroom <[email protected]> Subject: FINAL Meeting Agenda and Materials Sydney, We have refined our proposed topics for today's CEO Council meeting with the administrator. Attached, please find: Revised "Final Proposed Agenda Topics," which includes the list of those CEO Council members who will attend our meeting today, and their short bios Introduction / Mission Overview of the CEO Council CEO Council Letter to President Trump, dated February 9, 2017 We assume we can skip a formal "round table of introductions" at the beginning of the meeting as our time is short and we want to maximize time spent talking about issues. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000061-00001 MJ Mary Jo Tomalewski Executive Assistant to the President & CEO CropLife America 1156 15th Street, NW Suite 400 Washington, DC 20005 Direct Dial (202) 872-3849 Main Switchboard (202) 296-1585 Mobile Ex. 6 Personal Privacy Fax (202)466-5832 Email [email protected] Web www.croplifeamerica.org How can I serve you today? Future Meetings 2017 Spring Regulator Conference - April 6-7, Arlington, VA 2017 Annual Meeting - September 22-27, Dana Point, CA 2018 Winter Board of Directors Meeting - March 5-7, Washington, DC 2018 Annual Meeting - September 21-26, The Ritz-Carlton Amelia Island Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000061-00002 FINAL PROPOSED AGENDA TOPICS Meeting Information: Office of EPA Administrator Scott Pruitt 1200 Pennsylvania Avenue, NW Washington, DC Thursday, March 30, 2017 3:45-4:30 PM Topic 1. Thanks to Trump Administration and Administrator Pruitt for early decisive actions: a. WOTUS b. Chlorpyrifos Petition 2. Top Priority Issues a. Ag Advisor Position - We recommend adding additional title of "Assistant Deputy Administrator" as a title b. Water i. Next steps to refine / clarify beyond WOTUS ii. NPDES permits (CAFO Program needs work; legislation to fix water permits NOT needed for lawful use of pesticides) c. Pesticides Policy i. Endangered Species Act conflicts with Pesticide Regulation and Biotech Regulation ii. Epidemiology Study Policy (as aftermath from Chlorpyrifos matter) iii. Reform Certification & Training and Worker Protection Rules - Suspend implementation and revise d. Renewable Fuels Standard - current program kept consistent e. Communication / Messaging / Opinion Polling - vital to all parties' ability to advance sound policy f. EPA and USDA Cooperation and Coordination - Already vast progress; more can be done! g. Environmental Justice, Research & Development, and Children's Health Offices - Better integration with and reform of EPA program offices; sound science h. Regulation of Manufacturing & Mining Facilities for Ag Inputs - Restore science and process i. Public and Science Advisory Panels at EPA - Balance, strategic agendas j. "Air Emissions" from farming operations CEO Attendees American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Corn Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Barb Glenn, CEO, ex-officio Departments of Agriculture Others American Farm Bureau Federation Dale Moore, Deputy Executive Director Corn Refiners Association John Bode, President & CEO National Farmers Union Rob Larew, Senior VP Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00001 Production Agriculture's CEO Council Introduction/Mission Statement: The production agriculture "CEO Council" coordinates alignment on core issues of modern agricultural systems through telling our story, sharing information and leveraging our strengths, while serving as a resource for government decision makers and others interested in USA food, fiber and renewable fuels. Core Focus of Interest Research and innovation Technology access Science and risk-based regulation Sustainability, environment, and weather Marketability, trade, and economic prosperity Government leadership and partnership with private sector Food access and food safety Plant and animal health Ag labor The Council supports principles/themes): Accelerating rural economic growth and improving productivity through innovation and technology Promoting research and innovation that enables development oftools and techniques necessary for discovering new products that hold tremendous potential for farmers and society at large Enabling a regulatory and commercial environment in which agricultural products are marketable, both domestically and internationally Appropriate balance between Federal and State Governments and a cooperative regulatory approach Access to essential labor in balance with an effective Federal immigration policy and adequate worker safety protections Support for all methods of agricultural production Transparency and dialogue with consumers Members of the CEO Council (see reversed) March 30, 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00002 CEO Council Members American Farm Bureau Vincent "Zippy" Duvall, President American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Cattlemen's Beef Association Kendal Frazier, CEO National Chicken Council Michael Brown, President National Com Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Farmers Union Roger Johnson, President National Milk Producers Federation Jim Mulhern, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Departments of Barb Glenn, CEO, ex-officio Agriculture March 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00003 February 9, 2017 The President The White House Washington, D.C. 20500 Dear Mr. President, We, the CEO Council (undersigned herein), representing the production agricultural value chain, including many agricultural producers and farm input developers and suppliers, look forward to working with you and your Administration on matters of importance to American agriculture. The challenges we face in agriculture are significant. Many experts emphasize that producers must grow as much food in the next 50 years as was produced over all previous history to meet the demands of our expanding global population. A firm commitment by the U.S. government to aggressively support agricultural innovation and science-based regulatory decisions will be necessary to ensure farmers have the tools they need to produce a safe and abundant supply of nutritious food, in addition to feed, fuel and fiber, in an environmentally sound and sustainable manner. The policy and regulatory environment your Administration establishes can ensure that agricultural innovation flourishes and American farmers are able to meet the food production goals necessary to feed billions more people. We are ready to provide the White House and the Executive Branch Departments and Agencies, as well as Congress, with policy concepts that foster stability in the U.S. agriculture economy with a strong and predictable farm safety net and promotes American competitiveness through research; marketability and trade of agricultural commodities; rural economic growth; and plant, animal, and environmental health, among many other things. We appreciate your attention to these and other issues of value to American production agriculture and food consumers everywhere. Sincerely, American Farm Bureau Foundation, Zippy Duvall American Seed Trade Association, Andy LaVigne American Soybean Association, Steve Censky Biotechnology Innovation Organization, Dana O'Brien CropLife America, Jay Vroom The Fertilizer Institute, Chris Jahn National Association of Wheat Growers, Chandler Goule National Cattlemen's Beef Association, Kendal Frazier National Corn Growers Association, Chris Novak National Cotton Council, Gary Adams National Council of Farmer Cooperatives, Chuck Conner National Farmers Union, Roger Johnson National Milk Producers Federation, Jim Mulhern National Pork Producers Council, Neil Dierks United Fresh Produce Association, Tom Stenzel USA Rice Federation, Betsy Ward Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00004 National Gotton Council OF MERTOA Gary M. Adams President and Chief Executive Officer National Cotton Council of America Gary Adams assumed the position of President and Chief Executive Officer of the National Cotton Council in February 2015. He plays a key role in guiding the industry's seven segments to reach consensus on critical policies affecting U.S. cotton, with the mission of helping all U.S. cotton industry segments compete effectively and profitably in global markets. Prior to that, Gary served the Council for 13 years as the Vice President of Economic and Policy Analysis. As the Council's chief economist, he provided economic outlooks for global cotton markets, as well as analyzing the impacts of farm and trade policies. Gary also represents the U.S. cotton industry as a member of USDA's Agricultural Policy Advisory Committee. Previously, Gary served on USDA's Advisory Committee on Trade from 2005 through 2011 and the NASS Advisory Committee on Agricultural Statistics from 2003 through 2009. Prior to joining the Council, Gary was a Research Assistant Professor in the Department of Agricultural Economics at the University of Missouri. During his 13-year tenure at the university, Gary's primary responsibilities included policy analysis and market outlook for the Food and Agricultural Policy Research Institute, also known as FAPRI. While at FAPRI, Gary and his colleagues were recognized by the American Agricultural Economics Association for their distinguished policy contributions. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00005 Gary has B.S. and M.A. degrees in Applied Mathematics from the University of Alabama and a Ph.D. in Agricultural Economics from the University of Missouri. Gary and his wife, Ex. 6 Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00006 FASA American Soybean Associatión & Stephen L Censky Chief Executive Officer Stephen L. Censky is the American Soybean Association's (ASA) C hief Executive Officer, a staff position he accepted in April 1996. As ASA's top executive, Ce nsky is in charge of managing ASA's legislative, trade policy, membership and education and training programs. The American Soybean Association is a national, not-for-profit commodity organization with over 22,000 members. ASA works as the domestic and international policy advocate for soybean producer members. Prior to joining ASA, Censky worked in Washington, D.C. for ove a decade. He began his career on Capitol Hill as a legislative assistant for agricultural and transportation matters to Senator Jim Abdnor (R-SD). Later he served in both the Reagan and Bush Administrations at the U.S. Department of Agriculture, helping to craft the 1990 Farm Bill and eventually serving as Administrator of the Foreign Agricultural Service where he was involved in global trade negotiations and running our nation's export programs. Censky received his Bachelor's of Science degree of Agriculture from South Dakota State University and his Master's Diploma in Agriculture St of Melbourne, Australia. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00007 NCFC. National Council of Farmer Cooperatives Charles F. (Chuck) Conner President and CEO National Council of Farmer Cooperatives Charles F. (Chuck) Conner became president & CEO of the National Council of Farmer Cooperatives (NCFC) on January 22, 2009. As president of NCFC, Conner will oversee the organization's work to promote and protect the business and public policy interests of America's farmer-owned cooperatives. He will also provide the strategic vision for the trade association as it continues to seek new ways in which to add value for its membership. Prior to joining NCFC, Conner had served as the Deputy Secretary at the U.S. Department of Agriculture since mid-2005. In this capacity, he was the Chief Operating Officer (COO) overseeing day-to-day operations of the department. Conner interacted directly with President George W. Bush and his senior staff to formulate domestic and international food, trade, security and energy policy. He led development of the Bush Administration's $300 billion Farm Bill proposal and the strategy to educate and inform industry, constituents and Congress. From August 2007 to January 2008, Conner served as both USDA Secretary and Deputy Secretary. He played a key role in developing the Administration's immigration policy including important changes to the H2A program. Conner's experience also includes the assignment of Special Assistant to the President, Executive Office of the President, from October 2001 to May 2005, working on the 2001/2 Farm Bill to develop the strategy behind the transfer of several USDA agency functions to the newly formed Department of Homeland Security. From May 1997 to October 2001 Conner served as President of the Corn Refiners Association. He also served for 17 years as an advisor to U.S. Senator Richard Lugar of Indiana. Conner is a graduate of Purdue University, with a Bachelor's of Science degree and is the recipient of Purdue's Distinguished Alumni Award. He and his wife Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00008 NATIONAL PORK PRODUCERS COUNCIL Neil Dierks, Chief Executive Officer Neil Dierks is Chief Executive Officer of the National Pork Producers Council (NPPC). In this position, he is responsible for the overall implementation of all NPPC programs. Dierks' position requires him to spend time in both Des Moines, Iowa, the national office of NPPC, and Washington, D.C. Beginning in 1990, Dierks served NPPC in a series of senior executive positions, including Executive Director of Operations, Vice President for Research and Education and Senior Vice President for Programs. Prior to his service with NPPC, Dierks was the Special Activities Director for the Iowa Pork Producers Association and Marketing Director for the Iowa Corn Promotion Board. Neil grew up on a livestock farm in eastern lowa and remains involved in a family farming operation. He is a graduate of Iowa State University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00009 NASDA Dr. Barbara Glenn recently joined the National Association of State Departments of Agriculture (NASDA) as CEO on August 18, 2014. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. Dr. Glenn is a scientist with decades of experience as a policy researcher and advocate for agriculture. She previously served as Senior Vice President of Science and Regulatory Affairs for CropLife America, where she was responsible for developing policies and regulations to support agriculture through crop protection. Prior to joining CropLife America, Dr. Glenn served as Managing Director of the Animal Bi otechnology, Food and Agriculture Section of the Biotechnology Industry Association in Washington, DC. Dr. Glenn holds a B.S. in animal science and a Ph.D. in ruminan t nutrition from the University of Kentucky. She previously worked for the U.S. Department of Agriculture, Agric ultural Research Service and the Federation of Animal Science Societies. Born in Lincoln, Nebraska and raised in Centerville, Ohio, Dr. Glenn developed a passion for agriculture from her parents and her involvement in 4-H. She lives Ex. 6 - Personal Privacy and serves on various boards for farm bureau and 4-H. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00010 National Association of Wheat Growers Chandler Goule CEO Chandler Goule assumed his responsibilities as CEO of the National Association of Wheat Growers on July 5, 2016. In addition, he also serves as the executive director of the National Wheat Foundation. Most recently, Goule served as senior vice president of programs at the National Farmers Union (NFU) where he was heavily involved in farm bill legislation. Originally from Texas, Goule holds degrees from Texas A&M and George Washington University and served as a subcommittee staff director for the House Agriculture Committee before moving to the National Farmers Union in 2009 as vice president of government relations. He was appointed senior vice president of NFU programs in 2014. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00011 The Fertilizer Institute Nourish, Replenish, Grow BIOGRAPHY OF CHRISTOPHER JAHN President The Fertilizer Institute and the Nutrients for Life Foundation Christopher L. Jahn is president of The Fertilizer Institute (TFI), the fertilizer industry's national trade association. As TFI president, Jahn works to represent, promote and protect a sound fertilizer industry through legislative and regulatory activities and to promote a favorable public image of the fertilizer industry and agriculture. Jahn also serves as president of the Nutrients for Life Foundation (NFL). Jahn comes to TFI having served as president of the National Association of Chemical Distributors (NACD) since 2006. Prior to leading NACD, Jahn served as president of the Contract Services Association (CSA). Before joining CSA, Jahn had an active role in the United States Senate working for nearly 10 years for U.S. Senator Craig Thomas (R-Wyo.) in a variety of roles, including legislative assistant, legislative director and Chief of Staff. After graduating from Columbia University with a B.A. in Political Science, Jahn co-founded a book distribution business. He also earned an MBA from the University of Maryland. A native of Wyoming, Chris and his wife, Ex. 6 - Personal Privacy Ex. Personal Privacy Capitol View 202.962.0490 425 Third Street, S.W., Suite 950 202.962.0577 fax Washington, DC 20024 www.tfi.org Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00012 National Farmers Union Roger Johnson President Roger Johnson is president of the National Farmers Union (NFU), a grassroots organization that represents more than 200,000 family farmers, ranchers, fisherman and rural communities across the Unites States. Johnson was elected to lead the family farm organization at NFU's 107th anniversary convention in 2009. He has since expanded the education department by providing more programs for beginning, college-aged and women farmers, increased the number of Farmers Union state divisions, and developed a strategic plan for the organization. Johnson has also overseen a number of important policy initiatives important to family farmers including: passage of the 2014 Farm Bill; maintaining a strong Renewable Fuel Standard and Country-of-Origir Labeling, promoting policies that allow farmers to address the growing threat of climate change; and renewing the nation's focus on eliminating an overwhelming trade deficit that results in lost jobs and prosperity for rural America. Prior to leading National Farmers Union, Johnson, a third-generation family farmer from Turtle Lake, N.D., served as North Dakota Agriculture Commissioner, a position he was first elected to in 1996. While Agriculture Commissioner, Johnson served on the State Industrial Commission, the North Dakota Trade Office Advisory Board, and the State Board of Agricultural Research and Education, among many other boards and commissions. From 2007-2008, Johnson served as president of the National Association of State Departments of Agriculture (NASDA). He is a past president of the Midwestern Association of State Departments of Agriculture (MASDA), past president of the Food Export Association of the Midwest and a former chairman of the Interstate Pest Control Compact. Johnson graduated from North Dakota State University with a degree in agricultural economics. Johnson and his wife Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00013 AMERICAN SEED TRADE ASSOCIATION asta first-the - seed R Andrew W. "Andy" LaVigne President & CEO Andrew W. LaVigne is currently the President and CEO of the Ame rican Seed Trade Association. He joined ASTA in February, 2006. Andy has had a 30-year career i n government relations, industry representation, public affairs advocacy, and management. His C ore areas of expertise include agriculture, food policy and international trade. Prior to joining ASTA, Andy was Executive Vice President/CEC of Florida Citrus Mutual, representing citrus growers on issues affecting their business. Prejaiming tFdorida Citrus Mutual, Andy spent four years as Florida Fertilizer and Agrichemical Association's (FFAA) President and Executive Director. FFAA is a non-profit, agricultural trade organization representing companies that specialize in crop protection and plant nutrition products. Before his position at FFAA, Andy spent eight years in Washingt on, D.C. working in the U.S. Congress and the U.S. Department of Agriculture. He served as Legislative Director for Congressman Charles Canady, Agriculture Committee staffer for Congressman Tom Lewis , and on the staff of USDA Secretary Ed Madigan. Andy is a native of Florida with a BA degree in Political Scien ce, with a minor in economics, from the University of Florida. 1701 Duke Street Suite 275 Alexandria, VA 22314 Phone: (703)837-8140 Fax: (703)837-9365 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00014 Biotechnology Innovation Organization Dana O'Brien Executive Vice President, Food & Agriculture Dana O'Brien is Executive Vice President for Food and Agriculture and is responsible for the development of public policy and strategic advocacy, public affairo, and legal strategies that advance industry and stakeholder objectives in the United States. Prior to becoming EVP, Dana served bs BIO Food and Agriculture's chief legislative advocate as Senior Director of Federal Government Relations aince March 2011. Before BIO, Dana worked in Congress for the late Representative lke Skelton (D-MO) managing his legislative team and concentrating on a variety of agricultural, energy, and trade matters. A native of Sedalia, Missouri, and a graduate of Missouri University with a bachelor's degree in psychology, Dana joined the Skelton team immediately out of college and served there for nearly 14 years Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00015 UNITED FRESH is PRODUCE ASSOCIATION Tom Stenzel President and CEO United Fresh Produce Association 1901 Pennsylvania Avenue NW, Suite 1100 Washington, DC 20006 202/303-3400 [email protected] Tom Stenzel is President and CEO of the United Fresh Produce Association, a position he has held since 1993. United Fresh is the pre-eminent trade association for the produce industry in shaping legislative and regulatory policies; providing scientific and technical leadership in food safety and nutrition; and developing educational programs for its members. Founded in 1904, United Fresh represents the interests of companies from small family businesses to the largest international corporations throughout the global fresh produce supply chain. United Fresh is widely known for its work in government affairs, agricultural policy, food safety and nutrition, working to promote political and environmental change to help the next generation of children double their consumption of fresh produce. The United Fresh Start Foundation is committed to increasing children's access to fresh fruits and vegetables, and is a founding partner of the Let's Move Salad Bars to Schools campaign. The campaign has donated salad bars to more than 6,000 schools across the country. Tom is a frequent speaker on industry issues and has been recognized often by the produce industry throughout his career. He was honored as the 2002 Produce Man of the Year by The Packer newspaper, and is the past Chairman of the International Federation for Produce Standards, a global body representing national produce associations around the world. He is a member of the U.S. Chamber of Commerce Committee of 100 leading association executives, the Advisory Board of the International Food Protection Training Institute, and the Key Industry Associations Committee of the American Society of Association Executives, from which he achieved the Certified Association Executive (CAE) designation in 1990. He has served in many government and industry leadership positions, including the first U.S. Department of Agriculture Fruit and Vegetable Industry Advisory Committee, President George W. Bush's Transition Advisory Team for Agriculture, and as an advisor on the U.S. Agricultural Policy Advisory Committee for Trade. Tom was the founding President of the International Food Information Council (IFIC) in 1986, and was previously director of public affairs for the National Soft Drink Association. Tom is a 1977 graduate of the University of Richmond. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00016 as of January 17, 2017 Jay Vroom has served as President and CEO of the trade association known as CropLife America (CLA) since 1989. CLA is the leading U.S. trade group for the crop protection industry in the U.S. Vroom is a founding member of the CropLife Foundation, serving as chairman since its inception in 2001, and now serves as the Foundation's Vice-Chair, since 2015. His sits of the Board of Directors for the Agricultural Retailers Association, Asmark, National Wheat Foundation, the National Association of Manufacturers Council of Manufacturing Associations, and the Soil Health Institute. He is also a member of the Farm Foundation Roundtable Steering Committee, and the North American Climate Smart Ag Alliance Steering Committee. Vroom was a member of the youth organization, Future Farmers of America, and served as an elected state officer in Illinois. Today, he is a member of the FFA Foundation's Individual Giving Council and Board of Trustees. Vroom co-chairs the Coalition for the Advancement of Precision Agriculture and the CEO Council. He is a member of the Friends of the National Arboretum (FONA) FONA Council. He graduated with honors from the College of Agriculture, Consumer and Environmental Sciences at the University of Illinois Urbana-Champaign. Vroom was raised on a grain and livestock farm in north-central Illinois and continues to own the farming operation. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00017 Elizabeth Ward Betsy Ward was appointed President & CEO of the USA Rice Federation in 2007. From 2003- 2005, Ward was the Vice President of International and Domestic Promotion at USA Rice where she was in charge of developing and implementing domestic and international promotion, and food aid programs. From 2005-2007, Ward served as the chief executive for the Hardwood Federation, a trade association representing over 15,000 hardwood producers across the United States. From 1995 to 2003, she ran the Wood Products International Group at the American Forest & Paper Association, directing the wood trade policy and global forestry agenda for the industry. In 2011, Ward was elected Chairman of the U.S. Agricultural Export Development Council (USAEDC) which represents the interests of more than 80 commodity organizations who grow and process a wide variety of U.S. agricultural products. She currently serves as Past Chair. Since 2011, Ward has also served on the Board of Directors of the Sustainable Fisheries Partnership, an independent non-governmental organization (NGO) working to ensure healthy marine and aquatic tecosystems; secure seafood supplies; and a thriving, responsible seafood economy. Ward served for six years as a cleared advisor on the Industry Trade Advisory Committee for forest and paper products (ITAC-7) and was appointed forest products representative to USDA's Agricultural Policy Advisory Committee (APAC) in 2001. Ward holds a Bachelor's degree in History and Political Science from the University of New Hampshire and a Master's degree in International Security Affairs from the School of International Affairs at Columbia University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00018 To: Brown, Byron[[email protected]]; Jackson, Ryan[[email protected]] From: Rebeckah Adcock Sent: Thur 3/30/2017 4:10:52 PM Subject: FW: FINAL CEO Council Meeting Agenda and Materials Pruitt Meeting Materials.pdf ATT00001.htm FYI - final materials for today's meeting. Reb From: "Mary Jo Tomalewski" <[email protected]> To: "Hupp, Sydney" <[email protected]> Cc: "Jay Vroom" <[email protected]> Subject: FINAL Meeting Agenda and Materials Sydney, We have refined our proposed topics for today's CEO Council meeting with the administrator. Attached, please find: Revised "Final Proposed Agenda Topics," which includes the list of those CEO Council members who will attend our meeting today, and their short bios Introduction / Mission Overview of the CEO Council CEO Council Letter to President Trump, dated February 9, 2017 We assume we can skip a formal "round table of introductions" at the beginning of the meeting as our time is short and we want to maximize time spent talking about issues. MJ Mary Jo Tomalewski Executive Assistant to the President & CEO CropLife America Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000063-00001 1156 15th Street, NW Suite 400 Washington, DC 20005 Direct Dial (202) 872-3849 Main Switchboard (202) 296-1585 Mobilé Ex. 6 Personal Privacy Fax (202) 466-5832 Email [email protected] Web www.croplifeamerica.org How can I serve you today? Future Meetings 2017 Spring Regulator Conference - April 6-7, Arlington, VA 2017 Annual Meeting - September 22-27, Dana Point, CA 2018 Winter Board of Directors Meeting - March 5-7, Washington, DC 2018 Annual Meeting - September 21-26, The Ritz-Carlton Amelia Island Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000063-00002 FINAL PROPOSED AGENDA TOPICS Meeting Information: Office of EPA Administrator Scott Pruitt 1200 Pennsylvania Avenue, NW Washington, DC Thursday, March 30, 2017 3:45-4:30 PM Topic 1. Thanks to Trump Administration and Administrator Pruitt for early decisive actions: a. WOTUS b. Chlorpyrifos Petition 2. Top Priority Issues a. Ag Advisor Position - We recommend adding additional title of "Assistant Deputy Administrator" as a title b. Water i. Next steps to refine / clarify beyond WOTUS ii. NPDES permits (CAFO Program needs work; legislation to fix water permits NOT needed for lawful use of pesticides) c. Pesticides Policy i. Endangered Species Act conflicts with Pesticide Regulation and Biotech Regulation ii. Epidemiology Study Policy (as aftermath from Chlorpyrifos matter) iii. Reform Certification & Training and Worker Protection Rules - Suspend implementation and revise d. Renewable Fuels Standard - current program kept consistent e. Communication / Messaging / Opinion Polling - vital to all parties' ability to advance sound policy f. EPA and USDA Cooperation and Coordination - Already vast progress; more can be done! g. Environmental Justice, Research & Development, and Children's Health Offices - Better integration with and reform of EPA program offices; sound science h. Regulation of Manufacturing & Mining Facilities for Ag Inputs - Restore science and process i. Public and Science Advisory Panels at EPA - Balance, strategic agendas j. "Air Emissions" from farming operations CEO Attendees American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Corn Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Barb Glenn, CEO, ex-officio Departments of Agriculture Others American Farm Bureau Federation Dale Moore, Deputy Executive Director Corn Refiners Association John Bode, President & CEO National Farmers Union Rob Larew, Senior VP Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00001 Production Agriculture's CEO Council Introduction/Mission Statement: The production agriculture "CEO Council" coordinates alignment on core issues of modern agricultural systems through telling our story, sharing information and leveraging our strengths, while serving as a resource for government decision makers and others interested in USA food, fiber and renewable fuels. Core Focus of Interest Research and innovation Technology access Science and risk-based regulation Sustainability, environment, and weather Marketability, trade, and economic prosperity Government leadership and partnership with private sector Food access and food safety Plant and animal health Ag labor The Council supports principles/themes): Accelerating rural economic growth and improving productivity through innovation and technology Promoting research and innovation that enables development oftools and techniques necessary for discovering new products that hold tremendous potential for farmers and society at large Enabling a regulatory and commercial environment in which agricultural products are marketable, both domestically and internationally Appropriate balance between Federal and State Governments and a cooperative regulatory approach Access to essential labor in balance with an effective Federal immigration policy and adequate worker safety protections Support for all methods of agricultural production Transparency and dialogue with consumers Members of the CEO Council (see reversed) March 30, 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00002 CEO Council Members American Farm Bureau Vincent "Zippy" Duvall, President American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Cattlemen's Beef Association Kendal Frazier, CEO National Chicken Council Michael Brown, President National Com Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Farmers Union Roger Johnson, President National Milk Producers Federation Jim Mulhern, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Departments of Barb Glenn, CEO, ex-officio Agriculture March 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00003 February 9, 2017 The President The White House Washington, D.C. 20500 Dear Mr. President, We, the CEO Council (undersigned herein), representing the production agricultural value chain, including many agricultural producers and farm input developers and suppliers, look forward to working with you and your Administration on matters of importance to American agriculture. The challenges we face in agriculture are significant. Many experts emphasize that producers must grow as much food in the next 50 years as was produced over all previous history to meet the demands of our expanding global population. A firm commitment by the U.S. government to aggressively support agricultural innovation and science-based regulatory decisions will be necessary to ensure farmers have the tools they need to produce a safe and abundant supply of nutritious food, in addition to feed, fuel and fiber, in an environmentally sound and sustainable manner. The policy and regulatory environment your Administration establishes can ensure that agricultural innovation flourishes and American farmers are able to meet the food production goals necessary to feed billions more people. We are ready to provide the White House and the Executive Branch Departments and Agencies, as well as Congress, with policy concepts that foster stability in the U.S. agriculture economy with a strong and predictable farm safety net and promotes American competitiveness through research; marketability and trade of agricultural commodities; rural economic growth; and plant, animal, and environmental health, among many other things. We appreciate your attention to these and other issues of value to American production agriculture and food consumers everywhere. Sincerely, American Farm Bureau Foundation, Zippy Duvall American Seed Trade Association, Andy LaVigne American Soybean Association, Steve Censky Biotechnology Innovation Organization, Dana O'Brien CropLife America, Jay Vroom The Fertilizer Institute, Chris Jahn National Association of Wheat Growers, Chandler Goule National Cattlemen's Beef Association, Kendal Frazier National Corn Growers Association, Chris Novak National Cotton Council, Gary Adams National Council of Farmer Cooperatives, Chuck Conner National Farmers Union, Roger Johnson National Milk Producers Federation, Jim Mulhern National Pork Producers Council, Neil Dierks United Fresh Produce Association, Tom Stenzel USA Rice Federation, Betsy Ward Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00004 National Gotton Council OF MERTOA Gary M. Adams President and Chief Executive Officer National Cotton Council of America Gary Adams assumed the position of President and Chief Executive Officer of the National Cotton Council in February 2015. He plays a key role in guiding the industry's seven segments to reach consensus on critical policies affecting U.S. cotton, with the mission of helping all U.S. cotton industry segments compete effectively and profitably in global markets. Prior to that, Gary served the Council for 13 years as the Vice President of Economic and Policy Analysis. As the Council's chief economist, he provided economic outlooks for global cotton markets, as well as analyzing the impacts of farm and trade policies. Gary also represents the U.S. cotton industry as a member of USDA's Agricultural Policy Advisory Committee. Previously, Gary served on USDA's Advisory Committee on Trade from 2005 through 2011 and the NASS Advisory Committee on Agricultural Statistics from 2003 through 2009. Prior to joining the Council, Gary was a Research Assistant Professor in the Department of Agricultural Economics at the University of Missouri. During his 13-year tenure at the university, Gary's primary responsibilities included policy analysis and market outlook for the Food and Agricultural Policy Research Institute, also known as FAPRI. While at FAPRI, Gary and his colleagues were recognized by the American Agricultural Economics Association for their distinguished policy contributions. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00005 Gary has B.S. and M.A. degrees in Applied Mathematics from the University of Alabama. and a Ph.D. in Agricultural Economics from the University of Missouri. Gary and his wife, Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00006 FASA American Soybean Associatión & Stephen L Censky Chief Executive Officer Stephen L. Censky is the American Soybean Association's (ASA) C hief Executive Officer, a staff position he accepted in April 1996. As ASA's top executive, Ce nsky is in charge of managing ASA's legislative, trade policy, membership and education and training programs. The American Soybean Association is a national, not-for-profit commodity organization with over 22,000 members. ASA works as the domestic and international policy advocate for soybean producer members. Prior to joining ASA, Censky worked in Washington, D.C. for ove a decade. He began his career on Capitol Hill as a legislative assistant for agricultural and transportation matters to Senator Jim Abdnor (R-SD). Later he served in both the Reagan and Bush Administrations at the U.S. Department of Agriculture, helping to craft the 1990 Farm Bill and eventually serving as Administrator of the Foreign Agricultural Service where he was involved in global trade negotiations and running our nation's export programs. Censky received his Bachelor's of Science degree of Agriculture from South Dakota State University and his Master's Diploma in Agriculture St of Melbourne, Australia. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00007 NCFC. National Council of Farmer Cooperatives Charles F. (Chuck) Conner President and CEO National Council of Farmer Cooperatives Charles F. (Chuck) Conner became president & CEO of the National Council of Farmer Cooperatives (NCFC) on January 22, 2009. As president of NCFC, Conner will oversee the organization's work to promote and protect the business and public policy interests of America's farmer-owned cooperatives. He will also provide the strategic vision for the trade association as it continues to seek new ways in which to add value for its membership. Prior to joining NCFC, Conner had served as the Deputy Secretary at the U.S. Department of Agriculture since mid-2005. In this capacity, he was the Chief Operating Officer (COO) overseeing day-to-day operations of the department. Conner interacted directly with President George W. Bush and his senior staff to formulate domestic and international food, trade, security and energy policy. He led development of the Bush Administration's $300 billion Farm Bill proposal and the strategy to educate and inform industry, constituents and Congress. From August 2007 to January 2008, Conner served as both USDA Secretary and Deputy Secretary. He played a key role in developing the Administration's immigration policy including important changes to the H2A program. Conner's experience also includes the assignment of Special Assistant to the President, Executive Office of the President, from October 2001 to May 2005, working on the 2001/2 Farm Bill to develop the strategy behind the transfer of several USDA agency functions to the newly formed Department of Homeland Security. From May 1997 to October 2001 Conner served as President of the Corn Refiners Association. He also served for 17 years as an advisor to U.S. Senator Richard Lugar of Indiana. Conner is a graduate of Purdue University, with a Bachelor's of Science degree and is the recipient of Purdue's Distinguished Alumni Award. He and his wife Ex. 6 - Personal Privacy Source: :https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00008 NATIONAL PORK PRODUCERS COUNCIL Neil Dierks, Chief Executive Officer Neil Dierks is Chief Executive Officer of the National Pork Producers Council (NPPC). In this position, he is responsible for the overall implementation of all NPPC programs. Dierks' position requires him to spend time in both Des Moines, Iowa, the national office of NPPC, and Washington, D.C. Beginning in 1990, Dierks served NPPC in a series of senior executive positions, including Executive Director of Operations, Vice President for Research and Education and Senior Vice President for Programs. Prior to his service with NPPC, Dierks was the Special Activities Director for the Iowa Pork Producers Association and Marketing Director for the Iowa Corn Promotion Board. Neil grew up on a livestock farm in eastern lowa and remains involved in a family farming operation. He is a graduate of Iowa State University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00009 NASDA Dr. Barbara Glenn recently joined the National Association of State Departments of Agriculture (NASDA) as CEO on August 18, 2014. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. Dr. Glenn is a scientist with decades of experience as a policy researcher and advocate for agriculture. She previously served as Senior Vice President of Science and Regulatory Affairs for CropLife America, where she was responsible for developing policies and regulations to support agriculture through crop protection. Prior to joining CropLife America, Dr. Glenn served as Managing Director of the Animal Bi otechnology, Food and Agriculture Section of the Biotechnology Industry Association in Washington, DC. Dr. Glenn holds a B.S. in animal science and a Ph.D. in ruminan t nutrition from the University of Kentucky. She previously worked for the U.S. Department of Agriculture, Agric ultural Research Service and the Federation of Animal Science Societies. Born in Lincoln, Nebraska and raised in Centerville, Ohio, Dr. Glenn developed a passion for agriculture from her parents and her involvement in 4-H. She lives on a small farm in Maryland with her husband: Ex. 6 - Personal Privacy and serves on various boards for farm bureau and 4-H. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00010

what is an example for risk -based screening prioritization process?

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"ACCs prioritization approach"

endpoints, criteria are similarly available for both acute and chronic classification. The use of one common system allows for appropriate assessment of all substances. GHS classification information is readily available for all substances, as U.S. manufacturers have developed GHS classifications for their products to meet international requirements. ACC's support of the GHS criteria for purposes of this prioritization tool is not a categorical endorsement of the GHS criteria for any other purpose. ACC has been an active participant in the development of GHS and supports the system in principle. The GHS has not been broadly implemented to date in the U.S., although the Occupational Safety and Health Administration (OSHA) has indicated an intent to publish a regulation applying GHS in the workplace. ACC's December 29, 2009, comments on OSHA's proposed rule to modify the existing Hazard Communication Standard (HCS) to reflect the GHS urged that implementation of the GHS adhere to certain principles (e.g., continued application of the "Building Block Approach" of the Purple Book). ACC made specific recommendations concerning details of the Hazard Classification definitions, cut-off values, among others. ACC stands behind those comments. In ACC's view, the use of GHS criteria in a screening-level prioritization of chemicals can materially assist in determining which chemicals receive additional evaluation by the Environmental Protection Agency, but does not necessarily preclude the use of other appropriate, applicable criteria developed under other systems. To classify a chemical in a hazard based priority ranking where there is not direct data on the chemical, EPA can employ the full range of approaches, such as QSAR, SAR, read- across and other modeling tools in which EPA has confidence based on molecular structure. In those situations where there still remains insufficient information on either environmental or human health hazards, the chemical would be classified as "high" for its environmental or health ranking. 1. Environmental Ranking Table 1 provides a summary of how GHS criteria could be logically used for chemical management prioritization. Table 1. Environmental Safety - Hazard Ranking GHS Classification - Ranking Environmental Rank Environmental Score Acute I or Chronic I or Insufficient Information to High 4 Classify Acute II or Chronic II Medium High 3 Acute III or Chronic III/IV or Medium 2 none Not classified Low 1 August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 2. Human Health Ranking Table 2. Human Health - Hazard Ranking Health Rank GHS Classification - Human Health Ranking Score GHS CMR Cat 1a, 1b; OR Repeat Dose </= 10 mg/kg/day (oral); </= 20 mg/kg/day (dermal); </= 50 ppm/6hr/day (gas inhalation); High 4 <<= 0.2 mg/1/6h/day (vapour inhalation); </= 0.02 mg/l/6h/day (dust mist fume inhal). OR insufficient information to classify GHS CMR Cat 2; OR Repeat Dose 10 - 100 mg/kg/day (oral); 20 - 200 mg/kg/day (dermal); Medium High 50 - 250 ppm/6hr/day (gas inhalation); 3 0.2 - 1.0 mg/l/6h/day (vapour inhalation); 0.02 - 0.2 mg/l/6h/day (dust mist fume inhal). Not carcinogen/mutagen/repro/develop;OR Repeat Dose 100 - 1000 mg/kg/day (oral); 200 - 2000 mg/kg/day (dermal); Medium 250 - 1000 ppm/6hr/day (gas inhalation); 2 1.0 - 5.0 mg/l/6h/day (vapour inhalation); 0.2 - 1.0 mg/l/6h/day (dust mist fume inhal). Not carcinogen/mutagen/repro/develop; OR Repeat Dose >1000 mg/kg/day (oral); > 2000 mg/kg/day (dermal); Low > 1000 ppm/6hr/day (gas inhalation); 1 >5.0 mg/l/6h/day (vapour inhalation); > 1.0 mg/l/6h/day (dust mist fume inhal). It is important to note that specific concerns about children's health (specifically potential hazards and adverse effects on the nervous system) and those caused by endocrine disruption mechanisms are addressed in this prioritization process: The GHS CMR "R" classification includes specific evaluation of effects on development in utero and upon growth, maturation and reproduction. ("R" stands for reproductive toxicity and includes adverse effects on sexual function and fertility, as well as developmental toxicity in offspring). Endocrine activity is not a distinct toxicological hazard per se, but rather a measure of a compound's ability to interact with components of the endocrine system. The prioritization process evaluates data and information on relevant apical tests, including tests for reproduction and developmental toxicity (potential endocrine pathways). Thus, even if specific August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 screening for potential endocrine activity has not yet been conducted on certain compounds, hazard identification based on observable outcomes from apical toxicity tests (e.g., outcomes such as pathologic states indicative of disease conditions) covers all modes of action, including endocrine pathways. The toxicity information evaluated (CMR and repeat dose toxicity) is directly relevant to evaluating potential hazards to all individuals, including children. Such data typically includes: 1) identification and definition of possible hazards upon all major organ systems from both acute and repeated exposures, including the nervous system; 2) detection of potential hazards arising from in utero exposures, including possible effects on the nervous system; 3) evaluation of potential of a substance to affect reproduction; and 4) evaluation of the potential of a substance to damage DNA. Integration of Hazard Elements: Each of the environmental and human health classifications is assigned a numeric value based upon its ranking, with 1 being the lowest value and 4 the highest. The greatest ranking (highest hazard potential score) of either Environmental or Human Health is used in a substance- specific priority ranking. The numeric value does not imply relative weighting, but rather a numerical order of priority. B. Exposure Potential Ranking The screening method allows for an initial indication of the extent of exposure potential by considering: 1. The chemical's uses and use pattern(s) 2. Production volume as a first pass indicator of relative emission/release potential since magnitude and route (i.e. air, water, soil) of emissions is not available for all substances. 3. Persistence and bioaccumulation characteristics of the substance. Together the 3 elements are used to rank exposure potential. 1. Use Patterns The proposed approach applies the most current 2006 TSCA Inventory Update Reporting rule (IUR, now called the Chemical Data Reporting rule (CDR) data. To keep the initial prioritization simple and transparent, the approach "bins" different use patterns to align with general exposure potential - intermediates, industrial use, commercial use and consumer use. These patterns are the same as those reported in the IUR and are consistent with REACH exposure categories (intermediates, worker, professional, consumer). Chemicals with consumer product use are likely to have widespread potential for general population exposures and are given high priority ranking within the approach. For the initial prioritization approach, child specific products are captured under general consumer products and all consumer products are weighted equally (see additional discussion below under Second Tier Considerations). Intermediates will have low general population exposures, since these substances are consumed, by definition, within the workplace. Therefore, they are given the lowest priority ranking within the approach. In the context of the proposed approach, the intermediates category includes both intermediates and non-isolated intermediates. A chemical used in multiple use patterns is August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 assigned the priority of the highest use, e.g., a chemical in both industrial and commercial uses would be assigned the commercial Medium-High rank. Table 3. Use Patterns - Exposure Ranking Use Pattern Ranking Use Pattern Score Consumer High 4 Commercial Medium-High 3 Industrial Medium 2 Intermediates Low 1 The IUR Definitions of these terms are (40 CFR 710.3, 710.43): "consumer use" means the use of a chemical substance or a mixture containing a chemical substance (including as part of article) when sold to or made available to consumers for their use. "commercial use" means the use of a chemical substance or a mixture containing a chemical substance (including as part of an article) in a commercial enterprise providing saleable goods or services. "industrial use" means use at a site at which one or more chemical substances or mixtures are manufactured (including imported). "intermediate" means any chemical substance: which is intentionally removed from the equipment in which it is manufactured, and which either is consumed in whole or in part in chemical reaction(s) used for the intentional manufacture of other chemical substance(s) or mixture(s), or is intentionally present for the purpose of altering the rate of such chemical reaction(s) "non-isolated intermediate" means any intermediate that is not intentionally removed from the equipment in which is it manufactured, including the reaction vessel in which it is manufactured, equipment which is ancillary to the reaction vessel, and any equipment through which the substance passes during a continuous flow process, but not including tanks or other vessels in which the substance is stored after its manufacture. 2. Production Volume Recognizing that detailed exposure information will not be available for all substances to be screened, the proposed approach uses production volume as an indicator of exposure, which is widely used in many prioritization schemes. As production volume is just a rough surrogate of emissions, ACC suggests only very broad categories, covering about two orders of magnitude each. It may be useful to consider how additional exposure estimates may be applied in the second tier assessment. Table 4. Production Volume as Emission Surrogate - Exposure Ranking Production Volume as Emission Surrogate Ranking Volume Score >= 100,000,000 lbs national aggregate High 4 1,000,000 lbs to < 100,000,000 lbs national Medium - High 3 aggregate August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 >= 25,000 lbs to < 1,000,000 lbs national Medium 2 aggregate < 25,000 lbs (below IUR site reporting limit) Low 1 3. Persistence and Bioaccumulation Persistence and bioaccumulation are viewed as indicators of exposure, and therefore are considered under the exposure axis of the approach. A persistent substance that is emitted to the environment at the same rate as a non-persistent substance with similar partitioning properties will result in higher exposure to humans and the environment. In fact, multimedia modeling clearly indicates that environmental persistence in the compartment to which a substance partitions is a good indicator of human exposure potential (MacLeod & McKone et al. 2004). Similarly, substances that are not subject to biotransformation by higher organisms will exhibit a high bioaccumulation potential that results in higher exposures via the food chain (Arnot et al. 2010). Therefore, it is recommended to apply the proposed persistence and bioaccumulation criteria in assessment of exposure potential as described below. The persistent and bioaccumulative (P&B) criteria of the proposed approach are targeted toward organic chemicals. Separate assessment criteria are likely needed for P&B evaluation for inorganics/metals, as in the approach taken by Canada's Chemical Management Program (CMP). For assessing persistence, based upon recent expert consensus (Boethling et al., 2009) it is recommended to distinguish persistent from non-persistent chemicals using the following criteria: Volatile chemicals can be defined using a vapor pressure cut-off (i.e., > 1000 Pa) For volatile chemicals, persistent versus non-persistent chemicals are differentiated using a half-life cut-off in air (e.g., a substance is not persistent if air half life is < 2 days). For non-volatile chemicals, non-persistent substances can be defined as substances that are deemed: readily or inherently biodegradable using standard biodegradation tests (OECD 301, 302, 306 test guidelines) or SAR or read across from measured data on a related substance, show an equivalent degree of degradation (i.e. >20% in 28 days) via an abiotic degradation mechanism such as photolysis (OECD 316) or hydrolysi (OECD 111), evaluation of simulation data from transformation in soil, marine water/sediment, brackish water/sediment, surface water/sediment, oceanic water die away (e.g. OECD 308/309) have half lives below 180 days, OR if data are lacking, evaluation via BIOWIN model (EPIWEB 4) Non-volatile substances that are not biodegradable or subject to abiotic losses based on the above criteria would be considered persistent. For assessing bioaccumulation, the key question for screening is the potential for biomagnification based on recent expert consensus (Gobas et al. 2009). To determine if a substance has the potential to biomagnify the following metrics have been agreed: Trophic Magnification Factor (TMF)>1, fish Biomagnification Factor (BMF)>1 fish Bioaccumulation Factor (BAF)/Bioconcentration Factor (BCF) > 5000. These metrics can be August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 derived using lab or field measurements (where available) or recently improved computational models that are included in EPA's EPIWEB model that can be freely downloaded at www.epa.gov/oppt/exposure/pubs/episuite.htm. This approach allows all organics to be addressed and is a scientifically updated version of the approach used in Canada's CMP. Based on the above recommendations, substances can be grouped with regard to persistence and bioaccumulation as follows: Table 5. Persistence and Bioaccumulation - Exposure Ranking Persistence and P&B Ranking P&B Score Bioaccumulation Persistent and High 5 Bioaccumulative Persistent and Not Medium 3 Bioaccumulative OR Not Persistent and Bioaccumulative Not Persistent and Not Low 1 Bioaccumulative Integration of Exposure Elements: As demonstrated in the tables, each factor (use pattern, P&B, and production volume) would be assigned a numeric score based upon its ranking. All 3 factors are added to arrive at an overall value. These values are then separated into categories from low to high exposure potential. A proposed "banding" approach is illustrated in Table 6. Table 6. Integration of Exposure Rankings Combined Score - All 3 Exposure Rank Exposure Ranking elements Score 11 13 High 5 9 10 Medium High 4 7 8 Medium 3 5 6 Medium Low 2 3 4 Low 1 Overall Priority Grouping: In the overall approach, both hazard and exposure elements are considered when placing a substance in a risk-based prioritization ranking. The overall prioritization score for priority grouping and risk evaluation is based on the combined consideration of the hazard and exposure rankings. Priority Groups 7, 8, and 9 are deemed High Priority; Priority Groups 4, 5, and 6 are Medium Priority; and Priority Groups 2 and 3 are Low Priority. August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Review and Comment: It is important that screening be done in an open and transparent way and that the best available information be used. When screening for thousands of chemicals, EPA may not have access to all available information. The process should provide an opportunity for review and comment on initial rankings and an opportunity to submit additional relevant data and information to update proposed rankings with improved information. III. Second Tier Considerations: After the initial screening, some substances within individual priority groupings may require further rank ordering, particularly where a large number of chemicals are in the same priority group. Listed below are the types of information that will be useful to consider in this Second Tier rank ordering: Biomonitoring/Environmental Monitoring Data: Mere detection of chemicals in humans or the environment, i.e., "found in biomonitoring (CDC), found in water (NCOD), and found in air", while providing an indication of exposure, does not provide a useful criterion for exposure potential because almost any industrial or commercial chemical could be detected at trace levels, given increasingly sensitive analytical methods. Therefore, detection alone primarily reflects only the fact that a specific chemical was included in a measurement program. This criterion will also tend to bias the prioritization of chemicals for which well-established analytical methods are available. Consequently, this criterion is not used in the initial prioritization scheme. However, within a particular priority grouping, reliable monitoring information should be considered for Second Tier rank ordering within a quantitative process that assesses if the data is above a level of concern (i.e., places it in a risk context). Use in Children's Products: Protection of childrens' health is a top priority and, in the initial ranking, child-specific products are captured under general consumer products and all consumer products are weighted equally. The specific IUR reporting of information on chemical use in products intended for children would be considered further within a particular priority grouping for Second Tier rank ordering, noting the following points: the IUR definition is based upon use in a child specific product rather than child specific exposure potential¹ (see below). Without knowing a specific product type, it is difficult to understand if 1 IUR definition (Federal Register Volume 75, Number 156, Friday August 30, 2010, p. 49686): Intended for use by children means the chemical substance or mixture is used in or on a product that is specifically intended for use by children age 14 or younger. A chemical substance or mixture is intended for use by children when the submitter answers "yes" to at least on of the following questions for the product into which the submitter's chemical substance or mixture is incorporated: (1) Is the product commonly recognized (i.e., by a reasonable person) as being intended for children age 14 or younger? (2) Does the manufacturer of the product state through product labeling or other written materials that the product is intended for or will be used by children age 14 or younger? (3) Is the advertising, promotion, or marketing of the product aimed at children age 14 or younger? August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 potential child exposure is greater than for a non-child specific product. For example, how does child exposure to a general use cleaner compare to exposure from use in a child's raincoat. In the VCCEP assessments, there are examples for inhalation exposures where estimates of passive child exposure during adult product use exceeded conservative estimates of child exposure during active use of a child-specific product (such as a hobby product) - differences were related to the amount of product used and substance concentration within the product (MEK VCCEP Submission). the IUR definition targets children age 14 and younger. Younger children may be exposed to a variety of non-child specific products that are in general household use. Older children may be exposed to a variety of additional products. the IUR information request is targeted to manufacturers, which may not have direct knowledge of all uses, particularly the presence in products for specific subpopulations, such as children. Therefore, it is not clear that the information requested for the IUR information would be consistently available across all substances being screened. Ideally, this information should be requested from formulators of child-specific products. Therefore, for the initial prioritization approach, which represents a broad, unrefined categorization, child specific products are captured under general consumer products and all consumer products are weighted equally. The IUR information on child specific use would be utilized within a particular priority grouping for Second Tier rank ordering. If the IUR information is utilized, it is important that the limitations above be considered in its application. Emissions Data: Production volume, which is readily available for substances, is used in this proposed approach, but only serves as a surrogate for environmental emissions. For further prioritization, data or estimates of environmental emissions can be used to refine prioritization. Estimates of environmental emissions will be available for some substances (e.g., TRI data). When TRI data are utilized it should be recognized that it addresses only emissions that result from industrial and not wide dispersive uses. In other cases, emissions estimates can be developed as a percentage of production volume based upon consideration of use categories. Within a particular priority grouping, available emissions information can be considered for Second Tier rank ordering, with the understanding that emissions information is not an indicator of actual exposure. Similarly, non-isolated system intermediates, by definition, would have de minimis exposure potential. Therefore, this IUR information could be considered within a particular priority grouping for Second Tier rank ordering. International Risk Management Actions: An initial screening approach for chemical prioritization should be based upon consistent application of specific hazard and exposure science elements that define risk potential. The hazard and exposure elements should be applicable across all substances being evaluated. For initial screening, existence of international risk management action plans should not be a factor that determines priority grouping. Risk management plans may be based upon many factors, including political drivers. It is unclear how factors, their relative weighting, and the rigor of the evaluation may vary across agencies and substances. For initial screening August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 purposes, the same science-based criteria should be used to rank all substances. Consideration of existing international risk management plans could be utilized to check the functioning of the approach and could be considered within a particular priority grouping for Second Tier rank ordering with the possible effect of moving a chemical up in a grouping if actions are being taken internationally. IV. Summary ACC's prioritization approach is an example of a risk-based screening prioritization process that implements the general principles outlined at the outset of this document. It is based upon widely available information that can be utilized to understand the relative priority of chemicals for further evaluation from a risk perspective, i.e., integrating both hazard and exposure elements. Implementation of the screening framework will be most effective when utilizing the best available information. When conducting screening for thousands of chemicals, EPA may not have access to all available information. An open and iterative process that includes an opportunity for review and comment on initial rankings, together with the information that led to the result, and an opportunity to update the ranking with improved information will create a transparent and scientifically sound process. V. References Arnot, J.A., D. Mackay, T. F. Parkerton, R. T. Zaleski, C.S. Warren (2010), Multimedia modeling of human exposure to chemical substances: The roles of food web biomagnification and biotransformation, Environmental Toxicology and Chemistry 29(1):45-55. Boethling, R., K. Fenner, P. Howard, G. Klecka, T. Madsen, J.R. Snape, M.J. Whelan (2009). Environmental persistence of organic pollutants: guidance for development and review of POP risk profiles. Integrated Environmental Assessment and Management 5(4): 539 - 556. Gobas, F.A.P.C, W. de Wolf, L. P Burkhard, E. Verbruggen, K. Plotzke (2009). Revisiting Bioaccumulation Criteria for POPs and PBT Assessments Integrated Environmental Assessment and Management, 5(4):624-637. MacLeod, M., T. E. McKone (2004). Multimedia persistence as an indicator of potential for population-level intake of environmental contaminants, Environmental Toxicology and Chemistry 23(10):2465-2472. van Wijk,D., R. Chénier, T. Henry, M. D Hernando, C. Schulte (2009). Integrated Approach to PBT and POP Prioritization and Risk Assessment' Integrated Environmental Assessment and Management, 5(4):697-711. August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Proposed Prioritization Approach DRAFT May & 2011 Exposure Elements nat commental consumer 20 2 3 a 33 3 not 8 or Persuntence S not 3 mai 35 a & not 3 Pas $ 3 S the iss = the Tormages RUN $ 3 3 SUM - P8 - Tavamage ranow 3 -13 Expesure Ramking $5 Based os Sum (UN# + pa * Townage PRIORITY GROUPING - Hazard * Expasure Ramkings - 1-8 3-10 11-13 mad Jow Hazard - Highter and Human $ 3 3 & $ Human Mazard Not on Dase 3 low mai * anou % 1000 numour 3 1.8 (duet Nume " 3 & 3 8 Not 100 Acure mi os : 3 A 2000 and not data) 280 v 1000 (pas 1.0 8.0 nomour 8.3 miss Nome 3 & % x CMR Cat 2, on Dawe Call 3: 10 - 3 is # 200 50 ase Igas 0.3 1.0 0.0% - 0.2 mis forme * # $ y GMS CMR Can on OHS Clowe Clat % Repeat Close 10 § on 8 on insurticient 20 information to - - - 0.3 wis 0,00 mist on information to $ 3 a $ August 29, 2011 Source: :https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Hazard and Exposure Criteria for Prioritization Approach HAZARD EXPOSURE Environment and Human Health Classifications based upon GHS Use Elements - based upon IUR Intermediate consumed during industrial processing Envirommental: industrial (not intermediate) - used in an industrial setting From GHS classification guidance document: commercial occupational use in nonindustrial setting Table 4.1.2: scheme for substances hazardous so the aquatic environment. consumer general population residential use Clacufication Persistence: Loag-term Votalile substance (VPS 1000 Pax: Not Persistent if air half life <2 days a (Nate 2) Nonvolatile (VP < 1000 Pa): Not Persistent if: Adequate dass Adequnte voriciny dasa aux a) ready biodegradability (OBCD 301) Rapidly 3 b) inherent biodegradability (OBCD 301, 302, 306) degredable 0) read across from measured data on a related substance. 28 (Note. 3) d) equivalent degree of degradation (i.e. >20% in 28 days) via an abjotic Arute 3 Categorys Chronic 1 Categury: 1 Categasy: I degradation mechanism such as photolysis (OBCD 316) or hydrolysis (OBCD NOEC ar ECA 0.1 NOE - EC cass L 1.00 md of maid 111) and/ar BCF a 200 OR, a substance is Not Persistent if: if e) evaluation of simulation data from transformation in soil, marine water/sediment, Caregusy: Acore 2 Category: Chronic 2 Caregury: Chrumin 2 Caregusy: Chruaic 2 brackish water/sediment, surface water/sediment, oceanic water die away (e.g., OECD 3.00 s: s 10.9 0.1 - NOEC er EC. 13 0.00 <: NOEC - EC, 502 3.00 L(EXC) 10.8 and of andies 308/309) have half lives below 180 days. BCF = 500 as if K. 2 4 OR, if data are lacking: Caregusy: Arnie 3 Caregury: 3 Chrinia 3 f) evaluation via BIOWIN model (EPIWEB 4) 01 EC. : 30,00 1- 100 and fack of Bioaccomulation: stapoid andier BOF: Re 300 if absent log x 3 4 A substance is not bioaccumulative if: 4 4) a) measured TMF < 1 (field study) 3) b) measured fish BMF <1 (lab study) Ne tericity and lack of and BCF 2 500 ase, lag E 4, c) measured fish BCF < 5000 (lab study) MOECA 1 mal d) predicted BCP< 5000 using the BCFBAF model included in EPIWIN 4 The above order reflects the preference for use in decision- making NOTE -- P&B CRITERIA ARB FOR ORGANICS Tonnage - based upon JUR reporting ranges <. 25,000 lbs (below IUR site reporting limit) Human Health: 25.000 - <1 MM lbs national aggregate As above, based upon GHS 1MM - <100 MM lbs national aggregate >100 MM lbs national aggregate August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Risk-Based Prioritization Matrix Ancreasing Exposure Two-Step towest Prionies Prioritization Process Incregaling Second Tier Rank Ordering within Priority Groups Biomonitoring / Environmental Monitoring Use in Children's Products Emissions (e.g. TRI) International Risk Management Actions Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226

When was he appointed as senior vice president of NFU programs?

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2014

To: Greenwalt, Sarah[[email protected]]; Dravis, Samantha[[email protected]] Brown, Byron[[email protected]];Wagner, Kenneth[[email protected]] From: Hupp, Sydney Sent: Thur 3/30/2017 5:11:34 PM Subject: FW: FINAL Meeting Agenda and Materials Pruitt Meeting Materials.pd FYI. Sydney Hupp Office of the Administrator- Scheduling 202.816.1659 From: Mary Jo Tomalewski [mailto:[email protected]] Sent: Thursday, March 30, 2017 11:22 AM To: Hupp, Sydney <[email protected]> Cc: Jay Vroom <[email protected]> Subject: FINAL Meeting Agenda and Materials Sydney, We have refined our proposed topics for today's CEO Council meeting with the administrator. Attached, please find: Revised "Final Proposed Agenda Topics," which includes the list of those CEO Council members who will attend our meeting today, and their short bios Introduction / Mission Overview of the CEO Council CEO Council Letter to President Trump, dated February 9, 2017 We assume we can skip a formal "round table of introductions" at the beginning of the meeting as our time is short and we want to maximize time spent talking about issues. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000061-00001 MJ Mary Jo Tomalewski Executive Assistant to the President & CEO CropLife America 1156 15th Street, NW Suite 400 Washington, DC 20005 Direct Dial (202) 872-3849 Main Switchboard (202) 296-1585 Mobile Ex. 6 Personal Privacy Fax (202)466-5832 Email [email protected] Web www.croplifeamerica.org How can I serve you today? Future Meetings 2017 Spring Regulator Conference - April 6-7, Arlington, VA 2017 Annual Meeting - September 22-27, Dana Point, CA 2018 Winter Board of Directors Meeting - March 5-7, Washington, DC 2018 Annual Meeting - September 21-26, The Ritz-Carlton Amelia Island Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000061-00002 FINAL PROPOSED AGENDA TOPICS Meeting Information: Office of EPA Administrator Scott Pruitt 1200 Pennsylvania Avenue, NW Washington, DC Thursday, March 30, 2017 3:45-4:30 PM Topic 1. Thanks to Trump Administration and Administrator Pruitt for early decisive actions: a. WOTUS b. Chlorpyrifos Petition 2. Top Priority Issues a. Ag Advisor Position - We recommend adding additional title of "Assistant Deputy Administrator" as a title b. Water i. Next steps to refine / clarify beyond WOTUS ii. NPDES permits (CAFO Program needs work; legislation to fix water permits NOT needed for lawful use of pesticides) c. Pesticides Policy i. Endangered Species Act conflicts with Pesticide Regulation and Biotech Regulation ii. Epidemiology Study Policy (as aftermath from Chlorpyrifos matter) iii. Reform Certification & Training and Worker Protection Rules - Suspend implementation and revise d. Renewable Fuels Standard - current program kept consistent e. Communication / Messaging / Opinion Polling - vital to all parties' ability to advance sound policy f. EPA and USDA Cooperation and Coordination - Already vast progress; more can be done! g. Environmental Justice, Research & Development, and Children's Health Offices - Better integration with and reform of EPA program offices; sound science h. Regulation of Manufacturing & Mining Facilities for Ag Inputs - Restore science and process i. Public and Science Advisory Panels at EPA - Balance, strategic agendas j. "Air Emissions" from farming operations CEO Attendees American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Corn Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Barb Glenn, CEO, ex-officio Departments of Agriculture Others American Farm Bureau Federation Dale Moore, Deputy Executive Director Corn Refiners Association John Bode, President & CEO National Farmers Union Rob Larew, Senior VP Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00001 Production Agriculture's CEO Council Introduction/Mission Statement: The production agriculture "CEO Council" coordinates alignment on core issues of modern agricultural systems through telling our story, sharing information and leveraging our strengths, while serving as a resource for government decision makers and others interested in USA food, fiber and renewable fuels. Core Focus of Interest Research and innovation Technology access Science and risk-based regulation Sustainability, environment, and weather Marketability, trade, and economic prosperity Government leadership and partnership with private sector Food access and food safety Plant and animal health Ag labor The Council supports principles/themes): Accelerating rural economic growth and improving productivity through innovation and technology Promoting research and innovation that enables development oftools and techniques necessary for discovering new products that hold tremendous potential for farmers and society at large Enabling a regulatory and commercial environment in which agricultural products are marketable, both domestically and internationally Appropriate balance between Federal and State Governments and a cooperative regulatory approach Access to essential labor in balance with an effective Federal immigration policy and adequate worker safety protections Support for all methods of agricultural production Transparency and dialogue with consumers Members of the CEO Council (see reversed) March 30, 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00002 CEO Council Members American Farm Bureau Vincent "Zippy" Duvall, President American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Cattlemen's Beef Association Kendal Frazier, CEO National Chicken Council Michael Brown, President National Com Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Farmers Union Roger Johnson, President National Milk Producers Federation Jim Mulhern, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Departments of Barb Glenn, CEO, ex-officio Agriculture March 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00003 February 9, 2017 The President The White House Washington, D.C. 20500 Dear Mr. President, We, the CEO Council (undersigned herein), representing the production agricultural value chain, including many agricultural producers and farm input developers and suppliers, look forward to working with you and your Administration on matters of importance to American agriculture. The challenges we face in agriculture are significant. Many experts emphasize that producers must grow as much food in the next 50 years as was produced over all previous history to meet the demands of our expanding global population. A firm commitment by the U.S. government to aggressively support agricultural innovation and science-based regulatory decisions will be necessary to ensure farmers have the tools they need to produce a safe and abundant supply of nutritious food, in addition to feed, fuel and fiber, in an environmentally sound and sustainable manner. The policy and regulatory environment your Administration establishes can ensure that agricultural innovation flourishes and American farmers are able to meet the food production goals necessary to feed billions more people. We are ready to provide the White House and the Executive Branch Departments and Agencies, as well as Congress, with policy concepts that foster stability in the U.S. agriculture economy with a strong and predictable farm safety net and promotes American competitiveness through research; marketability and trade of agricultural commodities; rural economic growth; and plant, animal, and environmental health, among many other things. We appreciate your attention to these and other issues of value to American production agriculture and food consumers everywhere. Sincerely, American Farm Bureau Foundation, Zippy Duvall American Seed Trade Association, Andy LaVigne American Soybean Association, Steve Censky Biotechnology Innovation Organization, Dana O'Brien CropLife America, Jay Vroom The Fertilizer Institute, Chris Jahn National Association of Wheat Growers, Chandler Goule National Cattlemen's Beef Association, Kendal Frazier National Corn Growers Association, Chris Novak National Cotton Council, Gary Adams National Council of Farmer Cooperatives, Chuck Conner National Farmers Union, Roger Johnson National Milk Producers Federation, Jim Mulhern National Pork Producers Council, Neil Dierks United Fresh Produce Association, Tom Stenzel USA Rice Federation, Betsy Ward Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00004 National Gotton Council OF MERTOA Gary M. Adams President and Chief Executive Officer National Cotton Council of America Gary Adams assumed the position of President and Chief Executive Officer of the National Cotton Council in February 2015. He plays a key role in guiding the industry's seven segments to reach consensus on critical policies affecting U.S. cotton, with the mission of helping all U.S. cotton industry segments compete effectively and profitably in global markets. Prior to that, Gary served the Council for 13 years as the Vice President of Economic and Policy Analysis. As the Council's chief economist, he provided economic outlooks for global cotton markets, as well as analyzing the impacts of farm and trade policies. Gary also represents the U.S. cotton industry as a member of USDA's Agricultural Policy Advisory Committee. Previously, Gary served on USDA's Advisory Committee on Trade from 2005 through 2011 and the NASS Advisory Committee on Agricultural Statistics from 2003 through 2009. Prior to joining the Council, Gary was a Research Assistant Professor in the Department of Agricultural Economics at the University of Missouri. During his 13-year tenure at the university, Gary's primary responsibilities included policy analysis and market outlook for the Food and Agricultural Policy Research Institute, also known as FAPRI. While at FAPRI, Gary and his colleagues were recognized by the American Agricultural Economics Association for their distinguished policy contributions. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00005 Gary has B.S. and M.A. degrees in Applied Mathematics from the University of Alabama and a Ph.D. in Agricultural Economics from the University of Missouri. Gary and his wife, Ex. 6 Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00006 FASA American Soybean Associatión & Stephen L Censky Chief Executive Officer Stephen L. Censky is the American Soybean Association's (ASA) C hief Executive Officer, a staff position he accepted in April 1996. As ASA's top executive, Ce nsky is in charge of managing ASA's legislative, trade policy, membership and education and training programs. The American Soybean Association is a national, not-for-profit commodity organization with over 22,000 members. ASA works as the domestic and international policy advocate for soybean producer members. Prior to joining ASA, Censky worked in Washington, D.C. for ove a decade. He began his career on Capitol Hill as a legislative assistant for agricultural and transportation matters to Senator Jim Abdnor (R-SD). Later he served in both the Reagan and Bush Administrations at the U.S. Department of Agriculture, helping to craft the 1990 Farm Bill and eventually serving as Administrator of the Foreign Agricultural Service where he was involved in global trade negotiations and running our nation's export programs. Censky received his Bachelor's of Science degree of Agriculture from South Dakota State University and his Master's Diploma in Agriculture St of Melbourne, Australia. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00007 NCFC. National Council of Farmer Cooperatives Charles F. (Chuck) Conner President and CEO National Council of Farmer Cooperatives Charles F. (Chuck) Conner became president & CEO of the National Council of Farmer Cooperatives (NCFC) on January 22, 2009. As president of NCFC, Conner will oversee the organization's work to promote and protect the business and public policy interests of America's farmer-owned cooperatives. He will also provide the strategic vision for the trade association as it continues to seek new ways in which to add value for its membership. Prior to joining NCFC, Conner had served as the Deputy Secretary at the U.S. Department of Agriculture since mid-2005. In this capacity, he was the Chief Operating Officer (COO) overseeing day-to-day operations of the department. Conner interacted directly with President George W. Bush and his senior staff to formulate domestic and international food, trade, security and energy policy. He led development of the Bush Administration's $300 billion Farm Bill proposal and the strategy to educate and inform industry, constituents and Congress. From August 2007 to January 2008, Conner served as both USDA Secretary and Deputy Secretary. He played a key role in developing the Administration's immigration policy including important changes to the H2A program. Conner's experience also includes the assignment of Special Assistant to the President, Executive Office of the President, from October 2001 to May 2005, working on the 2001/2 Farm Bill to develop the strategy behind the transfer of several USDA agency functions to the newly formed Department of Homeland Security. From May 1997 to October 2001 Conner served as President of the Corn Refiners Association. He also served for 17 years as an advisor to U.S. Senator Richard Lugar of Indiana. Conner is a graduate of Purdue University, with a Bachelor's of Science degree and is the recipient of Purdue's Distinguished Alumni Award. He and his wife Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00008 NATIONAL PORK PRODUCERS COUNCIL Neil Dierks, Chief Executive Officer Neil Dierks is Chief Executive Officer of the National Pork Producers Council (NPPC). In this position, he is responsible for the overall implementation of all NPPC programs. Dierks' position requires him to spend time in both Des Moines, Iowa, the national office of NPPC, and Washington, D.C. Beginning in 1990, Dierks served NPPC in a series of senior executive positions, including Executive Director of Operations, Vice President for Research and Education and Senior Vice President for Programs. Prior to his service with NPPC, Dierks was the Special Activities Director for the Iowa Pork Producers Association and Marketing Director for the Iowa Corn Promotion Board. Neil grew up on a livestock farm in eastern lowa and remains involved in a family farming operation. He is a graduate of Iowa State University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00009 NASDA Dr. Barbara Glenn recently joined the National Association of State Departments of Agriculture (NASDA) as CEO on August 18, 2014. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. Dr. Glenn is a scientist with decades of experience as a policy researcher and advocate for agriculture. She previously served as Senior Vice President of Science and Regulatory Affairs for CropLife America, where she was responsible for developing policies and regulations to support agriculture through crop protection. Prior to joining CropLife America, Dr. Glenn served as Managing Director of the Animal Bi otechnology, Food and Agriculture Section of the Biotechnology Industry Association in Washington, DC. Dr. Glenn holds a B.S. in animal science and a Ph.D. in ruminan t nutrition from the University of Kentucky. She previously worked for the U.S. Department of Agriculture, Agric ultural Research Service and the Federation of Animal Science Societies. Born in Lincoln, Nebraska and raised in Centerville, Ohio, Dr. Glenn developed a passion for agriculture from her parents and her involvement in 4-H. She lives Ex. 6 - Personal Privacy and serves on various boards for farm bureau and 4-H. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00010 National Association of Wheat Growers Chandler Goule CEO Chandler Goule assumed his responsibilities as CEO of the National Association of Wheat Growers on July 5, 2016. In addition, he also serves as the executive director of the National Wheat Foundation. Most recently, Goule served as senior vice president of programs at the National Farmers Union (NFU) where he was heavily involved in farm bill legislation. Originally from Texas, Goule holds degrees from Texas A&M and George Washington University and served as a subcommittee staff director for the House Agriculture Committee before moving to the National Farmers Union in 2009 as vice president of government relations. He was appointed senior vice president of NFU programs in 2014. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00011 The Fertilizer Institute Nourish, Replenish, Grow BIOGRAPHY OF CHRISTOPHER JAHN President The Fertilizer Institute and the Nutrients for Life Foundation Christopher L. Jahn is president of The Fertilizer Institute (TFI), the fertilizer industry's national trade association. As TFI president, Jahn works to represent, promote and protect a sound fertilizer industry through legislative and regulatory activities and to promote a favorable public image of the fertilizer industry and agriculture. Jahn also serves as president of the Nutrients for Life Foundation (NFL). Jahn comes to TFI having served as president of the National Association of Chemical Distributors (NACD) since 2006. Prior to leading NACD, Jahn served as president of the Contract Services Association (CSA). Before joining CSA, Jahn had an active role in the United States Senate working for nearly 10 years for U.S. Senator Craig Thomas (R-Wyo.) in a variety of roles, including legislative assistant, legislative director and Chief of Staff. After graduating from Columbia University with a B.A. in Political Science, Jahn co-founded a book distribution business. He also earned an MBA from the University of Maryland. A native of Wyoming, Chris and his wife, Ex. 6 - Personal Privacy Ex. Personal Privacy Capitol View 202.962.0490 425 Third Street, S.W., Suite 950 202.962.0577 fax Washington, DC 20024 www.tfi.org Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00012 National Farmers Union Roger Johnson President Roger Johnson is president of the National Farmers Union (NFU), a grassroots organization that represents more than 200,000 family farmers, ranchers, fisherman and rural communities across the Unites States. Johnson was elected to lead the family farm organization at NFU's 107th anniversary convention in 2009. He has since expanded the education department by providing more programs for beginning, college-aged and women farmers, increased the number of Farmers Union state divisions, and developed a strategic plan for the organization. Johnson has also overseen a number of important policy initiatives important to family farmers including: passage of the 2014 Farm Bill; maintaining a strong Renewable Fuel Standard and Country-of-Origir Labeling, promoting policies that allow farmers to address the growing threat of climate change; and renewing the nation's focus on eliminating an overwhelming trade deficit that results in lost jobs and prosperity for rural America. Prior to leading National Farmers Union, Johnson, a third-generation family farmer from Turtle Lake, N.D., served as North Dakota Agriculture Commissioner, a position he was first elected to in 1996. While Agriculture Commissioner, Johnson served on the State Industrial Commission, the North Dakota Trade Office Advisory Board, and the State Board of Agricultural Research and Education, among many other boards and commissions. From 2007-2008, Johnson served as president of the National Association of State Departments of Agriculture (NASDA). He is a past president of the Midwestern Association of State Departments of Agriculture (MASDA), past president of the Food Export Association of the Midwest and a former chairman of the Interstate Pest Control Compact. Johnson graduated from North Dakota State University with a degree in agricultural economics. Johnson and his wife Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00013 AMERICAN SEED TRADE ASSOCIATION asta first-the - seed R Andrew W. "Andy" LaVigne President & CEO Andrew W. LaVigne is currently the President and CEO of the Ame rican Seed Trade Association. He joined ASTA in February, 2006. Andy has had a 30-year career i n government relations, industry representation, public affairs advocacy, and management. His C ore areas of expertise include agriculture, food policy and international trade. Prior to joining ASTA, Andy was Executive Vice President/CEC of Florida Citrus Mutual, representing citrus growers on issues affecting their business. Prejaiming tFdorida Citrus Mutual, Andy spent four years as Florida Fertilizer and Agrichemical Association's (FFAA) President and Executive Director. FFAA is a non-profit, agricultural trade organization representing companies that specialize in crop protection and plant nutrition products. Before his position at FFAA, Andy spent eight years in Washingt on, D.C. working in the U.S. Congress and the U.S. Department of Agriculture. He served as Legislative Director for Congressman Charles Canady, Agriculture Committee staffer for Congressman Tom Lewis , and on the staff of USDA Secretary Ed Madigan. Andy is a native of Florida with a BA degree in Political Scien ce, with a minor in economics, from the University of Florida. 1701 Duke Street Suite 275 Alexandria, VA 22314 Phone: (703)837-8140 Fax: (703)837-9365 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00014 Biotechnology Innovation Organization Dana O'Brien Executive Vice President, Food & Agriculture Dana O'Brien is Executive Vice President for Food and Agriculture and is responsible for the development of public policy and strategic advocacy, public affairo, and legal strategies that advance industry and stakeholder objectives in the United States. Prior to becoming EVP, Dana served bs BIO Food and Agriculture's chief legislative advocate as Senior Director of Federal Government Relations aince March 2011. Before BIO, Dana worked in Congress for the late Representative lke Skelton (D-MO) managing his legislative team and concentrating on a variety of agricultural, energy, and trade matters. A native of Sedalia, Missouri, and a graduate of Missouri University with a bachelor's degree in psychology, Dana joined the Skelton team immediately out of college and served there for nearly 14 years Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00015 UNITED FRESH is PRODUCE ASSOCIATION Tom Stenzel President and CEO United Fresh Produce Association 1901 Pennsylvania Avenue NW, Suite 1100 Washington, DC 20006 202/303-3400 [email protected] Tom Stenzel is President and CEO of the United Fresh Produce Association, a position he has held since 1993. United Fresh is the pre-eminent trade association for the produce industry in shaping legislative and regulatory policies; providing scientific and technical leadership in food safety and nutrition; and developing educational programs for its members. Founded in 1904, United Fresh represents the interests of companies from small family businesses to the largest international corporations throughout the global fresh produce supply chain. United Fresh is widely known for its work in government affairs, agricultural policy, food safety and nutrition, working to promote political and environmental change to help the next generation of children double their consumption of fresh produce. The United Fresh Start Foundation is committed to increasing children's access to fresh fruits and vegetables, and is a founding partner of the Let's Move Salad Bars to Schools campaign. The campaign has donated salad bars to more than 6,000 schools across the country. Tom is a frequent speaker on industry issues and has been recognized often by the produce industry throughout his career. He was honored as the 2002 Produce Man of the Year by The Packer newspaper, and is the past Chairman of the International Federation for Produce Standards, a global body representing national produce associations around the world. He is a member of the U.S. Chamber of Commerce Committee of 100 leading association executives, the Advisory Board of the International Food Protection Training Institute, and the Key Industry Associations Committee of the American Society of Association Executives, from which he achieved the Certified Association Executive (CAE) designation in 1990. He has served in many government and industry leadership positions, including the first U.S. Department of Agriculture Fruit and Vegetable Industry Advisory Committee, President George W. Bush's Transition Advisory Team for Agriculture, and as an advisor on the U.S. Agricultural Policy Advisory Committee for Trade. Tom was the founding President of the International Food Information Council (IFIC) in 1986, and was previously director of public affairs for the National Soft Drink Association. Tom is a 1977 graduate of the University of Richmond. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00016 as of January 17, 2017 Jay Vroom has served as President and CEO of the trade association known as CropLife America (CLA) since 1989. CLA is the leading U.S. trade group for the crop protection industry in the U.S. Vroom is a founding member of the CropLife Foundation, serving as chairman since its inception in 2001, and now serves as the Foundation's Vice-Chair, since 2015. His sits of the Board of Directors for the Agricultural Retailers Association, Asmark, National Wheat Foundation, the National Association of Manufacturers Council of Manufacturing Associations, and the Soil Health Institute. He is also a member of the Farm Foundation Roundtable Steering Committee, and the North American Climate Smart Ag Alliance Steering Committee. Vroom was a member of the youth organization, Future Farmers of America, and served as an elected state officer in Illinois. Today, he is a member of the FFA Foundation's Individual Giving Council and Board of Trustees. Vroom co-chairs the Coalition for the Advancement of Precision Agriculture and the CEO Council. He is a member of the Friends of the National Arboretum (FONA) FONA Council. He graduated with honors from the College of Agriculture, Consumer and Environmental Sciences at the University of Illinois Urbana-Champaign. Vroom was raised on a grain and livestock farm in north-central Illinois and continues to own the farming operation. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00017 Elizabeth Ward Betsy Ward was appointed President & CEO of the USA Rice Federation in 2007. From 2003- 2005, Ward was the Vice President of International and Domestic Promotion at USA Rice where she was in charge of developing and implementing domestic and international promotion, and food aid programs. From 2005-2007, Ward served as the chief executive for the Hardwood Federation, a trade association representing over 15,000 hardwood producers across the United States. From 1995 to 2003, she ran the Wood Products International Group at the American Forest & Paper Association, directing the wood trade policy and global forestry agenda for the industry. In 2011, Ward was elected Chairman of the U.S. Agricultural Export Development Council (USAEDC) which represents the interests of more than 80 commodity organizations who grow and process a wide variety of U.S. agricultural products. She currently serves as Past Chair. Since 2011, Ward has also served on the Board of Directors of the Sustainable Fisheries Partnership, an independent non-governmental organization (NGO) working to ensure healthy marine and aquatic tecosystems; secure seafood supplies; and a thriving, responsible seafood economy. Ward served for six years as a cleared advisor on the Industry Trade Advisory Committee for forest and paper products (ITAC-7) and was appointed forest products representative to USDA's Agricultural Policy Advisory Committee (APAC) in 2001. Ward holds a Bachelor's degree in History and Political Science from the University of New Hampshire and a Master's degree in International Security Affairs from the School of International Affairs at Columbia University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00018 To: Brown, Byron[[email protected]]; Jackson, Ryan[[email protected]] From: Rebeckah Adcock Sent: Thur 3/30/2017 4:10:52 PM Subject: FW: FINAL CEO Council Meeting Agenda and Materials Pruitt Meeting Materials.pdf ATT00001.htm FYI - final materials for today's meeting. Reb From: "Mary Jo Tomalewski" <[email protected]> To: "Hupp, Sydney" <[email protected]> Cc: "Jay Vroom" <[email protected]> Subject: FINAL Meeting Agenda and Materials Sydney, We have refined our proposed topics for today's CEO Council meeting with the administrator. Attached, please find: Revised "Final Proposed Agenda Topics," which includes the list of those CEO Council members who will attend our meeting today, and their short bios Introduction / Mission Overview of the CEO Council CEO Council Letter to President Trump, dated February 9, 2017 We assume we can skip a formal "round table of introductions" at the beginning of the meeting as our time is short and we want to maximize time spent talking about issues. MJ Mary Jo Tomalewski Executive Assistant to the President & CEO CropLife America Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000063-00001 1156 15th Street, NW Suite 400 Washington, DC 20005 Direct Dial (202) 872-3849 Main Switchboard (202) 296-1585 Mobilé Ex. 6 Personal Privacy Fax (202) 466-5832 Email [email protected] Web www.croplifeamerica.org How can I serve you today? Future Meetings 2017 Spring Regulator Conference - April 6-7, Arlington, VA 2017 Annual Meeting - September 22-27, Dana Point, CA 2018 Winter Board of Directors Meeting - March 5-7, Washington, DC 2018 Annual Meeting - September 21-26, The Ritz-Carlton Amelia Island Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000063-00002 FINAL PROPOSED AGENDA TOPICS Meeting Information: Office of EPA Administrator Scott Pruitt 1200 Pennsylvania Avenue, NW Washington, DC Thursday, March 30, 2017 3:45-4:30 PM Topic 1. Thanks to Trump Administration and Administrator Pruitt for early decisive actions: a. WOTUS b. Chlorpyrifos Petition 2. Top Priority Issues a. Ag Advisor Position - We recommend adding additional title of "Assistant Deputy Administrator" as a title b. Water i. Next steps to refine / clarify beyond WOTUS ii. NPDES permits (CAFO Program needs work; legislation to fix water permits NOT needed for lawful use of pesticides) c. Pesticides Policy i. Endangered Species Act conflicts with Pesticide Regulation and Biotech Regulation ii. Epidemiology Study Policy (as aftermath from Chlorpyrifos matter) iii. Reform Certification & Training and Worker Protection Rules - Suspend implementation and revise d. Renewable Fuels Standard - current program kept consistent e. Communication / Messaging / Opinion Polling - vital to all parties' ability to advance sound policy f. EPA and USDA Cooperation and Coordination - Already vast progress; more can be done! g. Environmental Justice, Research & Development, and Children's Health Offices - Better integration with and reform of EPA program offices; sound science h. Regulation of Manufacturing & Mining Facilities for Ag Inputs - Restore science and process i. Public and Science Advisory Panels at EPA - Balance, strategic agendas j. "Air Emissions" from farming operations CEO Attendees American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Corn Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Barb Glenn, CEO, ex-officio Departments of Agriculture Others American Farm Bureau Federation Dale Moore, Deputy Executive Director Corn Refiners Association John Bode, President & CEO National Farmers Union Rob Larew, Senior VP Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00001 Production Agriculture's CEO Council Introduction/Mission Statement: The production agriculture "CEO Council" coordinates alignment on core issues of modern agricultural systems through telling our story, sharing information and leveraging our strengths, while serving as a resource for government decision makers and others interested in USA food, fiber and renewable fuels. Core Focus of Interest Research and innovation Technology access Science and risk-based regulation Sustainability, environment, and weather Marketability, trade, and economic prosperity Government leadership and partnership with private sector Food access and food safety Plant and animal health Ag labor The Council supports principles/themes): Accelerating rural economic growth and improving productivity through innovation and technology Promoting research and innovation that enables development oftools and techniques necessary for discovering new products that hold tremendous potential for farmers and society at large Enabling a regulatory and commercial environment in which agricultural products are marketable, both domestically and internationally Appropriate balance between Federal and State Governments and a cooperative regulatory approach Access to essential labor in balance with an effective Federal immigration policy and adequate worker safety protections Support for all methods of agricultural production Transparency and dialogue with consumers Members of the CEO Council (see reversed) March 30, 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00002 CEO Council Members American Farm Bureau Vincent "Zippy" Duvall, President American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Cattlemen's Beef Association Kendal Frazier, CEO National Chicken Council Michael Brown, President National Com Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Farmers Union Roger Johnson, President National Milk Producers Federation Jim Mulhern, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Departments of Barb Glenn, CEO, ex-officio Agriculture March 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00003 February 9, 2017 The President The White House Washington, D.C. 20500 Dear Mr. President, We, the CEO Council (undersigned herein), representing the production agricultural value chain, including many agricultural producers and farm input developers and suppliers, look forward to working with you and your Administration on matters of importance to American agriculture. The challenges we face in agriculture are significant. Many experts emphasize that producers must grow as much food in the next 50 years as was produced over all previous history to meet the demands of our expanding global population. A firm commitment by the U.S. government to aggressively support agricultural innovation and science-based regulatory decisions will be necessary to ensure farmers have the tools they need to produce a safe and abundant supply of nutritious food, in addition to feed, fuel and fiber, in an environmentally sound and sustainable manner. The policy and regulatory environment your Administration establishes can ensure that agricultural innovation flourishes and American farmers are able to meet the food production goals necessary to feed billions more people. We are ready to provide the White House and the Executive Branch Departments and Agencies, as well as Congress, with policy concepts that foster stability in the U.S. agriculture economy with a strong and predictable farm safety net and promotes American competitiveness through research; marketability and trade of agricultural commodities; rural economic growth; and plant, animal, and environmental health, among many other things. We appreciate your attention to these and other issues of value to American production agriculture and food consumers everywhere. Sincerely, American Farm Bureau Foundation, Zippy Duvall American Seed Trade Association, Andy LaVigne American Soybean Association, Steve Censky Biotechnology Innovation Organization, Dana O'Brien CropLife America, Jay Vroom The Fertilizer Institute, Chris Jahn National Association of Wheat Growers, Chandler Goule National Cattlemen's Beef Association, Kendal Frazier National Corn Growers Association, Chris Novak National Cotton Council, Gary Adams National Council of Farmer Cooperatives, Chuck Conner National Farmers Union, Roger Johnson National Milk Producers Federation, Jim Mulhern National Pork Producers Council, Neil Dierks United Fresh Produce Association, Tom Stenzel USA Rice Federation, Betsy Ward Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00004 National Gotton Council OF MERTOA Gary M. Adams President and Chief Executive Officer National Cotton Council of America Gary Adams assumed the position of President and Chief Executive Officer of the National Cotton Council in February 2015. He plays a key role in guiding the industry's seven segments to reach consensus on critical policies affecting U.S. cotton, with the mission of helping all U.S. cotton industry segments compete effectively and profitably in global markets. Prior to that, Gary served the Council for 13 years as the Vice President of Economic and Policy Analysis. As the Council's chief economist, he provided economic outlooks for global cotton markets, as well as analyzing the impacts of farm and trade policies. Gary also represents the U.S. cotton industry as a member of USDA's Agricultural Policy Advisory Committee. Previously, Gary served on USDA's Advisory Committee on Trade from 2005 through 2011 and the NASS Advisory Committee on Agricultural Statistics from 2003 through 2009. Prior to joining the Council, Gary was a Research Assistant Professor in the Department of Agricultural Economics at the University of Missouri. During his 13-year tenure at the university, Gary's primary responsibilities included policy analysis and market outlook for the Food and Agricultural Policy Research Institute, also known as FAPRI. While at FAPRI, Gary and his colleagues were recognized by the American Agricultural Economics Association for their distinguished policy contributions. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00005 Gary has B.S. and M.A. degrees in Applied Mathematics from the University of Alabama. and a Ph.D. in Agricultural Economics from the University of Missouri. Gary and his wife, Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00006 FASA American Soybean Associatión & Stephen L Censky Chief Executive Officer Stephen L. Censky is the American Soybean Association's (ASA) C hief Executive Officer, a staff position he accepted in April 1996. As ASA's top executive, Ce nsky is in charge of managing ASA's legislative, trade policy, membership and education and training programs. The American Soybean Association is a national, not-for-profit commodity organization with over 22,000 members. ASA works as the domestic and international policy advocate for soybean producer members. Prior to joining ASA, Censky worked in Washington, D.C. for ove a decade. He began his career on Capitol Hill as a legislative assistant for agricultural and transportation matters to Senator Jim Abdnor (R-SD). Later he served in both the Reagan and Bush Administrations at the U.S. Department of Agriculture, helping to craft the 1990 Farm Bill and eventually serving as Administrator of the Foreign Agricultural Service where he was involved in global trade negotiations and running our nation's export programs. Censky received his Bachelor's of Science degree of Agriculture from South Dakota State University and his Master's Diploma in Agriculture St of Melbourne, Australia. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00007 NCFC. National Council of Farmer Cooperatives Charles F. (Chuck) Conner President and CEO National Council of Farmer Cooperatives Charles F. (Chuck) Conner became president & CEO of the National Council of Farmer Cooperatives (NCFC) on January 22, 2009. As president of NCFC, Conner will oversee the organization's work to promote and protect the business and public policy interests of America's farmer-owned cooperatives. He will also provide the strategic vision for the trade association as it continues to seek new ways in which to add value for its membership. Prior to joining NCFC, Conner had served as the Deputy Secretary at the U.S. Department of Agriculture since mid-2005. In this capacity, he was the Chief Operating Officer (COO) overseeing day-to-day operations of the department. Conner interacted directly with President George W. Bush and his senior staff to formulate domestic and international food, trade, security and energy policy. He led development of the Bush Administration's $300 billion Farm Bill proposal and the strategy to educate and inform industry, constituents and Congress. From August 2007 to January 2008, Conner served as both USDA Secretary and Deputy Secretary. He played a key role in developing the Administration's immigration policy including important changes to the H2A program. Conner's experience also includes the assignment of Special Assistant to the President, Executive Office of the President, from October 2001 to May 2005, working on the 2001/2 Farm Bill to develop the strategy behind the transfer of several USDA agency functions to the newly formed Department of Homeland Security. From May 1997 to October 2001 Conner served as President of the Corn Refiners Association. He also served for 17 years as an advisor to U.S. Senator Richard Lugar of Indiana. Conner is a graduate of Purdue University, with a Bachelor's of Science degree and is the recipient of Purdue's Distinguished Alumni Award. He and his wife Ex. 6 - Personal Privacy Source: :https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00008 NATIONAL PORK PRODUCERS COUNCIL Neil Dierks, Chief Executive Officer Neil Dierks is Chief Executive Officer of the National Pork Producers Council (NPPC). In this position, he is responsible for the overall implementation of all NPPC programs. Dierks' position requires him to spend time in both Des Moines, Iowa, the national office of NPPC, and Washington, D.C. Beginning in 1990, Dierks served NPPC in a series of senior executive positions, including Executive Director of Operations, Vice President for Research and Education and Senior Vice President for Programs. Prior to his service with NPPC, Dierks was the Special Activities Director for the Iowa Pork Producers Association and Marketing Director for the Iowa Corn Promotion Board. Neil grew up on a livestock farm in eastern lowa and remains involved in a family farming operation. He is a graduate of Iowa State University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00009 NASDA Dr. Barbara Glenn recently joined the National Association of State Departments of Agriculture (NASDA) as CEO on August 18, 2014. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. Dr. Glenn is a scientist with decades of experience as a policy researcher and advocate for agriculture. She previously served as Senior Vice President of Science and Regulatory Affairs for CropLife America, where she was responsible for developing policies and regulations to support agriculture through crop protection. Prior to joining CropLife America, Dr. Glenn served as Managing Director of the Animal Bi otechnology, Food and Agriculture Section of the Biotechnology Industry Association in Washington, DC. Dr. Glenn holds a B.S. in animal science and a Ph.D. in ruminan t nutrition from the University of Kentucky. She previously worked for the U.S. Department of Agriculture, Agric ultural Research Service and the Federation of Animal Science Societies. Born in Lincoln, Nebraska and raised in Centerville, Ohio, Dr. Glenn developed a passion for agriculture from her parents and her involvement in 4-H. She lives on a small farm in Maryland with her husband: Ex. 6 - Personal Privacy and serves on various boards for farm bureau and 4-H. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00010

what is the total amount in the given invoice ?

hpbn0226

hpbn0226_p0, hpbn0226_p1

$5,476.50

368 From: Ehrhardt. Clinton (ehrharon) To: Chilli AP Invoices Cc: Burleigh-Flaver, Heather; Dourson. Michael (doursomi); Maier Michael (maierma); Avers, Valerie (aversvi) Subject: Invoice for UC - PPG PO F2D71625 Date: Friday, May 12, 2017 12:05:55 PM Attachments: PPG2Mav17.pp Attached you will find an invoice for work on PO F2D71625. Please let me know if you have any questions. Thank you, Clinton Ehrhardt Grant Administrator University of Cincinnati, College of Medicine Department of Environmental Health 3223 Eden Ave PO Box 670056 Cincinnati, OH 45267-0056 (513)558-5067 [email protected] Source: https://www.industrydocuments.ucsf.edu/docs/hpbn0226 University of Cincinnati INVOICE Physicians Company University Environmental Health Foundation Invoice# PPGMay17 Date: May 12, 2017 To: For: Heather Burleigh-Flayer, Ph.D., DABT Project: Support for Packaging SBU Global Manager of Toxicology Corporate EHS, PPG 440 College Park Drive Monroeville, PA 15146 DESCRIPTION RATE HOURS AMOUNT Support for Packaging SBU for the period of 4/1/17 - 4/30/17 PO F2D71625 For the following tasks: Reviewed the text entitled "Buyer Beware Report" Revised a 1 page description of TMBFstudies testing potential endocrine disruption based on sponsor review Attended a 1 day meeting with sponsors at their facility; discussed briefly with Rsik Science Center staff the likely work flow from this meeting Michael Dourson. PhD $ 299.00 13.5 $ 4,036.50 Jacqueline Patterson M En $ 288.00 5 $ 1,440.00 TOTAL $5,476.50 Please make Checks payable to: University Environmental Health Foundation Mail Checks to: Department of Environmental Health University of Cincinnati PO Box 670056 Cincinnati, OH 45267-0056 Source: https://www.industrydocuments.ucsf.edu/docs/hpbn0226

when conducting screening for thousands of chemicals, EPA may not have access to what ?

jzbn0226

jzbn0226_p28, jzbn0226_p29, jzbn0226_p30, jzbn0226_p31, jzbn0226_p32, jzbn0226_p33, jzbn0226_p34, jzbn0226_p35, jzbn0226_p36, jzbn0226_p37, jzbn0226_p38, jzbn0226_p39

all available information, to all available information

endpoints, criteria are similarly available for both acute and chronic classification. The use of one common system allows for appropriate assessment of all substances. GHS classification information is readily available for all substances, as U.S. manufacturers have developed GHS classifications for their products to meet international requirements. ACC's support of the GHS criteria for purposes of this prioritization tool is not a categorical endorsement of the GHS criteria for any other purpose. ACC has been an active participant in the development of GHS and supports the system in principle. The GHS has not been broadly implemented to date in the U.S., although the Occupational Safety and Health Administration (OSHA) has indicated an intent to publish a regulation applying GHS in the workplace. ACC's December 29, 2009, comments on OSHA's proposed rule to modify the existing Hazard Communication Standard (HCS) to reflect the GHS urged that implementation of the GHS adhere to certain principles (e.g., continued application of the "Building Block Approach" of the Purple Book). ACC made specific recommendations concerning details of the Hazard Classification definitions, cut-off values, among others. ACC stands behind those comments. In ACC's view, the use of GHS criteria in a screening-level prioritization of chemicals can materially assist in determining which chemicals receive additional evaluation by the Environmental Protection Agency, but does not necessarily preclude the use of other appropriate, applicable criteria developed under other systems. To classify a chemical in a hazard based priority ranking where there is not direct data on the chemical, EPA can employ the full range of approaches, such as QSAR, SAR, read- across and other modeling tools in which EPA has confidence based on molecular structure. In those situations where there still remains insufficient information on either environmental or human health hazards, the chemical would be classified as "high" for its environmental or health ranking. 1. Environmental Ranking Table 1 provides a summary of how GHS criteria could be logically used for chemical management prioritization. Table 1. Environmental Safety - Hazard Ranking GHS Classification - Ranking Environmental Rank Environmental Score Acute I or Chronic I or Insufficient Information to High 4 Classify Acute II or Chronic II Medium High 3 Acute III or Chronic III/IV or Medium 2 none Not classified Low 1 August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 2. Human Health Ranking Table 2. Human Health - Hazard Ranking Health Rank GHS Classification - Human Health Ranking Score GHS CMR Cat 1a, 1b; OR Repeat Dose </= 10 mg/kg/day (oral); </= 20 mg/kg/day (dermal); </= 50 ppm/6hr/day (gas inhalation); High 4 <<= 0.2 mg/1/6h/day (vapour inhalation); </= 0.02 mg/l/6h/day (dust mist fume inhal). OR insufficient information to classify GHS CMR Cat 2; OR Repeat Dose 10 - 100 mg/kg/day (oral); 20 - 200 mg/kg/day (dermal); Medium High 50 - 250 ppm/6hr/day (gas inhalation); 3 0.2 - 1.0 mg/l/6h/day (vapour inhalation); 0.02 - 0.2 mg/l/6h/day (dust mist fume inhal). Not carcinogen/mutagen/repro/develop;OR Repeat Dose 100 - 1000 mg/kg/day (oral); 200 - 2000 mg/kg/day (dermal); Medium 250 - 1000 ppm/6hr/day (gas inhalation); 2 1.0 - 5.0 mg/l/6h/day (vapour inhalation); 0.2 - 1.0 mg/l/6h/day (dust mist fume inhal). Not carcinogen/mutagen/repro/develop; OR Repeat Dose >1000 mg/kg/day (oral); > 2000 mg/kg/day (dermal); Low > 1000 ppm/6hr/day (gas inhalation); 1 >5.0 mg/l/6h/day (vapour inhalation); > 1.0 mg/l/6h/day (dust mist fume inhal). It is important to note that specific concerns about children's health (specifically potential hazards and adverse effects on the nervous system) and those caused by endocrine disruption mechanisms are addressed in this prioritization process: The GHS CMR "R" classification includes specific evaluation of effects on development in utero and upon growth, maturation and reproduction. ("R" stands for reproductive toxicity and includes adverse effects on sexual function and fertility, as well as developmental toxicity in offspring). Endocrine activity is not a distinct toxicological hazard per se, but rather a measure of a compound's ability to interact with components of the endocrine system. The prioritization process evaluates data and information on relevant apical tests, including tests for reproduction and developmental toxicity (potential endocrine pathways). Thus, even if specific August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 screening for potential endocrine activity has not yet been conducted on certain compounds, hazard identification based on observable outcomes from apical toxicity tests (e.g., outcomes such as pathologic states indicative of disease conditions) covers all modes of action, including endocrine pathways. The toxicity information evaluated (CMR and repeat dose toxicity) is directly relevant to evaluating potential hazards to all individuals, including children. Such data typically includes: 1) identification and definition of possible hazards upon all major organ systems from both acute and repeated exposures, including the nervous system; 2) detection of potential hazards arising from in utero exposures, including possible effects on the nervous system; 3) evaluation of potential of a substance to affect reproduction; and 4) evaluation of the potential of a substance to damage DNA. Integration of Hazard Elements: Each of the environmental and human health classifications is assigned a numeric value based upon its ranking, with 1 being the lowest value and 4 the highest. The greatest ranking (highest hazard potential score) of either Environmental or Human Health is used in a substance- specific priority ranking. The numeric value does not imply relative weighting, but rather a numerical order of priority. B. Exposure Potential Ranking The screening method allows for an initial indication of the extent of exposure potential by considering: 1. The chemical's uses and use pattern(s) 2. Production volume as a first pass indicator of relative emission/release potential since magnitude and route (i.e. air, water, soil) of emissions is not available for all substances. 3. Persistence and bioaccumulation characteristics of the substance. Together the 3 elements are used to rank exposure potential. 1. Use Patterns The proposed approach applies the most current 2006 TSCA Inventory Update Reporting rule (IUR, now called the Chemical Data Reporting rule (CDR) data. To keep the initial prioritization simple and transparent, the approach "bins" different use patterns to align with general exposure potential - intermediates, industrial use, commercial use and consumer use. These patterns are the same as those reported in the IUR and are consistent with REACH exposure categories (intermediates, worker, professional, consumer). Chemicals with consumer product use are likely to have widespread potential for general population exposures and are given high priority ranking within the approach. For the initial prioritization approach, child specific products are captured under general consumer products and all consumer products are weighted equally (see additional discussion below under Second Tier Considerations). Intermediates will have low general population exposures, since these substances are consumed, by definition, within the workplace. Therefore, they are given the lowest priority ranking within the approach. In the context of the proposed approach, the intermediates category includes both intermediates and non-isolated intermediates. A chemical used in multiple use patterns is August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 assigned the priority of the highest use, e.g., a chemical in both industrial and commercial uses would be assigned the commercial Medium-High rank. Table 3. Use Patterns - Exposure Ranking Use Pattern Ranking Use Pattern Score Consumer High 4 Commercial Medium-High 3 Industrial Medium 2 Intermediates Low 1 The IUR Definitions of these terms are (40 CFR 710.3, 710.43): "consumer use" means the use of a chemical substance or a mixture containing a chemical substance (including as part of article) when sold to or made available to consumers for their use. "commercial use" means the use of a chemical substance or a mixture containing a chemical substance (including as part of an article) in a commercial enterprise providing saleable goods or services. "industrial use" means use at a site at which one or more chemical substances or mixtures are manufactured (including imported). "intermediate" means any chemical substance: which is intentionally removed from the equipment in which it is manufactured, and which either is consumed in whole or in part in chemical reaction(s) used for the intentional manufacture of other chemical substance(s) or mixture(s), or is intentionally present for the purpose of altering the rate of such chemical reaction(s) "non-isolated intermediate" means any intermediate that is not intentionally removed from the equipment in which is it manufactured, including the reaction vessel in which it is manufactured, equipment which is ancillary to the reaction vessel, and any equipment through which the substance passes during a continuous flow process, but not including tanks or other vessels in which the substance is stored after its manufacture. 2. Production Volume Recognizing that detailed exposure information will not be available for all substances to be screened, the proposed approach uses production volume as an indicator of exposure, which is widely used in many prioritization schemes. As production volume is just a rough surrogate of emissions, ACC suggests only very broad categories, covering about two orders of magnitude each. It may be useful to consider how additional exposure estimates may be applied in the second tier assessment. Table 4. Production Volume as Emission Surrogate - Exposure Ranking Production Volume as Emission Surrogate Ranking Volume Score >= 100,000,000 lbs national aggregate High 4 1,000,000 lbs to < 100,000,000 lbs national Medium - High 3 aggregate August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 >= 25,000 lbs to < 1,000,000 lbs national Medium 2 aggregate < 25,000 lbs (below IUR site reporting limit) Low 1 3. Persistence and Bioaccumulation Persistence and bioaccumulation are viewed as indicators of exposure, and therefore are considered under the exposure axis of the approach. A persistent substance that is emitted to the environment at the same rate as a non-persistent substance with similar partitioning properties will result in higher exposure to humans and the environment. In fact, multimedia modeling clearly indicates that environmental persistence in the compartment to which a substance partitions is a good indicator of human exposure potential (MacLeod & McKone et al. 2004). Similarly, substances that are not subject to biotransformation by higher organisms will exhibit a high bioaccumulation potential that results in higher exposures via the food chain (Arnot et al. 2010). Therefore, it is recommended to apply the proposed persistence and bioaccumulation criteria in assessment of exposure potential as described below. The persistent and bioaccumulative (P&B) criteria of the proposed approach are targeted toward organic chemicals. Separate assessment criteria are likely needed for P&B evaluation for inorganics/metals, as in the approach taken by Canada's Chemical Management Program (CMP). For assessing persistence, based upon recent expert consensus (Boethling et al., 2009) it is recommended to distinguish persistent from non-persistent chemicals using the following criteria: Volatile chemicals can be defined using a vapor pressure cut-off (i.e., > 1000 Pa) For volatile chemicals, persistent versus non-persistent chemicals are differentiated using a half-life cut-off in air (e.g., a substance is not persistent if air half life is < 2 days). For non-volatile chemicals, non-persistent substances can be defined as substances that are deemed: readily or inherently biodegradable using standard biodegradation tests (OECD 301, 302, 306 test guidelines) or SAR or read across from measured data on a related substance, show an equivalent degree of degradation (i.e. >20% in 28 days) via an abiotic degradation mechanism such as photolysis (OECD 316) or hydrolysi (OECD 111), evaluation of simulation data from transformation in soil, marine water/sediment, brackish water/sediment, surface water/sediment, oceanic water die away (e.g. OECD 308/309) have half lives below 180 days, OR if data are lacking, evaluation via BIOWIN model (EPIWEB 4) Non-volatile substances that are not biodegradable or subject to abiotic losses based on the above criteria would be considered persistent. For assessing bioaccumulation, the key question for screening is the potential for biomagnification based on recent expert consensus (Gobas et al. 2009). To determine if a substance has the potential to biomagnify the following metrics have been agreed: Trophic Magnification Factor (TMF)>1, fish Biomagnification Factor (BMF)>1 fish Bioaccumulation Factor (BAF)/Bioconcentration Factor (BCF) > 5000. These metrics can be August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 derived using lab or field measurements (where available) or recently improved computational models that are included in EPA's EPIWEB model that can be freely downloaded at www.epa.gov/oppt/exposure/pubs/episuite.htm. This approach allows all organics to be addressed and is a scientifically updated version of the approach used in Canada's CMP. Based on the above recommendations, substances can be grouped with regard to persistence and bioaccumulation as follows: Table 5. Persistence and Bioaccumulation - Exposure Ranking Persistence and P&B Ranking P&B Score Bioaccumulation Persistent and High 5 Bioaccumulative Persistent and Not Medium 3 Bioaccumulative OR Not Persistent and Bioaccumulative Not Persistent and Not Low 1 Bioaccumulative Integration of Exposure Elements: As demonstrated in the tables, each factor (use pattern, P&B, and production volume) would be assigned a numeric score based upon its ranking. All 3 factors are added to arrive at an overall value. These values are then separated into categories from low to high exposure potential. A proposed "banding" approach is illustrated in Table 6. Table 6. Integration of Exposure Rankings Combined Score - All 3 Exposure Rank Exposure Ranking elements Score 11 13 High 5 9 10 Medium High 4 7 8 Medium 3 5 6 Medium Low 2 3 4 Low 1 Overall Priority Grouping: In the overall approach, both hazard and exposure elements are considered when placing a substance in a risk-based prioritization ranking. The overall prioritization score for priority grouping and risk evaluation is based on the combined consideration of the hazard and exposure rankings. Priority Groups 7, 8, and 9 are deemed High Priority; Priority Groups 4, 5, and 6 are Medium Priority; and Priority Groups 2 and 3 are Low Priority. August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Review and Comment: It is important that screening be done in an open and transparent way and that the best available information be used. When screening for thousands of chemicals, EPA may not have access to all available information. The process should provide an opportunity for review and comment on initial rankings and an opportunity to submit additional relevant data and information to update proposed rankings with improved information. III. Second Tier Considerations: After the initial screening, some substances within individual priority groupings may require further rank ordering, particularly where a large number of chemicals are in the same priority group. Listed below are the types of information that will be useful to consider in this Second Tier rank ordering: Biomonitoring/Environmental Monitoring Data: Mere detection of chemicals in humans or the environment, i.e., "found in biomonitoring (CDC), found in water (NCOD), and found in air", while providing an indication of exposure, does not provide a useful criterion for exposure potential because almost any industrial or commercial chemical could be detected at trace levels, given increasingly sensitive analytical methods. Therefore, detection alone primarily reflects only the fact that a specific chemical was included in a measurement program. This criterion will also tend to bias the prioritization of chemicals for which well-established analytical methods are available. Consequently, this criterion is not used in the initial prioritization scheme. However, within a particular priority grouping, reliable monitoring information should be considered for Second Tier rank ordering within a quantitative process that assesses if the data is above a level of concern (i.e., places it in a risk context). Use in Children's Products: Protection of childrens' health is a top priority and, in the initial ranking, child-specific products are captured under general consumer products and all consumer products are weighted equally. The specific IUR reporting of information on chemical use in products intended for children would be considered further within a particular priority grouping for Second Tier rank ordering, noting the following points: the IUR definition is based upon use in a child specific product rather than child specific exposure potential¹ (see below). Without knowing a specific product type, it is difficult to understand if 1 IUR definition (Federal Register Volume 75, Number 156, Friday August 30, 2010, p. 49686): Intended for use by children means the chemical substance or mixture is used in or on a product that is specifically intended for use by children age 14 or younger. A chemical substance or mixture is intended for use by children when the submitter answers "yes" to at least on of the following questions for the product into which the submitter's chemical substance or mixture is incorporated: (1) Is the product commonly recognized (i.e., by a reasonable person) as being intended for children age 14 or younger? (2) Does the manufacturer of the product state through product labeling or other written materials that the product is intended for or will be used by children age 14 or younger? (3) Is the advertising, promotion, or marketing of the product aimed at children age 14 or younger? August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 potential child exposure is greater than for a non-child specific product. For example, how does child exposure to a general use cleaner compare to exposure from use in a child's raincoat. In the VCCEP assessments, there are examples for inhalation exposures where estimates of passive child exposure during adult product use exceeded conservative estimates of child exposure during active use of a child-specific product (such as a hobby product) - differences were related to the amount of product used and substance concentration within the product (MEK VCCEP Submission). the IUR definition targets children age 14 and younger. Younger children may be exposed to a variety of non-child specific products that are in general household use. Older children may be exposed to a variety of additional products. the IUR information request is targeted to manufacturers, which may not have direct knowledge of all uses, particularly the presence in products for specific subpopulations, such as children. Therefore, it is not clear that the information requested for the IUR information would be consistently available across all substances being screened. Ideally, this information should be requested from formulators of child-specific products. Therefore, for the initial prioritization approach, which represents a broad, unrefined categorization, child specific products are captured under general consumer products and all consumer products are weighted equally. The IUR information on child specific use would be utilized within a particular priority grouping for Second Tier rank ordering. If the IUR information is utilized, it is important that the limitations above be considered in its application. Emissions Data: Production volume, which is readily available for substances, is used in this proposed approach, but only serves as a surrogate for environmental emissions. For further prioritization, data or estimates of environmental emissions can be used to refine prioritization. Estimates of environmental emissions will be available for some substances (e.g., TRI data). When TRI data are utilized it should be recognized that it addresses only emissions that result from industrial and not wide dispersive uses. In other cases, emissions estimates can be developed as a percentage of production volume based upon consideration of use categories. Within a particular priority grouping, available emissions information can be considered for Second Tier rank ordering, with the understanding that emissions information is not an indicator of actual exposure. Similarly, non-isolated system intermediates, by definition, would have de minimis exposure potential. Therefore, this IUR information could be considered within a particular priority grouping for Second Tier rank ordering. International Risk Management Actions: An initial screening approach for chemical prioritization should be based upon consistent application of specific hazard and exposure science elements that define risk potential. The hazard and exposure elements should be applicable across all substances being evaluated. For initial screening, existence of international risk management action plans should not be a factor that determines priority grouping. Risk management plans may be based upon many factors, including political drivers. It is unclear how factors, their relative weighting, and the rigor of the evaluation may vary across agencies and substances. For initial screening August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 purposes, the same science-based criteria should be used to rank all substances. Consideration of existing international risk management plans could be utilized to check the functioning of the approach and could be considered within a particular priority grouping for Second Tier rank ordering with the possible effect of moving a chemical up in a grouping if actions are being taken internationally. IV. Summary ACC's prioritization approach is an example of a risk-based screening prioritization process that implements the general principles outlined at the outset of this document. It is based upon widely available information that can be utilized to understand the relative priority of chemicals for further evaluation from a risk perspective, i.e., integrating both hazard and exposure elements. Implementation of the screening framework will be most effective when utilizing the best available information. When conducting screening for thousands of chemicals, EPA may not have access to all available information. An open and iterative process that includes an opportunity for review and comment on initial rankings, together with the information that led to the result, and an opportunity to update the ranking with improved information will create a transparent and scientifically sound process. V. References Arnot, J.A., D. Mackay, T. F. Parkerton, R. T. Zaleski, C.S. Warren (2010), Multimedia modeling of human exposure to chemical substances: The roles of food web biomagnification and biotransformation, Environmental Toxicology and Chemistry 29(1):45-55. Boethling, R., K. Fenner, P. Howard, G. Klecka, T. Madsen, J.R. Snape, M.J. Whelan (2009). Environmental persistence of organic pollutants: guidance for development and review of POP risk profiles. Integrated Environmental Assessment and Management 5(4): 539 - 556. Gobas, F.A.P.C, W. de Wolf, L. P Burkhard, E. Verbruggen, K. Plotzke (2009). Revisiting Bioaccumulation Criteria for POPs and PBT Assessments Integrated Environmental Assessment and Management, 5(4):624-637. MacLeod, M., T. E. McKone (2004). Multimedia persistence as an indicator of potential for population-level intake of environmental contaminants, Environmental Toxicology and Chemistry 23(10):2465-2472. van Wijk,D., R. Chénier, T. Henry, M. D Hernando, C. Schulte (2009). Integrated Approach to PBT and POP Prioritization and Risk Assessment' Integrated Environmental Assessment and Management, 5(4):697-711. August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Proposed Prioritization Approach DRAFT May & 2011 Exposure Elements nat commental consumer 20 2 3 a 33 3 not 8 or Persuntence S not 3 mai 35 a & not 3 Pas $ 3 S the iss = the Tormages RUN $ 3 3 SUM - P8 - Tavamage ranow 3 -13 Expesure Ramking $5 Based os Sum (UN# + pa * Townage PRIORITY GROUPING - Hazard * Expasure Ramkings - 1-8 3-10 11-13 mad Jow Hazard - Highter and Human $ 3 3 & $ Human Mazard Not on Dase 3 low mai * anou % 1000 numour 3 1.8 (duet Nume " 3 & 3 8 Not 100 Acure mi os : 3 A 2000 and not data) 280 v 1000 (pas 1.0 8.0 nomour 8.3 miss Nome 3 & % x CMR Cat 2, on Dawe Call 3: 10 - 3 is # 200 50 ase Igas 0.3 1.0 0.0% - 0.2 mis forme * # $ y GMS CMR Can on OHS Clowe Clat % Repeat Close 10 § on 8 on insurticient 20 information to - - - 0.3 wis 0,00 mist on information to $ 3 a $ August 29, 2011 Source: :https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Hazard and Exposure Criteria for Prioritization Approach HAZARD EXPOSURE Environment and Human Health Classifications based upon GHS Use Elements - based upon IUR Intermediate consumed during industrial processing Envirommental: industrial (not intermediate) - used in an industrial setting From GHS classification guidance document: commercial occupational use in nonindustrial setting Table 4.1.2: scheme for substances hazardous so the aquatic environment. consumer general population residential use Clacufication Persistence: Loag-term Votalile substance (VPS 1000 Pax: Not Persistent if air half life <2 days a (Nate 2) Nonvolatile (VP < 1000 Pa): Not Persistent if: Adequate dass Adequnte voriciny dasa aux a) ready biodegradability (OBCD 301) Rapidly 3 b) inherent biodegradability (OBCD 301, 302, 306) degredable 0) read across from measured data on a related substance. 28 (Note. 3) d) equivalent degree of degradation (i.e. >20% in 28 days) via an abjotic Arute 3 Categorys Chronic 1 Categury: 1 Categasy: I degradation mechanism such as photolysis (OBCD 316) or hydrolysis (OBCD NOEC ar ECA 0.1 NOE - EC cass L 1.00 md of maid 111) and/ar BCF a 200 OR, a substance is Not Persistent if: if e) evaluation of simulation data from transformation in soil, marine water/sediment, Caregusy: Acore 2 Category: Chronic 2 Caregury: Chrumin 2 Caregusy: Chruaic 2 brackish water/sediment, surface water/sediment, oceanic water die away (e.g., OECD 3.00 s: s 10.9 0.1 - NOEC er EC. 13 0.00 <: NOEC - EC, 502 3.00 L(EXC) 10.8 and of andies 308/309) have half lives below 180 days. BCF = 500 as if K. 2 4 OR, if data are lacking: Caregusy: Arnie 3 Caregury: 3 Chrinia 3 f) evaluation via BIOWIN model (EPIWEB 4) 01 EC. : 30,00 1- 100 and fack of Bioaccomulation: stapoid andier BOF: Re 300 if absent log x 3 4 A substance is not bioaccumulative if: 4 4) a) measured TMF < 1 (field study) 3) b) measured fish BMF <1 (lab study) Ne tericity and lack of and BCF 2 500 ase, lag E 4, c) measured fish BCF < 5000 (lab study) MOECA 1 mal d) predicted BCP< 5000 using the BCFBAF model included in EPIWIN 4 The above order reflects the preference for use in decision- making NOTE -- P&B CRITERIA ARB FOR ORGANICS Tonnage - based upon JUR reporting ranges <. 25,000 lbs (below IUR site reporting limit) Human Health: 25.000 - <1 MM lbs national aggregate As above, based upon GHS 1MM - <100 MM lbs national aggregate >100 MM lbs national aggregate August 29, 2011 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Risk-Based Prioritization Matrix Ancreasing Exposure Two-Step towest Prionies Prioritization Process Incregaling Second Tier Rank Ordering within Priority Groups Biomonitoring / Environmental Monitoring Use in Children's Products Emissions (e.g. TRI) International Risk Management Actions Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226

what is mentioned in phase 1 task 1.2 ?

hlcn0226

hlcn0226_p0, hlcn0226_p1, hlcn0226_p2, hlcn0226_p3, hlcn0226_p4, hlcn0226_p5, hlcn0226_p6, hlcn0226_p7, hlcn0226_p8, hlcn0226_p9, hlcn0226_p10, hlcn0226_p11

review prior studies/literature

129 From: Jürgen Troitzsch To: Osimitz Thomas; Dr. Blais Matthew; Prof. Rein Guillermo; Dr. Hayes Wallace; Dourson. Michael (doursomi); Kacew Sam; Dr. Wise Kimberly Subject: Fwd: Project on FF PPE Cleaning Validation Date: Monday, June 12, 2017 1:11:46 PM Attachments: PROU PANEL - PPE Cleaning (33) pdf PROJ SUMMARY - PPE Cleaning (7) pot FLYER FF Contam Control Workshop (6) odf HOTELS - Contam Control Wrkshp on 2017Jul19.pd PROJS JMMARY- FE Cancer Cohort Study (4) odf Dear All, I came across this project, which may be of interest in the frame of our fire fighters cancer activities. Kind regards/Viele Grüße Jürgen Dr. Jürgen Troitzsch Fire and Environment Protection Service FEPS Via Patrizia 32 CH-6612 Ascona, Switzerland Mobile: +41 79 289 17 16 Phone: +41 91 791 14 22 Email: [email protected] Web: www.troitzsch.com De : Grant, Casey Envoyé : lundi 22 mai 2017 17:58 À : [email protected]; [email protected]. tis.com; mlambetamallN u.edu; dwardmecarthyebostengoy ark.a.miller@ehoen ix.gov; james.riley@bosta nagov; [email protected] Thomas [email protected]; ;timügearcleaningsolutions.s om [email protected]; Ken.Wiles @fire.jacounty.gov Farrell, Christopher cobtlogiobefiresuits.com; pattogiobefiresults.com; Diane.Hess@ Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 130 PBIProducts.com; Kebtonen@lionprotedscon leur.gouv.fr; GUILLAUME Eric <eric [email protected] ;[email protected]; mamiefortunes-collide.com Cc : lasonallendintertekeor [email protected]; [email protected] wlindslev@ cdc.gov; [email protected] [email protected]; [email protected]; ; istendice OY; Objet : Project on FF PPE Cleaning Validation To: Panel, Research Team and Liaisons for Project on "Fire Fighter PPE Cleaning Validation" It has been some time since we last spoke, and I have the following three items to be addressed: 1) A lot has been happening with our project and we want to hold a 90 minute conference call in early August 2017 to bring everyone up-to-date. I've created a scheduling poll to determine the optimum date/time Please respond before Noon ET on Wednesday 31/May/2017 so that we can get this on our calendars. I've attached the Project Roster and Project Summary in case anyone needs a refresher for this project addressing "how clean is clean". Thanks. 2) I've been asked to participate in a webinar tomorrow (23/Mav/2017) from noon ET to 1:30 pm ET on "Factors Relating to Cancer and Contamination in the US Fire Service". I've been assigned a portion of this webinar (among two other speakers) to address on-going research and I'm planning to address our project among several other on-going efforts. The link is on the NFPA home page at: FYI.. 3) Some of you are already aware of the Workshop in Columbus, Ohio on 19- 20/Julv/2017, and if not I want to call it to your attention. This is for the separate one year AFG project on "Campaign for Fire Service Contamination Control". Attached is a Flyer that provides additional details, and also attached is a list of hotels in the area to assist with travel. The workshop will be held from Noon to Noon on 19-20/July and we still have room if you would like to attend. In addition, the separate project (i.e., a third related project) on "Fire Fighter Cancer Cohort Study" will hold a separate planning meeting on the afternoon of 20/July from 1 pm to 5 pm (Project Summary is attached). All are welcome to attend this as well. If you are a fire service panel member we can cover your travel, and I can send follow-up instructions to you separately. For anyone interested in attending the Columbus meetings on 19-20/July, please let us know by email to [email protected] and Thanks.. Casey C. Grant, P.E. Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION "CAMPAIGN FOR FIRE SERVICE CONTAMINATION CONTROL" WORKSHOP Location: Columbus Fire Fighters Union Hall, 379 W Broad St, Columbus, OH 43215 Workshop Dates: 19-20 July 2017 (Last Updated: 21 April 2017; subject to update) Background: Exposure to chemical and biological contaminants on the fire ground is an increasing concern for long-term fire fighter health. Cancer and other diseases resulting from chronic exposures has become a leading concern for the fire service. This is presumed to be associated with fireground exposures relating to protection/hygiene practices and persistent harmful contamination found in fire fighter equipment, apparatus carrying that equipment, and stations where the equipment resides. Workshop Goal and Objectives: The goal of this Workshop is to identify concepts and materials that are or can be useful to control the spread of harmful fire ground contaminants, ultimately in support of improved fire fighter long-term health. The following objectives support this goal (and reflect anticipated deliverables): Identify, review and recommend baseline materials (existing and proposed) addressing best practices, standards, research, equipment, facilities, and other areas of focus. Identify and prioritize gaps that are barriers to enhancing best practices, standards, research, equipment, facilities, and other areas of focus. Identify and review key characteristics for effective promotion and communication. Clarify target audiences for outreach and consider stakeholder research prior to developing a comprehensive communications plan to improve outcome. Prioritize messages for year one. Agenda: Wed; 19/July 1:00 pm Day One: Welcome and Call to Order Casey Grant, FPRF 1:15 pm Overview of Baseline Materials and Review of Gaps Jeff Stull, IPP 2:00 pm Review of Outreach Peg, Paul, PPA 2:30 pm Case Study: Best Practice Information Beth Gallup, KFD 3:00 pm PM Break 3:15 pm Casey Study: Standards Revisions Dave Bernzweig, CFD 3:45 pm Case Study: Equipment & Facilities Paul Erickson, LEWA 4:15 pm Breakout Groups Workshop Attendees 5:00 pm Adjourn for Day One (& Evening Networking Reception) Thur; 20/July 8:30 am Day Two: Group Review of Baseline Materials Jeff Stull, IPP 8:45 am Breakout Groups Continue Workshop Attendees 9:45 am AM Break 10:00 am Breakout Group Report Workshop Attendees 11:00 am Plenary Discussion Workshop Attendees 11:30 am Workshop Wrap-up & Summary Observations Casey Grant, FPRF 12:00 pm Adjournment Registration: Workshop attendance is limited to the first 50 attendees, and others will be placed the on a waiting list. To request attendance or for more information, please contact [email protected]. After the Workshop a report will be available. This Workshop is funded through an AFG Fire Prevention & Safety Grant from U.S.DHS/FEMA. 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7281 Fax: +1.617.984.7010 Email: [email protected] www.NFPA.org/Foundation Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 WORKSHOP ON FIRE SERVICE CONTAMINATION CONTROL 19-20 July 2017 (Noon to Noon ET) Columbus Fire Fighters Union Hall 379 W Broad St, Columbus, OH 43215 Note: For flights, Workshop starts at Noon ET on 19/July/2017 and finishes at Noon ET on 20/July/2017 Drury Inn & Suites: 88 East Nationwide Blvd, Columbus, OH 43215 Phone: 1-614-221-7008 ttos://www.drurvhotels.com/locations/columbus-ob/drurv-inn-and-suites-columbus-convention: center Approximate Rate: $130 Distance (in miles) from Hotel to Columbus Union Hall: 1.3 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars. Red Roof Plus Columbus Downtown Convention Center 111 East Nationwide Blvd, Columbus, OH 43215 Phone: 1-614-224-6539 ittps://www.redroof.com/property/Columbus/OH/43215/Hotels-close-to-Greater-columbus- Convention-Center-US-23-1-670/RRI262/ Approximate Rate: $130 Distance (in miles) from Hotel to Columbus Union Hall: 1.4 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars. Sheraton Columbus Hotel at Capital Square 75 East State Street, Columbus, OH, 43215 Phone: 1-614-365-4500 http://www.sheratoncolumbuscapitolsquare.com/ Approximate Rate: $170 Distance (in miles) from Hotel to Columbus Union Hall: 0.8 Notes: Central downtown area Hampton Inn and Suites Columbus Downtown 501 North High Street, Columbus, OH 43215 Phone: 1-614-559-2000 htto://hamptoninns.bilton.com/en/hotels/ohio/hampton-inn-and-suites-columbus-downtown- CMHHSHK/index.htmi?WT.mc. Approximate Rate: $175 Distance (in miles) from Hotel to Columbus Union Hall: 1.3 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars. Page 1 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Courtyard Columbus Downtown 35 West Spring Street, Columbus, Ohio 43215 Phone: 1-614-228-3200 4d19-a255-54ba596febe2 Approximate Rate: $175 Distance (in miles) from Hotel to Columbus Union Hall: 0.8 Notes: Downtown west area; walkable Doubletree Suites by Hilton Columbus Downtown 50 South Front St, Columbus, Ohio, 43215-4145 Phone: 1-614-228-4600 CMHSBOT/index.htmi Approximate Rate: $200 Distance (in miles) from Hotel to Columbus Union Hall: 0.5 Notes: Closest hotel to meeting site; very short walk Residence Inn Columbus Downtown 36 East Gay Street, Columbus, Ohio 43215-3108 Phone: 1-614-222-2610 ec3-4d19-a255-54ba596febe2 Approximate Rate: $230 Distance (in miles) from Hotel to Columbus Union Hall: 0.8 Renaissance Columbus Downtown 50 North Third Street, Columbus, Ohio 43215 Phone: 1-614-228-5050 ttp://www.marriott.com/hotels/travel/cmhbr-renaissance-columbus-downtown-hotel/ Approximate Rate: $240 Distance (in miles) from Hotel to Columbus Union Hall: 1.0 Notes: Central downtown area Hilton Columbus Downtown 401 North High Street, Columbus, OH 43215 Phone: 1-614-384-8600 Approximate Rate: $240 Distance (in miles) from Hotel to Columbus Union Hall: 1.1 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars; New facility and nice. Page 2 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION PPE Cleaning Validation Validation of Cleaning Procedures for Fire Fighter Personal Protective Equipment (PPE) PROJECT CONTACTS Last Updated: 22 May 2017 Project Technical Panel Phone: 614-774-7446 David Bernzweig, Columbus Fire Department (OH) Email: [email protected] Phone: 780-496-3801 Ken Block, Edmonton Fire/Rescue & Metro Chiefs Representative Email: [email protected] Phone: 804-971-7983 Ken Brown, VA State Firefighter's Association & NVFC (Alt to B. McQueen) Email; [email protected] Phone: 510-839-5111 Cell: 213-321-9393 Roger Curtis, ECMS Curtis & Sons (CA) Email: [email protected] Phone: Paul Curtis, ECMS Curtis & Sons (CA) (Alt to Roger Curtis) Email: [email protected] Phone: 253-277-4131 Cell: 503-314-4832 Steve Lakey, Northwest Safety Clean (WA) Email: [email protected] Phone: 304-406-7479 Mark Lambert, WV Fire Academy & NAFTD (WV) Email: [email protected] Phone: 617-828-3978 Ed McCarthy, Boston Fire Department (MA) Email: [email protected] Phone: 315-736-7479 Cell: 315-552-8245 Brian McQueen, FASNY & National Volunteer Fire Council (NY) Email: [email protected] Phone: 602-534-2396 Mark Miller, Phoenix Fire Dept. (AZ) Email: [email protected] Phone: 919-524-1569 Bryan Ormond, NCSU (NC) Email: [email protected] Phone: Russ Osgood, Firefighter Cancer Support Network (NH) (Alt to Keith Tyson) Email: [email protected] Phone: Larry Petrick, IAFF (DC) Email: [email protected] Phone: 617-549-9850 Jim Riley, Boston Fire Department (MA) (Alt to E. McCarthy) Email: [email protected] Phone: 757-385-2892 Molly Riley, Virginia Beach Fire Dept. (VA) Email: [email protected] Phone: 718-999-2922 Thomas Smith, FDNY (NY) Email: [email protected] Phone: 214-774-2213 Cell: 940-300-5718 Tim Tomlinson, Gear Cleaning Solutions (TX) Email: [email protected] Phone: Robert Tutterow, NFPA Fire Service Section (NC) Email: [email protected] Phone: 786-351-3276 Keith Tyson, Firefighter Cancer Support Network (FL) Email: [email protected] Phone: 951-807-1914 Dick Weise, LA County Fire Dept. (CA) Email: [email protected] Phone: 949-291-0637 Ken Wiles, LA County Fire Dept. (CA) (Alt to Dick Weiss) Email: [email protected] Phone: 512-974-0286 Chris Youngblood, Austin Fire Dept. (TX) Email: [email protected] 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7281 Fax: +1.617.984.7010 Email: [email protected] www.NFPA.org/Foundation Source: :https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Phase 1 Project Contacts Phone: 330-723-0000, x365 Steve Allison, Fire-Dex (OH) Email: [email protected] Phone: 800-401-4780 Jack Binder, Edmar Chemical Company (OH) Email: [email protected] Phone: 920-570-0824 Bill Brooks, Alliance Corp. (WI) Email: [email protected] Phone: Charlie Dunn, TenCate Protective Fabrics Email: [email protected] Phone: 617-984-7325 Chris Farrell, NFPA & Staff Liaison for NFPA 1851 (MA) Email: [email protected] Phone: 800-232-8323 Rob Freese, Globe Manufacturing (NH) Email: [email protected] Phone: Pat Freeman, Globe Manufacturing (NH) (Alternate to Rob Freese) Email: [email protected] Phone: 704-554-3313 Diane Hess, PBI Performance Products (NC) Email: [email protected] Phone: 937-415-2932 Karen Lehtonen, LionFirst Responder Products (OH) Email: [email protected] Phone: 484-433-4072 Dan Silvestri, 9-1-1 Safety (PA) Email: [email protected] Liaison Contacts Phone: Pierre Carlotti, Ministry of Interior & Liaison for ISO TC92/SC3 (France) Email: [email protected] Phone: Eric Guillaume, Efectis & Liaison for ISO TC92/SC3 (France) Email: [email protected] Phone: Bill Haskell, NIOSH NPPTL (MA) Email: [email protected] Phone: James Hoar, Boston Fire Department (MA) Email: [email protected] Phone: 631-242-0621 Steve King, Chair NFPA 1851 (NY) Email: [email protected] Phone: +33(0)1.55.76.26.18 Fanny Rieunier, Ministry of Interior & Liaison for ISO TC92/SC3 (France) Email: [email protected] Phone: 612-247-6429 Marni Schmid, Fortunes Collide & Secretariat NFPA 1851 (MI) Email: [email protected] Page 2 of 3 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Core Research Team Phone: 607-758-6537 Cell: 607-423-5617 Jason Allen, Intertek (NY) Email: [email protected] Phone: 304-285-6076 Daniel Farcas, NIOSH HELD (WV) Email: [email protected] Phone: Crystal Forester, NIOSH NPPTL (WV) Email: [email protected] Phone: 617-984-7284 Cell: 617-659-1159 Casey Grant, Fire Protection Research Foundation (MA) Email: [email protected] Phone: Lee Greenawald, NIOSH NPPTL (WV) Email: [email protected] Phone: Bill Lindsley, NIOSH HELD (WV) Email: [email protected] Phone: Stephen Martin, NIOSH DRDS (WV) Email: [email protected] Phone: John Noti, NIOSH HELD (WV) Email: [email protected] Phone: Deborah Sbarra, NIOSH NPPTL (WV) Email: [email protected] Phone: 512-288-8272 cell: 512-623-9558 Jeff Stull, International Personal Protection (TX) Email: [email protected] Phone: 304-285-5858 cell: 681-209-2571 Jay Tarley, NIOSH NPPTL (WV) Email: [email protected] Additional Research Team Contacts Phone: 304-285-5884 Francoise Blachere, NIOSH HELD (WV) Email: [email protected] Phone: Renee Dotson, NIOSH HELD (WV) Email: [email protected] Phone: James Harris, NIOSH NPPTL (WV) Email: [email protected] Phone: Ryan Lebouf, NIOSH DRDS (WV) Email: [email protected] Phone: 617-984-7281 Eric Peterson, Fire Protection Research Foundation (MA) Email: [email protected] Phone: John Powers, NIOSH (WV) Email: [email protected] Phone: 412-386-4621 Cell: 412-463-9561 Heather Reed, NIOSH NPPTL (PA) Email: [email protected] Page 3 of 3 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION PPE Cleaning Validation Validation of Cleaning Procedures for Fire Fighter Personal Protective Equipment (PPE) (for more information see www.nfpa.org/PPECleaning) PROJECT SUMMARY Last updated: 5 February 2016 Background: Fire fighter exposure to personal protective equipment (PPE) that is dirty, soiled, and contaminated is an increasing concern for long-term fire fighter health. This exposure to persistent harmful contaminants in PPE is an extremely serious problem both on the fireground to highly toxic substances including a variety of carcinogens, and more insidiously to an increasing range of infectious pathogens that are encountered in patient care and different emergency operations. Fire fighter PPE becomes contaminated during these exposures and there are no industry standards that conclusively and reliably show that clothing is being adequately cleaned. While general cleaning procedures have been established in NFPA 1851, Standard on Selection, Care, and Maintenance of Protective Ensembles for Structural Fire Fighting and Proximity Fire Fighting, there are no procedures or requirements to demonstrate whether current cleaning practices, including those specified in NFPA 1851, will remove contaminants from fire fighter protective clothing. This project is intended to establish clear and definitive guidance to the fire service for applying cleaning and decontamination procedures that effectively remove both chemical and biological contaminants. Research Goal and Objectives, and Conceptual Approach: The overall goal of this project is to improve fire fighter safety and health by reducing continuing exposure to harmful contaminants in unclean or inadequately cleaned PPE. The objectives to achieve this goal are twofold: (1) To characterize fireground and emergency scene contamination leading to these exposures and develop the methodology for the consistent measurement of cleaning effectiveness; and (2) determine implementable cleaning, decontamination, and disinfection strategies that effectively reduce fire fighter exposures to persistent contaminants. The approach taken by this project is illustrated in Figure 1: Project Conceptual Approach. - Ensure Identify Devise Validate lab - - chemical and methods to methods - at biologicat conteminate againet field ses target clothing in contaminants laboratory exposures acceptance Project Direction Figure 1: Project Conceptual Approach 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7281 Fax: +1.617.984.7010 Email: [email protected] www.NFPA.org/Foundation Source: :ttps://www.industrydocuments.ucsf.edu/docs/hlcn0226 Project Phases and Tasks: This project involves the following four key phases of activity: 1) Identification of Contaminants: Confirm identification and ability to characterize persistent chemical and biological contaminants in fire fighter PPE through target substances and microorganisms. 2) Establishment of Soil and Chemical Contamination/Decontamination Procedures: Develop and validate specific procedures that determine the effectiveness of laundering and other cleaning methods in removing specific soils and chemical contaminants. 3) Establishment of Biological Contamination/Disinfection or Sanitization Procedures: Develop and validate specific procedures that determine the effectiveness of laundering or disinfection/sanitization processes that remove/deactivate biologically-based contaminants. 4) Creation of Overall Fire Service Guidance: Prepare clear and definitive information for the fire service industry (fire fighters, fire departments, clothing manufacturers, material suppliers, cleaning/care organizations, and cleaning agent or equipment manufacturers) on appropriate approaches for properly cleaning fire fighter protective clothing and equipment. The specific tasks of this project are based on these four phases of the project, and these are illustrated in Figure 2: Project Tasks. PHASE 2 PHASEZ Task 2.4 Task 2.5 Task 1.1 Task 2.1 Validate testsat Refine test Appoint Technical Select cleaning selected ISPS methodology Review Panel methods/agents (chemical) (chemical) PHASE $ Task 4.1 Task 1.2 Task 2.2 Write qualification Review Prigr Put together test plan methods studies/literature (chemical) Task 2.3 Task 4.2 Task 1.3 PHASE 3 Perform laboratory Establish cleaning Setup analytical chemical Task 3.3 acceptance criteria capabilities decontaminant Put together test plan testing (biological) Task 4.3 Task 1.4 Perform Task 3.4 Prepare public inputs for NFPA 1851 demonstration tests Task 3.1 Perform laboratory Task 3.6 Select study biological Refine test microorganisms decontaminant methodology Task 1.5 testing (biological) Task 4.4 Refine biological Prepare industry decontamination Task 3.2 Task 3.5 guidance document scope Select biological Validate testsat cleaning methods selected ISPs (biological) Task 1.6 Task 4,5 Establish cleanliness Prepare project final metrics report Figure 2: Project Tasks Implementation and Schedule: This three year project is due to be completed no later than " August 2018, and is funded through an AFG Fire Prevention & Safety Grant from the U.S. Department of Homeland Security / Federal Emergency Management Agency. The Research Foundation will lead a unique research team partnership composed of the FPRF, National Institute for Occupational Safety and Health (NIOSH), International Personal Protection (IPP), and Intertek. The research team, along with several Independent Service Providers (ISPs), will work with the fire service partners and others to validate and optimize fire fighter PPE cleaning validation methods. For more information see www.nfpa.org/PPECleaning. Page 2 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION Fire Fighter Cancer Cohort Study Full Title: The Firefighter Multicenter Cancer Cohort Study: Framework Development and Testing PROJECT SUMMARY Last Updated: 20 September 2016 Background: Cancer is a leading cause of fire service morbidity and mortality. Firefighter exposure to carcinogens occurs through skin contamination and through inhalation when respiratory protection is not worn when combustion products are present such as during overhaul, standby, and operation of apparatus, as well as through off-gassing of equipment and exposures in the fire station. However, we currently do not understand which exposures are responsible for cancer in firefighters, the mechanisms by which firefighter exposures cause cancer, nor the most effective means of reducing exposures. Since cancer has a long latency period, biomarkers are also needed that can measure the toxicological effects of carcinogen exposure well before the development of cancer, when interventions to prevent disease could be effective. Development of a large (>10,000 firefighter) multicenter firefighter cancer prospective cohort study will address these needs, but the framework for such a study needs to be first developed and tested among a smaller initial set of fire service partners. Implementation and Schedule: This research project is led by University of Arizona with collaborative support from multiple other research partners, including the University of Miami, National Institute for Occupational Safety and Health; National Fallen Firefighter Foundation, Fire Protection Research Foundation, and others. Initial funding for this project is through a 3-year DHS/FEMA Assistance to Fire Fighter (AFG) Fire Grant, with the intention to identify and obtain additional funding for the duration of the 30 year effort. The project start date is August 2016. The Principal Investigator for this project is: Jefferey L. Burgess, MD, MS, MPH, University of Arizona, email: [email protected]. Project Goal and Aims: The goal of the initial 3-year effort of this overall project is to develop and test a framework for establishing a long-term fire fighter multicenter prospective cohort study focused on carcinogenic exposures and effects. The specific aims are to: 1) Establish an oversight and planning board to provide study oversight, foster communication among fire organizations and help develop a long-term funding plan; 2) Create and test a cohort study data coordinating center and harmonized survey data protocols; 3) Develop and validate a firefighter carcinogen exposure matrix and data collection system; and 4) Create a biomarker assessment center and evaluate the association between cumulative firefighter exposures and epigenetic effects. For more information, contact: Casey Grant, Fire Protection Research Foundation 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7284 Fax: +1.617.984.7010 Email: [email protected] Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Project Methodology: This study will harmonize and build on recent and developing firefighter cancer prevention studies in Arizona, Florida and Massachusetts, adding volunteer fire departments. An oversight and planning board will be established by the Fire Protection Research Foundation (FPRF) in association with the National Fallen Firefighter Foundation (NFFF) Fire Service Occupational Cancer Alliance (FSOCA) to provide oversight of the study through collaboration among fire service organizations, academia, and government agencies, and develop a long-term funding and sustainability plan. A data coordination center team will design, develop and evaluate a framework for a multicenter prospective cohort study of firefighters and cancer risk, including standardized participant survey data collection tools and analysis protocols sufficient to address the short- and long-term study objectives as well as linkage with long-term outcome data including cancer development. An exposure assessment center team will develop a carcinogen exposure matrix and data collection system to provide improved occupational exposure data for comparison with epigenetic outcomes and eventual cancer outcomes. Carcinogen exposures associated with specific fire types will be evaluated across fire departments through industrial hygiene monitoring and analysis of urine for absorbed contaminants, supplementing existing FEMA-funded and other studies of firefighter exposures and allowing for participating fire departments to design interventions to reduce current exposures. Expansion of the National Fire Operations Reporting System (NFORS) will be explored as one option to uniformly collect incident and exposure data. Blood and buccal cells will be collected during annual medical surveillance evaluations, including both new recruits and incumbent firefighters. Pilot studies of epigenetic markers of cancer effect and cancer risk will be analyzed comparing municipal firefighters with high chronic exposures, volunteer firefighters with low chronic exposures, and non- firefighter friends of the municipal firefighters (serving as controls). Project Deliverables: The anticipated outcomes from this 3-year effort is to establish and test the framework necessary for the subsequent development of a large multicenter cohort study of cancer in the fire service. Page 2 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226

ICR Stands for ?

kzbn0226

kzbn0226_p41, kzbn0226_p42, kzbn0226_p43, kzbn0226_p44, kzbn0226_p45, kzbn0226_p46

Information Collection Request, information collection request

Perhaps for simplification purposes, EPA has provided a succinct definition. However, as noted above, this definition does not appropriately capture how the sentinel exposure approach is currently used. Relying on the highest exposure scenario does not mean that the "maximal" exposure is used. Reasonable values from that highest exposure scenario should be used instead. A risk evaluation should not use a "maximal" exposure value as these values are typically unstable. More appropriate language would include the term "plausible exposure" or "plausible upper bound exposure." In the environmental toxicology field, it is common to use the 95th percentile under average exposure conditions. The "plausible maximum exposure" is not used. Significant revisions are needed to EPA's definition to capture the appropriate use of the sentinel exposure concept. E. Uncertainty EPA provides a definition for uncertainty and cites EPA's 2014 Human Health Risk Assessment 90 Framework as the source. However, as written, the definition EPA provides is actually not consistent with the source. EPA's definition should conforms to the edits below to ensure the definition is fully consistent. Uncertainty means the imperfect knowledge or lack of precise knowledge of the real world, either for specific values of interest or in the description of a the system. VIII. The Process for Manufacturer Requested Evaluations A. EPA-Initiated and Manufacturer-Requested Evaluations Should Follow the Same Review Process. LCSA allows chemical manufacturers to request EPA to conduct a risk evaluation at Section 6(b)(4)(C)(ii). By law, a manufacturer may only request a risk evaluation of a chemical it manufacturers (not of a competitor). By rule, EPA is to specify the "form and manner" for manufacturer requests, as well as to prescribe the criteria for the risk evaluation. In our view, EPA should largely follow the same process - and apply the same criteria - to manufacturer requested risk evaluations as it does to EPA-initiated risk evaluations arising out of the prioritization process. There is one notable difference: EPA has authority under LCSA to flexibly scope risk evaluations for chemicals with high priority designations to focus on conditions of use that are most relevant and meaningful to risk, and it should do so on a case-by- case basis. The result of this process might be that some risk evaluations cover all conditions of use; others a few; others only one. In the case of manufacturer-requested risk evaluations, a manufacturer may support only certain conditions of use - in other words, it may sell the chemical only for use in certain kinds of products or processes. A manufacturer may strongly support risk evaluation of its chemical under the conditions of use it supports, but may not be willing to fund evaluation of its chemical for uses supported by its competitors. While we believe EPA can expand the scope of a risk evaluation beyond that requested by a manufacturer, the agency should not impose fees on a 90 See 82 Fed. Reg. at 7568. 37/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 company that requests a risk evaluation in a manner that enriches its competitors. (Similarly, if only one manufacturer requests a risk evaluation on a chemical in a particular condition of use, it would not be appropriate to impose costs on manufacturers that did not request the risk evaluation). It will be important for EPA to address fees equitably in the upcoming fees rule; if not, the agency will discourage manufacturer requests. This is an important observation, because Congress contemplated that EPA would receive manufacturer requests for risk evaluation, and mandates that a certain number of them be accepted. At full implementation, the law anticipates that EPA will be undertaking 5-10 manufacturer-requested evaluations (assuming that not more than 20 EPA-initiated evaluations are underway). EPA should therefore promulgate criteria that make it sufficiently attractive and possible for manufacturers to avail themselves of the option. EPA should not promulgate criteria that make it largely unworkable and impossible to seek and obtain manufacturer-requested evaluations. EPA's insistence that manufacturer-requested evaluations must include "all" conditions of use obviates the use and utility of the law's provision that allows - and requires EPA to accept manufacturer-requested evaluations in the first place, leads to an absurd result, and undermines the function and purposes of the statute. B. EPA Should Respond Within Six Months from the End of the Comment Period to the Time it Notifies a Manufacturer of Acceptance of a Request. EPA should align the six months established for scoping EPA-initiated risk evaluations with those requested by manufacturers. EPA should not require more than 6 months to decide whether to accept or deny a request from a manufacturer for review. C. EPA Should Not Award "Preference" to Any Manufacturer-Requested Risk Evaluations Until the Statutory Cap is Met. EPA is required by statute to give preference to manufacturer-requested evaluations for which EPA determines that restrictions by one or more states have the potential to have a significant impact on interstate commerce or health or the environment.91 There is no other statutory basis for differentiating between requests. EPA proposes to treat this as a required "initial prioritization," after which it will further prioritize chemical substances for risk evaluation "based on initial estimates of exposure(s) and/or hazard(s) under one or more conditions of use or any other factor that EPA determines may be relevant." ACC believes this suggested approach, which could result in manufacturer requests being inappropriately rejected by EPA, is inconsistent with legislative intent, and the efficient flow of risk evaluations under LCSA. We believe that until EPA's cap on manufacturer-requested risk evaluations is met, and except for mandatory preference under TSCA 6(b)(4)(E)(iii), the Agency should accept requests for manufacturer-requested risk evaluations on a first-come, first-served basis. EPA arguably cannot, and should not, deny any otherwise compliant request until 5 evaluations are underway, since there may not be a rational basis to be able to compare requests for evaluation. After EPA has 5 manufacturer-requested evaluations underway, it should apply the same prioritization criteria set out in the prioritization rule for selection of chemicals for evaluation. It should not 91 TSCA 6(b)(4)(E)(iii). 92 82 Fed. Reg. 7569. 38/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 impose new criteria of "high hazard" and "high exposure" divorced from the criteria established in the prioritization rule. We also strongly urge EPA to delete the catch-all provision, "any other factor EPA determines may be relevant." For the manufacturer-requested risk evaluation process to function, manufacturers must have fair notice of the criteria they must meet to have a request considered. An open-ended catchall provision not only undermines congressional intent; it eliminates fair notice to manufacturers of what information they need to gather and prepare in order to have a request considered. This is particularly the case given that manufacturers may need to conduct testing and incur significant costs before they request a risk evaluation. D. EPA Should Not Require Submission of "All" Prior Risk Assessments by Manufacturers as a Precondition to Accepting a Manufacturer Request. Section 702.37(b)(4) proposes that manufacturer requests must include a commitment to provide to EPA any referenced information on request, an appropriate request (subject to CBI protection, if applicable). This section provides further, however, that a manufacturer must submit any previous risk assessment conducted by a manufacturer as well as any it "possesses" or "can reasonably obtain." While we appreciate that TSCA § 26(k) requires EPA to take into consideration reasonably available information as part of Section 6 risk evaluations, this should not devolve into a blanket request for certain proprietary reviews undertaken by manufacturers. Many risk assessments fall into that category. EPA may properly request manufacturers to produce information with a manufacturer request for a risk evaluation where the Agency has legal authority to make the request and the information is otherwise relevant to the risk evaluation, meets data quality standards, and meets Section 26 scientific standards. EPA cannot, however, create new legal authority for itself to demand otherwise protected information as a condition of considering a manufacturer request for risk evaluation. This is to be contrasted with health and safety results, which may be inputs in a risk assessment but are distinct from a risk assessment. ACC, in fact, has long had a policy in its Chemical Products and Technology Division to make publicly available the final reports or validated final results of environmental, health, and safety research managed or sponsored under the group (subject to exceptions needed to preserve legal rights, such as proprietary rights, data compensation rights or to protect confidential business information). EPA also may appropriately request a manufacturer to provide, as part of its request, any information that EPA could otherwise require under TSCA Sections 8(a), 8(c), 8(d) (health and safety studies), and 8(e) (which would already have been reported to the agency). We urge EPA to revise the proposal accordingly to clarify that manufacturers will be expected to produce information relevant to the risk evaluation, and that EPA confirm it will protect CBI and respect other legal doctrines protecting against disclosure. 39/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 E. EPA Should Limit Public Comments Accepted on a Manufacturer Request to the Expected Scope of the Risk Evaluation. As EPA properly notes in the preamble, the agency must grant any manufacturer request that complies with EPA's criteria, until the statutory minimum of 25 percent has been met. EPA may set criteria by rule. Section 702.37(e)(2) proposes a public comment period on valid manufacturer requests for risk evaluations which injects inappropriate criteria - the public is invited to submit comments and information "relevant to whether the chemical substance presents an unreasonable risk of injury to health or the environment." For EPA-initiated risk evaluations, the legal standard that begins the risk evaluation process is EPA's determination that a chemical "may present" an unreasonable risk of injury. A determination that a chemical "presents" an unreasonable risk is not made, if at all, until the end of the risk evaluation process. A determination that a chemical "presents" unreasonable risk triggers risk management action by EPA. EPA's proposal to accept public comment on whether the chemical "presents an unreasonable risk of injury" is thus inappropriate for three reasons. First, it applies a standard that should not apply at all to manufacturer-requested risk evaluations. These requests bypass the prioritization process, and are not subject to the same requirement that EPA make a high-priority designation based on a particular risk finding. Instead, Congress intended a separate path for manufacturer- requested evaluations, and the only statutory criteria is that EPA must give preference to chemicals where restrictions by one or more states could have a "significant impact" on interstate commerce or health or the environment. EPA's proposed regulations must respect this statutory mandate for prioritizing manufacturer requests. Second, under no circumstances should EPA apply the legal standard for risk management to its decision whether to accept a chemical for risk evaluation. The "presents" standard is thus inappropriate. Third, determinations whether a chemical "may present" or "presents" unreasonable risk belong to EPA alone, by statute. The public should not be invited to opine on whether this legal standard has been met. EPA should revise this proposal. EPA should treat a valid manufacturer request for a risk evaluation as equivalent to a draft scope, and publish the document and accept public comment accordingly. F. EPA Should Remove the Certification Requirement for Manufacturer- Requested Risk Evaluations. Section 702.37(b)(5) requires manufacturers to include a signed certification that the information contained in the manufacturer request is "complete" and "accurate." This requirement is impossible to meet; manufacturers cannot simultaneously be asked to provide all reasonably available information, regardless of accuracy, and then be asked to certify its accuracy. Manufacturers cannot reasonably certify the accuracy of information produced by third parties, 40/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 or even EPA itself; they can only be asked to certify the accuracy of their own corporate information they collect and manage. They cannot reasonably be asked to provide a citation list and certify the accuracy of the internal information within every citation. Likewise, manufacturers cannot be reasonably requested to certify the "completeness" of studies or other information, or even internet searches. The very fact that EPA proposes to publish manufacturer requests and seek public comment supports this point - if manufacturers were themselves capable of locating and producing third party information, there would be no need or value for public comment. IX. Information Collection Request (ICR) Burden Estimates Associated with the proposed rule, EPA is taking comment on ICR No. 2559.01. ACC is concerned that the burden estimates provided by EPA are far too low. For each manufacture request, EPA estimates that the burden on the public will be 96 hours and $6,935. EPA assumes the hourly wage of the person submitting the request will be $72.22. The information that EPA expects industry to provide in a manufacturer request is similar to compiling all the information that EPA will provide in prioritization and scoping. As scoping will take approximately six months, acknowledging that EPA intends to collect all the data during prioritization, it is fair to assume that it will take at least as long for manufacturers to collect, assemble, review and ensure the integrity of all the hazard and exposure information for all the conditions of use that are 93 relevant. Consistent with EPA's approach, compiling all this information will require staff with expertise in human health, ecotoxicology, fate, engineering and exposure assessment. EPA assumes, for its own staff, conducting a full risk evaluation will take 5,920 hours per chemical. If we divide this over 3 years, that is approximately 1973 hours/year. If we assume scoping takes six months, that equates to approximately 987 hours excluding any contractor resources which EPA will likely also use ($75,000/chemical). Based on this calculation, ACC cannot understand why EPA thinks the collection, assembling, review, integrity assurance, and reporting will take a manufacturer only 96 hours. This assumption appears extremely low, in fact perhaps 10 fold too low. In addition, as manufacturers will be certifying their submissions, to ensure accuracy and completion, any submission to EPA will need to be reviewed at the highest levels of an organization. EPA assumes that this work will be done at the equivalent of a GS-13 step 5, or $72.22/hour. Looking at the most recent Office of Personnel Management website, for the 94 Washington DC area, a GS-13, step 5, in 2017 will earn an annual salary of $107,435.95 Considering the importance of this information, as well as the review required to inform the certification, it is likely that senior employees of manufacturers will complete this task. Using the Ninth Triennial Toxicology Survey as our source, 96 it appears that in the chemical industry, 93 See EPA ICR Attachment 1 in the rulemaking docket. 94 ACC notes that this value seems incorrect as the most recent OPM tables show a Washington DC employee at the GS-14 step 5 level making an hourly rate of $51.48. See ottps://ww.opm.gov/policy-data-oversight/pay leave/salaries-wages/salarv-tables/pdf/2017/DCB. h.pdf. 95 See OPM salary tables, available at: https://www.opm.gov/policy-data-oversight/pay-leave/salaries-wages/salary- tables/pdf/2017/DCB.pdi 96 See Ninth Triennial Toxicology Salary Survey, Table 25, available at table 25. 41/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 those with experience above 9 years (thus likely more senior) make a salary ranging from $141,000-177,000, with over 50% of the respondents in this bracket making more than $165,000. Not only is EPA's estimate of the hours needed to develop a manufacturer request too low, but the wage rate is also far too low based on the most recently available published survey results. ACC would be happy to engage further with EPA to assist the Agency in making much needed refinements to both the hours needed and wage estimates assumed in the ICR. 42/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226

EPA is taking comment on ICR No ?

kzbn0226

kzbn0226_p41, kzbn0226_p42, kzbn0226_p43, kzbn0226_p44, kzbn0226_p45, kzbn0226_p46

2559.01., 2559.01

Perhaps for simplification purposes, EPA has provided a succinct definition. However, as noted above, this definition does not appropriately capture how the sentinel exposure approach is currently used. Relying on the highest exposure scenario does not mean that the "maximal" exposure is used. Reasonable values from that highest exposure scenario should be used instead. A risk evaluation should not use a "maximal" exposure value as these values are typically unstable. More appropriate language would include the term "plausible exposure" or "plausible upper bound exposure." In the environmental toxicology field, it is common to use the 95th percentile under average exposure conditions. The "plausible maximum exposure" is not used. Significant revisions are needed to EPA's definition to capture the appropriate use of the sentinel exposure concept. E. Uncertainty EPA provides a definition for uncertainty and cites EPA's 2014 Human Health Risk Assessment 90 Framework as the source. However, as written, the definition EPA provides is actually not consistent with the source. EPA's definition should conforms to the edits below to ensure the definition is fully consistent. Uncertainty means the imperfect knowledge or lack of precise knowledge of the real world, either for specific values of interest or in the description of a the system. VIII. The Process for Manufacturer Requested Evaluations A. EPA-Initiated and Manufacturer-Requested Evaluations Should Follow the Same Review Process. LCSA allows chemical manufacturers to request EPA to conduct a risk evaluation at Section 6(b)(4)(C)(ii). By law, a manufacturer may only request a risk evaluation of a chemical it manufacturers (not of a competitor). By rule, EPA is to specify the "form and manner" for manufacturer requests, as well as to prescribe the criteria for the risk evaluation. In our view, EPA should largely follow the same process - and apply the same criteria - to manufacturer requested risk evaluations as it does to EPA-initiated risk evaluations arising out of the prioritization process. There is one notable difference: EPA has authority under LCSA to flexibly scope risk evaluations for chemicals with high priority designations to focus on conditions of use that are most relevant and meaningful to risk, and it should do so on a case-by- case basis. The result of this process might be that some risk evaluations cover all conditions of use; others a few; others only one. In the case of manufacturer-requested risk evaluations, a manufacturer may support only certain conditions of use - in other words, it may sell the chemical only for use in certain kinds of products or processes. A manufacturer may strongly support risk evaluation of its chemical under the conditions of use it supports, but may not be willing to fund evaluation of its chemical for uses supported by its competitors. While we believe EPA can expand the scope of a risk evaluation beyond that requested by a manufacturer, the agency should not impose fees on a 90 See 82 Fed. Reg. at 7568. 37/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 company that requests a risk evaluation in a manner that enriches its competitors. (Similarly, if only one manufacturer requests a risk evaluation on a chemical in a particular condition of use, it would not be appropriate to impose costs on manufacturers that did not request the risk evaluation). It will be important for EPA to address fees equitably in the upcoming fees rule; if not, the agency will discourage manufacturer requests. This is an important observation, because Congress contemplated that EPA would receive manufacturer requests for risk evaluation, and mandates that a certain number of them be accepted. At full implementation, the law anticipates that EPA will be undertaking 5-10 manufacturer-requested evaluations (assuming that not more than 20 EPA-initiated evaluations are underway). EPA should therefore promulgate criteria that make it sufficiently attractive and possible for manufacturers to avail themselves of the option. EPA should not promulgate criteria that make it largely unworkable and impossible to seek and obtain manufacturer-requested evaluations. EPA's insistence that manufacturer-requested evaluations must include "all" conditions of use obviates the use and utility of the law's provision that allows - and requires EPA to accept manufacturer-requested evaluations in the first place, leads to an absurd result, and undermines the function and purposes of the statute. B. EPA Should Respond Within Six Months from the End of the Comment Period to the Time it Notifies a Manufacturer of Acceptance of a Request. EPA should align the six months established for scoping EPA-initiated risk evaluations with those requested by manufacturers. EPA should not require more than 6 months to decide whether to accept or deny a request from a manufacturer for review. C. EPA Should Not Award "Preference" to Any Manufacturer-Requested Risk Evaluations Until the Statutory Cap is Met. EPA is required by statute to give preference to manufacturer-requested evaluations for which EPA determines that restrictions by one or more states have the potential to have a significant impact on interstate commerce or health or the environment.91 There is no other statutory basis for differentiating between requests. EPA proposes to treat this as a required "initial prioritization," after which it will further prioritize chemical substances for risk evaluation "based on initial estimates of exposure(s) and/or hazard(s) under one or more conditions of use or any other factor that EPA determines may be relevant." ACC believes this suggested approach, which could result in manufacturer requests being inappropriately rejected by EPA, is inconsistent with legislative intent, and the efficient flow of risk evaluations under LCSA. We believe that until EPA's cap on manufacturer-requested risk evaluations is met, and except for mandatory preference under TSCA 6(b)(4)(E)(iii), the Agency should accept requests for manufacturer-requested risk evaluations on a first-come, first-served basis. EPA arguably cannot, and should not, deny any otherwise compliant request until 5 evaluations are underway, since there may not be a rational basis to be able to compare requests for evaluation. After EPA has 5 manufacturer-requested evaluations underway, it should apply the same prioritization criteria set out in the prioritization rule for selection of chemicals for evaluation. It should not 91 TSCA 6(b)(4)(E)(iii). 92 82 Fed. Reg. 7569. 38/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 impose new criteria of "high hazard" and "high exposure" divorced from the criteria established in the prioritization rule. We also strongly urge EPA to delete the catch-all provision, "any other factor EPA determines may be relevant." For the manufacturer-requested risk evaluation process to function, manufacturers must have fair notice of the criteria they must meet to have a request considered. An open-ended catchall provision not only undermines congressional intent; it eliminates fair notice to manufacturers of what information they need to gather and prepare in order to have a request considered. This is particularly the case given that manufacturers may need to conduct testing and incur significant costs before they request a risk evaluation. D. EPA Should Not Require Submission of "All" Prior Risk Assessments by Manufacturers as a Precondition to Accepting a Manufacturer Request. Section 702.37(b)(4) proposes that manufacturer requests must include a commitment to provide to EPA any referenced information on request, an appropriate request (subject to CBI protection, if applicable). This section provides further, however, that a manufacturer must submit any previous risk assessment conducted by a manufacturer as well as any it "possesses" or "can reasonably obtain." While we appreciate that TSCA § 26(k) requires EPA to take into consideration reasonably available information as part of Section 6 risk evaluations, this should not devolve into a blanket request for certain proprietary reviews undertaken by manufacturers. Many risk assessments fall into that category. EPA may properly request manufacturers to produce information with a manufacturer request for a risk evaluation where the Agency has legal authority to make the request and the information is otherwise relevant to the risk evaluation, meets data quality standards, and meets Section 26 scientific standards. EPA cannot, however, create new legal authority for itself to demand otherwise protected information as a condition of considering a manufacturer request for risk evaluation. This is to be contrasted with health and safety results, which may be inputs in a risk assessment but are distinct from a risk assessment. ACC, in fact, has long had a policy in its Chemical Products and Technology Division to make publicly available the final reports or validated final results of environmental, health, and safety research managed or sponsored under the group (subject to exceptions needed to preserve legal rights, such as proprietary rights, data compensation rights or to protect confidential business information). EPA also may appropriately request a manufacturer to provide, as part of its request, any information that EPA could otherwise require under TSCA Sections 8(a), 8(c), 8(d) (health and safety studies), and 8(e) (which would already have been reported to the agency). We urge EPA to revise the proposal accordingly to clarify that manufacturers will be expected to produce information relevant to the risk evaluation, and that EPA confirm it will protect CBI and respect other legal doctrines protecting against disclosure. 39/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 E. EPA Should Limit Public Comments Accepted on a Manufacturer Request to the Expected Scope of the Risk Evaluation. As EPA properly notes in the preamble, the agency must grant any manufacturer request that complies with EPA's criteria, until the statutory minimum of 25 percent has been met. EPA may set criteria by rule. Section 702.37(e)(2) proposes a public comment period on valid manufacturer requests for risk evaluations which injects inappropriate criteria - the public is invited to submit comments and information "relevant to whether the chemical substance presents an unreasonable risk of injury to health or the environment." For EPA-initiated risk evaluations, the legal standard that begins the risk evaluation process is EPA's determination that a chemical "may present" an unreasonable risk of injury. A determination that a chemical "presents" an unreasonable risk is not made, if at all, until the end of the risk evaluation process. A determination that a chemical "presents" unreasonable risk triggers risk management action by EPA. EPA's proposal to accept public comment on whether the chemical "presents an unreasonable risk of injury" is thus inappropriate for three reasons. First, it applies a standard that should not apply at all to manufacturer-requested risk evaluations. These requests bypass the prioritization process, and are not subject to the same requirement that EPA make a high-priority designation based on a particular risk finding. Instead, Congress intended a separate path for manufacturer- requested evaluations, and the only statutory criteria is that EPA must give preference to chemicals where restrictions by one or more states could have a "significant impact" on interstate commerce or health or the environment. EPA's proposed regulations must respect this statutory mandate for prioritizing manufacturer requests. Second, under no circumstances should EPA apply the legal standard for risk management to its decision whether to accept a chemical for risk evaluation. The "presents" standard is thus inappropriate. Third, determinations whether a chemical "may present" or "presents" unreasonable risk belong to EPA alone, by statute. The public should not be invited to opine on whether this legal standard has been met. EPA should revise this proposal. EPA should treat a valid manufacturer request for a risk evaluation as equivalent to a draft scope, and publish the document and accept public comment accordingly. F. EPA Should Remove the Certification Requirement for Manufacturer- Requested Risk Evaluations. Section 702.37(b)(5) requires manufacturers to include a signed certification that the information contained in the manufacturer request is "complete" and "accurate." This requirement is impossible to meet; manufacturers cannot simultaneously be asked to provide all reasonably available information, regardless of accuracy, and then be asked to certify its accuracy. Manufacturers cannot reasonably certify the accuracy of information produced by third parties, 40/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 or even EPA itself; they can only be asked to certify the accuracy of their own corporate information they collect and manage. They cannot reasonably be asked to provide a citation list and certify the accuracy of the internal information within every citation. Likewise, manufacturers cannot be reasonably requested to certify the "completeness" of studies or other information, or even internet searches. The very fact that EPA proposes to publish manufacturer requests and seek public comment supports this point - if manufacturers were themselves capable of locating and producing third party information, there would be no need or value for public comment. IX. Information Collection Request (ICR) Burden Estimates Associated with the proposed rule, EPA is taking comment on ICR No. 2559.01. ACC is concerned that the burden estimates provided by EPA are far too low. For each manufacture request, EPA estimates that the burden on the public will be 96 hours and $6,935. EPA assumes the hourly wage of the person submitting the request will be $72.22. The information that EPA expects industry to provide in a manufacturer request is similar to compiling all the information that EPA will provide in prioritization and scoping. As scoping will take approximately six months, acknowledging that EPA intends to collect all the data during prioritization, it is fair to assume that it will take at least as long for manufacturers to collect, assemble, review and ensure the integrity of all the hazard and exposure information for all the conditions of use that are 93 relevant. Consistent with EPA's approach, compiling all this information will require staff with expertise in human health, ecotoxicology, fate, engineering and exposure assessment. EPA assumes, for its own staff, conducting a full risk evaluation will take 5,920 hours per chemical. If we divide this over 3 years, that is approximately 1973 hours/year. If we assume scoping takes six months, that equates to approximately 987 hours excluding any contractor resources which EPA will likely also use ($75,000/chemical). Based on this calculation, ACC cannot understand why EPA thinks the collection, assembling, review, integrity assurance, and reporting will take a manufacturer only 96 hours. This assumption appears extremely low, in fact perhaps 10 fold too low. In addition, as manufacturers will be certifying their submissions, to ensure accuracy and completion, any submission to EPA will need to be reviewed at the highest levels of an organization. EPA assumes that this work will be done at the equivalent of a GS-13 step 5, or $72.22/hour. Looking at the most recent Office of Personnel Management website, for the 94 Washington DC area, a GS-13, step 5, in 2017 will earn an annual salary of $107,435.95 Considering the importance of this information, as well as the review required to inform the certification, it is likely that senior employees of manufacturers will complete this task. Using the Ninth Triennial Toxicology Survey as our source, 96 it appears that in the chemical industry, 93 See EPA ICR Attachment 1 in the rulemaking docket. 94 ACC notes that this value seems incorrect as the most recent OPM tables show a Washington DC employee at the GS-14 step 5 level making an hourly rate of $51.48. See ottps://ww.opm.gov/policy-data-oversight/pay leave/salaries-wages/salarv-tables/pdf/2017/DCB. h.pdf. 95 See OPM salary tables, available at: https://www.opm.gov/policy-data-oversight/pay-leave/salaries-wages/salary- tables/pdf/2017/DCB.pdi 96 See Ninth Triennial Toxicology Salary Survey, Table 25, available at table 25. 41/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 those with experience above 9 years (thus likely more senior) make a salary ranging from $141,000-177,000, with over 50% of the respondents in this bracket making more than $165,000. Not only is EPA's estimate of the hours needed to develop a manufacturer request too low, but the wage rate is also far too low based on the most recently available published survey results. ACC would be happy to engage further with EPA to assist the Agency in making much needed refinements to both the hours needed and wage estimates assumed in the ICR. 42/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226

what is IPP stands for ?

hlcn0226

hlcn0226_p0, hlcn0226_p1, hlcn0226_p2, hlcn0226_p3, hlcn0226_p4, hlcn0226_p5, hlcn0226_p6, hlcn0226_p7, hlcn0226_p8, hlcn0226_p9, hlcn0226_p10, hlcn0226_p11

International Personal Protection, international personal protection

129 From: Jürgen Troitzsch To: Osimitz Thomas; Dr. Blais Matthew; Prof. Rein Guillermo; Dr. Hayes Wallace; Dourson. Michael (doursomi); Kacew Sam; Dr. Wise Kimberly Subject: Fwd: Project on FF PPE Cleaning Validation Date: Monday, June 12, 2017 1:11:46 PM Attachments: PROU PANEL - PPE Cleaning (33) pdf PROJ SUMMARY - PPE Cleaning (7) pot FLYER FF Contam Control Workshop (6) odf HOTELS - Contam Control Wrkshp on 2017Jul19.pd PROJS JMMARY- FE Cancer Cohort Study (4) odf Dear All, I came across this project, which may be of interest in the frame of our fire fighters cancer activities. Kind regards/Viele Grüße Jürgen Dr. Jürgen Troitzsch Fire and Environment Protection Service FEPS Via Patrizia 32 CH-6612 Ascona, Switzerland Mobile: +41 79 289 17 16 Phone: +41 91 791 14 22 Email: [email protected] Web: www.troitzsch.com De : Grant, Casey Envoyé : lundi 22 mai 2017 17:58 À : [email protected]; [email protected]. tis.com; mlambetamallN u.edu; dwardmecarthyebostengoy ark.a.miller@ehoen ix.gov; james.riley@bosta nagov; [email protected] Thomas [email protected]; ;timügearcleaningsolutions.s om [email protected]; Ken.Wiles @fire.jacounty.gov Farrell, Christopher cobtlogiobefiresuits.com; pattogiobefiresults.com; Diane.Hess@ Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 130 PBIProducts.com; Kebtonen@lionprotedscon leur.gouv.fr; GUILLAUME Eric <eric [email protected] ;[email protected]; mamiefortunes-collide.com Cc : lasonallendintertekeor [email protected]; [email protected] wlindslev@ cdc.gov; [email protected] [email protected]; [email protected]; ; istendice OY; Objet : Project on FF PPE Cleaning Validation To: Panel, Research Team and Liaisons for Project on "Fire Fighter PPE Cleaning Validation" It has been some time since we last spoke, and I have the following three items to be addressed: 1) A lot has been happening with our project and we want to hold a 90 minute conference call in early August 2017 to bring everyone up-to-date. I've created a scheduling poll to determine the optimum date/time Please respond before Noon ET on Wednesday 31/May/2017 so that we can get this on our calendars. I've attached the Project Roster and Project Summary in case anyone needs a refresher for this project addressing "how clean is clean". Thanks. 2) I've been asked to participate in a webinar tomorrow (23/Mav/2017) from noon ET to 1:30 pm ET on "Factors Relating to Cancer and Contamination in the US Fire Service". I've been assigned a portion of this webinar (among two other speakers) to address on-going research and I'm planning to address our project among several other on-going efforts. The link is on the NFPA home page at: FYI.. 3) Some of you are already aware of the Workshop in Columbus, Ohio on 19- 20/Julv/2017, and if not I want to call it to your attention. This is for the separate one year AFG project on "Campaign for Fire Service Contamination Control". Attached is a Flyer that provides additional details, and also attached is a list of hotels in the area to assist with travel. The workshop will be held from Noon to Noon on 19-20/July and we still have room if you would like to attend. In addition, the separate project (i.e., a third related project) on "Fire Fighter Cancer Cohort Study" will hold a separate planning meeting on the afternoon of 20/July from 1 pm to 5 pm (Project Summary is attached). All are welcome to attend this as well. If you are a fire service panel member we can cover your travel, and I can send follow-up instructions to you separately. For anyone interested in attending the Columbus meetings on 19-20/July, please let us know by email to [email protected] and Thanks.. Casey C. Grant, P.E. Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION "CAMPAIGN FOR FIRE SERVICE CONTAMINATION CONTROL" WORKSHOP Location: Columbus Fire Fighters Union Hall, 379 W Broad St, Columbus, OH 43215 Workshop Dates: 19-20 July 2017 (Last Updated: 21 April 2017; subject to update) Background: Exposure to chemical and biological contaminants on the fire ground is an increasing concern for long-term fire fighter health. Cancer and other diseases resulting from chronic exposures has become a leading concern for the fire service. This is presumed to be associated with fireground exposures relating to protection/hygiene practices and persistent harmful contamination found in fire fighter equipment, apparatus carrying that equipment, and stations where the equipment resides. Workshop Goal and Objectives: The goal of this Workshop is to identify concepts and materials that are or can be useful to control the spread of harmful fire ground contaminants, ultimately in support of improved fire fighter long-term health. The following objectives support this goal (and reflect anticipated deliverables): Identify, review and recommend baseline materials (existing and proposed) addressing best practices, standards, research, equipment, facilities, and other areas of focus. Identify and prioritize gaps that are barriers to enhancing best practices, standards, research, equipment, facilities, and other areas of focus. Identify and review key characteristics for effective promotion and communication. Clarify target audiences for outreach and consider stakeholder research prior to developing a comprehensive communications plan to improve outcome. Prioritize messages for year one. Agenda: Wed; 19/July 1:00 pm Day One: Welcome and Call to Order Casey Grant, FPRF 1:15 pm Overview of Baseline Materials and Review of Gaps Jeff Stull, IPP 2:00 pm Review of Outreach Peg, Paul, PPA 2:30 pm Case Study: Best Practice Information Beth Gallup, KFD 3:00 pm PM Break 3:15 pm Casey Study: Standards Revisions Dave Bernzweig, CFD 3:45 pm Case Study: Equipment & Facilities Paul Erickson, LEWA 4:15 pm Breakout Groups Workshop Attendees 5:00 pm Adjourn for Day One (& Evening Networking Reception) Thur; 20/July 8:30 am Day Two: Group Review of Baseline Materials Jeff Stull, IPP 8:45 am Breakout Groups Continue Workshop Attendees 9:45 am AM Break 10:00 am Breakout Group Report Workshop Attendees 11:00 am Plenary Discussion Workshop Attendees 11:30 am Workshop Wrap-up & Summary Observations Casey Grant, FPRF 12:00 pm Adjournment Registration: Workshop attendance is limited to the first 50 attendees, and others will be placed the on a waiting list. To request attendance or for more information, please contact [email protected]. After the Workshop a report will be available. This Workshop is funded through an AFG Fire Prevention & Safety Grant from U.S.DHS/FEMA. 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7281 Fax: +1.617.984.7010 Email: [email protected] www.NFPA.org/Foundation Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 WORKSHOP ON FIRE SERVICE CONTAMINATION CONTROL 19-20 July 2017 (Noon to Noon ET) Columbus Fire Fighters Union Hall 379 W Broad St, Columbus, OH 43215 Note: For flights, Workshop starts at Noon ET on 19/July/2017 and finishes at Noon ET on 20/July/2017 Drury Inn & Suites: 88 East Nationwide Blvd, Columbus, OH 43215 Phone: 1-614-221-7008 ttos://www.drurvhotels.com/locations/columbus-ob/drurv-inn-and-suites-columbus-convention: center Approximate Rate: $130 Distance (in miles) from Hotel to Columbus Union Hall: 1.3 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars. Red Roof Plus Columbus Downtown Convention Center 111 East Nationwide Blvd, Columbus, OH 43215 Phone: 1-614-224-6539 ittps://www.redroof.com/property/Columbus/OH/43215/Hotels-close-to-Greater-columbus- Convention-Center-US-23-1-670/RRI262/ Approximate Rate: $130 Distance (in miles) from Hotel to Columbus Union Hall: 1.4 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars. Sheraton Columbus Hotel at Capital Square 75 East State Street, Columbus, OH, 43215 Phone: 1-614-365-4500 http://www.sheratoncolumbuscapitolsquare.com/ Approximate Rate: $170 Distance (in miles) from Hotel to Columbus Union Hall: 0.8 Notes: Central downtown area Hampton Inn and Suites Columbus Downtown 501 North High Street, Columbus, OH 43215 Phone: 1-614-559-2000 htto://hamptoninns.bilton.com/en/hotels/ohio/hampton-inn-and-suites-columbus-downtown- CMHHSHK/index.htmi?WT.mc. Approximate Rate: $175 Distance (in miles) from Hotel to Columbus Union Hall: 1.3 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars. Page 1 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Courtyard Columbus Downtown 35 West Spring Street, Columbus, Ohio 43215 Phone: 1-614-228-3200 4d19-a255-54ba596febe2 Approximate Rate: $175 Distance (in miles) from Hotel to Columbus Union Hall: 0.8 Notes: Downtown west area; walkable Doubletree Suites by Hilton Columbus Downtown 50 South Front St, Columbus, Ohio, 43215-4145 Phone: 1-614-228-4600 CMHSBOT/index.htmi Approximate Rate: $200 Distance (in miles) from Hotel to Columbus Union Hall: 0.5 Notes: Closest hotel to meeting site; very short walk Residence Inn Columbus Downtown 36 East Gay Street, Columbus, Ohio 43215-3108 Phone: 1-614-222-2610 ec3-4d19-a255-54ba596febe2 Approximate Rate: $230 Distance (in miles) from Hotel to Columbus Union Hall: 0.8 Renaissance Columbus Downtown 50 North Third Street, Columbus, Ohio 43215 Phone: 1-614-228-5050 ttp://www.marriott.com/hotels/travel/cmhbr-renaissance-columbus-downtown-hotel/ Approximate Rate: $240 Distance (in miles) from Hotel to Columbus Union Hall: 1.0 Notes: Central downtown area Hilton Columbus Downtown 401 North High Street, Columbus, OH 43215 Phone: 1-614-384-8600 Approximate Rate: $240 Distance (in miles) from Hotel to Columbus Union Hall: 1.1 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars; New facility and nice. Page 2 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION PPE Cleaning Validation Validation of Cleaning Procedures for Fire Fighter Personal Protective Equipment (PPE) PROJECT CONTACTS Last Updated: 22 May 2017 Project Technical Panel Phone: 614-774-7446 David Bernzweig, Columbus Fire Department (OH) Email: [email protected] Phone: 780-496-3801 Ken Block, Edmonton Fire/Rescue & Metro Chiefs Representative Email: [email protected] Phone: 804-971-7983 Ken Brown, VA State Firefighter's Association & NVFC (Alt to B. McQueen) Email; [email protected] Phone: 510-839-5111 Cell: 213-321-9393 Roger Curtis, ECMS Curtis & Sons (CA) Email: [email protected] Phone: Paul Curtis, ECMS Curtis & Sons (CA) (Alt to Roger Curtis) Email: [email protected] Phone: 253-277-4131 Cell: 503-314-4832 Steve Lakey, Northwest Safety Clean (WA) Email: [email protected] Phone: 304-406-7479 Mark Lambert, WV Fire Academy & NAFTD (WV) Email: [email protected] Phone: 617-828-3978 Ed McCarthy, Boston Fire Department (MA) Email: [email protected] Phone: 315-736-7479 Cell: 315-552-8245 Brian McQueen, FASNY & National Volunteer Fire Council (NY) Email: [email protected] Phone: 602-534-2396 Mark Miller, Phoenix Fire Dept. (AZ) Email: [email protected] Phone: 919-524-1569 Bryan Ormond, NCSU (NC) Email: [email protected] Phone: Russ Osgood, Firefighter Cancer Support Network (NH) (Alt to Keith Tyson) Email: [email protected] Phone: Larry Petrick, IAFF (DC) Email: [email protected] Phone: 617-549-9850 Jim Riley, Boston Fire Department (MA) (Alt to E. McCarthy) Email: [email protected] Phone: 757-385-2892 Molly Riley, Virginia Beach Fire Dept. (VA) Email: [email protected] Phone: 718-999-2922 Thomas Smith, FDNY (NY) Email: [email protected] Phone: 214-774-2213 Cell: 940-300-5718 Tim Tomlinson, Gear Cleaning Solutions (TX) Email: [email protected] Phone: Robert Tutterow, NFPA Fire Service Section (NC) Email: [email protected] Phone: 786-351-3276 Keith Tyson, Firefighter Cancer Support Network (FL) Email: [email protected] Phone: 951-807-1914 Dick Weise, LA County Fire Dept. (CA) Email: [email protected] Phone: 949-291-0637 Ken Wiles, LA County Fire Dept. (CA) (Alt to Dick Weiss) Email: [email protected] Phone: 512-974-0286 Chris Youngblood, Austin Fire Dept. (TX) Email: [email protected] 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7281 Fax: +1.617.984.7010 Email: [email protected] www.NFPA.org/Foundation Source: :https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Phase 1 Project Contacts Phone: 330-723-0000, x365 Steve Allison, Fire-Dex (OH) Email: [email protected] Phone: 800-401-4780 Jack Binder, Edmar Chemical Company (OH) Email: [email protected] Phone: 920-570-0824 Bill Brooks, Alliance Corp. (WI) Email: [email protected] Phone: Charlie Dunn, TenCate Protective Fabrics Email: [email protected] Phone: 617-984-7325 Chris Farrell, NFPA & Staff Liaison for NFPA 1851 (MA) Email: [email protected] Phone: 800-232-8323 Rob Freese, Globe Manufacturing (NH) Email: [email protected] Phone: Pat Freeman, Globe Manufacturing (NH) (Alternate to Rob Freese) Email: [email protected] Phone: 704-554-3313 Diane Hess, PBI Performance Products (NC) Email: [email protected] Phone: 937-415-2932 Karen Lehtonen, LionFirst Responder Products (OH) Email: [email protected] Phone: 484-433-4072 Dan Silvestri, 9-1-1 Safety (PA) Email: [email protected] Liaison Contacts Phone: Pierre Carlotti, Ministry of Interior & Liaison for ISO TC92/SC3 (France) Email: [email protected] Phone: Eric Guillaume, Efectis & Liaison for ISO TC92/SC3 (France) Email: [email protected] Phone: Bill Haskell, NIOSH NPPTL (MA) Email: [email protected] Phone: James Hoar, Boston Fire Department (MA) Email: [email protected] Phone: 631-242-0621 Steve King, Chair NFPA 1851 (NY) Email: [email protected] Phone: +33(0)1.55.76.26.18 Fanny Rieunier, Ministry of Interior & Liaison for ISO TC92/SC3 (France) Email: [email protected] Phone: 612-247-6429 Marni Schmid, Fortunes Collide & Secretariat NFPA 1851 (MI) Email: [email protected] Page 2 of 3 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Core Research Team Phone: 607-758-6537 Cell: 607-423-5617 Jason Allen, Intertek (NY) Email: [email protected] Phone: 304-285-6076 Daniel Farcas, NIOSH HELD (WV) Email: [email protected] Phone: Crystal Forester, NIOSH NPPTL (WV) Email: [email protected] Phone: 617-984-7284 Cell: 617-659-1159 Casey Grant, Fire Protection Research Foundation (MA) Email: [email protected] Phone: Lee Greenawald, NIOSH NPPTL (WV) Email: [email protected] Phone: Bill Lindsley, NIOSH HELD (WV) Email: [email protected] Phone: Stephen Martin, NIOSH DRDS (WV) Email: [email protected] Phone: John Noti, NIOSH HELD (WV) Email: [email protected] Phone: Deborah Sbarra, NIOSH NPPTL (WV) Email: [email protected] Phone: 512-288-8272 cell: 512-623-9558 Jeff Stull, International Personal Protection (TX) Email: [email protected] Phone: 304-285-5858 cell: 681-209-2571 Jay Tarley, NIOSH NPPTL (WV) Email: [email protected] Additional Research Team Contacts Phone: 304-285-5884 Francoise Blachere, NIOSH HELD (WV) Email: [email protected] Phone: Renee Dotson, NIOSH HELD (WV) Email: [email protected] Phone: James Harris, NIOSH NPPTL (WV) Email: [email protected] Phone: Ryan Lebouf, NIOSH DRDS (WV) Email: [email protected] Phone: 617-984-7281 Eric Peterson, Fire Protection Research Foundation (MA) Email: [email protected] Phone: John Powers, NIOSH (WV) Email: [email protected] Phone: 412-386-4621 Cell: 412-463-9561 Heather Reed, NIOSH NPPTL (PA) Email: [email protected] Page 3 of 3 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION PPE Cleaning Validation Validation of Cleaning Procedures for Fire Fighter Personal Protective Equipment (PPE) (for more information see www.nfpa.org/PPECleaning) PROJECT SUMMARY Last updated: 5 February 2016 Background: Fire fighter exposure to personal protective equipment (PPE) that is dirty, soiled, and contaminated is an increasing concern for long-term fire fighter health. This exposure to persistent harmful contaminants in PPE is an extremely serious problem both on the fireground to highly toxic substances including a variety of carcinogens, and more insidiously to an increasing range of infectious pathogens that are encountered in patient care and different emergency operations. Fire fighter PPE becomes contaminated during these exposures and there are no industry standards that conclusively and reliably show that clothing is being adequately cleaned. While general cleaning procedures have been established in NFPA 1851, Standard on Selection, Care, and Maintenance of Protective Ensembles for Structural Fire Fighting and Proximity Fire Fighting, there are no procedures or requirements to demonstrate whether current cleaning practices, including those specified in NFPA 1851, will remove contaminants from fire fighter protective clothing. This project is intended to establish clear and definitive guidance to the fire service for applying cleaning and decontamination procedures that effectively remove both chemical and biological contaminants. Research Goal and Objectives, and Conceptual Approach: The overall goal of this project is to improve fire fighter safety and health by reducing continuing exposure to harmful contaminants in unclean or inadequately cleaned PPE. The objectives to achieve this goal are twofold: (1) To characterize fireground and emergency scene contamination leading to these exposures and develop the methodology for the consistent measurement of cleaning effectiveness; and (2) determine implementable cleaning, decontamination, and disinfection strategies that effectively reduce fire fighter exposures to persistent contaminants. The approach taken by this project is illustrated in Figure 1: Project Conceptual Approach. - Ensure Identify Devise Validate lab - - chemical and methods to methods - at biologicat conteminate againet field ses target clothing in contaminants laboratory exposures acceptance Project Direction Figure 1: Project Conceptual Approach 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7281 Fax: +1.617.984.7010 Email: [email protected] www.NFPA.org/Foundation Source: :ttps://www.industrydocuments.ucsf.edu/docs/hlcn0226 Project Phases and Tasks: This project involves the following four key phases of activity: 1) Identification of Contaminants: Confirm identification and ability to characterize persistent chemical and biological contaminants in fire fighter PPE through target substances and microorganisms. 2) Establishment of Soil and Chemical Contamination/Decontamination Procedures: Develop and validate specific procedures that determine the effectiveness of laundering and other cleaning methods in removing specific soils and chemical contaminants. 3) Establishment of Biological Contamination/Disinfection or Sanitization Procedures: Develop and validate specific procedures that determine the effectiveness of laundering or disinfection/sanitization processes that remove/deactivate biologically-based contaminants. 4) Creation of Overall Fire Service Guidance: Prepare clear and definitive information for the fire service industry (fire fighters, fire departments, clothing manufacturers, material suppliers, cleaning/care organizations, and cleaning agent or equipment manufacturers) on appropriate approaches for properly cleaning fire fighter protective clothing and equipment. The specific tasks of this project are based on these four phases of the project, and these are illustrated in Figure 2: Project Tasks. PHASE 2 PHASEZ Task 2.4 Task 2.5 Task 1.1 Task 2.1 Validate testsat Refine test Appoint Technical Select cleaning selected ISPS methodology Review Panel methods/agents (chemical) (chemical) PHASE $ Task 4.1 Task 1.2 Task 2.2 Write qualification Review Prigr Put together test plan methods studies/literature (chemical) Task 2.3 Task 4.2 Task 1.3 PHASE 3 Perform laboratory Establish cleaning Setup analytical chemical Task 3.3 acceptance criteria capabilities decontaminant Put together test plan testing (biological) Task 4.3 Task 1.4 Perform Task 3.4 Prepare public inputs for NFPA 1851 demonstration tests Task 3.1 Perform laboratory Task 3.6 Select study biological Refine test microorganisms decontaminant methodology Task 1.5 testing (biological) Task 4.4 Refine biological Prepare industry decontamination Task 3.2 Task 3.5 guidance document scope Select biological Validate testsat cleaning methods selected ISPs (biological) Task 1.6 Task 4,5 Establish cleanliness Prepare project final metrics report Figure 2: Project Tasks Implementation and Schedule: This three year project is due to be completed no later than " August 2018, and is funded through an AFG Fire Prevention & Safety Grant from the U.S. Department of Homeland Security / Federal Emergency Management Agency. The Research Foundation will lead a unique research team partnership composed of the FPRF, National Institute for Occupational Safety and Health (NIOSH), International Personal Protection (IPP), and Intertek. The research team, along with several Independent Service Providers (ISPs), will work with the fire service partners and others to validate and optimize fire fighter PPE cleaning validation methods. For more information see www.nfpa.org/PPECleaning. Page 2 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION Fire Fighter Cancer Cohort Study Full Title: The Firefighter Multicenter Cancer Cohort Study: Framework Development and Testing PROJECT SUMMARY Last Updated: 20 September 2016 Background: Cancer is a leading cause of fire service morbidity and mortality. Firefighter exposure to carcinogens occurs through skin contamination and through inhalation when respiratory protection is not worn when combustion products are present such as during overhaul, standby, and operation of apparatus, as well as through off-gassing of equipment and exposures in the fire station. However, we currently do not understand which exposures are responsible for cancer in firefighters, the mechanisms by which firefighter exposures cause cancer, nor the most effective means of reducing exposures. Since cancer has a long latency period, biomarkers are also needed that can measure the toxicological effects of carcinogen exposure well before the development of cancer, when interventions to prevent disease could be effective. Development of a large (>10,000 firefighter) multicenter firefighter cancer prospective cohort study will address these needs, but the framework for such a study needs to be first developed and tested among a smaller initial set of fire service partners. Implementation and Schedule: This research project is led by University of Arizona with collaborative support from multiple other research partners, including the University of Miami, National Institute for Occupational Safety and Health; National Fallen Firefighter Foundation, Fire Protection Research Foundation, and others. Initial funding for this project is through a 3-year DHS/FEMA Assistance to Fire Fighter (AFG) Fire Grant, with the intention to identify and obtain additional funding for the duration of the 30 year effort. The project start date is August 2016. The Principal Investigator for this project is: Jefferey L. Burgess, MD, MS, MPH, University of Arizona, email: [email protected]. Project Goal and Aims: The goal of the initial 3-year effort of this overall project is to develop and test a framework for establishing a long-term fire fighter multicenter prospective cohort study focused on carcinogenic exposures and effects. The specific aims are to: 1) Establish an oversight and planning board to provide study oversight, foster communication among fire organizations and help develop a long-term funding plan; 2) Create and test a cohort study data coordinating center and harmonized survey data protocols; 3) Develop and validate a firefighter carcinogen exposure matrix and data collection system; and 4) Create a biomarker assessment center and evaluate the association between cumulative firefighter exposures and epigenetic effects. For more information, contact: Casey Grant, Fire Protection Research Foundation 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7284 Fax: +1.617.984.7010 Email: [email protected] Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Project Methodology: This study will harmonize and build on recent and developing firefighter cancer prevention studies in Arizona, Florida and Massachusetts, adding volunteer fire departments. An oversight and planning board will be established by the Fire Protection Research Foundation (FPRF) in association with the National Fallen Firefighter Foundation (NFFF) Fire Service Occupational Cancer Alliance (FSOCA) to provide oversight of the study through collaboration among fire service organizations, academia, and government agencies, and develop a long-term funding and sustainability plan. A data coordination center team will design, develop and evaluate a framework for a multicenter prospective cohort study of firefighters and cancer risk, including standardized participant survey data collection tools and analysis protocols sufficient to address the short- and long-term study objectives as well as linkage with long-term outcome data including cancer development. An exposure assessment center team will develop a carcinogen exposure matrix and data collection system to provide improved occupational exposure data for comparison with epigenetic outcomes and eventual cancer outcomes. Carcinogen exposures associated with specific fire types will be evaluated across fire departments through industrial hygiene monitoring and analysis of urine for absorbed contaminants, supplementing existing FEMA-funded and other studies of firefighter exposures and allowing for participating fire departments to design interventions to reduce current exposures. Expansion of the National Fire Operations Reporting System (NFORS) will be explored as one option to uniformly collect incident and exposure data. Blood and buccal cells will be collected during annual medical surveillance evaluations, including both new recruits and incumbent firefighters. Pilot studies of epigenetic markers of cancer effect and cancer risk will be analyzed comparing municipal firefighters with high chronic exposures, volunteer firefighters with low chronic exposures, and non- firefighter friends of the municipal firefighters (serving as controls). Project Deliverables: The anticipated outcomes from this 3-year effort is to establish and test the framework necessary for the subsequent development of a large multicenter cohort study of cancer in the fire service. Page 2 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226

what is NIOSH stands for ?

hlcn0226

hlcn0226_p0, hlcn0226_p1, hlcn0226_p2, hlcn0226_p3, hlcn0226_p4, hlcn0226_p5, hlcn0226_p6, hlcn0226_p7, hlcn0226_p8, hlcn0226_p9, hlcn0226_p10, hlcn0226_p11

National Institute for Occupational Safety and Health, national institute for occupational safety and health

129 From: Jürgen Troitzsch To: Osimitz Thomas; Dr. Blais Matthew; Prof. Rein Guillermo; Dr. Hayes Wallace; Dourson. Michael (doursomi); Kacew Sam; Dr. Wise Kimberly Subject: Fwd: Project on FF PPE Cleaning Validation Date: Monday, June 12, 2017 1:11:46 PM Attachments: PROU PANEL - PPE Cleaning (33) pdf PROJ SUMMARY - PPE Cleaning (7) pot FLYER FF Contam Control Workshop (6) odf HOTELS - Contam Control Wrkshp on 2017Jul19.pd PROJS JMMARY- FE Cancer Cohort Study (4) odf Dear All, I came across this project, which may be of interest in the frame of our fire fighters cancer activities. Kind regards/Viele Grüße Jürgen Dr. Jürgen Troitzsch Fire and Environment Protection Service FEPS Via Patrizia 32 CH-6612 Ascona, Switzerland Mobile: +41 79 289 17 16 Phone: +41 91 791 14 22 Email: [email protected] Web: www.troitzsch.com De : Grant, Casey Envoyé : lundi 22 mai 2017 17:58 À : [email protected]; [email protected]. tis.com; mlambetamallN u.edu; dwardmecarthyebostengoy ark.a.miller@ehoen ix.gov; james.riley@bosta nagov; [email protected] Thomas [email protected]; ;timügearcleaningsolutions.s om [email protected]; Ken.Wiles @fire.jacounty.gov Farrell, Christopher cobtlogiobefiresuits.com; pattogiobefiresults.com; Diane.Hess@ Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 130 PBIProducts.com; Kebtonen@lionprotedscon leur.gouv.fr; GUILLAUME Eric <eric [email protected] ;[email protected]; mamiefortunes-collide.com Cc : lasonallendintertekeor [email protected]; [email protected] wlindslev@ cdc.gov; [email protected] [email protected]; [email protected]; ; istendice OY; Objet : Project on FF PPE Cleaning Validation To: Panel, Research Team and Liaisons for Project on "Fire Fighter PPE Cleaning Validation" It has been some time since we last spoke, and I have the following three items to be addressed: 1) A lot has been happening with our project and we want to hold a 90 minute conference call in early August 2017 to bring everyone up-to-date. I've created a scheduling poll to determine the optimum date/time Please respond before Noon ET on Wednesday 31/May/2017 so that we can get this on our calendars. I've attached the Project Roster and Project Summary in case anyone needs a refresher for this project addressing "how clean is clean". Thanks. 2) I've been asked to participate in a webinar tomorrow (23/Mav/2017) from noon ET to 1:30 pm ET on "Factors Relating to Cancer and Contamination in the US Fire Service". I've been assigned a portion of this webinar (among two other speakers) to address on-going research and I'm planning to address our project among several other on-going efforts. The link is on the NFPA home page at: FYI.. 3) Some of you are already aware of the Workshop in Columbus, Ohio on 19- 20/Julv/2017, and if not I want to call it to your attention. This is for the separate one year AFG project on "Campaign for Fire Service Contamination Control". Attached is a Flyer that provides additional details, and also attached is a list of hotels in the area to assist with travel. The workshop will be held from Noon to Noon on 19-20/July and we still have room if you would like to attend. In addition, the separate project (i.e., a third related project) on "Fire Fighter Cancer Cohort Study" will hold a separate planning meeting on the afternoon of 20/July from 1 pm to 5 pm (Project Summary is attached). All are welcome to attend this as well. If you are a fire service panel member we can cover your travel, and I can send follow-up instructions to you separately. For anyone interested in attending the Columbus meetings on 19-20/July, please let us know by email to [email protected] and Thanks.. Casey C. Grant, P.E. Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION "CAMPAIGN FOR FIRE SERVICE CONTAMINATION CONTROL" WORKSHOP Location: Columbus Fire Fighters Union Hall, 379 W Broad St, Columbus, OH 43215 Workshop Dates: 19-20 July 2017 (Last Updated: 21 April 2017; subject to update) Background: Exposure to chemical and biological contaminants on the fire ground is an increasing concern for long-term fire fighter health. Cancer and other diseases resulting from chronic exposures has become a leading concern for the fire service. This is presumed to be associated with fireground exposures relating to protection/hygiene practices and persistent harmful contamination found in fire fighter equipment, apparatus carrying that equipment, and stations where the equipment resides. Workshop Goal and Objectives: The goal of this Workshop is to identify concepts and materials that are or can be useful to control the spread of harmful fire ground contaminants, ultimately in support of improved fire fighter long-term health. The following objectives support this goal (and reflect anticipated deliverables): Identify, review and recommend baseline materials (existing and proposed) addressing best practices, standards, research, equipment, facilities, and other areas of focus. Identify and prioritize gaps that are barriers to enhancing best practices, standards, research, equipment, facilities, and other areas of focus. Identify and review key characteristics for effective promotion and communication. Clarify target audiences for outreach and consider stakeholder research prior to developing a comprehensive communications plan to improve outcome. Prioritize messages for year one. Agenda: Wed; 19/July 1:00 pm Day One: Welcome and Call to Order Casey Grant, FPRF 1:15 pm Overview of Baseline Materials and Review of Gaps Jeff Stull, IPP 2:00 pm Review of Outreach Peg, Paul, PPA 2:30 pm Case Study: Best Practice Information Beth Gallup, KFD 3:00 pm PM Break 3:15 pm Casey Study: Standards Revisions Dave Bernzweig, CFD 3:45 pm Case Study: Equipment & Facilities Paul Erickson, LEWA 4:15 pm Breakout Groups Workshop Attendees 5:00 pm Adjourn for Day One (& Evening Networking Reception) Thur; 20/July 8:30 am Day Two: Group Review of Baseline Materials Jeff Stull, IPP 8:45 am Breakout Groups Continue Workshop Attendees 9:45 am AM Break 10:00 am Breakout Group Report Workshop Attendees 11:00 am Plenary Discussion Workshop Attendees 11:30 am Workshop Wrap-up & Summary Observations Casey Grant, FPRF 12:00 pm Adjournment Registration: Workshop attendance is limited to the first 50 attendees, and others will be placed the on a waiting list. To request attendance or for more information, please contact [email protected]. After the Workshop a report will be available. This Workshop is funded through an AFG Fire Prevention & Safety Grant from U.S.DHS/FEMA. 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7281 Fax: +1.617.984.7010 Email: [email protected] www.NFPA.org/Foundation Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 WORKSHOP ON FIRE SERVICE CONTAMINATION CONTROL 19-20 July 2017 (Noon to Noon ET) Columbus Fire Fighters Union Hall 379 W Broad St, Columbus, OH 43215 Note: For flights, Workshop starts at Noon ET on 19/July/2017 and finishes at Noon ET on 20/July/2017 Drury Inn & Suites: 88 East Nationwide Blvd, Columbus, OH 43215 Phone: 1-614-221-7008 ttos://www.drurvhotels.com/locations/columbus-ob/drurv-inn-and-suites-columbus-convention: center Approximate Rate: $130 Distance (in miles) from Hotel to Columbus Union Hall: 1.3 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars. Red Roof Plus Columbus Downtown Convention Center 111 East Nationwide Blvd, Columbus, OH 43215 Phone: 1-614-224-6539 ittps://www.redroof.com/property/Columbus/OH/43215/Hotels-close-to-Greater-columbus- Convention-Center-US-23-1-670/RRI262/ Approximate Rate: $130 Distance (in miles) from Hotel to Columbus Union Hall: 1.4 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars. Sheraton Columbus Hotel at Capital Square 75 East State Street, Columbus, OH, 43215 Phone: 1-614-365-4500 http://www.sheratoncolumbuscapitolsquare.com/ Approximate Rate: $170 Distance (in miles) from Hotel to Columbus Union Hall: 0.8 Notes: Central downtown area Hampton Inn and Suites Columbus Downtown 501 North High Street, Columbus, OH 43215 Phone: 1-614-559-2000 htto://hamptoninns.bilton.com/en/hotels/ohio/hampton-inn-and-suites-columbus-downtown- CMHHSHK/index.htmi?WT.mc. Approximate Rate: $175 Distance (in miles) from Hotel to Columbus Union Hall: 1.3 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars. Page 1 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Courtyard Columbus Downtown 35 West Spring Street, Columbus, Ohio 43215 Phone: 1-614-228-3200 4d19-a255-54ba596febe2 Approximate Rate: $175 Distance (in miles) from Hotel to Columbus Union Hall: 0.8 Notes: Downtown west area; walkable Doubletree Suites by Hilton Columbus Downtown 50 South Front St, Columbus, Ohio, 43215-4145 Phone: 1-614-228-4600 CMHSBOT/index.htmi Approximate Rate: $200 Distance (in miles) from Hotel to Columbus Union Hall: 0.5 Notes: Closest hotel to meeting site; very short walk Residence Inn Columbus Downtown 36 East Gay Street, Columbus, Ohio 43215-3108 Phone: 1-614-222-2610 ec3-4d19-a255-54ba596febe2 Approximate Rate: $230 Distance (in miles) from Hotel to Columbus Union Hall: 0.8 Renaissance Columbus Downtown 50 North Third Street, Columbus, Ohio 43215 Phone: 1-614-228-5050 ttp://www.marriott.com/hotels/travel/cmhbr-renaissance-columbus-downtown-hotel/ Approximate Rate: $240 Distance (in miles) from Hotel to Columbus Union Hall: 1.0 Notes: Central downtown area Hilton Columbus Downtown 401 North High Street, Columbus, OH 43215 Phone: 1-614-384-8600 Approximate Rate: $240 Distance (in miles) from Hotel to Columbus Union Hall: 1.1 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars; New facility and nice. Page 2 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION PPE Cleaning Validation Validation of Cleaning Procedures for Fire Fighter Personal Protective Equipment (PPE) PROJECT CONTACTS Last Updated: 22 May 2017 Project Technical Panel Phone: 614-774-7446 David Bernzweig, Columbus Fire Department (OH) Email: [email protected] Phone: 780-496-3801 Ken Block, Edmonton Fire/Rescue & Metro Chiefs Representative Email: [email protected] Phone: 804-971-7983 Ken Brown, VA State Firefighter's Association & NVFC (Alt to B. McQueen) Email; [email protected] Phone: 510-839-5111 Cell: 213-321-9393 Roger Curtis, ECMS Curtis & Sons (CA) Email: [email protected] Phone: Paul Curtis, ECMS Curtis & Sons (CA) (Alt to Roger Curtis) Email: [email protected] Phone: 253-277-4131 Cell: 503-314-4832 Steve Lakey, Northwest Safety Clean (WA) Email: [email protected] Phone: 304-406-7479 Mark Lambert, WV Fire Academy & NAFTD (WV) Email: [email protected] Phone: 617-828-3978 Ed McCarthy, Boston Fire Department (MA) Email: [email protected] Phone: 315-736-7479 Cell: 315-552-8245 Brian McQueen, FASNY & National Volunteer Fire Council (NY) Email: [email protected] Phone: 602-534-2396 Mark Miller, Phoenix Fire Dept. (AZ) Email: [email protected] Phone: 919-524-1569 Bryan Ormond, NCSU (NC) Email: [email protected] Phone: Russ Osgood, Firefighter Cancer Support Network (NH) (Alt to Keith Tyson) Email: [email protected] Phone: Larry Petrick, IAFF (DC) Email: [email protected] Phone: 617-549-9850 Jim Riley, Boston Fire Department (MA) (Alt to E. McCarthy) Email: [email protected] Phone: 757-385-2892 Molly Riley, Virginia Beach Fire Dept. (VA) Email: [email protected] Phone: 718-999-2922 Thomas Smith, FDNY (NY) Email: [email protected] Phone: 214-774-2213 Cell: 940-300-5718 Tim Tomlinson, Gear Cleaning Solutions (TX) Email: [email protected] Phone: Robert Tutterow, NFPA Fire Service Section (NC) Email: [email protected] Phone: 786-351-3276 Keith Tyson, Firefighter Cancer Support Network (FL) Email: [email protected] Phone: 951-807-1914 Dick Weise, LA County Fire Dept. (CA) Email: [email protected] Phone: 949-291-0637 Ken Wiles, LA County Fire Dept. (CA) (Alt to Dick Weiss) Email: [email protected] Phone: 512-974-0286 Chris Youngblood, Austin Fire Dept. (TX) Email: [email protected] 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7281 Fax: +1.617.984.7010 Email: [email protected] www.NFPA.org/Foundation Source: :https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Phase 1 Project Contacts Phone: 330-723-0000, x365 Steve Allison, Fire-Dex (OH) Email: [email protected] Phone: 800-401-4780 Jack Binder, Edmar Chemical Company (OH) Email: [email protected] Phone: 920-570-0824 Bill Brooks, Alliance Corp. (WI) Email: [email protected] Phone: Charlie Dunn, TenCate Protective Fabrics Email: [email protected] Phone: 617-984-7325 Chris Farrell, NFPA & Staff Liaison for NFPA 1851 (MA) Email: [email protected] Phone: 800-232-8323 Rob Freese, Globe Manufacturing (NH) Email: [email protected] Phone: Pat Freeman, Globe Manufacturing (NH) (Alternate to Rob Freese) Email: [email protected] Phone: 704-554-3313 Diane Hess, PBI Performance Products (NC) Email: [email protected] Phone: 937-415-2932 Karen Lehtonen, LionFirst Responder Products (OH) Email: [email protected] Phone: 484-433-4072 Dan Silvestri, 9-1-1 Safety (PA) Email: [email protected] Liaison Contacts Phone: Pierre Carlotti, Ministry of Interior & Liaison for ISO TC92/SC3 (France) Email: [email protected] Phone: Eric Guillaume, Efectis & Liaison for ISO TC92/SC3 (France) Email: [email protected] Phone: Bill Haskell, NIOSH NPPTL (MA) Email: [email protected] Phone: James Hoar, Boston Fire Department (MA) Email: [email protected] Phone: 631-242-0621 Steve King, Chair NFPA 1851 (NY) Email: [email protected] Phone: +33(0)1.55.76.26.18 Fanny Rieunier, Ministry of Interior & Liaison for ISO TC92/SC3 (France) Email: [email protected] Phone: 612-247-6429 Marni Schmid, Fortunes Collide & Secretariat NFPA 1851 (MI) Email: [email protected] Page 2 of 3 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Core Research Team Phone: 607-758-6537 Cell: 607-423-5617 Jason Allen, Intertek (NY) Email: [email protected] Phone: 304-285-6076 Daniel Farcas, NIOSH HELD (WV) Email: [email protected] Phone: Crystal Forester, NIOSH NPPTL (WV) Email: [email protected] Phone: 617-984-7284 Cell: 617-659-1159 Casey Grant, Fire Protection Research Foundation (MA) Email: [email protected] Phone: Lee Greenawald, NIOSH NPPTL (WV) Email: [email protected] Phone: Bill Lindsley, NIOSH HELD (WV) Email: [email protected] Phone: Stephen Martin, NIOSH DRDS (WV) Email: [email protected] Phone: John Noti, NIOSH HELD (WV) Email: [email protected] Phone: Deborah Sbarra, NIOSH NPPTL (WV) Email: [email protected] Phone: 512-288-8272 cell: 512-623-9558 Jeff Stull, International Personal Protection (TX) Email: [email protected] Phone: 304-285-5858 cell: 681-209-2571 Jay Tarley, NIOSH NPPTL (WV) Email: [email protected] Additional Research Team Contacts Phone: 304-285-5884 Francoise Blachere, NIOSH HELD (WV) Email: [email protected] Phone: Renee Dotson, NIOSH HELD (WV) Email: [email protected] Phone: James Harris, NIOSH NPPTL (WV) Email: [email protected] Phone: Ryan Lebouf, NIOSH DRDS (WV) Email: [email protected] Phone: 617-984-7281 Eric Peterson, Fire Protection Research Foundation (MA) Email: [email protected] Phone: John Powers, NIOSH (WV) Email: [email protected] Phone: 412-386-4621 Cell: 412-463-9561 Heather Reed, NIOSH NPPTL (PA) Email: [email protected] Page 3 of 3 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION PPE Cleaning Validation Validation of Cleaning Procedures for Fire Fighter Personal Protective Equipment (PPE) (for more information see www.nfpa.org/PPECleaning) PROJECT SUMMARY Last updated: 5 February 2016 Background: Fire fighter exposure to personal protective equipment (PPE) that is dirty, soiled, and contaminated is an increasing concern for long-term fire fighter health. This exposure to persistent harmful contaminants in PPE is an extremely serious problem both on the fireground to highly toxic substances including a variety of carcinogens, and more insidiously to an increasing range of infectious pathogens that are encountered in patient care and different emergency operations. Fire fighter PPE becomes contaminated during these exposures and there are no industry standards that conclusively and reliably show that clothing is being adequately cleaned. While general cleaning procedures have been established in NFPA 1851, Standard on Selection, Care, and Maintenance of Protective Ensembles for Structural Fire Fighting and Proximity Fire Fighting, there are no procedures or requirements to demonstrate whether current cleaning practices, including those specified in NFPA 1851, will remove contaminants from fire fighter protective clothing. This project is intended to establish clear and definitive guidance to the fire service for applying cleaning and decontamination procedures that effectively remove both chemical and biological contaminants. Research Goal and Objectives, and Conceptual Approach: The overall goal of this project is to improve fire fighter safety and health by reducing continuing exposure to harmful contaminants in unclean or inadequately cleaned PPE. The objectives to achieve this goal are twofold: (1) To characterize fireground and emergency scene contamination leading to these exposures and develop the methodology for the consistent measurement of cleaning effectiveness; and (2) determine implementable cleaning, decontamination, and disinfection strategies that effectively reduce fire fighter exposures to persistent contaminants. The approach taken by this project is illustrated in Figure 1: Project Conceptual Approach. - Ensure Identify Devise Validate lab - - chemical and methods to methods - at biologicat conteminate againet field ses target clothing in contaminants laboratory exposures acceptance Project Direction Figure 1: Project Conceptual Approach 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7281 Fax: +1.617.984.7010 Email: [email protected] www.NFPA.org/Foundation Source: :ttps://www.industrydocuments.ucsf.edu/docs/hlcn0226 Project Phases and Tasks: This project involves the following four key phases of activity: 1) Identification of Contaminants: Confirm identification and ability to characterize persistent chemical and biological contaminants in fire fighter PPE through target substances and microorganisms. 2) Establishment of Soil and Chemical Contamination/Decontamination Procedures: Develop and validate specific procedures that determine the effectiveness of laundering and other cleaning methods in removing specific soils and chemical contaminants. 3) Establishment of Biological Contamination/Disinfection or Sanitization Procedures: Develop and validate specific procedures that determine the effectiveness of laundering or disinfection/sanitization processes that remove/deactivate biologically-based contaminants. 4) Creation of Overall Fire Service Guidance: Prepare clear and definitive information for the fire service industry (fire fighters, fire departments, clothing manufacturers, material suppliers, cleaning/care organizations, and cleaning agent or equipment manufacturers) on appropriate approaches for properly cleaning fire fighter protective clothing and equipment. The specific tasks of this project are based on these four phases of the project, and these are illustrated in Figure 2: Project Tasks. PHASE 2 PHASEZ Task 2.4 Task 2.5 Task 1.1 Task 2.1 Validate testsat Refine test Appoint Technical Select cleaning selected ISPS methodology Review Panel methods/agents (chemical) (chemical) PHASE $ Task 4.1 Task 1.2 Task 2.2 Write qualification Review Prigr Put together test plan methods studies/literature (chemical) Task 2.3 Task 4.2 Task 1.3 PHASE 3 Perform laboratory Establish cleaning Setup analytical chemical Task 3.3 acceptance criteria capabilities decontaminant Put together test plan testing (biological) Task 4.3 Task 1.4 Perform Task 3.4 Prepare public inputs for NFPA 1851 demonstration tests Task 3.1 Perform laboratory Task 3.6 Select study biological Refine test microorganisms decontaminant methodology Task 1.5 testing (biological) Task 4.4 Refine biological Prepare industry decontamination Task 3.2 Task 3.5 guidance document scope Select biological Validate testsat cleaning methods selected ISPs (biological) Task 1.6 Task 4,5 Establish cleanliness Prepare project final metrics report Figure 2: Project Tasks Implementation and Schedule: This three year project is due to be completed no later than " August 2018, and is funded through an AFG Fire Prevention & Safety Grant from the U.S. Department of Homeland Security / Federal Emergency Management Agency. The Research Foundation will lead a unique research team partnership composed of the FPRF, National Institute for Occupational Safety and Health (NIOSH), International Personal Protection (IPP), and Intertek. The research team, along with several Independent Service Providers (ISPs), will work with the fire service partners and others to validate and optimize fire fighter PPE cleaning validation methods. For more information see www.nfpa.org/PPECleaning. Page 2 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION Fire Fighter Cancer Cohort Study Full Title: The Firefighter Multicenter Cancer Cohort Study: Framework Development and Testing PROJECT SUMMARY Last Updated: 20 September 2016 Background: Cancer is a leading cause of fire service morbidity and mortality. Firefighter exposure to carcinogens occurs through skin contamination and through inhalation when respiratory protection is not worn when combustion products are present such as during overhaul, standby, and operation of apparatus, as well as through off-gassing of equipment and exposures in the fire station. However, we currently do not understand which exposures are responsible for cancer in firefighters, the mechanisms by which firefighter exposures cause cancer, nor the most effective means of reducing exposures. Since cancer has a long latency period, biomarkers are also needed that can measure the toxicological effects of carcinogen exposure well before the development of cancer, when interventions to prevent disease could be effective. Development of a large (>10,000 firefighter) multicenter firefighter cancer prospective cohort study will address these needs, but the framework for such a study needs to be first developed and tested among a smaller initial set of fire service partners. Implementation and Schedule: This research project is led by University of Arizona with collaborative support from multiple other research partners, including the University of Miami, National Institute for Occupational Safety and Health; National Fallen Firefighter Foundation, Fire Protection Research Foundation, and others. Initial funding for this project is through a 3-year DHS/FEMA Assistance to Fire Fighter (AFG) Fire Grant, with the intention to identify and obtain additional funding for the duration of the 30 year effort. The project start date is August 2016. The Principal Investigator for this project is: Jefferey L. Burgess, MD, MS, MPH, University of Arizona, email: [email protected]. Project Goal and Aims: The goal of the initial 3-year effort of this overall project is to develop and test a framework for establishing a long-term fire fighter multicenter prospective cohort study focused on carcinogenic exposures and effects. The specific aims are to: 1) Establish an oversight and planning board to provide study oversight, foster communication among fire organizations and help develop a long-term funding plan; 2) Create and test a cohort study data coordinating center and harmonized survey data protocols; 3) Develop and validate a firefighter carcinogen exposure matrix and data collection system; and 4) Create a biomarker assessment center and evaluate the association between cumulative firefighter exposures and epigenetic effects. For more information, contact: Casey Grant, Fire Protection Research Foundation 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7284 Fax: +1.617.984.7010 Email: [email protected] Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Project Methodology: This study will harmonize and build on recent and developing firefighter cancer prevention studies in Arizona, Florida and Massachusetts, adding volunteer fire departments. An oversight and planning board will be established by the Fire Protection Research Foundation (FPRF) in association with the National Fallen Firefighter Foundation (NFFF) Fire Service Occupational Cancer Alliance (FSOCA) to provide oversight of the study through collaboration among fire service organizations, academia, and government agencies, and develop a long-term funding and sustainability plan. A data coordination center team will design, develop and evaluate a framework for a multicenter prospective cohort study of firefighters and cancer risk, including standardized participant survey data collection tools and analysis protocols sufficient to address the short- and long-term study objectives as well as linkage with long-term outcome data including cancer development. An exposure assessment center team will develop a carcinogen exposure matrix and data collection system to provide improved occupational exposure data for comparison with epigenetic outcomes and eventual cancer outcomes. Carcinogen exposures associated with specific fire types will be evaluated across fire departments through industrial hygiene monitoring and analysis of urine for absorbed contaminants, supplementing existing FEMA-funded and other studies of firefighter exposures and allowing for participating fire departments to design interventions to reduce current exposures. Expansion of the National Fire Operations Reporting System (NFORS) will be explored as one option to uniformly collect incident and exposure data. Blood and buccal cells will be collected during annual medical surveillance evaluations, including both new recruits and incumbent firefighters. Pilot studies of epigenetic markers of cancer effect and cancer risk will be analyzed comparing municipal firefighters with high chronic exposures, volunteer firefighters with low chronic exposures, and non- firefighter friends of the municipal firefighters (serving as controls). Project Deliverables: The anticipated outcomes from this 3-year effort is to establish and test the framework necessary for the subsequent development of a large multicenter cohort study of cancer in the fire service. Page 2 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226

for each manufacture request , EPA estimates that the burden on public will be how many hours ?

kzbn0226

kzbn0226_p41, kzbn0226_p42, kzbn0226_p43, kzbn0226_p44, kzbn0226_p45, kzbn0226_p46

96 hours

Perhaps for simplification purposes, EPA has provided a succinct definition. However, as noted above, this definition does not appropriately capture how the sentinel exposure approach is currently used. Relying on the highest exposure scenario does not mean that the "maximal" exposure is used. Reasonable values from that highest exposure scenario should be used instead. A risk evaluation should not use a "maximal" exposure value as these values are typically unstable. More appropriate language would include the term "plausible exposure" or "plausible upper bound exposure." In the environmental toxicology field, it is common to use the 95th percentile under average exposure conditions. The "plausible maximum exposure" is not used. Significant revisions are needed to EPA's definition to capture the appropriate use of the sentinel exposure concept. E. Uncertainty EPA provides a definition for uncertainty and cites EPA's 2014 Human Health Risk Assessment 90 Framework as the source. However, as written, the definition EPA provides is actually not consistent with the source. EPA's definition should conforms to the edits below to ensure the definition is fully consistent. Uncertainty means the imperfect knowledge or lack of precise knowledge of the real world, either for specific values of interest or in the description of a the system. VIII. The Process for Manufacturer Requested Evaluations A. EPA-Initiated and Manufacturer-Requested Evaluations Should Follow the Same Review Process. LCSA allows chemical manufacturers to request EPA to conduct a risk evaluation at Section 6(b)(4)(C)(ii). By law, a manufacturer may only request a risk evaluation of a chemical it manufacturers (not of a competitor). By rule, EPA is to specify the "form and manner" for manufacturer requests, as well as to prescribe the criteria for the risk evaluation. In our view, EPA should largely follow the same process - and apply the same criteria - to manufacturer requested risk evaluations as it does to EPA-initiated risk evaluations arising out of the prioritization process. There is one notable difference: EPA has authority under LCSA to flexibly scope risk evaluations for chemicals with high priority designations to focus on conditions of use that are most relevant and meaningful to risk, and it should do so on a case-by- case basis. The result of this process might be that some risk evaluations cover all conditions of use; others a few; others only one. In the case of manufacturer-requested risk evaluations, a manufacturer may support only certain conditions of use - in other words, it may sell the chemical only for use in certain kinds of products or processes. A manufacturer may strongly support risk evaluation of its chemical under the conditions of use it supports, but may not be willing to fund evaluation of its chemical for uses supported by its competitors. While we believe EPA can expand the scope of a risk evaluation beyond that requested by a manufacturer, the agency should not impose fees on a 90 See 82 Fed. Reg. at 7568. 37/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 company that requests a risk evaluation in a manner that enriches its competitors. (Similarly, if only one manufacturer requests a risk evaluation on a chemical in a particular condition of use, it would not be appropriate to impose costs on manufacturers that did not request the risk evaluation). It will be important for EPA to address fees equitably in the upcoming fees rule; if not, the agency will discourage manufacturer requests. This is an important observation, because Congress contemplated that EPA would receive manufacturer requests for risk evaluation, and mandates that a certain number of them be accepted. At full implementation, the law anticipates that EPA will be undertaking 5-10 manufacturer-requested evaluations (assuming that not more than 20 EPA-initiated evaluations are underway). EPA should therefore promulgate criteria that make it sufficiently attractive and possible for manufacturers to avail themselves of the option. EPA should not promulgate criteria that make it largely unworkable and impossible to seek and obtain manufacturer-requested evaluations. EPA's insistence that manufacturer-requested evaluations must include "all" conditions of use obviates the use and utility of the law's provision that allows - and requires EPA to accept manufacturer-requested evaluations in the first place, leads to an absurd result, and undermines the function and purposes of the statute. B. EPA Should Respond Within Six Months from the End of the Comment Period to the Time it Notifies a Manufacturer of Acceptance of a Request. EPA should align the six months established for scoping EPA-initiated risk evaluations with those requested by manufacturers. EPA should not require more than 6 months to decide whether to accept or deny a request from a manufacturer for review. C. EPA Should Not Award "Preference" to Any Manufacturer-Requested Risk Evaluations Until the Statutory Cap is Met. EPA is required by statute to give preference to manufacturer-requested evaluations for which EPA determines that restrictions by one or more states have the potential to have a significant impact on interstate commerce or health or the environment.91 There is no other statutory basis for differentiating between requests. EPA proposes to treat this as a required "initial prioritization," after which it will further prioritize chemical substances for risk evaluation "based on initial estimates of exposure(s) and/or hazard(s) under one or more conditions of use or any other factor that EPA determines may be relevant." ACC believes this suggested approach, which could result in manufacturer requests being inappropriately rejected by EPA, is inconsistent with legislative intent, and the efficient flow of risk evaluations under LCSA. We believe that until EPA's cap on manufacturer-requested risk evaluations is met, and except for mandatory preference under TSCA 6(b)(4)(E)(iii), the Agency should accept requests for manufacturer-requested risk evaluations on a first-come, first-served basis. EPA arguably cannot, and should not, deny any otherwise compliant request until 5 evaluations are underway, since there may not be a rational basis to be able to compare requests for evaluation. After EPA has 5 manufacturer-requested evaluations underway, it should apply the same prioritization criteria set out in the prioritization rule for selection of chemicals for evaluation. It should not 91 TSCA 6(b)(4)(E)(iii). 92 82 Fed. Reg. 7569. 38/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 impose new criteria of "high hazard" and "high exposure" divorced from the criteria established in the prioritization rule. We also strongly urge EPA to delete the catch-all provision, "any other factor EPA determines may be relevant." For the manufacturer-requested risk evaluation process to function, manufacturers must have fair notice of the criteria they must meet to have a request considered. An open-ended catchall provision not only undermines congressional intent; it eliminates fair notice to manufacturers of what information they need to gather and prepare in order to have a request considered. This is particularly the case given that manufacturers may need to conduct testing and incur significant costs before they request a risk evaluation. D. EPA Should Not Require Submission of "All" Prior Risk Assessments by Manufacturers as a Precondition to Accepting a Manufacturer Request. Section 702.37(b)(4) proposes that manufacturer requests must include a commitment to provide to EPA any referenced information on request, an appropriate request (subject to CBI protection, if applicable). This section provides further, however, that a manufacturer must submit any previous risk assessment conducted by a manufacturer as well as any it "possesses" or "can reasonably obtain." While we appreciate that TSCA § 26(k) requires EPA to take into consideration reasonably available information as part of Section 6 risk evaluations, this should not devolve into a blanket request for certain proprietary reviews undertaken by manufacturers. Many risk assessments fall into that category. EPA may properly request manufacturers to produce information with a manufacturer request for a risk evaluation where the Agency has legal authority to make the request and the information is otherwise relevant to the risk evaluation, meets data quality standards, and meets Section 26 scientific standards. EPA cannot, however, create new legal authority for itself to demand otherwise protected information as a condition of considering a manufacturer request for risk evaluation. This is to be contrasted with health and safety results, which may be inputs in a risk assessment but are distinct from a risk assessment. ACC, in fact, has long had a policy in its Chemical Products and Technology Division to make publicly available the final reports or validated final results of environmental, health, and safety research managed or sponsored under the group (subject to exceptions needed to preserve legal rights, such as proprietary rights, data compensation rights or to protect confidential business information). EPA also may appropriately request a manufacturer to provide, as part of its request, any information that EPA could otherwise require under TSCA Sections 8(a), 8(c), 8(d) (health and safety studies), and 8(e) (which would already have been reported to the agency). We urge EPA to revise the proposal accordingly to clarify that manufacturers will be expected to produce information relevant to the risk evaluation, and that EPA confirm it will protect CBI and respect other legal doctrines protecting against disclosure. 39/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 E. EPA Should Limit Public Comments Accepted on a Manufacturer Request to the Expected Scope of the Risk Evaluation. As EPA properly notes in the preamble, the agency must grant any manufacturer request that complies with EPA's criteria, until the statutory minimum of 25 percent has been met. EPA may set criteria by rule. Section 702.37(e)(2) proposes a public comment period on valid manufacturer requests for risk evaluations which injects inappropriate criteria - the public is invited to submit comments and information "relevant to whether the chemical substance presents an unreasonable risk of injury to health or the environment." For EPA-initiated risk evaluations, the legal standard that begins the risk evaluation process is EPA's determination that a chemical "may present" an unreasonable risk of injury. A determination that a chemical "presents" an unreasonable risk is not made, if at all, until the end of the risk evaluation process. A determination that a chemical "presents" unreasonable risk triggers risk management action by EPA. EPA's proposal to accept public comment on whether the chemical "presents an unreasonable risk of injury" is thus inappropriate for three reasons. First, it applies a standard that should not apply at all to manufacturer-requested risk evaluations. These requests bypass the prioritization process, and are not subject to the same requirement that EPA make a high-priority designation based on a particular risk finding. Instead, Congress intended a separate path for manufacturer- requested evaluations, and the only statutory criteria is that EPA must give preference to chemicals where restrictions by one or more states could have a "significant impact" on interstate commerce or health or the environment. EPA's proposed regulations must respect this statutory mandate for prioritizing manufacturer requests. Second, under no circumstances should EPA apply the legal standard for risk management to its decision whether to accept a chemical for risk evaluation. The "presents" standard is thus inappropriate. Third, determinations whether a chemical "may present" or "presents" unreasonable risk belong to EPA alone, by statute. The public should not be invited to opine on whether this legal standard has been met. EPA should revise this proposal. EPA should treat a valid manufacturer request for a risk evaluation as equivalent to a draft scope, and publish the document and accept public comment accordingly. F. EPA Should Remove the Certification Requirement for Manufacturer- Requested Risk Evaluations. Section 702.37(b)(5) requires manufacturers to include a signed certification that the information contained in the manufacturer request is "complete" and "accurate." This requirement is impossible to meet; manufacturers cannot simultaneously be asked to provide all reasonably available information, regardless of accuracy, and then be asked to certify its accuracy. Manufacturers cannot reasonably certify the accuracy of information produced by third parties, 40/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 or even EPA itself; they can only be asked to certify the accuracy of their own corporate information they collect and manage. They cannot reasonably be asked to provide a citation list and certify the accuracy of the internal information within every citation. Likewise, manufacturers cannot be reasonably requested to certify the "completeness" of studies or other information, or even internet searches. The very fact that EPA proposes to publish manufacturer requests and seek public comment supports this point - if manufacturers were themselves capable of locating and producing third party information, there would be no need or value for public comment. IX. Information Collection Request (ICR) Burden Estimates Associated with the proposed rule, EPA is taking comment on ICR No. 2559.01. ACC is concerned that the burden estimates provided by EPA are far too low. For each manufacture request, EPA estimates that the burden on the public will be 96 hours and $6,935. EPA assumes the hourly wage of the person submitting the request will be $72.22. The information that EPA expects industry to provide in a manufacturer request is similar to compiling all the information that EPA will provide in prioritization and scoping. As scoping will take approximately six months, acknowledging that EPA intends to collect all the data during prioritization, it is fair to assume that it will take at least as long for manufacturers to collect, assemble, review and ensure the integrity of all the hazard and exposure information for all the conditions of use that are 93 relevant. Consistent with EPA's approach, compiling all this information will require staff with expertise in human health, ecotoxicology, fate, engineering and exposure assessment. EPA assumes, for its own staff, conducting a full risk evaluation will take 5,920 hours per chemical. If we divide this over 3 years, that is approximately 1973 hours/year. If we assume scoping takes six months, that equates to approximately 987 hours excluding any contractor resources which EPA will likely also use ($75,000/chemical). Based on this calculation, ACC cannot understand why EPA thinks the collection, assembling, review, integrity assurance, and reporting will take a manufacturer only 96 hours. This assumption appears extremely low, in fact perhaps 10 fold too low. In addition, as manufacturers will be certifying their submissions, to ensure accuracy and completion, any submission to EPA will need to be reviewed at the highest levels of an organization. EPA assumes that this work will be done at the equivalent of a GS-13 step 5, or $72.22/hour. Looking at the most recent Office of Personnel Management website, for the 94 Washington DC area, a GS-13, step 5, in 2017 will earn an annual salary of $107,435.95 Considering the importance of this information, as well as the review required to inform the certification, it is likely that senior employees of manufacturers will complete this task. Using the Ninth Triennial Toxicology Survey as our source, 96 it appears that in the chemical industry, 93 See EPA ICR Attachment 1 in the rulemaking docket. 94 ACC notes that this value seems incorrect as the most recent OPM tables show a Washington DC employee at the GS-14 step 5 level making an hourly rate of $51.48. See ottps://ww.opm.gov/policy-data-oversight/pay leave/salaries-wages/salarv-tables/pdf/2017/DCB. h.pdf. 95 See OPM salary tables, available at: https://www.opm.gov/policy-data-oversight/pay-leave/salaries-wages/salary- tables/pdf/2017/DCB.pdi 96 See Ninth Triennial Toxicology Salary Survey, Table 25, available at table 25. 41/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 those with experience above 9 years (thus likely more senior) make a salary ranging from $141,000-177,000, with over 50% of the respondents in this bracket making more than $165,000. Not only is EPA's estimate of the hours needed to develop a manufacturer request too low, but the wage rate is also far too low based on the most recently available published survey results. ACC would be happy to engage further with EPA to assist the Agency in making much needed refinements to both the hours needed and wage estimates assumed in the ICR. 42/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226

what is mentioned in phase 3 task 3.3 ?

hlcn0226

hlcn0226_p0, hlcn0226_p1, hlcn0226_p2, hlcn0226_p3, hlcn0226_p4, hlcn0226_p5, hlcn0226_p6, hlcn0226_p7, hlcn0226_p8, hlcn0226_p9, hlcn0226_p10, hlcn0226_p11

Put together test plan (biological), put together test plan (biological)

129 From: Jürgen Troitzsch To: Osimitz Thomas; Dr. Blais Matthew; Prof. Rein Guillermo; Dr. Hayes Wallace; Dourson. Michael (doursomi); Kacew Sam; Dr. Wise Kimberly Subject: Fwd: Project on FF PPE Cleaning Validation Date: Monday, June 12, 2017 1:11:46 PM Attachments: PROU PANEL - PPE Cleaning (33) pdf PROJ SUMMARY - PPE Cleaning (7) pot FLYER FF Contam Control Workshop (6) odf HOTELS - Contam Control Wrkshp on 2017Jul19.pd PROJS JMMARY- FE Cancer Cohort Study (4) odf Dear All, I came across this project, which may be of interest in the frame of our fire fighters cancer activities. Kind regards/Viele Grüße Jürgen Dr. Jürgen Troitzsch Fire and Environment Protection Service FEPS Via Patrizia 32 CH-6612 Ascona, Switzerland Mobile: +41 79 289 17 16 Phone: +41 91 791 14 22 Email: [email protected] Web: www.troitzsch.com De : Grant, Casey Envoyé : lundi 22 mai 2017 17:58 À : [email protected]; [email protected]. tis.com; mlambetamallN u.edu; dwardmecarthyebostengoy ark.a.miller@ehoen ix.gov; james.riley@bosta nagov; [email protected] Thomas [email protected]; ;timügearcleaningsolutions.s om [email protected]; Ken.Wiles @fire.jacounty.gov Farrell, Christopher cobtlogiobefiresuits.com; pattogiobefiresults.com; Diane.Hess@ Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 130 PBIProducts.com; Kebtonen@lionprotedscon leur.gouv.fr; GUILLAUME Eric <eric [email protected] ;[email protected]; mamiefortunes-collide.com Cc : lasonallendintertekeor [email protected]; [email protected] wlindslev@ cdc.gov; [email protected] [email protected]; [email protected]; ; istendice OY; Objet : Project on FF PPE Cleaning Validation To: Panel, Research Team and Liaisons for Project on "Fire Fighter PPE Cleaning Validation" It has been some time since we last spoke, and I have the following three items to be addressed: 1) A lot has been happening with our project and we want to hold a 90 minute conference call in early August 2017 to bring everyone up-to-date. I've created a scheduling poll to determine the optimum date/time Please respond before Noon ET on Wednesday 31/May/2017 so that we can get this on our calendars. I've attached the Project Roster and Project Summary in case anyone needs a refresher for this project addressing "how clean is clean". Thanks. 2) I've been asked to participate in a webinar tomorrow (23/Mav/2017) from noon ET to 1:30 pm ET on "Factors Relating to Cancer and Contamination in the US Fire Service". I've been assigned a portion of this webinar (among two other speakers) to address on-going research and I'm planning to address our project among several other on-going efforts. The link is on the NFPA home page at: FYI.. 3) Some of you are already aware of the Workshop in Columbus, Ohio on 19- 20/Julv/2017, and if not I want to call it to your attention. This is for the separate one year AFG project on "Campaign for Fire Service Contamination Control". Attached is a Flyer that provides additional details, and also attached is a list of hotels in the area to assist with travel. The workshop will be held from Noon to Noon on 19-20/July and we still have room if you would like to attend. In addition, the separate project (i.e., a third related project) on "Fire Fighter Cancer Cohort Study" will hold a separate planning meeting on the afternoon of 20/July from 1 pm to 5 pm (Project Summary is attached). All are welcome to attend this as well. If you are a fire service panel member we can cover your travel, and I can send follow-up instructions to you separately. For anyone interested in attending the Columbus meetings on 19-20/July, please let us know by email to [email protected] and Thanks.. Casey C. Grant, P.E. Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION "CAMPAIGN FOR FIRE SERVICE CONTAMINATION CONTROL" WORKSHOP Location: Columbus Fire Fighters Union Hall, 379 W Broad St, Columbus, OH 43215 Workshop Dates: 19-20 July 2017 (Last Updated: 21 April 2017; subject to update) Background: Exposure to chemical and biological contaminants on the fire ground is an increasing concern for long-term fire fighter health. Cancer and other diseases resulting from chronic exposures has become a leading concern for the fire service. This is presumed to be associated with fireground exposures relating to protection/hygiene practices and persistent harmful contamination found in fire fighter equipment, apparatus carrying that equipment, and stations where the equipment resides. Workshop Goal and Objectives: The goal of this Workshop is to identify concepts and materials that are or can be useful to control the spread of harmful fire ground contaminants, ultimately in support of improved fire fighter long-term health. The following objectives support this goal (and reflect anticipated deliverables): Identify, review and recommend baseline materials (existing and proposed) addressing best practices, standards, research, equipment, facilities, and other areas of focus. Identify and prioritize gaps that are barriers to enhancing best practices, standards, research, equipment, facilities, and other areas of focus. Identify and review key characteristics for effective promotion and communication. Clarify target audiences for outreach and consider stakeholder research prior to developing a comprehensive communications plan to improve outcome. Prioritize messages for year one. Agenda: Wed; 19/July 1:00 pm Day One: Welcome and Call to Order Casey Grant, FPRF 1:15 pm Overview of Baseline Materials and Review of Gaps Jeff Stull, IPP 2:00 pm Review of Outreach Peg, Paul, PPA 2:30 pm Case Study: Best Practice Information Beth Gallup, KFD 3:00 pm PM Break 3:15 pm Casey Study: Standards Revisions Dave Bernzweig, CFD 3:45 pm Case Study: Equipment & Facilities Paul Erickson, LEWA 4:15 pm Breakout Groups Workshop Attendees 5:00 pm Adjourn for Day One (& Evening Networking Reception) Thur; 20/July 8:30 am Day Two: Group Review of Baseline Materials Jeff Stull, IPP 8:45 am Breakout Groups Continue Workshop Attendees 9:45 am AM Break 10:00 am Breakout Group Report Workshop Attendees 11:00 am Plenary Discussion Workshop Attendees 11:30 am Workshop Wrap-up & Summary Observations Casey Grant, FPRF 12:00 pm Adjournment Registration: Workshop attendance is limited to the first 50 attendees, and others will be placed the on a waiting list. To request attendance or for more information, please contact [email protected]. After the Workshop a report will be available. This Workshop is funded through an AFG Fire Prevention & Safety Grant from U.S.DHS/FEMA. 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7281 Fax: +1.617.984.7010 Email: [email protected] www.NFPA.org/Foundation Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 WORKSHOP ON FIRE SERVICE CONTAMINATION CONTROL 19-20 July 2017 (Noon to Noon ET) Columbus Fire Fighters Union Hall 379 W Broad St, Columbus, OH 43215 Note: For flights, Workshop starts at Noon ET on 19/July/2017 and finishes at Noon ET on 20/July/2017 Drury Inn & Suites: 88 East Nationwide Blvd, Columbus, OH 43215 Phone: 1-614-221-7008 ttos://www.drurvhotels.com/locations/columbus-ob/drurv-inn-and-suites-columbus-convention: center Approximate Rate: $130 Distance (in miles) from Hotel to Columbus Union Hall: 1.3 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars. Red Roof Plus Columbus Downtown Convention Center 111 East Nationwide Blvd, Columbus, OH 43215 Phone: 1-614-224-6539 ittps://www.redroof.com/property/Columbus/OH/43215/Hotels-close-to-Greater-columbus- Convention-Center-US-23-1-670/RRI262/ Approximate Rate: $130 Distance (in miles) from Hotel to Columbus Union Hall: 1.4 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars. Sheraton Columbus Hotel at Capital Square 75 East State Street, Columbus, OH, 43215 Phone: 1-614-365-4500 http://www.sheratoncolumbuscapitolsquare.com/ Approximate Rate: $170 Distance (in miles) from Hotel to Columbus Union Hall: 0.8 Notes: Central downtown area Hampton Inn and Suites Columbus Downtown 501 North High Street, Columbus, OH 43215 Phone: 1-614-559-2000 htto://hamptoninns.bilton.com/en/hotels/ohio/hampton-inn-and-suites-columbus-downtown- CMHHSHK/index.htmi?WT.mc. Approximate Rate: $175 Distance (in miles) from Hotel to Columbus Union Hall: 1.3 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars. Page 1 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Courtyard Columbus Downtown 35 West Spring Street, Columbus, Ohio 43215 Phone: 1-614-228-3200 4d19-a255-54ba596febe2 Approximate Rate: $175 Distance (in miles) from Hotel to Columbus Union Hall: 0.8 Notes: Downtown west area; walkable Doubletree Suites by Hilton Columbus Downtown 50 South Front St, Columbus, Ohio, 43215-4145 Phone: 1-614-228-4600 CMHSBOT/index.htmi Approximate Rate: $200 Distance (in miles) from Hotel to Columbus Union Hall: 0.5 Notes: Closest hotel to meeting site; very short walk Residence Inn Columbus Downtown 36 East Gay Street, Columbus, Ohio 43215-3108 Phone: 1-614-222-2610 ec3-4d19-a255-54ba596febe2 Approximate Rate: $230 Distance (in miles) from Hotel to Columbus Union Hall: 0.8 Renaissance Columbus Downtown 50 North Third Street, Columbus, Ohio 43215 Phone: 1-614-228-5050 ttp://www.marriott.com/hotels/travel/cmhbr-renaissance-columbus-downtown-hotel/ Approximate Rate: $240 Distance (in miles) from Hotel to Columbus Union Hall: 1.0 Notes: Central downtown area Hilton Columbus Downtown 401 North High Street, Columbus, OH 43215 Phone: 1-614-384-8600 Approximate Rate: $240 Distance (in miles) from Hotel to Columbus Union Hall: 1.1 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars; New facility and nice. Page 2 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION PPE Cleaning Validation Validation of Cleaning Procedures for Fire Fighter Personal Protective Equipment (PPE) PROJECT CONTACTS Last Updated: 22 May 2017 Project Technical Panel Phone: 614-774-7446 David Bernzweig, Columbus Fire Department (OH) Email: [email protected] Phone: 780-496-3801 Ken Block, Edmonton Fire/Rescue & Metro Chiefs Representative Email: [email protected] Phone: 804-971-7983 Ken Brown, VA State Firefighter's Association & NVFC (Alt to B. McQueen) Email; [email protected] Phone: 510-839-5111 Cell: 213-321-9393 Roger Curtis, ECMS Curtis & Sons (CA) Email: [email protected] Phone: Paul Curtis, ECMS Curtis & Sons (CA) (Alt to Roger Curtis) Email: [email protected] Phone: 253-277-4131 Cell: 503-314-4832 Steve Lakey, Northwest Safety Clean (WA) Email: [email protected] Phone: 304-406-7479 Mark Lambert, WV Fire Academy & NAFTD (WV) Email: [email protected] Phone: 617-828-3978 Ed McCarthy, Boston Fire Department (MA) Email: [email protected] Phone: 315-736-7479 Cell: 315-552-8245 Brian McQueen, FASNY & National Volunteer Fire Council (NY) Email: [email protected] Phone: 602-534-2396 Mark Miller, Phoenix Fire Dept. (AZ) Email: [email protected] Phone: 919-524-1569 Bryan Ormond, NCSU (NC) Email: [email protected] Phone: Russ Osgood, Firefighter Cancer Support Network (NH) (Alt to Keith Tyson) Email: [email protected] Phone: Larry Petrick, IAFF (DC) Email: [email protected] Phone: 617-549-9850 Jim Riley, Boston Fire Department (MA) (Alt to E. McCarthy) Email: [email protected] Phone: 757-385-2892 Molly Riley, Virginia Beach Fire Dept. (VA) Email: [email protected] Phone: 718-999-2922 Thomas Smith, FDNY (NY) Email: [email protected] Phone: 214-774-2213 Cell: 940-300-5718 Tim Tomlinson, Gear Cleaning Solutions (TX) Email: [email protected] Phone: Robert Tutterow, NFPA Fire Service Section (NC) Email: [email protected] Phone: 786-351-3276 Keith Tyson, Firefighter Cancer Support Network (FL) Email: [email protected] Phone: 951-807-1914 Dick Weise, LA County Fire Dept. (CA) Email: [email protected] Phone: 949-291-0637 Ken Wiles, LA County Fire Dept. (CA) (Alt to Dick Weiss) Email: [email protected] Phone: 512-974-0286 Chris Youngblood, Austin Fire Dept. (TX) Email: [email protected] 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7281 Fax: +1.617.984.7010 Email: [email protected] www.NFPA.org/Foundation Source: :https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Phase 1 Project Contacts Phone: 330-723-0000, x365 Steve Allison, Fire-Dex (OH) Email: [email protected] Phone: 800-401-4780 Jack Binder, Edmar Chemical Company (OH) Email: [email protected] Phone: 920-570-0824 Bill Brooks, Alliance Corp. (WI) Email: [email protected] Phone: Charlie Dunn, TenCate Protective Fabrics Email: [email protected] Phone: 617-984-7325 Chris Farrell, NFPA & Staff Liaison for NFPA 1851 (MA) Email: [email protected] Phone: 800-232-8323 Rob Freese, Globe Manufacturing (NH) Email: [email protected] Phone: Pat Freeman, Globe Manufacturing (NH) (Alternate to Rob Freese) Email: [email protected] Phone: 704-554-3313 Diane Hess, PBI Performance Products (NC) Email: [email protected] Phone: 937-415-2932 Karen Lehtonen, LionFirst Responder Products (OH) Email: [email protected] Phone: 484-433-4072 Dan Silvestri, 9-1-1 Safety (PA) Email: [email protected] Liaison Contacts Phone: Pierre Carlotti, Ministry of Interior & Liaison for ISO TC92/SC3 (France) Email: [email protected] Phone: Eric Guillaume, Efectis & Liaison for ISO TC92/SC3 (France) Email: [email protected] Phone: Bill Haskell, NIOSH NPPTL (MA) Email: [email protected] Phone: James Hoar, Boston Fire Department (MA) Email: [email protected] Phone: 631-242-0621 Steve King, Chair NFPA 1851 (NY) Email: [email protected] Phone: +33(0)1.55.76.26.18 Fanny Rieunier, Ministry of Interior & Liaison for ISO TC92/SC3 (France) Email: [email protected] Phone: 612-247-6429 Marni Schmid, Fortunes Collide & Secretariat NFPA 1851 (MI) Email: [email protected] Page 2 of 3 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Core Research Team Phone: 607-758-6537 Cell: 607-423-5617 Jason Allen, Intertek (NY) Email: [email protected] Phone: 304-285-6076 Daniel Farcas, NIOSH HELD (WV) Email: [email protected] Phone: Crystal Forester, NIOSH NPPTL (WV) Email: [email protected] Phone: 617-984-7284 Cell: 617-659-1159 Casey Grant, Fire Protection Research Foundation (MA) Email: [email protected] Phone: Lee Greenawald, NIOSH NPPTL (WV) Email: [email protected] Phone: Bill Lindsley, NIOSH HELD (WV) Email: [email protected] Phone: Stephen Martin, NIOSH DRDS (WV) Email: [email protected] Phone: John Noti, NIOSH HELD (WV) Email: [email protected] Phone: Deborah Sbarra, NIOSH NPPTL (WV) Email: [email protected] Phone: 512-288-8272 cell: 512-623-9558 Jeff Stull, International Personal Protection (TX) Email: [email protected] Phone: 304-285-5858 cell: 681-209-2571 Jay Tarley, NIOSH NPPTL (WV) Email: [email protected] Additional Research Team Contacts Phone: 304-285-5884 Francoise Blachere, NIOSH HELD (WV) Email: [email protected] Phone: Renee Dotson, NIOSH HELD (WV) Email: [email protected] Phone: James Harris, NIOSH NPPTL (WV) Email: [email protected] Phone: Ryan Lebouf, NIOSH DRDS (WV) Email: [email protected] Phone: 617-984-7281 Eric Peterson, Fire Protection Research Foundation (MA) Email: [email protected] Phone: John Powers, NIOSH (WV) Email: [email protected] Phone: 412-386-4621 Cell: 412-463-9561 Heather Reed, NIOSH NPPTL (PA) Email: [email protected] Page 3 of 3 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION PPE Cleaning Validation Validation of Cleaning Procedures for Fire Fighter Personal Protective Equipment (PPE) (for more information see www.nfpa.org/PPECleaning) PROJECT SUMMARY Last updated: 5 February 2016 Background: Fire fighter exposure to personal protective equipment (PPE) that is dirty, soiled, and contaminated is an increasing concern for long-term fire fighter health. This exposure to persistent harmful contaminants in PPE is an extremely serious problem both on the fireground to highly toxic substances including a variety of carcinogens, and more insidiously to an increasing range of infectious pathogens that are encountered in patient care and different emergency operations. Fire fighter PPE becomes contaminated during these exposures and there are no industry standards that conclusively and reliably show that clothing is being adequately cleaned. While general cleaning procedures have been established in NFPA 1851, Standard on Selection, Care, and Maintenance of Protective Ensembles for Structural Fire Fighting and Proximity Fire Fighting, there are no procedures or requirements to demonstrate whether current cleaning practices, including those specified in NFPA 1851, will remove contaminants from fire fighter protective clothing. This project is intended to establish clear and definitive guidance to the fire service for applying cleaning and decontamination procedures that effectively remove both chemical and biological contaminants. Research Goal and Objectives, and Conceptual Approach: The overall goal of this project is to improve fire fighter safety and health by reducing continuing exposure to harmful contaminants in unclean or inadequately cleaned PPE. The objectives to achieve this goal are twofold: (1) To characterize fireground and emergency scene contamination leading to these exposures and develop the methodology for the consistent measurement of cleaning effectiveness; and (2) determine implementable cleaning, decontamination, and disinfection strategies that effectively reduce fire fighter exposures to persistent contaminants. The approach taken by this project is illustrated in Figure 1: Project Conceptual Approach. - Ensure Identify Devise Validate lab - - chemical and methods to methods - at biologicat conteminate againet field ses target clothing in contaminants laboratory exposures acceptance Project Direction Figure 1: Project Conceptual Approach 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7281 Fax: +1.617.984.7010 Email: [email protected] www.NFPA.org/Foundation Source: :ttps://www.industrydocuments.ucsf.edu/docs/hlcn0226 Project Phases and Tasks: This project involves the following four key phases of activity: 1) Identification of Contaminants: Confirm identification and ability to characterize persistent chemical and biological contaminants in fire fighter PPE through target substances and microorganisms. 2) Establishment of Soil and Chemical Contamination/Decontamination Procedures: Develop and validate specific procedures that determine the effectiveness of laundering and other cleaning methods in removing specific soils and chemical contaminants. 3) Establishment of Biological Contamination/Disinfection or Sanitization Procedures: Develop and validate specific procedures that determine the effectiveness of laundering or disinfection/sanitization processes that remove/deactivate biologically-based contaminants. 4) Creation of Overall Fire Service Guidance: Prepare clear and definitive information for the fire service industry (fire fighters, fire departments, clothing manufacturers, material suppliers, cleaning/care organizations, and cleaning agent or equipment manufacturers) on appropriate approaches for properly cleaning fire fighter protective clothing and equipment. The specific tasks of this project are based on these four phases of the project, and these are illustrated in Figure 2: Project Tasks. PHASE 2 PHASEZ Task 2.4 Task 2.5 Task 1.1 Task 2.1 Validate testsat Refine test Appoint Technical Select cleaning selected ISPS methodology Review Panel methods/agents (chemical) (chemical) PHASE $ Task 4.1 Task 1.2 Task 2.2 Write qualification Review Prigr Put together test plan methods studies/literature (chemical) Task 2.3 Task 4.2 Task 1.3 PHASE 3 Perform laboratory Establish cleaning Setup analytical chemical Task 3.3 acceptance criteria capabilities decontaminant Put together test plan testing (biological) Task 4.3 Task 1.4 Perform Task 3.4 Prepare public inputs for NFPA 1851 demonstration tests Task 3.1 Perform laboratory Task 3.6 Select study biological Refine test microorganisms decontaminant methodology Task 1.5 testing (biological) Task 4.4 Refine biological Prepare industry decontamination Task 3.2 Task 3.5 guidance document scope Select biological Validate testsat cleaning methods selected ISPs (biological) Task 1.6 Task 4,5 Establish cleanliness Prepare project final metrics report Figure 2: Project Tasks Implementation and Schedule: This three year project is due to be completed no later than " August 2018, and is funded through an AFG Fire Prevention & Safety Grant from the U.S. Department of Homeland Security / Federal Emergency Management Agency. The Research Foundation will lead a unique research team partnership composed of the FPRF, National Institute for Occupational Safety and Health (NIOSH), International Personal Protection (IPP), and Intertek. The research team, along with several Independent Service Providers (ISPs), will work with the fire service partners and others to validate and optimize fire fighter PPE cleaning validation methods. For more information see www.nfpa.org/PPECleaning. Page 2 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION Fire Fighter Cancer Cohort Study Full Title: The Firefighter Multicenter Cancer Cohort Study: Framework Development and Testing PROJECT SUMMARY Last Updated: 20 September 2016 Background: Cancer is a leading cause of fire service morbidity and mortality. Firefighter exposure to carcinogens occurs through skin contamination and through inhalation when respiratory protection is not worn when combustion products are present such as during overhaul, standby, and operation of apparatus, as well as through off-gassing of equipment and exposures in the fire station. However, we currently do not understand which exposures are responsible for cancer in firefighters, the mechanisms by which firefighter exposures cause cancer, nor the most effective means of reducing exposures. Since cancer has a long latency period, biomarkers are also needed that can measure the toxicological effects of carcinogen exposure well before the development of cancer, when interventions to prevent disease could be effective. Development of a large (>10,000 firefighter) multicenter firefighter cancer prospective cohort study will address these needs, but the framework for such a study needs to be first developed and tested among a smaller initial set of fire service partners. Implementation and Schedule: This research project is led by University of Arizona with collaborative support from multiple other research partners, including the University of Miami, National Institute for Occupational Safety and Health; National Fallen Firefighter Foundation, Fire Protection Research Foundation, and others. Initial funding for this project is through a 3-year DHS/FEMA Assistance to Fire Fighter (AFG) Fire Grant, with the intention to identify and obtain additional funding for the duration of the 30 year effort. The project start date is August 2016. The Principal Investigator for this project is: Jefferey L. Burgess, MD, MS, MPH, University of Arizona, email: [email protected]. Project Goal and Aims: The goal of the initial 3-year effort of this overall project is to develop and test a framework for establishing a long-term fire fighter multicenter prospective cohort study focused on carcinogenic exposures and effects. The specific aims are to: 1) Establish an oversight and planning board to provide study oversight, foster communication among fire organizations and help develop a long-term funding plan; 2) Create and test a cohort study data coordinating center and harmonized survey data protocols; 3) Develop and validate a firefighter carcinogen exposure matrix and data collection system; and 4) Create a biomarker assessment center and evaluate the association between cumulative firefighter exposures and epigenetic effects. For more information, contact: Casey Grant, Fire Protection Research Foundation 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7284 Fax: +1.617.984.7010 Email: [email protected] Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Project Methodology: This study will harmonize and build on recent and developing firefighter cancer prevention studies in Arizona, Florida and Massachusetts, adding volunteer fire departments. An oversight and planning board will be established by the Fire Protection Research Foundation (FPRF) in association with the National Fallen Firefighter Foundation (NFFF) Fire Service Occupational Cancer Alliance (FSOCA) to provide oversight of the study through collaboration among fire service organizations, academia, and government agencies, and develop a long-term funding and sustainability plan. A data coordination center team will design, develop and evaluate a framework for a multicenter prospective cohort study of firefighters and cancer risk, including standardized participant survey data collection tools and analysis protocols sufficient to address the short- and long-term study objectives as well as linkage with long-term outcome data including cancer development. An exposure assessment center team will develop a carcinogen exposure matrix and data collection system to provide improved occupational exposure data for comparison with epigenetic outcomes and eventual cancer outcomes. Carcinogen exposures associated with specific fire types will be evaluated across fire departments through industrial hygiene monitoring and analysis of urine for absorbed contaminants, supplementing existing FEMA-funded and other studies of firefighter exposures and allowing for participating fire departments to design interventions to reduce current exposures. Expansion of the National Fire Operations Reporting System (NFORS) will be explored as one option to uniformly collect incident and exposure data. Blood and buccal cells will be collected during annual medical surveillance evaluations, including both new recruits and incumbent firefighters. Pilot studies of epigenetic markers of cancer effect and cancer risk will be analyzed comparing municipal firefighters with high chronic exposures, volunteer firefighters with low chronic exposures, and non- firefighter friends of the municipal firefighters (serving as controls). Project Deliverables: The anticipated outcomes from this 3-year effort is to establish and test the framework necessary for the subsequent development of a large multicenter cohort study of cancer in the fire service. Page 2 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226

Who is currently the President and CEO of the American Seed Trade Association?

ffcn0226

ffcn0226_p0, ffcn0226_p1, ffcn0226_p2, ffcn0226_p3, ffcn0226_p4, ffcn0226_p5, ffcn0226_p6, ffcn0226_p7, ffcn0226_p8, ffcn0226_p9, ffcn0226_p10, ffcn0226_p11, ffcn0226_p12, ffcn0226_p13, ffcn0226_p14, ffcn0226_p15, ffcn0226_p16, ffcn0226_p17, ffcn0226_p18, ffcn0226_p19, ffcn0226_p20, ffcn0226_p21, ffcn0226_p22, ffcn0226_p23, ffcn0226_p24, ffcn0226_p25, ffcn0226_p26, ffcn0226_p27, ffcn0226_p28, ffcn0226_p29, ffcn0226_p30, ffcn0226_p31, ffcn0226_p32, ffcn0226_p33, ffcn0226_p34

Andrew W. "Andy" LaVigne, Andrew W. LaVigne, Andrew W.LaVigne

To: Greenwalt, Sarah[[email protected]]; Dravis, Samantha[[email protected]] Brown, Byron[[email protected]];Wagner, Kenneth[[email protected]] From: Hupp, Sydney Sent: Thur 3/30/2017 5:11:34 PM Subject: FW: FINAL Meeting Agenda and Materials Pruitt Meeting Materials.pd FYI. Sydney Hupp Office of the Administrator- Scheduling 202.816.1659 From: Mary Jo Tomalewski [mailto:[email protected]] Sent: Thursday, March 30, 2017 11:22 AM To: Hupp, Sydney <[email protected]> Cc: Jay Vroom <[email protected]> Subject: FINAL Meeting Agenda and Materials Sydney, We have refined our proposed topics for today's CEO Council meeting with the administrator. Attached, please find: Revised "Final Proposed Agenda Topics," which includes the list of those CEO Council members who will attend our meeting today, and their short bios Introduction / Mission Overview of the CEO Council CEO Council Letter to President Trump, dated February 9, 2017 We assume we can skip a formal "round table of introductions" at the beginning of the meeting as our time is short and we want to maximize time spent talking about issues. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000061-00001 MJ Mary Jo Tomalewski Executive Assistant to the President & CEO CropLife America 1156 15th Street, NW Suite 400 Washington, DC 20005 Direct Dial (202) 872-3849 Main Switchboard (202) 296-1585 Mobile Ex. 6 Personal Privacy Fax (202)466-5832 Email [email protected] Web www.croplifeamerica.org How can I serve you today? Future Meetings 2017 Spring Regulator Conference - April 6-7, Arlington, VA 2017 Annual Meeting - September 22-27, Dana Point, CA 2018 Winter Board of Directors Meeting - March 5-7, Washington, DC 2018 Annual Meeting - September 21-26, The Ritz-Carlton Amelia Island Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000061-00002 FINAL PROPOSED AGENDA TOPICS Meeting Information: Office of EPA Administrator Scott Pruitt 1200 Pennsylvania Avenue, NW Washington, DC Thursday, March 30, 2017 3:45-4:30 PM Topic 1. Thanks to Trump Administration and Administrator Pruitt for early decisive actions: a. WOTUS b. Chlorpyrifos Petition 2. Top Priority Issues a. Ag Advisor Position - We recommend adding additional title of "Assistant Deputy Administrator" as a title b. Water i. Next steps to refine / clarify beyond WOTUS ii. NPDES permits (CAFO Program needs work; legislation to fix water permits NOT needed for lawful use of pesticides) c. Pesticides Policy i. Endangered Species Act conflicts with Pesticide Regulation and Biotech Regulation ii. Epidemiology Study Policy (as aftermath from Chlorpyrifos matter) iii. Reform Certification & Training and Worker Protection Rules - Suspend implementation and revise d. Renewable Fuels Standard - current program kept consistent e. Communication / Messaging / Opinion Polling - vital to all parties' ability to advance sound policy f. EPA and USDA Cooperation and Coordination - Already vast progress; more can be done! g. Environmental Justice, Research & Development, and Children's Health Offices - Better integration with and reform of EPA program offices; sound science h. Regulation of Manufacturing & Mining Facilities for Ag Inputs - Restore science and process i. Public and Science Advisory Panels at EPA - Balance, strategic agendas j. "Air Emissions" from farming operations CEO Attendees American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Corn Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Barb Glenn, CEO, ex-officio Departments of Agriculture Others American Farm Bureau Federation Dale Moore, Deputy Executive Director Corn Refiners Association John Bode, President & CEO National Farmers Union Rob Larew, Senior VP Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00001 Production Agriculture's CEO Council Introduction/Mission Statement: The production agriculture "CEO Council" coordinates alignment on core issues of modern agricultural systems through telling our story, sharing information and leveraging our strengths, while serving as a resource for government decision makers and others interested in USA food, fiber and renewable fuels. Core Focus of Interest Research and innovation Technology access Science and risk-based regulation Sustainability, environment, and weather Marketability, trade, and economic prosperity Government leadership and partnership with private sector Food access and food safety Plant and animal health Ag labor The Council supports principles/themes): Accelerating rural economic growth and improving productivity through innovation and technology Promoting research and innovation that enables development oftools and techniques necessary for discovering new products that hold tremendous potential for farmers and society at large Enabling a regulatory and commercial environment in which agricultural products are marketable, both domestically and internationally Appropriate balance between Federal and State Governments and a cooperative regulatory approach Access to essential labor in balance with an effective Federal immigration policy and adequate worker safety protections Support for all methods of agricultural production Transparency and dialogue with consumers Members of the CEO Council (see reversed) March 30, 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00002 CEO Council Members American Farm Bureau Vincent "Zippy" Duvall, President American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Cattlemen's Beef Association Kendal Frazier, CEO National Chicken Council Michael Brown, President National Com Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Farmers Union Roger Johnson, President National Milk Producers Federation Jim Mulhern, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Departments of Barb Glenn, CEO, ex-officio Agriculture March 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00003 February 9, 2017 The President The White House Washington, D.C. 20500 Dear Mr. President, We, the CEO Council (undersigned herein), representing the production agricultural value chain, including many agricultural producers and farm input developers and suppliers, look forward to working with you and your Administration on matters of importance to American agriculture. The challenges we face in agriculture are significant. Many experts emphasize that producers must grow as much food in the next 50 years as was produced over all previous history to meet the demands of our expanding global population. A firm commitment by the U.S. government to aggressively support agricultural innovation and science-based regulatory decisions will be necessary to ensure farmers have the tools they need to produce a safe and abundant supply of nutritious food, in addition to feed, fuel and fiber, in an environmentally sound and sustainable manner. The policy and regulatory environment your Administration establishes can ensure that agricultural innovation flourishes and American farmers are able to meet the food production goals necessary to feed billions more people. We are ready to provide the White House and the Executive Branch Departments and Agencies, as well as Congress, with policy concepts that foster stability in the U.S. agriculture economy with a strong and predictable farm safety net and promotes American competitiveness through research; marketability and trade of agricultural commodities; rural economic growth; and plant, animal, and environmental health, among many other things. We appreciate your attention to these and other issues of value to American production agriculture and food consumers everywhere. Sincerely, American Farm Bureau Foundation, Zippy Duvall American Seed Trade Association, Andy LaVigne American Soybean Association, Steve Censky Biotechnology Innovation Organization, Dana O'Brien CropLife America, Jay Vroom The Fertilizer Institute, Chris Jahn National Association of Wheat Growers, Chandler Goule National Cattlemen's Beef Association, Kendal Frazier National Corn Growers Association, Chris Novak National Cotton Council, Gary Adams National Council of Farmer Cooperatives, Chuck Conner National Farmers Union, Roger Johnson National Milk Producers Federation, Jim Mulhern National Pork Producers Council, Neil Dierks United Fresh Produce Association, Tom Stenzel USA Rice Federation, Betsy Ward Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00004 National Gotton Council OF MERTOA Gary M. Adams President and Chief Executive Officer National Cotton Council of America Gary Adams assumed the position of President and Chief Executive Officer of the National Cotton Council in February 2015. He plays a key role in guiding the industry's seven segments to reach consensus on critical policies affecting U.S. cotton, with the mission of helping all U.S. cotton industry segments compete effectively and profitably in global markets. Prior to that, Gary served the Council for 13 years as the Vice President of Economic and Policy Analysis. As the Council's chief economist, he provided economic outlooks for global cotton markets, as well as analyzing the impacts of farm and trade policies. Gary also represents the U.S. cotton industry as a member of USDA's Agricultural Policy Advisory Committee. Previously, Gary served on USDA's Advisory Committee on Trade from 2005 through 2011 and the NASS Advisory Committee on Agricultural Statistics from 2003 through 2009. Prior to joining the Council, Gary was a Research Assistant Professor in the Department of Agricultural Economics at the University of Missouri. During his 13-year tenure at the university, Gary's primary responsibilities included policy analysis and market outlook for the Food and Agricultural Policy Research Institute, also known as FAPRI. While at FAPRI, Gary and his colleagues were recognized by the American Agricultural Economics Association for their distinguished policy contributions. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00005 Gary has B.S. and M.A. degrees in Applied Mathematics from the University of Alabama and a Ph.D. in Agricultural Economics from the University of Missouri. Gary and his wife, Ex. 6 Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00006 FASA American Soybean Associatión & Stephen L Censky Chief Executive Officer Stephen L. Censky is the American Soybean Association's (ASA) C hief Executive Officer, a staff position he accepted in April 1996. As ASA's top executive, Ce nsky is in charge of managing ASA's legislative, trade policy, membership and education and training programs. The American Soybean Association is a national, not-for-profit commodity organization with over 22,000 members. ASA works as the domestic and international policy advocate for soybean producer members. Prior to joining ASA, Censky worked in Washington, D.C. for ove a decade. He began his career on Capitol Hill as a legislative assistant for agricultural and transportation matters to Senator Jim Abdnor (R-SD). Later he served in both the Reagan and Bush Administrations at the U.S. Department of Agriculture, helping to craft the 1990 Farm Bill and eventually serving as Administrator of the Foreign Agricultural Service where he was involved in global trade negotiations and running our nation's export programs. Censky received his Bachelor's of Science degree of Agriculture from South Dakota State University and his Master's Diploma in Agriculture St of Melbourne, Australia. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00007 NCFC. National Council of Farmer Cooperatives Charles F. (Chuck) Conner President and CEO National Council of Farmer Cooperatives Charles F. (Chuck) Conner became president & CEO of the National Council of Farmer Cooperatives (NCFC) on January 22, 2009. As president of NCFC, Conner will oversee the organization's work to promote and protect the business and public policy interests of America's farmer-owned cooperatives. He will also provide the strategic vision for the trade association as it continues to seek new ways in which to add value for its membership. Prior to joining NCFC, Conner had served as the Deputy Secretary at the U.S. Department of Agriculture since mid-2005. In this capacity, he was the Chief Operating Officer (COO) overseeing day-to-day operations of the department. Conner interacted directly with President George W. Bush and his senior staff to formulate domestic and international food, trade, security and energy policy. He led development of the Bush Administration's $300 billion Farm Bill proposal and the strategy to educate and inform industry, constituents and Congress. From August 2007 to January 2008, Conner served as both USDA Secretary and Deputy Secretary. He played a key role in developing the Administration's immigration policy including important changes to the H2A program. Conner's experience also includes the assignment of Special Assistant to the President, Executive Office of the President, from October 2001 to May 2005, working on the 2001/2 Farm Bill to develop the strategy behind the transfer of several USDA agency functions to the newly formed Department of Homeland Security. From May 1997 to October 2001 Conner served as President of the Corn Refiners Association. He also served for 17 years as an advisor to U.S. Senator Richard Lugar of Indiana. Conner is a graduate of Purdue University, with a Bachelor's of Science degree and is the recipient of Purdue's Distinguished Alumni Award. He and his wife Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00008 NATIONAL PORK PRODUCERS COUNCIL Neil Dierks, Chief Executive Officer Neil Dierks is Chief Executive Officer of the National Pork Producers Council (NPPC). In this position, he is responsible for the overall implementation of all NPPC programs. Dierks' position requires him to spend time in both Des Moines, Iowa, the national office of NPPC, and Washington, D.C. Beginning in 1990, Dierks served NPPC in a series of senior executive positions, including Executive Director of Operations, Vice President for Research and Education and Senior Vice President for Programs. Prior to his service with NPPC, Dierks was the Special Activities Director for the Iowa Pork Producers Association and Marketing Director for the Iowa Corn Promotion Board. Neil grew up on a livestock farm in eastern lowa and remains involved in a family farming operation. He is a graduate of Iowa State University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00009 NASDA Dr. Barbara Glenn recently joined the National Association of State Departments of Agriculture (NASDA) as CEO on August 18, 2014. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. Dr. Glenn is a scientist with decades of experience as a policy researcher and advocate for agriculture. She previously served as Senior Vice President of Science and Regulatory Affairs for CropLife America, where she was responsible for developing policies and regulations to support agriculture through crop protection. Prior to joining CropLife America, Dr. Glenn served as Managing Director of the Animal Bi otechnology, Food and Agriculture Section of the Biotechnology Industry Association in Washington, DC. Dr. Glenn holds a B.S. in animal science and a Ph.D. in ruminan t nutrition from the University of Kentucky. She previously worked for the U.S. Department of Agriculture, Agric ultural Research Service and the Federation of Animal Science Societies. Born in Lincoln, Nebraska and raised in Centerville, Ohio, Dr. Glenn developed a passion for agriculture from her parents and her involvement in 4-H. She lives Ex. 6 - Personal Privacy and serves on various boards for farm bureau and 4-H. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00010 National Association of Wheat Growers Chandler Goule CEO Chandler Goule assumed his responsibilities as CEO of the National Association of Wheat Growers on July 5, 2016. In addition, he also serves as the executive director of the National Wheat Foundation. Most recently, Goule served as senior vice president of programs at the National Farmers Union (NFU) where he was heavily involved in farm bill legislation. Originally from Texas, Goule holds degrees from Texas A&M and George Washington University and served as a subcommittee staff director for the House Agriculture Committee before moving to the National Farmers Union in 2009 as vice president of government relations. He was appointed senior vice president of NFU programs in 2014. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00011 The Fertilizer Institute Nourish, Replenish, Grow BIOGRAPHY OF CHRISTOPHER JAHN President The Fertilizer Institute and the Nutrients for Life Foundation Christopher L. Jahn is president of The Fertilizer Institute (TFI), the fertilizer industry's national trade association. As TFI president, Jahn works to represent, promote and protect a sound fertilizer industry through legislative and regulatory activities and to promote a favorable public image of the fertilizer industry and agriculture. Jahn also serves as president of the Nutrients for Life Foundation (NFL). Jahn comes to TFI having served as president of the National Association of Chemical Distributors (NACD) since 2006. Prior to leading NACD, Jahn served as president of the Contract Services Association (CSA). Before joining CSA, Jahn had an active role in the United States Senate working for nearly 10 years for U.S. Senator Craig Thomas (R-Wyo.) in a variety of roles, including legislative assistant, legislative director and Chief of Staff. After graduating from Columbia University with a B.A. in Political Science, Jahn co-founded a book distribution business. He also earned an MBA from the University of Maryland. A native of Wyoming, Chris and his wife, Ex. 6 - Personal Privacy Ex. Personal Privacy Capitol View 202.962.0490 425 Third Street, S.W., Suite 950 202.962.0577 fax Washington, DC 20024 www.tfi.org Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00012 National Farmers Union Roger Johnson President Roger Johnson is president of the National Farmers Union (NFU), a grassroots organization that represents more than 200,000 family farmers, ranchers, fisherman and rural communities across the Unites States. Johnson was elected to lead the family farm organization at NFU's 107th anniversary convention in 2009. He has since expanded the education department by providing more programs for beginning, college-aged and women farmers, increased the number of Farmers Union state divisions, and developed a strategic plan for the organization. Johnson has also overseen a number of important policy initiatives important to family farmers including: passage of the 2014 Farm Bill; maintaining a strong Renewable Fuel Standard and Country-of-Origir Labeling, promoting policies that allow farmers to address the growing threat of climate change; and renewing the nation's focus on eliminating an overwhelming trade deficit that results in lost jobs and prosperity for rural America. Prior to leading National Farmers Union, Johnson, a third-generation family farmer from Turtle Lake, N.D., served as North Dakota Agriculture Commissioner, a position he was first elected to in 1996. While Agriculture Commissioner, Johnson served on the State Industrial Commission, the North Dakota Trade Office Advisory Board, and the State Board of Agricultural Research and Education, among many other boards and commissions. From 2007-2008, Johnson served as president of the National Association of State Departments of Agriculture (NASDA). He is a past president of the Midwestern Association of State Departments of Agriculture (MASDA), past president of the Food Export Association of the Midwest and a former chairman of the Interstate Pest Control Compact. Johnson graduated from North Dakota State University with a degree in agricultural economics. Johnson and his wife Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00013 AMERICAN SEED TRADE ASSOCIATION asta first-the - seed R Andrew W. "Andy" LaVigne President & CEO Andrew W. LaVigne is currently the President and CEO of the Ame rican Seed Trade Association. He joined ASTA in February, 2006. Andy has had a 30-year career i n government relations, industry representation, public affairs advocacy, and management. His C ore areas of expertise include agriculture, food policy and international trade. Prior to joining ASTA, Andy was Executive Vice President/CEC of Florida Citrus Mutual, representing citrus growers on issues affecting their business. Prejaiming tFdorida Citrus Mutual, Andy spent four years as Florida Fertilizer and Agrichemical Association's (FFAA) President and Executive Director. FFAA is a non-profit, agricultural trade organization representing companies that specialize in crop protection and plant nutrition products. Before his position at FFAA, Andy spent eight years in Washingt on, D.C. working in the U.S. Congress and the U.S. Department of Agriculture. He served as Legislative Director for Congressman Charles Canady, Agriculture Committee staffer for Congressman Tom Lewis , and on the staff of USDA Secretary Ed Madigan. Andy is a native of Florida with a BA degree in Political Scien ce, with a minor in economics, from the University of Florida. 1701 Duke Street Suite 275 Alexandria, VA 22314 Phone: (703)837-8140 Fax: (703)837-9365 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00014 Biotechnology Innovation Organization Dana O'Brien Executive Vice President, Food & Agriculture Dana O'Brien is Executive Vice President for Food and Agriculture and is responsible for the development of public policy and strategic advocacy, public affairo, and legal strategies that advance industry and stakeholder objectives in the United States. Prior to becoming EVP, Dana served bs BIO Food and Agriculture's chief legislative advocate as Senior Director of Federal Government Relations aince March 2011. Before BIO, Dana worked in Congress for the late Representative lke Skelton (D-MO) managing his legislative team and concentrating on a variety of agricultural, energy, and trade matters. A native of Sedalia, Missouri, and a graduate of Missouri University with a bachelor's degree in psychology, Dana joined the Skelton team immediately out of college and served there for nearly 14 years Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00015 UNITED FRESH is PRODUCE ASSOCIATION Tom Stenzel President and CEO United Fresh Produce Association 1901 Pennsylvania Avenue NW, Suite 1100 Washington, DC 20006 202/303-3400 [email protected] Tom Stenzel is President and CEO of the United Fresh Produce Association, a position he has held since 1993. United Fresh is the pre-eminent trade association for the produce industry in shaping legislative and regulatory policies; providing scientific and technical leadership in food safety and nutrition; and developing educational programs for its members. Founded in 1904, United Fresh represents the interests of companies from small family businesses to the largest international corporations throughout the global fresh produce supply chain. United Fresh is widely known for its work in government affairs, agricultural policy, food safety and nutrition, working to promote political and environmental change to help the next generation of children double their consumption of fresh produce. The United Fresh Start Foundation is committed to increasing children's access to fresh fruits and vegetables, and is a founding partner of the Let's Move Salad Bars to Schools campaign. The campaign has donated salad bars to more than 6,000 schools across the country. Tom is a frequent speaker on industry issues and has been recognized often by the produce industry throughout his career. He was honored as the 2002 Produce Man of the Year by The Packer newspaper, and is the past Chairman of the International Federation for Produce Standards, a global body representing national produce associations around the world. He is a member of the U.S. Chamber of Commerce Committee of 100 leading association executives, the Advisory Board of the International Food Protection Training Institute, and the Key Industry Associations Committee of the American Society of Association Executives, from which he achieved the Certified Association Executive (CAE) designation in 1990. He has served in many government and industry leadership positions, including the first U.S. Department of Agriculture Fruit and Vegetable Industry Advisory Committee, President George W. Bush's Transition Advisory Team for Agriculture, and as an advisor on the U.S. Agricultural Policy Advisory Committee for Trade. Tom was the founding President of the International Food Information Council (IFIC) in 1986, and was previously director of public affairs for the National Soft Drink Association. Tom is a 1977 graduate of the University of Richmond. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00016 as of January 17, 2017 Jay Vroom has served as President and CEO of the trade association known as CropLife America (CLA) since 1989. CLA is the leading U.S. trade group for the crop protection industry in the U.S. Vroom is a founding member of the CropLife Foundation, serving as chairman since its inception in 2001, and now serves as the Foundation's Vice-Chair, since 2015. His sits of the Board of Directors for the Agricultural Retailers Association, Asmark, National Wheat Foundation, the National Association of Manufacturers Council of Manufacturing Associations, and the Soil Health Institute. He is also a member of the Farm Foundation Roundtable Steering Committee, and the North American Climate Smart Ag Alliance Steering Committee. Vroom was a member of the youth organization, Future Farmers of America, and served as an elected state officer in Illinois. Today, he is a member of the FFA Foundation's Individual Giving Council and Board of Trustees. Vroom co-chairs the Coalition for the Advancement of Precision Agriculture and the CEO Council. He is a member of the Friends of the National Arboretum (FONA) FONA Council. He graduated with honors from the College of Agriculture, Consumer and Environmental Sciences at the University of Illinois Urbana-Champaign. Vroom was raised on a grain and livestock farm in north-central Illinois and continues to own the farming operation. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00017 Elizabeth Ward Betsy Ward was appointed President & CEO of the USA Rice Federation in 2007. From 2003- 2005, Ward was the Vice President of International and Domestic Promotion at USA Rice where she was in charge of developing and implementing domestic and international promotion, and food aid programs. From 2005-2007, Ward served as the chief executive for the Hardwood Federation, a trade association representing over 15,000 hardwood producers across the United States. From 1995 to 2003, she ran the Wood Products International Group at the American Forest & Paper Association, directing the wood trade policy and global forestry agenda for the industry. In 2011, Ward was elected Chairman of the U.S. Agricultural Export Development Council (USAEDC) which represents the interests of more than 80 commodity organizations who grow and process a wide variety of U.S. agricultural products. She currently serves as Past Chair. Since 2011, Ward has also served on the Board of Directors of the Sustainable Fisheries Partnership, an independent non-governmental organization (NGO) working to ensure healthy marine and aquatic tecosystems; secure seafood supplies; and a thriving, responsible seafood economy. Ward served for six years as a cleared advisor on the Industry Trade Advisory Committee for forest and paper products (ITAC-7) and was appointed forest products representative to USDA's Agricultural Policy Advisory Committee (APAC) in 2001. Ward holds a Bachelor's degree in History and Political Science from the University of New Hampshire and a Master's degree in International Security Affairs from the School of International Affairs at Columbia University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00018 To: Brown, Byron[[email protected]]; Jackson, Ryan[[email protected]] From: Rebeckah Adcock Sent: Thur 3/30/2017 4:10:52 PM Subject: FW: FINAL CEO Council Meeting Agenda and Materials Pruitt Meeting Materials.pdf ATT00001.htm FYI - final materials for today's meeting. Reb From: "Mary Jo Tomalewski" <[email protected]> To: "Hupp, Sydney" <[email protected]> Cc: "Jay Vroom" <[email protected]> Subject: FINAL Meeting Agenda and Materials Sydney, We have refined our proposed topics for today's CEO Council meeting with the administrator. Attached, please find: Revised "Final Proposed Agenda Topics," which includes the list of those CEO Council members who will attend our meeting today, and their short bios Introduction / Mission Overview of the CEO Council CEO Council Letter to President Trump, dated February 9, 2017 We assume we can skip a formal "round table of introductions" at the beginning of the meeting as our time is short and we want to maximize time spent talking about issues. MJ Mary Jo Tomalewski Executive Assistant to the President & CEO CropLife America Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000063-00001 1156 15th Street, NW Suite 400 Washington, DC 20005 Direct Dial (202) 872-3849 Main Switchboard (202) 296-1585 Mobilé Ex. 6 Personal Privacy Fax (202) 466-5832 Email [email protected] Web www.croplifeamerica.org How can I serve you today? Future Meetings 2017 Spring Regulator Conference - April 6-7, Arlington, VA 2017 Annual Meeting - September 22-27, Dana Point, CA 2018 Winter Board of Directors Meeting - March 5-7, Washington, DC 2018 Annual Meeting - September 21-26, The Ritz-Carlton Amelia Island Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000063-00002 FINAL PROPOSED AGENDA TOPICS Meeting Information: Office of EPA Administrator Scott Pruitt 1200 Pennsylvania Avenue, NW Washington, DC Thursday, March 30, 2017 3:45-4:30 PM Topic 1. Thanks to Trump Administration and Administrator Pruitt for early decisive actions: a. WOTUS b. Chlorpyrifos Petition 2. Top Priority Issues a. Ag Advisor Position - We recommend adding additional title of "Assistant Deputy Administrator" as a title b. Water i. Next steps to refine / clarify beyond WOTUS ii. NPDES permits (CAFO Program needs work; legislation to fix water permits NOT needed for lawful use of pesticides) c. Pesticides Policy i. Endangered Species Act conflicts with Pesticide Regulation and Biotech Regulation ii. Epidemiology Study Policy (as aftermath from Chlorpyrifos matter) iii. Reform Certification & Training and Worker Protection Rules - Suspend implementation and revise d. Renewable Fuels Standard - current program kept consistent e. Communication / Messaging / Opinion Polling - vital to all parties' ability to advance sound policy f. EPA and USDA Cooperation and Coordination - Already vast progress; more can be done! g. Environmental Justice, Research & Development, and Children's Health Offices - Better integration with and reform of EPA program offices; sound science h. Regulation of Manufacturing & Mining Facilities for Ag Inputs - Restore science and process i. Public and Science Advisory Panels at EPA - Balance, strategic agendas j. "Air Emissions" from farming operations CEO Attendees American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Corn Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Barb Glenn, CEO, ex-officio Departments of Agriculture Others American Farm Bureau Federation Dale Moore, Deputy Executive Director Corn Refiners Association John Bode, President & CEO National Farmers Union Rob Larew, Senior VP Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00001 Production Agriculture's CEO Council Introduction/Mission Statement: The production agriculture "CEO Council" coordinates alignment on core issues of modern agricultural systems through telling our story, sharing information and leveraging our strengths, while serving as a resource for government decision makers and others interested in USA food, fiber and renewable fuels. Core Focus of Interest Research and innovation Technology access Science and risk-based regulation Sustainability, environment, and weather Marketability, trade, and economic prosperity Government leadership and partnership with private sector Food access and food safety Plant and animal health Ag labor The Council supports principles/themes): Accelerating rural economic growth and improving productivity through innovation and technology Promoting research and innovation that enables development oftools and techniques necessary for discovering new products that hold tremendous potential for farmers and society at large Enabling a regulatory and commercial environment in which agricultural products are marketable, both domestically and internationally Appropriate balance between Federal and State Governments and a cooperative regulatory approach Access to essential labor in balance with an effective Federal immigration policy and adequate worker safety protections Support for all methods of agricultural production Transparency and dialogue with consumers Members of the CEO Council (see reversed) March 30, 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00002 CEO Council Members American Farm Bureau Vincent "Zippy" Duvall, President American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Cattlemen's Beef Association Kendal Frazier, CEO National Chicken Council Michael Brown, President National Com Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Farmers Union Roger Johnson, President National Milk Producers Federation Jim Mulhern, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Departments of Barb Glenn, CEO, ex-officio Agriculture March 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00003 February 9, 2017 The President The White House Washington, D.C. 20500 Dear Mr. President, We, the CEO Council (undersigned herein), representing the production agricultural value chain, including many agricultural producers and farm input developers and suppliers, look forward to working with you and your Administration on matters of importance to American agriculture. The challenges we face in agriculture are significant. Many experts emphasize that producers must grow as much food in the next 50 years as was produced over all previous history to meet the demands of our expanding global population. A firm commitment by the U.S. government to aggressively support agricultural innovation and science-based regulatory decisions will be necessary to ensure farmers have the tools they need to produce a safe and abundant supply of nutritious food, in addition to feed, fuel and fiber, in an environmentally sound and sustainable manner. The policy and regulatory environment your Administration establishes can ensure that agricultural innovation flourishes and American farmers are able to meet the food production goals necessary to feed billions more people. We are ready to provide the White House and the Executive Branch Departments and Agencies, as well as Congress, with policy concepts that foster stability in the U.S. agriculture economy with a strong and predictable farm safety net and promotes American competitiveness through research; marketability and trade of agricultural commodities; rural economic growth; and plant, animal, and environmental health, among many other things. We appreciate your attention to these and other issues of value to American production agriculture and food consumers everywhere. Sincerely, American Farm Bureau Foundation, Zippy Duvall American Seed Trade Association, Andy LaVigne American Soybean Association, Steve Censky Biotechnology Innovation Organization, Dana O'Brien CropLife America, Jay Vroom The Fertilizer Institute, Chris Jahn National Association of Wheat Growers, Chandler Goule National Cattlemen's Beef Association, Kendal Frazier National Corn Growers Association, Chris Novak National Cotton Council, Gary Adams National Council of Farmer Cooperatives, Chuck Conner National Farmers Union, Roger Johnson National Milk Producers Federation, Jim Mulhern National Pork Producers Council, Neil Dierks United Fresh Produce Association, Tom Stenzel USA Rice Federation, Betsy Ward Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00004 National Gotton Council OF MERTOA Gary M. Adams President and Chief Executive Officer National Cotton Council of America Gary Adams assumed the position of President and Chief Executive Officer of the National Cotton Council in February 2015. He plays a key role in guiding the industry's seven segments to reach consensus on critical policies affecting U.S. cotton, with the mission of helping all U.S. cotton industry segments compete effectively and profitably in global markets. Prior to that, Gary served the Council for 13 years as the Vice President of Economic and Policy Analysis. As the Council's chief economist, he provided economic outlooks for global cotton markets, as well as analyzing the impacts of farm and trade policies. Gary also represents the U.S. cotton industry as a member of USDA's Agricultural Policy Advisory Committee. Previously, Gary served on USDA's Advisory Committee on Trade from 2005 through 2011 and the NASS Advisory Committee on Agricultural Statistics from 2003 through 2009. Prior to joining the Council, Gary was a Research Assistant Professor in the Department of Agricultural Economics at the University of Missouri. During his 13-year tenure at the university, Gary's primary responsibilities included policy analysis and market outlook for the Food and Agricultural Policy Research Institute, also known as FAPRI. While at FAPRI, Gary and his colleagues were recognized by the American Agricultural Economics Association for their distinguished policy contributions. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00005 Gary has B.S. and M.A. degrees in Applied Mathematics from the University of Alabama. and a Ph.D. in Agricultural Economics from the University of Missouri. Gary and his wife, Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00006 FASA American Soybean Associatión & Stephen L Censky Chief Executive Officer Stephen L. Censky is the American Soybean Association's (ASA) C hief Executive Officer, a staff position he accepted in April 1996. As ASA's top executive, Ce nsky is in charge of managing ASA's legislative, trade policy, membership and education and training programs. The American Soybean Association is a national, not-for-profit commodity organization with over 22,000 members. ASA works as the domestic and international policy advocate for soybean producer members. Prior to joining ASA, Censky worked in Washington, D.C. for ove a decade. He began his career on Capitol Hill as a legislative assistant for agricultural and transportation matters to Senator Jim Abdnor (R-SD). Later he served in both the Reagan and Bush Administrations at the U.S. Department of Agriculture, helping to craft the 1990 Farm Bill and eventually serving as Administrator of the Foreign Agricultural Service where he was involved in global trade negotiations and running our nation's export programs. Censky received his Bachelor's of Science degree of Agriculture from South Dakota State University and his Master's Diploma in Agriculture St of Melbourne, Australia. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00007 NCFC. National Council of Farmer Cooperatives Charles F. (Chuck) Conner President and CEO National Council of Farmer Cooperatives Charles F. (Chuck) Conner became president & CEO of the National Council of Farmer Cooperatives (NCFC) on January 22, 2009. As president of NCFC, Conner will oversee the organization's work to promote and protect the business and public policy interests of America's farmer-owned cooperatives. He will also provide the strategic vision for the trade association as it continues to seek new ways in which to add value for its membership. Prior to joining NCFC, Conner had served as the Deputy Secretary at the U.S. Department of Agriculture since mid-2005. In this capacity, he was the Chief Operating Officer (COO) overseeing day-to-day operations of the department. Conner interacted directly with President George W. Bush and his senior staff to formulate domestic and international food, trade, security and energy policy. He led development of the Bush Administration's $300 billion Farm Bill proposal and the strategy to educate and inform industry, constituents and Congress. From August 2007 to January 2008, Conner served as both USDA Secretary and Deputy Secretary. He played a key role in developing the Administration's immigration policy including important changes to the H2A program. Conner's experience also includes the assignment of Special Assistant to the President, Executive Office of the President, from October 2001 to May 2005, working on the 2001/2 Farm Bill to develop the strategy behind the transfer of several USDA agency functions to the newly formed Department of Homeland Security. From May 1997 to October 2001 Conner served as President of the Corn Refiners Association. He also served for 17 years as an advisor to U.S. Senator Richard Lugar of Indiana. Conner is a graduate of Purdue University, with a Bachelor's of Science degree and is the recipient of Purdue's Distinguished Alumni Award. He and his wife Ex. 6 - Personal Privacy Source: :https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00008 NATIONAL PORK PRODUCERS COUNCIL Neil Dierks, Chief Executive Officer Neil Dierks is Chief Executive Officer of the National Pork Producers Council (NPPC). In this position, he is responsible for the overall implementation of all NPPC programs. Dierks' position requires him to spend time in both Des Moines, Iowa, the national office of NPPC, and Washington, D.C. Beginning in 1990, Dierks served NPPC in a series of senior executive positions, including Executive Director of Operations, Vice President for Research and Education and Senior Vice President for Programs. Prior to his service with NPPC, Dierks was the Special Activities Director for the Iowa Pork Producers Association and Marketing Director for the Iowa Corn Promotion Board. Neil grew up on a livestock farm in eastern lowa and remains involved in a family farming operation. He is a graduate of Iowa State University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00009 NASDA Dr. Barbara Glenn recently joined the National Association of State Departments of Agriculture (NASDA) as CEO on August 18, 2014. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. Dr. Glenn is a scientist with decades of experience as a policy researcher and advocate for agriculture. She previously served as Senior Vice President of Science and Regulatory Affairs for CropLife America, where she was responsible for developing policies and regulations to support agriculture through crop protection. Prior to joining CropLife America, Dr. Glenn served as Managing Director of the Animal Bi otechnology, Food and Agriculture Section of the Biotechnology Industry Association in Washington, DC. Dr. Glenn holds a B.S. in animal science and a Ph.D. in ruminan t nutrition from the University of Kentucky. She previously worked for the U.S. Department of Agriculture, Agric ultural Research Service and the Federation of Animal Science Societies. Born in Lincoln, Nebraska and raised in Centerville, Ohio, Dr. Glenn developed a passion for agriculture from her parents and her involvement in 4-H. She lives on a small farm in Maryland with her husband: Ex. 6 - Personal Privacy and serves on various boards for farm bureau and 4-H. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00010 National Association of Wheat Growers Chandler Goule CEO Chandler Goule assumed his responsibilities as CEO of the National Association of Wheat Growers on July 5, 2016. In addition, he also serves as the executive director of the National Wheat Foundation. Most recently, Goule served as senior vice president of programs at the National Farmers Union (NFU) where he was heavily involved in farm bill legislation. Originally from Texas, Goule holds degrees from Texas A&M and George Washington University and served as a subcommittee staff director for the House Agriculture Committee before moving to the National Farmers Union in 2009 as vice president of government relations. He was appointed senior vice president of NFU programs in 2014. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00011 The Fertilizer Institute Nourish, Replenish, Grow BIOGRAPHY OF CHRISTOPHER JAHN President The Fertilizer Institute and the Nutrients for Life Foundation Christopher L. Jahn is president of The Fertilizer Institute (TFI), the fertilizer industry's national trade association. As TFI president, Jahn works to represent, promote and protect a sound fertilizer industry through legislative and regulatory activities and to promote a favorable public image of the fertilizer industry and agriculture. Jahn also serves as president of the Nutrients for Life Foundation (NFL). Jahn comes to TFI having served as president of the National Association of Chemical Distributors (NACD) since 2006. Prior to leading NACD, Jahn served as president of the Contract Services Association (CSA). Before joining CSA, Jahn had an active role in the United States Senate working for nearly 10 years for U.S. Senator Craig Thomas (R-Wyo.) in a variety of roles, including legislative assistant, legislative director and Chief of Staff. After graduating from Columbia University with a B.A. in Political Science, Jahn co-founded a book distribution business. He also earned an MBA from the University of Maryland. A native of Wyoming, Chris and his wife Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Capitol View 202.962.0490 425 Third Street, S.W., Suite 950 202.962.0577 fax Washington, DC 20024 www.tfi.org Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00012 National Farmers Union Roger Johnson President Roger Johnson is president of the National Farmers Union (NFU), a grassroots organization that represents more than 200,000 family farmers, ranchers, fisherman and rural communities across the Unites States. Johnson was elected to lead the family farm organization at NFU's 107th anniversary convention in 2009. He has since expanded the education department by providing more programs for beginning, college-aged and women farmers, increased the number of Farmers Union state divisions, and developed a strategic plan for the organization. Johnson has also overseen a number of important policy initiatives important to family farmers including: passage of the 2014 Farm Bill; maintaining a strong Renewable Fuel Standard and Country-of-Origir Labeling, promoting policies that allow farmers to address the growing threat of climate change; and renewing the nation's focus on eliminating an overwhelming trade deficit that results in lost jobs and prosperity for rural America. Prior to leading National Farmers Union, Johnson, a third-generation family farmer from Turtle Lake, N.D., served as North Dakota Agriculture Commissioner, a position he was first elected to in 1996. While Agriculture Commissioner, Johnson served on the State Industrial Commission, the North Dakota Trade Office Advisory Board, and the State Board of Agricultural Research and Education, among many other boards and commissions. From 2007-2008, Johnson served as president of the National Association of State Departments of Agriculture (NASDA). He is a past president of the Midwestern Association of State Departments of Agriculture (MASDA), past president of the Food Export Association of the Midwest and a former chairman of the Interstate Pest Control Compact. Johnson graduated from North Dakota State University with a degree in agricultural economics. Johnson and his wife, Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00013

When Andrew W.LaVigne joined ASTA

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February, 2006

To: Greenwalt, Sarah[[email protected]]; Dravis, Samantha[[email protected]] Brown, Byron[[email protected]];Wagner, Kenneth[[email protected]] From: Hupp, Sydney Sent: Thur 3/30/2017 5:11:34 PM Subject: FW: FINAL Meeting Agenda and Materials Pruitt Meeting Materials.pd FYI. Sydney Hupp Office of the Administrator- Scheduling 202.816.1659 From: Mary Jo Tomalewski [mailto:[email protected]] Sent: Thursday, March 30, 2017 11:22 AM To: Hupp, Sydney <[email protected]> Cc: Jay Vroom <[email protected]> Subject: FINAL Meeting Agenda and Materials Sydney, We have refined our proposed topics for today's CEO Council meeting with the administrator. Attached, please find: Revised "Final Proposed Agenda Topics," which includes the list of those CEO Council members who will attend our meeting today, and their short bios Introduction / Mission Overview of the CEO Council CEO Council Letter to President Trump, dated February 9, 2017 We assume we can skip a formal "round table of introductions" at the beginning of the meeting as our time is short and we want to maximize time spent talking about issues. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000061-00001 MJ Mary Jo Tomalewski Executive Assistant to the President & CEO CropLife America 1156 15th Street, NW Suite 400 Washington, DC 20005 Direct Dial (202) 872-3849 Main Switchboard (202) 296-1585 Mobile Ex. 6 Personal Privacy Fax (202)466-5832 Email [email protected] Web www.croplifeamerica.org How can I serve you today? Future Meetings 2017 Spring Regulator Conference - April 6-7, Arlington, VA 2017 Annual Meeting - September 22-27, Dana Point, CA 2018 Winter Board of Directors Meeting - March 5-7, Washington, DC 2018 Annual Meeting - September 21-26, The Ritz-Carlton Amelia Island Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000061-00002 FINAL PROPOSED AGENDA TOPICS Meeting Information: Office of EPA Administrator Scott Pruitt 1200 Pennsylvania Avenue, NW Washington, DC Thursday, March 30, 2017 3:45-4:30 PM Topic 1. Thanks to Trump Administration and Administrator Pruitt for early decisive actions: a. WOTUS b. Chlorpyrifos Petition 2. Top Priority Issues a. Ag Advisor Position - We recommend adding additional title of "Assistant Deputy Administrator" as a title b. Water i. Next steps to refine / clarify beyond WOTUS ii. NPDES permits (CAFO Program needs work; legislation to fix water permits NOT needed for lawful use of pesticides) c. Pesticides Policy i. Endangered Species Act conflicts with Pesticide Regulation and Biotech Regulation ii. Epidemiology Study Policy (as aftermath from Chlorpyrifos matter) iii. Reform Certification & Training and Worker Protection Rules - Suspend implementation and revise d. Renewable Fuels Standard - current program kept consistent e. Communication / Messaging / Opinion Polling - vital to all parties' ability to advance sound policy f. EPA and USDA Cooperation and Coordination - Already vast progress; more can be done! g. Environmental Justice, Research & Development, and Children's Health Offices - Better integration with and reform of EPA program offices; sound science h. Regulation of Manufacturing & Mining Facilities for Ag Inputs - Restore science and process i. Public and Science Advisory Panels at EPA - Balance, strategic agendas j. "Air Emissions" from farming operations CEO Attendees American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Corn Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Barb Glenn, CEO, ex-officio Departments of Agriculture Others American Farm Bureau Federation Dale Moore, Deputy Executive Director Corn Refiners Association John Bode, President & CEO National Farmers Union Rob Larew, Senior VP Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00001 Production Agriculture's CEO Council Introduction/Mission Statement: The production agriculture "CEO Council" coordinates alignment on core issues of modern agricultural systems through telling our story, sharing information and leveraging our strengths, while serving as a resource for government decision makers and others interested in USA food, fiber and renewable fuels. Core Focus of Interest Research and innovation Technology access Science and risk-based regulation Sustainability, environment, and weather Marketability, trade, and economic prosperity Government leadership and partnership with private sector Food access and food safety Plant and animal health Ag labor The Council supports principles/themes): Accelerating rural economic growth and improving productivity through innovation and technology Promoting research and innovation that enables development oftools and techniques necessary for discovering new products that hold tremendous potential for farmers and society at large Enabling a regulatory and commercial environment in which agricultural products are marketable, both domestically and internationally Appropriate balance between Federal and State Governments and a cooperative regulatory approach Access to essential labor in balance with an effective Federal immigration policy and adequate worker safety protections Support for all methods of agricultural production Transparency and dialogue with consumers Members of the CEO Council (see reversed) March 30, 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00002 CEO Council Members American Farm Bureau Vincent "Zippy" Duvall, President American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Cattlemen's Beef Association Kendal Frazier, CEO National Chicken Council Michael Brown, President National Com Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Farmers Union Roger Johnson, President National Milk Producers Federation Jim Mulhern, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Departments of Barb Glenn, CEO, ex-officio Agriculture March 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00003 February 9, 2017 The President The White House Washington, D.C. 20500 Dear Mr. President, We, the CEO Council (undersigned herein), representing the production agricultural value chain, including many agricultural producers and farm input developers and suppliers, look forward to working with you and your Administration on matters of importance to American agriculture. The challenges we face in agriculture are significant. Many experts emphasize that producers must grow as much food in the next 50 years as was produced over all previous history to meet the demands of our expanding global population. A firm commitment by the U.S. government to aggressively support agricultural innovation and science-based regulatory decisions will be necessary to ensure farmers have the tools they need to produce a safe and abundant supply of nutritious food, in addition to feed, fuel and fiber, in an environmentally sound and sustainable manner. The policy and regulatory environment your Administration establishes can ensure that agricultural innovation flourishes and American farmers are able to meet the food production goals necessary to feed billions more people. We are ready to provide the White House and the Executive Branch Departments and Agencies, as well as Congress, with policy concepts that foster stability in the U.S. agriculture economy with a strong and predictable farm safety net and promotes American competitiveness through research; marketability and trade of agricultural commodities; rural economic growth; and plant, animal, and environmental health, among many other things. We appreciate your attention to these and other issues of value to American production agriculture and food consumers everywhere. Sincerely, American Farm Bureau Foundation, Zippy Duvall American Seed Trade Association, Andy LaVigne American Soybean Association, Steve Censky Biotechnology Innovation Organization, Dana O'Brien CropLife America, Jay Vroom The Fertilizer Institute, Chris Jahn National Association of Wheat Growers, Chandler Goule National Cattlemen's Beef Association, Kendal Frazier National Corn Growers Association, Chris Novak National Cotton Council, Gary Adams National Council of Farmer Cooperatives, Chuck Conner National Farmers Union, Roger Johnson National Milk Producers Federation, Jim Mulhern National Pork Producers Council, Neil Dierks United Fresh Produce Association, Tom Stenzel USA Rice Federation, Betsy Ward Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00004 National Gotton Council OF MERTOA Gary M. Adams President and Chief Executive Officer National Cotton Council of America Gary Adams assumed the position of President and Chief Executive Officer of the National Cotton Council in February 2015. He plays a key role in guiding the industry's seven segments to reach consensus on critical policies affecting U.S. cotton, with the mission of helping all U.S. cotton industry segments compete effectively and profitably in global markets. Prior to that, Gary served the Council for 13 years as the Vice President of Economic and Policy Analysis. As the Council's chief economist, he provided economic outlooks for global cotton markets, as well as analyzing the impacts of farm and trade policies. Gary also represents the U.S. cotton industry as a member of USDA's Agricultural Policy Advisory Committee. Previously, Gary served on USDA's Advisory Committee on Trade from 2005 through 2011 and the NASS Advisory Committee on Agricultural Statistics from 2003 through 2009. Prior to joining the Council, Gary was a Research Assistant Professor in the Department of Agricultural Economics at the University of Missouri. During his 13-year tenure at the university, Gary's primary responsibilities included policy analysis and market outlook for the Food and Agricultural Policy Research Institute, also known as FAPRI. While at FAPRI, Gary and his colleagues were recognized by the American Agricultural Economics Association for their distinguished policy contributions. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00005 Gary has B.S. and M.A. degrees in Applied Mathematics from the University of Alabama and a Ph.D. in Agricultural Economics from the University of Missouri. Gary and his wife, Ex. 6 Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00006 FASA American Soybean Associatión & Stephen L Censky Chief Executive Officer Stephen L. Censky is the American Soybean Association's (ASA) C hief Executive Officer, a staff position he accepted in April 1996. As ASA's top executive, Ce nsky is in charge of managing ASA's legislative, trade policy, membership and education and training programs. The American Soybean Association is a national, not-for-profit commodity organization with over 22,000 members. ASA works as the domestic and international policy advocate for soybean producer members. Prior to joining ASA, Censky worked in Washington, D.C. for ove a decade. He began his career on Capitol Hill as a legislative assistant for agricultural and transportation matters to Senator Jim Abdnor (R-SD). Later he served in both the Reagan and Bush Administrations at the U.S. Department of Agriculture, helping to craft the 1990 Farm Bill and eventually serving as Administrator of the Foreign Agricultural Service where he was involved in global trade negotiations and running our nation's export programs. Censky received his Bachelor's of Science degree of Agriculture from South Dakota State University and his Master's Diploma in Agriculture St of Melbourne, Australia. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00007 NCFC. National Council of Farmer Cooperatives Charles F. (Chuck) Conner President and CEO National Council of Farmer Cooperatives Charles F. (Chuck) Conner became president & CEO of the National Council of Farmer Cooperatives (NCFC) on January 22, 2009. As president of NCFC, Conner will oversee the organization's work to promote and protect the business and public policy interests of America's farmer-owned cooperatives. He will also provide the strategic vision for the trade association as it continues to seek new ways in which to add value for its membership. Prior to joining NCFC, Conner had served as the Deputy Secretary at the U.S. Department of Agriculture since mid-2005. In this capacity, he was the Chief Operating Officer (COO) overseeing day-to-day operations of the department. Conner interacted directly with President George W. Bush and his senior staff to formulate domestic and international food, trade, security and energy policy. He led development of the Bush Administration's $300 billion Farm Bill proposal and the strategy to educate and inform industry, constituents and Congress. From August 2007 to January 2008, Conner served as both USDA Secretary and Deputy Secretary. He played a key role in developing the Administration's immigration policy including important changes to the H2A program. Conner's experience also includes the assignment of Special Assistant to the President, Executive Office of the President, from October 2001 to May 2005, working on the 2001/2 Farm Bill to develop the strategy behind the transfer of several USDA agency functions to the newly formed Department of Homeland Security. From May 1997 to October 2001 Conner served as President of the Corn Refiners Association. He also served for 17 years as an advisor to U.S. Senator Richard Lugar of Indiana. Conner is a graduate of Purdue University, with a Bachelor's of Science degree and is the recipient of Purdue's Distinguished Alumni Award. He and his wife Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00008 NATIONAL PORK PRODUCERS COUNCIL Neil Dierks, Chief Executive Officer Neil Dierks is Chief Executive Officer of the National Pork Producers Council (NPPC). In this position, he is responsible for the overall implementation of all NPPC programs. Dierks' position requires him to spend time in both Des Moines, Iowa, the national office of NPPC, and Washington, D.C. Beginning in 1990, Dierks served NPPC in a series of senior executive positions, including Executive Director of Operations, Vice President for Research and Education and Senior Vice President for Programs. Prior to his service with NPPC, Dierks was the Special Activities Director for the Iowa Pork Producers Association and Marketing Director for the Iowa Corn Promotion Board. Neil grew up on a livestock farm in eastern lowa and remains involved in a family farming operation. He is a graduate of Iowa State University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00009 NASDA Dr. Barbara Glenn recently joined the National Association of State Departments of Agriculture (NASDA) as CEO on August 18, 2014. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. Dr. Glenn is a scientist with decades of experience as a policy researcher and advocate for agriculture. She previously served as Senior Vice President of Science and Regulatory Affairs for CropLife America, where she was responsible for developing policies and regulations to support agriculture through crop protection. Prior to joining CropLife America, Dr. Glenn served as Managing Director of the Animal Bi otechnology, Food and Agriculture Section of the Biotechnology Industry Association in Washington, DC. Dr. Glenn holds a B.S. in animal science and a Ph.D. in ruminan t nutrition from the University of Kentucky. She previously worked for the U.S. Department of Agriculture, Agric ultural Research Service and the Federation of Animal Science Societies. Born in Lincoln, Nebraska and raised in Centerville, Ohio, Dr. Glenn developed a passion for agriculture from her parents and her involvement in 4-H. She lives Ex. 6 - Personal Privacy and serves on various boards for farm bureau and 4-H. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00010 National Association of Wheat Growers Chandler Goule CEO Chandler Goule assumed his responsibilities as CEO of the National Association of Wheat Growers on July 5, 2016. In addition, he also serves as the executive director of the National Wheat Foundation. Most recently, Goule served as senior vice president of programs at the National Farmers Union (NFU) where he was heavily involved in farm bill legislation. Originally from Texas, Goule holds degrees from Texas A&M and George Washington University and served as a subcommittee staff director for the House Agriculture Committee before moving to the National Farmers Union in 2009 as vice president of government relations. He was appointed senior vice president of NFU programs in 2014. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00011 The Fertilizer Institute Nourish, Replenish, Grow BIOGRAPHY OF CHRISTOPHER JAHN President The Fertilizer Institute and the Nutrients for Life Foundation Christopher L. Jahn is president of The Fertilizer Institute (TFI), the fertilizer industry's national trade association. As TFI president, Jahn works to represent, promote and protect a sound fertilizer industry through legislative and regulatory activities and to promote a favorable public image of the fertilizer industry and agriculture. Jahn also serves as president of the Nutrients for Life Foundation (NFL). Jahn comes to TFI having served as president of the National Association of Chemical Distributors (NACD) since 2006. Prior to leading NACD, Jahn served as president of the Contract Services Association (CSA). Before joining CSA, Jahn had an active role in the United States Senate working for nearly 10 years for U.S. Senator Craig Thomas (R-Wyo.) in a variety of roles, including legislative assistant, legislative director and Chief of Staff. After graduating from Columbia University with a B.A. in Political Science, Jahn co-founded a book distribution business. He also earned an MBA from the University of Maryland. A native of Wyoming, Chris and his wife, Ex. 6 - Personal Privacy Ex. Personal Privacy Capitol View 202.962.0490 425 Third Street, S.W., Suite 950 202.962.0577 fax Washington, DC 20024 www.tfi.org Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00012 National Farmers Union Roger Johnson President Roger Johnson is president of the National Farmers Union (NFU), a grassroots organization that represents more than 200,000 family farmers, ranchers, fisherman and rural communities across the Unites States. Johnson was elected to lead the family farm organization at NFU's 107th anniversary convention in 2009. He has since expanded the education department by providing more programs for beginning, college-aged and women farmers, increased the number of Farmers Union state divisions, and developed a strategic plan for the organization. Johnson has also overseen a number of important policy initiatives important to family farmers including: passage of the 2014 Farm Bill; maintaining a strong Renewable Fuel Standard and Country-of-Origir Labeling, promoting policies that allow farmers to address the growing threat of climate change; and renewing the nation's focus on eliminating an overwhelming trade deficit that results in lost jobs and prosperity for rural America. Prior to leading National Farmers Union, Johnson, a third-generation family farmer from Turtle Lake, N.D., served as North Dakota Agriculture Commissioner, a position he was first elected to in 1996. While Agriculture Commissioner, Johnson served on the State Industrial Commission, the North Dakota Trade Office Advisory Board, and the State Board of Agricultural Research and Education, among many other boards and commissions. From 2007-2008, Johnson served as president of the National Association of State Departments of Agriculture (NASDA). He is a past president of the Midwestern Association of State Departments of Agriculture (MASDA), past president of the Food Export Association of the Midwest and a former chairman of the Interstate Pest Control Compact. Johnson graduated from North Dakota State University with a degree in agricultural economics. Johnson and his wife Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00013 AMERICAN SEED TRADE ASSOCIATION asta first-the - seed R Andrew W. "Andy" LaVigne President & CEO Andrew W. LaVigne is currently the President and CEO of the Ame rican Seed Trade Association. He joined ASTA in February, 2006. Andy has had a 30-year career i n government relations, industry representation, public affairs advocacy, and management. His C ore areas of expertise include agriculture, food policy and international trade. Prior to joining ASTA, Andy was Executive Vice President/CEC of Florida Citrus Mutual, representing citrus growers on issues affecting their business. Prejaiming tFdorida Citrus Mutual, Andy spent four years as Florida Fertilizer and Agrichemical Association's (FFAA) President and Executive Director. FFAA is a non-profit, agricultural trade organization representing companies that specialize in crop protection and plant nutrition products. Before his position at FFAA, Andy spent eight years in Washingt on, D.C. working in the U.S. Congress and the U.S. Department of Agriculture. He served as Legislative Director for Congressman Charles Canady, Agriculture Committee staffer for Congressman Tom Lewis , and on the staff of USDA Secretary Ed Madigan. Andy is a native of Florida with a BA degree in Political Scien ce, with a minor in economics, from the University of Florida. 1701 Duke Street Suite 275 Alexandria, VA 22314 Phone: (703)837-8140 Fax: (703)837-9365 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00014 Biotechnology Innovation Organization Dana O'Brien Executive Vice President, Food & Agriculture Dana O'Brien is Executive Vice President for Food and Agriculture and is responsible for the development of public policy and strategic advocacy, public affairo, and legal strategies that advance industry and stakeholder objectives in the United States. Prior to becoming EVP, Dana served bs BIO Food and Agriculture's chief legislative advocate as Senior Director of Federal Government Relations aince March 2011. Before BIO, Dana worked in Congress for the late Representative lke Skelton (D-MO) managing his legislative team and concentrating on a variety of agricultural, energy, and trade matters. A native of Sedalia, Missouri, and a graduate of Missouri University with a bachelor's degree in psychology, Dana joined the Skelton team immediately out of college and served there for nearly 14 years Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00015 UNITED FRESH is PRODUCE ASSOCIATION Tom Stenzel President and CEO United Fresh Produce Association 1901 Pennsylvania Avenue NW, Suite 1100 Washington, DC 20006 202/303-3400 [email protected] Tom Stenzel is President and CEO of the United Fresh Produce Association, a position he has held since 1993. United Fresh is the pre-eminent trade association for the produce industry in shaping legislative and regulatory policies; providing scientific and technical leadership in food safety and nutrition; and developing educational programs for its members. Founded in 1904, United Fresh represents the interests of companies from small family businesses to the largest international corporations throughout the global fresh produce supply chain. United Fresh is widely known for its work in government affairs, agricultural policy, food safety and nutrition, working to promote political and environmental change to help the next generation of children double their consumption of fresh produce. The United Fresh Start Foundation is committed to increasing children's access to fresh fruits and vegetables, and is a founding partner of the Let's Move Salad Bars to Schools campaign. The campaign has donated salad bars to more than 6,000 schools across the country. Tom is a frequent speaker on industry issues and has been recognized often by the produce industry throughout his career. He was honored as the 2002 Produce Man of the Year by The Packer newspaper, and is the past Chairman of the International Federation for Produce Standards, a global body representing national produce associations around the world. He is a member of the U.S. Chamber of Commerce Committee of 100 leading association executives, the Advisory Board of the International Food Protection Training Institute, and the Key Industry Associations Committee of the American Society of Association Executives, from which he achieved the Certified Association Executive (CAE) designation in 1990. He has served in many government and industry leadership positions, including the first U.S. Department of Agriculture Fruit and Vegetable Industry Advisory Committee, President George W. Bush's Transition Advisory Team for Agriculture, and as an advisor on the U.S. Agricultural Policy Advisory Committee for Trade. Tom was the founding President of the International Food Information Council (IFIC) in 1986, and was previously director of public affairs for the National Soft Drink Association. Tom is a 1977 graduate of the University of Richmond. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00016 as of January 17, 2017 Jay Vroom has served as President and CEO of the trade association known as CropLife America (CLA) since 1989. CLA is the leading U.S. trade group for the crop protection industry in the U.S. Vroom is a founding member of the CropLife Foundation, serving as chairman since its inception in 2001, and now serves as the Foundation's Vice-Chair, since 2015. His sits of the Board of Directors for the Agricultural Retailers Association, Asmark, National Wheat Foundation, the National Association of Manufacturers Council of Manufacturing Associations, and the Soil Health Institute. He is also a member of the Farm Foundation Roundtable Steering Committee, and the North American Climate Smart Ag Alliance Steering Committee. Vroom was a member of the youth organization, Future Farmers of America, and served as an elected state officer in Illinois. Today, he is a member of the FFA Foundation's Individual Giving Council and Board of Trustees. Vroom co-chairs the Coalition for the Advancement of Precision Agriculture and the CEO Council. He is a member of the Friends of the National Arboretum (FONA) FONA Council. He graduated with honors from the College of Agriculture, Consumer and Environmental Sciences at the University of Illinois Urbana-Champaign. Vroom was raised on a grain and livestock farm in north-central Illinois and continues to own the farming operation. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00017 Elizabeth Ward Betsy Ward was appointed President & CEO of the USA Rice Federation in 2007. From 2003- 2005, Ward was the Vice President of International and Domestic Promotion at USA Rice where she was in charge of developing and implementing domestic and international promotion, and food aid programs. From 2005-2007, Ward served as the chief executive for the Hardwood Federation, a trade association representing over 15,000 hardwood producers across the United States. From 1995 to 2003, she ran the Wood Products International Group at the American Forest & Paper Association, directing the wood trade policy and global forestry agenda for the industry. In 2011, Ward was elected Chairman of the U.S. Agricultural Export Development Council (USAEDC) which represents the interests of more than 80 commodity organizations who grow and process a wide variety of U.S. agricultural products. She currently serves as Past Chair. Since 2011, Ward has also served on the Board of Directors of the Sustainable Fisheries Partnership, an independent non-governmental organization (NGO) working to ensure healthy marine and aquatic tecosystems; secure seafood supplies; and a thriving, responsible seafood economy. Ward served for six years as a cleared advisor on the Industry Trade Advisory Committee for forest and paper products (ITAC-7) and was appointed forest products representative to USDA's Agricultural Policy Advisory Committee (APAC) in 2001. Ward holds a Bachelor's degree in History and Political Science from the University of New Hampshire and a Master's degree in International Security Affairs from the School of International Affairs at Columbia University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00018 To: Brown, Byron[[email protected]]; Jackson, Ryan[[email protected]] From: Rebeckah Adcock Sent: Thur 3/30/2017 4:10:52 PM Subject: FW: FINAL CEO Council Meeting Agenda and Materials Pruitt Meeting Materials.pdf ATT00001.htm FYI - final materials for today's meeting. Reb From: "Mary Jo Tomalewski" <[email protected]> To: "Hupp, Sydney" <[email protected]> Cc: "Jay Vroom" <[email protected]> Subject: FINAL Meeting Agenda and Materials Sydney, We have refined our proposed topics for today's CEO Council meeting with the administrator. Attached, please find: Revised "Final Proposed Agenda Topics," which includes the list of those CEO Council members who will attend our meeting today, and their short bios Introduction / Mission Overview of the CEO Council CEO Council Letter to President Trump, dated February 9, 2017 We assume we can skip a formal "round table of introductions" at the beginning of the meeting as our time is short and we want to maximize time spent talking about issues. MJ Mary Jo Tomalewski Executive Assistant to the President & CEO CropLife America Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000063-00001 1156 15th Street, NW Suite 400 Washington, DC 20005 Direct Dial (202) 872-3849 Main Switchboard (202) 296-1585 Mobilé Ex. 6 Personal Privacy Fax (202) 466-5832 Email [email protected] Web www.croplifeamerica.org How can I serve you today? Future Meetings 2017 Spring Regulator Conference - April 6-7, Arlington, VA 2017 Annual Meeting - September 22-27, Dana Point, CA 2018 Winter Board of Directors Meeting - March 5-7, Washington, DC 2018 Annual Meeting - September 21-26, The Ritz-Carlton Amelia Island Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000063-00002 FINAL PROPOSED AGENDA TOPICS Meeting Information: Office of EPA Administrator Scott Pruitt 1200 Pennsylvania Avenue, NW Washington, DC Thursday, March 30, 2017 3:45-4:30 PM Topic 1. Thanks to Trump Administration and Administrator Pruitt for early decisive actions: a. WOTUS b. Chlorpyrifos Petition 2. Top Priority Issues a. Ag Advisor Position - We recommend adding additional title of "Assistant Deputy Administrator" as a title b. Water i. Next steps to refine / clarify beyond WOTUS ii. NPDES permits (CAFO Program needs work; legislation to fix water permits NOT needed for lawful use of pesticides) c. Pesticides Policy i. Endangered Species Act conflicts with Pesticide Regulation and Biotech Regulation ii. Epidemiology Study Policy (as aftermath from Chlorpyrifos matter) iii. Reform Certification & Training and Worker Protection Rules - Suspend implementation and revise d. Renewable Fuels Standard - current program kept consistent e. Communication / Messaging / Opinion Polling - vital to all parties' ability to advance sound policy f. EPA and USDA Cooperation and Coordination - Already vast progress; more can be done! g. Environmental Justice, Research & Development, and Children's Health Offices - Better integration with and reform of EPA program offices; sound science h. Regulation of Manufacturing & Mining Facilities for Ag Inputs - Restore science and process i. Public and Science Advisory Panels at EPA - Balance, strategic agendas j. "Air Emissions" from farming operations CEO Attendees American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Corn Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Barb Glenn, CEO, ex-officio Departments of Agriculture Others American Farm Bureau Federation Dale Moore, Deputy Executive Director Corn Refiners Association John Bode, President & CEO National Farmers Union Rob Larew, Senior VP Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00001 Production Agriculture's CEO Council Introduction/Mission Statement: The production agriculture "CEO Council" coordinates alignment on core issues of modern agricultural systems through telling our story, sharing information and leveraging our strengths, while serving as a resource for government decision makers and others interested in USA food, fiber and renewable fuels. Core Focus of Interest Research and innovation Technology access Science and risk-based regulation Sustainability, environment, and weather Marketability, trade, and economic prosperity Government leadership and partnership with private sector Food access and food safety Plant and animal health Ag labor The Council supports principles/themes): Accelerating rural economic growth and improving productivity through innovation and technology Promoting research and innovation that enables development oftools and techniques necessary for discovering new products that hold tremendous potential for farmers and society at large Enabling a regulatory and commercial environment in which agricultural products are marketable, both domestically and internationally Appropriate balance between Federal and State Governments and a cooperative regulatory approach Access to essential labor in balance with an effective Federal immigration policy and adequate worker safety protections Support for all methods of agricultural production Transparency and dialogue with consumers Members of the CEO Council (see reversed) March 30, 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00002 CEO Council Members American Farm Bureau Vincent "Zippy" Duvall, President American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Cattlemen's Beef Association Kendal Frazier, CEO National Chicken Council Michael Brown, President National Com Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Farmers Union Roger Johnson, President National Milk Producers Federation Jim Mulhern, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Departments of Barb Glenn, CEO, ex-officio Agriculture March 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00003 February 9, 2017 The President The White House Washington, D.C. 20500 Dear Mr. President, We, the CEO Council (undersigned herein), representing the production agricultural value chain, including many agricultural producers and farm input developers and suppliers, look forward to working with you and your Administration on matters of importance to American agriculture. The challenges we face in agriculture are significant. Many experts emphasize that producers must grow as much food in the next 50 years as was produced over all previous history to meet the demands of our expanding global population. A firm commitment by the U.S. government to aggressively support agricultural innovation and science-based regulatory decisions will be necessary to ensure farmers have the tools they need to produce a safe and abundant supply of nutritious food, in addition to feed, fuel and fiber, in an environmentally sound and sustainable manner. The policy and regulatory environment your Administration establishes can ensure that agricultural innovation flourishes and American farmers are able to meet the food production goals necessary to feed billions more people. We are ready to provide the White House and the Executive Branch Departments and Agencies, as well as Congress, with policy concepts that foster stability in the U.S. agriculture economy with a strong and predictable farm safety net and promotes American competitiveness through research; marketability and trade of agricultural commodities; rural economic growth; and plant, animal, and environmental health, among many other things. We appreciate your attention to these and other issues of value to American production agriculture and food consumers everywhere. Sincerely, American Farm Bureau Foundation, Zippy Duvall American Seed Trade Association, Andy LaVigne American Soybean Association, Steve Censky Biotechnology Innovation Organization, Dana O'Brien CropLife America, Jay Vroom The Fertilizer Institute, Chris Jahn National Association of Wheat Growers, Chandler Goule National Cattlemen's Beef Association, Kendal Frazier National Corn Growers Association, Chris Novak National Cotton Council, Gary Adams National Council of Farmer Cooperatives, Chuck Conner National Farmers Union, Roger Johnson National Milk Producers Federation, Jim Mulhern National Pork Producers Council, Neil Dierks United Fresh Produce Association, Tom Stenzel USA Rice Federation, Betsy Ward Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00004 National Gotton Council OF MERTOA Gary M. Adams President and Chief Executive Officer National Cotton Council of America Gary Adams assumed the position of President and Chief Executive Officer of the National Cotton Council in February 2015. He plays a key role in guiding the industry's seven segments to reach consensus on critical policies affecting U.S. cotton, with the mission of helping all U.S. cotton industry segments compete effectively and profitably in global markets. Prior to that, Gary served the Council for 13 years as the Vice President of Economic and Policy Analysis. As the Council's chief economist, he provided economic outlooks for global cotton markets, as well as analyzing the impacts of farm and trade policies. Gary also represents the U.S. cotton industry as a member of USDA's Agricultural Policy Advisory Committee. Previously, Gary served on USDA's Advisory Committee on Trade from 2005 through 2011 and the NASS Advisory Committee on Agricultural Statistics from 2003 through 2009. Prior to joining the Council, Gary was a Research Assistant Professor in the Department of Agricultural Economics at the University of Missouri. During his 13-year tenure at the university, Gary's primary responsibilities included policy analysis and market outlook for the Food and Agricultural Policy Research Institute, also known as FAPRI. While at FAPRI, Gary and his colleagues were recognized by the American Agricultural Economics Association for their distinguished policy contributions. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00005 Gary has B.S. and M.A. degrees in Applied Mathematics from the University of Alabama. and a Ph.D. in Agricultural Economics from the University of Missouri. Gary and his wife, Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00006 FASA American Soybean Associatión & Stephen L Censky Chief Executive Officer Stephen L. Censky is the American Soybean Association's (ASA) C hief Executive Officer, a staff position he accepted in April 1996. As ASA's top executive, Ce nsky is in charge of managing ASA's legislative, trade policy, membership and education and training programs. The American Soybean Association is a national, not-for-profit commodity organization with over 22,000 members. ASA works as the domestic and international policy advocate for soybean producer members. Prior to joining ASA, Censky worked in Washington, D.C. for ove a decade. He began his career on Capitol Hill as a legislative assistant for agricultural and transportation matters to Senator Jim Abdnor (R-SD). Later he served in both the Reagan and Bush Administrations at the U.S. Department of Agriculture, helping to craft the 1990 Farm Bill and eventually serving as Administrator of the Foreign Agricultural Service where he was involved in global trade negotiations and running our nation's export programs. Censky received his Bachelor's of Science degree of Agriculture from South Dakota State University and his Master's Diploma in Agriculture St of Melbourne, Australia. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00007 NCFC. National Council of Farmer Cooperatives Charles F. (Chuck) Conner President and CEO National Council of Farmer Cooperatives Charles F. (Chuck) Conner became president & CEO of the National Council of Farmer Cooperatives (NCFC) on January 22, 2009. As president of NCFC, Conner will oversee the organization's work to promote and protect the business and public policy interests of America's farmer-owned cooperatives. He will also provide the strategic vision for the trade association as it continues to seek new ways in which to add value for its membership. Prior to joining NCFC, Conner had served as the Deputy Secretary at the U.S. Department of Agriculture since mid-2005. In this capacity, he was the Chief Operating Officer (COO) overseeing day-to-day operations of the department. Conner interacted directly with President George W. Bush and his senior staff to formulate domestic and international food, trade, security and energy policy. He led development of the Bush Administration's $300 billion Farm Bill proposal and the strategy to educate and inform industry, constituents and Congress. From August 2007 to January 2008, Conner served as both USDA Secretary and Deputy Secretary. He played a key role in developing the Administration's immigration policy including important changes to the H2A program. Conner's experience also includes the assignment of Special Assistant to the President, Executive Office of the President, from October 2001 to May 2005, working on the 2001/2 Farm Bill to develop the strategy behind the transfer of several USDA agency functions to the newly formed Department of Homeland Security. From May 1997 to October 2001 Conner served as President of the Corn Refiners Association. He also served for 17 years as an advisor to U.S. Senator Richard Lugar of Indiana. Conner is a graduate of Purdue University, with a Bachelor's of Science degree and is the recipient of Purdue's Distinguished Alumni Award. He and his wife Ex. 6 - Personal Privacy Source: :https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00008 NATIONAL PORK PRODUCERS COUNCIL Neil Dierks, Chief Executive Officer Neil Dierks is Chief Executive Officer of the National Pork Producers Council (NPPC). In this position, he is responsible for the overall implementation of all NPPC programs. Dierks' position requires him to spend time in both Des Moines, Iowa, the national office of NPPC, and Washington, D.C. Beginning in 1990, Dierks served NPPC in a series of senior executive positions, including Executive Director of Operations, Vice President for Research and Education and Senior Vice President for Programs. Prior to his service with NPPC, Dierks was the Special Activities Director for the Iowa Pork Producers Association and Marketing Director for the Iowa Corn Promotion Board. Neil grew up on a livestock farm in eastern lowa and remains involved in a family farming operation. He is a graduate of Iowa State University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00009 NASDA Dr. Barbara Glenn recently joined the National Association of State Departments of Agriculture (NASDA) as CEO on August 18, 2014. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. Dr. Glenn is a scientist with decades of experience as a policy researcher and advocate for agriculture. She previously served as Senior Vice President of Science and Regulatory Affairs for CropLife America, where she was responsible for developing policies and regulations to support agriculture through crop protection. Prior to joining CropLife America, Dr. Glenn served as Managing Director of the Animal Bi otechnology, Food and Agriculture Section of the Biotechnology Industry Association in Washington, DC. Dr. Glenn holds a B.S. in animal science and a Ph.D. in ruminan t nutrition from the University of Kentucky. She previously worked for the U.S. Department of Agriculture, Agric ultural Research Service and the Federation of Animal Science Societies. Born in Lincoln, Nebraska and raised in Centerville, Ohio, Dr. Glenn developed a passion for agriculture from her parents and her involvement in 4-H. She lives on a small farm in Maryland with her husband: Ex. 6 - Personal Privacy and serves on various boards for farm bureau and 4-H. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00010 National Association of Wheat Growers Chandler Goule CEO Chandler Goule assumed his responsibilities as CEO of the National Association of Wheat Growers on July 5, 2016. In addition, he also serves as the executive director of the National Wheat Foundation. Most recently, Goule served as senior vice president of programs at the National Farmers Union (NFU) where he was heavily involved in farm bill legislation. Originally from Texas, Goule holds degrees from Texas A&M and George Washington University and served as a subcommittee staff director for the House Agriculture Committee before moving to the National Farmers Union in 2009 as vice president of government relations. He was appointed senior vice president of NFU programs in 2014. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00011 The Fertilizer Institute Nourish, Replenish, Grow BIOGRAPHY OF CHRISTOPHER JAHN President The Fertilizer Institute and the Nutrients for Life Foundation Christopher L. Jahn is president of The Fertilizer Institute (TFI), the fertilizer industry's national trade association. As TFI president, Jahn works to represent, promote and protect a sound fertilizer industry through legislative and regulatory activities and to promote a favorable public image of the fertilizer industry and agriculture. Jahn also serves as president of the Nutrients for Life Foundation (NFL). Jahn comes to TFI having served as president of the National Association of Chemical Distributors (NACD) since 2006. Prior to leading NACD, Jahn served as president of the Contract Services Association (CSA). Before joining CSA, Jahn had an active role in the United States Senate working for nearly 10 years for U.S. Senator Craig Thomas (R-Wyo.) in a variety of roles, including legislative assistant, legislative director and Chief of Staff. After graduating from Columbia University with a B.A. in Political Science, Jahn co-founded a book distribution business. He also earned an MBA from the University of Maryland. A native of Wyoming, Chris and his wife Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Capitol View 202.962.0490 425 Third Street, S.W., Suite 950 202.962.0577 fax Washington, DC 20024 www.tfi.org Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00012 National Farmers Union Roger Johnson President Roger Johnson is president of the National Farmers Union (NFU), a grassroots organization that represents more than 200,000 family farmers, ranchers, fisherman and rural communities across the Unites States. Johnson was elected to lead the family farm organization at NFU's 107th anniversary convention in 2009. He has since expanded the education department by providing more programs for beginning, college-aged and women farmers, increased the number of Farmers Union state divisions, and developed a strategic plan for the organization. Johnson has also overseen a number of important policy initiatives important to family farmers including: passage of the 2014 Farm Bill; maintaining a strong Renewable Fuel Standard and Country-of-Origir Labeling, promoting policies that allow farmers to address the growing threat of climate change; and renewing the nation's focus on eliminating an overwhelming trade deficit that results in lost jobs and prosperity for rural America. Prior to leading National Farmers Union, Johnson, a third-generation family farmer from Turtle Lake, N.D., served as North Dakota Agriculture Commissioner, a position he was first elected to in 1996. While Agriculture Commissioner, Johnson served on the State Industrial Commission, the North Dakota Trade Office Advisory Board, and the State Board of Agricultural Research and Education, among many other boards and commissions. From 2007-2008, Johnson served as president of the National Association of State Departments of Agriculture (NASDA). He is a past president of the Midwestern Association of State Departments of Agriculture (MASDA), past president of the Food Export Association of the Midwest and a former chairman of the Interstate Pest Control Compact. Johnson graduated from North Dakota State University with a degree in agricultural economics. Johnson and his wife, Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00013

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agriculture, food policy and international trade, Agriculture, food policy and international trade

To: Greenwalt, Sarah[[email protected]]; Dravis, Samantha[[email protected]] Brown, Byron[[email protected]];Wagner, Kenneth[[email protected]] From: Hupp, Sydney Sent: Thur 3/30/2017 5:11:34 PM Subject: FW: FINAL Meeting Agenda and Materials Pruitt Meeting Materials.pd FYI. Sydney Hupp Office of the Administrator- Scheduling 202.816.1659 From: Mary Jo Tomalewski [mailto:[email protected]] Sent: Thursday, March 30, 2017 11:22 AM To: Hupp, Sydney <[email protected]> Cc: Jay Vroom <[email protected]> Subject: FINAL Meeting Agenda and Materials Sydney, We have refined our proposed topics for today's CEO Council meeting with the administrator. Attached, please find: Revised "Final Proposed Agenda Topics," which includes the list of those CEO Council members who will attend our meeting today, and their short bios Introduction / Mission Overview of the CEO Council CEO Council Letter to President Trump, dated February 9, 2017 We assume we can skip a formal "round table of introductions" at the beginning of the meeting as our time is short and we want to maximize time spent talking about issues. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000061-00001 MJ Mary Jo Tomalewski Executive Assistant to the President & CEO CropLife America 1156 15th Street, NW Suite 400 Washington, DC 20005 Direct Dial (202) 872-3849 Main Switchboard (202) 296-1585 Mobile Ex. 6 Personal Privacy Fax (202)466-5832 Email [email protected] Web www.croplifeamerica.org How can I serve you today? Future Meetings 2017 Spring Regulator Conference - April 6-7, Arlington, VA 2017 Annual Meeting - September 22-27, Dana Point, CA 2018 Winter Board of Directors Meeting - March 5-7, Washington, DC 2018 Annual Meeting - September 21-26, The Ritz-Carlton Amelia Island Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000061-00002 FINAL PROPOSED AGENDA TOPICS Meeting Information: Office of EPA Administrator Scott Pruitt 1200 Pennsylvania Avenue, NW Washington, DC Thursday, March 30, 2017 3:45-4:30 PM Topic 1. Thanks to Trump Administration and Administrator Pruitt for early decisive actions: a. WOTUS b. Chlorpyrifos Petition 2. Top Priority Issues a. Ag Advisor Position - We recommend adding additional title of "Assistant Deputy Administrator" as a title b. Water i. Next steps to refine / clarify beyond WOTUS ii. NPDES permits (CAFO Program needs work; legislation to fix water permits NOT needed for lawful use of pesticides) c. Pesticides Policy i. Endangered Species Act conflicts with Pesticide Regulation and Biotech Regulation ii. Epidemiology Study Policy (as aftermath from Chlorpyrifos matter) iii. Reform Certification & Training and Worker Protection Rules - Suspend implementation and revise d. Renewable Fuels Standard - current program kept consistent e. Communication / Messaging / Opinion Polling - vital to all parties' ability to advance sound policy f. EPA and USDA Cooperation and Coordination - Already vast progress; more can be done! g. Environmental Justice, Research & Development, and Children's Health Offices - Better integration with and reform of EPA program offices; sound science h. Regulation of Manufacturing & Mining Facilities for Ag Inputs - Restore science and process i. Public and Science Advisory Panels at EPA - Balance, strategic agendas j. "Air Emissions" from farming operations CEO Attendees American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Corn Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Barb Glenn, CEO, ex-officio Departments of Agriculture Others American Farm Bureau Federation Dale Moore, Deputy Executive Director Corn Refiners Association John Bode, President & CEO National Farmers Union Rob Larew, Senior VP Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00001 Production Agriculture's CEO Council Introduction/Mission Statement: The production agriculture "CEO Council" coordinates alignment on core issues of modern agricultural systems through telling our story, sharing information and leveraging our strengths, while serving as a resource for government decision makers and others interested in USA food, fiber and renewable fuels. Core Focus of Interest Research and innovation Technology access Science and risk-based regulation Sustainability, environment, and weather Marketability, trade, and economic prosperity Government leadership and partnership with private sector Food access and food safety Plant and animal health Ag labor The Council supports principles/themes): Accelerating rural economic growth and improving productivity through innovation and technology Promoting research and innovation that enables development oftools and techniques necessary for discovering new products that hold tremendous potential for farmers and society at large Enabling a regulatory and commercial environment in which agricultural products are marketable, both domestically and internationally Appropriate balance between Federal and State Governments and a cooperative regulatory approach Access to essential labor in balance with an effective Federal immigration policy and adequate worker safety protections Support for all methods of agricultural production Transparency and dialogue with consumers Members of the CEO Council (see reversed) March 30, 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00002 CEO Council Members American Farm Bureau Vincent "Zippy" Duvall, President American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Cattlemen's Beef Association Kendal Frazier, CEO National Chicken Council Michael Brown, President National Com Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Farmers Union Roger Johnson, President National Milk Producers Federation Jim Mulhern, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Departments of Barb Glenn, CEO, ex-officio Agriculture March 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00003 February 9, 2017 The President The White House Washington, D.C. 20500 Dear Mr. President, We, the CEO Council (undersigned herein), representing the production agricultural value chain, including many agricultural producers and farm input developers and suppliers, look forward to working with you and your Administration on matters of importance to American agriculture. The challenges we face in agriculture are significant. Many experts emphasize that producers must grow as much food in the next 50 years as was produced over all previous history to meet the demands of our expanding global population. A firm commitment by the U.S. government to aggressively support agricultural innovation and science-based regulatory decisions will be necessary to ensure farmers have the tools they need to produce a safe and abundant supply of nutritious food, in addition to feed, fuel and fiber, in an environmentally sound and sustainable manner. The policy and regulatory environment your Administration establishes can ensure that agricultural innovation flourishes and American farmers are able to meet the food production goals necessary to feed billions more people. We are ready to provide the White House and the Executive Branch Departments and Agencies, as well as Congress, with policy concepts that foster stability in the U.S. agriculture economy with a strong and predictable farm safety net and promotes American competitiveness through research; marketability and trade of agricultural commodities; rural economic growth; and plant, animal, and environmental health, among many other things. We appreciate your attention to these and other issues of value to American production agriculture and food consumers everywhere. Sincerely, American Farm Bureau Foundation, Zippy Duvall American Seed Trade Association, Andy LaVigne American Soybean Association, Steve Censky Biotechnology Innovation Organization, Dana O'Brien CropLife America, Jay Vroom The Fertilizer Institute, Chris Jahn National Association of Wheat Growers, Chandler Goule National Cattlemen's Beef Association, Kendal Frazier National Corn Growers Association, Chris Novak National Cotton Council, Gary Adams National Council of Farmer Cooperatives, Chuck Conner National Farmers Union, Roger Johnson National Milk Producers Federation, Jim Mulhern National Pork Producers Council, Neil Dierks United Fresh Produce Association, Tom Stenzel USA Rice Federation, Betsy Ward Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00004 National Gotton Council OF MERTOA Gary M. Adams President and Chief Executive Officer National Cotton Council of America Gary Adams assumed the position of President and Chief Executive Officer of the National Cotton Council in February 2015. He plays a key role in guiding the industry's seven segments to reach consensus on critical policies affecting U.S. cotton, with the mission of helping all U.S. cotton industry segments compete effectively and profitably in global markets. Prior to that, Gary served the Council for 13 years as the Vice President of Economic and Policy Analysis. As the Council's chief economist, he provided economic outlooks for global cotton markets, as well as analyzing the impacts of farm and trade policies. Gary also represents the U.S. cotton industry as a member of USDA's Agricultural Policy Advisory Committee. Previously, Gary served on USDA's Advisory Committee on Trade from 2005 through 2011 and the NASS Advisory Committee on Agricultural Statistics from 2003 through 2009. Prior to joining the Council, Gary was a Research Assistant Professor in the Department of Agricultural Economics at the University of Missouri. During his 13-year tenure at the university, Gary's primary responsibilities included policy analysis and market outlook for the Food and Agricultural Policy Research Institute, also known as FAPRI. While at FAPRI, Gary and his colleagues were recognized by the American Agricultural Economics Association for their distinguished policy contributions. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00005 Gary has B.S. and M.A. degrees in Applied Mathematics from the University of Alabama and a Ph.D. in Agricultural Economics from the University of Missouri. Gary and his wife, Ex. 6 Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00006 FASA American Soybean Associatión & Stephen L Censky Chief Executive Officer Stephen L. Censky is the American Soybean Association's (ASA) C hief Executive Officer, a staff position he accepted in April 1996. As ASA's top executive, Ce nsky is in charge of managing ASA's legislative, trade policy, membership and education and training programs. The American Soybean Association is a national, not-for-profit commodity organization with over 22,000 members. ASA works as the domestic and international policy advocate for soybean producer members. Prior to joining ASA, Censky worked in Washington, D.C. for ove a decade. He began his career on Capitol Hill as a legislative assistant for agricultural and transportation matters to Senator Jim Abdnor (R-SD). Later he served in both the Reagan and Bush Administrations at the U.S. Department of Agriculture, helping to craft the 1990 Farm Bill and eventually serving as Administrator of the Foreign Agricultural Service where he was involved in global trade negotiations and running our nation's export programs. Censky received his Bachelor's of Science degree of Agriculture from South Dakota State University and his Master's Diploma in Agriculture St of Melbourne, Australia. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00007 NCFC. National Council of Farmer Cooperatives Charles F. (Chuck) Conner President and CEO National Council of Farmer Cooperatives Charles F. (Chuck) Conner became president & CEO of the National Council of Farmer Cooperatives (NCFC) on January 22, 2009. As president of NCFC, Conner will oversee the organization's work to promote and protect the business and public policy interests of America's farmer-owned cooperatives. He will also provide the strategic vision for the trade association as it continues to seek new ways in which to add value for its membership. Prior to joining NCFC, Conner had served as the Deputy Secretary at the U.S. Department of Agriculture since mid-2005. In this capacity, he was the Chief Operating Officer (COO) overseeing day-to-day operations of the department. Conner interacted directly with President George W. Bush and his senior staff to formulate domestic and international food, trade, security and energy policy. He led development of the Bush Administration's $300 billion Farm Bill proposal and the strategy to educate and inform industry, constituents and Congress. From August 2007 to January 2008, Conner served as both USDA Secretary and Deputy Secretary. He played a key role in developing the Administration's immigration policy including important changes to the H2A program. Conner's experience also includes the assignment of Special Assistant to the President, Executive Office of the President, from October 2001 to May 2005, working on the 2001/2 Farm Bill to develop the strategy behind the transfer of several USDA agency functions to the newly formed Department of Homeland Security. From May 1997 to October 2001 Conner served as President of the Corn Refiners Association. He also served for 17 years as an advisor to U.S. Senator Richard Lugar of Indiana. Conner is a graduate of Purdue University, with a Bachelor's of Science degree and is the recipient of Purdue's Distinguished Alumni Award. He and his wife Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00008 NATIONAL PORK PRODUCERS COUNCIL Neil Dierks, Chief Executive Officer Neil Dierks is Chief Executive Officer of the National Pork Producers Council (NPPC). In this position, he is responsible for the overall implementation of all NPPC programs. Dierks' position requires him to spend time in both Des Moines, Iowa, the national office of NPPC, and Washington, D.C. Beginning in 1990, Dierks served NPPC in a series of senior executive positions, including Executive Director of Operations, Vice President for Research and Education and Senior Vice President for Programs. Prior to his service with NPPC, Dierks was the Special Activities Director for the Iowa Pork Producers Association and Marketing Director for the Iowa Corn Promotion Board. Neil grew up on a livestock farm in eastern lowa and remains involved in a family farming operation. He is a graduate of Iowa State University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00009 NASDA Dr. Barbara Glenn recently joined the National Association of State Departments of Agriculture (NASDA) as CEO on August 18, 2014. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. Dr. Glenn is a scientist with decades of experience as a policy researcher and advocate for agriculture. She previously served as Senior Vice President of Science and Regulatory Affairs for CropLife America, where she was responsible for developing policies and regulations to support agriculture through crop protection. Prior to joining CropLife America, Dr. Glenn served as Managing Director of the Animal Bi otechnology, Food and Agriculture Section of the Biotechnology Industry Association in Washington, DC. Dr. Glenn holds a B.S. in animal science and a Ph.D. in ruminan t nutrition from the University of Kentucky. She previously worked for the U.S. Department of Agriculture, Agric ultural Research Service and the Federation of Animal Science Societies. Born in Lincoln, Nebraska and raised in Centerville, Ohio, Dr. Glenn developed a passion for agriculture from her parents and her involvement in 4-H. She lives Ex. 6 - Personal Privacy and serves on various boards for farm bureau and 4-H. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00010 National Association of Wheat Growers Chandler Goule CEO Chandler Goule assumed his responsibilities as CEO of the National Association of Wheat Growers on July 5, 2016. In addition, he also serves as the executive director of the National Wheat Foundation. Most recently, Goule served as senior vice president of programs at the National Farmers Union (NFU) where he was heavily involved in farm bill legislation. Originally from Texas, Goule holds degrees from Texas A&M and George Washington University and served as a subcommittee staff director for the House Agriculture Committee before moving to the National Farmers Union in 2009 as vice president of government relations. He was appointed senior vice president of NFU programs in 2014. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00011 The Fertilizer Institute Nourish, Replenish, Grow BIOGRAPHY OF CHRISTOPHER JAHN President The Fertilizer Institute and the Nutrients for Life Foundation Christopher L. Jahn is president of The Fertilizer Institute (TFI), the fertilizer industry's national trade association. As TFI president, Jahn works to represent, promote and protect a sound fertilizer industry through legislative and regulatory activities and to promote a favorable public image of the fertilizer industry and agriculture. Jahn also serves as president of the Nutrients for Life Foundation (NFL). Jahn comes to TFI having served as president of the National Association of Chemical Distributors (NACD) since 2006. Prior to leading NACD, Jahn served as president of the Contract Services Association (CSA). Before joining CSA, Jahn had an active role in the United States Senate working for nearly 10 years for U.S. Senator Craig Thomas (R-Wyo.) in a variety of roles, including legislative assistant, legislative director and Chief of Staff. After graduating from Columbia University with a B.A. in Political Science, Jahn co-founded a book distribution business. He also earned an MBA from the University of Maryland. A native of Wyoming, Chris and his wife, Ex. 6 - Personal Privacy Ex. Personal Privacy Capitol View 202.962.0490 425 Third Street, S.W., Suite 950 202.962.0577 fax Washington, DC 20024 www.tfi.org Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00012 National Farmers Union Roger Johnson President Roger Johnson is president of the National Farmers Union (NFU), a grassroots organization that represents more than 200,000 family farmers, ranchers, fisherman and rural communities across the Unites States. Johnson was elected to lead the family farm organization at NFU's 107th anniversary convention in 2009. He has since expanded the education department by providing more programs for beginning, college-aged and women farmers, increased the number of Farmers Union state divisions, and developed a strategic plan for the organization. Johnson has also overseen a number of important policy initiatives important to family farmers including: passage of the 2014 Farm Bill; maintaining a strong Renewable Fuel Standard and Country-of-Origir Labeling, promoting policies that allow farmers to address the growing threat of climate change; and renewing the nation's focus on eliminating an overwhelming trade deficit that results in lost jobs and prosperity for rural America. Prior to leading National Farmers Union, Johnson, a third-generation family farmer from Turtle Lake, N.D., served as North Dakota Agriculture Commissioner, a position he was first elected to in 1996. While Agriculture Commissioner, Johnson served on the State Industrial Commission, the North Dakota Trade Office Advisory Board, and the State Board of Agricultural Research and Education, among many other boards and commissions. From 2007-2008, Johnson served as president of the National Association of State Departments of Agriculture (NASDA). He is a past president of the Midwestern Association of State Departments of Agriculture (MASDA), past president of the Food Export Association of the Midwest and a former chairman of the Interstate Pest Control Compact. Johnson graduated from North Dakota State University with a degree in agricultural economics. Johnson and his wife Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00013 AMERICAN SEED TRADE ASSOCIATION asta first-the - seed R Andrew W. "Andy" LaVigne President & CEO Andrew W. LaVigne is currently the President and CEO of the Ame rican Seed Trade Association. He joined ASTA in February, 2006. Andy has had a 30-year career i n government relations, industry representation, public affairs advocacy, and management. His C ore areas of expertise include agriculture, food policy and international trade. Prior to joining ASTA, Andy was Executive Vice President/CEC of Florida Citrus Mutual, representing citrus growers on issues affecting their business. Prejaiming tFdorida Citrus Mutual, Andy spent four years as Florida Fertilizer and Agrichemical Association's (FFAA) President and Executive Director. FFAA is a non-profit, agricultural trade organization representing companies that specialize in crop protection and plant nutrition products. Before his position at FFAA, Andy spent eight years in Washingt on, D.C. working in the U.S. Congress and the U.S. Department of Agriculture. He served as Legislative Director for Congressman Charles Canady, Agriculture Committee staffer for Congressman Tom Lewis , and on the staff of USDA Secretary Ed Madigan. Andy is a native of Florida with a BA degree in Political Scien ce, with a minor in economics, from the University of Florida. 1701 Duke Street Suite 275 Alexandria, VA 22314 Phone: (703)837-8140 Fax: (703)837-9365 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00014 Biotechnology Innovation Organization Dana O'Brien Executive Vice President, Food & Agriculture Dana O'Brien is Executive Vice President for Food and Agriculture and is responsible for the development of public policy and strategic advocacy, public affairo, and legal strategies that advance industry and stakeholder objectives in the United States. Prior to becoming EVP, Dana served bs BIO Food and Agriculture's chief legislative advocate as Senior Director of Federal Government Relations aince March 2011. Before BIO, Dana worked in Congress for the late Representative lke Skelton (D-MO) managing his legislative team and concentrating on a variety of agricultural, energy, and trade matters. A native of Sedalia, Missouri, and a graduate of Missouri University with a bachelor's degree in psychology, Dana joined the Skelton team immediately out of college and served there for nearly 14 years Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00015 UNITED FRESH is PRODUCE ASSOCIATION Tom Stenzel President and CEO United Fresh Produce Association 1901 Pennsylvania Avenue NW, Suite 1100 Washington, DC 20006 202/303-3400 [email protected] Tom Stenzel is President and CEO of the United Fresh Produce Association, a position he has held since 1993. United Fresh is the pre-eminent trade association for the produce industry in shaping legislative and regulatory policies; providing scientific and technical leadership in food safety and nutrition; and developing educational programs for its members. Founded in 1904, United Fresh represents the interests of companies from small family businesses to the largest international corporations throughout the global fresh produce supply chain. United Fresh is widely known for its work in government affairs, agricultural policy, food safety and nutrition, working to promote political and environmental change to help the next generation of children double their consumption of fresh produce. The United Fresh Start Foundation is committed to increasing children's access to fresh fruits and vegetables, and is a founding partner of the Let's Move Salad Bars to Schools campaign. The campaign has donated salad bars to more than 6,000 schools across the country. Tom is a frequent speaker on industry issues and has been recognized often by the produce industry throughout his career. He was honored as the 2002 Produce Man of the Year by The Packer newspaper, and is the past Chairman of the International Federation for Produce Standards, a global body representing national produce associations around the world. He is a member of the U.S. Chamber of Commerce Committee of 100 leading association executives, the Advisory Board of the International Food Protection Training Institute, and the Key Industry Associations Committee of the American Society of Association Executives, from which he achieved the Certified Association Executive (CAE) designation in 1990. He has served in many government and industry leadership positions, including the first U.S. Department of Agriculture Fruit and Vegetable Industry Advisory Committee, President George W. Bush's Transition Advisory Team for Agriculture, and as an advisor on the U.S. Agricultural Policy Advisory Committee for Trade. Tom was the founding President of the International Food Information Council (IFIC) in 1986, and was previously director of public affairs for the National Soft Drink Association. Tom is a 1977 graduate of the University of Richmond. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00016 as of January 17, 2017 Jay Vroom has served as President and CEO of the trade association known as CropLife America (CLA) since 1989. CLA is the leading U.S. trade group for the crop protection industry in the U.S. Vroom is a founding member of the CropLife Foundation, serving as chairman since its inception in 2001, and now serves as the Foundation's Vice-Chair, since 2015. His sits of the Board of Directors for the Agricultural Retailers Association, Asmark, National Wheat Foundation, the National Association of Manufacturers Council of Manufacturing Associations, and the Soil Health Institute. He is also a member of the Farm Foundation Roundtable Steering Committee, and the North American Climate Smart Ag Alliance Steering Committee. Vroom was a member of the youth organization, Future Farmers of America, and served as an elected state officer in Illinois. Today, he is a member of the FFA Foundation's Individual Giving Council and Board of Trustees. Vroom co-chairs the Coalition for the Advancement of Precision Agriculture and the CEO Council. He is a member of the Friends of the National Arboretum (FONA) FONA Council. He graduated with honors from the College of Agriculture, Consumer and Environmental Sciences at the University of Illinois Urbana-Champaign. Vroom was raised on a grain and livestock farm in north-central Illinois and continues to own the farming operation. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00017 Elizabeth Ward Betsy Ward was appointed President & CEO of the USA Rice Federation in 2007. From 2003- 2005, Ward was the Vice President of International and Domestic Promotion at USA Rice where she was in charge of developing and implementing domestic and international promotion, and food aid programs. From 2005-2007, Ward served as the chief executive for the Hardwood Federation, a trade association representing over 15,000 hardwood producers across the United States. From 1995 to 2003, she ran the Wood Products International Group at the American Forest & Paper Association, directing the wood trade policy and global forestry agenda for the industry. In 2011, Ward was elected Chairman of the U.S. Agricultural Export Development Council (USAEDC) which represents the interests of more than 80 commodity organizations who grow and process a wide variety of U.S. agricultural products. She currently serves as Past Chair. Since 2011, Ward has also served on the Board of Directors of the Sustainable Fisheries Partnership, an independent non-governmental organization (NGO) working to ensure healthy marine and aquatic tecosystems; secure seafood supplies; and a thriving, responsible seafood economy. Ward served for six years as a cleared advisor on the Industry Trade Advisory Committee for forest and paper products (ITAC-7) and was appointed forest products representative to USDA's Agricultural Policy Advisory Committee (APAC) in 2001. Ward holds a Bachelor's degree in History and Political Science from the University of New Hampshire and a Master's degree in International Security Affairs from the School of International Affairs at Columbia University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00018 To: Brown, Byron[[email protected]]; Jackson, Ryan[[email protected]] From: Rebeckah Adcock Sent: Thur 3/30/2017 4:10:52 PM Subject: FW: FINAL CEO Council Meeting Agenda and Materials Pruitt Meeting Materials.pdf ATT00001.htm FYI - final materials for today's meeting. Reb From: "Mary Jo Tomalewski" <[email protected]> To: "Hupp, Sydney" <[email protected]> Cc: "Jay Vroom" <[email protected]> Subject: FINAL Meeting Agenda and Materials Sydney, We have refined our proposed topics for today's CEO Council meeting with the administrator. Attached, please find: Revised "Final Proposed Agenda Topics," which includes the list of those CEO Council members who will attend our meeting today, and their short bios Introduction / Mission Overview of the CEO Council CEO Council Letter to President Trump, dated February 9, 2017 We assume we can skip a formal "round table of introductions" at the beginning of the meeting as our time is short and we want to maximize time spent talking about issues. MJ Mary Jo Tomalewski Executive Assistant to the President & CEO CropLife America Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000063-00001 1156 15th Street, NW Suite 400 Washington, DC 20005 Direct Dial (202) 872-3849 Main Switchboard (202) 296-1585 Mobilé Ex. 6 Personal Privacy Fax (202) 466-5832 Email [email protected] Web www.croplifeamerica.org How can I serve you today? Future Meetings 2017 Spring Regulator Conference - April 6-7, Arlington, VA 2017 Annual Meeting - September 22-27, Dana Point, CA 2018 Winter Board of Directors Meeting - March 5-7, Washington, DC 2018 Annual Meeting - September 21-26, The Ritz-Carlton Amelia Island Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000063-00002 FINAL PROPOSED AGENDA TOPICS Meeting Information: Office of EPA Administrator Scott Pruitt 1200 Pennsylvania Avenue, NW Washington, DC Thursday, March 30, 2017 3:45-4:30 PM Topic 1. Thanks to Trump Administration and Administrator Pruitt for early decisive actions: a. WOTUS b. Chlorpyrifos Petition 2. Top Priority Issues a. Ag Advisor Position - We recommend adding additional title of "Assistant Deputy Administrator" as a title b. Water i. Next steps to refine / clarify beyond WOTUS ii. NPDES permits (CAFO Program needs work; legislation to fix water permits NOT needed for lawful use of pesticides) c. Pesticides Policy i. Endangered Species Act conflicts with Pesticide Regulation and Biotech Regulation ii. Epidemiology Study Policy (as aftermath from Chlorpyrifos matter) iii. Reform Certification & Training and Worker Protection Rules - Suspend implementation and revise d. Renewable Fuels Standard - current program kept consistent e. Communication / Messaging / Opinion Polling - vital to all parties' ability to advance sound policy f. EPA and USDA Cooperation and Coordination - Already vast progress; more can be done! g. Environmental Justice, Research & Development, and Children's Health Offices - Better integration with and reform of EPA program offices; sound science h. Regulation of Manufacturing & Mining Facilities for Ag Inputs - Restore science and process i. Public and Science Advisory Panels at EPA - Balance, strategic agendas j. "Air Emissions" from farming operations CEO Attendees American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Corn Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Barb Glenn, CEO, ex-officio Departments of Agriculture Others American Farm Bureau Federation Dale Moore, Deputy Executive Director Corn Refiners Association John Bode, President & CEO National Farmers Union Rob Larew, Senior VP Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00001 Production Agriculture's CEO Council Introduction/Mission Statement: The production agriculture "CEO Council" coordinates alignment on core issues of modern agricultural systems through telling our story, sharing information and leveraging our strengths, while serving as a resource for government decision makers and others interested in USA food, fiber and renewable fuels. Core Focus of Interest Research and innovation Technology access Science and risk-based regulation Sustainability, environment, and weather Marketability, trade, and economic prosperity Government leadership and partnership with private sector Food access and food safety Plant and animal health Ag labor The Council supports principles/themes): Accelerating rural economic growth and improving productivity through innovation and technology Promoting research and innovation that enables development oftools and techniques necessary for discovering new products that hold tremendous potential for farmers and society at large Enabling a regulatory and commercial environment in which agricultural products are marketable, both domestically and internationally Appropriate balance between Federal and State Governments and a cooperative regulatory approach Access to essential labor in balance with an effective Federal immigration policy and adequate worker safety protections Support for all methods of agricultural production Transparency and dialogue with consumers Members of the CEO Council (see reversed) March 30, 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00002 CEO Council Members American Farm Bureau Vincent "Zippy" Duvall, President American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Cattlemen's Beef Association Kendal Frazier, CEO National Chicken Council Michael Brown, President National Com Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Farmers Union Roger Johnson, President National Milk Producers Federation Jim Mulhern, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Departments of Barb Glenn, CEO, ex-officio Agriculture March 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00003 February 9, 2017 The President The White House Washington, D.C. 20500 Dear Mr. President, We, the CEO Council (undersigned herein), representing the production agricultural value chain, including many agricultural producers and farm input developers and suppliers, look forward to working with you and your Administration on matters of importance to American agriculture. The challenges we face in agriculture are significant. Many experts emphasize that producers must grow as much food in the next 50 years as was produced over all previous history to meet the demands of our expanding global population. A firm commitment by the U.S. government to aggressively support agricultural innovation and science-based regulatory decisions will be necessary to ensure farmers have the tools they need to produce a safe and abundant supply of nutritious food, in addition to feed, fuel and fiber, in an environmentally sound and sustainable manner. The policy and regulatory environment your Administration establishes can ensure that agricultural innovation flourishes and American farmers are able to meet the food production goals necessary to feed billions more people. We are ready to provide the White House and the Executive Branch Departments and Agencies, as well as Congress, with policy concepts that foster stability in the U.S. agriculture economy with a strong and predictable farm safety net and promotes American competitiveness through research; marketability and trade of agricultural commodities; rural economic growth; and plant, animal, and environmental health, among many other things. We appreciate your attention to these and other issues of value to American production agriculture and food consumers everywhere. Sincerely, American Farm Bureau Foundation, Zippy Duvall American Seed Trade Association, Andy LaVigne American Soybean Association, Steve Censky Biotechnology Innovation Organization, Dana O'Brien CropLife America, Jay Vroom The Fertilizer Institute, Chris Jahn National Association of Wheat Growers, Chandler Goule National Cattlemen's Beef Association, Kendal Frazier National Corn Growers Association, Chris Novak National Cotton Council, Gary Adams National Council of Farmer Cooperatives, Chuck Conner National Farmers Union, Roger Johnson National Milk Producers Federation, Jim Mulhern National Pork Producers Council, Neil Dierks United Fresh Produce Association, Tom Stenzel USA Rice Federation, Betsy Ward Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00004 National Gotton Council OF MERTOA Gary M. Adams President and Chief Executive Officer National Cotton Council of America Gary Adams assumed the position of President and Chief Executive Officer of the National Cotton Council in February 2015. He plays a key role in guiding the industry's seven segments to reach consensus on critical policies affecting U.S. cotton, with the mission of helping all U.S. cotton industry segments compete effectively and profitably in global markets. Prior to that, Gary served the Council for 13 years as the Vice President of Economic and Policy Analysis. As the Council's chief economist, he provided economic outlooks for global cotton markets, as well as analyzing the impacts of farm and trade policies. Gary also represents the U.S. cotton industry as a member of USDA's Agricultural Policy Advisory Committee. Previously, Gary served on USDA's Advisory Committee on Trade from 2005 through 2011 and the NASS Advisory Committee on Agricultural Statistics from 2003 through 2009. Prior to joining the Council, Gary was a Research Assistant Professor in the Department of Agricultural Economics at the University of Missouri. During his 13-year tenure at the university, Gary's primary responsibilities included policy analysis and market outlook for the Food and Agricultural Policy Research Institute, also known as FAPRI. While at FAPRI, Gary and his colleagues were recognized by the American Agricultural Economics Association for their distinguished policy contributions. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00005 Gary has B.S. and M.A. degrees in Applied Mathematics from the University of Alabama. and a Ph.D. in Agricultural Economics from the University of Missouri. Gary and his wife, Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00006 FASA American Soybean Associatión & Stephen L Censky Chief Executive Officer Stephen L. Censky is the American Soybean Association's (ASA) C hief Executive Officer, a staff position he accepted in April 1996. As ASA's top executive, Ce nsky is in charge of managing ASA's legislative, trade policy, membership and education and training programs. The American Soybean Association is a national, not-for-profit commodity organization with over 22,000 members. ASA works as the domestic and international policy advocate for soybean producer members. Prior to joining ASA, Censky worked in Washington, D.C. for ove a decade. He began his career on Capitol Hill as a legislative assistant for agricultural and transportation matters to Senator Jim Abdnor (R-SD). Later he served in both the Reagan and Bush Administrations at the U.S. Department of Agriculture, helping to craft the 1990 Farm Bill and eventually serving as Administrator of the Foreign Agricultural Service where he was involved in global trade negotiations and running our nation's export programs. Censky received his Bachelor's of Science degree of Agriculture from South Dakota State University and his Master's Diploma in Agriculture St of Melbourne, Australia. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00007 NCFC. National Council of Farmer Cooperatives Charles F. (Chuck) Conner President and CEO National Council of Farmer Cooperatives Charles F. (Chuck) Conner became president & CEO of the National Council of Farmer Cooperatives (NCFC) on January 22, 2009. As president of NCFC, Conner will oversee the organization's work to promote and protect the business and public policy interests of America's farmer-owned cooperatives. He will also provide the strategic vision for the trade association as it continues to seek new ways in which to add value for its membership. Prior to joining NCFC, Conner had served as the Deputy Secretary at the U.S. Department of Agriculture since mid-2005. In this capacity, he was the Chief Operating Officer (COO) overseeing day-to-day operations of the department. Conner interacted directly with President George W. Bush and his senior staff to formulate domestic and international food, trade, security and energy policy. He led development of the Bush Administration's $300 billion Farm Bill proposal and the strategy to educate and inform industry, constituents and Congress. From August 2007 to January 2008, Conner served as both USDA Secretary and Deputy Secretary. He played a key role in developing the Administration's immigration policy including important changes to the H2A program. Conner's experience also includes the assignment of Special Assistant to the President, Executive Office of the President, from October 2001 to May 2005, working on the 2001/2 Farm Bill to develop the strategy behind the transfer of several USDA agency functions to the newly formed Department of Homeland Security. From May 1997 to October 2001 Conner served as President of the Corn Refiners Association. He also served for 17 years as an advisor to U.S. Senator Richard Lugar of Indiana. Conner is a graduate of Purdue University, with a Bachelor's of Science degree and is the recipient of Purdue's Distinguished Alumni Award. He and his wife Ex. 6 - Personal Privacy Source: :https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00008 NATIONAL PORK PRODUCERS COUNCIL Neil Dierks, Chief Executive Officer Neil Dierks is Chief Executive Officer of the National Pork Producers Council (NPPC). In this position, he is responsible for the overall implementation of all NPPC programs. Dierks' position requires him to spend time in both Des Moines, Iowa, the national office of NPPC, and Washington, D.C. Beginning in 1990, Dierks served NPPC in a series of senior executive positions, including Executive Director of Operations, Vice President for Research and Education and Senior Vice President for Programs. Prior to his service with NPPC, Dierks was the Special Activities Director for the Iowa Pork Producers Association and Marketing Director for the Iowa Corn Promotion Board. Neil grew up on a livestock farm in eastern lowa and remains involved in a family farming operation. He is a graduate of Iowa State University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00009 NASDA Dr. Barbara Glenn recently joined the National Association of State Departments of Agriculture (NASDA) as CEO on August 18, 2014. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. Dr. Glenn is a scientist with decades of experience as a policy researcher and advocate for agriculture. She previously served as Senior Vice President of Science and Regulatory Affairs for CropLife America, where she was responsible for developing policies and regulations to support agriculture through crop protection. Prior to joining CropLife America, Dr. Glenn served as Managing Director of the Animal Bi otechnology, Food and Agriculture Section of the Biotechnology Industry Association in Washington, DC. Dr. Glenn holds a B.S. in animal science and a Ph.D. in ruminan t nutrition from the University of Kentucky. She previously worked for the U.S. Department of Agriculture, Agric ultural Research Service and the Federation of Animal Science Societies. Born in Lincoln, Nebraska and raised in Centerville, Ohio, Dr. Glenn developed a passion for agriculture from her parents and her involvement in 4-H. She lives on a small farm in Maryland with her husband: Ex. 6 - Personal Privacy and serves on various boards for farm bureau and 4-H. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00010 National Association of Wheat Growers Chandler Goule CEO Chandler Goule assumed his responsibilities as CEO of the National Association of Wheat Growers on July 5, 2016. In addition, he also serves as the executive director of the National Wheat Foundation. Most recently, Goule served as senior vice president of programs at the National Farmers Union (NFU) where he was heavily involved in farm bill legislation. Originally from Texas, Goule holds degrees from Texas A&M and George Washington University and served as a subcommittee staff director for the House Agriculture Committee before moving to the National Farmers Union in 2009 as vice president of government relations. He was appointed senior vice president of NFU programs in 2014. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00011 The Fertilizer Institute Nourish, Replenish, Grow BIOGRAPHY OF CHRISTOPHER JAHN President The Fertilizer Institute and the Nutrients for Life Foundation Christopher L. Jahn is president of The Fertilizer Institute (TFI), the fertilizer industry's national trade association. As TFI president, Jahn works to represent, promote and protect a sound fertilizer industry through legislative and regulatory activities and to promote a favorable public image of the fertilizer industry and agriculture. Jahn also serves as president of the Nutrients for Life Foundation (NFL). Jahn comes to TFI having served as president of the National Association of Chemical Distributors (NACD) since 2006. Prior to leading NACD, Jahn served as president of the Contract Services Association (CSA). Before joining CSA, Jahn had an active role in the United States Senate working for nearly 10 years for U.S. Senator Craig Thomas (R-Wyo.) in a variety of roles, including legislative assistant, legislative director and Chief of Staff. After graduating from Columbia University with a B.A. in Political Science, Jahn co-founded a book distribution business. He also earned an MBA from the University of Maryland. A native of Wyoming, Chris and his wife Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Capitol View 202.962.0490 425 Third Street, S.W., Suite 950 202.962.0577 fax Washington, DC 20024 www.tfi.org Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00012 National Farmers Union Roger Johnson President Roger Johnson is president of the National Farmers Union (NFU), a grassroots organization that represents more than 200,000 family farmers, ranchers, fisherman and rural communities across the Unites States. Johnson was elected to lead the family farm organization at NFU's 107th anniversary convention in 2009. He has since expanded the education department by providing more programs for beginning, college-aged and women farmers, increased the number of Farmers Union state divisions, and developed a strategic plan for the organization. Johnson has also overseen a number of important policy initiatives important to family farmers including: passage of the 2014 Farm Bill; maintaining a strong Renewable Fuel Standard and Country-of-Origir Labeling, promoting policies that allow farmers to address the growing threat of climate change; and renewing the nation's focus on eliminating an overwhelming trade deficit that results in lost jobs and prosperity for rural America. Prior to leading National Farmers Union, Johnson, a third-generation family farmer from Turtle Lake, N.D., served as North Dakota Agriculture Commissioner, a position he was first elected to in 1996. While Agriculture Commissioner, Johnson served on the State Industrial Commission, the North Dakota Trade Office Advisory Board, and the State Board of Agricultural Research and Education, among many other boards and commissions. From 2007-2008, Johnson served as president of the National Association of State Departments of Agriculture (NASDA). He is a past president of the Midwestern Association of State Departments of Agriculture (MASDA), past president of the Food Export Association of the Midwest and a former chairman of the Interstate Pest Control Compact. Johnson graduated from North Dakota State University with a degree in agricultural economics. Johnson and his wife, Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00013

What does FFAA stands for ?

ffcn0226

ffcn0226_p0, ffcn0226_p1, ffcn0226_p2, ffcn0226_p3, ffcn0226_p4, ffcn0226_p5, ffcn0226_p6, ffcn0226_p7, ffcn0226_p8, ffcn0226_p9, ffcn0226_p10, ffcn0226_p11, ffcn0226_p12, ffcn0226_p13, ffcn0226_p14, ffcn0226_p15, ffcn0226_p16, ffcn0226_p17, ffcn0226_p18, ffcn0226_p19, ffcn0226_p20, ffcn0226_p21, ffcn0226_p22, ffcn0226_p23, ffcn0226_p24, ffcn0226_p25, ffcn0226_p26, ffcn0226_p27, ffcn0226_p28, ffcn0226_p29, ffcn0226_p30, ffcn0226_p31, ffcn0226_p32, ffcn0226_p33, ffcn0226_p34

Florida Fertilizer and Agrichemical Association, "Florida Fertilizer and Agrichemical Associations"

To: Greenwalt, Sarah[[email protected]]; Dravis, Samantha[[email protected]] Brown, Byron[[email protected]];Wagner, Kenneth[[email protected]] From: Hupp, Sydney Sent: Thur 3/30/2017 5:11:34 PM Subject: FW: FINAL Meeting Agenda and Materials Pruitt Meeting Materials.pd FYI. Sydney Hupp Office of the Administrator- Scheduling 202.816.1659 From: Mary Jo Tomalewski [mailto:[email protected]] Sent: Thursday, March 30, 2017 11:22 AM To: Hupp, Sydney <[email protected]> Cc: Jay Vroom <[email protected]> Subject: FINAL Meeting Agenda and Materials Sydney, We have refined our proposed topics for today's CEO Council meeting with the administrator. Attached, please find: Revised "Final Proposed Agenda Topics," which includes the list of those CEO Council members who will attend our meeting today, and their short bios Introduction / Mission Overview of the CEO Council CEO Council Letter to President Trump, dated February 9, 2017 We assume we can skip a formal "round table of introductions" at the beginning of the meeting as our time is short and we want to maximize time spent talking about issues. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000061-00001 MJ Mary Jo Tomalewski Executive Assistant to the President & CEO CropLife America 1156 15th Street, NW Suite 400 Washington, DC 20005 Direct Dial (202) 872-3849 Main Switchboard (202) 296-1585 Mobile Ex. 6 Personal Privacy Fax (202)466-5832 Email [email protected] Web www.croplifeamerica.org How can I serve you today? Future Meetings 2017 Spring Regulator Conference - April 6-7, Arlington, VA 2017 Annual Meeting - September 22-27, Dana Point, CA 2018 Winter Board of Directors Meeting - March 5-7, Washington, DC 2018 Annual Meeting - September 21-26, The Ritz-Carlton Amelia Island Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000061-00002 FINAL PROPOSED AGENDA TOPICS Meeting Information: Office of EPA Administrator Scott Pruitt 1200 Pennsylvania Avenue, NW Washington, DC Thursday, March 30, 2017 3:45-4:30 PM Topic 1. Thanks to Trump Administration and Administrator Pruitt for early decisive actions: a. WOTUS b. Chlorpyrifos Petition 2. Top Priority Issues a. Ag Advisor Position - We recommend adding additional title of "Assistant Deputy Administrator" as a title b. Water i. Next steps to refine / clarify beyond WOTUS ii. NPDES permits (CAFO Program needs work; legislation to fix water permits NOT needed for lawful use of pesticides) c. Pesticides Policy i. Endangered Species Act conflicts with Pesticide Regulation and Biotech Regulation ii. Epidemiology Study Policy (as aftermath from Chlorpyrifos matter) iii. Reform Certification & Training and Worker Protection Rules - Suspend implementation and revise d. Renewable Fuels Standard - current program kept consistent e. Communication / Messaging / Opinion Polling - vital to all parties' ability to advance sound policy f. EPA and USDA Cooperation and Coordination - Already vast progress; more can be done! g. Environmental Justice, Research & Development, and Children's Health Offices - Better integration with and reform of EPA program offices; sound science h. Regulation of Manufacturing & Mining Facilities for Ag Inputs - Restore science and process i. Public and Science Advisory Panels at EPA - Balance, strategic agendas j. "Air Emissions" from farming operations CEO Attendees American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Corn Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Barb Glenn, CEO, ex-officio Departments of Agriculture Others American Farm Bureau Federation Dale Moore, Deputy Executive Director Corn Refiners Association John Bode, President & CEO National Farmers Union Rob Larew, Senior VP Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00001 Production Agriculture's CEO Council Introduction/Mission Statement: The production agriculture "CEO Council" coordinates alignment on core issues of modern agricultural systems through telling our story, sharing information and leveraging our strengths, while serving as a resource for government decision makers and others interested in USA food, fiber and renewable fuels. Core Focus of Interest Research and innovation Technology access Science and risk-based regulation Sustainability, environment, and weather Marketability, trade, and economic prosperity Government leadership and partnership with private sector Food access and food safety Plant and animal health Ag labor The Council supports principles/themes): Accelerating rural economic growth and improving productivity through innovation and technology Promoting research and innovation that enables development oftools and techniques necessary for discovering new products that hold tremendous potential for farmers and society at large Enabling a regulatory and commercial environment in which agricultural products are marketable, both domestically and internationally Appropriate balance between Federal and State Governments and a cooperative regulatory approach Access to essential labor in balance with an effective Federal immigration policy and adequate worker safety protections Support for all methods of agricultural production Transparency and dialogue with consumers Members of the CEO Council (see reversed) March 30, 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00002 CEO Council Members American Farm Bureau Vincent "Zippy" Duvall, President American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Cattlemen's Beef Association Kendal Frazier, CEO National Chicken Council Michael Brown, President National Com Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Farmers Union Roger Johnson, President National Milk Producers Federation Jim Mulhern, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Departments of Barb Glenn, CEO, ex-officio Agriculture March 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00003 February 9, 2017 The President The White House Washington, D.C. 20500 Dear Mr. President, We, the CEO Council (undersigned herein), representing the production agricultural value chain, including many agricultural producers and farm input developers and suppliers, look forward to working with you and your Administration on matters of importance to American agriculture. The challenges we face in agriculture are significant. Many experts emphasize that producers must grow as much food in the next 50 years as was produced over all previous history to meet the demands of our expanding global population. A firm commitment by the U.S. government to aggressively support agricultural innovation and science-based regulatory decisions will be necessary to ensure farmers have the tools they need to produce a safe and abundant supply of nutritious food, in addition to feed, fuel and fiber, in an environmentally sound and sustainable manner. The policy and regulatory environment your Administration establishes can ensure that agricultural innovation flourishes and American farmers are able to meet the food production goals necessary to feed billions more people. We are ready to provide the White House and the Executive Branch Departments and Agencies, as well as Congress, with policy concepts that foster stability in the U.S. agriculture economy with a strong and predictable farm safety net and promotes American competitiveness through research; marketability and trade of agricultural commodities; rural economic growth; and plant, animal, and environmental health, among many other things. We appreciate your attention to these and other issues of value to American production agriculture and food consumers everywhere. Sincerely, American Farm Bureau Foundation, Zippy Duvall American Seed Trade Association, Andy LaVigne American Soybean Association, Steve Censky Biotechnology Innovation Organization, Dana O'Brien CropLife America, Jay Vroom The Fertilizer Institute, Chris Jahn National Association of Wheat Growers, Chandler Goule National Cattlemen's Beef Association, Kendal Frazier National Corn Growers Association, Chris Novak National Cotton Council, Gary Adams National Council of Farmer Cooperatives, Chuck Conner National Farmers Union, Roger Johnson National Milk Producers Federation, Jim Mulhern National Pork Producers Council, Neil Dierks United Fresh Produce Association, Tom Stenzel USA Rice Federation, Betsy Ward Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00004 National Gotton Council OF MERTOA Gary M. Adams President and Chief Executive Officer National Cotton Council of America Gary Adams assumed the position of President and Chief Executive Officer of the National Cotton Council in February 2015. He plays a key role in guiding the industry's seven segments to reach consensus on critical policies affecting U.S. cotton, with the mission of helping all U.S. cotton industry segments compete effectively and profitably in global markets. Prior to that, Gary served the Council for 13 years as the Vice President of Economic and Policy Analysis. As the Council's chief economist, he provided economic outlooks for global cotton markets, as well as analyzing the impacts of farm and trade policies. Gary also represents the U.S. cotton industry as a member of USDA's Agricultural Policy Advisory Committee. Previously, Gary served on USDA's Advisory Committee on Trade from 2005 through 2011 and the NASS Advisory Committee on Agricultural Statistics from 2003 through 2009. Prior to joining the Council, Gary was a Research Assistant Professor in the Department of Agricultural Economics at the University of Missouri. During his 13-year tenure at the university, Gary's primary responsibilities included policy analysis and market outlook for the Food and Agricultural Policy Research Institute, also known as FAPRI. While at FAPRI, Gary and his colleagues were recognized by the American Agricultural Economics Association for their distinguished policy contributions. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00005 Gary has B.S. and M.A. degrees in Applied Mathematics from the University of Alabama and a Ph.D. in Agricultural Economics from the University of Missouri. Gary and his wife, Ex. 6 Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00006 FASA American Soybean Associatión & Stephen L Censky Chief Executive Officer Stephen L. Censky is the American Soybean Association's (ASA) C hief Executive Officer, a staff position he accepted in April 1996. As ASA's top executive, Ce nsky is in charge of managing ASA's legislative, trade policy, membership and education and training programs. The American Soybean Association is a national, not-for-profit commodity organization with over 22,000 members. ASA works as the domestic and international policy advocate for soybean producer members. Prior to joining ASA, Censky worked in Washington, D.C. for ove a decade. He began his career on Capitol Hill as a legislative assistant for agricultural and transportation matters to Senator Jim Abdnor (R-SD). Later he served in both the Reagan and Bush Administrations at the U.S. Department of Agriculture, helping to craft the 1990 Farm Bill and eventually serving as Administrator of the Foreign Agricultural Service where he was involved in global trade negotiations and running our nation's export programs. Censky received his Bachelor's of Science degree of Agriculture from South Dakota State University and his Master's Diploma in Agriculture St of Melbourne, Australia. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00007 NCFC. National Council of Farmer Cooperatives Charles F. (Chuck) Conner President and CEO National Council of Farmer Cooperatives Charles F. (Chuck) Conner became president & CEO of the National Council of Farmer Cooperatives (NCFC) on January 22, 2009. As president of NCFC, Conner will oversee the organization's work to promote and protect the business and public policy interests of America's farmer-owned cooperatives. He will also provide the strategic vision for the trade association as it continues to seek new ways in which to add value for its membership. Prior to joining NCFC, Conner had served as the Deputy Secretary at the U.S. Department of Agriculture since mid-2005. In this capacity, he was the Chief Operating Officer (COO) overseeing day-to-day operations of the department. Conner interacted directly with President George W. Bush and his senior staff to formulate domestic and international food, trade, security and energy policy. He led development of the Bush Administration's $300 billion Farm Bill proposal and the strategy to educate and inform industry, constituents and Congress. From August 2007 to January 2008, Conner served as both USDA Secretary and Deputy Secretary. He played a key role in developing the Administration's immigration policy including important changes to the H2A program. Conner's experience also includes the assignment of Special Assistant to the President, Executive Office of the President, from October 2001 to May 2005, working on the 2001/2 Farm Bill to develop the strategy behind the transfer of several USDA agency functions to the newly formed Department of Homeland Security. From May 1997 to October 2001 Conner served as President of the Corn Refiners Association. He also served for 17 years as an advisor to U.S. Senator Richard Lugar of Indiana. Conner is a graduate of Purdue University, with a Bachelor's of Science degree and is the recipient of Purdue's Distinguished Alumni Award. He and his wife Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00008 NATIONAL PORK PRODUCERS COUNCIL Neil Dierks, Chief Executive Officer Neil Dierks is Chief Executive Officer of the National Pork Producers Council (NPPC). In this position, he is responsible for the overall implementation of all NPPC programs. Dierks' position requires him to spend time in both Des Moines, Iowa, the national office of NPPC, and Washington, D.C. Beginning in 1990, Dierks served NPPC in a series of senior executive positions, including Executive Director of Operations, Vice President for Research and Education and Senior Vice President for Programs. Prior to his service with NPPC, Dierks was the Special Activities Director for the Iowa Pork Producers Association and Marketing Director for the Iowa Corn Promotion Board. Neil grew up on a livestock farm in eastern lowa and remains involved in a family farming operation. He is a graduate of Iowa State University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00009 NASDA Dr. Barbara Glenn recently joined the National Association of State Departments of Agriculture (NASDA) as CEO on August 18, 2014. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. Dr. Glenn is a scientist with decades of experience as a policy researcher and advocate for agriculture. She previously served as Senior Vice President of Science and Regulatory Affairs for CropLife America, where she was responsible for developing policies and regulations to support agriculture through crop protection. Prior to joining CropLife America, Dr. Glenn served as Managing Director of the Animal Bi otechnology, Food and Agriculture Section of the Biotechnology Industry Association in Washington, DC. Dr. Glenn holds a B.S. in animal science and a Ph.D. in ruminan t nutrition from the University of Kentucky. She previously worked for the U.S. Department of Agriculture, Agric ultural Research Service and the Federation of Animal Science Societies. Born in Lincoln, Nebraska and raised in Centerville, Ohio, Dr. Glenn developed a passion for agriculture from her parents and her involvement in 4-H. She lives Ex. 6 - Personal Privacy and serves on various boards for farm bureau and 4-H. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00010 National Association of Wheat Growers Chandler Goule CEO Chandler Goule assumed his responsibilities as CEO of the National Association of Wheat Growers on July 5, 2016. In addition, he also serves as the executive director of the National Wheat Foundation. Most recently, Goule served as senior vice president of programs at the National Farmers Union (NFU) where he was heavily involved in farm bill legislation. Originally from Texas, Goule holds degrees from Texas A&M and George Washington University and served as a subcommittee staff director for the House Agriculture Committee before moving to the National Farmers Union in 2009 as vice president of government relations. He was appointed senior vice president of NFU programs in 2014. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00011 The Fertilizer Institute Nourish, Replenish, Grow BIOGRAPHY OF CHRISTOPHER JAHN President The Fertilizer Institute and the Nutrients for Life Foundation Christopher L. Jahn is president of The Fertilizer Institute (TFI), the fertilizer industry's national trade association. As TFI president, Jahn works to represent, promote and protect a sound fertilizer industry through legislative and regulatory activities and to promote a favorable public image of the fertilizer industry and agriculture. Jahn also serves as president of the Nutrients for Life Foundation (NFL). Jahn comes to TFI having served as president of the National Association of Chemical Distributors (NACD) since 2006. Prior to leading NACD, Jahn served as president of the Contract Services Association (CSA). Before joining CSA, Jahn had an active role in the United States Senate working for nearly 10 years for U.S. Senator Craig Thomas (R-Wyo.) in a variety of roles, including legislative assistant, legislative director and Chief of Staff. After graduating from Columbia University with a B.A. in Political Science, Jahn co-founded a book distribution business. He also earned an MBA from the University of Maryland. A native of Wyoming, Chris and his wife, Ex. 6 - Personal Privacy Ex. Personal Privacy Capitol View 202.962.0490 425 Third Street, S.W., Suite 950 202.962.0577 fax Washington, DC 20024 www.tfi.org Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00012 National Farmers Union Roger Johnson President Roger Johnson is president of the National Farmers Union (NFU), a grassroots organization that represents more than 200,000 family farmers, ranchers, fisherman and rural communities across the Unites States. Johnson was elected to lead the family farm organization at NFU's 107th anniversary convention in 2009. He has since expanded the education department by providing more programs for beginning, college-aged and women farmers, increased the number of Farmers Union state divisions, and developed a strategic plan for the organization. Johnson has also overseen a number of important policy initiatives important to family farmers including: passage of the 2014 Farm Bill; maintaining a strong Renewable Fuel Standard and Country-of-Origir Labeling, promoting policies that allow farmers to address the growing threat of climate change; and renewing the nation's focus on eliminating an overwhelming trade deficit that results in lost jobs and prosperity for rural America. Prior to leading National Farmers Union, Johnson, a third-generation family farmer from Turtle Lake, N.D., served as North Dakota Agriculture Commissioner, a position he was first elected to in 1996. While Agriculture Commissioner, Johnson served on the State Industrial Commission, the North Dakota Trade Office Advisory Board, and the State Board of Agricultural Research and Education, among many other boards and commissions. From 2007-2008, Johnson served as president of the National Association of State Departments of Agriculture (NASDA). He is a past president of the Midwestern Association of State Departments of Agriculture (MASDA), past president of the Food Export Association of the Midwest and a former chairman of the Interstate Pest Control Compact. Johnson graduated from North Dakota State University with a degree in agricultural economics. Johnson and his wife Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00013 AMERICAN SEED TRADE ASSOCIATION asta first-the - seed R Andrew W. "Andy" LaVigne President & CEO Andrew W. LaVigne is currently the President and CEO of the Ame rican Seed Trade Association. He joined ASTA in February, 2006. Andy has had a 30-year career i n government relations, industry representation, public affairs advocacy, and management. His C ore areas of expertise include agriculture, food policy and international trade. Prior to joining ASTA, Andy was Executive Vice President/CEC of Florida Citrus Mutual, representing citrus growers on issues affecting their business. Prejaiming tFdorida Citrus Mutual, Andy spent four years as Florida Fertilizer and Agrichemical Association's (FFAA) President and Executive Director. FFAA is a non-profit, agricultural trade organization representing companies that specialize in crop protection and plant nutrition products. Before his position at FFAA, Andy spent eight years in Washingt on, D.C. working in the U.S. Congress and the U.S. Department of Agriculture. He served as Legislative Director for Congressman Charles Canady, Agriculture Committee staffer for Congressman Tom Lewis , and on the staff of USDA Secretary Ed Madigan. Andy is a native of Florida with a BA degree in Political Scien ce, with a minor in economics, from the University of Florida. 1701 Duke Street Suite 275 Alexandria, VA 22314 Phone: (703)837-8140 Fax: (703)837-9365 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00014 Biotechnology Innovation Organization Dana O'Brien Executive Vice President, Food & Agriculture Dana O'Brien is Executive Vice President for Food and Agriculture and is responsible for the development of public policy and strategic advocacy, public affairo, and legal strategies that advance industry and stakeholder objectives in the United States. Prior to becoming EVP, Dana served bs BIO Food and Agriculture's chief legislative advocate as Senior Director of Federal Government Relations aince March 2011. Before BIO, Dana worked in Congress for the late Representative lke Skelton (D-MO) managing his legislative team and concentrating on a variety of agricultural, energy, and trade matters. A native of Sedalia, Missouri, and a graduate of Missouri University with a bachelor's degree in psychology, Dana joined the Skelton team immediately out of college and served there for nearly 14 years Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000062-00015 UNITED FRESH is PRODUCE ASSOCIATION Tom Stenzel President and CEO United Fresh Produce Association 1901 Pennsylvania Avenue NW, Suite 1100 Washington, DC 20006 202/303-3400 [email protected] Tom Stenzel is President and CEO of the United Fresh Produce Association, a position he has held since 1993. United Fresh is the pre-eminent trade association for the produce industry in shaping legislative and regulatory policies; providing scientific and technical leadership in food safety and nutrition; and developing educational programs for its members. Founded in 1904, United Fresh represents the interests of companies from small family businesses to the largest international corporations throughout the global fresh produce supply chain. United Fresh is widely known for its work in government affairs, agricultural policy, food safety and nutrition, working to promote political and environmental change to help the next generation of children double their consumption of fresh produce. The United Fresh Start Foundation is committed to increasing children's access to fresh fruits and vegetables, and is a founding partner of the Let's Move Salad Bars to Schools campaign. The campaign has donated salad bars to more than 6,000 schools across the country. Tom is a frequent speaker on industry issues and has been recognized often by the produce industry throughout his career. He was honored as the 2002 Produce Man of the Year by The Packer newspaper, and is the past Chairman of the International Federation for Produce Standards, a global body representing national produce associations around the world. He is a member of the U.S. Chamber of Commerce Committee of 100 leading association executives, the Advisory Board of the International Food Protection Training Institute, and the Key Industry Associations Committee of the American Society of Association Executives, from which he achieved the Certified Association Executive (CAE) designation in 1990. He has served in many government and industry leadership positions, including the first U.S. Department of Agriculture Fruit and Vegetable Industry Advisory Committee, President George W. Bush's Transition Advisory Team for Agriculture, and as an advisor on the U.S. Agricultural Policy Advisory Committee for Trade. Tom was the founding President of the International Food Information Council (IFIC) in 1986, and was previously director of public affairs for the National Soft Drink Association. Tom is a 1977 graduate of the University of Richmond. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00016 as of January 17, 2017 Jay Vroom has served as President and CEO of the trade association known as CropLife America (CLA) since 1989. CLA is the leading U.S. trade group for the crop protection industry in the U.S. Vroom is a founding member of the CropLife Foundation, serving as chairman since its inception in 2001, and now serves as the Foundation's Vice-Chair, since 2015. His sits of the Board of Directors for the Agricultural Retailers Association, Asmark, National Wheat Foundation, the National Association of Manufacturers Council of Manufacturing Associations, and the Soil Health Institute. He is also a member of the Farm Foundation Roundtable Steering Committee, and the North American Climate Smart Ag Alliance Steering Committee. Vroom was a member of the youth organization, Future Farmers of America, and served as an elected state officer in Illinois. Today, he is a member of the FFA Foundation's Individual Giving Council and Board of Trustees. Vroom co-chairs the Coalition for the Advancement of Precision Agriculture and the CEO Council. He is a member of the Friends of the National Arboretum (FONA) FONA Council. He graduated with honors from the College of Agriculture, Consumer and Environmental Sciences at the University of Illinois Urbana-Champaign. Vroom was raised on a grain and livestock farm in north-central Illinois and continues to own the farming operation. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00017 Elizabeth Ward Betsy Ward was appointed President & CEO of the USA Rice Federation in 2007. From 2003- 2005, Ward was the Vice President of International and Domestic Promotion at USA Rice where she was in charge of developing and implementing domestic and international promotion, and food aid programs. From 2005-2007, Ward served as the chief executive for the Hardwood Federation, a trade association representing over 15,000 hardwood producers across the United States. From 1995 to 2003, she ran the Wood Products International Group at the American Forest & Paper Association, directing the wood trade policy and global forestry agenda for the industry. In 2011, Ward was elected Chairman of the U.S. Agricultural Export Development Council (USAEDC) which represents the interests of more than 80 commodity organizations who grow and process a wide variety of U.S. agricultural products. She currently serves as Past Chair. Since 2011, Ward has also served on the Board of Directors of the Sustainable Fisheries Partnership, an independent non-governmental organization (NGO) working to ensure healthy marine and aquatic tecosystems; secure seafood supplies; and a thriving, responsible seafood economy. Ward served for six years as a cleared advisor on the Industry Trade Advisory Committee for forest and paper products (ITAC-7) and was appointed forest products representative to USDA's Agricultural Policy Advisory Committee (APAC) in 2001. Ward holds a Bachelor's degree in History and Political Science from the University of New Hampshire and a Master's degree in International Security Affairs from the School of International Affairs at Columbia University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000062-00018 To: Brown, Byron[[email protected]]; Jackson, Ryan[[email protected]] From: Rebeckah Adcock Sent: Thur 3/30/2017 4:10:52 PM Subject: FW: FINAL CEO Council Meeting Agenda and Materials Pruitt Meeting Materials.pdf ATT00001.htm FYI - final materials for today's meeting. Reb From: "Mary Jo Tomalewski" <[email protected]> To: "Hupp, Sydney" <[email protected]> Cc: "Jay Vroom" <[email protected]> Subject: FINAL Meeting Agenda and Materials Sydney, We have refined our proposed topics for today's CEO Council meeting with the administrator. Attached, please find: Revised "Final Proposed Agenda Topics," which includes the list of those CEO Council members who will attend our meeting today, and their short bios Introduction / Mission Overview of the CEO Council CEO Council Letter to President Trump, dated February 9, 2017 We assume we can skip a formal "round table of introductions" at the beginning of the meeting as our time is short and we want to maximize time spent talking about issues. MJ Mary Jo Tomalewski Executive Assistant to the President & CEO CropLife America Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000063-00001 1156 15th Street, NW Suite 400 Washington, DC 20005 Direct Dial (202) 872-3849 Main Switchboard (202) 296-1585 Mobilé Ex. 6 Personal Privacy Fax (202) 466-5832 Email [email protected] Web www.croplifeamerica.org How can I serve you today? Future Meetings 2017 Spring Regulator Conference - April 6-7, Arlington, VA 2017 Annual Meeting - September 22-27, Dana Point, CA 2018 Winter Board of Directors Meeting - March 5-7, Washington, DC 2018 Annual Meeting - September 21-26, The Ritz-Carlton Amelia Island Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000063-00002 FINAL PROPOSED AGENDA TOPICS Meeting Information: Office of EPA Administrator Scott Pruitt 1200 Pennsylvania Avenue, NW Washington, DC Thursday, March 30, 2017 3:45-4:30 PM Topic 1. Thanks to Trump Administration and Administrator Pruitt for early decisive actions: a. WOTUS b. Chlorpyrifos Petition 2. Top Priority Issues a. Ag Advisor Position - We recommend adding additional title of "Assistant Deputy Administrator" as a title b. Water i. Next steps to refine / clarify beyond WOTUS ii. NPDES permits (CAFO Program needs work; legislation to fix water permits NOT needed for lawful use of pesticides) c. Pesticides Policy i. Endangered Species Act conflicts with Pesticide Regulation and Biotech Regulation ii. Epidemiology Study Policy (as aftermath from Chlorpyrifos matter) iii. Reform Certification & Training and Worker Protection Rules - Suspend implementation and revise d. Renewable Fuels Standard - current program kept consistent e. Communication / Messaging / Opinion Polling - vital to all parties' ability to advance sound policy f. EPA and USDA Cooperation and Coordination - Already vast progress; more can be done! g. Environmental Justice, Research & Development, and Children's Health Offices - Better integration with and reform of EPA program offices; sound science h. Regulation of Manufacturing & Mining Facilities for Ag Inputs - Restore science and process i. Public and Science Advisory Panels at EPA - Balance, strategic agendas j. "Air Emissions" from farming operations CEO Attendees American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Corn Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Barb Glenn, CEO, ex-officio Departments of Agriculture Others American Farm Bureau Federation Dale Moore, Deputy Executive Director Corn Refiners Association John Bode, President & CEO National Farmers Union Rob Larew, Senior VP Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00001 Production Agriculture's CEO Council Introduction/Mission Statement: The production agriculture "CEO Council" coordinates alignment on core issues of modern agricultural systems through telling our story, sharing information and leveraging our strengths, while serving as a resource for government decision makers and others interested in USA food, fiber and renewable fuels. Core Focus of Interest Research and innovation Technology access Science and risk-based regulation Sustainability, environment, and weather Marketability, trade, and economic prosperity Government leadership and partnership with private sector Food access and food safety Plant and animal health Ag labor The Council supports principles/themes): Accelerating rural economic growth and improving productivity through innovation and technology Promoting research and innovation that enables development oftools and techniques necessary for discovering new products that hold tremendous potential for farmers and society at large Enabling a regulatory and commercial environment in which agricultural products are marketable, both domestically and internationally Appropriate balance between Federal and State Governments and a cooperative regulatory approach Access to essential labor in balance with an effective Federal immigration policy and adequate worker safety protections Support for all methods of agricultural production Transparency and dialogue with consumers Members of the CEO Council (see reversed) March 30, 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00002 CEO Council Members American Farm Bureau Vincent "Zippy" Duvall, President American Seed Trade Association Andrew "Andy" LaVigne, President and CEO American Soybean Association Steve Censky, Chief Executive Officer (Co-Chair) Biotechnology Innovation Organization Dana O'Brien, Executive Vice President CropLife America Jay Vroom, President and CEO (Co-Chair) The Fertilizer Institute Chris Jahn, President National Association of Wheat Growers Chandler Goule, CEO National Cattlemen's Beef Association Kendal Frazier, CEO National Chicken Council Michael Brown, President National Com Growers Association Chris Novak, CEO (Co-Chair) National Cotton Council Gary Adams, President and CEO National Council of Farmer Cooperatives Chuck Conner, President and CEO National Farmers Union Roger Johnson, President National Milk Producers Federation Jim Mulhern, President and CEO National Pork Producers Council Neil Dierks, CEO United Fresh Produce Association Tom Stenzel, President and CEO USA Rice Federation Betsy Ward, President & CEO National Association of State Departments of Barb Glenn, CEO, ex-officio Agriculture March 2017 Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00003 February 9, 2017 The President The White House Washington, D.C. 20500 Dear Mr. President, We, the CEO Council (undersigned herein), representing the production agricultural value chain, including many agricultural producers and farm input developers and suppliers, look forward to working with you and your Administration on matters of importance to American agriculture. The challenges we face in agriculture are significant. Many experts emphasize that producers must grow as much food in the next 50 years as was produced over all previous history to meet the demands of our expanding global population. A firm commitment by the U.S. government to aggressively support agricultural innovation and science-based regulatory decisions will be necessary to ensure farmers have the tools they need to produce a safe and abundant supply of nutritious food, in addition to feed, fuel and fiber, in an environmentally sound and sustainable manner. The policy and regulatory environment your Administration establishes can ensure that agricultural innovation flourishes and American farmers are able to meet the food production goals necessary to feed billions more people. We are ready to provide the White House and the Executive Branch Departments and Agencies, as well as Congress, with policy concepts that foster stability in the U.S. agriculture economy with a strong and predictable farm safety net and promotes American competitiveness through research; marketability and trade of agricultural commodities; rural economic growth; and plant, animal, and environmental health, among many other things. We appreciate your attention to these and other issues of value to American production agriculture and food consumers everywhere. Sincerely, American Farm Bureau Foundation, Zippy Duvall American Seed Trade Association, Andy LaVigne American Soybean Association, Steve Censky Biotechnology Innovation Organization, Dana O'Brien CropLife America, Jay Vroom The Fertilizer Institute, Chris Jahn National Association of Wheat Growers, Chandler Goule National Cattlemen's Beef Association, Kendal Frazier National Corn Growers Association, Chris Novak National Cotton Council, Gary Adams National Council of Farmer Cooperatives, Chuck Conner National Farmers Union, Roger Johnson National Milk Producers Federation, Jim Mulhern National Pork Producers Council, Neil Dierks United Fresh Produce Association, Tom Stenzel USA Rice Federation, Betsy Ward Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00004 National Gotton Council OF MERTOA Gary M. Adams President and Chief Executive Officer National Cotton Council of America Gary Adams assumed the position of President and Chief Executive Officer of the National Cotton Council in February 2015. He plays a key role in guiding the industry's seven segments to reach consensus on critical policies affecting U.S. cotton, with the mission of helping all U.S. cotton industry segments compete effectively and profitably in global markets. Prior to that, Gary served the Council for 13 years as the Vice President of Economic and Policy Analysis. As the Council's chief economist, he provided economic outlooks for global cotton markets, as well as analyzing the impacts of farm and trade policies. Gary also represents the U.S. cotton industry as a member of USDA's Agricultural Policy Advisory Committee. Previously, Gary served on USDA's Advisory Committee on Trade from 2005 through 2011 and the NASS Advisory Committee on Agricultural Statistics from 2003 through 2009. Prior to joining the Council, Gary was a Research Assistant Professor in the Department of Agricultural Economics at the University of Missouri. During his 13-year tenure at the university, Gary's primary responsibilities included policy analysis and market outlook for the Food and Agricultural Policy Research Institute, also known as FAPRI. While at FAPRI, Gary and his colleagues were recognized by the American Agricultural Economics Association for their distinguished policy contributions. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00005 Gary has B.S. and M.A. degrees in Applied Mathematics from the University of Alabama. and a Ph.D. in Agricultural Economics from the University of Missouri. Gary and his wife, Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00006 FASA American Soybean Associatión & Stephen L Censky Chief Executive Officer Stephen L. Censky is the American Soybean Association's (ASA) C hief Executive Officer, a staff position he accepted in April 1996. As ASA's top executive, Ce nsky is in charge of managing ASA's legislative, trade policy, membership and education and training programs. The American Soybean Association is a national, not-for-profit commodity organization with over 22,000 members. ASA works as the domestic and international policy advocate for soybean producer members. Prior to joining ASA, Censky worked in Washington, D.C. for ove a decade. He began his career on Capitol Hill as a legislative assistant for agricultural and transportation matters to Senator Jim Abdnor (R-SD). Later he served in both the Reagan and Bush Administrations at the U.S. Department of Agriculture, helping to craft the 1990 Farm Bill and eventually serving as Administrator of the Foreign Agricultural Service where he was involved in global trade negotiations and running our nation's export programs. Censky received his Bachelor's of Science degree of Agriculture from South Dakota State University and his Master's Diploma in Agriculture St of Melbourne, Australia. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00007 NCFC. National Council of Farmer Cooperatives Charles F. (Chuck) Conner President and CEO National Council of Farmer Cooperatives Charles F. (Chuck) Conner became president & CEO of the National Council of Farmer Cooperatives (NCFC) on January 22, 2009. As president of NCFC, Conner will oversee the organization's work to promote and protect the business and public policy interests of America's farmer-owned cooperatives. He will also provide the strategic vision for the trade association as it continues to seek new ways in which to add value for its membership. Prior to joining NCFC, Conner had served as the Deputy Secretary at the U.S. Department of Agriculture since mid-2005. In this capacity, he was the Chief Operating Officer (COO) overseeing day-to-day operations of the department. Conner interacted directly with President George W. Bush and his senior staff to formulate domestic and international food, trade, security and energy policy. He led development of the Bush Administration's $300 billion Farm Bill proposal and the strategy to educate and inform industry, constituents and Congress. From August 2007 to January 2008, Conner served as both USDA Secretary and Deputy Secretary. He played a key role in developing the Administration's immigration policy including important changes to the H2A program. Conner's experience also includes the assignment of Special Assistant to the President, Executive Office of the President, from October 2001 to May 2005, working on the 2001/2 Farm Bill to develop the strategy behind the transfer of several USDA agency functions to the newly formed Department of Homeland Security. From May 1997 to October 2001 Conner served as President of the Corn Refiners Association. He also served for 17 years as an advisor to U.S. Senator Richard Lugar of Indiana. Conner is a graduate of Purdue University, with a Bachelor's of Science degree and is the recipient of Purdue's Distinguished Alumni Award. He and his wife Ex. 6 - Personal Privacy Source: :https://www.industrydocuments.ucsf.edu/docs/ffcn0226_001225_00000065-00008 NATIONAL PORK PRODUCERS COUNCIL Neil Dierks, Chief Executive Officer Neil Dierks is Chief Executive Officer of the National Pork Producers Council (NPPC). In this position, he is responsible for the overall implementation of all NPPC programs. Dierks' position requires him to spend time in both Des Moines, Iowa, the national office of NPPC, and Washington, D.C. Beginning in 1990, Dierks served NPPC in a series of senior executive positions, including Executive Director of Operations, Vice President for Research and Education and Senior Vice President for Programs. Prior to his service with NPPC, Dierks was the Special Activities Director for the Iowa Pork Producers Association and Marketing Director for the Iowa Corn Promotion Board. Neil grew up on a livestock farm in eastern lowa and remains involved in a family farming operation. He is a graduate of Iowa State University. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00009 NASDA Dr. Barbara Glenn recently joined the National Association of State Departments of Agriculture (NASDA) as CEO on August 18, 2014. NASDA is a nonpartisan, nonprofit association which represents the elected and appointed commissioners, secretaries, and directors of the departments of agriculture in all fifty states and four U.S. territories. Dr. Glenn is a scientist with decades of experience as a policy researcher and advocate for agriculture. She previously served as Senior Vice President of Science and Regulatory Affairs for CropLife America, where she was responsible for developing policies and regulations to support agriculture through crop protection. Prior to joining CropLife America, Dr. Glenn served as Managing Director of the Animal Bi otechnology, Food and Agriculture Section of the Biotechnology Industry Association in Washington, DC. Dr. Glenn holds a B.S. in animal science and a Ph.D. in ruminan t nutrition from the University of Kentucky. She previously worked for the U.S. Department of Agriculture, Agric ultural Research Service and the Federation of Animal Science Societies. Born in Lincoln, Nebraska and raised in Centerville, Ohio, Dr. Glenn developed a passion for agriculture from her parents and her involvement in 4-H. She lives on a small farm in Maryland with her husband: Ex. 6 - Personal Privacy and serves on various boards for farm bureau and 4-H. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00010 National Association of Wheat Growers Chandler Goule CEO Chandler Goule assumed his responsibilities as CEO of the National Association of Wheat Growers on July 5, 2016. In addition, he also serves as the executive director of the National Wheat Foundation. Most recently, Goule served as senior vice president of programs at the National Farmers Union (NFU) where he was heavily involved in farm bill legislation. Originally from Texas, Goule holds degrees from Texas A&M and George Washington University and served as a subcommittee staff director for the House Agriculture Committee before moving to the National Farmers Union in 2009 as vice president of government relations. He was appointed senior vice president of NFU programs in 2014. Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00011 The Fertilizer Institute Nourish, Replenish, Grow BIOGRAPHY OF CHRISTOPHER JAHN President The Fertilizer Institute and the Nutrients for Life Foundation Christopher L. Jahn is president of The Fertilizer Institute (TFI), the fertilizer industry's national trade association. As TFI president, Jahn works to represent, promote and protect a sound fertilizer industry through legislative and regulatory activities and to promote a favorable public image of the fertilizer industry and agriculture. Jahn also serves as president of the Nutrients for Life Foundation (NFL). Jahn comes to TFI having served as president of the National Association of Chemical Distributors (NACD) since 2006. Prior to leading NACD, Jahn served as president of the Contract Services Association (CSA). Before joining CSA, Jahn had an active role in the United States Senate working for nearly 10 years for U.S. Senator Craig Thomas (R-Wyo.) in a variety of roles, including legislative assistant, legislative director and Chief of Staff. After graduating from Columbia University with a B.A. in Political Science, Jahn co-founded a book distribution business. He also earned an MBA from the University of Maryland. A native of Wyoming, Chris and his wife Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Capitol View 202.962.0490 425 Third Street, S.W., Suite 950 202.962.0577 fax Washington, DC 20024 www.tfi.org Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00012 National Farmers Union Roger Johnson President Roger Johnson is president of the National Farmers Union (NFU), a grassroots organization that represents more than 200,000 family farmers, ranchers, fisherman and rural communities across the Unites States. Johnson was elected to lead the family farm organization at NFU's 107th anniversary convention in 2009. He has since expanded the education department by providing more programs for beginning, college-aged and women farmers, increased the number of Farmers Union state divisions, and developed a strategic plan for the organization. Johnson has also overseen a number of important policy initiatives important to family farmers including: passage of the 2014 Farm Bill; maintaining a strong Renewable Fuel Standard and Country-of-Origir Labeling, promoting policies that allow farmers to address the growing threat of climate change; and renewing the nation's focus on eliminating an overwhelming trade deficit that results in lost jobs and prosperity for rural America. Prior to leading National Farmers Union, Johnson, a third-generation family farmer from Turtle Lake, N.D., served as North Dakota Agriculture Commissioner, a position he was first elected to in 1996. While Agriculture Commissioner, Johnson served on the State Industrial Commission, the North Dakota Trade Office Advisory Board, and the State Board of Agricultural Research and Education, among many other boards and commissions. From 2007-2008, Johnson served as president of the National Association of State Departments of Agriculture (NASDA). He is a past president of the Midwestern Association of State Departments of Agriculture (MASDA), past president of the Food Export Association of the Midwest and a former chairman of the Interstate Pest Control Compact. Johnson graduated from North Dakota State University with a degree in agricultural economics. Johnson and his wife, Ex. 6 - Personal Privacy Ex. 6 - Personal Privacy Source: https://www.industrydocuments.ucsf.edu/docs/ffcn0226 001225 00000065-00013

What is the Urgent/Immediate Action Commercial of Connecticut?

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187 From: Ed Pfau To: Risotto, Steve Cc: Dourson, Michael (doursoml) Subject: RE: your slides from MSECA Date: Thursday, May 18, 2017 2:36:18 PM Attachments: Pfau Dourson Thompson Using Safety Bange for Risk Mat and Action Levels MSECA 2017-05-04.pdf Steve, Please find attached a pdf of the slides from the recent presentation at MSECA. Michael, Rod and I have a brief draft agenda that has been circulating for comment and revision. I will need to check with my colleagues on its status. We will get a copy to you soon. Please feel free to contact me if you have any questions. Thanks! Ed Pfau PRINCIPAL SCIENTIST HULL I Dublin, Ohio ALTERNATIVE ENERGY I BROWNFIELDS / ENVIRONMENTAL I SHALE OIL & GAS | WASTE MANAGEMENT p: 614.793.8777 f: 614.793.9070 C: 614.579.4749 web I directions to offices From: Risotto, Steve [mailto:[email protected]] Sent: Thursday, May 18, 2017 2:26 1 PM To: Ed Pfau <[email protected]> Cc: Dourson, Michael (doursoml) ([email protected]) <[email protected]> Subject: your slides from MSECA Ed - Can you send me your slides from the presentation at MSECA? Also, do you guys have syllabus or outline for the training sessions that you're contemplating? Some of my members have been asking. Thanks. Steve Steve Risotto | American Chemistry Council Senior Director, Chemical Products & Technology Division [email protected] O: (202) 249-6727 C: (571) 255-0381 https://www.americanchemistry.com This message may contain confidential information and is intended only for the individual named. If you are not the named addressee do not Source: https://www.industrydocuments.ucsf.edu/docs/kqbn0226 188 disseminate, distribute or copy this email. Please notify the sender immediately by email if you have received this email by mistake and delete this email from your system. E-mail transmission cannot be guaranteed to be secure or error-free as information could be intercepted, corrupted, lost, destroyed, arrive late or incomplete, or contain viruses. The sender therefore does not accept liability for any errors or omissions in the contents of this message which arise as a result of email transmission. American Chemistry Council, 700 - 2nd Street NE, Washington, DC 20002, www.americanchemistry.com Source: https://www.industrydocuments.ucsf.edu/docs/kqbn0226 Using the Non-cancer Safety Range to Develop Risk Management Options and Action Levels for TCE Edward J. Pfau, Hull & Associates, Inc. Michael L. Dourson, Risk Science Center at the University of Cincinnati Rod B.Thompson, Indiana University Purdue University Indianapolis Midwestern States Environmental Consultants Association Conference Spring Seminar 2017: Innovative Sampling Strategies and Regulatory Insights on Vapor Intrusion Indianapolis, Indiana: Thursday 4 May 2017 1 Source: https://www.industrydocuments.ucsf.edu/docs/kqbn0226 The Problem: Assessment and Management of Indoor Air Risks Associated with TCE Widely used solvent Common environmental contaminant Fate and transport in the environment Vapor intrusion chemical of concern Current Toxicity Criteria: US EPA IRIS (October 2011) RfC = 0.002 mg/m³ = 2 g/m³ Inhalation Unit Risk = 4.1 X 10-6 (g/m³)- I 2 Source: ittps://www.industrydocuments.ucsf.edu/docs/kqbn0226 TCE Indoor Air Acceptable Exposure Levels Based on IRIS Toxicity Values (October 2011) Based on Residential Land Use HQ = O.I: 0.21 g/m³ HQ = I: 2.1 g/m³ ELCR = I X 10-6: 0.48 g/m³ ELCR = I X 10-5: 4.8 g/m³ ELCR = I X 10-4: 48 g/m³ Based on Industrial Land Use HQ = 0.1: 0.88 g/m³ HQ = I: 8.8 g/m³ ELCR = I X 10-6: 3.0 g/m³ ELCR = I X 10-5: 30 g/m³ ELCR = I X 10-4: 300 g/m³ 3 Source: ittps://www.industrydocuments.ucsf.edu/docs/kqbn0226 Consequences of the Current TCE Toxicity Values (Problem Formulation) Risk-based indoor air levels now based upon non- cancer endpoint (RfC) The RfC is based on both chronic and short-term (developmental) endpoints Prompt/short term exposure action levels Application of lifetime RfC to subchronic and acute exposures Confounding effects of assessing ambient background concentrations of TCE in air Source: Ittps://www.industrydocuments.ucsf.edu/docs/kqbn0226 State and Regional Action Levels Imminent Urgent/Immediate Imminent Action Urgent/Immediate Action Action Commerci State Action Residential Commercial Residential al Alaska 2 8.4 California 6 (24) Connecticut 5 8 Indiana 20 Massachuset ts 6 24 20 60 New Hampshire 2 8.8 New Jersey 4 18 New York 20 Ohio 6.3 26 20 60 Region 09 6 24 Region 10 2 8 Region 7 2 8 Source: ittps://www.industrydocuments.ucsf.edu/docs/kqbn0226 State and Regional Action Levels Imminent Urgent/Immediat Urgent/Immediat Imminent Action e Action e Action Action Commerci State Residential Commercial Residential al Alaska 2 8.4 California 6 (24) Connectiout 5 8 Indiana 20 Massachusetts 6 24 20 60 New Hampshire 2 8.8 New Jersey 4 18 New York 20 Ohio 6.3 26 20 60 Region 09 6 24 Region 10 2 8 Region 7 2 8 6 Source: State and Regional Guidance on Short-term Risk Management of the RfC for TCE EPA Region 7: strict RfC New Hampshire DES: strict RfC EPA Region 9: HQ = 3 California DTSC: HQ = 3 Massachusetts DEP: UF adjustment on FCM RfC Ohio EPA: HQ = 3 / UF adjustment on FCM RfC New York DOH: implicit order of magnitude Indiana DEM: implicit order of magnitude 7 Source: https://www.industrydocuments.ucsf.edu/docs/kqbn0226

What is the Imminent Action Residential of Massachusetts ?

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187 From: Ed Pfau To: Risotto, Steve Cc: Dourson, Michael (doursoml) Subject: RE: your slides from MSECA Date: Thursday, May 18, 2017 2:36:18 PM Attachments: Pfau Dourson Thompson Using Safety Bange for Risk Mat and Action Levels MSECA 2017-05-04.pdf Steve, Please find attached a pdf of the slides from the recent presentation at MSECA. Michael, Rod and I have a brief draft agenda that has been circulating for comment and revision. I will need to check with my colleagues on its status. We will get a copy to you soon. Please feel free to contact me if you have any questions. Thanks! Ed Pfau PRINCIPAL SCIENTIST HULL I Dublin, Ohio ALTERNATIVE ENERGY I BROWNFIELDS / ENVIRONMENTAL I SHALE OIL & GAS | WASTE MANAGEMENT p: 614.793.8777 f: 614.793.9070 C: 614.579.4749 web I directions to offices From: Risotto, Steve [mailto:[email protected]] Sent: Thursday, May 18, 2017 2:26 1 PM To: Ed Pfau <[email protected]> Cc: Dourson, Michael (doursoml) ([email protected]) <[email protected]> Subject: your slides from MSECA Ed - Can you send me your slides from the presentation at MSECA? Also, do you guys have syllabus or outline for the training sessions that you're contemplating? Some of my members have been asking. Thanks. Steve Steve Risotto | American Chemistry Council Senior Director, Chemical Products & Technology Division [email protected] O: (202) 249-6727 C: (571) 255-0381 https://www.americanchemistry.com This message may contain confidential information and is intended only for the individual named. If you are not the named addressee do not Source: https://www.industrydocuments.ucsf.edu/docs/kqbn0226 188 disseminate, distribute or copy this email. Please notify the sender immediately by email if you have received this email by mistake and delete this email from your system. E-mail transmission cannot be guaranteed to be secure or error-free as information could be intercepted, corrupted, lost, destroyed, arrive late or incomplete, or contain viruses. The sender therefore does not accept liability for any errors or omissions in the contents of this message which arise as a result of email transmission. American Chemistry Council, 700 - 2nd Street NE, Washington, DC 20002, www.americanchemistry.com Source: https://www.industrydocuments.ucsf.edu/docs/kqbn0226 Using the Non-cancer Safety Range to Develop Risk Management Options and Action Levels for TCE Edward J. Pfau, Hull & Associates, Inc. Michael L. Dourson, Risk Science Center at the University of Cincinnati Rod B.Thompson, Indiana University Purdue University Indianapolis Midwestern States Environmental Consultants Association Conference Spring Seminar 2017: Innovative Sampling Strategies and Regulatory Insights on Vapor Intrusion Indianapolis, Indiana: Thursday 4 May 2017 1 Source: https://www.industrydocuments.ucsf.edu/docs/kqbn0226 The Problem: Assessment and Management of Indoor Air Risks Associated with TCE Widely used solvent Common environmental contaminant Fate and transport in the environment Vapor intrusion chemical of concern Current Toxicity Criteria: US EPA IRIS (October 2011) RfC = 0.002 mg/m³ = 2 g/m³ Inhalation Unit Risk = 4.1 X 10-6 (g/m³)- I 2 Source: ittps://www.industrydocuments.ucsf.edu/docs/kqbn0226 TCE Indoor Air Acceptable Exposure Levels Based on IRIS Toxicity Values (October 2011) Based on Residential Land Use HQ = O.I: 0.21 g/m³ HQ = I: 2.1 g/m³ ELCR = I X 10-6: 0.48 g/m³ ELCR = I X 10-5: 4.8 g/m³ ELCR = I X 10-4: 48 g/m³ Based on Industrial Land Use HQ = 0.1: 0.88 g/m³ HQ = I: 8.8 g/m³ ELCR = I X 10-6: 3.0 g/m³ ELCR = I X 10-5: 30 g/m³ ELCR = I X 10-4: 300 g/m³ 3 Source: ittps://www.industrydocuments.ucsf.edu/docs/kqbn0226 Consequences of the Current TCE Toxicity Values (Problem Formulation) Risk-based indoor air levels now based upon non- cancer endpoint (RfC) The RfC is based on both chronic and short-term (developmental) endpoints Prompt/short term exposure action levels Application of lifetime RfC to subchronic and acute exposures Confounding effects of assessing ambient background concentrations of TCE in air Source: Ittps://www.industrydocuments.ucsf.edu/docs/kqbn0226 State and Regional Action Levels Imminent Urgent/Immediate Imminent Action Urgent/Immediate Action Action Commerci State Action Residential Commercial Residential al Alaska 2 8.4 California 6 (24) Connecticut 5 8 Indiana 20 Massachuset ts 6 24 20 60 New Hampshire 2 8.8 New Jersey 4 18 New York 20 Ohio 6.3 26 20 60 Region 09 6 24 Region 10 2 8 Region 7 2 8 Source: ittps://www.industrydocuments.ucsf.edu/docs/kqbn0226 State and Regional Action Levels Imminent Urgent/Immediat Urgent/Immediat Imminent Action e Action e Action Action Commerci State Residential Commercial Residential al Alaska 2 8.4 California 6 (24) Connectiout 5 8 Indiana 20 Massachusetts 6 24 20 60 New Hampshire 2 8.8 New Jersey 4 18 New York 20 Ohio 6.3 26 20 60 Region 09 6 24 Region 10 2 8 Region 7 2 8 6 Source: State and Regional Guidance on Short-term Risk Management of the RfC for TCE EPA Region 7: strict RfC New Hampshire DES: strict RfC EPA Region 9: HQ = 3 California DTSC: HQ = 3 Massachusetts DEP: UF adjustment on FCM RfC Ohio EPA: HQ = 3 / UF adjustment on FCM RfC New York DOH: implicit order of magnitude Indiana DEM: implicit order of magnitude 7 Source: https://www.industrydocuments.ucsf.edu/docs/kqbn0226

What is the Imminent Action Commercial of Ohio?

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187 From: Ed Pfau To: Risotto, Steve Cc: Dourson, Michael (doursoml) Subject: RE: your slides from MSECA Date: Thursday, May 18, 2017 2:36:18 PM Attachments: Pfau Dourson Thompson Using Safety Bange for Risk Mat and Action Levels MSECA 2017-05-04.pdf Steve, Please find attached a pdf of the slides from the recent presentation at MSECA. Michael, Rod and I have a brief draft agenda that has been circulating for comment and revision. I will need to check with my colleagues on its status. We will get a copy to you soon. Please feel free to contact me if you have any questions. Thanks! Ed Pfau PRINCIPAL SCIENTIST HULL I Dublin, Ohio ALTERNATIVE ENERGY I BROWNFIELDS / ENVIRONMENTAL I SHALE OIL & GAS | WASTE MANAGEMENT p: 614.793.8777 f: 614.793.9070 C: 614.579.4749 web I directions to offices From: Risotto, Steve [mailto:[email protected]] Sent: Thursday, May 18, 2017 2:26 1 PM To: Ed Pfau <[email protected]> Cc: Dourson, Michael (doursoml) ([email protected]) <[email protected]> Subject: your slides from MSECA Ed - Can you send me your slides from the presentation at MSECA? Also, do you guys have syllabus or outline for the training sessions that you're contemplating? Some of my members have been asking. Thanks. Steve Steve Risotto | American Chemistry Council Senior Director, Chemical Products & Technology Division [email protected] O: (202) 249-6727 C: (571) 255-0381 https://www.americanchemistry.com This message may contain confidential information and is intended only for the individual named. If you are not the named addressee do not Source: https://www.industrydocuments.ucsf.edu/docs/kqbn0226 188 disseminate, distribute or copy this email. Please notify the sender immediately by email if you have received this email by mistake and delete this email from your system. E-mail transmission cannot be guaranteed to be secure or error-free as information could be intercepted, corrupted, lost, destroyed, arrive late or incomplete, or contain viruses. The sender therefore does not accept liability for any errors or omissions in the contents of this message which arise as a result of email transmission. American Chemistry Council, 700 - 2nd Street NE, Washington, DC 20002, www.americanchemistry.com Source: https://www.industrydocuments.ucsf.edu/docs/kqbn0226 Using the Non-cancer Safety Range to Develop Risk Management Options and Action Levels for TCE Edward J. Pfau, Hull & Associates, Inc. Michael L. Dourson, Risk Science Center at the University of Cincinnati Rod B.Thompson, Indiana University Purdue University Indianapolis Midwestern States Environmental Consultants Association Conference Spring Seminar 2017: Innovative Sampling Strategies and Regulatory Insights on Vapor Intrusion Indianapolis, Indiana: Thursday 4 May 2017 1 Source: https://www.industrydocuments.ucsf.edu/docs/kqbn0226 The Problem: Assessment and Management of Indoor Air Risks Associated with TCE Widely used solvent Common environmental contaminant Fate and transport in the environment Vapor intrusion chemical of concern Current Toxicity Criteria: US EPA IRIS (October 2011) RfC = 0.002 mg/m³ = 2 g/m³ Inhalation Unit Risk = 4.1 X 10-6 (g/m³)- I 2 Source: ittps://www.industrydocuments.ucsf.edu/docs/kqbn0226 TCE Indoor Air Acceptable Exposure Levels Based on IRIS Toxicity Values (October 2011) Based on Residential Land Use HQ = O.I: 0.21 g/m³ HQ = I: 2.1 g/m³ ELCR = I X 10-6: 0.48 g/m³ ELCR = I X 10-5: 4.8 g/m³ ELCR = I X 10-4: 48 g/m³ Based on Industrial Land Use HQ = 0.1: 0.88 g/m³ HQ = I: 8.8 g/m³ ELCR = I X 10-6: 3.0 g/m³ ELCR = I X 10-5: 30 g/m³ ELCR = I X 10-4: 300 g/m³ 3 Source: ittps://www.industrydocuments.ucsf.edu/docs/kqbn0226 Consequences of the Current TCE Toxicity Values (Problem Formulation) Risk-based indoor air levels now based upon non- cancer endpoint (RfC) The RfC is based on both chronic and short-term (developmental) endpoints Prompt/short term exposure action levels Application of lifetime RfC to subchronic and acute exposures Confounding effects of assessing ambient background concentrations of TCE in air Source: Ittps://www.industrydocuments.ucsf.edu/docs/kqbn0226 State and Regional Action Levels Imminent Urgent/Immediate Imminent Action Urgent/Immediate Action Action Commerci State Action Residential Commercial Residential al Alaska 2 8.4 California 6 (24) Connecticut 5 8 Indiana 20 Massachuset ts 6 24 20 60 New Hampshire 2 8.8 New Jersey 4 18 New York 20 Ohio 6.3 26 20 60 Region 09 6 24 Region 10 2 8 Region 7 2 8 Source: ittps://www.industrydocuments.ucsf.edu/docs/kqbn0226 State and Regional Action Levels Imminent Urgent/Immediat Urgent/Immediat Imminent Action e Action e Action Action Commerci State Residential Commercial Residential al Alaska 2 8.4 California 6 (24) Connectiout 5 8 Indiana 20 Massachusetts 6 24 20 60 New Hampshire 2 8.8 New Jersey 4 18 New York 20 Ohio 6.3 26 20 60 Region 09 6 24 Region 10 2 8 Region 7 2 8 6 Source: State and Regional Guidance on Short-term Risk Management of the RfC for TCE EPA Region 7: strict RfC New Hampshire DES: strict RfC EPA Region 9: HQ = 3 California DTSC: HQ = 3 Massachusetts DEP: UF adjustment on FCM RfC Ohio EPA: HQ = 3 / UF adjustment on FCM RfC New York DOH: implicit order of magnitude Indiana DEM: implicit order of magnitude 7 Source: https://www.industrydocuments.ucsf.edu/docs/kqbn0226

What is the p-Value of Gamma?

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1.0 Introduction Under the State of California's Proposition 65 (Prop65), a no significant risk level (NSRL) is developed for chemicals that are known to induce cancer in toxicological studies. The NSRL represents the "levels of exposure calculated to result in no more than one excess case of cancer in an exposed population of 100,000, assuming exposure over a 70-year lifetime (10-5 lifetime risk of cancer)" (OEHHA, 1989). California's Office of Environmental Health Hazard Assessment (OEHHA) recently announced its Prop65 notice of intent to list tetrabromobisphenol A (TBBPA) as known to the state to cause cancer. This is likely based on a recent International Agency for Research on Cancer (IARC) assessment that classified TBBPA as "Group 2A: probably carcinogenic to humans" (IARC Monograph in preparation, volume 115 - only the classification is available at the time of publication; Grosse et al., 2016). With the addition of TBBPA to the Prop65, a toxicological evaluation of TBBPA and derivation of an NSRL is needed. The methodology for NSRL derivation is similar to that of the U.S. EPA for developing cancer potency values. An evaluation of the available toxicological data in humans and animals is used to identify a significant biologic response of concern (critical effect) (OEHHA, 1989). In the absence of data to the contrary, noa threshold is assumed for the cancer effect of concern, and OEHHA then develops an NSRL through the use of no- threshold models (cancer slope factor development) based on U.S. EPA guidance (1986, 2005) (OEHHA, 2013). These NSRL values are then compared to exposure estimates to determine the potential to evoke a biological response at relevant environmental exposure levels (margin of safety) (OEHHA, 1989). However, when a threshold in response is supported based on available data, most risk agencies around the World support alternative approaches such as using threshold models. For example, the U.S. EPA (2005) methodology has advanced with the state of risk science, and includes a determination of a linear (non-threshold) or non-linear (threshold) mode of action (MOA) approach. Threshold models suggest that there are low doses of a chemical that do not cause effects and that a high enough dose is needed for effects to occur, while non- threshold models suggest that any dose above zero can lead to an effect (U.S. EPA, 2005). The-One basis for the non-threshold models relates to mutagenic chemicals that cause DNA damage that contribute to carcinogenesis regardless of dose. In fact, identification of mutagenicity mechanisms for cancer development is often a key diagnostic for identification of threshold versus non-threshold mechanisms. This determination impacts the choice of either the derivation of a cancer slope factor and a risk specific dose, or a threshold-based toxicity reference value for cancer effects (RfD 'cancer). TBBPA, a flame retardant chemical that is detected in the environment, albeit at low levels in the U.S., has been extensively studied for a number of years. In order to develop an NSRL, we first reviewed authoritative assessments for TBBPA from regulatory and other agencies to see if an extant cancer risk value had been derived that could be adapted for use as the NSRL. A literature search was conducted from the date of the most recent authoritative review to the present, to identify any new data published since the time of the last review that could inform or update the basis for the NSRL. Data from both the 3 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 authoritative reviews and the published literature were evaluated for toxicological data and mode of action (MOA) information pertinent to cancer development. A risk characterization was then conducted, building off of previous publications, by identification of the critical tumor effect, identification of a point of departure (POD) utilizing Benchmark Dose (BMD) modeling, review of the MOE for tumor formation, derivation of a cancer risk value, and adaptation to an NSRL. 2.0 Methods 2.1 Hazard Identification and Literature Search There are a number of authoritative reviews available from regulatory agencies and others summarizing the toxicology and potential health impacts from exposure to TBBPA. These authoritative reviews were identified through an Internet search in relevant regulatory databases. The Internet was searched by individual key agency web sites, and broadly with ToxPlanet (https://toxplanet.com/). Additionally, an updated literature search was conducted from a few years prior to the date of the most recent review document (Health Canada, 2013), in order to identify any newly published data that could be utilized in derivation of the NSRL. The literature used in this report was in part identified in a systematic literature search in Elsevier Embase, PubMed, and ToxPlanet databases conducted in September, 2016 for the previous 5 years (2011-2016). The results and details of these searches can be found in Table 1. A broad ranging search in each database was initially utilized by searching the chemical name, synonyms, CAS registry number, and relevant acronyms. Data were filtered by limiting to animal or human species. In PubMed, another filter was employed - "NOT preablumin" as this key word was not relevant to toxicology studies but appeared repeatedly in the search results. Identified literature was initially screened and reviewed by title and abstract for content and relevance, and selected literature was subsequently obtained and further reviewed for appropriate data. These studies were reviewed and evaluated in order to determine the most appropriate critical cancer effect for use in deriving the NSRL. Literature regarded as insufficiently reliable for supporting a health conclusion (e.g., inadequate description of methods or data, lack of appropriate dose- response data) were excluded from further consideration. Table 1. Detailed search terms and search strings and resulting number of hits for each database searched to identify literature for use in derivation of the TBBPA NSRL. Database: Search String (see Table 2) No. hits PubMed AI(tetrabromidiphenylolpropane) OR tetrabromodi) OR 6994 tetrabromodi) OR tetrabromobisphenol) OR Tetrabromo-4,4'- isopropylidenediphenol) OR fire guard 2000) OR 79-94-7) OR tbbpa) OR 3,5,3',5'-Tetrabromobisphenol A 4 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 PubMed Added NOT "prealbumin" 863 PubMed (((tetrabromidiphenylolpropane) OR tetrabromodi) OR 135 LAST 5 tetrabromodi) OR tetrabromobisphenol) OR Tetrabromo-4,4'- YRS isopropylidenediphenol) OR fire guard 2000) OR 79-94-7) OR tbbpa) OR 3,5,3',5'-Tetrabromobisphenol A Filter: published in the last 5 years; Animals PubMed E((tetrabromidiphenylolpropane) OR tetrabromodi) OR 78 LAST 5 tetrabromobisphenol a) OR Tetrabromo-4,4' YRS isopropylidenediphenol) OR "Great Lakes BA-59P") OR "BA 59") OR 4,4'-Isopropylidenebis (2,6-dibromophenol)) OR 3,5,3',5'-Tetrabromobisphenol A) OR 2,2',6,6'- Tetrabromobisphenol / A) OR ((79-94-7 OR tbbpa)|) AND "last 5 years"[PDat])) NOT PREALBUMIN Filters: published in the last 5 years; Humans EMBASE tetrabromidiphenylolpropan OR tetrabromodi OR 751 "tetrabromobisphenol a" OR "tetrabromo 4 4 sopropylidenediphenol" OR "4 4 isopropylidenebis (2,6- dibromophenol)" OR "3 5 3 tetrabromobisphenol a" OR "2 2 6 6 Tetrabromobisphenol A" OR 79-94-7 OR tbbpa EMBASE ABOVE (TBBPA STRING) AND ('animal experiment'/de OR 316 'animal tissue'/de OR 'controlled study'/de OR 'correlational study'/de OR 'human'/de OR 'in vivo study'/de OR 'intermethod comparison'/de OR 'nonhuman'/de OR 'normal human'/de OR 'validation process'/de OR 'validation study'/de) AND (2011:py OR 2012:py OR 2013:py OR 2014:py OR 2015:py OR 2016:py OR 2017:py) ToxPlanet TBBPA; 79-94-7 91 As detailed below, due to the lack of available cancer studies other than the NTP (2014) 2-year cancer bioassay, this study was chosen for use in identification of the critical effect. Additional authoritative review papers and published literature (described below) were evaluated to gain an understanding of the noncancer effects of TBBPA as well as the potential MOA for tumor formation. 2.2 Dose-Response Analysis to Derive Point of Departure Benchmark dose (BMD) modeling (BMDS 2.6; U.S. EPA, 2012) was used to evaluate the dose-response relationship between exposure to TBBPA and cancer outcomes. As detailed below, adenoma, adenocarcinoma, or malignant mixed Mullerian tumors 5 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 (MMMTs) (combined) of the uterus identified through both original and residual longitudinal reviews [see Table 2 of Dunnick et al. (2015); NTP (2014)] were modeled to identify a POD. Atypical hyperplasia of the endometrium was also considered [see Table 6 of NTP (2014)]. All standard dichotomous models were considered. BMDs corresponding to 10% extra risk, the benchmark response (BMR), and their 95% lower bounds (BMDLs) were determined. All BMD modeling was done using extra risk. Model parameters were restricted when possible; not all models offer an option for the restriction of the slope or power. The POD reported is the duration-adjusted dose (i.e., the dose x 5/7, to account for dosing on only 5 of 7 days/week). The criteria described in EFSA (2017) as measures of model acceptability are the goodness-of-fit p-value, BMD to BMDL ratio, and the Akaike Information Criterion (AIC). U.S. EPA's BMDS guidance document for interpreting modeling results recommends adequacy determinations based on p-value, scaled residuals, visual fit, consideration of variability among BMDLs across the candidate models, AIC, and professional judgment (U.S. EPA, 2012). Because U.S. EPA's criteria are more inclusive, we discuss each of these in turn. The decision statements below, e.g., what constitutes adequate fit, are based on and adapted from the U.S. EPA guidance. The first criterion is the global statistical goodness of fit test that represents the full dose range of the data. If the p-value is >0.1, then the model is considered to adequately fit the data. Values lower than 0.1 suggest that the model may be statistically significantly different than the data, with values of 0.05 or less decidedly so. Models with values lower than 0.1 are usually rejected. Models with values of 0.05 or less would be rejected unless special circumstances existed, such as a mechanistic motivation for the model. However, models with higher p-values are not necessarily better than models with lower p-values (say, p = 0.5 versus p = 0.2) if both have a p-value >0.1, which is why other criteria, described below, are then used. The second criterion; relatedto-iseal-fit-is the difference in scaled residuals (that is, the difference in the modeled estimate compared with the actual data scaled by the standard error) at the data point closest to the BMR (in this case, 10%), where it is most important that the model fits the data. A scaled residual of 0 means that the model aligns perfectly with the data at that point, although any scaled residual with an absolute value of less than 2 is acceptable. Models with residuals that have an absolute value greater than this value are rejected. Models with lower residuals are usually preferred. U.S. EPA has recently added a scaled residual at the zero dose to one output format for its BMDS software. This parameter may also prove to be useful for future evaluations. The third criterion, related to scaled residuals, is the visual fit. Arguably the least quantitative criterion, visual fit nevertheless allows consideration of how well the model fits the underlying data, especially at the lower end of the curve or how well the model reflects the biological mode of action, if known. Designations of visual fit can include good, acceptable, and poor. Models that have "poor" visual fit should be rejected. Models with good visual fits are generally preferred. 6 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 U.S. EPA's fourth criterion is two-fold. The first part asks whether the BMDL estimates from the remaining models are sufficiently close to each other and reflect no particular influence of the individual models. This emphasizes that the goal of the modeling is to calculate a BMDL. One way to view this is to compare the ratios between the BMD and BMDL among the models. The larger the ratio, the less accurate the model is likely to be. Another useful comparator in previous U.S. EPA guidance was to decide that model-dependence is evident if the BMDLs differed by more than a factor of 3, but this specificity was removed as being too prescriptive (Jeff Gift, U.S. EPA, personal communication). The second part of this fourth criterion is the Akaike Information Criterion (AIC). Of the remaining models, the one chosen will generally have the lowest AIC. However, AICs within a value of 2 of each other are considered to be similar. If several models are still available from which to choose, then the lowest BMD and BMDL can be selected as a conservative choice, or the BMDs and BMDLs of several models can be averaged¹, using either an arithmetic or geometric mean. Such an average BMDL, however, loses its statistical properties, i.e., it is not the 95% lower bound on the average BMD. 2.3 Derivation of NSRL Once the point of departure (POD) was derived using BMDS, standard risk assessment guidance was utilized for the derivation of and cancer risk value and adaptation to an NSRL based on the U.S. EPA and OEHHA methodology (U.S. EPA, 2005; OEHHA, 1989). We first adjusted the POD to a human equivalent dose using allometric scaling (Equation 1). Because the weight-of-evidence for mode of action (MOA) for tumor formation identified did not involve direct DNA interaction, traditional linear cancer slope factor derivation was not conducted (Wikoff et al., 2015, 2016; NTP, 2014). Instead, an RfD. cancer was derived for a non-linear threshold response following the guidance of U.S. EPA (2005). This includes an assessment of the uncertainty associated with the POD and the application of uncertainty factors (Equation 2). Uncertainty factors are used to add conservatism and additional safety to the RfDc: given unknowns about the chemical, to account for data gaps, such as animal to human uncertainty, subchronic to chronic exposures, and to account for intra-individual variability. The derived RfDcancer was then converted to an NSRL by adjusting for body weight (Equation 3). Equation 1. DoseH = Dosea x Where 1Note that this is not the same as model averaging, where the individual model results are combined by using weights, with higher weights for models that fit the data better (Wheeler and Bailer, 2007). 7 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 DoseH = dose in human (BMDL10[HED]) Dosea = dose in animal (the POD for the specified critical effect = BMDL10) BWA = body weight of animal (0.268 kg for control female Wistar from NTP) BWH = body weight of human (70 kg²) Equation 2. RfD cancer = BMDL10[HED/(UFH x UFAX UFs x UFLX UFD) Where BMDL10[HED = benchmark dose lower limit human equivalent dose UFH = uncertainty factor for human variability UFA = uncertainty factor for animal to human extrapolation UFs = uncertainty factor for subchronic to chronic extrapolation UFL = uncertainty factor for LOAEL to NOAEL UFD = uncertainty factor for database completeness Equation 3. NSRL (mg/day) = RfDcance (mg/kg-day) x BWH (kg) Where BWH = body weight of human (70 kg) 3.0 Results 3.1 Literature search results Authoritative reviews identified include the National Institute of Environmental Health Sciences (NIEHS, 2002), the European Union (EU, 2006), the European Commission Committee on Toxicology (COT, 2004), the European Food Safety Authority (EFSA, 2 The body weight of 70 kg is the default body weight for males used by OEHHA as listed in the California Code of Regulations (27 CCR § 25703, 27 CA ADC § 25703; OEHHA, 2013). However, the recommended body weight for females is 58 kg, which is the specific subpopulation of interest, as uterine tumors were identified as the critical effect. We chose to use the 70 kg default as the body weight because: 1) it is more conservative (results in a slightly lower HED) than 58 kg; 2) women in the U.S. tend to be heavier; 3) 70 kg was utilized in most of the previous NSRL documents that we reviewed; and 4) due to the nature of the assessment, the difference between 70 kg and 58 kg is not enough to significantly change the final NSRL value (within an order of magnitude). 8 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 2011), and Health Canada (2013). At the time of this publication, the IARC monograph on TBBPA was unavailable for public review, and only the classification was available (Grosse et al., 2016). The above mentioned and available authoritative regulatory toxicity reference values for cancer (and noncancer) effects for TBBPA were evaluated. However, of these authoritative reviews, only two oral toxicity reference values were derived (ECHA, 2017; COT, 2004). Our literature search identified three additional recently published papers that derived risk values for TBBPA (Wikoff et al., 2015; Yang et al., 2016; Colnot et al., 2014). All values were evaluated for relevance in adapting for use as the NSRL. Data were also mined from the two most recent authoritative reports (EFSA, 2011; Health Canada, 2013) relating to standard toxicological endpoints and agency conclusions on the potential for adverse health effects on humans. All publically available data were reviewed, synthesized, and, in the absence of an available cancer risk value for TBBPA from the authoritative agencies, a cancer risk value was derived and the OEHHA methodology was applied to translate this value into an NSRL. The literature search identified a carcinogenicity study of TBBPA by the U.S. National Toxicology Program (NTP, 2014), and associated published studies that evaluated these NTP (2014) tumor findings and the TBBPA cancer MOA (Dunnick et al., 2015; Wikoff et al., 2015; Harvey et al., 2015; Sanders et al., 2016; Lai et al., 2015; Wikoff et al., 2016; Hall et al., 2017). These data are pertinent as the lack of cancer data was identified as a data gap for developing a cancer potency value as reported in the most recent authoritative reviews for TBBPA (EFSA, 2011; Health Canada, 2013). Further studies were identified investigating non-cancer effects related to inhalation toxicity, dermal absorption, thyroid hormone disruption, endocrine activity, developmental toxicity, and neurotoxicity. Additional toxicokinetic studies reported the disposition and kinetics of TBBPA in rats and one investigated toxicokinetic parameters in humans. 3.2 Authoritative and Published Risk Values for TBBPA 3.2.1 Toxicity Reference Values Toxicity reference values for TBBPA from various agencies are summarized in Table 2. The UK Committee on Toxicity (COT, 2004) derived a tolerable daily intake (TDI) for oral exposure of 1 mg/kg-day for chronic exposure in the general population. This TDI was based upon a NOAEL of 1,000 mg/kg-day in an unpublished two-generation reproductive toxicity study and in an unpublished 90-day study (MPI Research, 2002a,b, as cited in COT, 2004). The COT applied a composite uncertainty factor of 1,000 based on 10 for human to animal (UFA), 10 for human variability (UFH), and 10 for database deficiencies (UFD). ECHA (2017) developed a derived no effect level (DNEL) for long-term systemic effects following oral exposure for the general population. The oral DNEL of 2.5 mg/kg-day available on the ECHA website does not provide enough detail to determine the NOAEL used or the uncertainty factors applied to derive the value. Colnot et al. (2014) reported four oral DNELs, two for the general population based on different endpoints (thyroid effects and no effect in a 90-day study) and two for reproductive endpoints (fertility and development). The lowest oral DNEL of 0.16 mg/kg-day was based on a BMDL10 of 16 mg/kg-day for thyroid hormone changes after application of a 100-fold uncertainty factor 9 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 (UFA = 10, UFH = 10). Two recently published reference values for TBBPA were identified in the literature search (Yang et al., 2016; Wikoff et al., 2015) (Table 2). Yang et al. (2016) compared previous PODs available in the literature for TBBPA with a POD generated in their own study investigating TBBPA toxicity to thyroid hormones. However, due to a lack of some methodological details in the publication, the Yang et al. (2016) assessment was not used in supporting the derivation of a cancer risk value. For example, the authors do not discuss the uncertainty factors used to derive the RfD or the details of the BMD model outputs and rationale for model choice. Without these methodological details, there is not enough information provided to assess the validity of the proposed RfD. In the other assessment, Wikoff et al. (2015) developed a number of non-cancer and cancer toxicity reference values, including an oral RfD, an oral cancer slope factor, an average daily dose estimate, and evaluated the margin of exposure (MOE) and margin of safety (MOS) based on these risk values. These toxicity reference values were based on the recent NTP 2-year bioassay in rats and mice (NTP, 2014) and followed standard U.S. EPA methodology including the use of BMD modeling (U.S. EPA, 2012). Wikoff et al. (2015) conducted a comprehensive literature search to identify published and unpublished TBBPA toxicity studies that identified a dataset of studies to review followed by an evaluation of study quality using Klimisch scoring that narrowed the database to the most relevant high quality studies (Klimisch et al., 1997). The authors then selected the NTP (2014) 2-year carcinogenicity assay from the high quality studies and identified the most sensitive cancer and non-cancer endpoints for their choice of PODs (Wikoff et al., 2015). For the noncancer RfD, Wikoff et al. (2015) selected female rat uterine hyperplasia from the 2-year NTP bioassay as the critical effect. The data were modeled using BMDS to derive a BMDL10 of 72.8 mg/kg-day and after adjustment for allometric scaling to humans, resulted in a human equivalent dose (HED) of 18.2 mg/kg-day. Using this POD, a composite uncertainty factor of 30 was applied (UFA = 3, UFH = 10) resulting in an RfD of 0.6 mg/kg-day. It is worth noting that the BMD model applied (unspecified in the publication) had poor fit (P = 0.08) even after dropping the high treatment dose (Wikoff et al., 2015). For cancer endpoints, Wikoff et al. (2015) considered uterine tumors from the NTP (2014) study as the most appropriate endpoint for use in derivation of a cancer toxicity value. Wikoff et al. (2015) applied the linear multistage BMD model to the duration- adjusted doses for the cancer dataset. Their BMDL10 was 127 mg/kg-day, and after adjustment for allometric scaling to humans, resulted in an HED of 31.7 mg/kg-day. Using this POD, the cancer slope factor was calculated to be 0.0032 per mg/kg-day, which corresponds to a risk specific dose (RSD) at the 10-5 level of 0.0032 mg/kg-day (Wikoff et al., 2015). This value has been through a quality assurance review and is posted on the International Toxicity Estimates for Risk (ITER) database, which is found on the U.S. National Library of Medicine's TOXNET (https://www.nlm.nih.gov/pubs/factsheets/toxnetfs.html). Only the Wikoff et al. (2015) toxicity reference values characterized the cancer human 10 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 health risks of exposure to TBBPA (Table 2). Several organizations concluded that there were not sufficient data available to derive cancer or noncancer toxicity reference values (prior to publication of the NTP report), and many applied a MOE approach. A MOE can be defined as the magnitude by which the POD (e.g., the NOAEL) of the most sensitive relevant toxic effect exceeds the estimated exposure (Barnes and Dourson, 1988). 11 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Table 2. Toxicity values identified in the literature for the general population and breakdown of how each value was derived. Reference CTV* Value Exposure Critical Effect Key Study Point of departure Composite Adjustment duration, Factor (individual route adjustments) ECHA, DNEL 2.5 mg/kg- Chronic, Unidentified, however Mice, oral NOAEL = 250 100 (UFA = 10, UFH = 10) 2017 day oral the registration dossier gavage (study mg/kg-day states "a chronic study citation not is used to set a chronic clear) DNEL. No correction required". Rats, Colnot et 5 mg/kg- Chronic, DNEL No reproductive/ oral gavage NOAEL = 1,000 200 (UFA = 10, UFH = 10, UFs (MPI al., 2014 day oral developmental effects Research, mg/kg-day = 2) 2002b) 0.16 Rats, dietary Colnot et DNEL, Chronic, Thyroid hormone (Van BMDL10 = 16 mg/kg- al., 2014 oral mg/kg- changes der Ven et 100 (UFA = 10, UFH = 10) oral day day al., 2008) Rats, oral Colnot et DNEL, 10 mg/kg- Chronic, No reproductive/ gavage (MPI NOAEL = 1,000 100 (UFA = 10, UFH = 10) al., 2014 oral day oral fertility effects Research, mg/kg-day 2001) Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 COT, TDI 1 mg/kg- Chronic, No embryotoxic / Rats, oral NOAEL of 1,000 1,000 (UFA = 10, UFH = 10, 2004 day oral teratogenic effects: gavage (MPI, mg/kg-day UFD = 10) effects 2002b) Wikoff et RfD 0.6 mg/kg- Chronic, Uterine endometrial Rats, oral BDML10 72.8 30 (UFA = 3; UFH = 10) al., 2015 day oral atypical hyperplasia gavage (NTP, mg/kg-day NSRL for cancer precursor 2014) HED - 18.2 mg/kg- effect for 70 kg human = 42 day mg/kg-day Pecquet et RfDcance 0.9 mg/kg- Chronic, Uterine tumors Rats, oral BDML10 102.5 30 (UFA = 3; UFH = 10) al., 2017 r day oral gavage (NTP, mg/kg-day NSRL for 70 kg human = 60 (this 2014) HED - 25.6 mg/kg- mg/kg-day paper) day Wikoff et Cancer 0.00315 Chronic, Uterine tumors Rats, oral BMDL10 126.6 RSD at 10-6 = 0.0032 mg/kg- al., 2015 slope mg/kg-day oral gavage (NTP, mg/kg-day day factor 2014) HED - 31.7 mg/kg- NSRL for 70 kg human = 0.22 day mg/kg-day * CTV = Chronic Toxicity Value? 13 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 3.3 Summary of TBBPA toxicology In order to understand the potential for toxicity from TBBPA exposure, the noncancer and cancer toxicity findings from recent authoritative agencies were reviewed. Overall, TBBPA is expected to have very low systemic noncancer toxicity, with low hazard for developmental or reproductive toxicity, as reviewed and reported in multiple regulatory and other published reports (ECHA, 2017; EFSA, 2011; Health Canada, 2013; NTP, 2014; Colnot et al., 2014; U.S. EPA, 2014; Cope et al., 2015; etc.). 3.3.1 Genotoxicity and Cancer EFSA (2011) found no in vivo studies available to assess the genotoxicity of TBBPA, and Health Canada (2013) identified no structural activity data suggesting TBBPA might be genotoxic. Further, a number of in vitro studies, such as several Ames tests and mutagenicity assays, a chromosomal aberration assay, a recombination assay, a sister chromatid exchange in Chinese hamster ovary (CHO) cells, and a rat hepatocyte unscheduled DNA synthesis assay were evaluated, all with negative findings (EFSA, 2011; Health Canada, 2013; Colnot et al., 2014). These data were supported by structure activity relationship data, where no structural alerts for genotoxicity were identified and a lack of suitable analogs were available for use in read-across (U.S. EPA, 2014). The overall WOE indicates that TBBPA does not exert genotoxic or mutagenic effects. EFSA (2011) and Health Canada (2013) also assessed studies to investigate the potential carcinogenicity of TBBPA. At the time of these reports, no long-term carcinogenicity data were available for TBBPA. Based upon the WOE that TBBPA was non-genotoxic in vitro (EU, 2006; EFSA, 2011) and that there was no significant evidence of carcinogenic potential in repeat dose toxicity tests, EFSA (2011) concluded that TBBPA was not likely a carcinogen. One study reported non-malignant tumors in response to oral TBBPA administration, including non-dose-responsive transitional cell papillomas in the urinary bladder that did not progress to malignancy, and thyroid follicular adenomas (Imai et al., 2009, as cited in EFSA, 2011). Colnot et al. (2014) discuss the available data and conclude that the thyroid tumors are unsuitable for use in human risk assessment on the basis on species sensitivity differences between rodents and humans. Health Canada (2013) concluded that the effect of TBBPA on thyroid hormones remains unclear, and therefore utilized a MOE approach to show that current human exposures are below those that are likely to produce thyroid effects. COT (2006) discussed a lack of consistency in the available thyroid data and the potential for the effect to be reversible. Additionally, neither thyroid tumors nor thyroid histopathology effects were seen in rats or mice treated in the 2-year NTP assay (NTP, 2014; Lai et al., 2015). However, EFSA (2011) identified disrupted thyroid homeostasis as the critical noncancer effect in their MOE analysis. There was only one cancer bioassay identified in our literature search; the 2-year cancer bioassay conducted by NTP (2014) in rats and mice exposed to 0, 250, 500, or 1,000 mg/kg for 5 days a week via oral gavage in corn oil. These study details and results have been extensively reported elsewhere (NTP, 2014; Dunnick et al., 2015; Lai et al., 2015; Wikoff et al., 2015, 2016; U.S. EPA, 2014). The primary tumors identified were uterine tumors (combined adenoma, adenocarcinoma, and malignant mixed Mullerian) in female Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 rats (U.S. EPA, 2014). Other tumors included testicular tumors in male rats; and in male mice hepatic tumors, hemangiomas/hemangiosarcomas, and intestinal tumors were found (U.S. EPA, 2014). The Cancer Assessment Review Committee (CARC) of the U.S. EPA determined TBBPA as "likely to be carcinogenic to humans" based on the female rat uterine tumors and the male mice hemangiomas/hemangiosarcomas, with no mutagenicity concerns (U.S. EPA, 2014). NTP (2014) reached the following conclusions regarding each of these tumor types: Testicular adenomas in male rats: "equivocal evidence of carcinogenic activity" Uterine epithelial tumors in female rats: "clear evidence of carcinogenic activity", Hepatoblastomas in male mice: "some evidence of carcinogenic activity"; Intestinal tumors and hemangiosarcomas: may have been related to chemical administration. 3.4 TBBPA uterine cancer mode of action and weight of evidence analysis The U.S. EPA (2005) guidelines for cancer risk assessment state that the MOA should be evaluated in determining the quantitative approach for dose-response assessment from positive human or experimental animal tumor data. This evaluation is accomplished by proposing a MOA including identification of key events, where data on these key events includes available in vivo, in vitro, and mechanistic studies. These studies are then evaluated relative to the modified Bradford Hill criteria, including strength, consistency, specificity of the association between the key event(s) and tumor outcomes, as well as consideration of the consistency of the dose-response and temporal relationship between the key event and tumors, biological plausibility of the proposed MOA, and coherence of the overall database (Meek et al., 2014). When sufficient data are available, a biologically based dose-response (BBDR) model is the preferred method for low dose extrapolation. Absent such data, U.S. EPA (2005) and other groups such as OEHHA (2013) usually conduct a low-dose extrapolation with a linear model if the chemical acts via a direct DNA-reactive MOA or if the MOA is not known, or via a threshold model based on one or more combinations of relevant tumors for a non-DNA-reactive MOA. Other authoritative groups often rely on a MOE approach for cancer evaluation. However, all these groups support the use of the best available science, including consideration of MOA, in their assessments. An abbreviated MOA and WOE analysis was previously applied by Wikoff et al. (2016) to inform the quantitative approach for derivation of a cancer risk value. In the NTP 2- year TBBPA bioassay, and as evaluated by Wikoff et al. (2015), uterine tumors in rats were identified as the most appropriate endpoint for use in derivation of a cancer toxicity value. Based on the considerable amount of evidence that TBBPA is not mutagenic, a nonlinear MOA was postulated for TBBPA induced uterine tumors based on interference with estrogen metabolism, as discussed by several authors (Borghoff et al., 2016; Lai et al. 2015; Sanders et al., 2016; Wikoff et al., 2015; Dunnick et al., 2015; Harvey et al., 2015; Hall et al., 2017), most comprehensively by Wikoff et al. (2016). The interference with estrogen is not thought to involve TBBPA binding directly to the estrogen receptor (ER). The weak affinity for the estrogen receptor and other in vitro and in vivo studies 15 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 suggests that TBBPA is not estrogenic (Colnot et al, 2014; Lai et al., 2015; Wikoff et al., 2016). Estrogenic effects of TBBPA are controversial since both negative and positive findings are reported in the literature, but the low TBBPA binding affinity to the ER suggests that TBBPA is not directly interacting with this receptor (Lai et al., 2015). Instead, interference with estrogen metabolism via competition for shared biotransformation pathways (glucuronidation and sulfation) is a plausible mechanism, resulting in increased estrogen concentrations that either disrupt hormonal balances or drive estrogen-induced cellular proliferation (Lai et al., 2015). Wikoff et al. (2016) proposed an adverse outcome pathway and presented data for a number of key events, including a WOE analysis for TBBPA induced uterine cancer (Figure 1; adapted from Wikoff et al., 2016). The proposed key events starting with the molecular initiating event are the following: 1) TBBPA binds to estrogen sulfotransferase (sultlel), which inhibits the estrogen sulfation pathway; 2) this inhibition of estrogen sulfation leads to increased estradiol bioavailability; 3a) increased estrogen leads to increased expression of estrogen responsive genes, 3b) alternative estrogen metabolic pathways are activated causing generation of reactive quinones and other reactive species that can interact with DNA, and 3c) potential for disruption of the hormonal balance (with potential for disrupted endocrine signaling); 4) interaction of estrogen responsive genes contributing to cellular proliferation of cells with increased DNA damage and p53 mutations; and 5) hyperplasia of cells leading to the adverse outcome (uterine tumors). These key events and supporting data are extensively discussed in Wikoff et al. (2016), and so are only briefly described below. 16 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Figure 1. Diagram of postulated mode of action for TBBPA-induced uterine tumors. [1] TBBPA binds to estrogen sulfotransferase (sultle1); [2] the estrogen sulfation pathway is inhibited; [3a] bioavailable estrogen can bind the estrogen receptor (ER), which translocates to the nucleus and leads to increased expression of estrogen responsive genes, [3b] alternative estrogen metabolic pathways (such as cytochrome P450s, CYPs) can generate reactive intermediates that can interact with DNA and cause DNA damage; [4] estrogen responsive genes contribute to cellular proliferation of cells, some of which have increased DNA damage and gene mutations. & de SK 22222 Suittes [1] ca s TBBPA [2] CHAPH ER I ER 1 [3a] 13 HO is - Estrogen - NO [3b] [4] on CH.9 [4] , HO 1) TBBPA binds to estrogen sulfotransferase (sultle1). which inhibits the estrogen sulfation pathway Toxicokinetic evidence exists that shows TBBPA utilizes the same sulfation metabolic pathway as estrogen (sultle1). Metabolites in humans include TBBPA-sulfate (Schauer et al., 2006, as cited in Health Canada, 2013; Ho et al., 2017). Computational modeling and quantitative structure activity relationship (QSAR) analysis suggest that TBBPA is structurally able to inhibit sulfotransferase (Wikoff et al., 2016; Gosavi et al., 2013). Additionally, in vitro IC50S for TBBPA inhibition of estradiol sulfotransferase ranges from 12-33 nM (Wikoff et al., 2016; Kester et al., 2002; Gosavi et al., 2013; Hamers et al., 2006, as cited by Borghoff et al., 2016). Thus, when high doses of TBBPA produce high plasma concentrations of TBBPA, the IC50 for sulfotransferase is surpassed and saturation can occur. For example, in vivo studies show that TBBPA doses as low as 50 mg/kg result in plasma concentrations (1,478 nM TBBPA) well above the reported IC50 values (Wikoff et al., 2016; Borghoff et al., 2016). 17 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Taken together with the in vitro data, inhibition of sulfotransferase activity is a plausible molecular initiating event in the mode of action for TBBPA induced uterine cancer (Wikoff et al., 2016). However, more data are required to support this key event, as target tissue dosimetry and temporal relationships are required to determine if TBBPA inhibits sulfotransferase in the uterus (Osimitz et al., 2014). 2) Inhibition of estrogen sulfation leads to increased estradiol bioavailability The binding of estrogen to estrogen sulfotranserase (sultle1) leads to its biotransformation by conferring a sulfate group. When TBBPA interferes in this pathway, estrogen is not biotransformed, meaning more estrogen should be bioavailable systemically. This bioavailable estrogen could result in increased estrogen receptor (ER) activation, metabolic switching to an alternative estrogen metabolic pathway, or imbalance of the estrogen/progesterone ratio that has been implicated in other tumor types (mammary, prostate) (Lai et al., 2015). However, there are currently no data on TBBPA modification of estrogen/progesterone ratios (Lai et al., 2015). Alternatively, the loss of estrogen sulfotransferase might result in increased plasma estrogen levels that are implicated in the development of estrogen dependent human endometrial cancer (Cornel et al., 2017). There are a paucity of data investigating TBBPA exposure resulting in increased estrogen bioavailability, although theoretically, competition for sulfation of estrogen would reduce estrogen-sulfate conjugates, resulting in bioavailable estrogen able to bind to the ER (sulfated estrogens are not able to bind the ER) (Fu et al., 2011). This increased non- sulfated, bioavailable estrogen could also shift the estrogen metabolic pathway to alternatives that can result in the generation of reactive species (Wikoff et al., 2016). However, Sanders et al. (2016) reported unchanged estrogen serum levels following 5 daily gavage doses of TBBPA at 250 mg/kg, although they note that the duration of exposure might have been insufficient to produce changes and that use of serum estrogen levels serve as a poor proxy for endometrium estrogen levels. While this step is biologically plausible, more data are needed for a definitive conclusion. 3a) Increased estrogen leads to increased expression of estrogen responsive genes, 3b) alternative estrogen metabolism causing generation of reactive quinones that can interact with DNA, and 3c) potential for disruption of the hormonal balance (with potential for disrupted endocrine signaling) Wikoff et al. (2016) discuss evidence related to increased estrogen and TBBPA-induced increases in estrogen responsive genes in tissues other than the uterus. Since the time of the Wikoff publication, an additional study was published that investigated changes in estrogen concentration and gene expression in response to TBBPA. In a repeat-dose oral gavage study, adult female Wistar Hans rats were treated with vehicle or TBBPA (250 mg/kg-day) for 5 consecutive days to investigate the role of estrogen homeostasis in the MOA of TBBPA (Sanders et al., 2016). In tissue samples taken 24 hours after the 5-day treatment, T4 serum levels were decreased but serum estrogen levels were unchanged. While estrogen levels were not measured in the uterus, there were changes in expression of genes in the uterus that are markers of cell division/growth and metabolism of 18 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 TBBPA/estrogen/thyroid hormones. The gene expression changes in both the proximal and distal sections of the uterus with the greatest significance included genes involved with metabolism and hormone binding, including significantly increased levels of ERa and ERB (Sanders et al., 2016). This data partially supports an increase in estrogen responsive genes from TBBPA exposure, however, more data is needed to show that this is directly resultant from increased bioavailable estrogen, and more data are need to identify these changes specific to uterine tissues. Wikoff et al. (2016) discuss estrogen homeostasis as a balance of various metabolic pathways. Once one pathway is disrupted, alternative estrogen metabolism pathways (other than sulfation) may compensate. One of these pathways, the catechol estrogen pathway, results in the oxidation of catechol estrogens with reactive quinone intermediates. These reactive quinones can interact with DNA, and have been implicated in some cancers (Wikoff et al., 2016). For example, these intermediates could be leading to DNA interactions that could contribute to or selectively increase the proliferation of altered genes, such as the tumor suppressor p53 gene. Finally, there is a potential contribution of disrupted endocrine signaling via hormonal imbalance. Increased estrogen levels have the potential to modify the estrogen/progesterone ratio, and this imbalance has been implicated in other tumor types (mammary, prostate, estrogen dependent human endometrial cancer) (Lai et al., 2015, Cornel et al., 2017). However, there are currently no data on TBBPA modification of estrogen/progesterone ratios (Lai et al., 2015). 4) Interaction of estrogen responsive genes contributing to cellular proliferation, and increased DNA damage and p53 mutations Cellular proliferation is a critical component of hyperplasia leading to tumor formation. It is well established that estrogen binding to the ER can lead to cellular proliferation, and induction of genes related to cell cycle regulation (Sanders et al., 2016). In the NTP (2014) bioassay, there was a clear dose-response with increased uterine adenocarcinomas/adenoma at each increased TBBPA dose; however, data are lacking to confirm temporal associations specifically between increased estrogen serum levels and incidence of cellular proliferation in uterine tissues (Lai et al., 2015). High doses of TBBPA may in part promote uterine tumors in rats by promoting growth of cells with pre-existing mutations in the p53 tumor suppressor gene driven by increased estrogen-dependent cellular proliferation, or through selective proliferation of these mutations caused by reactive quinone intermediates (NTP, 2014; Lai et al., 2015). Additionally, as noted above, TBBPA has low affinity for the ER and so is not likely acting directly on the ER itself. This is plausible as significantly increased p53 mutations were identified in tumors in the NTP study, but since TBBPA is non-mutagenic, TBBPA itself is not directly causing the p53 mutations (Lai et al., 2015). The mechanism of p53 mutation has been previously implicated in cancer development, including human endometrial cancers (Harvey et al., 2015; Wikoff et al., 2016). Harvey et al. (2015) reported on an evaluation and analysis of TBBPA-induced uterine carcinomas in female rats from the NTP study. Analysis using PCR found a high rate of p53 mutations suggesting that uterine carcinogenesis might be partially p53 dependent (Harvey et al., 19 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 2015). In this analysis, the TBBPA-treated samples included Wistar Han rat uterine carcinomas from all dose groups combined (250, 500, and 1,000 mg/kg), thus no p53 mutation dose-response data are available. Of interest, the analysis did not include the malignant mixed Müllerian tumors (MMMTs). While this data supports the proposed key event, more data are needed, specifically dose-response data for p53 mutations and increased proliferation in response to TBBPA, to confirm this. 5) Hyperplasia of cells with p53 mutations leading to the adverse outcome (uterine tumors) Hyperplasia resulting from cellular proliferation is a well-known precursor effect related to the development of tumors, and is associated with increased estrogen levels in humans (Sanders et al., 2016). As noted, by Wikoff, both preneoplastic and nonneoplastic hyperplasia occurred in the NTP study. Atypical endometrial hyperplasia was seen in the NTP 2-year assay and was significantly increased above control at all dose levels, however, it was only identified via the longitudinal inspection, but not the transverse (Wikoff et al., 2016). While there was not a strict dose-response (250 mg/kg-day = 26% incidence; 500 mg/kg-day = 22% incidence; 1,000 mg/kg-day = 26% incidence), preneoplastic lesions are by definition precursors to tumor formation (Wikoff et al., 2016). Additionally, as stated above, a high rate of p53 mutations was identified in the uterine carcinogenesis (Harvey et al., 2015). Finally, the adverse outcome, significantly increased incidence of uterine tumors (adenomas, adenocarcinomas, and malignant mixed Mullerian), was seen with increasing dose in the NTP (2014) 2-year assay. 3.4.5 Weight of evidence A human relevance and concordance analysis of the postulated MOA was conducted by Wikoff et al. (2016), and suggests that given the available data, the proposed MOA is plausible for the development of uterine tumors. Wikoff et al. (2016) conclude this is a plausible mechanism in humans qualitatively, but may be quantitatively excluded based on kinetic/dynamic factors between humans and rats. Given some of the data gaps associated with this MOA, we have given the greatest weight to the non-mutagenic threshold MOA, as multiple lines of evidence support that the MOA identified is non- mutagenic. This is seen in a number of tests showing negative mutagenicity results, which are supported by the recent NTP findings of a negative micronucleus test and two negative Salmonella tests. Finally, the specificity of uterine tumors to the uterine tissue only (and not systemically developed) supports the non-mutagenic assertion (Lai et al., 2015). Thus, wWhile we conclude that the Wikoff et al. (2016) WOE analysis was adequate to establish the postulated MOA. the additional information we cite is further supportive ofgiven-the-evaileble-dete;- this non-mutagenic threshold MOA. and leads us to propose a NSRL based on the threshold approach of EPA (2005). However, a more robust and transparent analysis of the modified Bradford Hill criteria for this MOA would be helofulie-needed. Particularly useful in this instance would be a quantitative WOE ranking, as recently demonstrated by Becker et al. (2017). 20 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Howerer there is eurrently sepport 808 threshold MOA 4.0 Derivation of the NSRL 4.1 Choice of critical study and BMD analysis for POD After an updated evaluation of the available carcinogenicity literature for TBBPA, we agree with the choice of Wikoff et al. (2015) that uterine tumors (adenomas, adenocarcinomas, and malignant mixed Mullerian combined) are the most appropriate cancer endpoint, and were chosen as the critical effect for derivation of the NSRL (Table 4). Uterine tumors in female rats were chosen as the critical cancer effect for derivation of a cancer risk value. In looking at the other tumor types, the testicular adenomas in male rats were considered "equivocal" and occurred at low incidence in the two highest doses (500 mg/kg - 1/50 incidence; 1,000 mg/kg - 3/50 incidence), and as such, were not a reliable choice for the critical effect. The hepatoblastomas in male mice had "some evidence" for carcinogenicity (250 mg/kg - 2/50 incidence; 500 mg/kg - 11/50 incidence; 1,000 mg/kg - 8/50 incidence) with a significant effect in the 500 mg/kg dose. NTP (2014) considered this tumor as "some evidence" because after combining incidences of hepatocellular carcinomas and hepatoblastomas, there was only a significant effect at 250 mg/kg and there was no trend across doses, and this was informed by the historical incidence of these tumor types as spontaneous and related to chemical administration. Therefore, these tumors were not considered for use as the critical effect. The uterine epithelial tumors in female rats were the only tumor type classified as "clear evidence" and occurred with the highest incidence (0 mg/kg - 6/50 incidence; 250 mg/kg - 11/50 incidence; 500 mg/kg - 16/50 incidence; 1,000 mg/kg - 19/50 incidence). Therefore, the uterine tumors were the best choice for the critical effect in derivation of a cancer risk value. Table 4. Dose-response and dose-adjustment of cancer effects (tumors) and precursor effects (hyperplasia) from the NTP (2014) assay for use in BMD analysis. Dose, mg/kg Duration- Hyperplasia Tumor response: (NTP, 2014) adjusted dose response: Uterus original a and residual Commented [MD1]: Doses cannot be more precise than those given in the bioassay. Is is 3 digits for two? Residual longitudinal longitudinal reviews review; endometrium, (combined); adenoma, hyperplasia, atypical adenocarcinoma, or MMMT (combined) 0 0 2 6 250 1798-6 13 11 Formatted: Highlight Formatted: Highlight 500 357-+ 11 16 Formatted: Highlight 21 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 1,000 714.3 13 19 Formatted: Highlight In line with the Wikoff et al. (2015) assessment, we modeled the incidence of combined uterine adenomas, adenocarcinomas, and malignant mixed Müllerian tumors observed in female rats (NTP, 2014). While we agree with Wikoff et al. (2015) on the choice of critical effect, the application of the BMD approach and use of the BMDL10, and allometric adjustment of the POD to an HED, we had the benefit of additional literature that allowed us to agree with them that of the Factor appreach- extrapolate to a riste specifie dese to elsewheresupport- a non-mutagenic, threshold MOAresponse, and the determination of a safe dose values are through the application of uncertainty factors to the POD analogous to an RfD or TDI approach (U.S. EPA, 2005). Specifically, conclusion is supported by Wikoff et al. (2015,2016), who suggest that the linear cancer slope factor approach is inappropriate for a non- mutagenic chemical, and suggested that a threshold approach based on a non-mutagenic MOA is most appropriate. This conclusion is also supported However, ai the time-of-their 2015 publication data investigating the TBBPA MOA not there were date avay the tinear defacia stope faeter and the stedies-by Sanders et al. (2016) and Lai et al. (2015), Thus. coupled the postalated MOA by Wikeff et at (2016) is adequate evidence exists to move away from the default linear approach to a threshold approach for this tumor type. Even-though-the MOA is enly postulated) addition, the negative mutagenicity and genotoxicity data and the specificity of the tumor response to specific tissue types are all sufficient to suggest that a threshold approach is most scientifically credible to develop an NSRL. The results of the BMD analysis on adenoma, adenocarcinoma, or MMMT (combined) incidence in relation to TBBPA exposure are shown in Table 5. The log-logistic model (Figure 2) best fits the data based on all quantitative fit criteria: p-value (0.845), scaled residuals (0.042) at the dose with the response closest to the BMR, and AIC (223), resulting in a dose-adjusted BMD10 of 169 mg/kg-day corresponding to the BMDL10 of 103 mg/kg-day. This model provides a similar BMD to that from the multistage model (i.e., the model chosen by Wilkoff et al., 2015), but the loglogistic model results are more conservative and better fit the data, particularly in the dose region of interest. Atypical hyperplasia of the endometrium was also modeled as a potential precursor effect to tumor formation, but no model provided adequate fit of the data (i.e., p < 0.1). Table 5. BMD models examining the relationship between TBBPA exposure* Formatted Table and uterine cancer incidence (adenoma, adenocarcinoma, or MMMTs, combined) in female rats from NTP (2014). 22 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Model p- Scaled Visual Fit Ratio AIC BMD10 BMDL10 Value Residual BMD/ at Dose BMDL Gamma 0.75 0.14 good 1.5 223.1 195 127 Logistic 0.46 0.88 acceptable 1.3 224.0 290 219 LogLogistic 0.85 0.042 good 1.7 222.8 169 103 LogProbit 0.32 0.89 acceptable 1.5 224,8 317 216 Multistage (1*) 0.75 0.14 good 1.5 223.1 195 127 Multistage (2*) 0.75 0.14 good 1.5 223,1 195 127 Multistage (3*) 0.75 0.14 good 1.5 223.1 195 127 Probit 0.49 0.84 acceptable 1.3 223.9 277 208 Weibull 0.75 0.14 good 1.5 223.1 195 127 Quantal- Linear 0.75 0.14 good 1.5 223.1 195 127 *Duration-adjusted dose (5/7 days) *The numbers correspond to the number of degrees of polynomial in the multistage model The bolded row indicates the best fitting model Figure 2. Log logistic modeling results of uterine cancer (adenoma, adenocarcinoma, or MMMTs, combined) in female rats from NTP (2014). 23 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Log-Logetic with of sos, Exta Risk for the BMD and 3.95 Lower for the ......... 0.8 0.4 0.3 0.2 0.: BMOL BMC o 200 aco 800 800 1000 does The resulting duration-adjusted BMDL10 of 103 mg/kg-day was adjusted to a human equivalent dose (HED) of 26 mg/kg-day using allometric scaling (Equation 1; [25.6 mg/kg-day = 103 mg/kg-day x 3 4.2 Uncertainty factors Uncertainty factors were applied to the BMDL10[HED] to derive an RfDcar of 0.9 mg/kg- day using Equation 2 (0.85 mg/kg-day = 25.6 mg/kg-day/(10 x 3 X 1 x 1 x 1 = 30). The uncertainty factor that addresses interindividual variability (UFH) (also referred to as intraspecies variability) accounts for toxicokinetic and toxicodynamic variation across humans and is intended to protect sensitive subpopulations. Unless a study is conducted in a sensitive human population or 3 As noted previously, the choice of default body weight (between female at 58 kg and male at 70 kg) does not significantly change the resulting HED (27.5 mg/kg-day versus 26.3 mg/kg-day, respectively). For this and the reasons listed in the footnote above, we have used the default body weight of 70 kg. 24 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 there are data on human variability in response, the default for the UFH is 10. Given the lack of available data to move away from the default, we recommend the application of a 10-fold factor. The uncertainty factor for interspecies extrapolation (UFA) (also referred to as animal-to-human extrapolation) accounts for the translation of data from experimental animals to humans, specifically the toxicokinetic and toxicodynamic variation between species. Because we adjusted the POD to a human equivalent dose, this is presumed to account for the toxicokinetic differences across species (Renwick et al., 1999). Therefore, a reduced factor of one half the power of 10 (~3-fold) should be applied to account for the toxicodynamic differences between species (Renwick et al., 1999). The uncertainty factor for use of a LOAEL and extrapolation to a NOAEL (UFL) is not needed, since a BMD analysis was conducted. Therefore, a factor of 1 is applied. Additionally, the uncertainty factor for extrapolation of a subchronic critical study to a chronic exposure (UFs) is also not necessary, since a 2-year cancer bioassay was selected as the critical study. Therefore, a factor of 1 is applied. The uncertainty factor for database completeness (UFD) represents a judgment on the quantity and quality of the toxicology information available on the substance. TBBPA has an adequate toxicological database, particularly for noncancer effects, to assess the toxicological outcomes and potential adverse effects from exposure. However, this factor has also been utilized on occasion to account for severity of effect aimed to introduce an additional margin of safety when a compound has produced some form of severe or irreversible toxicity that is not addressed directly by the POD. It is worth noting that the noncancer dataset identified sensitive reproductive effects from TBBPA exposure [BMDLs of 0.5 mg/kg-day for increased testes weight and 0.6 mg/kg-day for increased F1 pituitary weight in males (van der Ven et al., 2008; Lilienthal et al., 2008; as cited in Health Canada, 2013)], and additional thyroid effects were seen but were largely uncharacterized [F1 males and females had decreased T4 levels (BMDL10 31 and 16 mg/kg, respectively)]. However, these data would be relevant for noncancer assessment, and as we are specifically addressing cancer endpoints, the application of this factor is not warranted. Specifically, the availability of the NTP 2-year comprehensive cancer bioassay is sufficient to inform the database for cancer. In total, we recommend the application of a composite uncertainty factor of 30 (3 x 10) to protect for uncertainties in the database and extrapolations. Therefore, for the derivation of the oral NSRL, we divide the BMDL10[HED] of 25.6 mg/kg-day by 30 to derive a cancer safe dose of 0.9 mg/kg-day. Based on the default human body weight of 70 kg, the NSRL is 60 (59.5) mg/day using Equation 3 (60 mg/day = 0.85 mg/kg-day x 70 kg). There were not enough published data identified to derive an inhalation NSRL. There was at least one DNEL derived for inhalation exposure, the studies that those values were based on were not publically available, and the relevance to cancer development from 25 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 inhalation exposure remains uncharacterized. 5.0 Discussion 5.1 Comparison of NSRL to RSD published by Wikoff et al., 2015 An NSRL of 60 mg/day was adapted from an RfDcancer of 0.9 mg/kg-day for a threshold MOA leading to uterine cancer seen in the recent NTP (2014) bioassay. The NSRL value (60 mg/day) is roughly 300-fold higher than the cancer slope factor adjusted to an NSRL derived by Wikoff et al. (2015) for 10-5 risk for the same tumor data (the risk level assigned by the NSRL) (0.0032 mg/kg-day x 70 kg = 0.22 mg/day). This difference reflects the use of a point estimate instead of a slope factor for low dose extrapolation, and slight differences in the BMDL due to model selection. Table 4 shows the various BMD model outputs for the uterine tumor data. While our models appear to align with those of Wikoff et al. (2015), we chose a different model based on an evaluation of multiple parameters (p-value, scaled residuals, visual fit, ratio of BMD to BMDL, and AIC). This difference in model selection accounts for a roughly 20% difference in the chosen points of departure (126.6 mg/kg-day chosen by Wikoff and colleagues versus 103 mg/kg-day chosen for this assessment). The NSRL proposed here of 60 mg/day, however, is within an order of magnitude and roughly aligns with a potential NSRL of 42 mg/day based on the RfD of 0.6 mg/kg-day derived by Wikoff et al. (2015) for noncancer uterine hyperplasia (i.e., 0.6 mg/kg-day x 70 kg = 42 mg/day). As some types of uterine hyperplasia are considered an upstream precursor to uterine cancer, the alignment of these values makes sense biologically. Additionally, protection from precursor effects is typically anticipated to protect from the downstream cancer effect. However, BMD models were not able to adequately fit the uterine hyperplasia data (p-value <0.1), even when the responses at the highest dose were dropped from the model (an approach that is consistent with U.S. EPA guidance; U.S. EPA, 2012). We chose not to use the hyperplasia precursor for cancer effects for a few reasons: 1) there is little currently available practical experience in using a POD based on cancer precursor effects to develop an RfD for a tumor; and 2) poor BMD model fit (p-value < 0.1) limits confidence in, and interpretation of, model results. 5.2 Comparison of RfD cancer to available risk values A comparison was made between the RfDc: derived here and other available risk values (see Table 2; Figure 3). The derived RfD cancer cancer (0.9 mg/kg-day) falls appropriately in respect to the biology on the risk value continuum as shown in Figure 3. As expected, DNELs for noncancer reproductive and developmental effects (DNEL repro and DNEL dev, both = 10 mg/kg-day) and DNELs for noncancer no effect levels (5 and 2.5 mg/kg-day) are higher than the derived RfD cancer by ~2.7 to 11-fold. The TDI, which was also derived for a noncancer no effect level (1 mg/kg-day), is roughly the same as the RfDcancer. This makes biological sense given the thresholded MOA for uterine tumor formation. The RfD for uterine hyperplasia (0.6 mg/kg-day), is slightly lower than the RfD This is expected and makes biological sense given that uterine hyperplasia is a precursor effect to uterine tumors. One would expect an RfD for a precursors effect to be 26 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 lower than that for the apical effect. Finally, the DNEL for thyroid effects (0.16 mg/kg- day) is lower than all other available noncancer values. However, as noted above in Section 3.3.1, there is a large amount of uncertainty associated with the thyroid endpoint (species sensitivity differences between rodents and humans, a lack of consistency in the available thyroid data, the potential for the effect to be reversible, neither thyroid tumors nor thyroid histopathology effects were seen in rats or mice treated in the 2-year NTP assay). Finally, the cancer slope factor (0.0032 mg/kg-day) is significantly lower than all other available risk values (from 50- to ~3,000-fold lower). Typically, the expectation is for cancer risk values to be lower than those for noncancer, under a no-threshold assumption. However, given the evidence for a threshold MOA for the most sensitive uterine tumors, the cancer slope factor is likely highly conservative and not biologically appropriate (280-fold lower than the RfDcancer). Figure 3. Comparison of available cancer and non-cancer risk values for TBBPA. 11 10 10 10 9 8 7 6 5 5 4 2.5 3 2 0.6 0.9 1 1 0.0032 0.16 0 5.2 Uncertainties Uncertainties are associated with using the malignant mixed Müllerian tumor (MMMT) data combined with the uterine adenomas and adenocarcinomas because of the rarity in their occurrence, and the fact that a dose-dependent trend was not reported in TBBPA treated rats. MMMTs are a very rare, spontaneous neoplasm in rats (Dunnick et al., 2015). Furthermore the historical data "are limited in Wistar Han rats because few studies using this strain have been conducted" (NTP, 2014). However, a large body of evidence on the epithelial histogenesis of MMMTs and their relevance to uterine cancers was cited as reasoning to include the MMMTs (Dunnick et al., 2015). The use of a new method of examining the rat uterus (a secondary Residual Longitudinal Review combined with the initial standard Transverse Review) allowed for the identification of additional tumors; 27 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 the additional transverse review identified adenocarcinomas or adenomas in all female rats with MMMTs. Therefore, BMD models including only adenomas and adenocarcinomas would be identical to those for combined adenomas, adenocarcinomas, and MMMTs. The MOA for uterine tumor formation needs additional validation, specifically, it would highly benefit from a comparison to the modified Bradford Hill criteria (such as conducted in Meek et al., 2014) and a quantitative weight of evidence approach (such as conducted in Becker et al., 2017). For the MOA, in vivo data to confirm that TBBPA competes for estrogen sulfotransferases are lacking. Target tissue dosimetry and temporal relationships to determine if TBBPA inhibits sulfotransferase in the uterus are required to determine if this mechanism is viable (Osimitz et al., 2014). Other uncertainties in the estrogen metabolism pathway have not been addressed, including the role of the alternative estrogen metabolism pathways, such as inhibition of hydroxysteroid- dehydrogenase-17beta (leading to increased estrogen activity) and induction of phase I enzymes CYP1A1 and CYP1B1 (leading to reactive metabolite formation) (Sanders et al., 2016). Others reviewed the plausibility of these alternative pathways but a more in- depth review is needed (Wikoff et al., 2015; Dunnick et al., 2015; Sanders et al., 2016). Additionally, more data is needed to evaluate this MOA at human relevant exposure doses. Wikoff et al. (2016) and others suggest this MOA operates only at high doses where saturation of the estrogen metabolic pathway occurs. Wikoff et al. (2016) suggests extrapolation to lower doses for protection of human health may be inappropriate given human doses are not expected to be high enough to lead to this MOA. However, we provide clear rationale that our NSRL is appropriate and as applied, is protective of the development of uterine tumors for several reasons: 1) tumors appear to be formed only at high doses due to non-mutagenic mechanism, and no tumors were identified in previous studies except the non-malignant tumors (transitional cell papillomas in the urinary bladder and thyroid follicular adenomas) (Imai et al., 2009, as cited in EFSA, 2011). This suggests that the potential for carcinogenicity from TBBPA exposure is quite low, will only occur at high doses, and negates the need for low-dose extrapolation; and 2) Wikoff reports that doses of 50 mg/kg are enough to surpass the sulfotransferase IC50, suggesting that this mechanism could be activated at doses below those in the NTP study. However, this dose would need to be exceeded in a chronic fashion in order for tumor formation to occur, and the RfDcan is well below this IC50 (0.9 Therefore, the derived RfDcancer is protective of uterine tumors via a non-threshold mode of action, and low dose extrapolation is not necessary. A final caveat relates to the existence of other potential MOAs/AOPs. Effects on thyroid homeostasis have also been seen, and for noncancer effects have produced relatively low BMD/Ls. Studies have shown that high TBBPA concentrations in vitro inhibit thyroid hormone metabolism with an IC50 of 460 nM for SULT1A in human liver cytosol, and the contribution of this MOA remains unclear (Butt and Stapleton, 2013). However, there is no indication that thyroid tumors result from exposure to TBBPA as neither tumors nor histopathology was found in the NTP assay. Additionally, there were testicular adenomas and hepatoblastomas identified in the NTP (2014) report. It is possible that these tumor types might drive the RfD cancer value lower, but as for the uterine tumors, are anticipated 28 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 to be non-mutagenic thresholded responses due to the non-mutagenic nature of TBBPA. 6.0 Conclusions Building off of previously published work investigating the mode of action and toxicity of TBBPA (ESFA, 2011; Health Canada, 2013; Wikoff et al., 2015, 2016; Lai et al., 2015), and using the cancer results seen from the recent NTP 2-year cancer bioassay, we have derived a no-significant-risk-level (NSRL) for TBBPA of 60 mg/day. The NSRL is based on uterine tumors (adenomas, adenocarcinomas, and malignant mixed Mullerian) identified in female rats exposed to TBBPA for 2-years via oral gavage. TBBPA has been shown to be a non-mutagenic carcinogen acting through an estrogen interference mode of action, and as such the most appropriate approach to derivation of a cancer risk value is a threshold approach, akin to an RfD cancer. Using the NTP study data, we derived a BMDL10 point of departure of 103 mg/kg-day and adjusted this to a human equivalent dose (HED) of 25.6 mg/kg-day using allometric scaling. We applied a composite adjustment factor of 30 to the POD to derive an RfDcancer of 0.9 mg/kg-day. Based on an average human body weight of 70 kg, the cancer safe dose was adjusted to an NSRL of 60 mg/day. Acknowledgements Funding for this work was provided by the American Chemical Council (ACC) and the developmental reserve funds of the University of Cincinnati, Risk Science Center. References Barnes, D.G., & Dourson, M.L. (1988). Reference dose (RfD): Description and use in health risk assessments. Regul Toxicol Pharmacol. 8, 471-486. Becker, R.A., Dellarco, V., Seed, J., Kronenberg, J.M., Meek, B., Foreman, J., Manibusan, M.K. (2017). Quantitative weight of evidence to assess confidence in potential modes of action. Regul Toxicol Pharmacol. 86, 205-220. Doi: 10.1016/j.yrtph.2017.02.017 Borghoff, S.J., Wikoff, D., Harvey, S., & Haws, L. (2016). Dose- and time-dependent changes in tissue levels of tetrabromobisphenol A (TBBPA) and its sulfate and glucuronide conjugates following repeated administration to female Wistar Han Rats. Toxicol Rep, 3, 190-201. doi:10.1016/j.toxrep.2016.01.007 Butt, C.M., & Stapleton, H.M. (2013). Inhibition of thyroid hormone sulfotransferase activity by brominated flame retardants and halogenated phenolics. Chem Res Toxicol, 26(11), 10.1021/tx400342k. oi:10.1021/tx400342k Colnot, T., Kacew, S., & DeKant, W. (2014). Mammalian toxicology and human exposures to the flame retardant 2,2, 6,6,-tetrabromo-4,4-isoprpoylidenediphenol (TBBPA): Implications for risk assessment. Arch Toxicol, 88, 1180-1188. doi: 10.1007/s00204-013-1180-8 COT (Committee on Toxicology). (2004). COT statement on tetrabromobisphenol A- 29 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 review of toxicological data. Retrieved from UK Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment. Available at: https://cot.food.gov.uk/committee/committee-on- oxicity/cotstatements/cotstatementsyrs/cotstatements2004/cotstatements2004tbbp a [accessed July 10, 2017] Cope, R. B., Kacew, S., & Dourson, M. (2015). A reproductive, developmental and neurobehavioral study following oral exposure of tetrabromobisphenol A on Sprague-Dawley rats. Toxicology, 329, 49-59. doi: 10.1016/j.tox.2014.12.013 Cornel, K. M. C., Krakstad, C., Delvoux, B., Xanthoulea, S., Jori, B., Bongers, M. Y. Romano, A. (2017). High mRNA levels of 176-hydroxysteroic dehydrogenase type 1 correlate with poor prognosis in endometrial cancer. Mol Cell Endocrinol, 442, 51-57. doi: 10.1016/j.mce.2016.11.030 Dunnick, J. K., Sanders, J. M., Kissling, G.E., Johnson, C. L., Boyle, M. H., & Elmore, S. A. (2015). Environmental chemical exposure may contribute to uterine cancer development: studies with tetrabromobisphenol A. Toxicol Pathol, 43, 464-473. doi: 10.1177/0192623314557335 European Chemicals Agency (ECHA). (2017). 2017. 2,2',6,6'-tetrabromo-4,4'- isopropylidenediphenol. Information on Chemicals, Registration Dossier. Last modified: 11-Jul-2017. Available online at: https://echa.europa.eu/registration- dossier/-/registered-dossier/14760/1 [accessed July 17, 2017] European Food Safety Administration (EFSA). 2011. Scientific Opinion on Tetrabromobisphenol A (TBBPA) and its derivatives in food. EFSA J, 9: 2477. Available online at: hitps://www.efsa.europa.eu/en/efsajournal/pub/2477 [accessed July 17, 2017] European Food Safety Administration (EFSA). 2017. Update: use of benchmark dose approach in risk assessment. EFSA J, 15: 4658. Available online at: äle:///Users/pecqueam/Downloads/Hardy et al-2017-EFSA Journal.pdf [accessed July 17, 2017] European Union (EU). 2006. Risk Assessment Report: ",6,6'-Tetrabromo-4,4" Isopropylidenediphenol (Tetrabromobisphenol-A or TBBP-A), Part II - Human Health. European Chemicals Bureau, European Commission, 4th Priority List, Volume 63. Available online at: https://echa.europa.eu/documents/10162/326000fe-b4fe-4828-b3d3 93c24cledd51 [accessed July 17, 2017] Fu, J., Fang, H., Paulsen, M., Ljungman, M., Kocarek, T. A., & Runge-Morris, M. (2011). Regulation of estrogen sulfotransferase expression by confluence of MCF10A breast epithelial cells: Role of the aryl hydrocarbon receptor. J Pharmacol Exp Ther., 339(2), 597-606. doi: 10.1124/jpet.111.185173 Gosavi, R. A., Knudsen, G. A., Birnbaum, L. S., & Pedersen, L. C. (2013). Mimicking of estradiol binding by flame retardants and their metabolites: A crystallographic analysis. Environ Health Perspect, 121, 1194-1199. doi: 10.1289/ehp. 1306902 30 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Grosse, Y., Loomis, D., Guyton, K.Z., Ghissassi, F-E., Bouvard, V., Benbrahim-Tallaa, L., Straif, K. (2016). Carcinogenicity of some industrial chemicals. The Lancet Oncol, 17(4), 419-420. Hall, S.M., Coulter, S.J., Knudsen, G.A., Sanders, J.M., & Birnbaum, L.S. (2017). Gene expression changes in immune response pathways following oral administration of tetrabromobisphenol A (TBBPA) in female Wistar Han rats. Toxicol Lett, 272, 68-74. doi:10.1016/j.toxlet.2017.03.008 Hamers, T., Kamstra, J.H., Sonneveld, E., Murk, A.J., Kester, M.H., Andersson, P.L., Legler, J., & Brouwer, A. (2006). In vitro profiling of the endocrine-disrupting potency of brominated flame retardants. Toxicol. Sci. 92, 157e-173e. [as cited in Colnot et al., 2014] doi: 10.1093/toxsci/kfj187 Harvey, J. B., Osborne, T. S., Hong, H. H., Bhusari, S., Ton, T. V., Pandiri, A. R., Hoenerhoff, M. J. (2015). Uterine Carcinomas in Tetrabromobisphenol A- exposed Wistar Han Rats Harbor Increased Tp53 Mutations and Mimic High- grade Type I Endometrial Carcinomas in Women. Toxicol Pathol, 43, 1103-1113. doi: 10.1177/0192623315599256 Health Canada. (2013). Screening assessment report of Phenol, 4,4' -(1-methylethylidene) bis[2,6-dibromo- (Tetrabromobisphenol A, TBBPA; CAS 79-94-7), Ethanol, 2,2'-[(1-methylethylidene)bis[(2,6-dibromo-4,1-phenylene)oxy]lbis (known as TBBPA bis(2-hydroxyethyl ether, CAS 4162-45-2) and Benzene, 1,1'-(1- methylethylidene)bis[3,5-dibromo-4-(2-propenyloxy)-(TBBPA bis(allylether, CAS 25327-89-3). Government of Canada, Environment Canada, Health Canada. Cat. No.: En14-110/2013E-PDF. ISBN: 978-1-100-22898-3. Ho, K. L., Yuen, K. K., Yau, M. S., Murphy, M. B., Wan, Y., Fong, B. M., Lam, M. H. (2017). Glucuronide and sulfate conjugates of tetrabromobisphenol A (TBBPA): Chemical synthesis and correlation between their urinary levels and plasma TBBPA content in voluntary human donors. Environ Int, 98, 46-53. doi: 10.1016/j.envint.2016.09. Imai, T., Takami, S., Cho, Y. M., Hirose, M., & Nishikawa, A. (2009). Modifying effects of prepubertal exposure to potassium perchlorate and tetrabromobisphenol A on susceptibility to N-bis(2-hydroxypropyl)nitrosamine- and 7,12 dimethylbenz(a)anthracene-induced carcinogenesis in rats. Toxicol Lett, 185, 160- 167. [As cited in EFSA, 2011]. doi: 10.1016/j.toxlet.2008.12.013 International Toxicity Estimates for Risk (ITER). A TOXNET Database. U.S. National Library of Medicine, National Institutes of Health. Available online at: https://toxnet.nlm.nih.gov/newtoxnet/iter.htm [accessed July 17, 2017] Jeff Gift, U.S. EPA, personal communication via email. In reference to: questions on benchmark dose. November 18, 2016. Kester, M.H., Bulduk, S., van Toor, H., Tibboel, D., Meinl, W., Glatt, H., Visser, T.J. (2002). Potent inhibition of estrogen sulfotransferase by hydroxylated metabolites 31 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 of bolyhalogenated aromatic hydrocarbons reveals alternative mechanism for estrogenic activity of endocrine disrupters. J. Clin. Endocrinol. Metab 87, 1142e- 1150e. Klimisch, H.J., Andreae, M., & Tillmann, U. (1997). A systematic approach for evaluating the quality of experimental toxicological and ecotoxicological data. Regul. Toxicol. Pharm. 25, 1-5. Lai, D. Y., Kacew, S., & Dekant, W. (2015). Tetrabromobisphenol A (TBBPA): Possible modes of action of toxicity and carcinogenicity in rodents. Food Chem Toxicol, 80, 206-214. doi: 10.1016/j.fct.2015.03.023 Lilienthal, H., Verwer, C., van der Ven, L., Piersma, A., & Vos, J. (2008). Exposure to tetrabromobisphenol A (TBBPA) in Wistar rats: Neurobehavioral effects in offspring from a one-generation reproduction study. Toxicology, 246, 45-54. [as cited in Health Canada, 2013] doi: 10.1016/j.tox.2008.01.007 Meek, M.E., Palermo, C.M., Bachman, A.N., North, C.M., & Lewis, R.J. (2014). Mode of action human relevance (species concordance) framework: Evolution of the Bradford Hill considerations and comparative analysis of weight of evidence. J Appl Toxicol, 34, 595-606. doi: 10.1002/jat.2984 MPI Research, 2002a. A 90-day oral toxicity study of tetrabromobisphenol-A in rats with a recovery group (unpublished). As cited in COT (2004). MPI Research, 2002b. An oral two generation reproductive, fertility and developmental neurobehavioural study of tetrabromobisphenol-A in rats (unpublished). Performed by MPI Research Inc., Mattawan, MI for the American Chemistry Council BFRIP, Arlington, VA. Study Number: 474-004, pp 2199 [as cited in Colnot et al., 2014] MPI Research. (2001). Final report-an oral prenatal developmental toxicity study with tetrabromobisphenol-A in rats (unpublished). [as cited in Colnot et al., 2014]. National Institute of Environmental Health Sciences (NIEHS). (2002). Tetrabromobisphenol A [79-94-7]: Review of Toxicological Literature. National Institutes of Health, National Toxicology Program. Available online at: https://ntp.niehs.nib.gov/ntp/btdocs/chem_background/exsumpdf/tetrabromobisph enola 508.pdf [accessed July 17, 2017] NTP (National Toxicology Program). (2014). Technical Report on the Toxicology Studies of Tetrabromobisphenol A (CAS NO. 79-94-7) in F344/NTac rats and B6C3F1/N mice and Toxicology and Carcinogenesis Studies of Tetrabromobisphenol A in Wistar Han [Crl:WI(Han)] rats and B6C3F1/N mice (Gavage Studies). NTP TR 587, September, 2014. National Institutes of Health, U.S. Department of Health and Human Services, Research Triangle Park, NC. Available online at: https://ntp.niehs.nib.gov/ntp/htdocs/lt_xpts/tr587508.pd [accessed July 7, 2017] Office of Environmental Health Hazard Assessment (OEHHA). (1989). Final Statement of Reasons. No Significant Risk Levels and No Observable Effect Levels. 32 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Proposition 65, California Environmental Protection Agency. June, 1989. Available online at: https://oehha.ca.gov/media/downloads/emnr/art78fsrjune1989.pdf [accessed July 7, 2017] Office of Environmental Health Hazard Assessment (OEHHA). (2013). Article 7. No Significant Risk Levels. § 25703. Quantitative Risk Assessment. Title 27, California Code of Regulation. Available online at: ittps://oehha.ca.gov/media/downloads/proposition-65/general-info/regsart7.pdf [accessed July 19, 2017] Osimitz, T.G., Dourson, M.L., Hayes, A. W., & Kacew, S. (2014). Crystallographic analysis and mimicking of estradiol binding: Interpretation and speculation. Environ Health Perspect, 122: A91-A92. DOI:10.1289/ehp.1307987 Renwick, A.G. (1999). Subdivision of uncertainty factors to allow for toxicokinetics and toxicodynamics. Human and Ecological Risk Assessment, 5, 1035-1050. doi: 10.1080/10807039991289329 Sanders, J.M., Coulter, S.J., Knudsen, G.A., Dunnick, J.K., Kissling, G.E., & Birnbaum, L.S. (2016). Disruption of estrogen homeostasis as a mechanism for uterine toxicity in Wistar Han rats treated with tetrabromobisphenol A. Toxicol Appl Pharmacol, 298, 31-39. doi: 10.1016/j.taap.2016.03.007 Schauer, U.M.D., Völkel, W., & Dekant, W. (2006). Toxicokinetics of tetrabromobisphenol A in humans and rats after oral administration. Toxicol Sci 91, 49-58. [as cited in Health Canada, 2013] U.S. EPA (Environmental Protection Agency). (1986). Guidelines for Mutagenicity Risk Assessment. U.S. Environmental Protection Agency: Washington, DC, EPA/630/R-98/003. Available online at: ps://www.epa.gov/sites/production/files/2013-09/documents/mutagen2.pdf [accessed July 7, 2017] U.S. EPA (Environmental Protection Agency). (2005). Guidelines for Carcinogen Risk Assessment. U.S. Environmental Protection Agency: Washington, DC, EPA/630/P-03/001F. Available online at: https://www.epa.gov/risk/guidelines- carcinogen-risk-assessment [accessed July 7, 2017] U.S. EPA (Environmental Protection Agency). (2012). Benchmark Dose Technical Guidance. Risk Assessment Forum, U.S. Environmental Protection Agency: Washington, DC.100-R-12-001. Available online at: attps://www.epa.goy/risk/benchmark-dose-technical-guidance[accessed July 7, 2017] U.S. EPA (Environmental Protection Agency). (2014). Supplemental File 4: Tetrabromobisphenol A (TBBPA, CASRN: 79-94-7) Cancer Assessment Review Committee Report. Health Effects Division, Office of Pesticide Programs, U.S. Environmental Protection Agency: Washington, DC. Available online at: https://www.epa.gov/assessing-and-managing-chemicals-under. 33 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 scalsupplemental-file-4-tetrabromobisphenol-tbbpa-casmn-79 [accessed July 7, 2017] Van der Ven, L.T., Van de Kuil, T., Verhoef, A., Verwer, C.M., Lilienthal, H., Leonards, P.E., Piersma, A.H. (2008). Endocrine effects of tetrabromobisphenol-A (TBBPA) in Wistar rats as tested in a one-generation reproduction study and a subacute toxicity study. Toxicology, 245, 76-89. doi: 10.1016/j.tox.2007.12.009 [as cited in Health Canada, 2013, and EFSA, 2011] Wheeler, M.W., & Bailer, A.J. (2007). Properties of model-averaged BMDLs: a study of model averaging in dichotomous response risk estimation. Risk Anal, 27(3): 659- 70. doi: 10.1111/j.1539-6924.2007.00920.x Wikoff, D., Thompson, C., Perry, C., White, M., Borghoff, S., Fitzgerald, L., & Haws, L.C. (2015). Development of toxicity values and exposure estimates for tetrabromobisphenol A: Application in a margin of exposure assessment. J Appl Toxicol, 35, 1292-1308. doi: 10.1002/jat.3132 Wikoff, D.S., Rager, J.E., Haws, L.C., & Borghoff, S.J. (2016). A high dose mode of action for tetrabromobisphenol A-induced uterine adenocarcinomas in Wistar Han rats: A critical evaluation of key events in an adverse outcome pathway framework. Regul Toxicol Pharmacol, 77, 143-159. doi: 10.1016/j.yrtph.2016.01.018. Yang, Y., Ni, W.W., Yu, L., Cai, Z., Yu Y.J. (2016). Toxic effects of tetrabromobisphenol A on thyroid hormones in SD rats and the derived-reference dose. Biomed Environ Sci, 29(4), 295-299. 34 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226

What is the Scaled Residual at Dose of LogLogistic?

kxcn0226

kxcn0226_p4, kxcn0226_p5, kxcn0226_p6, kxcn0226_p7, kxcn0226_p8, kxcn0226_p9, kxcn0226_p10, kxcn0226_p11, kxcn0226_p12, kxcn0226_p13, kxcn0226_p14, kxcn0226_p15, kxcn0226_p16, kxcn0226_p17, kxcn0226_p18, kxcn0226_p19, kxcn0226_p20, kxcn0226_p21, kxcn0226_p22, kxcn0226_p23, kxcn0226_p24, kxcn0226_p25, kxcn0226_p26, kxcn0226_p27, kxcn0226_p28, kxcn0226_p29, kxcn0226_p30, kxcn0226_p31, kxcn0226_p32, kxcn0226_p33, kxcn0226_p34, kxcn0226_p35

0.042

1.0 Introduction Under the State of California's Proposition 65 (Prop65), a no significant risk level (NSRL) is developed for chemicals that are known to induce cancer in toxicological studies. The NSRL represents the "levels of exposure calculated to result in no more than one excess case of cancer in an exposed population of 100,000, assuming exposure over a 70-year lifetime (10-5 lifetime risk of cancer)" (OEHHA, 1989). California's Office of Environmental Health Hazard Assessment (OEHHA) recently announced its Prop65 notice of intent to list tetrabromobisphenol A (TBBPA) as known to the state to cause cancer. This is likely based on a recent International Agency for Research on Cancer (IARC) assessment that classified TBBPA as "Group 2A: probably carcinogenic to humans" (IARC Monograph in preparation, volume 115 - only the classification is available at the time of publication; Grosse et al., 2016). With the addition of TBBPA to the Prop65, a toxicological evaluation of TBBPA and derivation of an NSRL is needed. The methodology for NSRL derivation is similar to that of the U.S. EPA for developing cancer potency values. An evaluation of the available toxicological data in humans and animals is used to identify a significant biologic response of concern (critical effect) (OEHHA, 1989). In the absence of data to the contrary, noa threshold is assumed for the cancer effect of concern, and OEHHA then develops an NSRL through the use of no- threshold models (cancer slope factor development) based on U.S. EPA guidance (1986, 2005) (OEHHA, 2013). These NSRL values are then compared to exposure estimates to determine the potential to evoke a biological response at relevant environmental exposure levels (margin of safety) (OEHHA, 1989). However, when a threshold in response is supported based on available data, most risk agencies around the World support alternative approaches such as using threshold models. For example, the U.S. EPA (2005) methodology has advanced with the state of risk science, and includes a determination of a linear (non-threshold) or non-linear (threshold) mode of action (MOA) approach. Threshold models suggest that there are low doses of a chemical that do not cause effects and that a high enough dose is needed for effects to occur, while non- threshold models suggest that any dose above zero can lead to an effect (U.S. EPA, 2005). The-One basis for the non-threshold models relates to mutagenic chemicals that cause DNA damage that contribute to carcinogenesis regardless of dose. In fact, identification of mutagenicity mechanisms for cancer development is often a key diagnostic for identification of threshold versus non-threshold mechanisms. This determination impacts the choice of either the derivation of a cancer slope factor and a risk specific dose, or a threshold-based toxicity reference value for cancer effects (RfD 'cancer). TBBPA, a flame retardant chemical that is detected in the environment, albeit at low levels in the U.S., has been extensively studied for a number of years. In order to develop an NSRL, we first reviewed authoritative assessments for TBBPA from regulatory and other agencies to see if an extant cancer risk value had been derived that could be adapted for use as the NSRL. A literature search was conducted from the date of the most recent authoritative review to the present, to identify any new data published since the time of the last review that could inform or update the basis for the NSRL. Data from both the 3 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 authoritative reviews and the published literature were evaluated for toxicological data and mode of action (MOA) information pertinent to cancer development. A risk characterization was then conducted, building off of previous publications, by identification of the critical tumor effect, identification of a point of departure (POD) utilizing Benchmark Dose (BMD) modeling, review of the MOE for tumor formation, derivation of a cancer risk value, and adaptation to an NSRL. 2.0 Methods 2.1 Hazard Identification and Literature Search There are a number of authoritative reviews available from regulatory agencies and others summarizing the toxicology and potential health impacts from exposure to TBBPA. These authoritative reviews were identified through an Internet search in relevant regulatory databases. The Internet was searched by individual key agency web sites, and broadly with ToxPlanet (https://toxplanet.com/). Additionally, an updated literature search was conducted from a few years prior to the date of the most recent review document (Health Canada, 2013), in order to identify any newly published data that could be utilized in derivation of the NSRL. The literature used in this report was in part identified in a systematic literature search in Elsevier Embase, PubMed, and ToxPlanet databases conducted in September, 2016 for the previous 5 years (2011-2016). The results and details of these searches can be found in Table 1. A broad ranging search in each database was initially utilized by searching the chemical name, synonyms, CAS registry number, and relevant acronyms. Data were filtered by limiting to animal or human species. In PubMed, another filter was employed - "NOT preablumin" as this key word was not relevant to toxicology studies but appeared repeatedly in the search results. Identified literature was initially screened and reviewed by title and abstract for content and relevance, and selected literature was subsequently obtained and further reviewed for appropriate data. These studies were reviewed and evaluated in order to determine the most appropriate critical cancer effect for use in deriving the NSRL. Literature regarded as insufficiently reliable for supporting a health conclusion (e.g., inadequate description of methods or data, lack of appropriate dose- response data) were excluded from further consideration. Table 1. Detailed search terms and search strings and resulting number of hits for each database searched to identify literature for use in derivation of the TBBPA NSRL. Database: Search String (see Table 2) No. hits PubMed AI(tetrabromidiphenylolpropane) OR tetrabromodi) OR 6994 tetrabromodi) OR tetrabromobisphenol) OR Tetrabromo-4,4'- isopropylidenediphenol) OR fire guard 2000) OR 79-94-7) OR tbbpa) OR 3,5,3',5'-Tetrabromobisphenol A 4 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 PubMed Added NOT "prealbumin" 863 PubMed (((tetrabromidiphenylolpropane) OR tetrabromodi) OR 135 LAST 5 tetrabromodi) OR tetrabromobisphenol) OR Tetrabromo-4,4'- YRS isopropylidenediphenol) OR fire guard 2000) OR 79-94-7) OR tbbpa) OR 3,5,3',5'-Tetrabromobisphenol A Filter: published in the last 5 years; Animals PubMed E((tetrabromidiphenylolpropane) OR tetrabromodi) OR 78 LAST 5 tetrabromobisphenol a) OR Tetrabromo-4,4' YRS isopropylidenediphenol) OR "Great Lakes BA-59P") OR "BA 59") OR 4,4'-Isopropylidenebis (2,6-dibromophenol)) OR 3,5,3',5'-Tetrabromobisphenol A) OR 2,2',6,6'- Tetrabromobisphenol / A) OR ((79-94-7 OR tbbpa)|) AND "last 5 years"[PDat])) NOT PREALBUMIN Filters: published in the last 5 years; Humans EMBASE tetrabromidiphenylolpropan OR tetrabromodi OR 751 "tetrabromobisphenol a" OR "tetrabromo 4 4 sopropylidenediphenol" OR "4 4 isopropylidenebis (2,6- dibromophenol)" OR "3 5 3 tetrabromobisphenol a" OR "2 2 6 6 Tetrabromobisphenol A" OR 79-94-7 OR tbbpa EMBASE ABOVE (TBBPA STRING) AND ('animal experiment'/de OR 316 'animal tissue'/de OR 'controlled study'/de OR 'correlational study'/de OR 'human'/de OR 'in vivo study'/de OR 'intermethod comparison'/de OR 'nonhuman'/de OR 'normal human'/de OR 'validation process'/de OR 'validation study'/de) AND (2011:py OR 2012:py OR 2013:py OR 2014:py OR 2015:py OR 2016:py OR 2017:py) ToxPlanet TBBPA; 79-94-7 91 As detailed below, due to the lack of available cancer studies other than the NTP (2014) 2-year cancer bioassay, this study was chosen for use in identification of the critical effect. Additional authoritative review papers and published literature (described below) were evaluated to gain an understanding of the noncancer effects of TBBPA as well as the potential MOA for tumor formation. 2.2 Dose-Response Analysis to Derive Point of Departure Benchmark dose (BMD) modeling (BMDS 2.6; U.S. EPA, 2012) was used to evaluate the dose-response relationship between exposure to TBBPA and cancer outcomes. As detailed below, adenoma, adenocarcinoma, or malignant mixed Mullerian tumors 5 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 (MMMTs) (combined) of the uterus identified through both original and residual longitudinal reviews [see Table 2 of Dunnick et al. (2015); NTP (2014)] were modeled to identify a POD. Atypical hyperplasia of the endometrium was also considered [see Table 6 of NTP (2014)]. All standard dichotomous models were considered. BMDs corresponding to 10% extra risk, the benchmark response (BMR), and their 95% lower bounds (BMDLs) were determined. All BMD modeling was done using extra risk. Model parameters were restricted when possible; not all models offer an option for the restriction of the slope or power. The POD reported is the duration-adjusted dose (i.e., the dose x 5/7, to account for dosing on only 5 of 7 days/week). The criteria described in EFSA (2017) as measures of model acceptability are the goodness-of-fit p-value, BMD to BMDL ratio, and the Akaike Information Criterion (AIC). U.S. EPA's BMDS guidance document for interpreting modeling results recommends adequacy determinations based on p-value, scaled residuals, visual fit, consideration of variability among BMDLs across the candidate models, AIC, and professional judgment (U.S. EPA, 2012). Because U.S. EPA's criteria are more inclusive, we discuss each of these in turn. The decision statements below, e.g., what constitutes adequate fit, are based on and adapted from the U.S. EPA guidance. The first criterion is the global statistical goodness of fit test that represents the full dose range of the data. If the p-value is >0.1, then the model is considered to adequately fit the data. Values lower than 0.1 suggest that the model may be statistically significantly different than the data, with values of 0.05 or less decidedly so. Models with values lower than 0.1 are usually rejected. Models with values of 0.05 or less would be rejected unless special circumstances existed, such as a mechanistic motivation for the model. However, models with higher p-values are not necessarily better than models with lower p-values (say, p = 0.5 versus p = 0.2) if both have a p-value >0.1, which is why other criteria, described below, are then used. The second criterion; relatedto-iseal-fit-is the difference in scaled residuals (that is, the difference in the modeled estimate compared with the actual data scaled by the standard error) at the data point closest to the BMR (in this case, 10%), where it is most important that the model fits the data. A scaled residual of 0 means that the model aligns perfectly with the data at that point, although any scaled residual with an absolute value of less than 2 is acceptable. Models with residuals that have an absolute value greater than this value are rejected. Models with lower residuals are usually preferred. U.S. EPA has recently added a scaled residual at the zero dose to one output format for its BMDS software. This parameter may also prove to be useful for future evaluations. The third criterion, related to scaled residuals, is the visual fit. Arguably the least quantitative criterion, visual fit nevertheless allows consideration of how well the model fits the underlying data, especially at the lower end of the curve or how well the model reflects the biological mode of action, if known. Designations of visual fit can include good, acceptable, and poor. Models that have "poor" visual fit should be rejected. Models with good visual fits are generally preferred. 6 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 U.S. EPA's fourth criterion is two-fold. The first part asks whether the BMDL estimates from the remaining models are sufficiently close to each other and reflect no particular influence of the individual models. This emphasizes that the goal of the modeling is to calculate a BMDL. One way to view this is to compare the ratios between the BMD and BMDL among the models. The larger the ratio, the less accurate the model is likely to be. Another useful comparator in previous U.S. EPA guidance was to decide that model-dependence is evident if the BMDLs differed by more than a factor of 3, but this specificity was removed as being too prescriptive (Jeff Gift, U.S. EPA, personal communication). The second part of this fourth criterion is the Akaike Information Criterion (AIC). Of the remaining models, the one chosen will generally have the lowest AIC. However, AICs within a value of 2 of each other are considered to be similar. If several models are still available from which to choose, then the lowest BMD and BMDL can be selected as a conservative choice, or the BMDs and BMDLs of several models can be averaged¹, using either an arithmetic or geometric mean. Such an average BMDL, however, loses its statistical properties, i.e., it is not the 95% lower bound on the average BMD. 2.3 Derivation of NSRL Once the point of departure (POD) was derived using BMDS, standard risk assessment guidance was utilized for the derivation of and cancer risk value and adaptation to an NSRL based on the U.S. EPA and OEHHA methodology (U.S. EPA, 2005; OEHHA, 1989). We first adjusted the POD to a human equivalent dose using allometric scaling (Equation 1). Because the weight-of-evidence for mode of action (MOA) for tumor formation identified did not involve direct DNA interaction, traditional linear cancer slope factor derivation was not conducted (Wikoff et al., 2015, 2016; NTP, 2014). Instead, an RfD. cancer was derived for a non-linear threshold response following the guidance of U.S. EPA (2005). This includes an assessment of the uncertainty associated with the POD and the application of uncertainty factors (Equation 2). Uncertainty factors are used to add conservatism and additional safety to the RfDc: given unknowns about the chemical, to account for data gaps, such as animal to human uncertainty, subchronic to chronic exposures, and to account for intra-individual variability. The derived RfDcancer was then converted to an NSRL by adjusting for body weight (Equation 3). Equation 1. DoseH = Dosea x Where 1Note that this is not the same as model averaging, where the individual model results are combined by using weights, with higher weights for models that fit the data better (Wheeler and Bailer, 2007). 7 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 DoseH = dose in human (BMDL10[HED]) Dosea = dose in animal (the POD for the specified critical effect = BMDL10) BWA = body weight of animal (0.268 kg for control female Wistar from NTP) BWH = body weight of human (70 kg²) Equation 2. RfD cancer = BMDL10[HED/(UFH x UFAX UFs x UFLX UFD) Where BMDL10[HED = benchmark dose lower limit human equivalent dose UFH = uncertainty factor for human variability UFA = uncertainty factor for animal to human extrapolation UFs = uncertainty factor for subchronic to chronic extrapolation UFL = uncertainty factor for LOAEL to NOAEL UFD = uncertainty factor for database completeness Equation 3. NSRL (mg/day) = RfDcance (mg/kg-day) x BWH (kg) Where BWH = body weight of human (70 kg) 3.0 Results 3.1 Literature search results Authoritative reviews identified include the National Institute of Environmental Health Sciences (NIEHS, 2002), the European Union (EU, 2006), the European Commission Committee on Toxicology (COT, 2004), the European Food Safety Authority (EFSA, 2 The body weight of 70 kg is the default body weight for males used by OEHHA as listed in the California Code of Regulations (27 CCR § 25703, 27 CA ADC § 25703; OEHHA, 2013). However, the recommended body weight for females is 58 kg, which is the specific subpopulation of interest, as uterine tumors were identified as the critical effect. We chose to use the 70 kg default as the body weight because: 1) it is more conservative (results in a slightly lower HED) than 58 kg; 2) women in the U.S. tend to be heavier; 3) 70 kg was utilized in most of the previous NSRL documents that we reviewed; and 4) due to the nature of the assessment, the difference between 70 kg and 58 kg is not enough to significantly change the final NSRL value (within an order of magnitude). 8 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 2011), and Health Canada (2013). At the time of this publication, the IARC monograph on TBBPA was unavailable for public review, and only the classification was available (Grosse et al., 2016). The above mentioned and available authoritative regulatory toxicity reference values for cancer (and noncancer) effects for TBBPA were evaluated. However, of these authoritative reviews, only two oral toxicity reference values were derived (ECHA, 2017; COT, 2004). Our literature search identified three additional recently published papers that derived risk values for TBBPA (Wikoff et al., 2015; Yang et al., 2016; Colnot et al., 2014). All values were evaluated for relevance in adapting for use as the NSRL. Data were also mined from the two most recent authoritative reports (EFSA, 2011; Health Canada, 2013) relating to standard toxicological endpoints and agency conclusions on the potential for adverse health effects on humans. All publically available data were reviewed, synthesized, and, in the absence of an available cancer risk value for TBBPA from the authoritative agencies, a cancer risk value was derived and the OEHHA methodology was applied to translate this value into an NSRL. The literature search identified a carcinogenicity study of TBBPA by the U.S. National Toxicology Program (NTP, 2014), and associated published studies that evaluated these NTP (2014) tumor findings and the TBBPA cancer MOA (Dunnick et al., 2015; Wikoff et al., 2015; Harvey et al., 2015; Sanders et al., 2016; Lai et al., 2015; Wikoff et al., 2016; Hall et al., 2017). These data are pertinent as the lack of cancer data was identified as a data gap for developing a cancer potency value as reported in the most recent authoritative reviews for TBBPA (EFSA, 2011; Health Canada, 2013). Further studies were identified investigating non-cancer effects related to inhalation toxicity, dermal absorption, thyroid hormone disruption, endocrine activity, developmental toxicity, and neurotoxicity. Additional toxicokinetic studies reported the disposition and kinetics of TBBPA in rats and one investigated toxicokinetic parameters in humans. 3.2 Authoritative and Published Risk Values for TBBPA 3.2.1 Toxicity Reference Values Toxicity reference values for TBBPA from various agencies are summarized in Table 2. The UK Committee on Toxicity (COT, 2004) derived a tolerable daily intake (TDI) for oral exposure of 1 mg/kg-day for chronic exposure in the general population. This TDI was based upon a NOAEL of 1,000 mg/kg-day in an unpublished two-generation reproductive toxicity study and in an unpublished 90-day study (MPI Research, 2002a,b, as cited in COT, 2004). The COT applied a composite uncertainty factor of 1,000 based on 10 for human to animal (UFA), 10 for human variability (UFH), and 10 for database deficiencies (UFD). ECHA (2017) developed a derived no effect level (DNEL) for long-term systemic effects following oral exposure for the general population. The oral DNEL of 2.5 mg/kg-day available on the ECHA website does not provide enough detail to determine the NOAEL used or the uncertainty factors applied to derive the value. Colnot et al. (2014) reported four oral DNELs, two for the general population based on different endpoints (thyroid effects and no effect in a 90-day study) and two for reproductive endpoints (fertility and development). The lowest oral DNEL of 0.16 mg/kg-day was based on a BMDL10 of 16 mg/kg-day for thyroid hormone changes after application of a 100-fold uncertainty factor 9 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 (UFA = 10, UFH = 10). Two recently published reference values for TBBPA were identified in the literature search (Yang et al., 2016; Wikoff et al., 2015) (Table 2). Yang et al. (2016) compared previous PODs available in the literature for TBBPA with a POD generated in their own study investigating TBBPA toxicity to thyroid hormones. However, due to a lack of some methodological details in the publication, the Yang et al. (2016) assessment was not used in supporting the derivation of a cancer risk value. For example, the authors do not discuss the uncertainty factors used to derive the RfD or the details of the BMD model outputs and rationale for model choice. Without these methodological details, there is not enough information provided to assess the validity of the proposed RfD. In the other assessment, Wikoff et al. (2015) developed a number of non-cancer and cancer toxicity reference values, including an oral RfD, an oral cancer slope factor, an average daily dose estimate, and evaluated the margin of exposure (MOE) and margin of safety (MOS) based on these risk values. These toxicity reference values were based on the recent NTP 2-year bioassay in rats and mice (NTP, 2014) and followed standard U.S. EPA methodology including the use of BMD modeling (U.S. EPA, 2012). Wikoff et al. (2015) conducted a comprehensive literature search to identify published and unpublished TBBPA toxicity studies that identified a dataset of studies to review followed by an evaluation of study quality using Klimisch scoring that narrowed the database to the most relevant high quality studies (Klimisch et al., 1997). The authors then selected the NTP (2014) 2-year carcinogenicity assay from the high quality studies and identified the most sensitive cancer and non-cancer endpoints for their choice of PODs (Wikoff et al., 2015). For the noncancer RfD, Wikoff et al. (2015) selected female rat uterine hyperplasia from the 2-year NTP bioassay as the critical effect. The data were modeled using BMDS to derive a BMDL10 of 72.8 mg/kg-day and after adjustment for allometric scaling to humans, resulted in a human equivalent dose (HED) of 18.2 mg/kg-day. Using this POD, a composite uncertainty factor of 30 was applied (UFA = 3, UFH = 10) resulting in an RfD of 0.6 mg/kg-day. It is worth noting that the BMD model applied (unspecified in the publication) had poor fit (P = 0.08) even after dropping the high treatment dose (Wikoff et al., 2015). For cancer endpoints, Wikoff et al. (2015) considered uterine tumors from the NTP (2014) study as the most appropriate endpoint for use in derivation of a cancer toxicity value. Wikoff et al. (2015) applied the linear multistage BMD model to the duration- adjusted doses for the cancer dataset. Their BMDL10 was 127 mg/kg-day, and after adjustment for allometric scaling to humans, resulted in an HED of 31.7 mg/kg-day. Using this POD, the cancer slope factor was calculated to be 0.0032 per mg/kg-day, which corresponds to a risk specific dose (RSD) at the 10-5 level of 0.0032 mg/kg-day (Wikoff et al., 2015). This value has been through a quality assurance review and is posted on the International Toxicity Estimates for Risk (ITER) database, which is found on the U.S. National Library of Medicine's TOXNET (https://www.nlm.nih.gov/pubs/factsheets/toxnetfs.html). Only the Wikoff et al. (2015) toxicity reference values characterized the cancer human 10 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 health risks of exposure to TBBPA (Table 2). Several organizations concluded that there were not sufficient data available to derive cancer or noncancer toxicity reference values (prior to publication of the NTP report), and many applied a MOE approach. A MOE can be defined as the magnitude by which the POD (e.g., the NOAEL) of the most sensitive relevant toxic effect exceeds the estimated exposure (Barnes and Dourson, 1988). 11 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Table 2. Toxicity values identified in the literature for the general population and breakdown of how each value was derived. Reference CTV* Value Exposure Critical Effect Key Study Point of departure Composite Adjustment duration, Factor (individual route adjustments) ECHA, DNEL 2.5 mg/kg- Chronic, Unidentified, however Mice, oral NOAEL = 250 100 (UFA = 10, UFH = 10) 2017 day oral the registration dossier gavage (study mg/kg-day states "a chronic study citation not is used to set a chronic clear) DNEL. No correction required". Rats, Colnot et 5 mg/kg- Chronic, DNEL No reproductive/ oral gavage NOAEL = 1,000 200 (UFA = 10, UFH = 10, UFs (MPI al., 2014 day oral developmental effects Research, mg/kg-day = 2) 2002b) 0.16 Rats, dietary Colnot et DNEL, Chronic, Thyroid hormone (Van BMDL10 = 16 mg/kg- al., 2014 oral mg/kg- changes der Ven et 100 (UFA = 10, UFH = 10) oral day day al., 2008) Rats, oral Colnot et DNEL, 10 mg/kg- Chronic, No reproductive/ gavage (MPI NOAEL = 1,000 100 (UFA = 10, UFH = 10) al., 2014 oral day oral fertility effects Research, mg/kg-day 2001) Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 COT, TDI 1 mg/kg- Chronic, No embryotoxic / Rats, oral NOAEL of 1,000 1,000 (UFA = 10, UFH = 10, 2004 day oral teratogenic effects: gavage (MPI, mg/kg-day UFD = 10) effects 2002b) Wikoff et RfD 0.6 mg/kg- Chronic, Uterine endometrial Rats, oral BDML10 72.8 30 (UFA = 3; UFH = 10) al., 2015 day oral atypical hyperplasia gavage (NTP, mg/kg-day NSRL for cancer precursor 2014) HED - 18.2 mg/kg- effect for 70 kg human = 42 day mg/kg-day Pecquet et RfDcance 0.9 mg/kg- Chronic, Uterine tumors Rats, oral BDML10 102.5 30 (UFA = 3; UFH = 10) al., 2017 r day oral gavage (NTP, mg/kg-day NSRL for 70 kg human = 60 (this 2014) HED - 25.6 mg/kg- mg/kg-day paper) day Wikoff et Cancer 0.00315 Chronic, Uterine tumors Rats, oral BMDL10 126.6 RSD at 10-6 = 0.0032 mg/kg- al., 2015 slope mg/kg-day oral gavage (NTP, mg/kg-day day factor 2014) HED - 31.7 mg/kg- NSRL for 70 kg human = 0.22 day mg/kg-day * CTV = Chronic Toxicity Value? 13 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 3.3 Summary of TBBPA toxicology In order to understand the potential for toxicity from TBBPA exposure, the noncancer and cancer toxicity findings from recent authoritative agencies were reviewed. Overall, TBBPA is expected to have very low systemic noncancer toxicity, with low hazard for developmental or reproductive toxicity, as reviewed and reported in multiple regulatory and other published reports (ECHA, 2017; EFSA, 2011; Health Canada, 2013; NTP, 2014; Colnot et al., 2014; U.S. EPA, 2014; Cope et al., 2015; etc.). 3.3.1 Genotoxicity and Cancer EFSA (2011) found no in vivo studies available to assess the genotoxicity of TBBPA, and Health Canada (2013) identified no structural activity data suggesting TBBPA might be genotoxic. Further, a number of in vitro studies, such as several Ames tests and mutagenicity assays, a chromosomal aberration assay, a recombination assay, a sister chromatid exchange in Chinese hamster ovary (CHO) cells, and a rat hepatocyte unscheduled DNA synthesis assay were evaluated, all with negative findings (EFSA, 2011; Health Canada, 2013; Colnot et al., 2014). These data were supported by structure activity relationship data, where no structural alerts for genotoxicity were identified and a lack of suitable analogs were available for use in read-across (U.S. EPA, 2014). The overall WOE indicates that TBBPA does not exert genotoxic or mutagenic effects. EFSA (2011) and Health Canada (2013) also assessed studies to investigate the potential carcinogenicity of TBBPA. At the time of these reports, no long-term carcinogenicity data were available for TBBPA. Based upon the WOE that TBBPA was non-genotoxic in vitro (EU, 2006; EFSA, 2011) and that there was no significant evidence of carcinogenic potential in repeat dose toxicity tests, EFSA (2011) concluded that TBBPA was not likely a carcinogen. One study reported non-malignant tumors in response to oral TBBPA administration, including non-dose-responsive transitional cell papillomas in the urinary bladder that did not progress to malignancy, and thyroid follicular adenomas (Imai et al., 2009, as cited in EFSA, 2011). Colnot et al. (2014) discuss the available data and conclude that the thyroid tumors are unsuitable for use in human risk assessment on the basis on species sensitivity differences between rodents and humans. Health Canada (2013) concluded that the effect of TBBPA on thyroid hormones remains unclear, and therefore utilized a MOE approach to show that current human exposures are below those that are likely to produce thyroid effects. COT (2006) discussed a lack of consistency in the available thyroid data and the potential for the effect to be reversible. Additionally, neither thyroid tumors nor thyroid histopathology effects were seen in rats or mice treated in the 2-year NTP assay (NTP, 2014; Lai et al., 2015). However, EFSA (2011) identified disrupted thyroid homeostasis as the critical noncancer effect in their MOE analysis. There was only one cancer bioassay identified in our literature search; the 2-year cancer bioassay conducted by NTP (2014) in rats and mice exposed to 0, 250, 500, or 1,000 mg/kg for 5 days a week via oral gavage in corn oil. These study details and results have been extensively reported elsewhere (NTP, 2014; Dunnick et al., 2015; Lai et al., 2015; Wikoff et al., 2015, 2016; U.S. EPA, 2014). The primary tumors identified were uterine tumors (combined adenoma, adenocarcinoma, and malignant mixed Mullerian) in female Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 rats (U.S. EPA, 2014). Other tumors included testicular tumors in male rats; and in male mice hepatic tumors, hemangiomas/hemangiosarcomas, and intestinal tumors were found (U.S. EPA, 2014). The Cancer Assessment Review Committee (CARC) of the U.S. EPA determined TBBPA as "likely to be carcinogenic to humans" based on the female rat uterine tumors and the male mice hemangiomas/hemangiosarcomas, with no mutagenicity concerns (U.S. EPA, 2014). NTP (2014) reached the following conclusions regarding each of these tumor types: Testicular adenomas in male rats: "equivocal evidence of carcinogenic activity" Uterine epithelial tumors in female rats: "clear evidence of carcinogenic activity", Hepatoblastomas in male mice: "some evidence of carcinogenic activity"; Intestinal tumors and hemangiosarcomas: may have been related to chemical administration. 3.4 TBBPA uterine cancer mode of action and weight of evidence analysis The U.S. EPA (2005) guidelines for cancer risk assessment state that the MOA should be evaluated in determining the quantitative approach for dose-response assessment from positive human or experimental animal tumor data. This evaluation is accomplished by proposing a MOA including identification of key events, where data on these key events includes available in vivo, in vitro, and mechanistic studies. These studies are then evaluated relative to the modified Bradford Hill criteria, including strength, consistency, specificity of the association between the key event(s) and tumor outcomes, as well as consideration of the consistency of the dose-response and temporal relationship between the key event and tumors, biological plausibility of the proposed MOA, and coherence of the overall database (Meek et al., 2014). When sufficient data are available, a biologically based dose-response (BBDR) model is the preferred method for low dose extrapolation. Absent such data, U.S. EPA (2005) and other groups such as OEHHA (2013) usually conduct a low-dose extrapolation with a linear model if the chemical acts via a direct DNA-reactive MOA or if the MOA is not known, or via a threshold model based on one or more combinations of relevant tumors for a non-DNA-reactive MOA. Other authoritative groups often rely on a MOE approach for cancer evaluation. However, all these groups support the use of the best available science, including consideration of MOA, in their assessments. An abbreviated MOA and WOE analysis was previously applied by Wikoff et al. (2016) to inform the quantitative approach for derivation of a cancer risk value. In the NTP 2- year TBBPA bioassay, and as evaluated by Wikoff et al. (2015), uterine tumors in rats were identified as the most appropriate endpoint for use in derivation of a cancer toxicity value. Based on the considerable amount of evidence that TBBPA is not mutagenic, a nonlinear MOA was postulated for TBBPA induced uterine tumors based on interference with estrogen metabolism, as discussed by several authors (Borghoff et al., 2016; Lai et al. 2015; Sanders et al., 2016; Wikoff et al., 2015; Dunnick et al., 2015; Harvey et al., 2015; Hall et al., 2017), most comprehensively by Wikoff et al. (2016). The interference with estrogen is not thought to involve TBBPA binding directly to the estrogen receptor (ER). The weak affinity for the estrogen receptor and other in vitro and in vivo studies 15 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 suggests that TBBPA is not estrogenic (Colnot et al, 2014; Lai et al., 2015; Wikoff et al., 2016). Estrogenic effects of TBBPA are controversial since both negative and positive findings are reported in the literature, but the low TBBPA binding affinity to the ER suggests that TBBPA is not directly interacting with this receptor (Lai et al., 2015). Instead, interference with estrogen metabolism via competition for shared biotransformation pathways (glucuronidation and sulfation) is a plausible mechanism, resulting in increased estrogen concentrations that either disrupt hormonal balances or drive estrogen-induced cellular proliferation (Lai et al., 2015). Wikoff et al. (2016) proposed an adverse outcome pathway and presented data for a number of key events, including a WOE analysis for TBBPA induced uterine cancer (Figure 1; adapted from Wikoff et al., 2016). The proposed key events starting with the molecular initiating event are the following: 1) TBBPA binds to estrogen sulfotransferase (sultlel), which inhibits the estrogen sulfation pathway; 2) this inhibition of estrogen sulfation leads to increased estradiol bioavailability; 3a) increased estrogen leads to increased expression of estrogen responsive genes, 3b) alternative estrogen metabolic pathways are activated causing generation of reactive quinones and other reactive species that can interact with DNA, and 3c) potential for disruption of the hormonal balance (with potential for disrupted endocrine signaling); 4) interaction of estrogen responsive genes contributing to cellular proliferation of cells with increased DNA damage and p53 mutations; and 5) hyperplasia of cells leading to the adverse outcome (uterine tumors). These key events and supporting data are extensively discussed in Wikoff et al. (2016), and so are only briefly described below. 16 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Figure 1. Diagram of postulated mode of action for TBBPA-induced uterine tumors. [1] TBBPA binds to estrogen sulfotransferase (sultle1); [2] the estrogen sulfation pathway is inhibited; [3a] bioavailable estrogen can bind the estrogen receptor (ER), which translocates to the nucleus and leads to increased expression of estrogen responsive genes, [3b] alternative estrogen metabolic pathways (such as cytochrome P450s, CYPs) can generate reactive intermediates that can interact with DNA and cause DNA damage; [4] estrogen responsive genes contribute to cellular proliferation of cells, some of which have increased DNA damage and gene mutations. & de SK 22222 Suittes [1] ca s TBBPA [2] CHAPH ER I ER 1 [3a] 13 HO is - Estrogen - NO [3b] [4] on CH.9 [4] , HO 1) TBBPA binds to estrogen sulfotransferase (sultle1). which inhibits the estrogen sulfation pathway Toxicokinetic evidence exists that shows TBBPA utilizes the same sulfation metabolic pathway as estrogen (sultle1). Metabolites in humans include TBBPA-sulfate (Schauer et al., 2006, as cited in Health Canada, 2013; Ho et al., 2017). Computational modeling and quantitative structure activity relationship (QSAR) analysis suggest that TBBPA is structurally able to inhibit sulfotransferase (Wikoff et al., 2016; Gosavi et al., 2013). Additionally, in vitro IC50S for TBBPA inhibition of estradiol sulfotransferase ranges from 12-33 nM (Wikoff et al., 2016; Kester et al., 2002; Gosavi et al., 2013; Hamers et al., 2006, as cited by Borghoff et al., 2016). Thus, when high doses of TBBPA produce high plasma concentrations of TBBPA, the IC50 for sulfotransferase is surpassed and saturation can occur. For example, in vivo studies show that TBBPA doses as low as 50 mg/kg result in plasma concentrations (1,478 nM TBBPA) well above the reported IC50 values (Wikoff et al., 2016; Borghoff et al., 2016). 17 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Taken together with the in vitro data, inhibition of sulfotransferase activity is a plausible molecular initiating event in the mode of action for TBBPA induced uterine cancer (Wikoff et al., 2016). However, more data are required to support this key event, as target tissue dosimetry and temporal relationships are required to determine if TBBPA inhibits sulfotransferase in the uterus (Osimitz et al., 2014). 2) Inhibition of estrogen sulfation leads to increased estradiol bioavailability The binding of estrogen to estrogen sulfotranserase (sultle1) leads to its biotransformation by conferring a sulfate group. When TBBPA interferes in this pathway, estrogen is not biotransformed, meaning more estrogen should be bioavailable systemically. This bioavailable estrogen could result in increased estrogen receptor (ER) activation, metabolic switching to an alternative estrogen metabolic pathway, or imbalance of the estrogen/progesterone ratio that has been implicated in other tumor types (mammary, prostate) (Lai et al., 2015). However, there are currently no data on TBBPA modification of estrogen/progesterone ratios (Lai et al., 2015). Alternatively, the loss of estrogen sulfotransferase might result in increased plasma estrogen levels that are implicated in the development of estrogen dependent human endometrial cancer (Cornel et al., 2017). There are a paucity of data investigating TBBPA exposure resulting in increased estrogen bioavailability, although theoretically, competition for sulfation of estrogen would reduce estrogen-sulfate conjugates, resulting in bioavailable estrogen able to bind to the ER (sulfated estrogens are not able to bind the ER) (Fu et al., 2011). This increased non- sulfated, bioavailable estrogen could also shift the estrogen metabolic pathway to alternatives that can result in the generation of reactive species (Wikoff et al., 2016). However, Sanders et al. (2016) reported unchanged estrogen serum levels following 5 daily gavage doses of TBBPA at 250 mg/kg, although they note that the duration of exposure might have been insufficient to produce changes and that use of serum estrogen levels serve as a poor proxy for endometrium estrogen levels. While this step is biologically plausible, more data are needed for a definitive conclusion. 3a) Increased estrogen leads to increased expression of estrogen responsive genes, 3b) alternative estrogen metabolism causing generation of reactive quinones that can interact with DNA, and 3c) potential for disruption of the hormonal balance (with potential for disrupted endocrine signaling) Wikoff et al. (2016) discuss evidence related to increased estrogen and TBBPA-induced increases in estrogen responsive genes in tissues other than the uterus. Since the time of the Wikoff publication, an additional study was published that investigated changes in estrogen concentration and gene expression in response to TBBPA. In a repeat-dose oral gavage study, adult female Wistar Hans rats were treated with vehicle or TBBPA (250 mg/kg-day) for 5 consecutive days to investigate the role of estrogen homeostasis in the MOA of TBBPA (Sanders et al., 2016). In tissue samples taken 24 hours after the 5-day treatment, T4 serum levels were decreased but serum estrogen levels were unchanged. While estrogen levels were not measured in the uterus, there were changes in expression of genes in the uterus that are markers of cell division/growth and metabolism of 18 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 TBBPA/estrogen/thyroid hormones. The gene expression changes in both the proximal and distal sections of the uterus with the greatest significance included genes involved with metabolism and hormone binding, including significantly increased levels of ERa and ERB (Sanders et al., 2016). This data partially supports an increase in estrogen responsive genes from TBBPA exposure, however, more data is needed to show that this is directly resultant from increased bioavailable estrogen, and more data are need to identify these changes specific to uterine tissues. Wikoff et al. (2016) discuss estrogen homeostasis as a balance of various metabolic pathways. Once one pathway is disrupted, alternative estrogen metabolism pathways (other than sulfation) may compensate. One of these pathways, the catechol estrogen pathway, results in the oxidation of catechol estrogens with reactive quinone intermediates. These reactive quinones can interact with DNA, and have been implicated in some cancers (Wikoff et al., 2016). For example, these intermediates could be leading to DNA interactions that could contribute to or selectively increase the proliferation of altered genes, such as the tumor suppressor p53 gene. Finally, there is a potential contribution of disrupted endocrine signaling via hormonal imbalance. Increased estrogen levels have the potential to modify the estrogen/progesterone ratio, and this imbalance has been implicated in other tumor types (mammary, prostate, estrogen dependent human endometrial cancer) (Lai et al., 2015, Cornel et al., 2017). However, there are currently no data on TBBPA modification of estrogen/progesterone ratios (Lai et al., 2015). 4) Interaction of estrogen responsive genes contributing to cellular proliferation, and increased DNA damage and p53 mutations Cellular proliferation is a critical component of hyperplasia leading to tumor formation. It is well established that estrogen binding to the ER can lead to cellular proliferation, and induction of genes related to cell cycle regulation (Sanders et al., 2016). In the NTP (2014) bioassay, there was a clear dose-response with increased uterine adenocarcinomas/adenoma at each increased TBBPA dose; however, data are lacking to confirm temporal associations specifically between increased estrogen serum levels and incidence of cellular proliferation in uterine tissues (Lai et al., 2015). High doses of TBBPA may in part promote uterine tumors in rats by promoting growth of cells with pre-existing mutations in the p53 tumor suppressor gene driven by increased estrogen-dependent cellular proliferation, or through selective proliferation of these mutations caused by reactive quinone intermediates (NTP, 2014; Lai et al., 2015). Additionally, as noted above, TBBPA has low affinity for the ER and so is not likely acting directly on the ER itself. This is plausible as significantly increased p53 mutations were identified in tumors in the NTP study, but since TBBPA is non-mutagenic, TBBPA itself is not directly causing the p53 mutations (Lai et al., 2015). The mechanism of p53 mutation has been previously implicated in cancer development, including human endometrial cancers (Harvey et al., 2015; Wikoff et al., 2016). Harvey et al. (2015) reported on an evaluation and analysis of TBBPA-induced uterine carcinomas in female rats from the NTP study. Analysis using PCR found a high rate of p53 mutations suggesting that uterine carcinogenesis might be partially p53 dependent (Harvey et al., 19 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 2015). In this analysis, the TBBPA-treated samples included Wistar Han rat uterine carcinomas from all dose groups combined (250, 500, and 1,000 mg/kg), thus no p53 mutation dose-response data are available. Of interest, the analysis did not include the malignant mixed Müllerian tumors (MMMTs). While this data supports the proposed key event, more data are needed, specifically dose-response data for p53 mutations and increased proliferation in response to TBBPA, to confirm this. 5) Hyperplasia of cells with p53 mutations leading to the adverse outcome (uterine tumors) Hyperplasia resulting from cellular proliferation is a well-known precursor effect related to the development of tumors, and is associated with increased estrogen levels in humans (Sanders et al., 2016). As noted, by Wikoff, both preneoplastic and nonneoplastic hyperplasia occurred in the NTP study. Atypical endometrial hyperplasia was seen in the NTP 2-year assay and was significantly increased above control at all dose levels, however, it was only identified via the longitudinal inspection, but not the transverse (Wikoff et al., 2016). While there was not a strict dose-response (250 mg/kg-day = 26% incidence; 500 mg/kg-day = 22% incidence; 1,000 mg/kg-day = 26% incidence), preneoplastic lesions are by definition precursors to tumor formation (Wikoff et al., 2016). Additionally, as stated above, a high rate of p53 mutations was identified in the uterine carcinogenesis (Harvey et al., 2015). Finally, the adverse outcome, significantly increased incidence of uterine tumors (adenomas, adenocarcinomas, and malignant mixed Mullerian), was seen with increasing dose in the NTP (2014) 2-year assay. 3.4.5 Weight of evidence A human relevance and concordance analysis of the postulated MOA was conducted by Wikoff et al. (2016), and suggests that given the available data, the proposed MOA is plausible for the development of uterine tumors. Wikoff et al. (2016) conclude this is a plausible mechanism in humans qualitatively, but may be quantitatively excluded based on kinetic/dynamic factors between humans and rats. Given some of the data gaps associated with this MOA, we have given the greatest weight to the non-mutagenic threshold MOA, as multiple lines of evidence support that the MOA identified is non- mutagenic. This is seen in a number of tests showing negative mutagenicity results, which are supported by the recent NTP findings of a negative micronucleus test and two negative Salmonella tests. Finally, the specificity of uterine tumors to the uterine tissue only (and not systemically developed) supports the non-mutagenic assertion (Lai et al., 2015). Thus, wWhile we conclude that the Wikoff et al. (2016) WOE analysis was adequate to establish the postulated MOA. the additional information we cite is further supportive ofgiven-the-evaileble-dete;- this non-mutagenic threshold MOA. and leads us to propose a NSRL based on the threshold approach of EPA (2005). However, a more robust and transparent analysis of the modified Bradford Hill criteria for this MOA would be helofulie-needed. Particularly useful in this instance would be a quantitative WOE ranking, as recently demonstrated by Becker et al. (2017). 20 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Howerer there is eurrently sepport 808 threshold MOA 4.0 Derivation of the NSRL 4.1 Choice of critical study and BMD analysis for POD After an updated evaluation of the available carcinogenicity literature for TBBPA, we agree with the choice of Wikoff et al. (2015) that uterine tumors (adenomas, adenocarcinomas, and malignant mixed Mullerian combined) are the most appropriate cancer endpoint, and were chosen as the critical effect for derivation of the NSRL (Table 4). Uterine tumors in female rats were chosen as the critical cancer effect for derivation of a cancer risk value. In looking at the other tumor types, the testicular adenomas in male rats were considered "equivocal" and occurred at low incidence in the two highest doses (500 mg/kg - 1/50 incidence; 1,000 mg/kg - 3/50 incidence), and as such, were not a reliable choice for the critical effect. The hepatoblastomas in male mice had "some evidence" for carcinogenicity (250 mg/kg - 2/50 incidence; 500 mg/kg - 11/50 incidence; 1,000 mg/kg - 8/50 incidence) with a significant effect in the 500 mg/kg dose. NTP (2014) considered this tumor as "some evidence" because after combining incidences of hepatocellular carcinomas and hepatoblastomas, there was only a significant effect at 250 mg/kg and there was no trend across doses, and this was informed by the historical incidence of these tumor types as spontaneous and related to chemical administration. Therefore, these tumors were not considered for use as the critical effect. The uterine epithelial tumors in female rats were the only tumor type classified as "clear evidence" and occurred with the highest incidence (0 mg/kg - 6/50 incidence; 250 mg/kg - 11/50 incidence; 500 mg/kg - 16/50 incidence; 1,000 mg/kg - 19/50 incidence). Therefore, the uterine tumors were the best choice for the critical effect in derivation of a cancer risk value. Table 4. Dose-response and dose-adjustment of cancer effects (tumors) and precursor effects (hyperplasia) from the NTP (2014) assay for use in BMD analysis. Dose, mg/kg Duration- Hyperplasia Tumor response: (NTP, 2014) adjusted dose response: Uterus original a and residual Commented [MD1]: Doses cannot be more precise than those given in the bioassay. Is is 3 digits for two? Residual longitudinal longitudinal reviews review; endometrium, (combined); adenoma, hyperplasia, atypical adenocarcinoma, or MMMT (combined) 0 0 2 6 250 1798-6 13 11 Formatted: Highlight Formatted: Highlight 500 357-+ 11 16 Formatted: Highlight 21 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 1,000 714.3 13 19 Formatted: Highlight In line with the Wikoff et al. (2015) assessment, we modeled the incidence of combined uterine adenomas, adenocarcinomas, and malignant mixed Müllerian tumors observed in female rats (NTP, 2014). While we agree with Wikoff et al. (2015) on the choice of critical effect, the application of the BMD approach and use of the BMDL10, and allometric adjustment of the POD to an HED, we had the benefit of additional literature that allowed us to agree with them that of the Factor appreach- extrapolate to a riste specifie dese to elsewheresupport- a non-mutagenic, threshold MOAresponse, and the determination of a safe dose values are through the application of uncertainty factors to the POD analogous to an RfD or TDI approach (U.S. EPA, 2005). Specifically, conclusion is supported by Wikoff et al. (2015,2016), who suggest that the linear cancer slope factor approach is inappropriate for a non- mutagenic chemical, and suggested that a threshold approach based on a non-mutagenic MOA is most appropriate. This conclusion is also supported However, ai the time-of-their 2015 publication data investigating the TBBPA MOA not there were date avay the tinear defacia stope faeter and the stedies-by Sanders et al. (2016) and Lai et al. (2015), Thus. coupled the postalated MOA by Wikeff et at (2016) is adequate evidence exists to move away from the default linear approach to a threshold approach for this tumor type. Even-though-the MOA is enly postulated) addition, the negative mutagenicity and genotoxicity data and the specificity of the tumor response to specific tissue types are all sufficient to suggest that a threshold approach is most scientifically credible to develop an NSRL. The results of the BMD analysis on adenoma, adenocarcinoma, or MMMT (combined) incidence in relation to TBBPA exposure are shown in Table 5. The log-logistic model (Figure 2) best fits the data based on all quantitative fit criteria: p-value (0.845), scaled residuals (0.042) at the dose with the response closest to the BMR, and AIC (223), resulting in a dose-adjusted BMD10 of 169 mg/kg-day corresponding to the BMDL10 of 103 mg/kg-day. This model provides a similar BMD to that from the multistage model (i.e., the model chosen by Wilkoff et al., 2015), but the loglogistic model results are more conservative and better fit the data, particularly in the dose region of interest. Atypical hyperplasia of the endometrium was also modeled as a potential precursor effect to tumor formation, but no model provided adequate fit of the data (i.e., p < 0.1). Table 5. BMD models examining the relationship between TBBPA exposure* Formatted Table and uterine cancer incidence (adenoma, adenocarcinoma, or MMMTs, combined) in female rats from NTP (2014). 22 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Model p- Scaled Visual Fit Ratio AIC BMD10 BMDL10 Value Residual BMD/ at Dose BMDL Gamma 0.75 0.14 good 1.5 223.1 195 127 Logistic 0.46 0.88 acceptable 1.3 224.0 290 219 LogLogistic 0.85 0.042 good 1.7 222.8 169 103 LogProbit 0.32 0.89 acceptable 1.5 224,8 317 216 Multistage (1*) 0.75 0.14 good 1.5 223.1 195 127 Multistage (2*) 0.75 0.14 good 1.5 223,1 195 127 Multistage (3*) 0.75 0.14 good 1.5 223.1 195 127 Probit 0.49 0.84 acceptable 1.3 223.9 277 208 Weibull 0.75 0.14 good 1.5 223.1 195 127 Quantal- Linear 0.75 0.14 good 1.5 223.1 195 127 *Duration-adjusted dose (5/7 days) *The numbers correspond to the number of degrees of polynomial in the multistage model The bolded row indicates the best fitting model Figure 2. Log logistic modeling results of uterine cancer (adenoma, adenocarcinoma, or MMMTs, combined) in female rats from NTP (2014). 23 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Log-Logetic with of sos, Exta Risk for the BMD and 3.95 Lower for the ......... 0.8 0.4 0.3 0.2 0.: BMOL BMC o 200 aco 800 800 1000 does The resulting duration-adjusted BMDL10 of 103 mg/kg-day was adjusted to a human equivalent dose (HED) of 26 mg/kg-day using allometric scaling (Equation 1; [25.6 mg/kg-day = 103 mg/kg-day x 3 4.2 Uncertainty factors Uncertainty factors were applied to the BMDL10[HED] to derive an RfDcar of 0.9 mg/kg- day using Equation 2 (0.85 mg/kg-day = 25.6 mg/kg-day/(10 x 3 X 1 x 1 x 1 = 30). The uncertainty factor that addresses interindividual variability (UFH) (also referred to as intraspecies variability) accounts for toxicokinetic and toxicodynamic variation across humans and is intended to protect sensitive subpopulations. Unless a study is conducted in a sensitive human population or 3 As noted previously, the choice of default body weight (between female at 58 kg and male at 70 kg) does not significantly change the resulting HED (27.5 mg/kg-day versus 26.3 mg/kg-day, respectively). For this and the reasons listed in the footnote above, we have used the default body weight of 70 kg. 24 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 there are data on human variability in response, the default for the UFH is 10. Given the lack of available data to move away from the default, we recommend the application of a 10-fold factor. The uncertainty factor for interspecies extrapolation (UFA) (also referred to as animal-to-human extrapolation) accounts for the translation of data from experimental animals to humans, specifically the toxicokinetic and toxicodynamic variation between species. Because we adjusted the POD to a human equivalent dose, this is presumed to account for the toxicokinetic differences across species (Renwick et al., 1999). Therefore, a reduced factor of one half the power of 10 (~3-fold) should be applied to account for the toxicodynamic differences between species (Renwick et al., 1999). The uncertainty factor for use of a LOAEL and extrapolation to a NOAEL (UFL) is not needed, since a BMD analysis was conducted. Therefore, a factor of 1 is applied. Additionally, the uncertainty factor for extrapolation of a subchronic critical study to a chronic exposure (UFs) is also not necessary, since a 2-year cancer bioassay was selected as the critical study. Therefore, a factor of 1 is applied. The uncertainty factor for database completeness (UFD) represents a judgment on the quantity and quality of the toxicology information available on the substance. TBBPA has an adequate toxicological database, particularly for noncancer effects, to assess the toxicological outcomes and potential adverse effects from exposure. However, this factor has also been utilized on occasion to account for severity of effect aimed to introduce an additional margin of safety when a compound has produced some form of severe or irreversible toxicity that is not addressed directly by the POD. It is worth noting that the noncancer dataset identified sensitive reproductive effects from TBBPA exposure [BMDLs of 0.5 mg/kg-day for increased testes weight and 0.6 mg/kg-day for increased F1 pituitary weight in males (van der Ven et al., 2008; Lilienthal et al., 2008; as cited in Health Canada, 2013)], and additional thyroid effects were seen but were largely uncharacterized [F1 males and females had decreased T4 levels (BMDL10 31 and 16 mg/kg, respectively)]. However, these data would be relevant for noncancer assessment, and as we are specifically addressing cancer endpoints, the application of this factor is not warranted. Specifically, the availability of the NTP 2-year comprehensive cancer bioassay is sufficient to inform the database for cancer. In total, we recommend the application of a composite uncertainty factor of 30 (3 x 10) to protect for uncertainties in the database and extrapolations. Therefore, for the derivation of the oral NSRL, we divide the BMDL10[HED] of 25.6 mg/kg-day by 30 to derive a cancer safe dose of 0.9 mg/kg-day. Based on the default human body weight of 70 kg, the NSRL is 60 (59.5) mg/day using Equation 3 (60 mg/day = 0.85 mg/kg-day x 70 kg). There were not enough published data identified to derive an inhalation NSRL. There was at least one DNEL derived for inhalation exposure, the studies that those values were based on were not publically available, and the relevance to cancer development from 25 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 inhalation exposure remains uncharacterized. 5.0 Discussion 5.1 Comparison of NSRL to RSD published by Wikoff et al., 2015 An NSRL of 60 mg/day was adapted from an RfDcancer of 0.9 mg/kg-day for a threshold MOA leading to uterine cancer seen in the recent NTP (2014) bioassay. The NSRL value (60 mg/day) is roughly 300-fold higher than the cancer slope factor adjusted to an NSRL derived by Wikoff et al. (2015) for 10-5 risk for the same tumor data (the risk level assigned by the NSRL) (0.0032 mg/kg-day x 70 kg = 0.22 mg/day). This difference reflects the use of a point estimate instead of a slope factor for low dose extrapolation, and slight differences in the BMDL due to model selection. Table 4 shows the various BMD model outputs for the uterine tumor data. While our models appear to align with those of Wikoff et al. (2015), we chose a different model based on an evaluation of multiple parameters (p-value, scaled residuals, visual fit, ratio of BMD to BMDL, and AIC). This difference in model selection accounts for a roughly 20% difference in the chosen points of departure (126.6 mg/kg-day chosen by Wikoff and colleagues versus 103 mg/kg-day chosen for this assessment). The NSRL proposed here of 60 mg/day, however, is within an order of magnitude and roughly aligns with a potential NSRL of 42 mg/day based on the RfD of 0.6 mg/kg-day derived by Wikoff et al. (2015) for noncancer uterine hyperplasia (i.e., 0.6 mg/kg-day x 70 kg = 42 mg/day). As some types of uterine hyperplasia are considered an upstream precursor to uterine cancer, the alignment of these values makes sense biologically. Additionally, protection from precursor effects is typically anticipated to protect from the downstream cancer effect. However, BMD models were not able to adequately fit the uterine hyperplasia data (p-value <0.1), even when the responses at the highest dose were dropped from the model (an approach that is consistent with U.S. EPA guidance; U.S. EPA, 2012). We chose not to use the hyperplasia precursor for cancer effects for a few reasons: 1) there is little currently available practical experience in using a POD based on cancer precursor effects to develop an RfD for a tumor; and 2) poor BMD model fit (p-value < 0.1) limits confidence in, and interpretation of, model results. 5.2 Comparison of RfD cancer to available risk values A comparison was made between the RfDc: derived here and other available risk values (see Table 2; Figure 3). The derived RfD cancer cancer (0.9 mg/kg-day) falls appropriately in respect to the biology on the risk value continuum as shown in Figure 3. As expected, DNELs for noncancer reproductive and developmental effects (DNEL repro and DNEL dev, both = 10 mg/kg-day) and DNELs for noncancer no effect levels (5 and 2.5 mg/kg-day) are higher than the derived RfD cancer by ~2.7 to 11-fold. The TDI, which was also derived for a noncancer no effect level (1 mg/kg-day), is roughly the same as the RfDcancer. This makes biological sense given the thresholded MOA for uterine tumor formation. The RfD for uterine hyperplasia (0.6 mg/kg-day), is slightly lower than the RfD This is expected and makes biological sense given that uterine hyperplasia is a precursor effect to uterine tumors. One would expect an RfD for a precursors effect to be 26 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 lower than that for the apical effect. Finally, the DNEL for thyroid effects (0.16 mg/kg- day) is lower than all other available noncancer values. However, as noted above in Section 3.3.1, there is a large amount of uncertainty associated with the thyroid endpoint (species sensitivity differences between rodents and humans, a lack of consistency in the available thyroid data, the potential for the effect to be reversible, neither thyroid tumors nor thyroid histopathology effects were seen in rats or mice treated in the 2-year NTP assay). Finally, the cancer slope factor (0.0032 mg/kg-day) is significantly lower than all other available risk values (from 50- to ~3,000-fold lower). Typically, the expectation is for cancer risk values to be lower than those for noncancer, under a no-threshold assumption. However, given the evidence for a threshold MOA for the most sensitive uterine tumors, the cancer slope factor is likely highly conservative and not biologically appropriate (280-fold lower than the RfDcancer). Figure 3. Comparison of available cancer and non-cancer risk values for TBBPA. 11 10 10 10 9 8 7 6 5 5 4 2.5 3 2 0.6 0.9 1 1 0.0032 0.16 0 5.2 Uncertainties Uncertainties are associated with using the malignant mixed Müllerian tumor (MMMT) data combined with the uterine adenomas and adenocarcinomas because of the rarity in their occurrence, and the fact that a dose-dependent trend was not reported in TBBPA treated rats. MMMTs are a very rare, spontaneous neoplasm in rats (Dunnick et al., 2015). Furthermore the historical data "are limited in Wistar Han rats because few studies using this strain have been conducted" (NTP, 2014). However, a large body of evidence on the epithelial histogenesis of MMMTs and their relevance to uterine cancers was cited as reasoning to include the MMMTs (Dunnick et al., 2015). The use of a new method of examining the rat uterus (a secondary Residual Longitudinal Review combined with the initial standard Transverse Review) allowed for the identification of additional tumors; 27 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 the additional transverse review identified adenocarcinomas or adenomas in all female rats with MMMTs. Therefore, BMD models including only adenomas and adenocarcinomas would be identical to those for combined adenomas, adenocarcinomas, and MMMTs. The MOA for uterine tumor formation needs additional validation, specifically, it would highly benefit from a comparison to the modified Bradford Hill criteria (such as conducted in Meek et al., 2014) and a quantitative weight of evidence approach (such as conducted in Becker et al., 2017). For the MOA, in vivo data to confirm that TBBPA competes for estrogen sulfotransferases are lacking. Target tissue dosimetry and temporal relationships to determine if TBBPA inhibits sulfotransferase in the uterus are required to determine if this mechanism is viable (Osimitz et al., 2014). Other uncertainties in the estrogen metabolism pathway have not been addressed, including the role of the alternative estrogen metabolism pathways, such as inhibition of hydroxysteroid- dehydrogenase-17beta (leading to increased estrogen activity) and induction of phase I enzymes CYP1A1 and CYP1B1 (leading to reactive metabolite formation) (Sanders et al., 2016). Others reviewed the plausibility of these alternative pathways but a more in- depth review is needed (Wikoff et al., 2015; Dunnick et al., 2015; Sanders et al., 2016). Additionally, more data is needed to evaluate this MOA at human relevant exposure doses. Wikoff et al. (2016) and others suggest this MOA operates only at high doses where saturation of the estrogen metabolic pathway occurs. Wikoff et al. (2016) suggests extrapolation to lower doses for protection of human health may be inappropriate given human doses are not expected to be high enough to lead to this MOA. However, we provide clear rationale that our NSRL is appropriate and as applied, is protective of the development of uterine tumors for several reasons: 1) tumors appear to be formed only at high doses due to non-mutagenic mechanism, and no tumors were identified in previous studies except the non-malignant tumors (transitional cell papillomas in the urinary bladder and thyroid follicular adenomas) (Imai et al., 2009, as cited in EFSA, 2011). This suggests that the potential for carcinogenicity from TBBPA exposure is quite low, will only occur at high doses, and negates the need for low-dose extrapolation; and 2) Wikoff reports that doses of 50 mg/kg are enough to surpass the sulfotransferase IC50, suggesting that this mechanism could be activated at doses below those in the NTP study. However, this dose would need to be exceeded in a chronic fashion in order for tumor formation to occur, and the RfDcan is well below this IC50 (0.9 Therefore, the derived RfDcancer is protective of uterine tumors via a non-threshold mode of action, and low dose extrapolation is not necessary. A final caveat relates to the existence of other potential MOAs/AOPs. Effects on thyroid homeostasis have also been seen, and for noncancer effects have produced relatively low BMD/Ls. Studies have shown that high TBBPA concentrations in vitro inhibit thyroid hormone metabolism with an IC50 of 460 nM for SULT1A in human liver cytosol, and the contribution of this MOA remains unclear (Butt and Stapleton, 2013). However, there is no indication that thyroid tumors result from exposure to TBBPA as neither tumors nor histopathology was found in the NTP assay. Additionally, there were testicular adenomas and hepatoblastomas identified in the NTP (2014) report. It is possible that these tumor types might drive the RfD cancer value lower, but as for the uterine tumors, are anticipated 28 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 to be non-mutagenic thresholded responses due to the non-mutagenic nature of TBBPA. 6.0 Conclusions Building off of previously published work investigating the mode of action and toxicity of TBBPA (ESFA, 2011; Health Canada, 2013; Wikoff et al., 2015, 2016; Lai et al., 2015), and using the cancer results seen from the recent NTP 2-year cancer bioassay, we have derived a no-significant-risk-level (NSRL) for TBBPA of 60 mg/day. The NSRL is based on uterine tumors (adenomas, adenocarcinomas, and malignant mixed Mullerian) identified in female rats exposed to TBBPA for 2-years via oral gavage. TBBPA has been shown to be a non-mutagenic carcinogen acting through an estrogen interference mode of action, and as such the most appropriate approach to derivation of a cancer risk value is a threshold approach, akin to an RfD cancer. Using the NTP study data, we derived a BMDL10 point of departure of 103 mg/kg-day and adjusted this to a human equivalent dose (HED) of 25.6 mg/kg-day using allometric scaling. We applied a composite adjustment factor of 30 to the POD to derive an RfDcancer of 0.9 mg/kg-day. Based on an average human body weight of 70 kg, the cancer safe dose was adjusted to an NSRL of 60 mg/day. Acknowledgements Funding for this work was provided by the American Chemical Council (ACC) and the developmental reserve funds of the University of Cincinnati, Risk Science Center. References Barnes, D.G., & Dourson, M.L. (1988). Reference dose (RfD): Description and use in health risk assessments. Regul Toxicol Pharmacol. 8, 471-486. Becker, R.A., Dellarco, V., Seed, J., Kronenberg, J.M., Meek, B., Foreman, J., Manibusan, M.K. (2017). Quantitative weight of evidence to assess confidence in potential modes of action. Regul Toxicol Pharmacol. 86, 205-220. Doi: 10.1016/j.yrtph.2017.02.017 Borghoff, S.J., Wikoff, D., Harvey, S., & Haws, L. (2016). Dose- and time-dependent changes in tissue levels of tetrabromobisphenol A (TBBPA) and its sulfate and glucuronide conjugates following repeated administration to female Wistar Han Rats. Toxicol Rep, 3, 190-201. doi:10.1016/j.toxrep.2016.01.007 Butt, C.M., & Stapleton, H.M. (2013). Inhibition of thyroid hormone sulfotransferase activity by brominated flame retardants and halogenated phenolics. Chem Res Toxicol, 26(11), 10.1021/tx400342k. oi:10.1021/tx400342k Colnot, T., Kacew, S., & DeKant, W. (2014). Mammalian toxicology and human exposures to the flame retardant 2,2, 6,6,-tetrabromo-4,4-isoprpoylidenediphenol (TBBPA): Implications for risk assessment. Arch Toxicol, 88, 1180-1188. doi: 10.1007/s00204-013-1180-8 COT (Committee on Toxicology). (2004). COT statement on tetrabromobisphenol A- 29 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 review of toxicological data. Retrieved from UK Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment. Available at: https://cot.food.gov.uk/committee/committee-on- oxicity/cotstatements/cotstatementsyrs/cotstatements2004/cotstatements2004tbbp a [accessed July 10, 2017] Cope, R. B., Kacew, S., & Dourson, M. (2015). A reproductive, developmental and neurobehavioral study following oral exposure of tetrabromobisphenol A on Sprague-Dawley rats. Toxicology, 329, 49-59. doi: 10.1016/j.tox.2014.12.013 Cornel, K. M. C., Krakstad, C., Delvoux, B., Xanthoulea, S., Jori, B., Bongers, M. Y. Romano, A. (2017). High mRNA levels of 176-hydroxysteroic dehydrogenase type 1 correlate with poor prognosis in endometrial cancer. Mol Cell Endocrinol, 442, 51-57. doi: 10.1016/j.mce.2016.11.030 Dunnick, J. K., Sanders, J. M., Kissling, G.E., Johnson, C. L., Boyle, M. H., & Elmore, S. A. (2015). Environmental chemical exposure may contribute to uterine cancer development: studies with tetrabromobisphenol A. Toxicol Pathol, 43, 464-473. doi: 10.1177/0192623314557335 European Chemicals Agency (ECHA). (2017). 2017. 2,2',6,6'-tetrabromo-4,4'- isopropylidenediphenol. Information on Chemicals, Registration Dossier. Last modified: 11-Jul-2017. Available online at: https://echa.europa.eu/registration- dossier/-/registered-dossier/14760/1 [accessed July 17, 2017] European Food Safety Administration (EFSA). 2011. Scientific Opinion on Tetrabromobisphenol A (TBBPA) and its derivatives in food. EFSA J, 9: 2477. Available online at: hitps://www.efsa.europa.eu/en/efsajournal/pub/2477 [accessed July 17, 2017] European Food Safety Administration (EFSA). 2017. Update: use of benchmark dose approach in risk assessment. EFSA J, 15: 4658. Available online at: äle:///Users/pecqueam/Downloads/Hardy et al-2017-EFSA Journal.pdf [accessed July 17, 2017] European Union (EU). 2006. Risk Assessment Report: ",6,6'-Tetrabromo-4,4" Isopropylidenediphenol (Tetrabromobisphenol-A or TBBP-A), Part II - Human Health. European Chemicals Bureau, European Commission, 4th Priority List, Volume 63. Available online at: https://echa.europa.eu/documents/10162/326000fe-b4fe-4828-b3d3 93c24cledd51 [accessed July 17, 2017] Fu, J., Fang, H., Paulsen, M., Ljungman, M., Kocarek, T. A., & Runge-Morris, M. (2011). Regulation of estrogen sulfotransferase expression by confluence of MCF10A breast epithelial cells: Role of the aryl hydrocarbon receptor. J Pharmacol Exp Ther., 339(2), 597-606. doi: 10.1124/jpet.111.185173 Gosavi, R. A., Knudsen, G. A., Birnbaum, L. S., & Pedersen, L. C. (2013). Mimicking of estradiol binding by flame retardants and their metabolites: A crystallographic analysis. Environ Health Perspect, 121, 1194-1199. doi: 10.1289/ehp. 1306902 30 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Grosse, Y., Loomis, D., Guyton, K.Z., Ghissassi, F-E., Bouvard, V., Benbrahim-Tallaa, L., Straif, K. (2016). Carcinogenicity of some industrial chemicals. The Lancet Oncol, 17(4), 419-420. Hall, S.M., Coulter, S.J., Knudsen, G.A., Sanders, J.M., & Birnbaum, L.S. (2017). Gene expression changes in immune response pathways following oral administration of tetrabromobisphenol A (TBBPA) in female Wistar Han rats. Toxicol Lett, 272, 68-74. doi:10.1016/j.toxlet.2017.03.008 Hamers, T., Kamstra, J.H., Sonneveld, E., Murk, A.J., Kester, M.H., Andersson, P.L., Legler, J., & Brouwer, A. (2006). In vitro profiling of the endocrine-disrupting potency of brominated flame retardants. Toxicol. Sci. 92, 157e-173e. [as cited in Colnot et al., 2014] doi: 10.1093/toxsci/kfj187 Harvey, J. B., Osborne, T. S., Hong, H. H., Bhusari, S., Ton, T. V., Pandiri, A. R., Hoenerhoff, M. J. (2015). Uterine Carcinomas in Tetrabromobisphenol A- exposed Wistar Han Rats Harbor Increased Tp53 Mutations and Mimic High- grade Type I Endometrial Carcinomas in Women. Toxicol Pathol, 43, 1103-1113. doi: 10.1177/0192623315599256 Health Canada. (2013). Screening assessment report of Phenol, 4,4' -(1-methylethylidene) bis[2,6-dibromo- (Tetrabromobisphenol A, TBBPA; CAS 79-94-7), Ethanol, 2,2'-[(1-methylethylidene)bis[(2,6-dibromo-4,1-phenylene)oxy]lbis (known as TBBPA bis(2-hydroxyethyl ether, CAS 4162-45-2) and Benzene, 1,1'-(1- methylethylidene)bis[3,5-dibromo-4-(2-propenyloxy)-(TBBPA bis(allylether, CAS 25327-89-3). Government of Canada, Environment Canada, Health Canada. Cat. No.: En14-110/2013E-PDF. ISBN: 978-1-100-22898-3. Ho, K. L., Yuen, K. K., Yau, M. S., Murphy, M. B., Wan, Y., Fong, B. M., Lam, M. H. (2017). Glucuronide and sulfate conjugates of tetrabromobisphenol A (TBBPA): Chemical synthesis and correlation between their urinary levels and plasma TBBPA content in voluntary human donors. Environ Int, 98, 46-53. doi: 10.1016/j.envint.2016.09. Imai, T., Takami, S., Cho, Y. M., Hirose, M., & Nishikawa, A. (2009). Modifying effects of prepubertal exposure to potassium perchlorate and tetrabromobisphenol A on susceptibility to N-bis(2-hydroxypropyl)nitrosamine- and 7,12 dimethylbenz(a)anthracene-induced carcinogenesis in rats. Toxicol Lett, 185, 160- 167. [As cited in EFSA, 2011]. doi: 10.1016/j.toxlet.2008.12.013 International Toxicity Estimates for Risk (ITER). A TOXNET Database. U.S. National Library of Medicine, National Institutes of Health. Available online at: https://toxnet.nlm.nih.gov/newtoxnet/iter.htm [accessed July 17, 2017] Jeff Gift, U.S. EPA, personal communication via email. In reference to: questions on benchmark dose. November 18, 2016. Kester, M.H., Bulduk, S., van Toor, H., Tibboel, D., Meinl, W., Glatt, H., Visser, T.J. (2002). Potent inhibition of estrogen sulfotransferase by hydroxylated metabolites 31 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 of bolyhalogenated aromatic hydrocarbons reveals alternative mechanism for estrogenic activity of endocrine disrupters. J. Clin. Endocrinol. Metab 87, 1142e- 1150e. Klimisch, H.J., Andreae, M., & Tillmann, U. (1997). A systematic approach for evaluating the quality of experimental toxicological and ecotoxicological data. Regul. Toxicol. Pharm. 25, 1-5. Lai, D. Y., Kacew, S., & Dekant, W. (2015). Tetrabromobisphenol A (TBBPA): Possible modes of action of toxicity and carcinogenicity in rodents. Food Chem Toxicol, 80, 206-214. doi: 10.1016/j.fct.2015.03.023 Lilienthal, H., Verwer, C., van der Ven, L., Piersma, A., & Vos, J. (2008). Exposure to tetrabromobisphenol A (TBBPA) in Wistar rats: Neurobehavioral effects in offspring from a one-generation reproduction study. Toxicology, 246, 45-54. [as cited in Health Canada, 2013] doi: 10.1016/j.tox.2008.01.007 Meek, M.E., Palermo, C.M., Bachman, A.N., North, C.M., & Lewis, R.J. (2014). Mode of action human relevance (species concordance) framework: Evolution of the Bradford Hill considerations and comparative analysis of weight of evidence. J Appl Toxicol, 34, 595-606. doi: 10.1002/jat.2984 MPI Research, 2002a. A 90-day oral toxicity study of tetrabromobisphenol-A in rats with a recovery group (unpublished). As cited in COT (2004). MPI Research, 2002b. An oral two generation reproductive, fertility and developmental neurobehavioural study of tetrabromobisphenol-A in rats (unpublished). Performed by MPI Research Inc., Mattawan, MI for the American Chemistry Council BFRIP, Arlington, VA. Study Number: 474-004, pp 2199 [as cited in Colnot et al., 2014] MPI Research. (2001). Final report-an oral prenatal developmental toxicity study with tetrabromobisphenol-A in rats (unpublished). [as cited in Colnot et al., 2014]. National Institute of Environmental Health Sciences (NIEHS). (2002). Tetrabromobisphenol A [79-94-7]: Review of Toxicological Literature. National Institutes of Health, National Toxicology Program. Available online at: https://ntp.niehs.nib.gov/ntp/btdocs/chem_background/exsumpdf/tetrabromobisph enola 508.pdf [accessed July 17, 2017] NTP (National Toxicology Program). (2014). Technical Report on the Toxicology Studies of Tetrabromobisphenol A (CAS NO. 79-94-7) in F344/NTac rats and B6C3F1/N mice and Toxicology and Carcinogenesis Studies of Tetrabromobisphenol A in Wistar Han [Crl:WI(Han)] rats and B6C3F1/N mice (Gavage Studies). NTP TR 587, September, 2014. National Institutes of Health, U.S. Department of Health and Human Services, Research Triangle Park, NC. Available online at: https://ntp.niehs.nib.gov/ntp/htdocs/lt_xpts/tr587508.pd [accessed July 7, 2017] Office of Environmental Health Hazard Assessment (OEHHA). (1989). Final Statement of Reasons. No Significant Risk Levels and No Observable Effect Levels. 32 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Proposition 65, California Environmental Protection Agency. June, 1989. Available online at: https://oehha.ca.gov/media/downloads/emnr/art78fsrjune1989.pdf [accessed July 7, 2017] Office of Environmental Health Hazard Assessment (OEHHA). (2013). Article 7. No Significant Risk Levels. § 25703. Quantitative Risk Assessment. Title 27, California Code of Regulation. Available online at: ittps://oehha.ca.gov/media/downloads/proposition-65/general-info/regsart7.pdf [accessed July 19, 2017] Osimitz, T.G., Dourson, M.L., Hayes, A. W., & Kacew, S. (2014). Crystallographic analysis and mimicking of estradiol binding: Interpretation and speculation. Environ Health Perspect, 122: A91-A92. DOI:10.1289/ehp.1307987 Renwick, A.G. (1999). Subdivision of uncertainty factors to allow for toxicokinetics and toxicodynamics. Human and Ecological Risk Assessment, 5, 1035-1050. doi: 10.1080/10807039991289329 Sanders, J.M., Coulter, S.J., Knudsen, G.A., Dunnick, J.K., Kissling, G.E., & Birnbaum, L.S. (2016). Disruption of estrogen homeostasis as a mechanism for uterine toxicity in Wistar Han rats treated with tetrabromobisphenol A. Toxicol Appl Pharmacol, 298, 31-39. doi: 10.1016/j.taap.2016.03.007 Schauer, U.M.D., Völkel, W., & Dekant, W. (2006). Toxicokinetics of tetrabromobisphenol A in humans and rats after oral administration. Toxicol Sci 91, 49-58. [as cited in Health Canada, 2013] U.S. EPA (Environmental Protection Agency). (1986). Guidelines for Mutagenicity Risk Assessment. U.S. Environmental Protection Agency: Washington, DC, EPA/630/R-98/003. Available online at: ps://www.epa.gov/sites/production/files/2013-09/documents/mutagen2.pdf [accessed July 7, 2017] U.S. EPA (Environmental Protection Agency). (2005). Guidelines for Carcinogen Risk Assessment. U.S. Environmental Protection Agency: Washington, DC, EPA/630/P-03/001F. Available online at: https://www.epa.gov/risk/guidelines- carcinogen-risk-assessment [accessed July 7, 2017] U.S. EPA (Environmental Protection Agency). (2012). Benchmark Dose Technical Guidance. Risk Assessment Forum, U.S. Environmental Protection Agency: Washington, DC.100-R-12-001. Available online at: attps://www.epa.goy/risk/benchmark-dose-technical-guidance[accessed July 7, 2017] U.S. EPA (Environmental Protection Agency). (2014). Supplemental File 4: Tetrabromobisphenol A (TBBPA, CASRN: 79-94-7) Cancer Assessment Review Committee Report. Health Effects Division, Office of Pesticide Programs, U.S. Environmental Protection Agency: Washington, DC. Available online at: https://www.epa.gov/assessing-and-managing-chemicals-under. 33 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 scalsupplemental-file-4-tetrabromobisphenol-tbbpa-casmn-79 [accessed July 7, 2017] Van der Ven, L.T., Van de Kuil, T., Verhoef, A., Verwer, C.M., Lilienthal, H., Leonards, P.E., Piersma, A.H. (2008). Endocrine effects of tetrabromobisphenol-A (TBBPA) in Wistar rats as tested in a one-generation reproduction study and a subacute toxicity study. Toxicology, 245, 76-89. doi: 10.1016/j.tox.2007.12.009 [as cited in Health Canada, 2013, and EFSA, 2011] Wheeler, M.W., & Bailer, A.J. (2007). Properties of model-averaged BMDLs: a study of model averaging in dichotomous response risk estimation. Risk Anal, 27(3): 659- 70. doi: 10.1111/j.1539-6924.2007.00920.x Wikoff, D., Thompson, C., Perry, C., White, M., Borghoff, S., Fitzgerald, L., & Haws, L.C. (2015). Development of toxicity values and exposure estimates for tetrabromobisphenol A: Application in a margin of exposure assessment. J Appl Toxicol, 35, 1292-1308. doi: 10.1002/jat.3132 Wikoff, D.S., Rager, J.E., Haws, L.C., & Borghoff, S.J. (2016). A high dose mode of action for tetrabromobisphenol A-induced uterine adenocarcinomas in Wistar Han rats: A critical evaluation of key events in an adverse outcome pathway framework. Regul Toxicol Pharmacol, 77, 143-159. doi: 10.1016/j.yrtph.2016.01.018. Yang, Y., Ni, W.W., Yu, L., Cai, Z., Yu Y.J. (2016). Toxic effects of tetrabromobisphenol A on thyroid hormones in SD rats and the derived-reference dose. Biomed Environ Sci, 29(4), 295-299. 34 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226

What is the Visual Fit of Logistic?

kxcn0226

kxcn0226_p4, kxcn0226_p5, kxcn0226_p6, kxcn0226_p7, kxcn0226_p8, kxcn0226_p9, kxcn0226_p10, kxcn0226_p11, kxcn0226_p12, kxcn0226_p13, kxcn0226_p14, kxcn0226_p15, kxcn0226_p16, kxcn0226_p17, kxcn0226_p18, kxcn0226_p19, kxcn0226_p20, kxcn0226_p21, kxcn0226_p22, kxcn0226_p23, kxcn0226_p24, kxcn0226_p25, kxcn0226_p26, kxcn0226_p27, kxcn0226_p28, kxcn0226_p29, kxcn0226_p30, kxcn0226_p31, kxcn0226_p32, kxcn0226_p33, kxcn0226_p34, kxcn0226_p35

acceptable, Acceptable

1.0 Introduction Under the State of California's Proposition 65 (Prop65), a no significant risk level (NSRL) is developed for chemicals that are known to induce cancer in toxicological studies. The NSRL represents the "levels of exposure calculated to result in no more than one excess case of cancer in an exposed population of 100,000, assuming exposure over a 70-year lifetime (10-5 lifetime risk of cancer)" (OEHHA, 1989). California's Office of Environmental Health Hazard Assessment (OEHHA) recently announced its Prop65 notice of intent to list tetrabromobisphenol A (TBBPA) as known to the state to cause cancer. This is likely based on a recent International Agency for Research on Cancer (IARC) assessment that classified TBBPA as "Group 2A: probably carcinogenic to humans" (IARC Monograph in preparation, volume 115 - only the classification is available at the time of publication; Grosse et al., 2016). With the addition of TBBPA to the Prop65, a toxicological evaluation of TBBPA and derivation of an NSRL is needed. The methodology for NSRL derivation is similar to that of the U.S. EPA for developing cancer potency values. An evaluation of the available toxicological data in humans and animals is used to identify a significant biologic response of concern (critical effect) (OEHHA, 1989). In the absence of data to the contrary, noa threshold is assumed for the cancer effect of concern, and OEHHA then develops an NSRL through the use of no- threshold models (cancer slope factor development) based on U.S. EPA guidance (1986, 2005) (OEHHA, 2013). These NSRL values are then compared to exposure estimates to determine the potential to evoke a biological response at relevant environmental exposure levels (margin of safety) (OEHHA, 1989). However, when a threshold in response is supported based on available data, most risk agencies around the World support alternative approaches such as using threshold models. For example, the U.S. EPA (2005) methodology has advanced with the state of risk science, and includes a determination of a linear (non-threshold) or non-linear (threshold) mode of action (MOA) approach. Threshold models suggest that there are low doses of a chemical that do not cause effects and that a high enough dose is needed for effects to occur, while non- threshold models suggest that any dose above zero can lead to an effect (U.S. EPA, 2005). The-One basis for the non-threshold models relates to mutagenic chemicals that cause DNA damage that contribute to carcinogenesis regardless of dose. In fact, identification of mutagenicity mechanisms for cancer development is often a key diagnostic for identification of threshold versus non-threshold mechanisms. This determination impacts the choice of either the derivation of a cancer slope factor and a risk specific dose, or a threshold-based toxicity reference value for cancer effects (RfD 'cancer). TBBPA, a flame retardant chemical that is detected in the environment, albeit at low levels in the U.S., has been extensively studied for a number of years. In order to develop an NSRL, we first reviewed authoritative assessments for TBBPA from regulatory and other agencies to see if an extant cancer risk value had been derived that could be adapted for use as the NSRL. A literature search was conducted from the date of the most recent authoritative review to the present, to identify any new data published since the time of the last review that could inform or update the basis for the NSRL. Data from both the 3 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 authoritative reviews and the published literature were evaluated for toxicological data and mode of action (MOA) information pertinent to cancer development. A risk characterization was then conducted, building off of previous publications, by identification of the critical tumor effect, identification of a point of departure (POD) utilizing Benchmark Dose (BMD) modeling, review of the MOE for tumor formation, derivation of a cancer risk value, and adaptation to an NSRL. 2.0 Methods 2.1 Hazard Identification and Literature Search There are a number of authoritative reviews available from regulatory agencies and others summarizing the toxicology and potential health impacts from exposure to TBBPA. These authoritative reviews were identified through an Internet search in relevant regulatory databases. The Internet was searched by individual key agency web sites, and broadly with ToxPlanet (https://toxplanet.com/). Additionally, an updated literature search was conducted from a few years prior to the date of the most recent review document (Health Canada, 2013), in order to identify any newly published data that could be utilized in derivation of the NSRL. The literature used in this report was in part identified in a systematic literature search in Elsevier Embase, PubMed, and ToxPlanet databases conducted in September, 2016 for the previous 5 years (2011-2016). The results and details of these searches can be found in Table 1. A broad ranging search in each database was initially utilized by searching the chemical name, synonyms, CAS registry number, and relevant acronyms. Data were filtered by limiting to animal or human species. In PubMed, another filter was employed - "NOT preablumin" as this key word was not relevant to toxicology studies but appeared repeatedly in the search results. Identified literature was initially screened and reviewed by title and abstract for content and relevance, and selected literature was subsequently obtained and further reviewed for appropriate data. These studies were reviewed and evaluated in order to determine the most appropriate critical cancer effect for use in deriving the NSRL. Literature regarded as insufficiently reliable for supporting a health conclusion (e.g., inadequate description of methods or data, lack of appropriate dose- response data) were excluded from further consideration. Table 1. Detailed search terms and search strings and resulting number of hits for each database searched to identify literature for use in derivation of the TBBPA NSRL. Database: Search String (see Table 2) No. hits PubMed AI(tetrabromidiphenylolpropane) OR tetrabromodi) OR 6994 tetrabromodi) OR tetrabromobisphenol) OR Tetrabromo-4,4'- isopropylidenediphenol) OR fire guard 2000) OR 79-94-7) OR tbbpa) OR 3,5,3',5'-Tetrabromobisphenol A 4 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 PubMed Added NOT "prealbumin" 863 PubMed (((tetrabromidiphenylolpropane) OR tetrabromodi) OR 135 LAST 5 tetrabromodi) OR tetrabromobisphenol) OR Tetrabromo-4,4'- YRS isopropylidenediphenol) OR fire guard 2000) OR 79-94-7) OR tbbpa) OR 3,5,3',5'-Tetrabromobisphenol A Filter: published in the last 5 years; Animals PubMed E((tetrabromidiphenylolpropane) OR tetrabromodi) OR 78 LAST 5 tetrabromobisphenol a) OR Tetrabromo-4,4' YRS isopropylidenediphenol) OR "Great Lakes BA-59P") OR "BA 59") OR 4,4'-Isopropylidenebis (2,6-dibromophenol)) OR 3,5,3',5'-Tetrabromobisphenol A) OR 2,2',6,6'- Tetrabromobisphenol / A) OR ((79-94-7 OR tbbpa)|) AND "last 5 years"[PDat])) NOT PREALBUMIN Filters: published in the last 5 years; Humans EMBASE tetrabromidiphenylolpropan OR tetrabromodi OR 751 "tetrabromobisphenol a" OR "tetrabromo 4 4 sopropylidenediphenol" OR "4 4 isopropylidenebis (2,6- dibromophenol)" OR "3 5 3 tetrabromobisphenol a" OR "2 2 6 6 Tetrabromobisphenol A" OR 79-94-7 OR tbbpa EMBASE ABOVE (TBBPA STRING) AND ('animal experiment'/de OR 316 'animal tissue'/de OR 'controlled study'/de OR 'correlational study'/de OR 'human'/de OR 'in vivo study'/de OR 'intermethod comparison'/de OR 'nonhuman'/de OR 'normal human'/de OR 'validation process'/de OR 'validation study'/de) AND (2011:py OR 2012:py OR 2013:py OR 2014:py OR 2015:py OR 2016:py OR 2017:py) ToxPlanet TBBPA; 79-94-7 91 As detailed below, due to the lack of available cancer studies other than the NTP (2014) 2-year cancer bioassay, this study was chosen for use in identification of the critical effect. Additional authoritative review papers and published literature (described below) were evaluated to gain an understanding of the noncancer effects of TBBPA as well as the potential MOA for tumor formation. 2.2 Dose-Response Analysis to Derive Point of Departure Benchmark dose (BMD) modeling (BMDS 2.6; U.S. EPA, 2012) was used to evaluate the dose-response relationship between exposure to TBBPA and cancer outcomes. As detailed below, adenoma, adenocarcinoma, or malignant mixed Mullerian tumors 5 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 (MMMTs) (combined) of the uterus identified through both original and residual longitudinal reviews [see Table 2 of Dunnick et al. (2015); NTP (2014)] were modeled to identify a POD. Atypical hyperplasia of the endometrium was also considered [see Table 6 of NTP (2014)]. All standard dichotomous models were considered. BMDs corresponding to 10% extra risk, the benchmark response (BMR), and their 95% lower bounds (BMDLs) were determined. All BMD modeling was done using extra risk. Model parameters were restricted when possible; not all models offer an option for the restriction of the slope or power. The POD reported is the duration-adjusted dose (i.e., the dose x 5/7, to account for dosing on only 5 of 7 days/week). The criteria described in EFSA (2017) as measures of model acceptability are the goodness-of-fit p-value, BMD to BMDL ratio, and the Akaike Information Criterion (AIC). U.S. EPA's BMDS guidance document for interpreting modeling results recommends adequacy determinations based on p-value, scaled residuals, visual fit, consideration of variability among BMDLs across the candidate models, AIC, and professional judgment (U.S. EPA, 2012). Because U.S. EPA's criteria are more inclusive, we discuss each of these in turn. The decision statements below, e.g., what constitutes adequate fit, are based on and adapted from the U.S. EPA guidance. The first criterion is the global statistical goodness of fit test that represents the full dose range of the data. If the p-value is >0.1, then the model is considered to adequately fit the data. Values lower than 0.1 suggest that the model may be statistically significantly different than the data, with values of 0.05 or less decidedly so. Models with values lower than 0.1 are usually rejected. Models with values of 0.05 or less would be rejected unless special circumstances existed, such as a mechanistic motivation for the model. However, models with higher p-values are not necessarily better than models with lower p-values (say, p = 0.5 versus p = 0.2) if both have a p-value >0.1, which is why other criteria, described below, are then used. The second criterion; relatedto-iseal-fit-is the difference in scaled residuals (that is, the difference in the modeled estimate compared with the actual data scaled by the standard error) at the data point closest to the BMR (in this case, 10%), where it is most important that the model fits the data. A scaled residual of 0 means that the model aligns perfectly with the data at that point, although any scaled residual with an absolute value of less than 2 is acceptable. Models with residuals that have an absolute value greater than this value are rejected. Models with lower residuals are usually preferred. U.S. EPA has recently added a scaled residual at the zero dose to one output format for its BMDS software. This parameter may also prove to be useful for future evaluations. The third criterion, related to scaled residuals, is the visual fit. Arguably the least quantitative criterion, visual fit nevertheless allows consideration of how well the model fits the underlying data, especially at the lower end of the curve or how well the model reflects the biological mode of action, if known. Designations of visual fit can include good, acceptable, and poor. Models that have "poor" visual fit should be rejected. Models with good visual fits are generally preferred. 6 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 U.S. EPA's fourth criterion is two-fold. The first part asks whether the BMDL estimates from the remaining models are sufficiently close to each other and reflect no particular influence of the individual models. This emphasizes that the goal of the modeling is to calculate a BMDL. One way to view this is to compare the ratios between the BMD and BMDL among the models. The larger the ratio, the less accurate the model is likely to be. Another useful comparator in previous U.S. EPA guidance was to decide that model-dependence is evident if the BMDLs differed by more than a factor of 3, but this specificity was removed as being too prescriptive (Jeff Gift, U.S. EPA, personal communication). The second part of this fourth criterion is the Akaike Information Criterion (AIC). Of the remaining models, the one chosen will generally have the lowest AIC. However, AICs within a value of 2 of each other are considered to be similar. If several models are still available from which to choose, then the lowest BMD and BMDL can be selected as a conservative choice, or the BMDs and BMDLs of several models can be averaged¹, using either an arithmetic or geometric mean. Such an average BMDL, however, loses its statistical properties, i.e., it is not the 95% lower bound on the average BMD. 2.3 Derivation of NSRL Once the point of departure (POD) was derived using BMDS, standard risk assessment guidance was utilized for the derivation of and cancer risk value and adaptation to an NSRL based on the U.S. EPA and OEHHA methodology (U.S. EPA, 2005; OEHHA, 1989). We first adjusted the POD to a human equivalent dose using allometric scaling (Equation 1). Because the weight-of-evidence for mode of action (MOA) for tumor formation identified did not involve direct DNA interaction, traditional linear cancer slope factor derivation was not conducted (Wikoff et al., 2015, 2016; NTP, 2014). Instead, an RfD. cancer was derived for a non-linear threshold response following the guidance of U.S. EPA (2005). This includes an assessment of the uncertainty associated with the POD and the application of uncertainty factors (Equation 2). Uncertainty factors are used to add conservatism and additional safety to the RfDc: given unknowns about the chemical, to account for data gaps, such as animal to human uncertainty, subchronic to chronic exposures, and to account for intra-individual variability. The derived RfDcancer was then converted to an NSRL by adjusting for body weight (Equation 3). Equation 1. DoseH = Dosea x Where 1Note that this is not the same as model averaging, where the individual model results are combined by using weights, with higher weights for models that fit the data better (Wheeler and Bailer, 2007). 7 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 DoseH = dose in human (BMDL10[HED]) Dosea = dose in animal (the POD for the specified critical effect = BMDL10) BWA = body weight of animal (0.268 kg for control female Wistar from NTP) BWH = body weight of human (70 kg²) Equation 2. RfD cancer = BMDL10[HED/(UFH x UFAX UFs x UFLX UFD) Where BMDL10[HED = benchmark dose lower limit human equivalent dose UFH = uncertainty factor for human variability UFA = uncertainty factor for animal to human extrapolation UFs = uncertainty factor for subchronic to chronic extrapolation UFL = uncertainty factor for LOAEL to NOAEL UFD = uncertainty factor for database completeness Equation 3. NSRL (mg/day) = RfDcance (mg/kg-day) x BWH (kg) Where BWH = body weight of human (70 kg) 3.0 Results 3.1 Literature search results Authoritative reviews identified include the National Institute of Environmental Health Sciences (NIEHS, 2002), the European Union (EU, 2006), the European Commission Committee on Toxicology (COT, 2004), the European Food Safety Authority (EFSA, 2 The body weight of 70 kg is the default body weight for males used by OEHHA as listed in the California Code of Regulations (27 CCR § 25703, 27 CA ADC § 25703; OEHHA, 2013). However, the recommended body weight for females is 58 kg, which is the specific subpopulation of interest, as uterine tumors were identified as the critical effect. We chose to use the 70 kg default as the body weight because: 1) it is more conservative (results in a slightly lower HED) than 58 kg; 2) women in the U.S. tend to be heavier; 3) 70 kg was utilized in most of the previous NSRL documents that we reviewed; and 4) due to the nature of the assessment, the difference between 70 kg and 58 kg is not enough to significantly change the final NSRL value (within an order of magnitude). 8 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 2011), and Health Canada (2013). At the time of this publication, the IARC monograph on TBBPA was unavailable for public review, and only the classification was available (Grosse et al., 2016). The above mentioned and available authoritative regulatory toxicity reference values for cancer (and noncancer) effects for TBBPA were evaluated. However, of these authoritative reviews, only two oral toxicity reference values were derived (ECHA, 2017; COT, 2004). Our literature search identified three additional recently published papers that derived risk values for TBBPA (Wikoff et al., 2015; Yang et al., 2016; Colnot et al., 2014). All values were evaluated for relevance in adapting for use as the NSRL. Data were also mined from the two most recent authoritative reports (EFSA, 2011; Health Canada, 2013) relating to standard toxicological endpoints and agency conclusions on the potential for adverse health effects on humans. All publically available data were reviewed, synthesized, and, in the absence of an available cancer risk value for TBBPA from the authoritative agencies, a cancer risk value was derived and the OEHHA methodology was applied to translate this value into an NSRL. The literature search identified a carcinogenicity study of TBBPA by the U.S. National Toxicology Program (NTP, 2014), and associated published studies that evaluated these NTP (2014) tumor findings and the TBBPA cancer MOA (Dunnick et al., 2015; Wikoff et al., 2015; Harvey et al., 2015; Sanders et al., 2016; Lai et al., 2015; Wikoff et al., 2016; Hall et al., 2017). These data are pertinent as the lack of cancer data was identified as a data gap for developing a cancer potency value as reported in the most recent authoritative reviews for TBBPA (EFSA, 2011; Health Canada, 2013). Further studies were identified investigating non-cancer effects related to inhalation toxicity, dermal absorption, thyroid hormone disruption, endocrine activity, developmental toxicity, and neurotoxicity. Additional toxicokinetic studies reported the disposition and kinetics of TBBPA in rats and one investigated toxicokinetic parameters in humans. 3.2 Authoritative and Published Risk Values for TBBPA 3.2.1 Toxicity Reference Values Toxicity reference values for TBBPA from various agencies are summarized in Table 2. The UK Committee on Toxicity (COT, 2004) derived a tolerable daily intake (TDI) for oral exposure of 1 mg/kg-day for chronic exposure in the general population. This TDI was based upon a NOAEL of 1,000 mg/kg-day in an unpublished two-generation reproductive toxicity study and in an unpublished 90-day study (MPI Research, 2002a,b, as cited in COT, 2004). The COT applied a composite uncertainty factor of 1,000 based on 10 for human to animal (UFA), 10 for human variability (UFH), and 10 for database deficiencies (UFD). ECHA (2017) developed a derived no effect level (DNEL) for long-term systemic effects following oral exposure for the general population. The oral DNEL of 2.5 mg/kg-day available on the ECHA website does not provide enough detail to determine the NOAEL used or the uncertainty factors applied to derive the value. Colnot et al. (2014) reported four oral DNELs, two for the general population based on different endpoints (thyroid effects and no effect in a 90-day study) and two for reproductive endpoints (fertility and development). The lowest oral DNEL of 0.16 mg/kg-day was based on a BMDL10 of 16 mg/kg-day for thyroid hormone changes after application of a 100-fold uncertainty factor 9 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 (UFA = 10, UFH = 10). Two recently published reference values for TBBPA were identified in the literature search (Yang et al., 2016; Wikoff et al., 2015) (Table 2). Yang et al. (2016) compared previous PODs available in the literature for TBBPA with a POD generated in their own study investigating TBBPA toxicity to thyroid hormones. However, due to a lack of some methodological details in the publication, the Yang et al. (2016) assessment was not used in supporting the derivation of a cancer risk value. For example, the authors do not discuss the uncertainty factors used to derive the RfD or the details of the BMD model outputs and rationale for model choice. Without these methodological details, there is not enough information provided to assess the validity of the proposed RfD. In the other assessment, Wikoff et al. (2015) developed a number of non-cancer and cancer toxicity reference values, including an oral RfD, an oral cancer slope factor, an average daily dose estimate, and evaluated the margin of exposure (MOE) and margin of safety (MOS) based on these risk values. These toxicity reference values were based on the recent NTP 2-year bioassay in rats and mice (NTP, 2014) and followed standard U.S. EPA methodology including the use of BMD modeling (U.S. EPA, 2012). Wikoff et al. (2015) conducted a comprehensive literature search to identify published and unpublished TBBPA toxicity studies that identified a dataset of studies to review followed by an evaluation of study quality using Klimisch scoring that narrowed the database to the most relevant high quality studies (Klimisch et al., 1997). The authors then selected the NTP (2014) 2-year carcinogenicity assay from the high quality studies and identified the most sensitive cancer and non-cancer endpoints for their choice of PODs (Wikoff et al., 2015). For the noncancer RfD, Wikoff et al. (2015) selected female rat uterine hyperplasia from the 2-year NTP bioassay as the critical effect. The data were modeled using BMDS to derive a BMDL10 of 72.8 mg/kg-day and after adjustment for allometric scaling to humans, resulted in a human equivalent dose (HED) of 18.2 mg/kg-day. Using this POD, a composite uncertainty factor of 30 was applied (UFA = 3, UFH = 10) resulting in an RfD of 0.6 mg/kg-day. It is worth noting that the BMD model applied (unspecified in the publication) had poor fit (P = 0.08) even after dropping the high treatment dose (Wikoff et al., 2015). For cancer endpoints, Wikoff et al. (2015) considered uterine tumors from the NTP (2014) study as the most appropriate endpoint for use in derivation of a cancer toxicity value. Wikoff et al. (2015) applied the linear multistage BMD model to the duration- adjusted doses for the cancer dataset. Their BMDL10 was 127 mg/kg-day, and after adjustment for allometric scaling to humans, resulted in an HED of 31.7 mg/kg-day. Using this POD, the cancer slope factor was calculated to be 0.0032 per mg/kg-day, which corresponds to a risk specific dose (RSD) at the 10-5 level of 0.0032 mg/kg-day (Wikoff et al., 2015). This value has been through a quality assurance review and is posted on the International Toxicity Estimates for Risk (ITER) database, which is found on the U.S. National Library of Medicine's TOXNET (https://www.nlm.nih.gov/pubs/factsheets/toxnetfs.html). Only the Wikoff et al. (2015) toxicity reference values characterized the cancer human 10 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 health risks of exposure to TBBPA (Table 2). Several organizations concluded that there were not sufficient data available to derive cancer or noncancer toxicity reference values (prior to publication of the NTP report), and many applied a MOE approach. A MOE can be defined as the magnitude by which the POD (e.g., the NOAEL) of the most sensitive relevant toxic effect exceeds the estimated exposure (Barnes and Dourson, 1988). 11 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Table 2. Toxicity values identified in the literature for the general population and breakdown of how each value was derived. Reference CTV* Value Exposure Critical Effect Key Study Point of departure Composite Adjustment duration, Factor (individual route adjustments) ECHA, DNEL 2.5 mg/kg- Chronic, Unidentified, however Mice, oral NOAEL = 250 100 (UFA = 10, UFH = 10) 2017 day oral the registration dossier gavage (study mg/kg-day states "a chronic study citation not is used to set a chronic clear) DNEL. No correction required". Rats, Colnot et 5 mg/kg- Chronic, DNEL No reproductive/ oral gavage NOAEL = 1,000 200 (UFA = 10, UFH = 10, UFs (MPI al., 2014 day oral developmental effects Research, mg/kg-day = 2) 2002b) 0.16 Rats, dietary Colnot et DNEL, Chronic, Thyroid hormone (Van BMDL10 = 16 mg/kg- al., 2014 oral mg/kg- changes der Ven et 100 (UFA = 10, UFH = 10) oral day day al., 2008) Rats, oral Colnot et DNEL, 10 mg/kg- Chronic, No reproductive/ gavage (MPI NOAEL = 1,000 100 (UFA = 10, UFH = 10) al., 2014 oral day oral fertility effects Research, mg/kg-day 2001) Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 COT, TDI 1 mg/kg- Chronic, No embryotoxic / Rats, oral NOAEL of 1,000 1,000 (UFA = 10, UFH = 10, 2004 day oral teratogenic effects: gavage (MPI, mg/kg-day UFD = 10) effects 2002b) Wikoff et RfD 0.6 mg/kg- Chronic, Uterine endometrial Rats, oral BDML10 72.8 30 (UFA = 3; UFH = 10) al., 2015 day oral atypical hyperplasia gavage (NTP, mg/kg-day NSRL for cancer precursor 2014) HED - 18.2 mg/kg- effect for 70 kg human = 42 day mg/kg-day Pecquet et RfDcance 0.9 mg/kg- Chronic, Uterine tumors Rats, oral BDML10 102.5 30 (UFA = 3; UFH = 10) al., 2017 r day oral gavage (NTP, mg/kg-day NSRL for 70 kg human = 60 (this 2014) HED - 25.6 mg/kg- mg/kg-day paper) day Wikoff et Cancer 0.00315 Chronic, Uterine tumors Rats, oral BMDL10 126.6 RSD at 10-6 = 0.0032 mg/kg- al., 2015 slope mg/kg-day oral gavage (NTP, mg/kg-day day factor 2014) HED - 31.7 mg/kg- NSRL for 70 kg human = 0.22 day mg/kg-day * CTV = Chronic Toxicity Value? 13 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 3.3 Summary of TBBPA toxicology In order to understand the potential for toxicity from TBBPA exposure, the noncancer and cancer toxicity findings from recent authoritative agencies were reviewed. Overall, TBBPA is expected to have very low systemic noncancer toxicity, with low hazard for developmental or reproductive toxicity, as reviewed and reported in multiple regulatory and other published reports (ECHA, 2017; EFSA, 2011; Health Canada, 2013; NTP, 2014; Colnot et al., 2014; U.S. EPA, 2014; Cope et al., 2015; etc.). 3.3.1 Genotoxicity and Cancer EFSA (2011) found no in vivo studies available to assess the genotoxicity of TBBPA, and Health Canada (2013) identified no structural activity data suggesting TBBPA might be genotoxic. Further, a number of in vitro studies, such as several Ames tests and mutagenicity assays, a chromosomal aberration assay, a recombination assay, a sister chromatid exchange in Chinese hamster ovary (CHO) cells, and a rat hepatocyte unscheduled DNA synthesis assay were evaluated, all with negative findings (EFSA, 2011; Health Canada, 2013; Colnot et al., 2014). These data were supported by structure activity relationship data, where no structural alerts for genotoxicity were identified and a lack of suitable analogs were available for use in read-across (U.S. EPA, 2014). The overall WOE indicates that TBBPA does not exert genotoxic or mutagenic effects. EFSA (2011) and Health Canada (2013) also assessed studies to investigate the potential carcinogenicity of TBBPA. At the time of these reports, no long-term carcinogenicity data were available for TBBPA. Based upon the WOE that TBBPA was non-genotoxic in vitro (EU, 2006; EFSA, 2011) and that there was no significant evidence of carcinogenic potential in repeat dose toxicity tests, EFSA (2011) concluded that TBBPA was not likely a carcinogen. One study reported non-malignant tumors in response to oral TBBPA administration, including non-dose-responsive transitional cell papillomas in the urinary bladder that did not progress to malignancy, and thyroid follicular adenomas (Imai et al., 2009, as cited in EFSA, 2011). Colnot et al. (2014) discuss the available data and conclude that the thyroid tumors are unsuitable for use in human risk assessment on the basis on species sensitivity differences between rodents and humans. Health Canada (2013) concluded that the effect of TBBPA on thyroid hormones remains unclear, and therefore utilized a MOE approach to show that current human exposures are below those that are likely to produce thyroid effects. COT (2006) discussed a lack of consistency in the available thyroid data and the potential for the effect to be reversible. Additionally, neither thyroid tumors nor thyroid histopathology effects were seen in rats or mice treated in the 2-year NTP assay (NTP, 2014; Lai et al., 2015). However, EFSA (2011) identified disrupted thyroid homeostasis as the critical noncancer effect in their MOE analysis. There was only one cancer bioassay identified in our literature search; the 2-year cancer bioassay conducted by NTP (2014) in rats and mice exposed to 0, 250, 500, or 1,000 mg/kg for 5 days a week via oral gavage in corn oil. These study details and results have been extensively reported elsewhere (NTP, 2014; Dunnick et al., 2015; Lai et al., 2015; Wikoff et al., 2015, 2016; U.S. EPA, 2014). The primary tumors identified were uterine tumors (combined adenoma, adenocarcinoma, and malignant mixed Mullerian) in female Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 rats (U.S. EPA, 2014). Other tumors included testicular tumors in male rats; and in male mice hepatic tumors, hemangiomas/hemangiosarcomas, and intestinal tumors were found (U.S. EPA, 2014). The Cancer Assessment Review Committee (CARC) of the U.S. EPA determined TBBPA as "likely to be carcinogenic to humans" based on the female rat uterine tumors and the male mice hemangiomas/hemangiosarcomas, with no mutagenicity concerns (U.S. EPA, 2014). NTP (2014) reached the following conclusions regarding each of these tumor types: Testicular adenomas in male rats: "equivocal evidence of carcinogenic activity" Uterine epithelial tumors in female rats: "clear evidence of carcinogenic activity", Hepatoblastomas in male mice: "some evidence of carcinogenic activity"; Intestinal tumors and hemangiosarcomas: may have been related to chemical administration. 3.4 TBBPA uterine cancer mode of action and weight of evidence analysis The U.S. EPA (2005) guidelines for cancer risk assessment state that the MOA should be evaluated in determining the quantitative approach for dose-response assessment from positive human or experimental animal tumor data. This evaluation is accomplished by proposing a MOA including identification of key events, where data on these key events includes available in vivo, in vitro, and mechanistic studies. These studies are then evaluated relative to the modified Bradford Hill criteria, including strength, consistency, specificity of the association between the key event(s) and tumor outcomes, as well as consideration of the consistency of the dose-response and temporal relationship between the key event and tumors, biological plausibility of the proposed MOA, and coherence of the overall database (Meek et al., 2014). When sufficient data are available, a biologically based dose-response (BBDR) model is the preferred method for low dose extrapolation. Absent such data, U.S. EPA (2005) and other groups such as OEHHA (2013) usually conduct a low-dose extrapolation with a linear model if the chemical acts via a direct DNA-reactive MOA or if the MOA is not known, or via a threshold model based on one or more combinations of relevant tumors for a non-DNA-reactive MOA. Other authoritative groups often rely on a MOE approach for cancer evaluation. However, all these groups support the use of the best available science, including consideration of MOA, in their assessments. An abbreviated MOA and WOE analysis was previously applied by Wikoff et al. (2016) to inform the quantitative approach for derivation of a cancer risk value. In the NTP 2- year TBBPA bioassay, and as evaluated by Wikoff et al. (2015), uterine tumors in rats were identified as the most appropriate endpoint for use in derivation of a cancer toxicity value. Based on the considerable amount of evidence that TBBPA is not mutagenic, a nonlinear MOA was postulated for TBBPA induced uterine tumors based on interference with estrogen metabolism, as discussed by several authors (Borghoff et al., 2016; Lai et al. 2015; Sanders et al., 2016; Wikoff et al., 2015; Dunnick et al., 2015; Harvey et al., 2015; Hall et al., 2017), most comprehensively by Wikoff et al. (2016). The interference with estrogen is not thought to involve TBBPA binding directly to the estrogen receptor (ER). The weak affinity for the estrogen receptor and other in vitro and in vivo studies 15 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 suggests that TBBPA is not estrogenic (Colnot et al, 2014; Lai et al., 2015; Wikoff et al., 2016). Estrogenic effects of TBBPA are controversial since both negative and positive findings are reported in the literature, but the low TBBPA binding affinity to the ER suggests that TBBPA is not directly interacting with this receptor (Lai et al., 2015). Instead, interference with estrogen metabolism via competition for shared biotransformation pathways (glucuronidation and sulfation) is a plausible mechanism, resulting in increased estrogen concentrations that either disrupt hormonal balances or drive estrogen-induced cellular proliferation (Lai et al., 2015). Wikoff et al. (2016) proposed an adverse outcome pathway and presented data for a number of key events, including a WOE analysis for TBBPA induced uterine cancer (Figure 1; adapted from Wikoff et al., 2016). The proposed key events starting with the molecular initiating event are the following: 1) TBBPA binds to estrogen sulfotransferase (sultlel), which inhibits the estrogen sulfation pathway; 2) this inhibition of estrogen sulfation leads to increased estradiol bioavailability; 3a) increased estrogen leads to increased expression of estrogen responsive genes, 3b) alternative estrogen metabolic pathways are activated causing generation of reactive quinones and other reactive species that can interact with DNA, and 3c) potential for disruption of the hormonal balance (with potential for disrupted endocrine signaling); 4) interaction of estrogen responsive genes contributing to cellular proliferation of cells with increased DNA damage and p53 mutations; and 5) hyperplasia of cells leading to the adverse outcome (uterine tumors). These key events and supporting data are extensively discussed in Wikoff et al. (2016), and so are only briefly described below. 16 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Figure 1. Diagram of postulated mode of action for TBBPA-induced uterine tumors. [1] TBBPA binds to estrogen sulfotransferase (sultle1); [2] the estrogen sulfation pathway is inhibited; [3a] bioavailable estrogen can bind the estrogen receptor (ER), which translocates to the nucleus and leads to increased expression of estrogen responsive genes, [3b] alternative estrogen metabolic pathways (such as cytochrome P450s, CYPs) can generate reactive intermediates that can interact with DNA and cause DNA damage; [4] estrogen responsive genes contribute to cellular proliferation of cells, some of which have increased DNA damage and gene mutations. & de SK 22222 Suittes [1] ca s TBBPA [2] CHAPH ER I ER 1 [3a] 13 HO is - Estrogen - NO [3b] [4] on CH.9 [4] , HO 1) TBBPA binds to estrogen sulfotransferase (sultle1). which inhibits the estrogen sulfation pathway Toxicokinetic evidence exists that shows TBBPA utilizes the same sulfation metabolic pathway as estrogen (sultle1). Metabolites in humans include TBBPA-sulfate (Schauer et al., 2006, as cited in Health Canada, 2013; Ho et al., 2017). Computational modeling and quantitative structure activity relationship (QSAR) analysis suggest that TBBPA is structurally able to inhibit sulfotransferase (Wikoff et al., 2016; Gosavi et al., 2013). Additionally, in vitro IC50S for TBBPA inhibition of estradiol sulfotransferase ranges from 12-33 nM (Wikoff et al., 2016; Kester et al., 2002; Gosavi et al., 2013; Hamers et al., 2006, as cited by Borghoff et al., 2016). Thus, when high doses of TBBPA produce high plasma concentrations of TBBPA, the IC50 for sulfotransferase is surpassed and saturation can occur. For example, in vivo studies show that TBBPA doses as low as 50 mg/kg result in plasma concentrations (1,478 nM TBBPA) well above the reported IC50 values (Wikoff et al., 2016; Borghoff et al., 2016). 17 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Taken together with the in vitro data, inhibition of sulfotransferase activity is a plausible molecular initiating event in the mode of action for TBBPA induced uterine cancer (Wikoff et al., 2016). However, more data are required to support this key event, as target tissue dosimetry and temporal relationships are required to determine if TBBPA inhibits sulfotransferase in the uterus (Osimitz et al., 2014). 2) Inhibition of estrogen sulfation leads to increased estradiol bioavailability The binding of estrogen to estrogen sulfotranserase (sultle1) leads to its biotransformation by conferring a sulfate group. When TBBPA interferes in this pathway, estrogen is not biotransformed, meaning more estrogen should be bioavailable systemically. This bioavailable estrogen could result in increased estrogen receptor (ER) activation, metabolic switching to an alternative estrogen metabolic pathway, or imbalance of the estrogen/progesterone ratio that has been implicated in other tumor types (mammary, prostate) (Lai et al., 2015). However, there are currently no data on TBBPA modification of estrogen/progesterone ratios (Lai et al., 2015). Alternatively, the loss of estrogen sulfotransferase might result in increased plasma estrogen levels that are implicated in the development of estrogen dependent human endometrial cancer (Cornel et al., 2017). There are a paucity of data investigating TBBPA exposure resulting in increased estrogen bioavailability, although theoretically, competition for sulfation of estrogen would reduce estrogen-sulfate conjugates, resulting in bioavailable estrogen able to bind to the ER (sulfated estrogens are not able to bind the ER) (Fu et al., 2011). This increased non- sulfated, bioavailable estrogen could also shift the estrogen metabolic pathway to alternatives that can result in the generation of reactive species (Wikoff et al., 2016). However, Sanders et al. (2016) reported unchanged estrogen serum levels following 5 daily gavage doses of TBBPA at 250 mg/kg, although they note that the duration of exposure might have been insufficient to produce changes and that use of serum estrogen levels serve as a poor proxy for endometrium estrogen levels. While this step is biologically plausible, more data are needed for a definitive conclusion. 3a) Increased estrogen leads to increased expression of estrogen responsive genes, 3b) alternative estrogen metabolism causing generation of reactive quinones that can interact with DNA, and 3c) potential for disruption of the hormonal balance (with potential for disrupted endocrine signaling) Wikoff et al. (2016) discuss evidence related to increased estrogen and TBBPA-induced increases in estrogen responsive genes in tissues other than the uterus. Since the time of the Wikoff publication, an additional study was published that investigated changes in estrogen concentration and gene expression in response to TBBPA. In a repeat-dose oral gavage study, adult female Wistar Hans rats were treated with vehicle or TBBPA (250 mg/kg-day) for 5 consecutive days to investigate the role of estrogen homeostasis in the MOA of TBBPA (Sanders et al., 2016). In tissue samples taken 24 hours after the 5-day treatment, T4 serum levels were decreased but serum estrogen levels were unchanged. While estrogen levels were not measured in the uterus, there were changes in expression of genes in the uterus that are markers of cell division/growth and metabolism of 18 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 TBBPA/estrogen/thyroid hormones. The gene expression changes in both the proximal and distal sections of the uterus with the greatest significance included genes involved with metabolism and hormone binding, including significantly increased levels of ERa and ERB (Sanders et al., 2016). This data partially supports an increase in estrogen responsive genes from TBBPA exposure, however, more data is needed to show that this is directly resultant from increased bioavailable estrogen, and more data are need to identify these changes specific to uterine tissues. Wikoff et al. (2016) discuss estrogen homeostasis as a balance of various metabolic pathways. Once one pathway is disrupted, alternative estrogen metabolism pathways (other than sulfation) may compensate. One of these pathways, the catechol estrogen pathway, results in the oxidation of catechol estrogens with reactive quinone intermediates. These reactive quinones can interact with DNA, and have been implicated in some cancers (Wikoff et al., 2016). For example, these intermediates could be leading to DNA interactions that could contribute to or selectively increase the proliferation of altered genes, such as the tumor suppressor p53 gene. Finally, there is a potential contribution of disrupted endocrine signaling via hormonal imbalance. Increased estrogen levels have the potential to modify the estrogen/progesterone ratio, and this imbalance has been implicated in other tumor types (mammary, prostate, estrogen dependent human endometrial cancer) (Lai et al., 2015, Cornel et al., 2017). However, there are currently no data on TBBPA modification of estrogen/progesterone ratios (Lai et al., 2015). 4) Interaction of estrogen responsive genes contributing to cellular proliferation, and increased DNA damage and p53 mutations Cellular proliferation is a critical component of hyperplasia leading to tumor formation. It is well established that estrogen binding to the ER can lead to cellular proliferation, and induction of genes related to cell cycle regulation (Sanders et al., 2016). In the NTP (2014) bioassay, there was a clear dose-response with increased uterine adenocarcinomas/adenoma at each increased TBBPA dose; however, data are lacking to confirm temporal associations specifically between increased estrogen serum levels and incidence of cellular proliferation in uterine tissues (Lai et al., 2015). High doses of TBBPA may in part promote uterine tumors in rats by promoting growth of cells with pre-existing mutations in the p53 tumor suppressor gene driven by increased estrogen-dependent cellular proliferation, or through selective proliferation of these mutations caused by reactive quinone intermediates (NTP, 2014; Lai et al., 2015). Additionally, as noted above, TBBPA has low affinity for the ER and so is not likely acting directly on the ER itself. This is plausible as significantly increased p53 mutations were identified in tumors in the NTP study, but since TBBPA is non-mutagenic, TBBPA itself is not directly causing the p53 mutations (Lai et al., 2015). The mechanism of p53 mutation has been previously implicated in cancer development, including human endometrial cancers (Harvey et al., 2015; Wikoff et al., 2016). Harvey et al. (2015) reported on an evaluation and analysis of TBBPA-induced uterine carcinomas in female rats from the NTP study. Analysis using PCR found a high rate of p53 mutations suggesting that uterine carcinogenesis might be partially p53 dependent (Harvey et al., 19 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 2015). In this analysis, the TBBPA-treated samples included Wistar Han rat uterine carcinomas from all dose groups combined (250, 500, and 1,000 mg/kg), thus no p53 mutation dose-response data are available. Of interest, the analysis did not include the malignant mixed Müllerian tumors (MMMTs). While this data supports the proposed key event, more data are needed, specifically dose-response data for p53 mutations and increased proliferation in response to TBBPA, to confirm this. 5) Hyperplasia of cells with p53 mutations leading to the adverse outcome (uterine tumors) Hyperplasia resulting from cellular proliferation is a well-known precursor effect related to the development of tumors, and is associated with increased estrogen levels in humans (Sanders et al., 2016). As noted, by Wikoff, both preneoplastic and nonneoplastic hyperplasia occurred in the NTP study. Atypical endometrial hyperplasia was seen in the NTP 2-year assay and was significantly increased above control at all dose levels, however, it was only identified via the longitudinal inspection, but not the transverse (Wikoff et al., 2016). While there was not a strict dose-response (250 mg/kg-day = 26% incidence; 500 mg/kg-day = 22% incidence; 1,000 mg/kg-day = 26% incidence), preneoplastic lesions are by definition precursors to tumor formation (Wikoff et al., 2016). Additionally, as stated above, a high rate of p53 mutations was identified in the uterine carcinogenesis (Harvey et al., 2015). Finally, the adverse outcome, significantly increased incidence of uterine tumors (adenomas, adenocarcinomas, and malignant mixed Mullerian), was seen with increasing dose in the NTP (2014) 2-year assay. 3.4.5 Weight of evidence A human relevance and concordance analysis of the postulated MOA was conducted by Wikoff et al. (2016), and suggests that given the available data, the proposed MOA is plausible for the development of uterine tumors. Wikoff et al. (2016) conclude this is a plausible mechanism in humans qualitatively, but may be quantitatively excluded based on kinetic/dynamic factors between humans and rats. Given some of the data gaps associated with this MOA, we have given the greatest weight to the non-mutagenic threshold MOA, as multiple lines of evidence support that the MOA identified is non- mutagenic. This is seen in a number of tests showing negative mutagenicity results, which are supported by the recent NTP findings of a negative micronucleus test and two negative Salmonella tests. Finally, the specificity of uterine tumors to the uterine tissue only (and not systemically developed) supports the non-mutagenic assertion (Lai et al., 2015). Thus, wWhile we conclude that the Wikoff et al. (2016) WOE analysis was adequate to establish the postulated MOA. the additional information we cite is further supportive ofgiven-the-evaileble-dete;- this non-mutagenic threshold MOA. and leads us to propose a NSRL based on the threshold approach of EPA (2005). However, a more robust and transparent analysis of the modified Bradford Hill criteria for this MOA would be helofulie-needed. Particularly useful in this instance would be a quantitative WOE ranking, as recently demonstrated by Becker et al. (2017). 20 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Howerer there is eurrently sepport 808 threshold MOA 4.0 Derivation of the NSRL 4.1 Choice of critical study and BMD analysis for POD After an updated evaluation of the available carcinogenicity literature for TBBPA, we agree with the choice of Wikoff et al. (2015) that uterine tumors (adenomas, adenocarcinomas, and malignant mixed Mullerian combined) are the most appropriate cancer endpoint, and were chosen as the critical effect for derivation of the NSRL (Table 4). Uterine tumors in female rats were chosen as the critical cancer effect for derivation of a cancer risk value. In looking at the other tumor types, the testicular adenomas in male rats were considered "equivocal" and occurred at low incidence in the two highest doses (500 mg/kg - 1/50 incidence; 1,000 mg/kg - 3/50 incidence), and as such, were not a reliable choice for the critical effect. The hepatoblastomas in male mice had "some evidence" for carcinogenicity (250 mg/kg - 2/50 incidence; 500 mg/kg - 11/50 incidence; 1,000 mg/kg - 8/50 incidence) with a significant effect in the 500 mg/kg dose. NTP (2014) considered this tumor as "some evidence" because after combining incidences of hepatocellular carcinomas and hepatoblastomas, there was only a significant effect at 250 mg/kg and there was no trend across doses, and this was informed by the historical incidence of these tumor types as spontaneous and related to chemical administration. Therefore, these tumors were not considered for use as the critical effect. The uterine epithelial tumors in female rats were the only tumor type classified as "clear evidence" and occurred with the highest incidence (0 mg/kg - 6/50 incidence; 250 mg/kg - 11/50 incidence; 500 mg/kg - 16/50 incidence; 1,000 mg/kg - 19/50 incidence). Therefore, the uterine tumors were the best choice for the critical effect in derivation of a cancer risk value. Table 4. Dose-response and dose-adjustment of cancer effects (tumors) and precursor effects (hyperplasia) from the NTP (2014) assay for use in BMD analysis. Dose, mg/kg Duration- Hyperplasia Tumor response: (NTP, 2014) adjusted dose response: Uterus original a and residual Commented [MD1]: Doses cannot be more precise than those given in the bioassay. Is is 3 digits for two? Residual longitudinal longitudinal reviews review; endometrium, (combined); adenoma, hyperplasia, atypical adenocarcinoma, or MMMT (combined) 0 0 2 6 250 1798-6 13 11 Formatted: Highlight Formatted: Highlight 500 357-+ 11 16 Formatted: Highlight 21 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 1,000 714.3 13 19 Formatted: Highlight In line with the Wikoff et al. (2015) assessment, we modeled the incidence of combined uterine adenomas, adenocarcinomas, and malignant mixed Müllerian tumors observed in female rats (NTP, 2014). While we agree with Wikoff et al. (2015) on the choice of critical effect, the application of the BMD approach and use of the BMDL10, and allometric adjustment of the POD to an HED, we had the benefit of additional literature that allowed us to agree with them that of the Factor appreach- extrapolate to a riste specifie dese to elsewheresupport- a non-mutagenic, threshold MOAresponse, and the determination of a safe dose values are through the application of uncertainty factors to the POD analogous to an RfD or TDI approach (U.S. EPA, 2005). Specifically, conclusion is supported by Wikoff et al. (2015,2016), who suggest that the linear cancer slope factor approach is inappropriate for a non- mutagenic chemical, and suggested that a threshold approach based on a non-mutagenic MOA is most appropriate. This conclusion is also supported However, ai the time-of-their 2015 publication data investigating the TBBPA MOA not there were date avay the tinear defacia stope faeter and the stedies-by Sanders et al. (2016) and Lai et al. (2015), Thus. coupled the postalated MOA by Wikeff et at (2016) is adequate evidence exists to move away from the default linear approach to a threshold approach for this tumor type. Even-though-the MOA is enly postulated) addition, the negative mutagenicity and genotoxicity data and the specificity of the tumor response to specific tissue types are all sufficient to suggest that a threshold approach is most scientifically credible to develop an NSRL. The results of the BMD analysis on adenoma, adenocarcinoma, or MMMT (combined) incidence in relation to TBBPA exposure are shown in Table 5. The log-logistic model (Figure 2) best fits the data based on all quantitative fit criteria: p-value (0.845), scaled residuals (0.042) at the dose with the response closest to the BMR, and AIC (223), resulting in a dose-adjusted BMD10 of 169 mg/kg-day corresponding to the BMDL10 of 103 mg/kg-day. This model provides a similar BMD to that from the multistage model (i.e., the model chosen by Wilkoff et al., 2015), but the loglogistic model results are more conservative and better fit the data, particularly in the dose region of interest. Atypical hyperplasia of the endometrium was also modeled as a potential precursor effect to tumor formation, but no model provided adequate fit of the data (i.e., p < 0.1). Table 5. BMD models examining the relationship between TBBPA exposure* Formatted Table and uterine cancer incidence (adenoma, adenocarcinoma, or MMMTs, combined) in female rats from NTP (2014). 22 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Model p- Scaled Visual Fit Ratio AIC BMD10 BMDL10 Value Residual BMD/ at Dose BMDL Gamma 0.75 0.14 good 1.5 223.1 195 127 Logistic 0.46 0.88 acceptable 1.3 224.0 290 219 LogLogistic 0.85 0.042 good 1.7 222.8 169 103 LogProbit 0.32 0.89 acceptable 1.5 224,8 317 216 Multistage (1*) 0.75 0.14 good 1.5 223.1 195 127 Multistage (2*) 0.75 0.14 good 1.5 223,1 195 127 Multistage (3*) 0.75 0.14 good 1.5 223.1 195 127 Probit 0.49 0.84 acceptable 1.3 223.9 277 208 Weibull 0.75 0.14 good 1.5 223.1 195 127 Quantal- Linear 0.75 0.14 good 1.5 223.1 195 127 *Duration-adjusted dose (5/7 days) *The numbers correspond to the number of degrees of polynomial in the multistage model The bolded row indicates the best fitting model Figure 2. Log logistic modeling results of uterine cancer (adenoma, adenocarcinoma, or MMMTs, combined) in female rats from NTP (2014). 23 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Log-Logetic with of sos, Exta Risk for the BMD and 3.95 Lower for the ......... 0.8 0.4 0.3 0.2 0.: BMOL BMC o 200 aco 800 800 1000 does The resulting duration-adjusted BMDL10 of 103 mg/kg-day was adjusted to a human equivalent dose (HED) of 26 mg/kg-day using allometric scaling (Equation 1; [25.6 mg/kg-day = 103 mg/kg-day x 3 4.2 Uncertainty factors Uncertainty factors were applied to the BMDL10[HED] to derive an RfDcar of 0.9 mg/kg- day using Equation 2 (0.85 mg/kg-day = 25.6 mg/kg-day/(10 x 3 X 1 x 1 x 1 = 30). The uncertainty factor that addresses interindividual variability (UFH) (also referred to as intraspecies variability) accounts for toxicokinetic and toxicodynamic variation across humans and is intended to protect sensitive subpopulations. Unless a study is conducted in a sensitive human population or 3 As noted previously, the choice of default body weight (between female at 58 kg and male at 70 kg) does not significantly change the resulting HED (27.5 mg/kg-day versus 26.3 mg/kg-day, respectively). For this and the reasons listed in the footnote above, we have used the default body weight of 70 kg. 24 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 there are data on human variability in response, the default for the UFH is 10. Given the lack of available data to move away from the default, we recommend the application of a 10-fold factor. The uncertainty factor for interspecies extrapolation (UFA) (also referred to as animal-to-human extrapolation) accounts for the translation of data from experimental animals to humans, specifically the toxicokinetic and toxicodynamic variation between species. Because we adjusted the POD to a human equivalent dose, this is presumed to account for the toxicokinetic differences across species (Renwick et al., 1999). Therefore, a reduced factor of one half the power of 10 (~3-fold) should be applied to account for the toxicodynamic differences between species (Renwick et al., 1999). The uncertainty factor for use of a LOAEL and extrapolation to a NOAEL (UFL) is not needed, since a BMD analysis was conducted. Therefore, a factor of 1 is applied. Additionally, the uncertainty factor for extrapolation of a subchronic critical study to a chronic exposure (UFs) is also not necessary, since a 2-year cancer bioassay was selected as the critical study. Therefore, a factor of 1 is applied. The uncertainty factor for database completeness (UFD) represents a judgment on the quantity and quality of the toxicology information available on the substance. TBBPA has an adequate toxicological database, particularly for noncancer effects, to assess the toxicological outcomes and potential adverse effects from exposure. However, this factor has also been utilized on occasion to account for severity of effect aimed to introduce an additional margin of safety when a compound has produced some form of severe or irreversible toxicity that is not addressed directly by the POD. It is worth noting that the noncancer dataset identified sensitive reproductive effects from TBBPA exposure [BMDLs of 0.5 mg/kg-day for increased testes weight and 0.6 mg/kg-day for increased F1 pituitary weight in males (van der Ven et al., 2008; Lilienthal et al., 2008; as cited in Health Canada, 2013)], and additional thyroid effects were seen but were largely uncharacterized [F1 males and females had decreased T4 levels (BMDL10 31 and 16 mg/kg, respectively)]. However, these data would be relevant for noncancer assessment, and as we are specifically addressing cancer endpoints, the application of this factor is not warranted. Specifically, the availability of the NTP 2-year comprehensive cancer bioassay is sufficient to inform the database for cancer. In total, we recommend the application of a composite uncertainty factor of 30 (3 x 10) to protect for uncertainties in the database and extrapolations. Therefore, for the derivation of the oral NSRL, we divide the BMDL10[HED] of 25.6 mg/kg-day by 30 to derive a cancer safe dose of 0.9 mg/kg-day. Based on the default human body weight of 70 kg, the NSRL is 60 (59.5) mg/day using Equation 3 (60 mg/day = 0.85 mg/kg-day x 70 kg). There were not enough published data identified to derive an inhalation NSRL. There was at least one DNEL derived for inhalation exposure, the studies that those values were based on were not publically available, and the relevance to cancer development from 25 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 inhalation exposure remains uncharacterized. 5.0 Discussion 5.1 Comparison of NSRL to RSD published by Wikoff et al., 2015 An NSRL of 60 mg/day was adapted from an RfDcancer of 0.9 mg/kg-day for a threshold MOA leading to uterine cancer seen in the recent NTP (2014) bioassay. The NSRL value (60 mg/day) is roughly 300-fold higher than the cancer slope factor adjusted to an NSRL derived by Wikoff et al. (2015) for 10-5 risk for the same tumor data (the risk level assigned by the NSRL) (0.0032 mg/kg-day x 70 kg = 0.22 mg/day). This difference reflects the use of a point estimate instead of a slope factor for low dose extrapolation, and slight differences in the BMDL due to model selection. Table 4 shows the various BMD model outputs for the uterine tumor data. While our models appear to align with those of Wikoff et al. (2015), we chose a different model based on an evaluation of multiple parameters (p-value, scaled residuals, visual fit, ratio of BMD to BMDL, and AIC). This difference in model selection accounts for a roughly 20% difference in the chosen points of departure (126.6 mg/kg-day chosen by Wikoff and colleagues versus 103 mg/kg-day chosen for this assessment). The NSRL proposed here of 60 mg/day, however, is within an order of magnitude and roughly aligns with a potential NSRL of 42 mg/day based on the RfD of 0.6 mg/kg-day derived by Wikoff et al. (2015) for noncancer uterine hyperplasia (i.e., 0.6 mg/kg-day x 70 kg = 42 mg/day). As some types of uterine hyperplasia are considered an upstream precursor to uterine cancer, the alignment of these values makes sense biologically. Additionally, protection from precursor effects is typically anticipated to protect from the downstream cancer effect. However, BMD models were not able to adequately fit the uterine hyperplasia data (p-value <0.1), even when the responses at the highest dose were dropped from the model (an approach that is consistent with U.S. EPA guidance; U.S. EPA, 2012). We chose not to use the hyperplasia precursor for cancer effects for a few reasons: 1) there is little currently available practical experience in using a POD based on cancer precursor effects to develop an RfD for a tumor; and 2) poor BMD model fit (p-value < 0.1) limits confidence in, and interpretation of, model results. 5.2 Comparison of RfD cancer to available risk values A comparison was made between the RfDc: derived here and other available risk values (see Table 2; Figure 3). The derived RfD cancer cancer (0.9 mg/kg-day) falls appropriately in respect to the biology on the risk value continuum as shown in Figure 3. As expected, DNELs for noncancer reproductive and developmental effects (DNEL repro and DNEL dev, both = 10 mg/kg-day) and DNELs for noncancer no effect levels (5 and 2.5 mg/kg-day) are higher than the derived RfD cancer by ~2.7 to 11-fold. The TDI, which was also derived for a noncancer no effect level (1 mg/kg-day), is roughly the same as the RfDcancer. This makes biological sense given the thresholded MOA for uterine tumor formation. The RfD for uterine hyperplasia (0.6 mg/kg-day), is slightly lower than the RfD This is expected and makes biological sense given that uterine hyperplasia is a precursor effect to uterine tumors. One would expect an RfD for a precursors effect to be 26 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 lower than that for the apical effect. Finally, the DNEL for thyroid effects (0.16 mg/kg- day) is lower than all other available noncancer values. However, as noted above in Section 3.3.1, there is a large amount of uncertainty associated with the thyroid endpoint (species sensitivity differences between rodents and humans, a lack of consistency in the available thyroid data, the potential for the effect to be reversible, neither thyroid tumors nor thyroid histopathology effects were seen in rats or mice treated in the 2-year NTP assay). Finally, the cancer slope factor (0.0032 mg/kg-day) is significantly lower than all other available risk values (from 50- to ~3,000-fold lower). Typically, the expectation is for cancer risk values to be lower than those for noncancer, under a no-threshold assumption. However, given the evidence for a threshold MOA for the most sensitive uterine tumors, the cancer slope factor is likely highly conservative and not biologically appropriate (280-fold lower than the RfDcancer). Figure 3. Comparison of available cancer and non-cancer risk values for TBBPA. 11 10 10 10 9 8 7 6 5 5 4 2.5 3 2 0.6 0.9 1 1 0.0032 0.16 0 5.2 Uncertainties Uncertainties are associated with using the malignant mixed Müllerian tumor (MMMT) data combined with the uterine adenomas and adenocarcinomas because of the rarity in their occurrence, and the fact that a dose-dependent trend was not reported in TBBPA treated rats. MMMTs are a very rare, spontaneous neoplasm in rats (Dunnick et al., 2015). Furthermore the historical data "are limited in Wistar Han rats because few studies using this strain have been conducted" (NTP, 2014). However, a large body of evidence on the epithelial histogenesis of MMMTs and their relevance to uterine cancers was cited as reasoning to include the MMMTs (Dunnick et al., 2015). The use of a new method of examining the rat uterus (a secondary Residual Longitudinal Review combined with the initial standard Transverse Review) allowed for the identification of additional tumors; 27 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 the additional transverse review identified adenocarcinomas or adenomas in all female rats with MMMTs. Therefore, BMD models including only adenomas and adenocarcinomas would be identical to those for combined adenomas, adenocarcinomas, and MMMTs. The MOA for uterine tumor formation needs additional validation, specifically, it would highly benefit from a comparison to the modified Bradford Hill criteria (such as conducted in Meek et al., 2014) and a quantitative weight of evidence approach (such as conducted in Becker et al., 2017). For the MOA, in vivo data to confirm that TBBPA competes for estrogen sulfotransferases are lacking. Target tissue dosimetry and temporal relationships to determine if TBBPA inhibits sulfotransferase in the uterus are required to determine if this mechanism is viable (Osimitz et al., 2014). Other uncertainties in the estrogen metabolism pathway have not been addressed, including the role of the alternative estrogen metabolism pathways, such as inhibition of hydroxysteroid- dehydrogenase-17beta (leading to increased estrogen activity) and induction of phase I enzymes CYP1A1 and CYP1B1 (leading to reactive metabolite formation) (Sanders et al., 2016). Others reviewed the plausibility of these alternative pathways but a more in- depth review is needed (Wikoff et al., 2015; Dunnick et al., 2015; Sanders et al., 2016). Additionally, more data is needed to evaluate this MOA at human relevant exposure doses. Wikoff et al. (2016) and others suggest this MOA operates only at high doses where saturation of the estrogen metabolic pathway occurs. Wikoff et al. (2016) suggests extrapolation to lower doses for protection of human health may be inappropriate given human doses are not expected to be high enough to lead to this MOA. However, we provide clear rationale that our NSRL is appropriate and as applied, is protective of the development of uterine tumors for several reasons: 1) tumors appear to be formed only at high doses due to non-mutagenic mechanism, and no tumors were identified in previous studies except the non-malignant tumors (transitional cell papillomas in the urinary bladder and thyroid follicular adenomas) (Imai et al., 2009, as cited in EFSA, 2011). This suggests that the potential for carcinogenicity from TBBPA exposure is quite low, will only occur at high doses, and negates the need for low-dose extrapolation; and 2) Wikoff reports that doses of 50 mg/kg are enough to surpass the sulfotransferase IC50, suggesting that this mechanism could be activated at doses below those in the NTP study. However, this dose would need to be exceeded in a chronic fashion in order for tumor formation to occur, and the RfDcan is well below this IC50 (0.9 Therefore, the derived RfDcancer is protective of uterine tumors via a non-threshold mode of action, and low dose extrapolation is not necessary. A final caveat relates to the existence of other potential MOAs/AOPs. Effects on thyroid homeostasis have also been seen, and for noncancer effects have produced relatively low BMD/Ls. Studies have shown that high TBBPA concentrations in vitro inhibit thyroid hormone metabolism with an IC50 of 460 nM for SULT1A in human liver cytosol, and the contribution of this MOA remains unclear (Butt and Stapleton, 2013). However, there is no indication that thyroid tumors result from exposure to TBBPA as neither tumors nor histopathology was found in the NTP assay. Additionally, there were testicular adenomas and hepatoblastomas identified in the NTP (2014) report. It is possible that these tumor types might drive the RfD cancer value lower, but as for the uterine tumors, are anticipated 28 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 to be non-mutagenic thresholded responses due to the non-mutagenic nature of TBBPA. 6.0 Conclusions Building off of previously published work investigating the mode of action and toxicity of TBBPA (ESFA, 2011; Health Canada, 2013; Wikoff et al., 2015, 2016; Lai et al., 2015), and using the cancer results seen from the recent NTP 2-year cancer bioassay, we have derived a no-significant-risk-level (NSRL) for TBBPA of 60 mg/day. The NSRL is based on uterine tumors (adenomas, adenocarcinomas, and malignant mixed Mullerian) identified in female rats exposed to TBBPA for 2-years via oral gavage. TBBPA has been shown to be a non-mutagenic carcinogen acting through an estrogen interference mode of action, and as such the most appropriate approach to derivation of a cancer risk value is a threshold approach, akin to an RfD cancer. Using the NTP study data, we derived a BMDL10 point of departure of 103 mg/kg-day and adjusted this to a human equivalent dose (HED) of 25.6 mg/kg-day using allometric scaling. We applied a composite adjustment factor of 30 to the POD to derive an RfDcancer of 0.9 mg/kg-day. Based on an average human body weight of 70 kg, the cancer safe dose was adjusted to an NSRL of 60 mg/day. Acknowledgements Funding for this work was provided by the American Chemical Council (ACC) and the developmental reserve funds of the University of Cincinnati, Risk Science Center. References Barnes, D.G., & Dourson, M.L. (1988). Reference dose (RfD): Description and use in health risk assessments. Regul Toxicol Pharmacol. 8, 471-486. Becker, R.A., Dellarco, V., Seed, J., Kronenberg, J.M., Meek, B., Foreman, J., Manibusan, M.K. (2017). Quantitative weight of evidence to assess confidence in potential modes of action. Regul Toxicol Pharmacol. 86, 205-220. Doi: 10.1016/j.yrtph.2017.02.017 Borghoff, S.J., Wikoff, D., Harvey, S., & Haws, L. (2016). Dose- and time-dependent changes in tissue levels of tetrabromobisphenol A (TBBPA) and its sulfate and glucuronide conjugates following repeated administration to female Wistar Han Rats. Toxicol Rep, 3, 190-201. doi:10.1016/j.toxrep.2016.01.007 Butt, C.M., & Stapleton, H.M. (2013). Inhibition of thyroid hormone sulfotransferase activity by brominated flame retardants and halogenated phenolics. Chem Res Toxicol, 26(11), 10.1021/tx400342k. oi:10.1021/tx400342k Colnot, T., Kacew, S., & DeKant, W. (2014). Mammalian toxicology and human exposures to the flame retardant 2,2, 6,6,-tetrabromo-4,4-isoprpoylidenediphenol (TBBPA): Implications for risk assessment. Arch Toxicol, 88, 1180-1188. doi: 10.1007/s00204-013-1180-8 COT (Committee on Toxicology). (2004). COT statement on tetrabromobisphenol A- 29 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 review of toxicological data. Retrieved from UK Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment. Available at: https://cot.food.gov.uk/committee/committee-on- oxicity/cotstatements/cotstatementsyrs/cotstatements2004/cotstatements2004tbbp a [accessed July 10, 2017] Cope, R. B., Kacew, S., & Dourson, M. (2015). A reproductive, developmental and neurobehavioral study following oral exposure of tetrabromobisphenol A on Sprague-Dawley rats. Toxicology, 329, 49-59. doi: 10.1016/j.tox.2014.12.013 Cornel, K. M. C., Krakstad, C., Delvoux, B., Xanthoulea, S., Jori, B., Bongers, M. Y. Romano, A. (2017). High mRNA levels of 176-hydroxysteroic dehydrogenase type 1 correlate with poor prognosis in endometrial cancer. Mol Cell Endocrinol, 442, 51-57. doi: 10.1016/j.mce.2016.11.030 Dunnick, J. K., Sanders, J. M., Kissling, G.E., Johnson, C. L., Boyle, M. H., & Elmore, S. A. (2015). Environmental chemical exposure may contribute to uterine cancer development: studies with tetrabromobisphenol A. Toxicol Pathol, 43, 464-473. doi: 10.1177/0192623314557335 European Chemicals Agency (ECHA). (2017). 2017. 2,2',6,6'-tetrabromo-4,4'- isopropylidenediphenol. Information on Chemicals, Registration Dossier. Last modified: 11-Jul-2017. Available online at: https://echa.europa.eu/registration- dossier/-/registered-dossier/14760/1 [accessed July 17, 2017] European Food Safety Administration (EFSA). 2011. Scientific Opinion on Tetrabromobisphenol A (TBBPA) and its derivatives in food. EFSA J, 9: 2477. Available online at: hitps://www.efsa.europa.eu/en/efsajournal/pub/2477 [accessed July 17, 2017] European Food Safety Administration (EFSA). 2017. Update: use of benchmark dose approach in risk assessment. EFSA J, 15: 4658. Available online at: äle:///Users/pecqueam/Downloads/Hardy et al-2017-EFSA Journal.pdf [accessed July 17, 2017] European Union (EU). 2006. Risk Assessment Report: ",6,6'-Tetrabromo-4,4" Isopropylidenediphenol (Tetrabromobisphenol-A or TBBP-A), Part II - Human Health. European Chemicals Bureau, European Commission, 4th Priority List, Volume 63. Available online at: https://echa.europa.eu/documents/10162/326000fe-b4fe-4828-b3d3 93c24cledd51 [accessed July 17, 2017] Fu, J., Fang, H., Paulsen, M., Ljungman, M., Kocarek, T. A., & Runge-Morris, M. (2011). Regulation of estrogen sulfotransferase expression by confluence of MCF10A breast epithelial cells: Role of the aryl hydrocarbon receptor. J Pharmacol Exp Ther., 339(2), 597-606. doi: 10.1124/jpet.111.185173 Gosavi, R. A., Knudsen, G. A., Birnbaum, L. S., & Pedersen, L. C. (2013). Mimicking of estradiol binding by flame retardants and their metabolites: A crystallographic analysis. Environ Health Perspect, 121, 1194-1199. doi: 10.1289/ehp. 1306902 30 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Grosse, Y., Loomis, D., Guyton, K.Z., Ghissassi, F-E., Bouvard, V., Benbrahim-Tallaa, L., Straif, K. (2016). Carcinogenicity of some industrial chemicals. The Lancet Oncol, 17(4), 419-420. Hall, S.M., Coulter, S.J., Knudsen, G.A., Sanders, J.M., & Birnbaum, L.S. (2017). Gene expression changes in immune response pathways following oral administration of tetrabromobisphenol A (TBBPA) in female Wistar Han rats. Toxicol Lett, 272, 68-74. doi:10.1016/j.toxlet.2017.03.008 Hamers, T., Kamstra, J.H., Sonneveld, E., Murk, A.J., Kester, M.H., Andersson, P.L., Legler, J., & Brouwer, A. (2006). In vitro profiling of the endocrine-disrupting potency of brominated flame retardants. Toxicol. Sci. 92, 157e-173e. [as cited in Colnot et al., 2014] doi: 10.1093/toxsci/kfj187 Harvey, J. B., Osborne, T. S., Hong, H. H., Bhusari, S., Ton, T. V., Pandiri, A. R., Hoenerhoff, M. J. (2015). Uterine Carcinomas in Tetrabromobisphenol A- exposed Wistar Han Rats Harbor Increased Tp53 Mutations and Mimic High- grade Type I Endometrial Carcinomas in Women. Toxicol Pathol, 43, 1103-1113. doi: 10.1177/0192623315599256 Health Canada. (2013). Screening assessment report of Phenol, 4,4' -(1-methylethylidene) bis[2,6-dibromo- (Tetrabromobisphenol A, TBBPA; CAS 79-94-7), Ethanol, 2,2'-[(1-methylethylidene)bis[(2,6-dibromo-4,1-phenylene)oxy]lbis (known as TBBPA bis(2-hydroxyethyl ether, CAS 4162-45-2) and Benzene, 1,1'-(1- methylethylidene)bis[3,5-dibromo-4-(2-propenyloxy)-(TBBPA bis(allylether, CAS 25327-89-3). Government of Canada, Environment Canada, Health Canada. Cat. No.: En14-110/2013E-PDF. ISBN: 978-1-100-22898-3. Ho, K. L., Yuen, K. K., Yau, M. S., Murphy, M. B., Wan, Y., Fong, B. M., Lam, M. H. (2017). Glucuronide and sulfate conjugates of tetrabromobisphenol A (TBBPA): Chemical synthesis and correlation between their urinary levels and plasma TBBPA content in voluntary human donors. Environ Int, 98, 46-53. doi: 10.1016/j.envint.2016.09. Imai, T., Takami, S., Cho, Y. M., Hirose, M., & Nishikawa, A. (2009). Modifying effects of prepubertal exposure to potassium perchlorate and tetrabromobisphenol A on susceptibility to N-bis(2-hydroxypropyl)nitrosamine- and 7,12 dimethylbenz(a)anthracene-induced carcinogenesis in rats. Toxicol Lett, 185, 160- 167. [As cited in EFSA, 2011]. doi: 10.1016/j.toxlet.2008.12.013 International Toxicity Estimates for Risk (ITER). A TOXNET Database. U.S. National Library of Medicine, National Institutes of Health. Available online at: https://toxnet.nlm.nih.gov/newtoxnet/iter.htm [accessed July 17, 2017] Jeff Gift, U.S. EPA, personal communication via email. In reference to: questions on benchmark dose. November 18, 2016. Kester, M.H., Bulduk, S., van Toor, H., Tibboel, D., Meinl, W., Glatt, H., Visser, T.J. (2002). Potent inhibition of estrogen sulfotransferase by hydroxylated metabolites 31 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 of bolyhalogenated aromatic hydrocarbons reveals alternative mechanism for estrogenic activity of endocrine disrupters. J. Clin. Endocrinol. Metab 87, 1142e- 1150e. Klimisch, H.J., Andreae, M., & Tillmann, U. (1997). A systematic approach for evaluating the quality of experimental toxicological and ecotoxicological data. Regul. Toxicol. Pharm. 25, 1-5. Lai, D. Y., Kacew, S., & Dekant, W. (2015). Tetrabromobisphenol A (TBBPA): Possible modes of action of toxicity and carcinogenicity in rodents. Food Chem Toxicol, 80, 206-214. doi: 10.1016/j.fct.2015.03.023 Lilienthal, H., Verwer, C., van der Ven, L., Piersma, A., & Vos, J. (2008). Exposure to tetrabromobisphenol A (TBBPA) in Wistar rats: Neurobehavioral effects in offspring from a one-generation reproduction study. Toxicology, 246, 45-54. [as cited in Health Canada, 2013] doi: 10.1016/j.tox.2008.01.007 Meek, M.E., Palermo, C.M., Bachman, A.N., North, C.M., & Lewis, R.J. (2014). Mode of action human relevance (species concordance) framework: Evolution of the Bradford Hill considerations and comparative analysis of weight of evidence. J Appl Toxicol, 34, 595-606. doi: 10.1002/jat.2984 MPI Research, 2002a. A 90-day oral toxicity study of tetrabromobisphenol-A in rats with a recovery group (unpublished). As cited in COT (2004). MPI Research, 2002b. An oral two generation reproductive, fertility and developmental neurobehavioural study of tetrabromobisphenol-A in rats (unpublished). Performed by MPI Research Inc., Mattawan, MI for the American Chemistry Council BFRIP, Arlington, VA. Study Number: 474-004, pp 2199 [as cited in Colnot et al., 2014] MPI Research. (2001). Final report-an oral prenatal developmental toxicity study with tetrabromobisphenol-A in rats (unpublished). [as cited in Colnot et al., 2014]. National Institute of Environmental Health Sciences (NIEHS). (2002). Tetrabromobisphenol A [79-94-7]: Review of Toxicological Literature. National Institutes of Health, National Toxicology Program. Available online at: https://ntp.niehs.nib.gov/ntp/btdocs/chem_background/exsumpdf/tetrabromobisph enola 508.pdf [accessed July 17, 2017] NTP (National Toxicology Program). (2014). Technical Report on the Toxicology Studies of Tetrabromobisphenol A (CAS NO. 79-94-7) in F344/NTac rats and B6C3F1/N mice and Toxicology and Carcinogenesis Studies of Tetrabromobisphenol A in Wistar Han [Crl:WI(Han)] rats and B6C3F1/N mice (Gavage Studies). NTP TR 587, September, 2014. National Institutes of Health, U.S. Department of Health and Human Services, Research Triangle Park, NC. Available online at: https://ntp.niehs.nib.gov/ntp/htdocs/lt_xpts/tr587508.pd [accessed July 7, 2017] Office of Environmental Health Hazard Assessment (OEHHA). (1989). Final Statement of Reasons. No Significant Risk Levels and No Observable Effect Levels. 32 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Proposition 65, California Environmental Protection Agency. June, 1989. Available online at: https://oehha.ca.gov/media/downloads/emnr/art78fsrjune1989.pdf [accessed July 7, 2017] Office of Environmental Health Hazard Assessment (OEHHA). (2013). Article 7. No Significant Risk Levels. § 25703. Quantitative Risk Assessment. Title 27, California Code of Regulation. Available online at: ittps://oehha.ca.gov/media/downloads/proposition-65/general-info/regsart7.pdf [accessed July 19, 2017] Osimitz, T.G., Dourson, M.L., Hayes, A. W., & Kacew, S. (2014). Crystallographic analysis and mimicking of estradiol binding: Interpretation and speculation. Environ Health Perspect, 122: A91-A92. DOI:10.1289/ehp.1307987 Renwick, A.G. (1999). Subdivision of uncertainty factors to allow for toxicokinetics and toxicodynamics. Human and Ecological Risk Assessment, 5, 1035-1050. doi: 10.1080/10807039991289329 Sanders, J.M., Coulter, S.J., Knudsen, G.A., Dunnick, J.K., Kissling, G.E., & Birnbaum, L.S. (2016). Disruption of estrogen homeostasis as a mechanism for uterine toxicity in Wistar Han rats treated with tetrabromobisphenol A. Toxicol Appl Pharmacol, 298, 31-39. doi: 10.1016/j.taap.2016.03.007 Schauer, U.M.D., Völkel, W., & Dekant, W. (2006). Toxicokinetics of tetrabromobisphenol A in humans and rats after oral administration. Toxicol Sci 91, 49-58. [as cited in Health Canada, 2013] U.S. EPA (Environmental Protection Agency). (1986). Guidelines for Mutagenicity Risk Assessment. U.S. Environmental Protection Agency: Washington, DC, EPA/630/R-98/003. Available online at: ps://www.epa.gov/sites/production/files/2013-09/documents/mutagen2.pdf [accessed July 7, 2017] U.S. EPA (Environmental Protection Agency). (2005). Guidelines for Carcinogen Risk Assessment. U.S. Environmental Protection Agency: Washington, DC, EPA/630/P-03/001F. Available online at: https://www.epa.gov/risk/guidelines- carcinogen-risk-assessment [accessed July 7, 2017] U.S. EPA (Environmental Protection Agency). (2012). Benchmark Dose Technical Guidance. Risk Assessment Forum, U.S. Environmental Protection Agency: Washington, DC.100-R-12-001. Available online at: attps://www.epa.goy/risk/benchmark-dose-technical-guidance[accessed July 7, 2017] U.S. EPA (Environmental Protection Agency). (2014). Supplemental File 4: Tetrabromobisphenol A (TBBPA, CASRN: 79-94-7) Cancer Assessment Review Committee Report. Health Effects Division, Office of Pesticide Programs, U.S. Environmental Protection Agency: Washington, DC. Available online at: https://www.epa.gov/assessing-and-managing-chemicals-under. 33 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 scalsupplemental-file-4-tetrabromobisphenol-tbbpa-casmn-79 [accessed July 7, 2017] Van der Ven, L.T., Van de Kuil, T., Verhoef, A., Verwer, C.M., Lilienthal, H., Leonards, P.E., Piersma, A.H. (2008). Endocrine effects of tetrabromobisphenol-A (TBBPA) in Wistar rats as tested in a one-generation reproduction study and a subacute toxicity study. Toxicology, 245, 76-89. doi: 10.1016/j.tox.2007.12.009 [as cited in Health Canada, 2013, and EFSA, 2011] Wheeler, M.W., & Bailer, A.J. (2007). Properties of model-averaged BMDLs: a study of model averaging in dichotomous response risk estimation. Risk Anal, 27(3): 659- 70. doi: 10.1111/j.1539-6924.2007.00920.x Wikoff, D., Thompson, C., Perry, C., White, M., Borghoff, S., Fitzgerald, L., & Haws, L.C. (2015). Development of toxicity values and exposure estimates for tetrabromobisphenol A: Application in a margin of exposure assessment. J Appl Toxicol, 35, 1292-1308. doi: 10.1002/jat.3132 Wikoff, D.S., Rager, J.E., Haws, L.C., & Borghoff, S.J. (2016). A high dose mode of action for tetrabromobisphenol A-induced uterine adenocarcinomas in Wistar Han rats: A critical evaluation of key events in an adverse outcome pathway framework. Regul Toxicol Pharmacol, 77, 143-159. doi: 10.1016/j.yrtph.2016.01.018. Yang, Y., Ni, W.W., Yu, L., Cai, Z., Yu Y.J. (2016). Toxic effects of tetrabromobisphenol A on thyroid hormones in SD rats and the derived-reference dose. Biomed Environ Sci, 29(4), 295-299. 34 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226

What is the Ratio BMD/BMDL of Multistage(1*)?

kxcn0226

kxcn0226_p4, kxcn0226_p5, kxcn0226_p6, kxcn0226_p7, kxcn0226_p8, kxcn0226_p9, kxcn0226_p10, kxcn0226_p11, kxcn0226_p12, kxcn0226_p13, kxcn0226_p14, kxcn0226_p15, kxcn0226_p16, kxcn0226_p17, kxcn0226_p18, kxcn0226_p19, kxcn0226_p20, kxcn0226_p21, kxcn0226_p22, kxcn0226_p23, kxcn0226_p24, kxcn0226_p25, kxcn0226_p26, kxcn0226_p27, kxcn0226_p28, kxcn0226_p29, kxcn0226_p30, kxcn0226_p31, kxcn0226_p32, kxcn0226_p33, kxcn0226_p34, kxcn0226_p35

1.5

1.0 Introduction Under the State of California's Proposition 65 (Prop65), a no significant risk level (NSRL) is developed for chemicals that are known to induce cancer in toxicological studies. The NSRL represents the "levels of exposure calculated to result in no more than one excess case of cancer in an exposed population of 100,000, assuming exposure over a 70-year lifetime (10-5 lifetime risk of cancer)" (OEHHA, 1989). California's Office of Environmental Health Hazard Assessment (OEHHA) recently announced its Prop65 notice of intent to list tetrabromobisphenol A (TBBPA) as known to the state to cause cancer. This is likely based on a recent International Agency for Research on Cancer (IARC) assessment that classified TBBPA as "Group 2A: probably carcinogenic to humans" (IARC Monograph in preparation, volume 115 - only the classification is available at the time of publication; Grosse et al., 2016). With the addition of TBBPA to the Prop65, a toxicological evaluation of TBBPA and derivation of an NSRL is needed. The methodology for NSRL derivation is similar to that of the U.S. EPA for developing cancer potency values. An evaluation of the available toxicological data in humans and animals is used to identify a significant biologic response of concern (critical effect) (OEHHA, 1989). In the absence of data to the contrary, noa threshold is assumed for the cancer effect of concern, and OEHHA then develops an NSRL through the use of no- threshold models (cancer slope factor development) based on U.S. EPA guidance (1986, 2005) (OEHHA, 2013). These NSRL values are then compared to exposure estimates to determine the potential to evoke a biological response at relevant environmental exposure levels (margin of safety) (OEHHA, 1989). However, when a threshold in response is supported based on available data, most risk agencies around the World support alternative approaches such as using threshold models. For example, the U.S. EPA (2005) methodology has advanced with the state of risk science, and includes a determination of a linear (non-threshold) or non-linear (threshold) mode of action (MOA) approach. Threshold models suggest that there are low doses of a chemical that do not cause effects and that a high enough dose is needed for effects to occur, while non- threshold models suggest that any dose above zero can lead to an effect (U.S. EPA, 2005). The-One basis for the non-threshold models relates to mutagenic chemicals that cause DNA damage that contribute to carcinogenesis regardless of dose. In fact, identification of mutagenicity mechanisms for cancer development is often a key diagnostic for identification of threshold versus non-threshold mechanisms. This determination impacts the choice of either the derivation of a cancer slope factor and a risk specific dose, or a threshold-based toxicity reference value for cancer effects (RfD 'cancer). TBBPA, a flame retardant chemical that is detected in the environment, albeit at low levels in the U.S., has been extensively studied for a number of years. In order to develop an NSRL, we first reviewed authoritative assessments for TBBPA from regulatory and other agencies to see if an extant cancer risk value had been derived that could be adapted for use as the NSRL. A literature search was conducted from the date of the most recent authoritative review to the present, to identify any new data published since the time of the last review that could inform or update the basis for the NSRL. Data from both the 3 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 authoritative reviews and the published literature were evaluated for toxicological data and mode of action (MOA) information pertinent to cancer development. A risk characterization was then conducted, building off of previous publications, by identification of the critical tumor effect, identification of a point of departure (POD) utilizing Benchmark Dose (BMD) modeling, review of the MOE for tumor formation, derivation of a cancer risk value, and adaptation to an NSRL. 2.0 Methods 2.1 Hazard Identification and Literature Search There are a number of authoritative reviews available from regulatory agencies and others summarizing the toxicology and potential health impacts from exposure to TBBPA. These authoritative reviews were identified through an Internet search in relevant regulatory databases. The Internet was searched by individual key agency web sites, and broadly with ToxPlanet (https://toxplanet.com/). Additionally, an updated literature search was conducted from a few years prior to the date of the most recent review document (Health Canada, 2013), in order to identify any newly published data that could be utilized in derivation of the NSRL. The literature used in this report was in part identified in a systematic literature search in Elsevier Embase, PubMed, and ToxPlanet databases conducted in September, 2016 for the previous 5 years (2011-2016). The results and details of these searches can be found in Table 1. A broad ranging search in each database was initially utilized by searching the chemical name, synonyms, CAS registry number, and relevant acronyms. Data were filtered by limiting to animal or human species. In PubMed, another filter was employed - "NOT preablumin" as this key word was not relevant to toxicology studies but appeared repeatedly in the search results. Identified literature was initially screened and reviewed by title and abstract for content and relevance, and selected literature was subsequently obtained and further reviewed for appropriate data. These studies were reviewed and evaluated in order to determine the most appropriate critical cancer effect for use in deriving the NSRL. Literature regarded as insufficiently reliable for supporting a health conclusion (e.g., inadequate description of methods or data, lack of appropriate dose- response data) were excluded from further consideration. Table 1. Detailed search terms and search strings and resulting number of hits for each database searched to identify literature for use in derivation of the TBBPA NSRL. Database: Search String (see Table 2) No. hits PubMed AI(tetrabromidiphenylolpropane) OR tetrabromodi) OR 6994 tetrabromodi) OR tetrabromobisphenol) OR Tetrabromo-4,4'- isopropylidenediphenol) OR fire guard 2000) OR 79-94-7) OR tbbpa) OR 3,5,3',5'-Tetrabromobisphenol A 4 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 PubMed Added NOT "prealbumin" 863 PubMed (((tetrabromidiphenylolpropane) OR tetrabromodi) OR 135 LAST 5 tetrabromodi) OR tetrabromobisphenol) OR Tetrabromo-4,4'- YRS isopropylidenediphenol) OR fire guard 2000) OR 79-94-7) OR tbbpa) OR 3,5,3',5'-Tetrabromobisphenol A Filter: published in the last 5 years; Animals PubMed E((tetrabromidiphenylolpropane) OR tetrabromodi) OR 78 LAST 5 tetrabromobisphenol a) OR Tetrabromo-4,4' YRS isopropylidenediphenol) OR "Great Lakes BA-59P") OR "BA 59") OR 4,4'-Isopropylidenebis (2,6-dibromophenol)) OR 3,5,3',5'-Tetrabromobisphenol A) OR 2,2',6,6'- Tetrabromobisphenol / A) OR ((79-94-7 OR tbbpa)|) AND "last 5 years"[PDat])) NOT PREALBUMIN Filters: published in the last 5 years; Humans EMBASE tetrabromidiphenylolpropan OR tetrabromodi OR 751 "tetrabromobisphenol a" OR "tetrabromo 4 4 sopropylidenediphenol" OR "4 4 isopropylidenebis (2,6- dibromophenol)" OR "3 5 3 tetrabromobisphenol a" OR "2 2 6 6 Tetrabromobisphenol A" OR 79-94-7 OR tbbpa EMBASE ABOVE (TBBPA STRING) AND ('animal experiment'/de OR 316 'animal tissue'/de OR 'controlled study'/de OR 'correlational study'/de OR 'human'/de OR 'in vivo study'/de OR 'intermethod comparison'/de OR 'nonhuman'/de OR 'normal human'/de OR 'validation process'/de OR 'validation study'/de) AND (2011:py OR 2012:py OR 2013:py OR 2014:py OR 2015:py OR 2016:py OR 2017:py) ToxPlanet TBBPA; 79-94-7 91 As detailed below, due to the lack of available cancer studies other than the NTP (2014) 2-year cancer bioassay, this study was chosen for use in identification of the critical effect. Additional authoritative review papers and published literature (described below) were evaluated to gain an understanding of the noncancer effects of TBBPA as well as the potential MOA for tumor formation. 2.2 Dose-Response Analysis to Derive Point of Departure Benchmark dose (BMD) modeling (BMDS 2.6; U.S. EPA, 2012) was used to evaluate the dose-response relationship between exposure to TBBPA and cancer outcomes. As detailed below, adenoma, adenocarcinoma, or malignant mixed Mullerian tumors 5 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 (MMMTs) (combined) of the uterus identified through both original and residual longitudinal reviews [see Table 2 of Dunnick et al. (2015); NTP (2014)] were modeled to identify a POD. Atypical hyperplasia of the endometrium was also considered [see Table 6 of NTP (2014)]. All standard dichotomous models were considered. BMDs corresponding to 10% extra risk, the benchmark response (BMR), and their 95% lower bounds (BMDLs) were determined. All BMD modeling was done using extra risk. Model parameters were restricted when possible; not all models offer an option for the restriction of the slope or power. The POD reported is the duration-adjusted dose (i.e., the dose x 5/7, to account for dosing on only 5 of 7 days/week). The criteria described in EFSA (2017) as measures of model acceptability are the goodness-of-fit p-value, BMD to BMDL ratio, and the Akaike Information Criterion (AIC). U.S. EPA's BMDS guidance document for interpreting modeling results recommends adequacy determinations based on p-value, scaled residuals, visual fit, consideration of variability among BMDLs across the candidate models, AIC, and professional judgment (U.S. EPA, 2012). Because U.S. EPA's criteria are more inclusive, we discuss each of these in turn. The decision statements below, e.g., what constitutes adequate fit, are based on and adapted from the U.S. EPA guidance. The first criterion is the global statistical goodness of fit test that represents the full dose range of the data. If the p-value is >0.1, then the model is considered to adequately fit the data. Values lower than 0.1 suggest that the model may be statistically significantly different than the data, with values of 0.05 or less decidedly so. Models with values lower than 0.1 are usually rejected. Models with values of 0.05 or less would be rejected unless special circumstances existed, such as a mechanistic motivation for the model. However, models with higher p-values are not necessarily better than models with lower p-values (say, p = 0.5 versus p = 0.2) if both have a p-value >0.1, which is why other criteria, described below, are then used. The second criterion; relatedto-iseal-fit-is the difference in scaled residuals (that is, the difference in the modeled estimate compared with the actual data scaled by the standard error) at the data point closest to the BMR (in this case, 10%), where it is most important that the model fits the data. A scaled residual of 0 means that the model aligns perfectly with the data at that point, although any scaled residual with an absolute value of less than 2 is acceptable. Models with residuals that have an absolute value greater than this value are rejected. Models with lower residuals are usually preferred. U.S. EPA has recently added a scaled residual at the zero dose to one output format for its BMDS software. This parameter may also prove to be useful for future evaluations. The third criterion, related to scaled residuals, is the visual fit. Arguably the least quantitative criterion, visual fit nevertheless allows consideration of how well the model fits the underlying data, especially at the lower end of the curve or how well the model reflects the biological mode of action, if known. Designations of visual fit can include good, acceptable, and poor. Models that have "poor" visual fit should be rejected. Models with good visual fits are generally preferred. 6 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 U.S. EPA's fourth criterion is two-fold. The first part asks whether the BMDL estimates from the remaining models are sufficiently close to each other and reflect no particular influence of the individual models. This emphasizes that the goal of the modeling is to calculate a BMDL. One way to view this is to compare the ratios between the BMD and BMDL among the models. The larger the ratio, the less accurate the model is likely to be. Another useful comparator in previous U.S. EPA guidance was to decide that model-dependence is evident if the BMDLs differed by more than a factor of 3, but this specificity was removed as being too prescriptive (Jeff Gift, U.S. EPA, personal communication). The second part of this fourth criterion is the Akaike Information Criterion (AIC). Of the remaining models, the one chosen will generally have the lowest AIC. However, AICs within a value of 2 of each other are considered to be similar. If several models are still available from which to choose, then the lowest BMD and BMDL can be selected as a conservative choice, or the BMDs and BMDLs of several models can be averaged¹, using either an arithmetic or geometric mean. Such an average BMDL, however, loses its statistical properties, i.e., it is not the 95% lower bound on the average BMD. 2.3 Derivation of NSRL Once the point of departure (POD) was derived using BMDS, standard risk assessment guidance was utilized for the derivation of and cancer risk value and adaptation to an NSRL based on the U.S. EPA and OEHHA methodology (U.S. EPA, 2005; OEHHA, 1989). We first adjusted the POD to a human equivalent dose using allometric scaling (Equation 1). Because the weight-of-evidence for mode of action (MOA) for tumor formation identified did not involve direct DNA interaction, traditional linear cancer slope factor derivation was not conducted (Wikoff et al., 2015, 2016; NTP, 2014). Instead, an RfD. cancer was derived for a non-linear threshold response following the guidance of U.S. EPA (2005). This includes an assessment of the uncertainty associated with the POD and the application of uncertainty factors (Equation 2). Uncertainty factors are used to add conservatism and additional safety to the RfDc: given unknowns about the chemical, to account for data gaps, such as animal to human uncertainty, subchronic to chronic exposures, and to account for intra-individual variability. The derived RfDcancer was then converted to an NSRL by adjusting for body weight (Equation 3). Equation 1. DoseH = Dosea x Where 1Note that this is not the same as model averaging, where the individual model results are combined by using weights, with higher weights for models that fit the data better (Wheeler and Bailer, 2007). 7 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 DoseH = dose in human (BMDL10[HED]) Dosea = dose in animal (the POD for the specified critical effect = BMDL10) BWA = body weight of animal (0.268 kg for control female Wistar from NTP) BWH = body weight of human (70 kg²) Equation 2. RfD cancer = BMDL10[HED/(UFH x UFAX UFs x UFLX UFD) Where BMDL10[HED = benchmark dose lower limit human equivalent dose UFH = uncertainty factor for human variability UFA = uncertainty factor for animal to human extrapolation UFs = uncertainty factor for subchronic to chronic extrapolation UFL = uncertainty factor for LOAEL to NOAEL UFD = uncertainty factor for database completeness Equation 3. NSRL (mg/day) = RfDcance (mg/kg-day) x BWH (kg) Where BWH = body weight of human (70 kg) 3.0 Results 3.1 Literature search results Authoritative reviews identified include the National Institute of Environmental Health Sciences (NIEHS, 2002), the European Union (EU, 2006), the European Commission Committee on Toxicology (COT, 2004), the European Food Safety Authority (EFSA, 2 The body weight of 70 kg is the default body weight for males used by OEHHA as listed in the California Code of Regulations (27 CCR § 25703, 27 CA ADC § 25703; OEHHA, 2013). However, the recommended body weight for females is 58 kg, which is the specific subpopulation of interest, as uterine tumors were identified as the critical effect. We chose to use the 70 kg default as the body weight because: 1) it is more conservative (results in a slightly lower HED) than 58 kg; 2) women in the U.S. tend to be heavier; 3) 70 kg was utilized in most of the previous NSRL documents that we reviewed; and 4) due to the nature of the assessment, the difference between 70 kg and 58 kg is not enough to significantly change the final NSRL value (within an order of magnitude). 8 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 2011), and Health Canada (2013). At the time of this publication, the IARC monograph on TBBPA was unavailable for public review, and only the classification was available (Grosse et al., 2016). The above mentioned and available authoritative regulatory toxicity reference values for cancer (and noncancer) effects for TBBPA were evaluated. However, of these authoritative reviews, only two oral toxicity reference values were derived (ECHA, 2017; COT, 2004). Our literature search identified three additional recently published papers that derived risk values for TBBPA (Wikoff et al., 2015; Yang et al., 2016; Colnot et al., 2014). All values were evaluated for relevance in adapting for use as the NSRL. Data were also mined from the two most recent authoritative reports (EFSA, 2011; Health Canada, 2013) relating to standard toxicological endpoints and agency conclusions on the potential for adverse health effects on humans. All publically available data were reviewed, synthesized, and, in the absence of an available cancer risk value for TBBPA from the authoritative agencies, a cancer risk value was derived and the OEHHA methodology was applied to translate this value into an NSRL. The literature search identified a carcinogenicity study of TBBPA by the U.S. National Toxicology Program (NTP, 2014), and associated published studies that evaluated these NTP (2014) tumor findings and the TBBPA cancer MOA (Dunnick et al., 2015; Wikoff et al., 2015; Harvey et al., 2015; Sanders et al., 2016; Lai et al., 2015; Wikoff et al., 2016; Hall et al., 2017). These data are pertinent as the lack of cancer data was identified as a data gap for developing a cancer potency value as reported in the most recent authoritative reviews for TBBPA (EFSA, 2011; Health Canada, 2013). Further studies were identified investigating non-cancer effects related to inhalation toxicity, dermal absorption, thyroid hormone disruption, endocrine activity, developmental toxicity, and neurotoxicity. Additional toxicokinetic studies reported the disposition and kinetics of TBBPA in rats and one investigated toxicokinetic parameters in humans. 3.2 Authoritative and Published Risk Values for TBBPA 3.2.1 Toxicity Reference Values Toxicity reference values for TBBPA from various agencies are summarized in Table 2. The UK Committee on Toxicity (COT, 2004) derived a tolerable daily intake (TDI) for oral exposure of 1 mg/kg-day for chronic exposure in the general population. This TDI was based upon a NOAEL of 1,000 mg/kg-day in an unpublished two-generation reproductive toxicity study and in an unpublished 90-day study (MPI Research, 2002a,b, as cited in COT, 2004). The COT applied a composite uncertainty factor of 1,000 based on 10 for human to animal (UFA), 10 for human variability (UFH), and 10 for database deficiencies (UFD). ECHA (2017) developed a derived no effect level (DNEL) for long-term systemic effects following oral exposure for the general population. The oral DNEL of 2.5 mg/kg-day available on the ECHA website does not provide enough detail to determine the NOAEL used or the uncertainty factors applied to derive the value. Colnot et al. (2014) reported four oral DNELs, two for the general population based on different endpoints (thyroid effects and no effect in a 90-day study) and two for reproductive endpoints (fertility and development). The lowest oral DNEL of 0.16 mg/kg-day was based on a BMDL10 of 16 mg/kg-day for thyroid hormone changes after application of a 100-fold uncertainty factor 9 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 (UFA = 10, UFH = 10). Two recently published reference values for TBBPA were identified in the literature search (Yang et al., 2016; Wikoff et al., 2015) (Table 2). Yang et al. (2016) compared previous PODs available in the literature for TBBPA with a POD generated in their own study investigating TBBPA toxicity to thyroid hormones. However, due to a lack of some methodological details in the publication, the Yang et al. (2016) assessment was not used in supporting the derivation of a cancer risk value. For example, the authors do not discuss the uncertainty factors used to derive the RfD or the details of the BMD model outputs and rationale for model choice. Without these methodological details, there is not enough information provided to assess the validity of the proposed RfD. In the other assessment, Wikoff et al. (2015) developed a number of non-cancer and cancer toxicity reference values, including an oral RfD, an oral cancer slope factor, an average daily dose estimate, and evaluated the margin of exposure (MOE) and margin of safety (MOS) based on these risk values. These toxicity reference values were based on the recent NTP 2-year bioassay in rats and mice (NTP, 2014) and followed standard U.S. EPA methodology including the use of BMD modeling (U.S. EPA, 2012). Wikoff et al. (2015) conducted a comprehensive literature search to identify published and unpublished TBBPA toxicity studies that identified a dataset of studies to review followed by an evaluation of study quality using Klimisch scoring that narrowed the database to the most relevant high quality studies (Klimisch et al., 1997). The authors then selected the NTP (2014) 2-year carcinogenicity assay from the high quality studies and identified the most sensitive cancer and non-cancer endpoints for their choice of PODs (Wikoff et al., 2015). For the noncancer RfD, Wikoff et al. (2015) selected female rat uterine hyperplasia from the 2-year NTP bioassay as the critical effect. The data were modeled using BMDS to derive a BMDL10 of 72.8 mg/kg-day and after adjustment for allometric scaling to humans, resulted in a human equivalent dose (HED) of 18.2 mg/kg-day. Using this POD, a composite uncertainty factor of 30 was applied (UFA = 3, UFH = 10) resulting in an RfD of 0.6 mg/kg-day. It is worth noting that the BMD model applied (unspecified in the publication) had poor fit (P = 0.08) even after dropping the high treatment dose (Wikoff et al., 2015). For cancer endpoints, Wikoff et al. (2015) considered uterine tumors from the NTP (2014) study as the most appropriate endpoint for use in derivation of a cancer toxicity value. Wikoff et al. (2015) applied the linear multistage BMD model to the duration- adjusted doses for the cancer dataset. Their BMDL10 was 127 mg/kg-day, and after adjustment for allometric scaling to humans, resulted in an HED of 31.7 mg/kg-day. Using this POD, the cancer slope factor was calculated to be 0.0032 per mg/kg-day, which corresponds to a risk specific dose (RSD) at the 10-5 level of 0.0032 mg/kg-day (Wikoff et al., 2015). This value has been through a quality assurance review and is posted on the International Toxicity Estimates for Risk (ITER) database, which is found on the U.S. National Library of Medicine's TOXNET (https://www.nlm.nih.gov/pubs/factsheets/toxnetfs.html). Only the Wikoff et al. (2015) toxicity reference values characterized the cancer human 10 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 health risks of exposure to TBBPA (Table 2). Several organizations concluded that there were not sufficient data available to derive cancer or noncancer toxicity reference values (prior to publication of the NTP report), and many applied a MOE approach. A MOE can be defined as the magnitude by which the POD (e.g., the NOAEL) of the most sensitive relevant toxic effect exceeds the estimated exposure (Barnes and Dourson, 1988). 11 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Table 2. Toxicity values identified in the literature for the general population and breakdown of how each value was derived. Reference CTV* Value Exposure Critical Effect Key Study Point of departure Composite Adjustment duration, Factor (individual route adjustments) ECHA, DNEL 2.5 mg/kg- Chronic, Unidentified, however Mice, oral NOAEL = 250 100 (UFA = 10, UFH = 10) 2017 day oral the registration dossier gavage (study mg/kg-day states "a chronic study citation not is used to set a chronic clear) DNEL. No correction required". Rats, Colnot et 5 mg/kg- Chronic, DNEL No reproductive/ oral gavage NOAEL = 1,000 200 (UFA = 10, UFH = 10, UFs (MPI al., 2014 day oral developmental effects Research, mg/kg-day = 2) 2002b) 0.16 Rats, dietary Colnot et DNEL, Chronic, Thyroid hormone (Van BMDL10 = 16 mg/kg- al., 2014 oral mg/kg- changes der Ven et 100 (UFA = 10, UFH = 10) oral day day al., 2008) Rats, oral Colnot et DNEL, 10 mg/kg- Chronic, No reproductive/ gavage (MPI NOAEL = 1,000 100 (UFA = 10, UFH = 10) al., 2014 oral day oral fertility effects Research, mg/kg-day 2001) Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 COT, TDI 1 mg/kg- Chronic, No embryotoxic / Rats, oral NOAEL of 1,000 1,000 (UFA = 10, UFH = 10, 2004 day oral teratogenic effects: gavage (MPI, mg/kg-day UFD = 10) effects 2002b) Wikoff et RfD 0.6 mg/kg- Chronic, Uterine endometrial Rats, oral BDML10 72.8 30 (UFA = 3; UFH = 10) al., 2015 day oral atypical hyperplasia gavage (NTP, mg/kg-day NSRL for cancer precursor 2014) HED - 18.2 mg/kg- effect for 70 kg human = 42 day mg/kg-day Pecquet et RfDcance 0.9 mg/kg- Chronic, Uterine tumors Rats, oral BDML10 102.5 30 (UFA = 3; UFH = 10) al., 2017 r day oral gavage (NTP, mg/kg-day NSRL for 70 kg human = 60 (this 2014) HED - 25.6 mg/kg- mg/kg-day paper) day Wikoff et Cancer 0.00315 Chronic, Uterine tumors Rats, oral BMDL10 126.6 RSD at 10-6 = 0.0032 mg/kg- al., 2015 slope mg/kg-day oral gavage (NTP, mg/kg-day day factor 2014) HED - 31.7 mg/kg- NSRL for 70 kg human = 0.22 day mg/kg-day * CTV = Chronic Toxicity Value? 13 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 3.3 Summary of TBBPA toxicology In order to understand the potential for toxicity from TBBPA exposure, the noncancer and cancer toxicity findings from recent authoritative agencies were reviewed. Overall, TBBPA is expected to have very low systemic noncancer toxicity, with low hazard for developmental or reproductive toxicity, as reviewed and reported in multiple regulatory and other published reports (ECHA, 2017; EFSA, 2011; Health Canada, 2013; NTP, 2014; Colnot et al., 2014; U.S. EPA, 2014; Cope et al., 2015; etc.). 3.3.1 Genotoxicity and Cancer EFSA (2011) found no in vivo studies available to assess the genotoxicity of TBBPA, and Health Canada (2013) identified no structural activity data suggesting TBBPA might be genotoxic. Further, a number of in vitro studies, such as several Ames tests and mutagenicity assays, a chromosomal aberration assay, a recombination assay, a sister chromatid exchange in Chinese hamster ovary (CHO) cells, and a rat hepatocyte unscheduled DNA synthesis assay were evaluated, all with negative findings (EFSA, 2011; Health Canada, 2013; Colnot et al., 2014). These data were supported by structure activity relationship data, where no structural alerts for genotoxicity were identified and a lack of suitable analogs were available for use in read-across (U.S. EPA, 2014). The overall WOE indicates that TBBPA does not exert genotoxic or mutagenic effects. EFSA (2011) and Health Canada (2013) also assessed studies to investigate the potential carcinogenicity of TBBPA. At the time of these reports, no long-term carcinogenicity data were available for TBBPA. Based upon the WOE that TBBPA was non-genotoxic in vitro (EU, 2006; EFSA, 2011) and that there was no significant evidence of carcinogenic potential in repeat dose toxicity tests, EFSA (2011) concluded that TBBPA was not likely a carcinogen. One study reported non-malignant tumors in response to oral TBBPA administration, including non-dose-responsive transitional cell papillomas in the urinary bladder that did not progress to malignancy, and thyroid follicular adenomas (Imai et al., 2009, as cited in EFSA, 2011). Colnot et al. (2014) discuss the available data and conclude that the thyroid tumors are unsuitable for use in human risk assessment on the basis on species sensitivity differences between rodents and humans. Health Canada (2013) concluded that the effect of TBBPA on thyroid hormones remains unclear, and therefore utilized a MOE approach to show that current human exposures are below those that are likely to produce thyroid effects. COT (2006) discussed a lack of consistency in the available thyroid data and the potential for the effect to be reversible. Additionally, neither thyroid tumors nor thyroid histopathology effects were seen in rats or mice treated in the 2-year NTP assay (NTP, 2014; Lai et al., 2015). However, EFSA (2011) identified disrupted thyroid homeostasis as the critical noncancer effect in their MOE analysis. There was only one cancer bioassay identified in our literature search; the 2-year cancer bioassay conducted by NTP (2014) in rats and mice exposed to 0, 250, 500, or 1,000 mg/kg for 5 days a week via oral gavage in corn oil. These study details and results have been extensively reported elsewhere (NTP, 2014; Dunnick et al., 2015; Lai et al., 2015; Wikoff et al., 2015, 2016; U.S. EPA, 2014). The primary tumors identified were uterine tumors (combined adenoma, adenocarcinoma, and malignant mixed Mullerian) in female Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 rats (U.S. EPA, 2014). Other tumors included testicular tumors in male rats; and in male mice hepatic tumors, hemangiomas/hemangiosarcomas, and intestinal tumors were found (U.S. EPA, 2014). The Cancer Assessment Review Committee (CARC) of the U.S. EPA determined TBBPA as "likely to be carcinogenic to humans" based on the female rat uterine tumors and the male mice hemangiomas/hemangiosarcomas, with no mutagenicity concerns (U.S. EPA, 2014). NTP (2014) reached the following conclusions regarding each of these tumor types: Testicular adenomas in male rats: "equivocal evidence of carcinogenic activity" Uterine epithelial tumors in female rats: "clear evidence of carcinogenic activity", Hepatoblastomas in male mice: "some evidence of carcinogenic activity"; Intestinal tumors and hemangiosarcomas: may have been related to chemical administration. 3.4 TBBPA uterine cancer mode of action and weight of evidence analysis The U.S. EPA (2005) guidelines for cancer risk assessment state that the MOA should be evaluated in determining the quantitative approach for dose-response assessment from positive human or experimental animal tumor data. This evaluation is accomplished by proposing a MOA including identification of key events, where data on these key events includes available in vivo, in vitro, and mechanistic studies. These studies are then evaluated relative to the modified Bradford Hill criteria, including strength, consistency, specificity of the association between the key event(s) and tumor outcomes, as well as consideration of the consistency of the dose-response and temporal relationship between the key event and tumors, biological plausibility of the proposed MOA, and coherence of the overall database (Meek et al., 2014). When sufficient data are available, a biologically based dose-response (BBDR) model is the preferred method for low dose extrapolation. Absent such data, U.S. EPA (2005) and other groups such as OEHHA (2013) usually conduct a low-dose extrapolation with a linear model if the chemical acts via a direct DNA-reactive MOA or if the MOA is not known, or via a threshold model based on one or more combinations of relevant tumors for a non-DNA-reactive MOA. Other authoritative groups often rely on a MOE approach for cancer evaluation. However, all these groups support the use of the best available science, including consideration of MOA, in their assessments. An abbreviated MOA and WOE analysis was previously applied by Wikoff et al. (2016) to inform the quantitative approach for derivation of a cancer risk value. In the NTP 2- year TBBPA bioassay, and as evaluated by Wikoff et al. (2015), uterine tumors in rats were identified as the most appropriate endpoint for use in derivation of a cancer toxicity value. Based on the considerable amount of evidence that TBBPA is not mutagenic, a nonlinear MOA was postulated for TBBPA induced uterine tumors based on interference with estrogen metabolism, as discussed by several authors (Borghoff et al., 2016; Lai et al. 2015; Sanders et al., 2016; Wikoff et al., 2015; Dunnick et al., 2015; Harvey et al., 2015; Hall et al., 2017), most comprehensively by Wikoff et al. (2016). The interference with estrogen is not thought to involve TBBPA binding directly to the estrogen receptor (ER). The weak affinity for the estrogen receptor and other in vitro and in vivo studies 15 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 suggests that TBBPA is not estrogenic (Colnot et al, 2014; Lai et al., 2015; Wikoff et al., 2016). Estrogenic effects of TBBPA are controversial since both negative and positive findings are reported in the literature, but the low TBBPA binding affinity to the ER suggests that TBBPA is not directly interacting with this receptor (Lai et al., 2015). Instead, interference with estrogen metabolism via competition for shared biotransformation pathways (glucuronidation and sulfation) is a plausible mechanism, resulting in increased estrogen concentrations that either disrupt hormonal balances or drive estrogen-induced cellular proliferation (Lai et al., 2015). Wikoff et al. (2016) proposed an adverse outcome pathway and presented data for a number of key events, including a WOE analysis for TBBPA induced uterine cancer (Figure 1; adapted from Wikoff et al., 2016). The proposed key events starting with the molecular initiating event are the following: 1) TBBPA binds to estrogen sulfotransferase (sultlel), which inhibits the estrogen sulfation pathway; 2) this inhibition of estrogen sulfation leads to increased estradiol bioavailability; 3a) increased estrogen leads to increased expression of estrogen responsive genes, 3b) alternative estrogen metabolic pathways are activated causing generation of reactive quinones and other reactive species that can interact with DNA, and 3c) potential for disruption of the hormonal balance (with potential for disrupted endocrine signaling); 4) interaction of estrogen responsive genes contributing to cellular proliferation of cells with increased DNA damage and p53 mutations; and 5) hyperplasia of cells leading to the adverse outcome (uterine tumors). These key events and supporting data are extensively discussed in Wikoff et al. (2016), and so are only briefly described below. 16 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Figure 1. Diagram of postulated mode of action for TBBPA-induced uterine tumors. [1] TBBPA binds to estrogen sulfotransferase (sultle1); [2] the estrogen sulfation pathway is inhibited; [3a] bioavailable estrogen can bind the estrogen receptor (ER), which translocates to the nucleus and leads to increased expression of estrogen responsive genes, [3b] alternative estrogen metabolic pathways (such as cytochrome P450s, CYPs) can generate reactive intermediates that can interact with DNA and cause DNA damage; [4] estrogen responsive genes contribute to cellular proliferation of cells, some of which have increased DNA damage and gene mutations. & de SK 22222 Suittes [1] ca s TBBPA [2] CHAPH ER I ER 1 [3a] 13 HO is - Estrogen - NO [3b] [4] on CH.9 [4] , HO 1) TBBPA binds to estrogen sulfotransferase (sultle1). which inhibits the estrogen sulfation pathway Toxicokinetic evidence exists that shows TBBPA utilizes the same sulfation metabolic pathway as estrogen (sultle1). Metabolites in humans include TBBPA-sulfate (Schauer et al., 2006, as cited in Health Canada, 2013; Ho et al., 2017). Computational modeling and quantitative structure activity relationship (QSAR) analysis suggest that TBBPA is structurally able to inhibit sulfotransferase (Wikoff et al., 2016; Gosavi et al., 2013). Additionally, in vitro IC50S for TBBPA inhibition of estradiol sulfotransferase ranges from 12-33 nM (Wikoff et al., 2016; Kester et al., 2002; Gosavi et al., 2013; Hamers et al., 2006, as cited by Borghoff et al., 2016). Thus, when high doses of TBBPA produce high plasma concentrations of TBBPA, the IC50 for sulfotransferase is surpassed and saturation can occur. For example, in vivo studies show that TBBPA doses as low as 50 mg/kg result in plasma concentrations (1,478 nM TBBPA) well above the reported IC50 values (Wikoff et al., 2016; Borghoff et al., 2016). 17 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Taken together with the in vitro data, inhibition of sulfotransferase activity is a plausible molecular initiating event in the mode of action for TBBPA induced uterine cancer (Wikoff et al., 2016). However, more data are required to support this key event, as target tissue dosimetry and temporal relationships are required to determine if TBBPA inhibits sulfotransferase in the uterus (Osimitz et al., 2014). 2) Inhibition of estrogen sulfation leads to increased estradiol bioavailability The binding of estrogen to estrogen sulfotranserase (sultle1) leads to its biotransformation by conferring a sulfate group. When TBBPA interferes in this pathway, estrogen is not biotransformed, meaning more estrogen should be bioavailable systemically. This bioavailable estrogen could result in increased estrogen receptor (ER) activation, metabolic switching to an alternative estrogen metabolic pathway, or imbalance of the estrogen/progesterone ratio that has been implicated in other tumor types (mammary, prostate) (Lai et al., 2015). However, there are currently no data on TBBPA modification of estrogen/progesterone ratios (Lai et al., 2015). Alternatively, the loss of estrogen sulfotransferase might result in increased plasma estrogen levels that are implicated in the development of estrogen dependent human endometrial cancer (Cornel et al., 2017). There are a paucity of data investigating TBBPA exposure resulting in increased estrogen bioavailability, although theoretically, competition for sulfation of estrogen would reduce estrogen-sulfate conjugates, resulting in bioavailable estrogen able to bind to the ER (sulfated estrogens are not able to bind the ER) (Fu et al., 2011). This increased non- sulfated, bioavailable estrogen could also shift the estrogen metabolic pathway to alternatives that can result in the generation of reactive species (Wikoff et al., 2016). However, Sanders et al. (2016) reported unchanged estrogen serum levels following 5 daily gavage doses of TBBPA at 250 mg/kg, although they note that the duration of exposure might have been insufficient to produce changes and that use of serum estrogen levels serve as a poor proxy for endometrium estrogen levels. While this step is biologically plausible, more data are needed for a definitive conclusion. 3a) Increased estrogen leads to increased expression of estrogen responsive genes, 3b) alternative estrogen metabolism causing generation of reactive quinones that can interact with DNA, and 3c) potential for disruption of the hormonal balance (with potential for disrupted endocrine signaling) Wikoff et al. (2016) discuss evidence related to increased estrogen and TBBPA-induced increases in estrogen responsive genes in tissues other than the uterus. Since the time of the Wikoff publication, an additional study was published that investigated changes in estrogen concentration and gene expression in response to TBBPA. In a repeat-dose oral gavage study, adult female Wistar Hans rats were treated with vehicle or TBBPA (250 mg/kg-day) for 5 consecutive days to investigate the role of estrogen homeostasis in the MOA of TBBPA (Sanders et al., 2016). In tissue samples taken 24 hours after the 5-day treatment, T4 serum levels were decreased but serum estrogen levels were unchanged. While estrogen levels were not measured in the uterus, there were changes in expression of genes in the uterus that are markers of cell division/growth and metabolism of 18 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 TBBPA/estrogen/thyroid hormones. The gene expression changes in both the proximal and distal sections of the uterus with the greatest significance included genes involved with metabolism and hormone binding, including significantly increased levels of ERa and ERB (Sanders et al., 2016). This data partially supports an increase in estrogen responsive genes from TBBPA exposure, however, more data is needed to show that this is directly resultant from increased bioavailable estrogen, and more data are need to identify these changes specific to uterine tissues. Wikoff et al. (2016) discuss estrogen homeostasis as a balance of various metabolic pathways. Once one pathway is disrupted, alternative estrogen metabolism pathways (other than sulfation) may compensate. One of these pathways, the catechol estrogen pathway, results in the oxidation of catechol estrogens with reactive quinone intermediates. These reactive quinones can interact with DNA, and have been implicated in some cancers (Wikoff et al., 2016). For example, these intermediates could be leading to DNA interactions that could contribute to or selectively increase the proliferation of altered genes, such as the tumor suppressor p53 gene. Finally, there is a potential contribution of disrupted endocrine signaling via hormonal imbalance. Increased estrogen levels have the potential to modify the estrogen/progesterone ratio, and this imbalance has been implicated in other tumor types (mammary, prostate, estrogen dependent human endometrial cancer) (Lai et al., 2015, Cornel et al., 2017). However, there are currently no data on TBBPA modification of estrogen/progesterone ratios (Lai et al., 2015). 4) Interaction of estrogen responsive genes contributing to cellular proliferation, and increased DNA damage and p53 mutations Cellular proliferation is a critical component of hyperplasia leading to tumor formation. It is well established that estrogen binding to the ER can lead to cellular proliferation, and induction of genes related to cell cycle regulation (Sanders et al., 2016). In the NTP (2014) bioassay, there was a clear dose-response with increased uterine adenocarcinomas/adenoma at each increased TBBPA dose; however, data are lacking to confirm temporal associations specifically between increased estrogen serum levels and incidence of cellular proliferation in uterine tissues (Lai et al., 2015). High doses of TBBPA may in part promote uterine tumors in rats by promoting growth of cells with pre-existing mutations in the p53 tumor suppressor gene driven by increased estrogen-dependent cellular proliferation, or through selective proliferation of these mutations caused by reactive quinone intermediates (NTP, 2014; Lai et al., 2015). Additionally, as noted above, TBBPA has low affinity for the ER and so is not likely acting directly on the ER itself. This is plausible as significantly increased p53 mutations were identified in tumors in the NTP study, but since TBBPA is non-mutagenic, TBBPA itself is not directly causing the p53 mutations (Lai et al., 2015). The mechanism of p53 mutation has been previously implicated in cancer development, including human endometrial cancers (Harvey et al., 2015; Wikoff et al., 2016). Harvey et al. (2015) reported on an evaluation and analysis of TBBPA-induced uterine carcinomas in female rats from the NTP study. Analysis using PCR found a high rate of p53 mutations suggesting that uterine carcinogenesis might be partially p53 dependent (Harvey et al., 19 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 2015). In this analysis, the TBBPA-treated samples included Wistar Han rat uterine carcinomas from all dose groups combined (250, 500, and 1,000 mg/kg), thus no p53 mutation dose-response data are available. Of interest, the analysis did not include the malignant mixed Müllerian tumors (MMMTs). While this data supports the proposed key event, more data are needed, specifically dose-response data for p53 mutations and increased proliferation in response to TBBPA, to confirm this. 5) Hyperplasia of cells with p53 mutations leading to the adverse outcome (uterine tumors) Hyperplasia resulting from cellular proliferation is a well-known precursor effect related to the development of tumors, and is associated with increased estrogen levels in humans (Sanders et al., 2016). As noted, by Wikoff, both preneoplastic and nonneoplastic hyperplasia occurred in the NTP study. Atypical endometrial hyperplasia was seen in the NTP 2-year assay and was significantly increased above control at all dose levels, however, it was only identified via the longitudinal inspection, but not the transverse (Wikoff et al., 2016). While there was not a strict dose-response (250 mg/kg-day = 26% incidence; 500 mg/kg-day = 22% incidence; 1,000 mg/kg-day = 26% incidence), preneoplastic lesions are by definition precursors to tumor formation (Wikoff et al., 2016). Additionally, as stated above, a high rate of p53 mutations was identified in the uterine carcinogenesis (Harvey et al., 2015). Finally, the adverse outcome, significantly increased incidence of uterine tumors (adenomas, adenocarcinomas, and malignant mixed Mullerian), was seen with increasing dose in the NTP (2014) 2-year assay. 3.4.5 Weight of evidence A human relevance and concordance analysis of the postulated MOA was conducted by Wikoff et al. (2016), and suggests that given the available data, the proposed MOA is plausible for the development of uterine tumors. Wikoff et al. (2016) conclude this is a plausible mechanism in humans qualitatively, but may be quantitatively excluded based on kinetic/dynamic factors between humans and rats. Given some of the data gaps associated with this MOA, we have given the greatest weight to the non-mutagenic threshold MOA, as multiple lines of evidence support that the MOA identified is non- mutagenic. This is seen in a number of tests showing negative mutagenicity results, which are supported by the recent NTP findings of a negative micronucleus test and two negative Salmonella tests. Finally, the specificity of uterine tumors to the uterine tissue only (and not systemically developed) supports the non-mutagenic assertion (Lai et al., 2015). Thus, wWhile we conclude that the Wikoff et al. (2016) WOE analysis was adequate to establish the postulated MOA. the additional information we cite is further supportive ofgiven-the-evaileble-dete;- this non-mutagenic threshold MOA. and leads us to propose a NSRL based on the threshold approach of EPA (2005). However, a more robust and transparent analysis of the modified Bradford Hill criteria for this MOA would be helofulie-needed. Particularly useful in this instance would be a quantitative WOE ranking, as recently demonstrated by Becker et al. (2017). 20 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Howerer there is eurrently sepport 808 threshold MOA 4.0 Derivation of the NSRL 4.1 Choice of critical study and BMD analysis for POD After an updated evaluation of the available carcinogenicity literature for TBBPA, we agree with the choice of Wikoff et al. (2015) that uterine tumors (adenomas, adenocarcinomas, and malignant mixed Mullerian combined) are the most appropriate cancer endpoint, and were chosen as the critical effect for derivation of the NSRL (Table 4). Uterine tumors in female rats were chosen as the critical cancer effect for derivation of a cancer risk value. In looking at the other tumor types, the testicular adenomas in male rats were considered "equivocal" and occurred at low incidence in the two highest doses (500 mg/kg - 1/50 incidence; 1,000 mg/kg - 3/50 incidence), and as such, were not a reliable choice for the critical effect. The hepatoblastomas in male mice had "some evidence" for carcinogenicity (250 mg/kg - 2/50 incidence; 500 mg/kg - 11/50 incidence; 1,000 mg/kg - 8/50 incidence) with a significant effect in the 500 mg/kg dose. NTP (2014) considered this tumor as "some evidence" because after combining incidences of hepatocellular carcinomas and hepatoblastomas, there was only a significant effect at 250 mg/kg and there was no trend across doses, and this was informed by the historical incidence of these tumor types as spontaneous and related to chemical administration. Therefore, these tumors were not considered for use as the critical effect. The uterine epithelial tumors in female rats were the only tumor type classified as "clear evidence" and occurred with the highest incidence (0 mg/kg - 6/50 incidence; 250 mg/kg - 11/50 incidence; 500 mg/kg - 16/50 incidence; 1,000 mg/kg - 19/50 incidence). Therefore, the uterine tumors were the best choice for the critical effect in derivation of a cancer risk value. Table 4. Dose-response and dose-adjustment of cancer effects (tumors) and precursor effects (hyperplasia) from the NTP (2014) assay for use in BMD analysis. Dose, mg/kg Duration- Hyperplasia Tumor response: (NTP, 2014) adjusted dose response: Uterus original a and residual Commented [MD1]: Doses cannot be more precise than those given in the bioassay. Is is 3 digits for two? Residual longitudinal longitudinal reviews review; endometrium, (combined); adenoma, hyperplasia, atypical adenocarcinoma, or MMMT (combined) 0 0 2 6 250 1798-6 13 11 Formatted: Highlight Formatted: Highlight 500 357-+ 11 16 Formatted: Highlight 21 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 1,000 714.3 13 19 Formatted: Highlight In line with the Wikoff et al. (2015) assessment, we modeled the incidence of combined uterine adenomas, adenocarcinomas, and malignant mixed Müllerian tumors observed in female rats (NTP, 2014). While we agree with Wikoff et al. (2015) on the choice of critical effect, the application of the BMD approach and use of the BMDL10, and allometric adjustment of the POD to an HED, we had the benefit of additional literature that allowed us to agree with them that of the Factor appreach- extrapolate to a riste specifie dese to elsewheresupport- a non-mutagenic, threshold MOAresponse, and the determination of a safe dose values are through the application of uncertainty factors to the POD analogous to an RfD or TDI approach (U.S. EPA, 2005). Specifically, conclusion is supported by Wikoff et al. (2015,2016), who suggest that the linear cancer slope factor approach is inappropriate for a non- mutagenic chemical, and suggested that a threshold approach based on a non-mutagenic MOA is most appropriate. This conclusion is also supported However, ai the time-of-their 2015 publication data investigating the TBBPA MOA not there were date avay the tinear defacia stope faeter and the stedies-by Sanders et al. (2016) and Lai et al. (2015), Thus. coupled the postalated MOA by Wikeff et at (2016) is adequate evidence exists to move away from the default linear approach to a threshold approach for this tumor type. Even-though-the MOA is enly postulated) addition, the negative mutagenicity and genotoxicity data and the specificity of the tumor response to specific tissue types are all sufficient to suggest that a threshold approach is most scientifically credible to develop an NSRL. The results of the BMD analysis on adenoma, adenocarcinoma, or MMMT (combined) incidence in relation to TBBPA exposure are shown in Table 5. The log-logistic model (Figure 2) best fits the data based on all quantitative fit criteria: p-value (0.845), scaled residuals (0.042) at the dose with the response closest to the BMR, and AIC (223), resulting in a dose-adjusted BMD10 of 169 mg/kg-day corresponding to the BMDL10 of 103 mg/kg-day. This model provides a similar BMD to that from the multistage model (i.e., the model chosen by Wilkoff et al., 2015), but the loglogistic model results are more conservative and better fit the data, particularly in the dose region of interest. Atypical hyperplasia of the endometrium was also modeled as a potential precursor effect to tumor formation, but no model provided adequate fit of the data (i.e., p < 0.1). Table 5. BMD models examining the relationship between TBBPA exposure* Formatted Table and uterine cancer incidence (adenoma, adenocarcinoma, or MMMTs, combined) in female rats from NTP (2014). 22 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Model p- Scaled Visual Fit Ratio AIC BMD10 BMDL10 Value Residual BMD/ at Dose BMDL Gamma 0.75 0.14 good 1.5 223.1 195 127 Logistic 0.46 0.88 acceptable 1.3 224.0 290 219 LogLogistic 0.85 0.042 good 1.7 222.8 169 103 LogProbit 0.32 0.89 acceptable 1.5 224,8 317 216 Multistage (1*) 0.75 0.14 good 1.5 223.1 195 127 Multistage (2*) 0.75 0.14 good 1.5 223,1 195 127 Multistage (3*) 0.75 0.14 good 1.5 223.1 195 127 Probit 0.49 0.84 acceptable 1.3 223.9 277 208 Weibull 0.75 0.14 good 1.5 223.1 195 127 Quantal- Linear 0.75 0.14 good 1.5 223.1 195 127 *Duration-adjusted dose (5/7 days) *The numbers correspond to the number of degrees of polynomial in the multistage model The bolded row indicates the best fitting model Figure 2. Log logistic modeling results of uterine cancer (adenoma, adenocarcinoma, or MMMTs, combined) in female rats from NTP (2014). 23 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Log-Logetic with of sos, Exta Risk for the BMD and 3.95 Lower for the ......... 0.8 0.4 0.3 0.2 0.: BMOL BMC o 200 aco 800 800 1000 does The resulting duration-adjusted BMDL10 of 103 mg/kg-day was adjusted to a human equivalent dose (HED) of 26 mg/kg-day using allometric scaling (Equation 1; [25.6 mg/kg-day = 103 mg/kg-day x 3 4.2 Uncertainty factors Uncertainty factors were applied to the BMDL10[HED] to derive an RfDcar of 0.9 mg/kg- day using Equation 2 (0.85 mg/kg-day = 25.6 mg/kg-day/(10 x 3 X 1 x 1 x 1 = 30). The uncertainty factor that addresses interindividual variability (UFH) (also referred to as intraspecies variability) accounts for toxicokinetic and toxicodynamic variation across humans and is intended to protect sensitive subpopulations. Unless a study is conducted in a sensitive human population or 3 As noted previously, the choice of default body weight (between female at 58 kg and male at 70 kg) does not significantly change the resulting HED (27.5 mg/kg-day versus 26.3 mg/kg-day, respectively). For this and the reasons listed in the footnote above, we have used the default body weight of 70 kg. 24 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 there are data on human variability in response, the default for the UFH is 10. Given the lack of available data to move away from the default, we recommend the application of a 10-fold factor. The uncertainty factor for interspecies extrapolation (UFA) (also referred to as animal-to-human extrapolation) accounts for the translation of data from experimental animals to humans, specifically the toxicokinetic and toxicodynamic variation between species. Because we adjusted the POD to a human equivalent dose, this is presumed to account for the toxicokinetic differences across species (Renwick et al., 1999). Therefore, a reduced factor of one half the power of 10 (~3-fold) should be applied to account for the toxicodynamic differences between species (Renwick et al., 1999). The uncertainty factor for use of a LOAEL and extrapolation to a NOAEL (UFL) is not needed, since a BMD analysis was conducted. Therefore, a factor of 1 is applied. Additionally, the uncertainty factor for extrapolation of a subchronic critical study to a chronic exposure (UFs) is also not necessary, since a 2-year cancer bioassay was selected as the critical study. Therefore, a factor of 1 is applied. The uncertainty factor for database completeness (UFD) represents a judgment on the quantity and quality of the toxicology information available on the substance. TBBPA has an adequate toxicological database, particularly for noncancer effects, to assess the toxicological outcomes and potential adverse effects from exposure. However, this factor has also been utilized on occasion to account for severity of effect aimed to introduce an additional margin of safety when a compound has produced some form of severe or irreversible toxicity that is not addressed directly by the POD. It is worth noting that the noncancer dataset identified sensitive reproductive effects from TBBPA exposure [BMDLs of 0.5 mg/kg-day for increased testes weight and 0.6 mg/kg-day for increased F1 pituitary weight in males (van der Ven et al., 2008; Lilienthal et al., 2008; as cited in Health Canada, 2013)], and additional thyroid effects were seen but were largely uncharacterized [F1 males and females had decreased T4 levels (BMDL10 31 and 16 mg/kg, respectively)]. However, these data would be relevant for noncancer assessment, and as we are specifically addressing cancer endpoints, the application of this factor is not warranted. Specifically, the availability of the NTP 2-year comprehensive cancer bioassay is sufficient to inform the database for cancer. In total, we recommend the application of a composite uncertainty factor of 30 (3 x 10) to protect for uncertainties in the database and extrapolations. Therefore, for the derivation of the oral NSRL, we divide the BMDL10[HED] of 25.6 mg/kg-day by 30 to derive a cancer safe dose of 0.9 mg/kg-day. Based on the default human body weight of 70 kg, the NSRL is 60 (59.5) mg/day using Equation 3 (60 mg/day = 0.85 mg/kg-day x 70 kg). There were not enough published data identified to derive an inhalation NSRL. There was at least one DNEL derived for inhalation exposure, the studies that those values were based on were not publically available, and the relevance to cancer development from 25 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 inhalation exposure remains uncharacterized. 5.0 Discussion 5.1 Comparison of NSRL to RSD published by Wikoff et al., 2015 An NSRL of 60 mg/day was adapted from an RfDcancer of 0.9 mg/kg-day for a threshold MOA leading to uterine cancer seen in the recent NTP (2014) bioassay. The NSRL value (60 mg/day) is roughly 300-fold higher than the cancer slope factor adjusted to an NSRL derived by Wikoff et al. (2015) for 10-5 risk for the same tumor data (the risk level assigned by the NSRL) (0.0032 mg/kg-day x 70 kg = 0.22 mg/day). This difference reflects the use of a point estimate instead of a slope factor for low dose extrapolation, and slight differences in the BMDL due to model selection. Table 4 shows the various BMD model outputs for the uterine tumor data. While our models appear to align with those of Wikoff et al. (2015), we chose a different model based on an evaluation of multiple parameters (p-value, scaled residuals, visual fit, ratio of BMD to BMDL, and AIC). This difference in model selection accounts for a roughly 20% difference in the chosen points of departure (126.6 mg/kg-day chosen by Wikoff and colleagues versus 103 mg/kg-day chosen for this assessment). The NSRL proposed here of 60 mg/day, however, is within an order of magnitude and roughly aligns with a potential NSRL of 42 mg/day based on the RfD of 0.6 mg/kg-day derived by Wikoff et al. (2015) for noncancer uterine hyperplasia (i.e., 0.6 mg/kg-day x 70 kg = 42 mg/day). As some types of uterine hyperplasia are considered an upstream precursor to uterine cancer, the alignment of these values makes sense biologically. Additionally, protection from precursor effects is typically anticipated to protect from the downstream cancer effect. However, BMD models were not able to adequately fit the uterine hyperplasia data (p-value <0.1), even when the responses at the highest dose were dropped from the model (an approach that is consistent with U.S. EPA guidance; U.S. EPA, 2012). We chose not to use the hyperplasia precursor for cancer effects for a few reasons: 1) there is little currently available practical experience in using a POD based on cancer precursor effects to develop an RfD for a tumor; and 2) poor BMD model fit (p-value < 0.1) limits confidence in, and interpretation of, model results. 5.2 Comparison of RfD cancer to available risk values A comparison was made between the RfDc: derived here and other available risk values (see Table 2; Figure 3). The derived RfD cancer cancer (0.9 mg/kg-day) falls appropriately in respect to the biology on the risk value continuum as shown in Figure 3. As expected, DNELs for noncancer reproductive and developmental effects (DNEL repro and DNEL dev, both = 10 mg/kg-day) and DNELs for noncancer no effect levels (5 and 2.5 mg/kg-day) are higher than the derived RfD cancer by ~2.7 to 11-fold. The TDI, which was also derived for a noncancer no effect level (1 mg/kg-day), is roughly the same as the RfDcancer. This makes biological sense given the thresholded MOA for uterine tumor formation. The RfD for uterine hyperplasia (0.6 mg/kg-day), is slightly lower than the RfD This is expected and makes biological sense given that uterine hyperplasia is a precursor effect to uterine tumors. One would expect an RfD for a precursors effect to be 26 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 lower than that for the apical effect. Finally, the DNEL for thyroid effects (0.16 mg/kg- day) is lower than all other available noncancer values. However, as noted above in Section 3.3.1, there is a large amount of uncertainty associated with the thyroid endpoint (species sensitivity differences between rodents and humans, a lack of consistency in the available thyroid data, the potential for the effect to be reversible, neither thyroid tumors nor thyroid histopathology effects were seen in rats or mice treated in the 2-year NTP assay). Finally, the cancer slope factor (0.0032 mg/kg-day) is significantly lower than all other available risk values (from 50- to ~3,000-fold lower). Typically, the expectation is for cancer risk values to be lower than those for noncancer, under a no-threshold assumption. However, given the evidence for a threshold MOA for the most sensitive uterine tumors, the cancer slope factor is likely highly conservative and not biologically appropriate (280-fold lower than the RfDcancer). Figure 3. Comparison of available cancer and non-cancer risk values for TBBPA. 11 10 10 10 9 8 7 6 5 5 4 2.5 3 2 0.6 0.9 1 1 0.0032 0.16 0 5.2 Uncertainties Uncertainties are associated with using the malignant mixed Müllerian tumor (MMMT) data combined with the uterine adenomas and adenocarcinomas because of the rarity in their occurrence, and the fact that a dose-dependent trend was not reported in TBBPA treated rats. MMMTs are a very rare, spontaneous neoplasm in rats (Dunnick et al., 2015). Furthermore the historical data "are limited in Wistar Han rats because few studies using this strain have been conducted" (NTP, 2014). However, a large body of evidence on the epithelial histogenesis of MMMTs and their relevance to uterine cancers was cited as reasoning to include the MMMTs (Dunnick et al., 2015). The use of a new method of examining the rat uterus (a secondary Residual Longitudinal Review combined with the initial standard Transverse Review) allowed for the identification of additional tumors; 27 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 the additional transverse review identified adenocarcinomas or adenomas in all female rats with MMMTs. Therefore, BMD models including only adenomas and adenocarcinomas would be identical to those for combined adenomas, adenocarcinomas, and MMMTs. The MOA for uterine tumor formation needs additional validation, specifically, it would highly benefit from a comparison to the modified Bradford Hill criteria (such as conducted in Meek et al., 2014) and a quantitative weight of evidence approach (such as conducted in Becker et al., 2017). For the MOA, in vivo data to confirm that TBBPA competes for estrogen sulfotransferases are lacking. Target tissue dosimetry and temporal relationships to determine if TBBPA inhibits sulfotransferase in the uterus are required to determine if this mechanism is viable (Osimitz et al., 2014). Other uncertainties in the estrogen metabolism pathway have not been addressed, including the role of the alternative estrogen metabolism pathways, such as inhibition of hydroxysteroid- dehydrogenase-17beta (leading to increased estrogen activity) and induction of phase I enzymes CYP1A1 and CYP1B1 (leading to reactive metabolite formation) (Sanders et al., 2016). Others reviewed the plausibility of these alternative pathways but a more in- depth review is needed (Wikoff et al., 2015; Dunnick et al., 2015; Sanders et al., 2016). Additionally, more data is needed to evaluate this MOA at human relevant exposure doses. Wikoff et al. (2016) and others suggest this MOA operates only at high doses where saturation of the estrogen metabolic pathway occurs. Wikoff et al. (2016) suggests extrapolation to lower doses for protection of human health may be inappropriate given human doses are not expected to be high enough to lead to this MOA. However, we provide clear rationale that our NSRL is appropriate and as applied, is protective of the development of uterine tumors for several reasons: 1) tumors appear to be formed only at high doses due to non-mutagenic mechanism, and no tumors were identified in previous studies except the non-malignant tumors (transitional cell papillomas in the urinary bladder and thyroid follicular adenomas) (Imai et al., 2009, as cited in EFSA, 2011). This suggests that the potential for carcinogenicity from TBBPA exposure is quite low, will only occur at high doses, and negates the need for low-dose extrapolation; and 2) Wikoff reports that doses of 50 mg/kg are enough to surpass the sulfotransferase IC50, suggesting that this mechanism could be activated at doses below those in the NTP study. However, this dose would need to be exceeded in a chronic fashion in order for tumor formation to occur, and the RfDcan is well below this IC50 (0.9 Therefore, the derived RfDcancer is protective of uterine tumors via a non-threshold mode of action, and low dose extrapolation is not necessary. A final caveat relates to the existence of other potential MOAs/AOPs. Effects on thyroid homeostasis have also been seen, and for noncancer effects have produced relatively low BMD/Ls. Studies have shown that high TBBPA concentrations in vitro inhibit thyroid hormone metabolism with an IC50 of 460 nM for SULT1A in human liver cytosol, and the contribution of this MOA remains unclear (Butt and Stapleton, 2013). However, there is no indication that thyroid tumors result from exposure to TBBPA as neither tumors nor histopathology was found in the NTP assay. Additionally, there were testicular adenomas and hepatoblastomas identified in the NTP (2014) report. It is possible that these tumor types might drive the RfD cancer value lower, but as for the uterine tumors, are anticipated 28 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 to be non-mutagenic thresholded responses due to the non-mutagenic nature of TBBPA. 6.0 Conclusions Building off of previously published work investigating the mode of action and toxicity of TBBPA (ESFA, 2011; Health Canada, 2013; Wikoff et al., 2015, 2016; Lai et al., 2015), and using the cancer results seen from the recent NTP 2-year cancer bioassay, we have derived a no-significant-risk-level (NSRL) for TBBPA of 60 mg/day. The NSRL is based on uterine tumors (adenomas, adenocarcinomas, and malignant mixed Mullerian) identified in female rats exposed to TBBPA for 2-years via oral gavage. TBBPA has been shown to be a non-mutagenic carcinogen acting through an estrogen interference mode of action, and as such the most appropriate approach to derivation of a cancer risk value is a threshold approach, akin to an RfD cancer. Using the NTP study data, we derived a BMDL10 point of departure of 103 mg/kg-day and adjusted this to a human equivalent dose (HED) of 25.6 mg/kg-day using allometric scaling. We applied a composite adjustment factor of 30 to the POD to derive an RfDcancer of 0.9 mg/kg-day. Based on an average human body weight of 70 kg, the cancer safe dose was adjusted to an NSRL of 60 mg/day. Acknowledgements Funding for this work was provided by the American Chemical Council (ACC) and the developmental reserve funds of the University of Cincinnati, Risk Science Center. References Barnes, D.G., & Dourson, M.L. (1988). Reference dose (RfD): Description and use in health risk assessments. Regul Toxicol Pharmacol. 8, 471-486. Becker, R.A., Dellarco, V., Seed, J., Kronenberg, J.M., Meek, B., Foreman, J., Manibusan, M.K. (2017). Quantitative weight of evidence to assess confidence in potential modes of action. Regul Toxicol Pharmacol. 86, 205-220. Doi: 10.1016/j.yrtph.2017.02.017 Borghoff, S.J., Wikoff, D., Harvey, S., & Haws, L. (2016). Dose- and time-dependent changes in tissue levels of tetrabromobisphenol A (TBBPA) and its sulfate and glucuronide conjugates following repeated administration to female Wistar Han Rats. Toxicol Rep, 3, 190-201. doi:10.1016/j.toxrep.2016.01.007 Butt, C.M., & Stapleton, H.M. (2013). Inhibition of thyroid hormone sulfotransferase activity by brominated flame retardants and halogenated phenolics. Chem Res Toxicol, 26(11), 10.1021/tx400342k. oi:10.1021/tx400342k Colnot, T., Kacew, S., & DeKant, W. (2014). Mammalian toxicology and human exposures to the flame retardant 2,2, 6,6,-tetrabromo-4,4-isoprpoylidenediphenol (TBBPA): Implications for risk assessment. Arch Toxicol, 88, 1180-1188. doi: 10.1007/s00204-013-1180-8 COT (Committee on Toxicology). (2004). COT statement on tetrabromobisphenol A- 29 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 review of toxicological data. Retrieved from UK Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment. Available at: https://cot.food.gov.uk/committee/committee-on- oxicity/cotstatements/cotstatementsyrs/cotstatements2004/cotstatements2004tbbp a [accessed July 10, 2017] Cope, R. B., Kacew, S., & Dourson, M. (2015). A reproductive, developmental and neurobehavioral study following oral exposure of tetrabromobisphenol A on Sprague-Dawley rats. Toxicology, 329, 49-59. doi: 10.1016/j.tox.2014.12.013 Cornel, K. M. C., Krakstad, C., Delvoux, B., Xanthoulea, S., Jori, B., Bongers, M. Y. Romano, A. (2017). High mRNA levels of 176-hydroxysteroic dehydrogenase type 1 correlate with poor prognosis in endometrial cancer. Mol Cell Endocrinol, 442, 51-57. doi: 10.1016/j.mce.2016.11.030 Dunnick, J. K., Sanders, J. M., Kissling, G.E., Johnson, C. L., Boyle, M. H., & Elmore, S. A. (2015). Environmental chemical exposure may contribute to uterine cancer development: studies with tetrabromobisphenol A. Toxicol Pathol, 43, 464-473. doi: 10.1177/0192623314557335 European Chemicals Agency (ECHA). (2017). 2017. 2,2',6,6'-tetrabromo-4,4'- isopropylidenediphenol. Information on Chemicals, Registration Dossier. Last modified: 11-Jul-2017. Available online at: https://echa.europa.eu/registration- dossier/-/registered-dossier/14760/1 [accessed July 17, 2017] European Food Safety Administration (EFSA). 2011. Scientific Opinion on Tetrabromobisphenol A (TBBPA) and its derivatives in food. EFSA J, 9: 2477. Available online at: hitps://www.efsa.europa.eu/en/efsajournal/pub/2477 [accessed July 17, 2017] European Food Safety Administration (EFSA). 2017. Update: use of benchmark dose approach in risk assessment. EFSA J, 15: 4658. Available online at: äle:///Users/pecqueam/Downloads/Hardy et al-2017-EFSA Journal.pdf [accessed July 17, 2017] European Union (EU). 2006. Risk Assessment Report: ",6,6'-Tetrabromo-4,4" Isopropylidenediphenol (Tetrabromobisphenol-A or TBBP-A), Part II - Human Health. European Chemicals Bureau, European Commission, 4th Priority List, Volume 63. Available online at: https://echa.europa.eu/documents/10162/326000fe-b4fe-4828-b3d3 93c24cledd51 [accessed July 17, 2017] Fu, J., Fang, H., Paulsen, M., Ljungman, M., Kocarek, T. A., & Runge-Morris, M. (2011). Regulation of estrogen sulfotransferase expression by confluence of MCF10A breast epithelial cells: Role of the aryl hydrocarbon receptor. J Pharmacol Exp Ther., 339(2), 597-606. doi: 10.1124/jpet.111.185173 Gosavi, R. A., Knudsen, G. A., Birnbaum, L. S., & Pedersen, L. C. (2013). Mimicking of estradiol binding by flame retardants and their metabolites: A crystallographic analysis. Environ Health Perspect, 121, 1194-1199. doi: 10.1289/ehp. 1306902 30 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Grosse, Y., Loomis, D., Guyton, K.Z., Ghissassi, F-E., Bouvard, V., Benbrahim-Tallaa, L., Straif, K. (2016). Carcinogenicity of some industrial chemicals. The Lancet Oncol, 17(4), 419-420. Hall, S.M., Coulter, S.J., Knudsen, G.A., Sanders, J.M., & Birnbaum, L.S. (2017). Gene expression changes in immune response pathways following oral administration of tetrabromobisphenol A (TBBPA) in female Wistar Han rats. Toxicol Lett, 272, 68-74. doi:10.1016/j.toxlet.2017.03.008 Hamers, T., Kamstra, J.H., Sonneveld, E., Murk, A.J., Kester, M.H., Andersson, P.L., Legler, J., & Brouwer, A. (2006). In vitro profiling of the endocrine-disrupting potency of brominated flame retardants. Toxicol. Sci. 92, 157e-173e. [as cited in Colnot et al., 2014] doi: 10.1093/toxsci/kfj187 Harvey, J. B., Osborne, T. S., Hong, H. H., Bhusari, S., Ton, T. V., Pandiri, A. R., Hoenerhoff, M. J. (2015). Uterine Carcinomas in Tetrabromobisphenol A- exposed Wistar Han Rats Harbor Increased Tp53 Mutations and Mimic High- grade Type I Endometrial Carcinomas in Women. Toxicol Pathol, 43, 1103-1113. doi: 10.1177/0192623315599256 Health Canada. (2013). Screening assessment report of Phenol, 4,4' -(1-methylethylidene) bis[2,6-dibromo- (Tetrabromobisphenol A, TBBPA; CAS 79-94-7), Ethanol, 2,2'-[(1-methylethylidene)bis[(2,6-dibromo-4,1-phenylene)oxy]lbis (known as TBBPA bis(2-hydroxyethyl ether, CAS 4162-45-2) and Benzene, 1,1'-(1- methylethylidene)bis[3,5-dibromo-4-(2-propenyloxy)-(TBBPA bis(allylether, CAS 25327-89-3). Government of Canada, Environment Canada, Health Canada. Cat. No.: En14-110/2013E-PDF. ISBN: 978-1-100-22898-3. Ho, K. L., Yuen, K. K., Yau, M. S., Murphy, M. B., Wan, Y., Fong, B. M., Lam, M. H. (2017). Glucuronide and sulfate conjugates of tetrabromobisphenol A (TBBPA): Chemical synthesis and correlation between their urinary levels and plasma TBBPA content in voluntary human donors. Environ Int, 98, 46-53. doi: 10.1016/j.envint.2016.09. Imai, T., Takami, S., Cho, Y. M., Hirose, M., & Nishikawa, A. (2009). Modifying effects of prepubertal exposure to potassium perchlorate and tetrabromobisphenol A on susceptibility to N-bis(2-hydroxypropyl)nitrosamine- and 7,12 dimethylbenz(a)anthracene-induced carcinogenesis in rats. Toxicol Lett, 185, 160- 167. [As cited in EFSA, 2011]. doi: 10.1016/j.toxlet.2008.12.013 International Toxicity Estimates for Risk (ITER). A TOXNET Database. U.S. National Library of Medicine, National Institutes of Health. Available online at: https://toxnet.nlm.nih.gov/newtoxnet/iter.htm [accessed July 17, 2017] Jeff Gift, U.S. EPA, personal communication via email. In reference to: questions on benchmark dose. November 18, 2016. Kester, M.H., Bulduk, S., van Toor, H., Tibboel, D., Meinl, W., Glatt, H., Visser, T.J. (2002). Potent inhibition of estrogen sulfotransferase by hydroxylated metabolites 31 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 of bolyhalogenated aromatic hydrocarbons reveals alternative mechanism for estrogenic activity of endocrine disrupters. J. Clin. Endocrinol. Metab 87, 1142e- 1150e. Klimisch, H.J., Andreae, M., & Tillmann, U. (1997). A systematic approach for evaluating the quality of experimental toxicological and ecotoxicological data. Regul. Toxicol. Pharm. 25, 1-5. Lai, D. Y., Kacew, S., & Dekant, W. (2015). Tetrabromobisphenol A (TBBPA): Possible modes of action of toxicity and carcinogenicity in rodents. Food Chem Toxicol, 80, 206-214. doi: 10.1016/j.fct.2015.03.023 Lilienthal, H., Verwer, C., van der Ven, L., Piersma, A., & Vos, J. (2008). Exposure to tetrabromobisphenol A (TBBPA) in Wistar rats: Neurobehavioral effects in offspring from a one-generation reproduction study. Toxicology, 246, 45-54. [as cited in Health Canada, 2013] doi: 10.1016/j.tox.2008.01.007 Meek, M.E., Palermo, C.M., Bachman, A.N., North, C.M., & Lewis, R.J. (2014). Mode of action human relevance (species concordance) framework: Evolution of the Bradford Hill considerations and comparative analysis of weight of evidence. J Appl Toxicol, 34, 595-606. doi: 10.1002/jat.2984 MPI Research, 2002a. A 90-day oral toxicity study of tetrabromobisphenol-A in rats with a recovery group (unpublished). As cited in COT (2004). MPI Research, 2002b. An oral two generation reproductive, fertility and developmental neurobehavioural study of tetrabromobisphenol-A in rats (unpublished). Performed by MPI Research Inc., Mattawan, MI for the American Chemistry Council BFRIP, Arlington, VA. Study Number: 474-004, pp 2199 [as cited in Colnot et al., 2014] MPI Research. (2001). Final report-an oral prenatal developmental toxicity study with tetrabromobisphenol-A in rats (unpublished). [as cited in Colnot et al., 2014]. National Institute of Environmental Health Sciences (NIEHS). (2002). Tetrabromobisphenol A [79-94-7]: Review of Toxicological Literature. National Institutes of Health, National Toxicology Program. Available online at: https://ntp.niehs.nib.gov/ntp/btdocs/chem_background/exsumpdf/tetrabromobisph enola 508.pdf [accessed July 17, 2017] NTP (National Toxicology Program). (2014). Technical Report on the Toxicology Studies of Tetrabromobisphenol A (CAS NO. 79-94-7) in F344/NTac rats and B6C3F1/N mice and Toxicology and Carcinogenesis Studies of Tetrabromobisphenol A in Wistar Han [Crl:WI(Han)] rats and B6C3F1/N mice (Gavage Studies). NTP TR 587, September, 2014. National Institutes of Health, U.S. Department of Health and Human Services, Research Triangle Park, NC. Available online at: https://ntp.niehs.nib.gov/ntp/htdocs/lt_xpts/tr587508.pd [accessed July 7, 2017] Office of Environmental Health Hazard Assessment (OEHHA). (1989). Final Statement of Reasons. No Significant Risk Levels and No Observable Effect Levels. 32 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Proposition 65, California Environmental Protection Agency. June, 1989. Available online at: https://oehha.ca.gov/media/downloads/emnr/art78fsrjune1989.pdf [accessed July 7, 2017] Office of Environmental Health Hazard Assessment (OEHHA). (2013). Article 7. No Significant Risk Levels. § 25703. Quantitative Risk Assessment. Title 27, California Code of Regulation. Available online at: ittps://oehha.ca.gov/media/downloads/proposition-65/general-info/regsart7.pdf [accessed July 19, 2017] Osimitz, T.G., Dourson, M.L., Hayes, A. W., & Kacew, S. (2014). Crystallographic analysis and mimicking of estradiol binding: Interpretation and speculation. Environ Health Perspect, 122: A91-A92. DOI:10.1289/ehp.1307987 Renwick, A.G. (1999). Subdivision of uncertainty factors to allow for toxicokinetics and toxicodynamics. Human and Ecological Risk Assessment, 5, 1035-1050. doi: 10.1080/10807039991289329 Sanders, J.M., Coulter, S.J., Knudsen, G.A., Dunnick, J.K., Kissling, G.E., & Birnbaum, L.S. (2016). Disruption of estrogen homeostasis as a mechanism for uterine toxicity in Wistar Han rats treated with tetrabromobisphenol A. Toxicol Appl Pharmacol, 298, 31-39. doi: 10.1016/j.taap.2016.03.007 Schauer, U.M.D., Völkel, W., & Dekant, W. (2006). Toxicokinetics of tetrabromobisphenol A in humans and rats after oral administration. Toxicol Sci 91, 49-58. [as cited in Health Canada, 2013] U.S. EPA (Environmental Protection Agency). (1986). Guidelines for Mutagenicity Risk Assessment. U.S. Environmental Protection Agency: Washington, DC, EPA/630/R-98/003. Available online at: ps://www.epa.gov/sites/production/files/2013-09/documents/mutagen2.pdf [accessed July 7, 2017] U.S. EPA (Environmental Protection Agency). (2005). Guidelines for Carcinogen Risk Assessment. U.S. Environmental Protection Agency: Washington, DC, EPA/630/P-03/001F. Available online at: https://www.epa.gov/risk/guidelines- carcinogen-risk-assessment [accessed July 7, 2017] U.S. EPA (Environmental Protection Agency). (2012). Benchmark Dose Technical Guidance. Risk Assessment Forum, U.S. Environmental Protection Agency: Washington, DC.100-R-12-001. Available online at: attps://www.epa.goy/risk/benchmark-dose-technical-guidance[accessed July 7, 2017] U.S. EPA (Environmental Protection Agency). (2014). Supplemental File 4: Tetrabromobisphenol A (TBBPA, CASRN: 79-94-7) Cancer Assessment Review Committee Report. Health Effects Division, Office of Pesticide Programs, U.S. Environmental Protection Agency: Washington, DC. Available online at: https://www.epa.gov/assessing-and-managing-chemicals-under. 33 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 scalsupplemental-file-4-tetrabromobisphenol-tbbpa-casmn-79 [accessed July 7, 2017] Van der Ven, L.T., Van de Kuil, T., Verhoef, A., Verwer, C.M., Lilienthal, H., Leonards, P.E., Piersma, A.H. (2008). Endocrine effects of tetrabromobisphenol-A (TBBPA) in Wistar rats as tested in a one-generation reproduction study and a subacute toxicity study. Toxicology, 245, 76-89. doi: 10.1016/j.tox.2007.12.009 [as cited in Health Canada, 2013, and EFSA, 2011] Wheeler, M.W., & Bailer, A.J. (2007). Properties of model-averaged BMDLs: a study of model averaging in dichotomous response risk estimation. Risk Anal, 27(3): 659- 70. doi: 10.1111/j.1539-6924.2007.00920.x Wikoff, D., Thompson, C., Perry, C., White, M., Borghoff, S., Fitzgerald, L., & Haws, L.C. (2015). Development of toxicity values and exposure estimates for tetrabromobisphenol A: Application in a margin of exposure assessment. J Appl Toxicol, 35, 1292-1308. doi: 10.1002/jat.3132 Wikoff, D.S., Rager, J.E., Haws, L.C., & Borghoff, S.J. (2016). A high dose mode of action for tetrabromobisphenol A-induced uterine adenocarcinomas in Wistar Han rats: A critical evaluation of key events in an adverse outcome pathway framework. Regul Toxicol Pharmacol, 77, 143-159. doi: 10.1016/j.yrtph.2016.01.018. Yang, Y., Ni, W.W., Yu, L., Cai, Z., Yu Y.J. (2016). Toxic effects of tetrabromobisphenol A on thyroid hormones in SD rats and the derived-reference dose. Biomed Environ Sci, 29(4), 295-299. 34 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226

What is AIC of Weibull?

kxcn0226

kxcn0226_p4, kxcn0226_p5, kxcn0226_p6, kxcn0226_p7, kxcn0226_p8, kxcn0226_p9, kxcn0226_p10, kxcn0226_p11, kxcn0226_p12, kxcn0226_p13, kxcn0226_p14, kxcn0226_p15, kxcn0226_p16, kxcn0226_p17, kxcn0226_p18, kxcn0226_p19, kxcn0226_p20, kxcn0226_p21, kxcn0226_p22, kxcn0226_p23, kxcn0226_p24, kxcn0226_p25, kxcn0226_p26, kxcn0226_p27, kxcn0226_p28, kxcn0226_p29, kxcn0226_p30, kxcn0226_p31, kxcn0226_p32, kxcn0226_p33, kxcn0226_p34, kxcn0226_p35

223.1

1.0 Introduction Under the State of California's Proposition 65 (Prop65), a no significant risk level (NSRL) is developed for chemicals that are known to induce cancer in toxicological studies. The NSRL represents the "levels of exposure calculated to result in no more than one excess case of cancer in an exposed population of 100,000, assuming exposure over a 70-year lifetime (10-5 lifetime risk of cancer)" (OEHHA, 1989). California's Office of Environmental Health Hazard Assessment (OEHHA) recently announced its Prop65 notice of intent to list tetrabromobisphenol A (TBBPA) as known to the state to cause cancer. This is likely based on a recent International Agency for Research on Cancer (IARC) assessment that classified TBBPA as "Group 2A: probably carcinogenic to humans" (IARC Monograph in preparation, volume 115 - only the classification is available at the time of publication; Grosse et al., 2016). With the addition of TBBPA to the Prop65, a toxicological evaluation of TBBPA and derivation of an NSRL is needed. The methodology for NSRL derivation is similar to that of the U.S. EPA for developing cancer potency values. An evaluation of the available toxicological data in humans and animals is used to identify a significant biologic response of concern (critical effect) (OEHHA, 1989). In the absence of data to the contrary, noa threshold is assumed for the cancer effect of concern, and OEHHA then develops an NSRL through the use of no- threshold models (cancer slope factor development) based on U.S. EPA guidance (1986, 2005) (OEHHA, 2013). These NSRL values are then compared to exposure estimates to determine the potential to evoke a biological response at relevant environmental exposure levels (margin of safety) (OEHHA, 1989). However, when a threshold in response is supported based on available data, most risk agencies around the World support alternative approaches such as using threshold models. For example, the U.S. EPA (2005) methodology has advanced with the state of risk science, and includes a determination of a linear (non-threshold) or non-linear (threshold) mode of action (MOA) approach. Threshold models suggest that there are low doses of a chemical that do not cause effects and that a high enough dose is needed for effects to occur, while non- threshold models suggest that any dose above zero can lead to an effect (U.S. EPA, 2005). The-One basis for the non-threshold models relates to mutagenic chemicals that cause DNA damage that contribute to carcinogenesis regardless of dose. In fact, identification of mutagenicity mechanisms for cancer development is often a key diagnostic for identification of threshold versus non-threshold mechanisms. This determination impacts the choice of either the derivation of a cancer slope factor and a risk specific dose, or a threshold-based toxicity reference value for cancer effects (RfD 'cancer). TBBPA, a flame retardant chemical that is detected in the environment, albeit at low levels in the U.S., has been extensively studied for a number of years. In order to develop an NSRL, we first reviewed authoritative assessments for TBBPA from regulatory and other agencies to see if an extant cancer risk value had been derived that could be adapted for use as the NSRL. A literature search was conducted from the date of the most recent authoritative review to the present, to identify any new data published since the time of the last review that could inform or update the basis for the NSRL. Data from both the 3 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 authoritative reviews and the published literature were evaluated for toxicological data and mode of action (MOA) information pertinent to cancer development. A risk characterization was then conducted, building off of previous publications, by identification of the critical tumor effect, identification of a point of departure (POD) utilizing Benchmark Dose (BMD) modeling, review of the MOE for tumor formation, derivation of a cancer risk value, and adaptation to an NSRL. 2.0 Methods 2.1 Hazard Identification and Literature Search There are a number of authoritative reviews available from regulatory agencies and others summarizing the toxicology and potential health impacts from exposure to TBBPA. These authoritative reviews were identified through an Internet search in relevant regulatory databases. The Internet was searched by individual key agency web sites, and broadly with ToxPlanet (https://toxplanet.com/). Additionally, an updated literature search was conducted from a few years prior to the date of the most recent review document (Health Canada, 2013), in order to identify any newly published data that could be utilized in derivation of the NSRL. The literature used in this report was in part identified in a systematic literature search in Elsevier Embase, PubMed, and ToxPlanet databases conducted in September, 2016 for the previous 5 years (2011-2016). The results and details of these searches can be found in Table 1. A broad ranging search in each database was initially utilized by searching the chemical name, synonyms, CAS registry number, and relevant acronyms. Data were filtered by limiting to animal or human species. In PubMed, another filter was employed - "NOT preablumin" as this key word was not relevant to toxicology studies but appeared repeatedly in the search results. Identified literature was initially screened and reviewed by title and abstract for content and relevance, and selected literature was subsequently obtained and further reviewed for appropriate data. These studies were reviewed and evaluated in order to determine the most appropriate critical cancer effect for use in deriving the NSRL. Literature regarded as insufficiently reliable for supporting a health conclusion (e.g., inadequate description of methods or data, lack of appropriate dose- response data) were excluded from further consideration. Table 1. Detailed search terms and search strings and resulting number of hits for each database searched to identify literature for use in derivation of the TBBPA NSRL. Database: Search String (see Table 2) No. hits PubMed AI(tetrabromidiphenylolpropane) OR tetrabromodi) OR 6994 tetrabromodi) OR tetrabromobisphenol) OR Tetrabromo-4,4'- isopropylidenediphenol) OR fire guard 2000) OR 79-94-7) OR tbbpa) OR 3,5,3',5'-Tetrabromobisphenol A 4 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 PubMed Added NOT "prealbumin" 863 PubMed (((tetrabromidiphenylolpropane) OR tetrabromodi) OR 135 LAST 5 tetrabromodi) OR tetrabromobisphenol) OR Tetrabromo-4,4'- YRS isopropylidenediphenol) OR fire guard 2000) OR 79-94-7) OR tbbpa) OR 3,5,3',5'-Tetrabromobisphenol A Filter: published in the last 5 years; Animals PubMed E((tetrabromidiphenylolpropane) OR tetrabromodi) OR 78 LAST 5 tetrabromobisphenol a) OR Tetrabromo-4,4' YRS isopropylidenediphenol) OR "Great Lakes BA-59P") OR "BA 59") OR 4,4'-Isopropylidenebis (2,6-dibromophenol)) OR 3,5,3',5'-Tetrabromobisphenol A) OR 2,2',6,6'- Tetrabromobisphenol / A) OR ((79-94-7 OR tbbpa)|) AND "last 5 years"[PDat])) NOT PREALBUMIN Filters: published in the last 5 years; Humans EMBASE tetrabromidiphenylolpropan OR tetrabromodi OR 751 "tetrabromobisphenol a" OR "tetrabromo 4 4 sopropylidenediphenol" OR "4 4 isopropylidenebis (2,6- dibromophenol)" OR "3 5 3 tetrabromobisphenol a" OR "2 2 6 6 Tetrabromobisphenol A" OR 79-94-7 OR tbbpa EMBASE ABOVE (TBBPA STRING) AND ('animal experiment'/de OR 316 'animal tissue'/de OR 'controlled study'/de OR 'correlational study'/de OR 'human'/de OR 'in vivo study'/de OR 'intermethod comparison'/de OR 'nonhuman'/de OR 'normal human'/de OR 'validation process'/de OR 'validation study'/de) AND (2011:py OR 2012:py OR 2013:py OR 2014:py OR 2015:py OR 2016:py OR 2017:py) ToxPlanet TBBPA; 79-94-7 91 As detailed below, due to the lack of available cancer studies other than the NTP (2014) 2-year cancer bioassay, this study was chosen for use in identification of the critical effect. Additional authoritative review papers and published literature (described below) were evaluated to gain an understanding of the noncancer effects of TBBPA as well as the potential MOA for tumor formation. 2.2 Dose-Response Analysis to Derive Point of Departure Benchmark dose (BMD) modeling (BMDS 2.6; U.S. EPA, 2012) was used to evaluate the dose-response relationship between exposure to TBBPA and cancer outcomes. As detailed below, adenoma, adenocarcinoma, or malignant mixed Mullerian tumors 5 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 (MMMTs) (combined) of the uterus identified through both original and residual longitudinal reviews [see Table 2 of Dunnick et al. (2015); NTP (2014)] were modeled to identify a POD. Atypical hyperplasia of the endometrium was also considered [see Table 6 of NTP (2014)]. All standard dichotomous models were considered. BMDs corresponding to 10% extra risk, the benchmark response (BMR), and their 95% lower bounds (BMDLs) were determined. All BMD modeling was done using extra risk. Model parameters were restricted when possible; not all models offer an option for the restriction of the slope or power. The POD reported is the duration-adjusted dose (i.e., the dose x 5/7, to account for dosing on only 5 of 7 days/week). The criteria described in EFSA (2017) as measures of model acceptability are the goodness-of-fit p-value, BMD to BMDL ratio, and the Akaike Information Criterion (AIC). U.S. EPA's BMDS guidance document for interpreting modeling results recommends adequacy determinations based on p-value, scaled residuals, visual fit, consideration of variability among BMDLs across the candidate models, AIC, and professional judgment (U.S. EPA, 2012). Because U.S. EPA's criteria are more inclusive, we discuss each of these in turn. The decision statements below, e.g., what constitutes adequate fit, are based on and adapted from the U.S. EPA guidance. The first criterion is the global statistical goodness of fit test that represents the full dose range of the data. If the p-value is >0.1, then the model is considered to adequately fit the data. Values lower than 0.1 suggest that the model may be statistically significantly different than the data, with values of 0.05 or less decidedly so. Models with values lower than 0.1 are usually rejected. Models with values of 0.05 or less would be rejected unless special circumstances existed, such as a mechanistic motivation for the model. However, models with higher p-values are not necessarily better than models with lower p-values (say, p = 0.5 versus p = 0.2) if both have a p-value >0.1, which is why other criteria, described below, are then used. The second criterion; relatedto-iseal-fit-is the difference in scaled residuals (that is, the difference in the modeled estimate compared with the actual data scaled by the standard error) at the data point closest to the BMR (in this case, 10%), where it is most important that the model fits the data. A scaled residual of 0 means that the model aligns perfectly with the data at that point, although any scaled residual with an absolute value of less than 2 is acceptable. Models with residuals that have an absolute value greater than this value are rejected. Models with lower residuals are usually preferred. U.S. EPA has recently added a scaled residual at the zero dose to one output format for its BMDS software. This parameter may also prove to be useful for future evaluations. The third criterion, related to scaled residuals, is the visual fit. Arguably the least quantitative criterion, visual fit nevertheless allows consideration of how well the model fits the underlying data, especially at the lower end of the curve or how well the model reflects the biological mode of action, if known. Designations of visual fit can include good, acceptable, and poor. Models that have "poor" visual fit should be rejected. Models with good visual fits are generally preferred. 6 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 U.S. EPA's fourth criterion is two-fold. The first part asks whether the BMDL estimates from the remaining models are sufficiently close to each other and reflect no particular influence of the individual models. This emphasizes that the goal of the modeling is to calculate a BMDL. One way to view this is to compare the ratios between the BMD and BMDL among the models. The larger the ratio, the less accurate the model is likely to be. Another useful comparator in previous U.S. EPA guidance was to decide that model-dependence is evident if the BMDLs differed by more than a factor of 3, but this specificity was removed as being too prescriptive (Jeff Gift, U.S. EPA, personal communication). The second part of this fourth criterion is the Akaike Information Criterion (AIC). Of the remaining models, the one chosen will generally have the lowest AIC. However, AICs within a value of 2 of each other are considered to be similar. If several models are still available from which to choose, then the lowest BMD and BMDL can be selected as a conservative choice, or the BMDs and BMDLs of several models can be averaged¹, using either an arithmetic or geometric mean. Such an average BMDL, however, loses its statistical properties, i.e., it is not the 95% lower bound on the average BMD. 2.3 Derivation of NSRL Once the point of departure (POD) was derived using BMDS, standard risk assessment guidance was utilized for the derivation of and cancer risk value and adaptation to an NSRL based on the U.S. EPA and OEHHA methodology (U.S. EPA, 2005; OEHHA, 1989). We first adjusted the POD to a human equivalent dose using allometric scaling (Equation 1). Because the weight-of-evidence for mode of action (MOA) for tumor formation identified did not involve direct DNA interaction, traditional linear cancer slope factor derivation was not conducted (Wikoff et al., 2015, 2016; NTP, 2014). Instead, an RfD. cancer was derived for a non-linear threshold response following the guidance of U.S. EPA (2005). This includes an assessment of the uncertainty associated with the POD and the application of uncertainty factors (Equation 2). Uncertainty factors are used to add conservatism and additional safety to the RfDc: given unknowns about the chemical, to account for data gaps, such as animal to human uncertainty, subchronic to chronic exposures, and to account for intra-individual variability. The derived RfDcancer was then converted to an NSRL by adjusting for body weight (Equation 3). Equation 1. DoseH = Dosea x Where 1Note that this is not the same as model averaging, where the individual model results are combined by using weights, with higher weights for models that fit the data better (Wheeler and Bailer, 2007). 7 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 DoseH = dose in human (BMDL10[HED]) Dosea = dose in animal (the POD for the specified critical effect = BMDL10) BWA = body weight of animal (0.268 kg for control female Wistar from NTP) BWH = body weight of human (70 kg²) Equation 2. RfD cancer = BMDL10[HED/(UFH x UFAX UFs x UFLX UFD) Where BMDL10[HED = benchmark dose lower limit human equivalent dose UFH = uncertainty factor for human variability UFA = uncertainty factor for animal to human extrapolation UFs = uncertainty factor for subchronic to chronic extrapolation UFL = uncertainty factor for LOAEL to NOAEL UFD = uncertainty factor for database completeness Equation 3. NSRL (mg/day) = RfDcance (mg/kg-day) x BWH (kg) Where BWH = body weight of human (70 kg) 3.0 Results 3.1 Literature search results Authoritative reviews identified include the National Institute of Environmental Health Sciences (NIEHS, 2002), the European Union (EU, 2006), the European Commission Committee on Toxicology (COT, 2004), the European Food Safety Authority (EFSA, 2 The body weight of 70 kg is the default body weight for males used by OEHHA as listed in the California Code of Regulations (27 CCR § 25703, 27 CA ADC § 25703; OEHHA, 2013). However, the recommended body weight for females is 58 kg, which is the specific subpopulation of interest, as uterine tumors were identified as the critical effect. We chose to use the 70 kg default as the body weight because: 1) it is more conservative (results in a slightly lower HED) than 58 kg; 2) women in the U.S. tend to be heavier; 3) 70 kg was utilized in most of the previous NSRL documents that we reviewed; and 4) due to the nature of the assessment, the difference between 70 kg and 58 kg is not enough to significantly change the final NSRL value (within an order of magnitude). 8 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 2011), and Health Canada (2013). At the time of this publication, the IARC monograph on TBBPA was unavailable for public review, and only the classification was available (Grosse et al., 2016). The above mentioned and available authoritative regulatory toxicity reference values for cancer (and noncancer) effects for TBBPA were evaluated. However, of these authoritative reviews, only two oral toxicity reference values were derived (ECHA, 2017; COT, 2004). Our literature search identified three additional recently published papers that derived risk values for TBBPA (Wikoff et al., 2015; Yang et al., 2016; Colnot et al., 2014). All values were evaluated for relevance in adapting for use as the NSRL. Data were also mined from the two most recent authoritative reports (EFSA, 2011; Health Canada, 2013) relating to standard toxicological endpoints and agency conclusions on the potential for adverse health effects on humans. All publically available data were reviewed, synthesized, and, in the absence of an available cancer risk value for TBBPA from the authoritative agencies, a cancer risk value was derived and the OEHHA methodology was applied to translate this value into an NSRL. The literature search identified a carcinogenicity study of TBBPA by the U.S. National Toxicology Program (NTP, 2014), and associated published studies that evaluated these NTP (2014) tumor findings and the TBBPA cancer MOA (Dunnick et al., 2015; Wikoff et al., 2015; Harvey et al., 2015; Sanders et al., 2016; Lai et al., 2015; Wikoff et al., 2016; Hall et al., 2017). These data are pertinent as the lack of cancer data was identified as a data gap for developing a cancer potency value as reported in the most recent authoritative reviews for TBBPA (EFSA, 2011; Health Canada, 2013). Further studies were identified investigating non-cancer effects related to inhalation toxicity, dermal absorption, thyroid hormone disruption, endocrine activity, developmental toxicity, and neurotoxicity. Additional toxicokinetic studies reported the disposition and kinetics of TBBPA in rats and one investigated toxicokinetic parameters in humans. 3.2 Authoritative and Published Risk Values for TBBPA 3.2.1 Toxicity Reference Values Toxicity reference values for TBBPA from various agencies are summarized in Table 2. The UK Committee on Toxicity (COT, 2004) derived a tolerable daily intake (TDI) for oral exposure of 1 mg/kg-day for chronic exposure in the general population. This TDI was based upon a NOAEL of 1,000 mg/kg-day in an unpublished two-generation reproductive toxicity study and in an unpublished 90-day study (MPI Research, 2002a,b, as cited in COT, 2004). The COT applied a composite uncertainty factor of 1,000 based on 10 for human to animal (UFA), 10 for human variability (UFH), and 10 for database deficiencies (UFD). ECHA (2017) developed a derived no effect level (DNEL) for long-term systemic effects following oral exposure for the general population. The oral DNEL of 2.5 mg/kg-day available on the ECHA website does not provide enough detail to determine the NOAEL used or the uncertainty factors applied to derive the value. Colnot et al. (2014) reported four oral DNELs, two for the general population based on different endpoints (thyroid effects and no effect in a 90-day study) and two for reproductive endpoints (fertility and development). The lowest oral DNEL of 0.16 mg/kg-day was based on a BMDL10 of 16 mg/kg-day for thyroid hormone changes after application of a 100-fold uncertainty factor 9 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 (UFA = 10, UFH = 10). Two recently published reference values for TBBPA were identified in the literature search (Yang et al., 2016; Wikoff et al., 2015) (Table 2). Yang et al. (2016) compared previous PODs available in the literature for TBBPA with a POD generated in their own study investigating TBBPA toxicity to thyroid hormones. However, due to a lack of some methodological details in the publication, the Yang et al. (2016) assessment was not used in supporting the derivation of a cancer risk value. For example, the authors do not discuss the uncertainty factors used to derive the RfD or the details of the BMD model outputs and rationale for model choice. Without these methodological details, there is not enough information provided to assess the validity of the proposed RfD. In the other assessment, Wikoff et al. (2015) developed a number of non-cancer and cancer toxicity reference values, including an oral RfD, an oral cancer slope factor, an average daily dose estimate, and evaluated the margin of exposure (MOE) and margin of safety (MOS) based on these risk values. These toxicity reference values were based on the recent NTP 2-year bioassay in rats and mice (NTP, 2014) and followed standard U.S. EPA methodology including the use of BMD modeling (U.S. EPA, 2012). Wikoff et al. (2015) conducted a comprehensive literature search to identify published and unpublished TBBPA toxicity studies that identified a dataset of studies to review followed by an evaluation of study quality using Klimisch scoring that narrowed the database to the most relevant high quality studies (Klimisch et al., 1997). The authors then selected the NTP (2014) 2-year carcinogenicity assay from the high quality studies and identified the most sensitive cancer and non-cancer endpoints for their choice of PODs (Wikoff et al., 2015). For the noncancer RfD, Wikoff et al. (2015) selected female rat uterine hyperplasia from the 2-year NTP bioassay as the critical effect. The data were modeled using BMDS to derive a BMDL10 of 72.8 mg/kg-day and after adjustment for allometric scaling to humans, resulted in a human equivalent dose (HED) of 18.2 mg/kg-day. Using this POD, a composite uncertainty factor of 30 was applied (UFA = 3, UFH = 10) resulting in an RfD of 0.6 mg/kg-day. It is worth noting that the BMD model applied (unspecified in the publication) had poor fit (P = 0.08) even after dropping the high treatment dose (Wikoff et al., 2015). For cancer endpoints, Wikoff et al. (2015) considered uterine tumors from the NTP (2014) study as the most appropriate endpoint for use in derivation of a cancer toxicity value. Wikoff et al. (2015) applied the linear multistage BMD model to the duration- adjusted doses for the cancer dataset. Their BMDL10 was 127 mg/kg-day, and after adjustment for allometric scaling to humans, resulted in an HED of 31.7 mg/kg-day. Using this POD, the cancer slope factor was calculated to be 0.0032 per mg/kg-day, which corresponds to a risk specific dose (RSD) at the 10-5 level of 0.0032 mg/kg-day (Wikoff et al., 2015). This value has been through a quality assurance review and is posted on the International Toxicity Estimates for Risk (ITER) database, which is found on the U.S. National Library of Medicine's TOXNET (https://www.nlm.nih.gov/pubs/factsheets/toxnetfs.html). Only the Wikoff et al. (2015) toxicity reference values characterized the cancer human 10 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 health risks of exposure to TBBPA (Table 2). Several organizations concluded that there were not sufficient data available to derive cancer or noncancer toxicity reference values (prior to publication of the NTP report), and many applied a MOE approach. A MOE can be defined as the magnitude by which the POD (e.g., the NOAEL) of the most sensitive relevant toxic effect exceeds the estimated exposure (Barnes and Dourson, 1988). 11 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Table 2. Toxicity values identified in the literature for the general population and breakdown of how each value was derived. Reference CTV* Value Exposure Critical Effect Key Study Point of departure Composite Adjustment duration, Factor (individual route adjustments) ECHA, DNEL 2.5 mg/kg- Chronic, Unidentified, however Mice, oral NOAEL = 250 100 (UFA = 10, UFH = 10) 2017 day oral the registration dossier gavage (study mg/kg-day states "a chronic study citation not is used to set a chronic clear) DNEL. No correction required". Rats, Colnot et 5 mg/kg- Chronic, DNEL No reproductive/ oral gavage NOAEL = 1,000 200 (UFA = 10, UFH = 10, UFs (MPI al., 2014 day oral developmental effects Research, mg/kg-day = 2) 2002b) 0.16 Rats, dietary Colnot et DNEL, Chronic, Thyroid hormone (Van BMDL10 = 16 mg/kg- al., 2014 oral mg/kg- changes der Ven et 100 (UFA = 10, UFH = 10) oral day day al., 2008) Rats, oral Colnot et DNEL, 10 mg/kg- Chronic, No reproductive/ gavage (MPI NOAEL = 1,000 100 (UFA = 10, UFH = 10) al., 2014 oral day oral fertility effects Research, mg/kg-day 2001) Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 COT, TDI 1 mg/kg- Chronic, No embryotoxic / Rats, oral NOAEL of 1,000 1,000 (UFA = 10, UFH = 10, 2004 day oral teratogenic effects: gavage (MPI, mg/kg-day UFD = 10) effects 2002b) Wikoff et RfD 0.6 mg/kg- Chronic, Uterine endometrial Rats, oral BDML10 72.8 30 (UFA = 3; UFH = 10) al., 2015 day oral atypical hyperplasia gavage (NTP, mg/kg-day NSRL for cancer precursor 2014) HED - 18.2 mg/kg- effect for 70 kg human = 42 day mg/kg-day Pecquet et RfDcance 0.9 mg/kg- Chronic, Uterine tumors Rats, oral BDML10 102.5 30 (UFA = 3; UFH = 10) al., 2017 r day oral gavage (NTP, mg/kg-day NSRL for 70 kg human = 60 (this 2014) HED - 25.6 mg/kg- mg/kg-day paper) day Wikoff et Cancer 0.00315 Chronic, Uterine tumors Rats, oral BMDL10 126.6 RSD at 10-6 = 0.0032 mg/kg- al., 2015 slope mg/kg-day oral gavage (NTP, mg/kg-day day factor 2014) HED - 31.7 mg/kg- NSRL for 70 kg human = 0.22 day mg/kg-day * CTV = Chronic Toxicity Value? 13 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 3.3 Summary of TBBPA toxicology In order to understand the potential for toxicity from TBBPA exposure, the noncancer and cancer toxicity findings from recent authoritative agencies were reviewed. Overall, TBBPA is expected to have very low systemic noncancer toxicity, with low hazard for developmental or reproductive toxicity, as reviewed and reported in multiple regulatory and other published reports (ECHA, 2017; EFSA, 2011; Health Canada, 2013; NTP, 2014; Colnot et al., 2014; U.S. EPA, 2014; Cope et al., 2015; etc.). 3.3.1 Genotoxicity and Cancer EFSA (2011) found no in vivo studies available to assess the genotoxicity of TBBPA, and Health Canada (2013) identified no structural activity data suggesting TBBPA might be genotoxic. Further, a number of in vitro studies, such as several Ames tests and mutagenicity assays, a chromosomal aberration assay, a recombination assay, a sister chromatid exchange in Chinese hamster ovary (CHO) cells, and a rat hepatocyte unscheduled DNA synthesis assay were evaluated, all with negative findings (EFSA, 2011; Health Canada, 2013; Colnot et al., 2014). These data were supported by structure activity relationship data, where no structural alerts for genotoxicity were identified and a lack of suitable analogs were available for use in read-across (U.S. EPA, 2014). The overall WOE indicates that TBBPA does not exert genotoxic or mutagenic effects. EFSA (2011) and Health Canada (2013) also assessed studies to investigate the potential carcinogenicity of TBBPA. At the time of these reports, no long-term carcinogenicity data were available for TBBPA. Based upon the WOE that TBBPA was non-genotoxic in vitro (EU, 2006; EFSA, 2011) and that there was no significant evidence of carcinogenic potential in repeat dose toxicity tests, EFSA (2011) concluded that TBBPA was not likely a carcinogen. One study reported non-malignant tumors in response to oral TBBPA administration, including non-dose-responsive transitional cell papillomas in the urinary bladder that did not progress to malignancy, and thyroid follicular adenomas (Imai et al., 2009, as cited in EFSA, 2011). Colnot et al. (2014) discuss the available data and conclude that the thyroid tumors are unsuitable for use in human risk assessment on the basis on species sensitivity differences between rodents and humans. Health Canada (2013) concluded that the effect of TBBPA on thyroid hormones remains unclear, and therefore utilized a MOE approach to show that current human exposures are below those that are likely to produce thyroid effects. COT (2006) discussed a lack of consistency in the available thyroid data and the potential for the effect to be reversible. Additionally, neither thyroid tumors nor thyroid histopathology effects were seen in rats or mice treated in the 2-year NTP assay (NTP, 2014; Lai et al., 2015). However, EFSA (2011) identified disrupted thyroid homeostasis as the critical noncancer effect in their MOE analysis. There was only one cancer bioassay identified in our literature search; the 2-year cancer bioassay conducted by NTP (2014) in rats and mice exposed to 0, 250, 500, or 1,000 mg/kg for 5 days a week via oral gavage in corn oil. These study details and results have been extensively reported elsewhere (NTP, 2014; Dunnick et al., 2015; Lai et al., 2015; Wikoff et al., 2015, 2016; U.S. EPA, 2014). The primary tumors identified were uterine tumors (combined adenoma, adenocarcinoma, and malignant mixed Mullerian) in female Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 rats (U.S. EPA, 2014). Other tumors included testicular tumors in male rats; and in male mice hepatic tumors, hemangiomas/hemangiosarcomas, and intestinal tumors were found (U.S. EPA, 2014). The Cancer Assessment Review Committee (CARC) of the U.S. EPA determined TBBPA as "likely to be carcinogenic to humans" based on the female rat uterine tumors and the male mice hemangiomas/hemangiosarcomas, with no mutagenicity concerns (U.S. EPA, 2014). NTP (2014) reached the following conclusions regarding each of these tumor types: Testicular adenomas in male rats: "equivocal evidence of carcinogenic activity" Uterine epithelial tumors in female rats: "clear evidence of carcinogenic activity", Hepatoblastomas in male mice: "some evidence of carcinogenic activity"; Intestinal tumors and hemangiosarcomas: may have been related to chemical administration. 3.4 TBBPA uterine cancer mode of action and weight of evidence analysis The U.S. EPA (2005) guidelines for cancer risk assessment state that the MOA should be evaluated in determining the quantitative approach for dose-response assessment from positive human or experimental animal tumor data. This evaluation is accomplished by proposing a MOA including identification of key events, where data on these key events includes available in vivo, in vitro, and mechanistic studies. These studies are then evaluated relative to the modified Bradford Hill criteria, including strength, consistency, specificity of the association between the key event(s) and tumor outcomes, as well as consideration of the consistency of the dose-response and temporal relationship between the key event and tumors, biological plausibility of the proposed MOA, and coherence of the overall database (Meek et al., 2014). When sufficient data are available, a biologically based dose-response (BBDR) model is the preferred method for low dose extrapolation. Absent such data, U.S. EPA (2005) and other groups such as OEHHA (2013) usually conduct a low-dose extrapolation with a linear model if the chemical acts via a direct DNA-reactive MOA or if the MOA is not known, or via a threshold model based on one or more combinations of relevant tumors for a non-DNA-reactive MOA. Other authoritative groups often rely on a MOE approach for cancer evaluation. However, all these groups support the use of the best available science, including consideration of MOA, in their assessments. An abbreviated MOA and WOE analysis was previously applied by Wikoff et al. (2016) to inform the quantitative approach for derivation of a cancer risk value. In the NTP 2- year TBBPA bioassay, and as evaluated by Wikoff et al. (2015), uterine tumors in rats were identified as the most appropriate endpoint for use in derivation of a cancer toxicity value. Based on the considerable amount of evidence that TBBPA is not mutagenic, a nonlinear MOA was postulated for TBBPA induced uterine tumors based on interference with estrogen metabolism, as discussed by several authors (Borghoff et al., 2016; Lai et al. 2015; Sanders et al., 2016; Wikoff et al., 2015; Dunnick et al., 2015; Harvey et al., 2015; Hall et al., 2017), most comprehensively by Wikoff et al. (2016). The interference with estrogen is not thought to involve TBBPA binding directly to the estrogen receptor (ER). The weak affinity for the estrogen receptor and other in vitro and in vivo studies 15 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 suggests that TBBPA is not estrogenic (Colnot et al, 2014; Lai et al., 2015; Wikoff et al., 2016). Estrogenic effects of TBBPA are controversial since both negative and positive findings are reported in the literature, but the low TBBPA binding affinity to the ER suggests that TBBPA is not directly interacting with this receptor (Lai et al., 2015). Instead, interference with estrogen metabolism via competition for shared biotransformation pathways (glucuronidation and sulfation) is a plausible mechanism, resulting in increased estrogen concentrations that either disrupt hormonal balances or drive estrogen-induced cellular proliferation (Lai et al., 2015). Wikoff et al. (2016) proposed an adverse outcome pathway and presented data for a number of key events, including a WOE analysis for TBBPA induced uterine cancer (Figure 1; adapted from Wikoff et al., 2016). The proposed key events starting with the molecular initiating event are the following: 1) TBBPA binds to estrogen sulfotransferase (sultlel), which inhibits the estrogen sulfation pathway; 2) this inhibition of estrogen sulfation leads to increased estradiol bioavailability; 3a) increased estrogen leads to increased expression of estrogen responsive genes, 3b) alternative estrogen metabolic pathways are activated causing generation of reactive quinones and other reactive species that can interact with DNA, and 3c) potential for disruption of the hormonal balance (with potential for disrupted endocrine signaling); 4) interaction of estrogen responsive genes contributing to cellular proliferation of cells with increased DNA damage and p53 mutations; and 5) hyperplasia of cells leading to the adverse outcome (uterine tumors). These key events and supporting data are extensively discussed in Wikoff et al. (2016), and so are only briefly described below. 16 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Figure 1. Diagram of postulated mode of action for TBBPA-induced uterine tumors. [1] TBBPA binds to estrogen sulfotransferase (sultle1); [2] the estrogen sulfation pathway is inhibited; [3a] bioavailable estrogen can bind the estrogen receptor (ER), which translocates to the nucleus and leads to increased expression of estrogen responsive genes, [3b] alternative estrogen metabolic pathways (such as cytochrome P450s, CYPs) can generate reactive intermediates that can interact with DNA and cause DNA damage; [4] estrogen responsive genes contribute to cellular proliferation of cells, some of which have increased DNA damage and gene mutations. & de SK 22222 Suittes [1] ca s TBBPA [2] CHAPH ER I ER 1 [3a] 13 HO is - Estrogen - NO [3b] [4] on CH.9 [4] , HO 1) TBBPA binds to estrogen sulfotransferase (sultle1). which inhibits the estrogen sulfation pathway Toxicokinetic evidence exists that shows TBBPA utilizes the same sulfation metabolic pathway as estrogen (sultle1). Metabolites in humans include TBBPA-sulfate (Schauer et al., 2006, as cited in Health Canada, 2013; Ho et al., 2017). Computational modeling and quantitative structure activity relationship (QSAR) analysis suggest that TBBPA is structurally able to inhibit sulfotransferase (Wikoff et al., 2016; Gosavi et al., 2013). Additionally, in vitro IC50S for TBBPA inhibition of estradiol sulfotransferase ranges from 12-33 nM (Wikoff et al., 2016; Kester et al., 2002; Gosavi et al., 2013; Hamers et al., 2006, as cited by Borghoff et al., 2016). Thus, when high doses of TBBPA produce high plasma concentrations of TBBPA, the IC50 for sulfotransferase is surpassed and saturation can occur. For example, in vivo studies show that TBBPA doses as low as 50 mg/kg result in plasma concentrations (1,478 nM TBBPA) well above the reported IC50 values (Wikoff et al., 2016; Borghoff et al., 2016). 17 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Taken together with the in vitro data, inhibition of sulfotransferase activity is a plausible molecular initiating event in the mode of action for TBBPA induced uterine cancer (Wikoff et al., 2016). However, more data are required to support this key event, as target tissue dosimetry and temporal relationships are required to determine if TBBPA inhibits sulfotransferase in the uterus (Osimitz et al., 2014). 2) Inhibition of estrogen sulfation leads to increased estradiol bioavailability The binding of estrogen to estrogen sulfotranserase (sultle1) leads to its biotransformation by conferring a sulfate group. When TBBPA interferes in this pathway, estrogen is not biotransformed, meaning more estrogen should be bioavailable systemically. This bioavailable estrogen could result in increased estrogen receptor (ER) activation, metabolic switching to an alternative estrogen metabolic pathway, or imbalance of the estrogen/progesterone ratio that has been implicated in other tumor types (mammary, prostate) (Lai et al., 2015). However, there are currently no data on TBBPA modification of estrogen/progesterone ratios (Lai et al., 2015). Alternatively, the loss of estrogen sulfotransferase might result in increased plasma estrogen levels that are implicated in the development of estrogen dependent human endometrial cancer (Cornel et al., 2017). There are a paucity of data investigating TBBPA exposure resulting in increased estrogen bioavailability, although theoretically, competition for sulfation of estrogen would reduce estrogen-sulfate conjugates, resulting in bioavailable estrogen able to bind to the ER (sulfated estrogens are not able to bind the ER) (Fu et al., 2011). This increased non- sulfated, bioavailable estrogen could also shift the estrogen metabolic pathway to alternatives that can result in the generation of reactive species (Wikoff et al., 2016). However, Sanders et al. (2016) reported unchanged estrogen serum levels following 5 daily gavage doses of TBBPA at 250 mg/kg, although they note that the duration of exposure might have been insufficient to produce changes and that use of serum estrogen levels serve as a poor proxy for endometrium estrogen levels. While this step is biologically plausible, more data are needed for a definitive conclusion. 3a) Increased estrogen leads to increased expression of estrogen responsive genes, 3b) alternative estrogen metabolism causing generation of reactive quinones that can interact with DNA, and 3c) potential for disruption of the hormonal balance (with potential for disrupted endocrine signaling) Wikoff et al. (2016) discuss evidence related to increased estrogen and TBBPA-induced increases in estrogen responsive genes in tissues other than the uterus. Since the time of the Wikoff publication, an additional study was published that investigated changes in estrogen concentration and gene expression in response to TBBPA. In a repeat-dose oral gavage study, adult female Wistar Hans rats were treated with vehicle or TBBPA (250 mg/kg-day) for 5 consecutive days to investigate the role of estrogen homeostasis in the MOA of TBBPA (Sanders et al., 2016). In tissue samples taken 24 hours after the 5-day treatment, T4 serum levels were decreased but serum estrogen levels were unchanged. While estrogen levels were not measured in the uterus, there were changes in expression of genes in the uterus that are markers of cell division/growth and metabolism of 18 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 TBBPA/estrogen/thyroid hormones. The gene expression changes in both the proximal and distal sections of the uterus with the greatest significance included genes involved with metabolism and hormone binding, including significantly increased levels of ERa and ERB (Sanders et al., 2016). This data partially supports an increase in estrogen responsive genes from TBBPA exposure, however, more data is needed to show that this is directly resultant from increased bioavailable estrogen, and more data are need to identify these changes specific to uterine tissues. Wikoff et al. (2016) discuss estrogen homeostasis as a balance of various metabolic pathways. Once one pathway is disrupted, alternative estrogen metabolism pathways (other than sulfation) may compensate. One of these pathways, the catechol estrogen pathway, results in the oxidation of catechol estrogens with reactive quinone intermediates. These reactive quinones can interact with DNA, and have been implicated in some cancers (Wikoff et al., 2016). For example, these intermediates could be leading to DNA interactions that could contribute to or selectively increase the proliferation of altered genes, such as the tumor suppressor p53 gene. Finally, there is a potential contribution of disrupted endocrine signaling via hormonal imbalance. Increased estrogen levels have the potential to modify the estrogen/progesterone ratio, and this imbalance has been implicated in other tumor types (mammary, prostate, estrogen dependent human endometrial cancer) (Lai et al., 2015, Cornel et al., 2017). However, there are currently no data on TBBPA modification of estrogen/progesterone ratios (Lai et al., 2015). 4) Interaction of estrogen responsive genes contributing to cellular proliferation, and increased DNA damage and p53 mutations Cellular proliferation is a critical component of hyperplasia leading to tumor formation. It is well established that estrogen binding to the ER can lead to cellular proliferation, and induction of genes related to cell cycle regulation (Sanders et al., 2016). In the NTP (2014) bioassay, there was a clear dose-response with increased uterine adenocarcinomas/adenoma at each increased TBBPA dose; however, data are lacking to confirm temporal associations specifically between increased estrogen serum levels and incidence of cellular proliferation in uterine tissues (Lai et al., 2015). High doses of TBBPA may in part promote uterine tumors in rats by promoting growth of cells with pre-existing mutations in the p53 tumor suppressor gene driven by increased estrogen-dependent cellular proliferation, or through selective proliferation of these mutations caused by reactive quinone intermediates (NTP, 2014; Lai et al., 2015). Additionally, as noted above, TBBPA has low affinity for the ER and so is not likely acting directly on the ER itself. This is plausible as significantly increased p53 mutations were identified in tumors in the NTP study, but since TBBPA is non-mutagenic, TBBPA itself is not directly causing the p53 mutations (Lai et al., 2015). The mechanism of p53 mutation has been previously implicated in cancer development, including human endometrial cancers (Harvey et al., 2015; Wikoff et al., 2016). Harvey et al. (2015) reported on an evaluation and analysis of TBBPA-induced uterine carcinomas in female rats from the NTP study. Analysis using PCR found a high rate of p53 mutations suggesting that uterine carcinogenesis might be partially p53 dependent (Harvey et al., 19 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 2015). In this analysis, the TBBPA-treated samples included Wistar Han rat uterine carcinomas from all dose groups combined (250, 500, and 1,000 mg/kg), thus no p53 mutation dose-response data are available. Of interest, the analysis did not include the malignant mixed Müllerian tumors (MMMTs). While this data supports the proposed key event, more data are needed, specifically dose-response data for p53 mutations and increased proliferation in response to TBBPA, to confirm this. 5) Hyperplasia of cells with p53 mutations leading to the adverse outcome (uterine tumors) Hyperplasia resulting from cellular proliferation is a well-known precursor effect related to the development of tumors, and is associated with increased estrogen levels in humans (Sanders et al., 2016). As noted, by Wikoff, both preneoplastic and nonneoplastic hyperplasia occurred in the NTP study. Atypical endometrial hyperplasia was seen in the NTP 2-year assay and was significantly increased above control at all dose levels, however, it was only identified via the longitudinal inspection, but not the transverse (Wikoff et al., 2016). While there was not a strict dose-response (250 mg/kg-day = 26% incidence; 500 mg/kg-day = 22% incidence; 1,000 mg/kg-day = 26% incidence), preneoplastic lesions are by definition precursors to tumor formation (Wikoff et al., 2016). Additionally, as stated above, a high rate of p53 mutations was identified in the uterine carcinogenesis (Harvey et al., 2015). Finally, the adverse outcome, significantly increased incidence of uterine tumors (adenomas, adenocarcinomas, and malignant mixed Mullerian), was seen with increasing dose in the NTP (2014) 2-year assay. 3.4.5 Weight of evidence A human relevance and concordance analysis of the postulated MOA was conducted by Wikoff et al. (2016), and suggests that given the available data, the proposed MOA is plausible for the development of uterine tumors. Wikoff et al. (2016) conclude this is a plausible mechanism in humans qualitatively, but may be quantitatively excluded based on kinetic/dynamic factors between humans and rats. Given some of the data gaps associated with this MOA, we have given the greatest weight to the non-mutagenic threshold MOA, as multiple lines of evidence support that the MOA identified is non- mutagenic. This is seen in a number of tests showing negative mutagenicity results, which are supported by the recent NTP findings of a negative micronucleus test and two negative Salmonella tests. Finally, the specificity of uterine tumors to the uterine tissue only (and not systemically developed) supports the non-mutagenic assertion (Lai et al., 2015). Thus, wWhile we conclude that the Wikoff et al. (2016) WOE analysis was adequate to establish the postulated MOA. the additional information we cite is further supportive ofgiven-the-evaileble-dete;- this non-mutagenic threshold MOA. and leads us to propose a NSRL based on the threshold approach of EPA (2005). However, a more robust and transparent analysis of the modified Bradford Hill criteria for this MOA would be helofulie-needed. Particularly useful in this instance would be a quantitative WOE ranking, as recently demonstrated by Becker et al. (2017). 20 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Howerer there is eurrently sepport 808 threshold MOA 4.0 Derivation of the NSRL 4.1 Choice of critical study and BMD analysis for POD After an updated evaluation of the available carcinogenicity literature for TBBPA, we agree with the choice of Wikoff et al. (2015) that uterine tumors (adenomas, adenocarcinomas, and malignant mixed Mullerian combined) are the most appropriate cancer endpoint, and were chosen as the critical effect for derivation of the NSRL (Table 4). Uterine tumors in female rats were chosen as the critical cancer effect for derivation of a cancer risk value. In looking at the other tumor types, the testicular adenomas in male rats were considered "equivocal" and occurred at low incidence in the two highest doses (500 mg/kg - 1/50 incidence; 1,000 mg/kg - 3/50 incidence), and as such, were not a reliable choice for the critical effect. The hepatoblastomas in male mice had "some evidence" for carcinogenicity (250 mg/kg - 2/50 incidence; 500 mg/kg - 11/50 incidence; 1,000 mg/kg - 8/50 incidence) with a significant effect in the 500 mg/kg dose. NTP (2014) considered this tumor as "some evidence" because after combining incidences of hepatocellular carcinomas and hepatoblastomas, there was only a significant effect at 250 mg/kg and there was no trend across doses, and this was informed by the historical incidence of these tumor types as spontaneous and related to chemical administration. Therefore, these tumors were not considered for use as the critical effect. The uterine epithelial tumors in female rats were the only tumor type classified as "clear evidence" and occurred with the highest incidence (0 mg/kg - 6/50 incidence; 250 mg/kg - 11/50 incidence; 500 mg/kg - 16/50 incidence; 1,000 mg/kg - 19/50 incidence). Therefore, the uterine tumors were the best choice for the critical effect in derivation of a cancer risk value. Table 4. Dose-response and dose-adjustment of cancer effects (tumors) and precursor effects (hyperplasia) from the NTP (2014) assay for use in BMD analysis. Dose, mg/kg Duration- Hyperplasia Tumor response: (NTP, 2014) adjusted dose response: Uterus original a and residual Commented [MD1]: Doses cannot be more precise than those given in the bioassay. Is is 3 digits for two? Residual longitudinal longitudinal reviews review; endometrium, (combined); adenoma, hyperplasia, atypical adenocarcinoma, or MMMT (combined) 0 0 2 6 250 1798-6 13 11 Formatted: Highlight Formatted: Highlight 500 357-+ 11 16 Formatted: Highlight 21 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 1,000 714.3 13 19 Formatted: Highlight In line with the Wikoff et al. (2015) assessment, we modeled the incidence of combined uterine adenomas, adenocarcinomas, and malignant mixed Müllerian tumors observed in female rats (NTP, 2014). While we agree with Wikoff et al. (2015) on the choice of critical effect, the application of the BMD approach and use of the BMDL10, and allometric adjustment of the POD to an HED, we had the benefit of additional literature that allowed us to agree with them that of the Factor appreach- extrapolate to a riste specifie dese to elsewheresupport- a non-mutagenic, threshold MOAresponse, and the determination of a safe dose values are through the application of uncertainty factors to the POD analogous to an RfD or TDI approach (U.S. EPA, 2005). Specifically, conclusion is supported by Wikoff et al. (2015,2016), who suggest that the linear cancer slope factor approach is inappropriate for a non- mutagenic chemical, and suggested that a threshold approach based on a non-mutagenic MOA is most appropriate. This conclusion is also supported However, ai the time-of-their 2015 publication data investigating the TBBPA MOA not there were date avay the tinear defacia stope faeter and the stedies-by Sanders et al. (2016) and Lai et al. (2015), Thus. coupled the postalated MOA by Wikeff et at (2016) is adequate evidence exists to move away from the default linear approach to a threshold approach for this tumor type. Even-though-the MOA is enly postulated) addition, the negative mutagenicity and genotoxicity data and the specificity of the tumor response to specific tissue types are all sufficient to suggest that a threshold approach is most scientifically credible to develop an NSRL. The results of the BMD analysis on adenoma, adenocarcinoma, or MMMT (combined) incidence in relation to TBBPA exposure are shown in Table 5. The log-logistic model (Figure 2) best fits the data based on all quantitative fit criteria: p-value (0.845), scaled residuals (0.042) at the dose with the response closest to the BMR, and AIC (223), resulting in a dose-adjusted BMD10 of 169 mg/kg-day corresponding to the BMDL10 of 103 mg/kg-day. This model provides a similar BMD to that from the multistage model (i.e., the model chosen by Wilkoff et al., 2015), but the loglogistic model results are more conservative and better fit the data, particularly in the dose region of interest. Atypical hyperplasia of the endometrium was also modeled as a potential precursor effect to tumor formation, but no model provided adequate fit of the data (i.e., p < 0.1). Table 5. BMD models examining the relationship between TBBPA exposure* Formatted Table and uterine cancer incidence (adenoma, adenocarcinoma, or MMMTs, combined) in female rats from NTP (2014). 22 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Model p- Scaled Visual Fit Ratio AIC BMD10 BMDL10 Value Residual BMD/ at Dose BMDL Gamma 0.75 0.14 good 1.5 223.1 195 127 Logistic 0.46 0.88 acceptable 1.3 224.0 290 219 LogLogistic 0.85 0.042 good 1.7 222.8 169 103 LogProbit 0.32 0.89 acceptable 1.5 224,8 317 216 Multistage (1*) 0.75 0.14 good 1.5 223.1 195 127 Multistage (2*) 0.75 0.14 good 1.5 223,1 195 127 Multistage (3*) 0.75 0.14 good 1.5 223.1 195 127 Probit 0.49 0.84 acceptable 1.3 223.9 277 208 Weibull 0.75 0.14 good 1.5 223.1 195 127 Quantal- Linear 0.75 0.14 good 1.5 223.1 195 127 *Duration-adjusted dose (5/7 days) *The numbers correspond to the number of degrees of polynomial in the multistage model The bolded row indicates the best fitting model Figure 2. Log logistic modeling results of uterine cancer (adenoma, adenocarcinoma, or MMMTs, combined) in female rats from NTP (2014). 23 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Log-Logetic with of sos, Exta Risk for the BMD and 3.95 Lower for the ......... 0.8 0.4 0.3 0.2 0.: BMOL BMC o 200 aco 800 800 1000 does The resulting duration-adjusted BMDL10 of 103 mg/kg-day was adjusted to a human equivalent dose (HED) of 26 mg/kg-day using allometric scaling (Equation 1; [25.6 mg/kg-day = 103 mg/kg-day x 3 4.2 Uncertainty factors Uncertainty factors were applied to the BMDL10[HED] to derive an RfDcar of 0.9 mg/kg- day using Equation 2 (0.85 mg/kg-day = 25.6 mg/kg-day/(10 x 3 X 1 x 1 x 1 = 30). The uncertainty factor that addresses interindividual variability (UFH) (also referred to as intraspecies variability) accounts for toxicokinetic and toxicodynamic variation across humans and is intended to protect sensitive subpopulations. Unless a study is conducted in a sensitive human population or 3 As noted previously, the choice of default body weight (between female at 58 kg and male at 70 kg) does not significantly change the resulting HED (27.5 mg/kg-day versus 26.3 mg/kg-day, respectively). For this and the reasons listed in the footnote above, we have used the default body weight of 70 kg. 24 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 there are data on human variability in response, the default for the UFH is 10. Given the lack of available data to move away from the default, we recommend the application of a 10-fold factor. The uncertainty factor for interspecies extrapolation (UFA) (also referred to as animal-to-human extrapolation) accounts for the translation of data from experimental animals to humans, specifically the toxicokinetic and toxicodynamic variation between species. Because we adjusted the POD to a human equivalent dose, this is presumed to account for the toxicokinetic differences across species (Renwick et al., 1999). Therefore, a reduced factor of one half the power of 10 (~3-fold) should be applied to account for the toxicodynamic differences between species (Renwick et al., 1999). The uncertainty factor for use of a LOAEL and extrapolation to a NOAEL (UFL) is not needed, since a BMD analysis was conducted. Therefore, a factor of 1 is applied. Additionally, the uncertainty factor for extrapolation of a subchronic critical study to a chronic exposure (UFs) is also not necessary, since a 2-year cancer bioassay was selected as the critical study. Therefore, a factor of 1 is applied. The uncertainty factor for database completeness (UFD) represents a judgment on the quantity and quality of the toxicology information available on the substance. TBBPA has an adequate toxicological database, particularly for noncancer effects, to assess the toxicological outcomes and potential adverse effects from exposure. However, this factor has also been utilized on occasion to account for severity of effect aimed to introduce an additional margin of safety when a compound has produced some form of severe or irreversible toxicity that is not addressed directly by the POD. It is worth noting that the noncancer dataset identified sensitive reproductive effects from TBBPA exposure [BMDLs of 0.5 mg/kg-day for increased testes weight and 0.6 mg/kg-day for increased F1 pituitary weight in males (van der Ven et al., 2008; Lilienthal et al., 2008; as cited in Health Canada, 2013)], and additional thyroid effects were seen but were largely uncharacterized [F1 males and females had decreased T4 levels (BMDL10 31 and 16 mg/kg, respectively)]. However, these data would be relevant for noncancer assessment, and as we are specifically addressing cancer endpoints, the application of this factor is not warranted. Specifically, the availability of the NTP 2-year comprehensive cancer bioassay is sufficient to inform the database for cancer. In total, we recommend the application of a composite uncertainty factor of 30 (3 x 10) to protect for uncertainties in the database and extrapolations. Therefore, for the derivation of the oral NSRL, we divide the BMDL10[HED] of 25.6 mg/kg-day by 30 to derive a cancer safe dose of 0.9 mg/kg-day. Based on the default human body weight of 70 kg, the NSRL is 60 (59.5) mg/day using Equation 3 (60 mg/day = 0.85 mg/kg-day x 70 kg). There were not enough published data identified to derive an inhalation NSRL. There was at least one DNEL derived for inhalation exposure, the studies that those values were based on were not publically available, and the relevance to cancer development from 25 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 inhalation exposure remains uncharacterized. 5.0 Discussion 5.1 Comparison of NSRL to RSD published by Wikoff et al., 2015 An NSRL of 60 mg/day was adapted from an RfDcancer of 0.9 mg/kg-day for a threshold MOA leading to uterine cancer seen in the recent NTP (2014) bioassay. The NSRL value (60 mg/day) is roughly 300-fold higher than the cancer slope factor adjusted to an NSRL derived by Wikoff et al. (2015) for 10-5 risk for the same tumor data (the risk level assigned by the NSRL) (0.0032 mg/kg-day x 70 kg = 0.22 mg/day). This difference reflects the use of a point estimate instead of a slope factor for low dose extrapolation, and slight differences in the BMDL due to model selection. Table 4 shows the various BMD model outputs for the uterine tumor data. While our models appear to align with those of Wikoff et al. (2015), we chose a different model based on an evaluation of multiple parameters (p-value, scaled residuals, visual fit, ratio of BMD to BMDL, and AIC). This difference in model selection accounts for a roughly 20% difference in the chosen points of departure (126.6 mg/kg-day chosen by Wikoff and colleagues versus 103 mg/kg-day chosen for this assessment). The NSRL proposed here of 60 mg/day, however, is within an order of magnitude and roughly aligns with a potential NSRL of 42 mg/day based on the RfD of 0.6 mg/kg-day derived by Wikoff et al. (2015) for noncancer uterine hyperplasia (i.e., 0.6 mg/kg-day x 70 kg = 42 mg/day). As some types of uterine hyperplasia are considered an upstream precursor to uterine cancer, the alignment of these values makes sense biologically. Additionally, protection from precursor effects is typically anticipated to protect from the downstream cancer effect. However, BMD models were not able to adequately fit the uterine hyperplasia data (p-value <0.1), even when the responses at the highest dose were dropped from the model (an approach that is consistent with U.S. EPA guidance; U.S. EPA, 2012). We chose not to use the hyperplasia precursor for cancer effects for a few reasons: 1) there is little currently available practical experience in using a POD based on cancer precursor effects to develop an RfD for a tumor; and 2) poor BMD model fit (p-value < 0.1) limits confidence in, and interpretation of, model results. 5.2 Comparison of RfD cancer to available risk values A comparison was made between the RfDc: derived here and other available risk values (see Table 2; Figure 3). The derived RfD cancer cancer (0.9 mg/kg-day) falls appropriately in respect to the biology on the risk value continuum as shown in Figure 3. As expected, DNELs for noncancer reproductive and developmental effects (DNEL repro and DNEL dev, both = 10 mg/kg-day) and DNELs for noncancer no effect levels (5 and 2.5 mg/kg-day) are higher than the derived RfD cancer by ~2.7 to 11-fold. The TDI, which was also derived for a noncancer no effect level (1 mg/kg-day), is roughly the same as the RfDcancer. This makes biological sense given the thresholded MOA for uterine tumor formation. The RfD for uterine hyperplasia (0.6 mg/kg-day), is slightly lower than the RfD This is expected and makes biological sense given that uterine hyperplasia is a precursor effect to uterine tumors. One would expect an RfD for a precursors effect to be 26 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 lower than that for the apical effect. Finally, the DNEL for thyroid effects (0.16 mg/kg- day) is lower than all other available noncancer values. However, as noted above in Section 3.3.1, there is a large amount of uncertainty associated with the thyroid endpoint (species sensitivity differences between rodents and humans, a lack of consistency in the available thyroid data, the potential for the effect to be reversible, neither thyroid tumors nor thyroid histopathology effects were seen in rats or mice treated in the 2-year NTP assay). Finally, the cancer slope factor (0.0032 mg/kg-day) is significantly lower than all other available risk values (from 50- to ~3,000-fold lower). Typically, the expectation is for cancer risk values to be lower than those for noncancer, under a no-threshold assumption. However, given the evidence for a threshold MOA for the most sensitive uterine tumors, the cancer slope factor is likely highly conservative and not biologically appropriate (280-fold lower than the RfDcancer). Figure 3. Comparison of available cancer and non-cancer risk values for TBBPA. 11 10 10 10 9 8 7 6 5 5 4 2.5 3 2 0.6 0.9 1 1 0.0032 0.16 0 5.2 Uncertainties Uncertainties are associated with using the malignant mixed Müllerian tumor (MMMT) data combined with the uterine adenomas and adenocarcinomas because of the rarity in their occurrence, and the fact that a dose-dependent trend was not reported in TBBPA treated rats. MMMTs are a very rare, spontaneous neoplasm in rats (Dunnick et al., 2015). Furthermore the historical data "are limited in Wistar Han rats because few studies using this strain have been conducted" (NTP, 2014). However, a large body of evidence on the epithelial histogenesis of MMMTs and their relevance to uterine cancers was cited as reasoning to include the MMMTs (Dunnick et al., 2015). The use of a new method of examining the rat uterus (a secondary Residual Longitudinal Review combined with the initial standard Transverse Review) allowed for the identification of additional tumors; 27 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 the additional transverse review identified adenocarcinomas or adenomas in all female rats with MMMTs. Therefore, BMD models including only adenomas and adenocarcinomas would be identical to those for combined adenomas, adenocarcinomas, and MMMTs. The MOA for uterine tumor formation needs additional validation, specifically, it would highly benefit from a comparison to the modified Bradford Hill criteria (such as conducted in Meek et al., 2014) and a quantitative weight of evidence approach (such as conducted in Becker et al., 2017). For the MOA, in vivo data to confirm that TBBPA competes for estrogen sulfotransferases are lacking. Target tissue dosimetry and temporal relationships to determine if TBBPA inhibits sulfotransferase in the uterus are required to determine if this mechanism is viable (Osimitz et al., 2014). Other uncertainties in the estrogen metabolism pathway have not been addressed, including the role of the alternative estrogen metabolism pathways, such as inhibition of hydroxysteroid- dehydrogenase-17beta (leading to increased estrogen activity) and induction of phase I enzymes CYP1A1 and CYP1B1 (leading to reactive metabolite formation) (Sanders et al., 2016). Others reviewed the plausibility of these alternative pathways but a more in- depth review is needed (Wikoff et al., 2015; Dunnick et al., 2015; Sanders et al., 2016). Additionally, more data is needed to evaluate this MOA at human relevant exposure doses. Wikoff et al. (2016) and others suggest this MOA operates only at high doses where saturation of the estrogen metabolic pathway occurs. Wikoff et al. (2016) suggests extrapolation to lower doses for protection of human health may be inappropriate given human doses are not expected to be high enough to lead to this MOA. However, we provide clear rationale that our NSRL is appropriate and as applied, is protective of the development of uterine tumors for several reasons: 1) tumors appear to be formed only at high doses due to non-mutagenic mechanism, and no tumors were identified in previous studies except the non-malignant tumors (transitional cell papillomas in the urinary bladder and thyroid follicular adenomas) (Imai et al., 2009, as cited in EFSA, 2011). This suggests that the potential for carcinogenicity from TBBPA exposure is quite low, will only occur at high doses, and negates the need for low-dose extrapolation; and 2) Wikoff reports that doses of 50 mg/kg are enough to surpass the sulfotransferase IC50, suggesting that this mechanism could be activated at doses below those in the NTP study. However, this dose would need to be exceeded in a chronic fashion in order for tumor formation to occur, and the RfDcan is well below this IC50 (0.9 Therefore, the derived RfDcancer is protective of uterine tumors via a non-threshold mode of action, and low dose extrapolation is not necessary. A final caveat relates to the existence of other potential MOAs/AOPs. Effects on thyroid homeostasis have also been seen, and for noncancer effects have produced relatively low BMD/Ls. Studies have shown that high TBBPA concentrations in vitro inhibit thyroid hormone metabolism with an IC50 of 460 nM for SULT1A in human liver cytosol, and the contribution of this MOA remains unclear (Butt and Stapleton, 2013). However, there is no indication that thyroid tumors result from exposure to TBBPA as neither tumors nor histopathology was found in the NTP assay. Additionally, there were testicular adenomas and hepatoblastomas identified in the NTP (2014) report. It is possible that these tumor types might drive the RfD cancer value lower, but as for the uterine tumors, are anticipated 28 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 to be non-mutagenic thresholded responses due to the non-mutagenic nature of TBBPA. 6.0 Conclusions Building off of previously published work investigating the mode of action and toxicity of TBBPA (ESFA, 2011; Health Canada, 2013; Wikoff et al., 2015, 2016; Lai et al., 2015), and using the cancer results seen from the recent NTP 2-year cancer bioassay, we have derived a no-significant-risk-level (NSRL) for TBBPA of 60 mg/day. The NSRL is based on uterine tumors (adenomas, adenocarcinomas, and malignant mixed Mullerian) identified in female rats exposed to TBBPA for 2-years via oral gavage. TBBPA has been shown to be a non-mutagenic carcinogen acting through an estrogen interference mode of action, and as such the most appropriate approach to derivation of a cancer risk value is a threshold approach, akin to an RfD cancer. Using the NTP study data, we derived a BMDL10 point of departure of 103 mg/kg-day and adjusted this to a human equivalent dose (HED) of 25.6 mg/kg-day using allometric scaling. We applied a composite adjustment factor of 30 to the POD to derive an RfDcancer of 0.9 mg/kg-day. Based on an average human body weight of 70 kg, the cancer safe dose was adjusted to an NSRL of 60 mg/day. Acknowledgements Funding for this work was provided by the American Chemical Council (ACC) and the developmental reserve funds of the University of Cincinnati, Risk Science Center. References Barnes, D.G., & Dourson, M.L. (1988). Reference dose (RfD): Description and use in health risk assessments. Regul Toxicol Pharmacol. 8, 471-486. Becker, R.A., Dellarco, V., Seed, J., Kronenberg, J.M., Meek, B., Foreman, J., Manibusan, M.K. (2017). Quantitative weight of evidence to assess confidence in potential modes of action. Regul Toxicol Pharmacol. 86, 205-220. Doi: 10.1016/j.yrtph.2017.02.017 Borghoff, S.J., Wikoff, D., Harvey, S., & Haws, L. (2016). Dose- and time-dependent changes in tissue levels of tetrabromobisphenol A (TBBPA) and its sulfate and glucuronide conjugates following repeated administration to female Wistar Han Rats. Toxicol Rep, 3, 190-201. doi:10.1016/j.toxrep.2016.01.007 Butt, C.M., & Stapleton, H.M. (2013). Inhibition of thyroid hormone sulfotransferase activity by brominated flame retardants and halogenated phenolics. Chem Res Toxicol, 26(11), 10.1021/tx400342k. oi:10.1021/tx400342k Colnot, T., Kacew, S., & DeKant, W. (2014). Mammalian toxicology and human exposures to the flame retardant 2,2, 6,6,-tetrabromo-4,4-isoprpoylidenediphenol (TBBPA): Implications for risk assessment. Arch Toxicol, 88, 1180-1188. doi: 10.1007/s00204-013-1180-8 COT (Committee on Toxicology). (2004). COT statement on tetrabromobisphenol A- 29 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 review of toxicological data. Retrieved from UK Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment. Available at: https://cot.food.gov.uk/committee/committee-on- oxicity/cotstatements/cotstatementsyrs/cotstatements2004/cotstatements2004tbbp a [accessed July 10, 2017] Cope, R. B., Kacew, S., & Dourson, M. (2015). A reproductive, developmental and neurobehavioral study following oral exposure of tetrabromobisphenol A on Sprague-Dawley rats. Toxicology, 329, 49-59. doi: 10.1016/j.tox.2014.12.013 Cornel, K. M. C., Krakstad, C., Delvoux, B., Xanthoulea, S., Jori, B., Bongers, M. Y. Romano, A. (2017). High mRNA levels of 176-hydroxysteroic dehydrogenase type 1 correlate with poor prognosis in endometrial cancer. Mol Cell Endocrinol, 442, 51-57. doi: 10.1016/j.mce.2016.11.030 Dunnick, J. K., Sanders, J. M., Kissling, G.E., Johnson, C. L., Boyle, M. H., & Elmore, S. A. (2015). Environmental chemical exposure may contribute to uterine cancer development: studies with tetrabromobisphenol A. Toxicol Pathol, 43, 464-473. doi: 10.1177/0192623314557335 European Chemicals Agency (ECHA). (2017). 2017. 2,2',6,6'-tetrabromo-4,4'- isopropylidenediphenol. Information on Chemicals, Registration Dossier. Last modified: 11-Jul-2017. Available online at: https://echa.europa.eu/registration- dossier/-/registered-dossier/14760/1 [accessed July 17, 2017] European Food Safety Administration (EFSA). 2011. Scientific Opinion on Tetrabromobisphenol A (TBBPA) and its derivatives in food. EFSA J, 9: 2477. Available online at: hitps://www.efsa.europa.eu/en/efsajournal/pub/2477 [accessed July 17, 2017] European Food Safety Administration (EFSA). 2017. Update: use of benchmark dose approach in risk assessment. EFSA J, 15: 4658. Available online at: äle:///Users/pecqueam/Downloads/Hardy et al-2017-EFSA Journal.pdf [accessed July 17, 2017] European Union (EU). 2006. Risk Assessment Report: ",6,6'-Tetrabromo-4,4" Isopropylidenediphenol (Tetrabromobisphenol-A or TBBP-A), Part II - Human Health. European Chemicals Bureau, European Commission, 4th Priority List, Volume 63. Available online at: https://echa.europa.eu/documents/10162/326000fe-b4fe-4828-b3d3 93c24cledd51 [accessed July 17, 2017] Fu, J., Fang, H., Paulsen, M., Ljungman, M., Kocarek, T. A., & Runge-Morris, M. (2011). Regulation of estrogen sulfotransferase expression by confluence of MCF10A breast epithelial cells: Role of the aryl hydrocarbon receptor. J Pharmacol Exp Ther., 339(2), 597-606. doi: 10.1124/jpet.111.185173 Gosavi, R. A., Knudsen, G. A., Birnbaum, L. S., & Pedersen, L. C. (2013). Mimicking of estradiol binding by flame retardants and their metabolites: A crystallographic analysis. Environ Health Perspect, 121, 1194-1199. doi: 10.1289/ehp. 1306902 30 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Grosse, Y., Loomis, D., Guyton, K.Z., Ghissassi, F-E., Bouvard, V., Benbrahim-Tallaa, L., Straif, K. (2016). Carcinogenicity of some industrial chemicals. The Lancet Oncol, 17(4), 419-420. Hall, S.M., Coulter, S.J., Knudsen, G.A., Sanders, J.M., & Birnbaum, L.S. (2017). Gene expression changes in immune response pathways following oral administration of tetrabromobisphenol A (TBBPA) in female Wistar Han rats. Toxicol Lett, 272, 68-74. doi:10.1016/j.toxlet.2017.03.008 Hamers, T., Kamstra, J.H., Sonneveld, E., Murk, A.J., Kester, M.H., Andersson, P.L., Legler, J., & Brouwer, A. (2006). In vitro profiling of the endocrine-disrupting potency of brominated flame retardants. Toxicol. Sci. 92, 157e-173e. [as cited in Colnot et al., 2014] doi: 10.1093/toxsci/kfj187 Harvey, J. B., Osborne, T. S., Hong, H. H., Bhusari, S., Ton, T. V., Pandiri, A. R., Hoenerhoff, M. J. (2015). Uterine Carcinomas in Tetrabromobisphenol A- exposed Wistar Han Rats Harbor Increased Tp53 Mutations and Mimic High- grade Type I Endometrial Carcinomas in Women. Toxicol Pathol, 43, 1103-1113. doi: 10.1177/0192623315599256 Health Canada. (2013). Screening assessment report of Phenol, 4,4' -(1-methylethylidene) bis[2,6-dibromo- (Tetrabromobisphenol A, TBBPA; CAS 79-94-7), Ethanol, 2,2'-[(1-methylethylidene)bis[(2,6-dibromo-4,1-phenylene)oxy]lbis (known as TBBPA bis(2-hydroxyethyl ether, CAS 4162-45-2) and Benzene, 1,1'-(1- methylethylidene)bis[3,5-dibromo-4-(2-propenyloxy)-(TBBPA bis(allylether, CAS 25327-89-3). Government of Canada, Environment Canada, Health Canada. Cat. No.: En14-110/2013E-PDF. ISBN: 978-1-100-22898-3. Ho, K. L., Yuen, K. K., Yau, M. S., Murphy, M. B., Wan, Y., Fong, B. M., Lam, M. H. (2017). Glucuronide and sulfate conjugates of tetrabromobisphenol A (TBBPA): Chemical synthesis and correlation between their urinary levels and plasma TBBPA content in voluntary human donors. Environ Int, 98, 46-53. doi: 10.1016/j.envint.2016.09. Imai, T., Takami, S., Cho, Y. M., Hirose, M., & Nishikawa, A. (2009). Modifying effects of prepubertal exposure to potassium perchlorate and tetrabromobisphenol A on susceptibility to N-bis(2-hydroxypropyl)nitrosamine- and 7,12 dimethylbenz(a)anthracene-induced carcinogenesis in rats. Toxicol Lett, 185, 160- 167. [As cited in EFSA, 2011]. doi: 10.1016/j.toxlet.2008.12.013 International Toxicity Estimates for Risk (ITER). A TOXNET Database. U.S. National Library of Medicine, National Institutes of Health. Available online at: https://toxnet.nlm.nih.gov/newtoxnet/iter.htm [accessed July 17, 2017] Jeff Gift, U.S. EPA, personal communication via email. In reference to: questions on benchmark dose. November 18, 2016. Kester, M.H., Bulduk, S., van Toor, H., Tibboel, D., Meinl, W., Glatt, H., Visser, T.J. (2002). Potent inhibition of estrogen sulfotransferase by hydroxylated metabolites 31 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 of bolyhalogenated aromatic hydrocarbons reveals alternative mechanism for estrogenic activity of endocrine disrupters. J. Clin. Endocrinol. Metab 87, 1142e- 1150e. Klimisch, H.J., Andreae, M., & Tillmann, U. (1997). A systematic approach for evaluating the quality of experimental toxicological and ecotoxicological data. Regul. Toxicol. Pharm. 25, 1-5. Lai, D. Y., Kacew, S., & Dekant, W. (2015). Tetrabromobisphenol A (TBBPA): Possible modes of action of toxicity and carcinogenicity in rodents. Food Chem Toxicol, 80, 206-214. doi: 10.1016/j.fct.2015.03.023 Lilienthal, H., Verwer, C., van der Ven, L., Piersma, A., & Vos, J. (2008). Exposure to tetrabromobisphenol A (TBBPA) in Wistar rats: Neurobehavioral effects in offspring from a one-generation reproduction study. Toxicology, 246, 45-54. [as cited in Health Canada, 2013] doi: 10.1016/j.tox.2008.01.007 Meek, M.E., Palermo, C.M., Bachman, A.N., North, C.M., & Lewis, R.J. (2014). Mode of action human relevance (species concordance) framework: Evolution of the Bradford Hill considerations and comparative analysis of weight of evidence. J Appl Toxicol, 34, 595-606. doi: 10.1002/jat.2984 MPI Research, 2002a. A 90-day oral toxicity study of tetrabromobisphenol-A in rats with a recovery group (unpublished). As cited in COT (2004). MPI Research, 2002b. An oral two generation reproductive, fertility and developmental neurobehavioural study of tetrabromobisphenol-A in rats (unpublished). Performed by MPI Research Inc., Mattawan, MI for the American Chemistry Council BFRIP, Arlington, VA. Study Number: 474-004, pp 2199 [as cited in Colnot et al., 2014] MPI Research. (2001). Final report-an oral prenatal developmental toxicity study with tetrabromobisphenol-A in rats (unpublished). [as cited in Colnot et al., 2014]. National Institute of Environmental Health Sciences (NIEHS). (2002). Tetrabromobisphenol A [79-94-7]: Review of Toxicological Literature. National Institutes of Health, National Toxicology Program. Available online at: https://ntp.niehs.nib.gov/ntp/btdocs/chem_background/exsumpdf/tetrabromobisph enola 508.pdf [accessed July 17, 2017] NTP (National Toxicology Program). (2014). Technical Report on the Toxicology Studies of Tetrabromobisphenol A (CAS NO. 79-94-7) in F344/NTac rats and B6C3F1/N mice and Toxicology and Carcinogenesis Studies of Tetrabromobisphenol A in Wistar Han [Crl:WI(Han)] rats and B6C3F1/N mice (Gavage Studies). NTP TR 587, September, 2014. National Institutes of Health, U.S. Department of Health and Human Services, Research Triangle Park, NC. Available online at: https://ntp.niehs.nib.gov/ntp/htdocs/lt_xpts/tr587508.pd [accessed July 7, 2017] Office of Environmental Health Hazard Assessment (OEHHA). (1989). Final Statement of Reasons. No Significant Risk Levels and No Observable Effect Levels. 32 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 Proposition 65, California Environmental Protection Agency. June, 1989. Available online at: https://oehha.ca.gov/media/downloads/emnr/art78fsrjune1989.pdf [accessed July 7, 2017] Office of Environmental Health Hazard Assessment (OEHHA). (2013). Article 7. No Significant Risk Levels. § 25703. Quantitative Risk Assessment. Title 27, California Code of Regulation. Available online at: ittps://oehha.ca.gov/media/downloads/proposition-65/general-info/regsart7.pdf [accessed July 19, 2017] Osimitz, T.G., Dourson, M.L., Hayes, A. W., & Kacew, S. (2014). Crystallographic analysis and mimicking of estradiol binding: Interpretation and speculation. Environ Health Perspect, 122: A91-A92. DOI:10.1289/ehp.1307987 Renwick, A.G. (1999). Subdivision of uncertainty factors to allow for toxicokinetics and toxicodynamics. Human and Ecological Risk Assessment, 5, 1035-1050. doi: 10.1080/10807039991289329 Sanders, J.M., Coulter, S.J., Knudsen, G.A., Dunnick, J.K., Kissling, G.E., & Birnbaum, L.S. (2016). Disruption of estrogen homeostasis as a mechanism for uterine toxicity in Wistar Han rats treated with tetrabromobisphenol A. Toxicol Appl Pharmacol, 298, 31-39. doi: 10.1016/j.taap.2016.03.007 Schauer, U.M.D., Völkel, W., & Dekant, W. (2006). Toxicokinetics of tetrabromobisphenol A in humans and rats after oral administration. Toxicol Sci 91, 49-58. [as cited in Health Canada, 2013] U.S. EPA (Environmental Protection Agency). (1986). Guidelines for Mutagenicity Risk Assessment. U.S. Environmental Protection Agency: Washington, DC, EPA/630/R-98/003. Available online at: ps://www.epa.gov/sites/production/files/2013-09/documents/mutagen2.pdf [accessed July 7, 2017] U.S. EPA (Environmental Protection Agency). (2005). Guidelines for Carcinogen Risk Assessment. U.S. Environmental Protection Agency: Washington, DC, EPA/630/P-03/001F. Available online at: https://www.epa.gov/risk/guidelines- carcinogen-risk-assessment [accessed July 7, 2017] U.S. EPA (Environmental Protection Agency). (2012). Benchmark Dose Technical Guidance. Risk Assessment Forum, U.S. Environmental Protection Agency: Washington, DC.100-R-12-001. Available online at: attps://www.epa.goy/risk/benchmark-dose-technical-guidance[accessed July 7, 2017] U.S. EPA (Environmental Protection Agency). (2014). Supplemental File 4: Tetrabromobisphenol A (TBBPA, CASRN: 79-94-7) Cancer Assessment Review Committee Report. Health Effects Division, Office of Pesticide Programs, U.S. Environmental Protection Agency: Washington, DC. Available online at: https://www.epa.gov/assessing-and-managing-chemicals-under. 33 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226 scalsupplemental-file-4-tetrabromobisphenol-tbbpa-casmn-79 [accessed July 7, 2017] Van der Ven, L.T., Van de Kuil, T., Verhoef, A., Verwer, C.M., Lilienthal, H., Leonards, P.E., Piersma, A.H. (2008). Endocrine effects of tetrabromobisphenol-A (TBBPA) in Wistar rats as tested in a one-generation reproduction study and a subacute toxicity study. Toxicology, 245, 76-89. doi: 10.1016/j.tox.2007.12.009 [as cited in Health Canada, 2013, and EFSA, 2011] Wheeler, M.W., & Bailer, A.J. (2007). Properties of model-averaged BMDLs: a study of model averaging in dichotomous response risk estimation. Risk Anal, 27(3): 659- 70. doi: 10.1111/j.1539-6924.2007.00920.x Wikoff, D., Thompson, C., Perry, C., White, M., Borghoff, S., Fitzgerald, L., & Haws, L.C. (2015). Development of toxicity values and exposure estimates for tetrabromobisphenol A: Application in a margin of exposure assessment. J Appl Toxicol, 35, 1292-1308. doi: 10.1002/jat.3132 Wikoff, D.S., Rager, J.E., Haws, L.C., & Borghoff, S.J. (2016). A high dose mode of action for tetrabromobisphenol A-induced uterine adenocarcinomas in Wistar Han rats: A critical evaluation of key events in an adverse outcome pathway framework. Regul Toxicol Pharmacol, 77, 143-159. doi: 10.1016/j.yrtph.2016.01.018. Yang, Y., Ni, W.W., Yu, L., Cai, Z., Yu Y.J. (2016). Toxic effects of tetrabromobisphenol A on thyroid hormones in SD rats and the derived-reference dose. Biomed Environ Sci, 29(4), 295-299. 34 Source: https://www.industrydocuments.ucsf.edu/docs/kxcn0226

What is the Goal of this Workshop?

hlcn0226

hlcn0226_p0, hlcn0226_p1, hlcn0226_p2, hlcn0226_p3, hlcn0226_p4, hlcn0226_p5, hlcn0226_p6, hlcn0226_p7, hlcn0226_p8, hlcn0226_p9, hlcn0226_p10, hlcn0226_p11

is to identify concepts and materials that are or can be useful to control the spread of harmful fire ground contaminants, ultimately in support of improved fire fighter long-term health.

129 From: Jürgen Troitzsch To: Osimitz Thomas; Dr. Blais Matthew; Prof. Rein Guillermo; Dr. Hayes Wallace; Dourson. Michael (doursomi); Kacew Sam; Dr. Wise Kimberly Subject: Fwd: Project on FF PPE Cleaning Validation Date: Monday, June 12, 2017 1:11:46 PM Attachments: PROU PANEL - PPE Cleaning (33) pdf PROJ SUMMARY - PPE Cleaning (7) pot FLYER FF Contam Control Workshop (6) odf HOTELS - Contam Control Wrkshp on 2017Jul19.pd PROJS JMMARY- FE Cancer Cohort Study (4) odf Dear All, I came across this project, which may be of interest in the frame of our fire fighters cancer activities. Kind regards/Viele Grüße Jürgen Dr. Jürgen Troitzsch Fire and Environment Protection Service FEPS Via Patrizia 32 CH-6612 Ascona, Switzerland Mobile: +41 79 289 17 16 Phone: +41 91 791 14 22 Email: [email protected] Web: www.troitzsch.com De : Grant, Casey Envoyé : lundi 22 mai 2017 17:58 À : [email protected]; [email protected]. tis.com; mlambetamallN u.edu; dwardmecarthyebostengoy ark.a.miller@ehoen ix.gov; james.riley@bosta nagov; [email protected] Thomas [email protected]; ;timügearcleaningsolutions.s om [email protected]; Ken.Wiles @fire.jacounty.gov Farrell, Christopher cobtlogiobefiresuits.com; pattogiobefiresults.com; Diane.Hess@ Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 130 PBIProducts.com; Kebtonen@lionprotedscon leur.gouv.fr; GUILLAUME Eric <eric [email protected] ;[email protected]; mamiefortunes-collide.com Cc : lasonallendintertekeor [email protected]; [email protected] wlindslev@ cdc.gov; [email protected] [email protected]; [email protected]; ; istendice OY; Objet : Project on FF PPE Cleaning Validation To: Panel, Research Team and Liaisons for Project on "Fire Fighter PPE Cleaning Validation" It has been some time since we last spoke, and I have the following three items to be addressed: 1) A lot has been happening with our project and we want to hold a 90 minute conference call in early August 2017 to bring everyone up-to-date. I've created a scheduling poll to determine the optimum date/time Please respond before Noon ET on Wednesday 31/May/2017 so that we can get this on our calendars. I've attached the Project Roster and Project Summary in case anyone needs a refresher for this project addressing "how clean is clean". Thanks. 2) I've been asked to participate in a webinar tomorrow (23/Mav/2017) from noon ET to 1:30 pm ET on "Factors Relating to Cancer and Contamination in the US Fire Service". I've been assigned a portion of this webinar (among two other speakers) to address on-going research and I'm planning to address our project among several other on-going efforts. The link is on the NFPA home page at: FYI.. 3) Some of you are already aware of the Workshop in Columbus, Ohio on 19- 20/Julv/2017, and if not I want to call it to your attention. This is for the separate one year AFG project on "Campaign for Fire Service Contamination Control". Attached is a Flyer that provides additional details, and also attached is a list of hotels in the area to assist with travel. The workshop will be held from Noon to Noon on 19-20/July and we still have room if you would like to attend. In addition, the separate project (i.e., a third related project) on "Fire Fighter Cancer Cohort Study" will hold a separate planning meeting on the afternoon of 20/July from 1 pm to 5 pm (Project Summary is attached). All are welcome to attend this as well. If you are a fire service panel member we can cover your travel, and I can send follow-up instructions to you separately. For anyone interested in attending the Columbus meetings on 19-20/July, please let us know by email to [email protected] and Thanks.. Casey C. Grant, P.E. Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION "CAMPAIGN FOR FIRE SERVICE CONTAMINATION CONTROL" WORKSHOP Location: Columbus Fire Fighters Union Hall, 379 W Broad St, Columbus, OH 43215 Workshop Dates: 19-20 July 2017 (Last Updated: 21 April 2017; subject to update) Background: Exposure to chemical and biological contaminants on the fire ground is an increasing concern for long-term fire fighter health. Cancer and other diseases resulting from chronic exposures has become a leading concern for the fire service. This is presumed to be associated with fireground exposures relating to protection/hygiene practices and persistent harmful contamination found in fire fighter equipment, apparatus carrying that equipment, and stations where the equipment resides. Workshop Goal and Objectives: The goal of this Workshop is to identify concepts and materials that are or can be useful to control the spread of harmful fire ground contaminants, ultimately in support of improved fire fighter long-term health. The following objectives support this goal (and reflect anticipated deliverables): Identify, review and recommend baseline materials (existing and proposed) addressing best practices, standards, research, equipment, facilities, and other areas of focus. Identify and prioritize gaps that are barriers to enhancing best practices, standards, research, equipment, facilities, and other areas of focus. Identify and review key characteristics for effective promotion and communication. Clarify target audiences for outreach and consider stakeholder research prior to developing a comprehensive communications plan to improve outcome. Prioritize messages for year one. Agenda: Wed; 19/July 1:00 pm Day One: Welcome and Call to Order Casey Grant, FPRF 1:15 pm Overview of Baseline Materials and Review of Gaps Jeff Stull, IPP 2:00 pm Review of Outreach Peg, Paul, PPA 2:30 pm Case Study: Best Practice Information Beth Gallup, KFD 3:00 pm PM Break 3:15 pm Casey Study: Standards Revisions Dave Bernzweig, CFD 3:45 pm Case Study: Equipment & Facilities Paul Erickson, LEWA 4:15 pm Breakout Groups Workshop Attendees 5:00 pm Adjourn for Day One (& Evening Networking Reception) Thur; 20/July 8:30 am Day Two: Group Review of Baseline Materials Jeff Stull, IPP 8:45 am Breakout Groups Continue Workshop Attendees 9:45 am AM Break 10:00 am Breakout Group Report Workshop Attendees 11:00 am Plenary Discussion Workshop Attendees 11:30 am Workshop Wrap-up & Summary Observations Casey Grant, FPRF 12:00 pm Adjournment Registration: Workshop attendance is limited to the first 50 attendees, and others will be placed the on a waiting list. To request attendance or for more information, please contact [email protected]. After the Workshop a report will be available. This Workshop is funded through an AFG Fire Prevention & Safety Grant from U.S.DHS/FEMA. 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7281 Fax: +1.617.984.7010 Email: [email protected] www.NFPA.org/Foundation Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 WORKSHOP ON FIRE SERVICE CONTAMINATION CONTROL 19-20 July 2017 (Noon to Noon ET) Columbus Fire Fighters Union Hall 379 W Broad St, Columbus, OH 43215 Note: For flights, Workshop starts at Noon ET on 19/July/2017 and finishes at Noon ET on 20/July/2017 Drury Inn & Suites: 88 East Nationwide Blvd, Columbus, OH 43215 Phone: 1-614-221-7008 ttos://www.drurvhotels.com/locations/columbus-ob/drurv-inn-and-suites-columbus-convention: center Approximate Rate: $130 Distance (in miles) from Hotel to Columbus Union Hall: 1.3 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars. Red Roof Plus Columbus Downtown Convention Center 111 East Nationwide Blvd, Columbus, OH 43215 Phone: 1-614-224-6539 ittps://www.redroof.com/property/Columbus/OH/43215/Hotels-close-to-Greater-columbus- Convention-Center-US-23-1-670/RRI262/ Approximate Rate: $130 Distance (in miles) from Hotel to Columbus Union Hall: 1.4 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars. Sheraton Columbus Hotel at Capital Square 75 East State Street, Columbus, OH, 43215 Phone: 1-614-365-4500 http://www.sheratoncolumbuscapitolsquare.com/ Approximate Rate: $170 Distance (in miles) from Hotel to Columbus Union Hall: 0.8 Notes: Central downtown area Hampton Inn and Suites Columbus Downtown 501 North High Street, Columbus, OH 43215 Phone: 1-614-559-2000 htto://hamptoninns.bilton.com/en/hotels/ohio/hampton-inn-and-suites-columbus-downtown- CMHHSHK/index.htmi?WT.mc. Approximate Rate: $175 Distance (in miles) from Hotel to Columbus Union Hall: 1.3 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars. Page 1 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Courtyard Columbus Downtown 35 West Spring Street, Columbus, Ohio 43215 Phone: 1-614-228-3200 4d19-a255-54ba596febe2 Approximate Rate: $175 Distance (in miles) from Hotel to Columbus Union Hall: 0.8 Notes: Downtown west area; walkable Doubletree Suites by Hilton Columbus Downtown 50 South Front St, Columbus, Ohio, 43215-4145 Phone: 1-614-228-4600 CMHSBOT/index.htmi Approximate Rate: $200 Distance (in miles) from Hotel to Columbus Union Hall: 0.5 Notes: Closest hotel to meeting site; very short walk Residence Inn Columbus Downtown 36 East Gay Street, Columbus, Ohio 43215-3108 Phone: 1-614-222-2610 ec3-4d19-a255-54ba596febe2 Approximate Rate: $230 Distance (in miles) from Hotel to Columbus Union Hall: 0.8 Renaissance Columbus Downtown 50 North Third Street, Columbus, Ohio 43215 Phone: 1-614-228-5050 ttp://www.marriott.com/hotels/travel/cmhbr-renaissance-columbus-downtown-hotel/ Approximate Rate: $240 Distance (in miles) from Hotel to Columbus Union Hall: 1.0 Notes: Central downtown area Hilton Columbus Downtown 401 North High Street, Columbus, OH 43215 Phone: 1-614-384-8600 Approximate Rate: $240 Distance (in miles) from Hotel to Columbus Union Hall: 1.1 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars; New facility and nice. Page 2 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION PPE Cleaning Validation Validation of Cleaning Procedures for Fire Fighter Personal Protective Equipment (PPE) PROJECT CONTACTS Last Updated: 22 May 2017 Project Technical Panel Phone: 614-774-7446 David Bernzweig, Columbus Fire Department (OH) Email: [email protected] Phone: 780-496-3801 Ken Block, Edmonton Fire/Rescue & Metro Chiefs Representative Email: [email protected] Phone: 804-971-7983 Ken Brown, VA State Firefighter's Association & NVFC (Alt to B. McQueen) Email; [email protected] Phone: 510-839-5111 Cell: 213-321-9393 Roger Curtis, ECMS Curtis & Sons (CA) Email: [email protected] Phone: Paul Curtis, ECMS Curtis & Sons (CA) (Alt to Roger Curtis) Email: [email protected] Phone: 253-277-4131 Cell: 503-314-4832 Steve Lakey, Northwest Safety Clean (WA) Email: [email protected] Phone: 304-406-7479 Mark Lambert, WV Fire Academy & NAFTD (WV) Email: [email protected] Phone: 617-828-3978 Ed McCarthy, Boston Fire Department (MA) Email: [email protected] Phone: 315-736-7479 Cell: 315-552-8245 Brian McQueen, FASNY & National Volunteer Fire Council (NY) Email: [email protected] Phone: 602-534-2396 Mark Miller, Phoenix Fire Dept. (AZ) Email: [email protected] Phone: 919-524-1569 Bryan Ormond, NCSU (NC) Email: [email protected] Phone: Russ Osgood, Firefighter Cancer Support Network (NH) (Alt to Keith Tyson) Email: [email protected] Phone: Larry Petrick, IAFF (DC) Email: [email protected] Phone: 617-549-9850 Jim Riley, Boston Fire Department (MA) (Alt to E. McCarthy) Email: [email protected] Phone: 757-385-2892 Molly Riley, Virginia Beach Fire Dept. (VA) Email: [email protected] Phone: 718-999-2922 Thomas Smith, FDNY (NY) Email: [email protected] Phone: 214-774-2213 Cell: 940-300-5718 Tim Tomlinson, Gear Cleaning Solutions (TX) Email: [email protected] Phone: Robert Tutterow, NFPA Fire Service Section (NC) Email: [email protected] Phone: 786-351-3276 Keith Tyson, Firefighter Cancer Support Network (FL) Email: [email protected] Phone: 951-807-1914 Dick Weise, LA County Fire Dept. (CA) Email: [email protected] Phone: 949-291-0637 Ken Wiles, LA County Fire Dept. (CA) (Alt to Dick Weiss) Email: [email protected] Phone: 512-974-0286 Chris Youngblood, Austin Fire Dept. (TX) Email: [email protected] 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7281 Fax: +1.617.984.7010 Email: [email protected] www.NFPA.org/Foundation Source: :https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Phase 1 Project Contacts Phone: 330-723-0000, x365 Steve Allison, Fire-Dex (OH) Email: [email protected] Phone: 800-401-4780 Jack Binder, Edmar Chemical Company (OH) Email: [email protected] Phone: 920-570-0824 Bill Brooks, Alliance Corp. (WI) Email: [email protected] Phone: Charlie Dunn, TenCate Protective Fabrics Email: [email protected] Phone: 617-984-7325 Chris Farrell, NFPA & Staff Liaison for NFPA 1851 (MA) Email: [email protected] Phone: 800-232-8323 Rob Freese, Globe Manufacturing (NH) Email: [email protected] Phone: Pat Freeman, Globe Manufacturing (NH) (Alternate to Rob Freese) Email: [email protected] Phone: 704-554-3313 Diane Hess, PBI Performance Products (NC) Email: [email protected] Phone: 937-415-2932 Karen Lehtonen, LionFirst Responder Products (OH) Email: [email protected] Phone: 484-433-4072 Dan Silvestri, 9-1-1 Safety (PA) Email: [email protected] Liaison Contacts Phone: Pierre Carlotti, Ministry of Interior & Liaison for ISO TC92/SC3 (France) Email: [email protected] Phone: Eric Guillaume, Efectis & Liaison for ISO TC92/SC3 (France) Email: [email protected] Phone: Bill Haskell, NIOSH NPPTL (MA) Email: [email protected] Phone: James Hoar, Boston Fire Department (MA) Email: [email protected] Phone: 631-242-0621 Steve King, Chair NFPA 1851 (NY) Email: [email protected] Phone: +33(0)1.55.76.26.18 Fanny Rieunier, Ministry of Interior & Liaison for ISO TC92/SC3 (France) Email: [email protected] Phone: 612-247-6429 Marni Schmid, Fortunes Collide & Secretariat NFPA 1851 (MI) Email: [email protected] Page 2 of 3 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Core Research Team Phone: 607-758-6537 Cell: 607-423-5617 Jason Allen, Intertek (NY) Email: [email protected] Phone: 304-285-6076 Daniel Farcas, NIOSH HELD (WV) Email: [email protected] Phone: Crystal Forester, NIOSH NPPTL (WV) Email: [email protected] Phone: 617-984-7284 Cell: 617-659-1159 Casey Grant, Fire Protection Research Foundation (MA) Email: [email protected] Phone: Lee Greenawald, NIOSH NPPTL (WV) Email: [email protected] Phone: Bill Lindsley, NIOSH HELD (WV) Email: [email protected] Phone: Stephen Martin, NIOSH DRDS (WV) Email: [email protected] Phone: John Noti, NIOSH HELD (WV) Email: [email protected] Phone: Deborah Sbarra, NIOSH NPPTL (WV) Email: [email protected] Phone: 512-288-8272 cell: 512-623-9558 Jeff Stull, International Personal Protection (TX) Email: [email protected] Phone: 304-285-5858 cell: 681-209-2571 Jay Tarley, NIOSH NPPTL (WV) Email: [email protected] Additional Research Team Contacts Phone: 304-285-5884 Francoise Blachere, NIOSH HELD (WV) Email: [email protected] Phone: Renee Dotson, NIOSH HELD (WV) Email: [email protected] Phone: James Harris, NIOSH NPPTL (WV) Email: [email protected] Phone: Ryan Lebouf, NIOSH DRDS (WV) Email: [email protected] Phone: 617-984-7281 Eric Peterson, Fire Protection Research Foundation (MA) Email: [email protected] Phone: John Powers, NIOSH (WV) Email: [email protected] Phone: 412-386-4621 Cell: 412-463-9561 Heather Reed, NIOSH NPPTL (PA) Email: [email protected] Page 3 of 3 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION PPE Cleaning Validation Validation of Cleaning Procedures for Fire Fighter Personal Protective Equipment (PPE) (for more information see www.nfpa.org/PPECleaning) PROJECT SUMMARY Last updated: 5 February 2016 Background: Fire fighter exposure to personal protective equipment (PPE) that is dirty, soiled, and contaminated is an increasing concern for long-term fire fighter health. This exposure to persistent harmful contaminants in PPE is an extremely serious problem both on the fireground to highly toxic substances including a variety of carcinogens, and more insidiously to an increasing range of infectious pathogens that are encountered in patient care and different emergency operations. Fire fighter PPE becomes contaminated during these exposures and there are no industry standards that conclusively and reliably show that clothing is being adequately cleaned. While general cleaning procedures have been established in NFPA 1851, Standard on Selection, Care, and Maintenance of Protective Ensembles for Structural Fire Fighting and Proximity Fire Fighting, there are no procedures or requirements to demonstrate whether current cleaning practices, including those specified in NFPA 1851, will remove contaminants from fire fighter protective clothing. This project is intended to establish clear and definitive guidance to the fire service for applying cleaning and decontamination procedures that effectively remove both chemical and biological contaminants. Research Goal and Objectives, and Conceptual Approach: The overall goal of this project is to improve fire fighter safety and health by reducing continuing exposure to harmful contaminants in unclean or inadequately cleaned PPE. The objectives to achieve this goal are twofold: (1) To characterize fireground and emergency scene contamination leading to these exposures and develop the methodology for the consistent measurement of cleaning effectiveness; and (2) determine implementable cleaning, decontamination, and disinfection strategies that effectively reduce fire fighter exposures to persistent contaminants. The approach taken by this project is illustrated in Figure 1: Project Conceptual Approach. - Ensure Identify Devise Validate lab - - chemical and methods to methods - at biologicat conteminate againet field ses target clothing in contaminants laboratory exposures acceptance Project Direction Figure 1: Project Conceptual Approach 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7281 Fax: +1.617.984.7010 Email: [email protected] www.NFPA.org/Foundation Source: :ttps://www.industrydocuments.ucsf.edu/docs/hlcn0226 Project Phases and Tasks: This project involves the following four key phases of activity: 1) Identification of Contaminants: Confirm identification and ability to characterize persistent chemical and biological contaminants in fire fighter PPE through target substances and microorganisms. 2) Establishment of Soil and Chemical Contamination/Decontamination Procedures: Develop and validate specific procedures that determine the effectiveness of laundering and other cleaning methods in removing specific soils and chemical contaminants. 3) Establishment of Biological Contamination/Disinfection or Sanitization Procedures: Develop and validate specific procedures that determine the effectiveness of laundering or disinfection/sanitization processes that remove/deactivate biologically-based contaminants. 4) Creation of Overall Fire Service Guidance: Prepare clear and definitive information for the fire service industry (fire fighters, fire departments, clothing manufacturers, material suppliers, cleaning/care organizations, and cleaning agent or equipment manufacturers) on appropriate approaches for properly cleaning fire fighter protective clothing and equipment. The specific tasks of this project are based on these four phases of the project, and these are illustrated in Figure 2: Project Tasks. PHASE 2 PHASEZ Task 2.4 Task 2.5 Task 1.1 Task 2.1 Validate testsat Refine test Appoint Technical Select cleaning selected ISPS methodology Review Panel methods/agents (chemical) (chemical) PHASE $ Task 4.1 Task 1.2 Task 2.2 Write qualification Review Prigr Put together test plan methods studies/literature (chemical) Task 2.3 Task 4.2 Task 1.3 PHASE 3 Perform laboratory Establish cleaning Setup analytical chemical Task 3.3 acceptance criteria capabilities decontaminant Put together test plan testing (biological) Task 4.3 Task 1.4 Perform Task 3.4 Prepare public inputs for NFPA 1851 demonstration tests Task 3.1 Perform laboratory Task 3.6 Select study biological Refine test microorganisms decontaminant methodology Task 1.5 testing (biological) Task 4.4 Refine biological Prepare industry decontamination Task 3.2 Task 3.5 guidance document scope Select biological Validate testsat cleaning methods selected ISPs (biological) Task 1.6 Task 4,5 Establish cleanliness Prepare project final metrics report Figure 2: Project Tasks Implementation and Schedule: This three year project is due to be completed no later than " August 2018, and is funded through an AFG Fire Prevention & Safety Grant from the U.S. Department of Homeland Security / Federal Emergency Management Agency. The Research Foundation will lead a unique research team partnership composed of the FPRF, National Institute for Occupational Safety and Health (NIOSH), International Personal Protection (IPP), and Intertek. The research team, along with several Independent Service Providers (ISPs), will work with the fire service partners and others to validate and optimize fire fighter PPE cleaning validation methods. For more information see www.nfpa.org/PPECleaning. Page 2 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION Fire Fighter Cancer Cohort Study Full Title: The Firefighter Multicenter Cancer Cohort Study: Framework Development and Testing PROJECT SUMMARY Last Updated: 20 September 2016 Background: Cancer is a leading cause of fire service morbidity and mortality. Firefighter exposure to carcinogens occurs through skin contamination and through inhalation when respiratory protection is not worn when combustion products are present such as during overhaul, standby, and operation of apparatus, as well as through off-gassing of equipment and exposures in the fire station. However, we currently do not understand which exposures are responsible for cancer in firefighters, the mechanisms by which firefighter exposures cause cancer, nor the most effective means of reducing exposures. Since cancer has a long latency period, biomarkers are also needed that can measure the toxicological effects of carcinogen exposure well before the development of cancer, when interventions to prevent disease could be effective. Development of a large (>10,000 firefighter) multicenter firefighter cancer prospective cohort study will address these needs, but the framework for such a study needs to be first developed and tested among a smaller initial set of fire service partners. Implementation and Schedule: This research project is led by University of Arizona with collaborative support from multiple other research partners, including the University of Miami, National Institute for Occupational Safety and Health; National Fallen Firefighter Foundation, Fire Protection Research Foundation, and others. Initial funding for this project is through a 3-year DHS/FEMA Assistance to Fire Fighter (AFG) Fire Grant, with the intention to identify and obtain additional funding for the duration of the 30 year effort. The project start date is August 2016. The Principal Investigator for this project is: Jefferey L. Burgess, MD, MS, MPH, University of Arizona, email: [email protected]. Project Goal and Aims: The goal of the initial 3-year effort of this overall project is to develop and test a framework for establishing a long-term fire fighter multicenter prospective cohort study focused on carcinogenic exposures and effects. The specific aims are to: 1) Establish an oversight and planning board to provide study oversight, foster communication among fire organizations and help develop a long-term funding plan; 2) Create and test a cohort study data coordinating center and harmonized survey data protocols; 3) Develop and validate a firefighter carcinogen exposure matrix and data collection system; and 4) Create a biomarker assessment center and evaluate the association between cumulative firefighter exposures and epigenetic effects. For more information, contact: Casey Grant, Fire Protection Research Foundation 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7284 Fax: +1.617.984.7010 Email: [email protected] Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Project Methodology: This study will harmonize and build on recent and developing firefighter cancer prevention studies in Arizona, Florida and Massachusetts, adding volunteer fire departments. An oversight and planning board will be established by the Fire Protection Research Foundation (FPRF) in association with the National Fallen Firefighter Foundation (NFFF) Fire Service Occupational Cancer Alliance (FSOCA) to provide oversight of the study through collaboration among fire service organizations, academia, and government agencies, and develop a long-term funding and sustainability plan. A data coordination center team will design, develop and evaluate a framework for a multicenter prospective cohort study of firefighters and cancer risk, including standardized participant survey data collection tools and analysis protocols sufficient to address the short- and long-term study objectives as well as linkage with long-term outcome data including cancer development. An exposure assessment center team will develop a carcinogen exposure matrix and data collection system to provide improved occupational exposure data for comparison with epigenetic outcomes and eventual cancer outcomes. Carcinogen exposures associated with specific fire types will be evaluated across fire departments through industrial hygiene monitoring and analysis of urine for absorbed contaminants, supplementing existing FEMA-funded and other studies of firefighter exposures and allowing for participating fire departments to design interventions to reduce current exposures. Expansion of the National Fire Operations Reporting System (NFORS) will be explored as one option to uniformly collect incident and exposure data. Blood and buccal cells will be collected during annual medical surveillance evaluations, including both new recruits and incumbent firefighters. Pilot studies of epigenetic markers of cancer effect and cancer risk will be analyzed comparing municipal firefighters with high chronic exposures, volunteer firefighters with low chronic exposures, and non- firefighter friends of the municipal firefighters (serving as controls). Project Deliverables: The anticipated outcomes from this 3-year effort is to establish and test the framework necessary for the subsequent development of a large multicenter cohort study of cancer in the fire service. Page 2 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226

What is the limit of Workshop attendance?

hlcn0226

hlcn0226_p0, hlcn0226_p1, hlcn0226_p2, hlcn0226_p3, hlcn0226_p4, hlcn0226_p5, hlcn0226_p6, hlcn0226_p7, hlcn0226_p8, hlcn0226_p9, hlcn0226_p10, hlcn0226_p11

is limited to the first 50 attendees,

129 From: Jürgen Troitzsch To: Osimitz Thomas; Dr. Blais Matthew; Prof. Rein Guillermo; Dr. Hayes Wallace; Dourson. Michael (doursomi); Kacew Sam; Dr. Wise Kimberly Subject: Fwd: Project on FF PPE Cleaning Validation Date: Monday, June 12, 2017 1:11:46 PM Attachments: PROU PANEL - PPE Cleaning (33) pdf PROJ SUMMARY - PPE Cleaning (7) pot FLYER FF Contam Control Workshop (6) odf HOTELS - Contam Control Wrkshp on 2017Jul19.pd PROJS JMMARY- FE Cancer Cohort Study (4) odf Dear All, I came across this project, which may be of interest in the frame of our fire fighters cancer activities. Kind regards/Viele Grüße Jürgen Dr. Jürgen Troitzsch Fire and Environment Protection Service FEPS Via Patrizia 32 CH-6612 Ascona, Switzerland Mobile: +41 79 289 17 16 Phone: +41 91 791 14 22 Email: [email protected] Web: www.troitzsch.com De : Grant, Casey Envoyé : lundi 22 mai 2017 17:58 À : [email protected]; [email protected]. tis.com; mlambetamallN u.edu; dwardmecarthyebostengoy ark.a.miller@ehoen ix.gov; james.riley@bosta nagov; [email protected] Thomas [email protected]; ;timügearcleaningsolutions.s om [email protected]; Ken.Wiles @fire.jacounty.gov Farrell, Christopher cobtlogiobefiresuits.com; pattogiobefiresults.com; Diane.Hess@ Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 130 PBIProducts.com; Kebtonen@lionprotedscon leur.gouv.fr; GUILLAUME Eric <eric [email protected] ;[email protected]; mamiefortunes-collide.com Cc : lasonallendintertekeor [email protected]; [email protected] wlindslev@ cdc.gov; [email protected] [email protected]; [email protected]; ; istendice OY; Objet : Project on FF PPE Cleaning Validation To: Panel, Research Team and Liaisons for Project on "Fire Fighter PPE Cleaning Validation" It has been some time since we last spoke, and I have the following three items to be addressed: 1) A lot has been happening with our project and we want to hold a 90 minute conference call in early August 2017 to bring everyone up-to-date. I've created a scheduling poll to determine the optimum date/time Please respond before Noon ET on Wednesday 31/May/2017 so that we can get this on our calendars. I've attached the Project Roster and Project Summary in case anyone needs a refresher for this project addressing "how clean is clean". Thanks. 2) I've been asked to participate in a webinar tomorrow (23/Mav/2017) from noon ET to 1:30 pm ET on "Factors Relating to Cancer and Contamination in the US Fire Service". I've been assigned a portion of this webinar (among two other speakers) to address on-going research and I'm planning to address our project among several other on-going efforts. The link is on the NFPA home page at: FYI.. 3) Some of you are already aware of the Workshop in Columbus, Ohio on 19- 20/Julv/2017, and if not I want to call it to your attention. This is for the separate one year AFG project on "Campaign for Fire Service Contamination Control". Attached is a Flyer that provides additional details, and also attached is a list of hotels in the area to assist with travel. The workshop will be held from Noon to Noon on 19-20/July and we still have room if you would like to attend. In addition, the separate project (i.e., a third related project) on "Fire Fighter Cancer Cohort Study" will hold a separate planning meeting on the afternoon of 20/July from 1 pm to 5 pm (Project Summary is attached). All are welcome to attend this as well. If you are a fire service panel member we can cover your travel, and I can send follow-up instructions to you separately. For anyone interested in attending the Columbus meetings on 19-20/July, please let us know by email to [email protected] and Thanks.. Casey C. Grant, P.E. Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION "CAMPAIGN FOR FIRE SERVICE CONTAMINATION CONTROL" WORKSHOP Location: Columbus Fire Fighters Union Hall, 379 W Broad St, Columbus, OH 43215 Workshop Dates: 19-20 July 2017 (Last Updated: 21 April 2017; subject to update) Background: Exposure to chemical and biological contaminants on the fire ground is an increasing concern for long-term fire fighter health. Cancer and other diseases resulting from chronic exposures has become a leading concern for the fire service. This is presumed to be associated with fireground exposures relating to protection/hygiene practices and persistent harmful contamination found in fire fighter equipment, apparatus carrying that equipment, and stations where the equipment resides. Workshop Goal and Objectives: The goal of this Workshop is to identify concepts and materials that are or can be useful to control the spread of harmful fire ground contaminants, ultimately in support of improved fire fighter long-term health. The following objectives support this goal (and reflect anticipated deliverables): Identify, review and recommend baseline materials (existing and proposed) addressing best practices, standards, research, equipment, facilities, and other areas of focus. Identify and prioritize gaps that are barriers to enhancing best practices, standards, research, equipment, facilities, and other areas of focus. Identify and review key characteristics for effective promotion and communication. Clarify target audiences for outreach and consider stakeholder research prior to developing a comprehensive communications plan to improve outcome. Prioritize messages for year one. Agenda: Wed; 19/July 1:00 pm Day One: Welcome and Call to Order Casey Grant, FPRF 1:15 pm Overview of Baseline Materials and Review of Gaps Jeff Stull, IPP 2:00 pm Review of Outreach Peg, Paul, PPA 2:30 pm Case Study: Best Practice Information Beth Gallup, KFD 3:00 pm PM Break 3:15 pm Casey Study: Standards Revisions Dave Bernzweig, CFD 3:45 pm Case Study: Equipment & Facilities Paul Erickson, LEWA 4:15 pm Breakout Groups Workshop Attendees 5:00 pm Adjourn for Day One (& Evening Networking Reception) Thur; 20/July 8:30 am Day Two: Group Review of Baseline Materials Jeff Stull, IPP 8:45 am Breakout Groups Continue Workshop Attendees 9:45 am AM Break 10:00 am Breakout Group Report Workshop Attendees 11:00 am Plenary Discussion Workshop Attendees 11:30 am Workshop Wrap-up & Summary Observations Casey Grant, FPRF 12:00 pm Adjournment Registration: Workshop attendance is limited to the first 50 attendees, and others will be placed the on a waiting list. To request attendance or for more information, please contact [email protected]. After the Workshop a report will be available. This Workshop is funded through an AFG Fire Prevention & Safety Grant from U.S.DHS/FEMA. 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7281 Fax: +1.617.984.7010 Email: [email protected] www.NFPA.org/Foundation Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 WORKSHOP ON FIRE SERVICE CONTAMINATION CONTROL 19-20 July 2017 (Noon to Noon ET) Columbus Fire Fighters Union Hall 379 W Broad St, Columbus, OH 43215 Note: For flights, Workshop starts at Noon ET on 19/July/2017 and finishes at Noon ET on 20/July/2017 Drury Inn & Suites: 88 East Nationwide Blvd, Columbus, OH 43215 Phone: 1-614-221-7008 ttos://www.drurvhotels.com/locations/columbus-ob/drurv-inn-and-suites-columbus-convention: center Approximate Rate: $130 Distance (in miles) from Hotel to Columbus Union Hall: 1.3 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars. Red Roof Plus Columbus Downtown Convention Center 111 East Nationwide Blvd, Columbus, OH 43215 Phone: 1-614-224-6539 ittps://www.redroof.com/property/Columbus/OH/43215/Hotels-close-to-Greater-columbus- Convention-Center-US-23-1-670/RRI262/ Approximate Rate: $130 Distance (in miles) from Hotel to Columbus Union Hall: 1.4 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars. Sheraton Columbus Hotel at Capital Square 75 East State Street, Columbus, OH, 43215 Phone: 1-614-365-4500 http://www.sheratoncolumbuscapitolsquare.com/ Approximate Rate: $170 Distance (in miles) from Hotel to Columbus Union Hall: 0.8 Notes: Central downtown area Hampton Inn and Suites Columbus Downtown 501 North High Street, Columbus, OH 43215 Phone: 1-614-559-2000 htto://hamptoninns.bilton.com/en/hotels/ohio/hampton-inn-and-suites-columbus-downtown- CMHHSHK/index.htmi?WT.mc. Approximate Rate: $175 Distance (in miles) from Hotel to Columbus Union Hall: 1.3 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars. Page 1 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Courtyard Columbus Downtown 35 West Spring Street, Columbus, Ohio 43215 Phone: 1-614-228-3200 4d19-a255-54ba596febe2 Approximate Rate: $175 Distance (in miles) from Hotel to Columbus Union Hall: 0.8 Notes: Downtown west area; walkable Doubletree Suites by Hilton Columbus Downtown 50 South Front St, Columbus, Ohio, 43215-4145 Phone: 1-614-228-4600 CMHSBOT/index.htmi Approximate Rate: $200 Distance (in miles) from Hotel to Columbus Union Hall: 0.5 Notes: Closest hotel to meeting site; very short walk Residence Inn Columbus Downtown 36 East Gay Street, Columbus, Ohio 43215-3108 Phone: 1-614-222-2610 ec3-4d19-a255-54ba596febe2 Approximate Rate: $230 Distance (in miles) from Hotel to Columbus Union Hall: 0.8 Renaissance Columbus Downtown 50 North Third Street, Columbus, Ohio 43215 Phone: 1-614-228-5050 ttp://www.marriott.com/hotels/travel/cmhbr-renaissance-columbus-downtown-hotel/ Approximate Rate: $240 Distance (in miles) from Hotel to Columbus Union Hall: 1.0 Notes: Central downtown area Hilton Columbus Downtown 401 North High Street, Columbus, OH 43215 Phone: 1-614-384-8600 Approximate Rate: $240 Distance (in miles) from Hotel to Columbus Union Hall: 1.1 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars; New facility and nice. Page 2 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION PPE Cleaning Validation Validation of Cleaning Procedures for Fire Fighter Personal Protective Equipment (PPE) PROJECT CONTACTS Last Updated: 22 May 2017 Project Technical Panel Phone: 614-774-7446 David Bernzweig, Columbus Fire Department (OH) Email: [email protected] Phone: 780-496-3801 Ken Block, Edmonton Fire/Rescue & Metro Chiefs Representative Email: [email protected] Phone: 804-971-7983 Ken Brown, VA State Firefighter's Association & NVFC (Alt to B. McQueen) Email; [email protected] Phone: 510-839-5111 Cell: 213-321-9393 Roger Curtis, ECMS Curtis & Sons (CA) Email: [email protected] Phone: Paul Curtis, ECMS Curtis & Sons (CA) (Alt to Roger Curtis) Email: [email protected] Phone: 253-277-4131 Cell: 503-314-4832 Steve Lakey, Northwest Safety Clean (WA) Email: [email protected] Phone: 304-406-7479 Mark Lambert, WV Fire Academy & NAFTD (WV) Email: [email protected] Phone: 617-828-3978 Ed McCarthy, Boston Fire Department (MA) Email: [email protected] Phone: 315-736-7479 Cell: 315-552-8245 Brian McQueen, FASNY & National Volunteer Fire Council (NY) Email: [email protected] Phone: 602-534-2396 Mark Miller, Phoenix Fire Dept. (AZ) Email: [email protected] Phone: 919-524-1569 Bryan Ormond, NCSU (NC) Email: [email protected] Phone: Russ Osgood, Firefighter Cancer Support Network (NH) (Alt to Keith Tyson) Email: [email protected] Phone: Larry Petrick, IAFF (DC) Email: [email protected] Phone: 617-549-9850 Jim Riley, Boston Fire Department (MA) (Alt to E. McCarthy) Email: [email protected] Phone: 757-385-2892 Molly Riley, Virginia Beach Fire Dept. (VA) Email: [email protected] Phone: 718-999-2922 Thomas Smith, FDNY (NY) Email: [email protected] Phone: 214-774-2213 Cell: 940-300-5718 Tim Tomlinson, Gear Cleaning Solutions (TX) Email: [email protected] Phone: Robert Tutterow, NFPA Fire Service Section (NC) Email: [email protected] Phone: 786-351-3276 Keith Tyson, Firefighter Cancer Support Network (FL) Email: [email protected] Phone: 951-807-1914 Dick Weise, LA County Fire Dept. (CA) Email: [email protected] Phone: 949-291-0637 Ken Wiles, LA County Fire Dept. (CA) (Alt to Dick Weiss) Email: [email protected] Phone: 512-974-0286 Chris Youngblood, Austin Fire Dept. (TX) Email: [email protected] 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7281 Fax: +1.617.984.7010 Email: [email protected] www.NFPA.org/Foundation Source: :https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Phase 1 Project Contacts Phone: 330-723-0000, x365 Steve Allison, Fire-Dex (OH) Email: [email protected] Phone: 800-401-4780 Jack Binder, Edmar Chemical Company (OH) Email: [email protected] Phone: 920-570-0824 Bill Brooks, Alliance Corp. (WI) Email: [email protected] Phone: Charlie Dunn, TenCate Protective Fabrics Email: [email protected] Phone: 617-984-7325 Chris Farrell, NFPA & Staff Liaison for NFPA 1851 (MA) Email: [email protected] Phone: 800-232-8323 Rob Freese, Globe Manufacturing (NH) Email: [email protected] Phone: Pat Freeman, Globe Manufacturing (NH) (Alternate to Rob Freese) Email: [email protected] Phone: 704-554-3313 Diane Hess, PBI Performance Products (NC) Email: [email protected] Phone: 937-415-2932 Karen Lehtonen, LionFirst Responder Products (OH) Email: [email protected] Phone: 484-433-4072 Dan Silvestri, 9-1-1 Safety (PA) Email: [email protected] Liaison Contacts Phone: Pierre Carlotti, Ministry of Interior & Liaison for ISO TC92/SC3 (France) Email: [email protected] Phone: Eric Guillaume, Efectis & Liaison for ISO TC92/SC3 (France) Email: [email protected] Phone: Bill Haskell, NIOSH NPPTL (MA) Email: [email protected] Phone: James Hoar, Boston Fire Department (MA) Email: [email protected] Phone: 631-242-0621 Steve King, Chair NFPA 1851 (NY) Email: [email protected] Phone: +33(0)1.55.76.26.18 Fanny Rieunier, Ministry of Interior & Liaison for ISO TC92/SC3 (France) Email: [email protected] Phone: 612-247-6429 Marni Schmid, Fortunes Collide & Secretariat NFPA 1851 (MI) Email: [email protected] Page 2 of 3 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Core Research Team Phone: 607-758-6537 Cell: 607-423-5617 Jason Allen, Intertek (NY) Email: [email protected] Phone: 304-285-6076 Daniel Farcas, NIOSH HELD (WV) Email: [email protected] Phone: Crystal Forester, NIOSH NPPTL (WV) Email: [email protected] Phone: 617-984-7284 Cell: 617-659-1159 Casey Grant, Fire Protection Research Foundation (MA) Email: [email protected] Phone: Lee Greenawald, NIOSH NPPTL (WV) Email: [email protected] Phone: Bill Lindsley, NIOSH HELD (WV) Email: [email protected] Phone: Stephen Martin, NIOSH DRDS (WV) Email: [email protected] Phone: John Noti, NIOSH HELD (WV) Email: [email protected] Phone: Deborah Sbarra, NIOSH NPPTL (WV) Email: [email protected] Phone: 512-288-8272 cell: 512-623-9558 Jeff Stull, International Personal Protection (TX) Email: [email protected] Phone: 304-285-5858 cell: 681-209-2571 Jay Tarley, NIOSH NPPTL (WV) Email: [email protected] Additional Research Team Contacts Phone: 304-285-5884 Francoise Blachere, NIOSH HELD (WV) Email: [email protected] Phone: Renee Dotson, NIOSH HELD (WV) Email: [email protected] Phone: James Harris, NIOSH NPPTL (WV) Email: [email protected] Phone: Ryan Lebouf, NIOSH DRDS (WV) Email: [email protected] Phone: 617-984-7281 Eric Peterson, Fire Protection Research Foundation (MA) Email: [email protected] Phone: John Powers, NIOSH (WV) Email: [email protected] Phone: 412-386-4621 Cell: 412-463-9561 Heather Reed, NIOSH NPPTL (PA) Email: [email protected] Page 3 of 3 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION PPE Cleaning Validation Validation of Cleaning Procedures for Fire Fighter Personal Protective Equipment (PPE) (for more information see www.nfpa.org/PPECleaning) PROJECT SUMMARY Last updated: 5 February 2016 Background: Fire fighter exposure to personal protective equipment (PPE) that is dirty, soiled, and contaminated is an increasing concern for long-term fire fighter health. This exposure to persistent harmful contaminants in PPE is an extremely serious problem both on the fireground to highly toxic substances including a variety of carcinogens, and more insidiously to an increasing range of infectious pathogens that are encountered in patient care and different emergency operations. Fire fighter PPE becomes contaminated during these exposures and there are no industry standards that conclusively and reliably show that clothing is being adequately cleaned. While general cleaning procedures have been established in NFPA 1851, Standard on Selection, Care, and Maintenance of Protective Ensembles for Structural Fire Fighting and Proximity Fire Fighting, there are no procedures or requirements to demonstrate whether current cleaning practices, including those specified in NFPA 1851, will remove contaminants from fire fighter protective clothing. This project is intended to establish clear and definitive guidance to the fire service for applying cleaning and decontamination procedures that effectively remove both chemical and biological contaminants. Research Goal and Objectives, and Conceptual Approach: The overall goal of this project is to improve fire fighter safety and health by reducing continuing exposure to harmful contaminants in unclean or inadequately cleaned PPE. The objectives to achieve this goal are twofold: (1) To characterize fireground and emergency scene contamination leading to these exposures and develop the methodology for the consistent measurement of cleaning effectiveness; and (2) determine implementable cleaning, decontamination, and disinfection strategies that effectively reduce fire fighter exposures to persistent contaminants. The approach taken by this project is illustrated in Figure 1: Project Conceptual Approach. - Ensure Identify Devise Validate lab - - chemical and methods to methods - at biologicat conteminate againet field ses target clothing in contaminants laboratory exposures acceptance Project Direction Figure 1: Project Conceptual Approach 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7281 Fax: +1.617.984.7010 Email: [email protected] www.NFPA.org/Foundation Source: :ttps://www.industrydocuments.ucsf.edu/docs/hlcn0226 Project Phases and Tasks: This project involves the following four key phases of activity: 1) Identification of Contaminants: Confirm identification and ability to characterize persistent chemical and biological contaminants in fire fighter PPE through target substances and microorganisms. 2) Establishment of Soil and Chemical Contamination/Decontamination Procedures: Develop and validate specific procedures that determine the effectiveness of laundering and other cleaning methods in removing specific soils and chemical contaminants. 3) Establishment of Biological Contamination/Disinfection or Sanitization Procedures: Develop and validate specific procedures that determine the effectiveness of laundering or disinfection/sanitization processes that remove/deactivate biologically-based contaminants. 4) Creation of Overall Fire Service Guidance: Prepare clear and definitive information for the fire service industry (fire fighters, fire departments, clothing manufacturers, material suppliers, cleaning/care organizations, and cleaning agent or equipment manufacturers) on appropriate approaches for properly cleaning fire fighter protective clothing and equipment. The specific tasks of this project are based on these four phases of the project, and these are illustrated in Figure 2: Project Tasks. PHASE 2 PHASEZ Task 2.4 Task 2.5 Task 1.1 Task 2.1 Validate testsat Refine test Appoint Technical Select cleaning selected ISPS methodology Review Panel methods/agents (chemical) (chemical) PHASE $ Task 4.1 Task 1.2 Task 2.2 Write qualification Review Prigr Put together test plan methods studies/literature (chemical) Task 2.3 Task 4.2 Task 1.3 PHASE 3 Perform laboratory Establish cleaning Setup analytical chemical Task 3.3 acceptance criteria capabilities decontaminant Put together test plan testing (biological) Task 4.3 Task 1.4 Perform Task 3.4 Prepare public inputs for NFPA 1851 demonstration tests Task 3.1 Perform laboratory Task 3.6 Select study biological Refine test microorganisms decontaminant methodology Task 1.5 testing (biological) Task 4.4 Refine biological Prepare industry decontamination Task 3.2 Task 3.5 guidance document scope Select biological Validate testsat cleaning methods selected ISPs (biological) Task 1.6 Task 4,5 Establish cleanliness Prepare project final metrics report Figure 2: Project Tasks Implementation and Schedule: This three year project is due to be completed no later than " August 2018, and is funded through an AFG Fire Prevention & Safety Grant from the U.S. Department of Homeland Security / Federal Emergency Management Agency. The Research Foundation will lead a unique research team partnership composed of the FPRF, National Institute for Occupational Safety and Health (NIOSH), International Personal Protection (IPP), and Intertek. The research team, along with several Independent Service Providers (ISPs), will work with the fire service partners and others to validate and optimize fire fighter PPE cleaning validation methods. For more information see www.nfpa.org/PPECleaning. Page 2 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION Fire Fighter Cancer Cohort Study Full Title: The Firefighter Multicenter Cancer Cohort Study: Framework Development and Testing PROJECT SUMMARY Last Updated: 20 September 2016 Background: Cancer is a leading cause of fire service morbidity and mortality. Firefighter exposure to carcinogens occurs through skin contamination and through inhalation when respiratory protection is not worn when combustion products are present such as during overhaul, standby, and operation of apparatus, as well as through off-gassing of equipment and exposures in the fire station. However, we currently do not understand which exposures are responsible for cancer in firefighters, the mechanisms by which firefighter exposures cause cancer, nor the most effective means of reducing exposures. Since cancer has a long latency period, biomarkers are also needed that can measure the toxicological effects of carcinogen exposure well before the development of cancer, when interventions to prevent disease could be effective. Development of a large (>10,000 firefighter) multicenter firefighter cancer prospective cohort study will address these needs, but the framework for such a study needs to be first developed and tested among a smaller initial set of fire service partners. Implementation and Schedule: This research project is led by University of Arizona with collaborative support from multiple other research partners, including the University of Miami, National Institute for Occupational Safety and Health; National Fallen Firefighter Foundation, Fire Protection Research Foundation, and others. Initial funding for this project is through a 3-year DHS/FEMA Assistance to Fire Fighter (AFG) Fire Grant, with the intention to identify and obtain additional funding for the duration of the 30 year effort. The project start date is August 2016. The Principal Investigator for this project is: Jefferey L. Burgess, MD, MS, MPH, University of Arizona, email: [email protected]. Project Goal and Aims: The goal of the initial 3-year effort of this overall project is to develop and test a framework for establishing a long-term fire fighter multicenter prospective cohort study focused on carcinogenic exposures and effects. The specific aims are to: 1) Establish an oversight and planning board to provide study oversight, foster communication among fire organizations and help develop a long-term funding plan; 2) Create and test a cohort study data coordinating center and harmonized survey data protocols; 3) Develop and validate a firefighter carcinogen exposure matrix and data collection system; and 4) Create a biomarker assessment center and evaluate the association between cumulative firefighter exposures and epigenetic effects. For more information, contact: Casey Grant, Fire Protection Research Foundation 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7284 Fax: +1.617.984.7010 Email: [email protected] Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Project Methodology: This study will harmonize and build on recent and developing firefighter cancer prevention studies in Arizona, Florida and Massachusetts, adding volunteer fire departments. An oversight and planning board will be established by the Fire Protection Research Foundation (FPRF) in association with the National Fallen Firefighter Foundation (NFFF) Fire Service Occupational Cancer Alliance (FSOCA) to provide oversight of the study through collaboration among fire service organizations, academia, and government agencies, and develop a long-term funding and sustainability plan. A data coordination center team will design, develop and evaluate a framework for a multicenter prospective cohort study of firefighters and cancer risk, including standardized participant survey data collection tools and analysis protocols sufficient to address the short- and long-term study objectives as well as linkage with long-term outcome data including cancer development. An exposure assessment center team will develop a carcinogen exposure matrix and data collection system to provide improved occupational exposure data for comparison with epigenetic outcomes and eventual cancer outcomes. Carcinogen exposures associated with specific fire types will be evaluated across fire departments through industrial hygiene monitoring and analysis of urine for absorbed contaminants, supplementing existing FEMA-funded and other studies of firefighter exposures and allowing for participating fire departments to design interventions to reduce current exposures. Expansion of the National Fire Operations Reporting System (NFORS) will be explored as one option to uniformly collect incident and exposure data. Blood and buccal cells will be collected during annual medical surveillance evaluations, including both new recruits and incumbent firefighters. Pilot studies of epigenetic markers of cancer effect and cancer risk will be analyzed comparing municipal firefighters with high chronic exposures, volunteer firefighters with low chronic exposures, and non- firefighter friends of the municipal firefighters (serving as controls). Project Deliverables: The anticipated outcomes from this 3-year effort is to establish and test the framework necessary for the subsequent development of a large multicenter cohort study of cancer in the fire service. Page 2 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226

When is the Workshop?

hlcn0226

hlcn0226_p0, hlcn0226_p1, hlcn0226_p2, hlcn0226_p3, hlcn0226_p4, hlcn0226_p5, hlcn0226_p6, hlcn0226_p7, hlcn0226_p8, hlcn0226_p9, hlcn0226_p10, hlcn0226_p11

19-20 July 2017

129 From: Jürgen Troitzsch To: Osimitz Thomas; Dr. Blais Matthew; Prof. Rein Guillermo; Dr. Hayes Wallace; Dourson. Michael (doursomi); Kacew Sam; Dr. Wise Kimberly Subject: Fwd: Project on FF PPE Cleaning Validation Date: Monday, June 12, 2017 1:11:46 PM Attachments: PROU PANEL - PPE Cleaning (33) pdf PROJ SUMMARY - PPE Cleaning (7) pot FLYER FF Contam Control Workshop (6) odf HOTELS - Contam Control Wrkshp on 2017Jul19.pd PROJS JMMARY- FE Cancer Cohort Study (4) odf Dear All, I came across this project, which may be of interest in the frame of our fire fighters cancer activities. Kind regards/Viele Grüße Jürgen Dr. Jürgen Troitzsch Fire and Environment Protection Service FEPS Via Patrizia 32 CH-6612 Ascona, Switzerland Mobile: +41 79 289 17 16 Phone: +41 91 791 14 22 Email: [email protected] Web: www.troitzsch.com De : Grant, Casey Envoyé : lundi 22 mai 2017 17:58 À : [email protected]; [email protected]. tis.com; mlambetamallN u.edu; dwardmecarthyebostengoy ark.a.miller@ehoen ix.gov; james.riley@bosta nagov; [email protected] Thomas [email protected]; ;timügearcleaningsolutions.s om [email protected]; Ken.Wiles @fire.jacounty.gov Farrell, Christopher cobtlogiobefiresuits.com; pattogiobefiresults.com; Diane.Hess@ Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 130 PBIProducts.com; Kebtonen@lionprotedscon leur.gouv.fr; GUILLAUME Eric <eric [email protected] ;[email protected]; mamiefortunes-collide.com Cc : lasonallendintertekeor [email protected]; [email protected] wlindslev@ cdc.gov; [email protected] [email protected]; [email protected]; ; istendice OY; Objet : Project on FF PPE Cleaning Validation To: Panel, Research Team and Liaisons for Project on "Fire Fighter PPE Cleaning Validation" It has been some time since we last spoke, and I have the following three items to be addressed: 1) A lot has been happening with our project and we want to hold a 90 minute conference call in early August 2017 to bring everyone up-to-date. I've created a scheduling poll to determine the optimum date/time Please respond before Noon ET on Wednesday 31/May/2017 so that we can get this on our calendars. I've attached the Project Roster and Project Summary in case anyone needs a refresher for this project addressing "how clean is clean". Thanks. 2) I've been asked to participate in a webinar tomorrow (23/Mav/2017) from noon ET to 1:30 pm ET on "Factors Relating to Cancer and Contamination in the US Fire Service". I've been assigned a portion of this webinar (among two other speakers) to address on-going research and I'm planning to address our project among several other on-going efforts. The link is on the NFPA home page at: FYI.. 3) Some of you are already aware of the Workshop in Columbus, Ohio on 19- 20/Julv/2017, and if not I want to call it to your attention. This is for the separate one year AFG project on "Campaign for Fire Service Contamination Control". Attached is a Flyer that provides additional details, and also attached is a list of hotels in the area to assist with travel. The workshop will be held from Noon to Noon on 19-20/July and we still have room if you would like to attend. In addition, the separate project (i.e., a third related project) on "Fire Fighter Cancer Cohort Study" will hold a separate planning meeting on the afternoon of 20/July from 1 pm to 5 pm (Project Summary is attached). All are welcome to attend this as well. If you are a fire service panel member we can cover your travel, and I can send follow-up instructions to you separately. For anyone interested in attending the Columbus meetings on 19-20/July, please let us know by email to [email protected] and Thanks.. Casey C. Grant, P.E. Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION "CAMPAIGN FOR FIRE SERVICE CONTAMINATION CONTROL" WORKSHOP Location: Columbus Fire Fighters Union Hall, 379 W Broad St, Columbus, OH 43215 Workshop Dates: 19-20 July 2017 (Last Updated: 21 April 2017; subject to update) Background: Exposure to chemical and biological contaminants on the fire ground is an increasing concern for long-term fire fighter health. Cancer and other diseases resulting from chronic exposures has become a leading concern for the fire service. This is presumed to be associated with fireground exposures relating to protection/hygiene practices and persistent harmful contamination found in fire fighter equipment, apparatus carrying that equipment, and stations where the equipment resides. Workshop Goal and Objectives: The goal of this Workshop is to identify concepts and materials that are or can be useful to control the spread of harmful fire ground contaminants, ultimately in support of improved fire fighter long-term health. The following objectives support this goal (and reflect anticipated deliverables): Identify, review and recommend baseline materials (existing and proposed) addressing best practices, standards, research, equipment, facilities, and other areas of focus. Identify and prioritize gaps that are barriers to enhancing best practices, standards, research, equipment, facilities, and other areas of focus. Identify and review key characteristics for effective promotion and communication. Clarify target audiences for outreach and consider stakeholder research prior to developing a comprehensive communications plan to improve outcome. Prioritize messages for year one. Agenda: Wed; 19/July 1:00 pm Day One: Welcome and Call to Order Casey Grant, FPRF 1:15 pm Overview of Baseline Materials and Review of Gaps Jeff Stull, IPP 2:00 pm Review of Outreach Peg, Paul, PPA 2:30 pm Case Study: Best Practice Information Beth Gallup, KFD 3:00 pm PM Break 3:15 pm Casey Study: Standards Revisions Dave Bernzweig, CFD 3:45 pm Case Study: Equipment & Facilities Paul Erickson, LEWA 4:15 pm Breakout Groups Workshop Attendees 5:00 pm Adjourn for Day One (& Evening Networking Reception) Thur; 20/July 8:30 am Day Two: Group Review of Baseline Materials Jeff Stull, IPP 8:45 am Breakout Groups Continue Workshop Attendees 9:45 am AM Break 10:00 am Breakout Group Report Workshop Attendees 11:00 am Plenary Discussion Workshop Attendees 11:30 am Workshop Wrap-up & Summary Observations Casey Grant, FPRF 12:00 pm Adjournment Registration: Workshop attendance is limited to the first 50 attendees, and others will be placed the on a waiting list. To request attendance or for more information, please contact [email protected]. After the Workshop a report will be available. This Workshop is funded through an AFG Fire Prevention & Safety Grant from U.S.DHS/FEMA. 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7281 Fax: +1.617.984.7010 Email: [email protected] www.NFPA.org/Foundation Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 WORKSHOP ON FIRE SERVICE CONTAMINATION CONTROL 19-20 July 2017 (Noon to Noon ET) Columbus Fire Fighters Union Hall 379 W Broad St, Columbus, OH 43215 Note: For flights, Workshop starts at Noon ET on 19/July/2017 and finishes at Noon ET on 20/July/2017 Drury Inn & Suites: 88 East Nationwide Blvd, Columbus, OH 43215 Phone: 1-614-221-7008 ttos://www.drurvhotels.com/locations/columbus-ob/drurv-inn-and-suites-columbus-convention: center Approximate Rate: $130 Distance (in miles) from Hotel to Columbus Union Hall: 1.3 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars. Red Roof Plus Columbus Downtown Convention Center 111 East Nationwide Blvd, Columbus, OH 43215 Phone: 1-614-224-6539 ittps://www.redroof.com/property/Columbus/OH/43215/Hotels-close-to-Greater-columbus- Convention-Center-US-23-1-670/RRI262/ Approximate Rate: $130 Distance (in miles) from Hotel to Columbus Union Hall: 1.4 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars. Sheraton Columbus Hotel at Capital Square 75 East State Street, Columbus, OH, 43215 Phone: 1-614-365-4500 http://www.sheratoncolumbuscapitolsquare.com/ Approximate Rate: $170 Distance (in miles) from Hotel to Columbus Union Hall: 0.8 Notes: Central downtown area Hampton Inn and Suites Columbus Downtown 501 North High Street, Columbus, OH 43215 Phone: 1-614-559-2000 htto://hamptoninns.bilton.com/en/hotels/ohio/hampton-inn-and-suites-columbus-downtown- CMHHSHK/index.htmi?WT.mc. Approximate Rate: $175 Distance (in miles) from Hotel to Columbus Union Hall: 1.3 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars. Page 1 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Courtyard Columbus Downtown 35 West Spring Street, Columbus, Ohio 43215 Phone: 1-614-228-3200 4d19-a255-54ba596febe2 Approximate Rate: $175 Distance (in miles) from Hotel to Columbus Union Hall: 0.8 Notes: Downtown west area; walkable Doubletree Suites by Hilton Columbus Downtown 50 South Front St, Columbus, Ohio, 43215-4145 Phone: 1-614-228-4600 CMHSBOT/index.htmi Approximate Rate: $200 Distance (in miles) from Hotel to Columbus Union Hall: 0.5 Notes: Closest hotel to meeting site; very short walk Residence Inn Columbus Downtown 36 East Gay Street, Columbus, Ohio 43215-3108 Phone: 1-614-222-2610 ec3-4d19-a255-54ba596febe2 Approximate Rate: $230 Distance (in miles) from Hotel to Columbus Union Hall: 0.8 Renaissance Columbus Downtown 50 North Third Street, Columbus, Ohio 43215 Phone: 1-614-228-5050 ttp://www.marriott.com/hotels/travel/cmhbr-renaissance-columbus-downtown-hotel/ Approximate Rate: $240 Distance (in miles) from Hotel to Columbus Union Hall: 1.0 Notes: Central downtown area Hilton Columbus Downtown 401 North High Street, Columbus, OH 43215 Phone: 1-614-384-8600 Approximate Rate: $240 Distance (in miles) from Hotel to Columbus Union Hall: 1.1 Notes: North area; not too far away; walkable, but you may want to Uber over; in a good part of downtown with lots of shops, restaurants, and bars; New facility and nice. Page 2 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION PPE Cleaning Validation Validation of Cleaning Procedures for Fire Fighter Personal Protective Equipment (PPE) PROJECT CONTACTS Last Updated: 22 May 2017 Project Technical Panel Phone: 614-774-7446 David Bernzweig, Columbus Fire Department (OH) Email: [email protected] Phone: 780-496-3801 Ken Block, Edmonton Fire/Rescue & Metro Chiefs Representative Email: [email protected] Phone: 804-971-7983 Ken Brown, VA State Firefighter's Association & NVFC (Alt to B. McQueen) Email; [email protected] Phone: 510-839-5111 Cell: 213-321-9393 Roger Curtis, ECMS Curtis & Sons (CA) Email: [email protected] Phone: Paul Curtis, ECMS Curtis & Sons (CA) (Alt to Roger Curtis) Email: [email protected] Phone: 253-277-4131 Cell: 503-314-4832 Steve Lakey, Northwest Safety Clean (WA) Email: [email protected] Phone: 304-406-7479 Mark Lambert, WV Fire Academy & NAFTD (WV) Email: [email protected] Phone: 617-828-3978 Ed McCarthy, Boston Fire Department (MA) Email: [email protected] Phone: 315-736-7479 Cell: 315-552-8245 Brian McQueen, FASNY & National Volunteer Fire Council (NY) Email: [email protected] Phone: 602-534-2396 Mark Miller, Phoenix Fire Dept. (AZ) Email: [email protected] Phone: 919-524-1569 Bryan Ormond, NCSU (NC) Email: [email protected] Phone: Russ Osgood, Firefighter Cancer Support Network (NH) (Alt to Keith Tyson) Email: [email protected] Phone: Larry Petrick, IAFF (DC) Email: [email protected] Phone: 617-549-9850 Jim Riley, Boston Fire Department (MA) (Alt to E. McCarthy) Email: [email protected] Phone: 757-385-2892 Molly Riley, Virginia Beach Fire Dept. (VA) Email: [email protected] Phone: 718-999-2922 Thomas Smith, FDNY (NY) Email: [email protected] Phone: 214-774-2213 Cell: 940-300-5718 Tim Tomlinson, Gear Cleaning Solutions (TX) Email: [email protected] Phone: Robert Tutterow, NFPA Fire Service Section (NC) Email: [email protected] Phone: 786-351-3276 Keith Tyson, Firefighter Cancer Support Network (FL) Email: [email protected] Phone: 951-807-1914 Dick Weise, LA County Fire Dept. (CA) Email: [email protected] Phone: 949-291-0637 Ken Wiles, LA County Fire Dept. (CA) (Alt to Dick Weiss) Email: [email protected] Phone: 512-974-0286 Chris Youngblood, Austin Fire Dept. (TX) Email: [email protected] 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7281 Fax: +1.617.984.7010 Email: [email protected] www.NFPA.org/Foundation Source: :https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Phase 1 Project Contacts Phone: 330-723-0000, x365 Steve Allison, Fire-Dex (OH) Email: [email protected] Phone: 800-401-4780 Jack Binder, Edmar Chemical Company (OH) Email: [email protected] Phone: 920-570-0824 Bill Brooks, Alliance Corp. (WI) Email: [email protected] Phone: Charlie Dunn, TenCate Protective Fabrics Email: [email protected] Phone: 617-984-7325 Chris Farrell, NFPA & Staff Liaison for NFPA 1851 (MA) Email: [email protected] Phone: 800-232-8323 Rob Freese, Globe Manufacturing (NH) Email: [email protected] Phone: Pat Freeman, Globe Manufacturing (NH) (Alternate to Rob Freese) Email: [email protected] Phone: 704-554-3313 Diane Hess, PBI Performance Products (NC) Email: [email protected] Phone: 937-415-2932 Karen Lehtonen, LionFirst Responder Products (OH) Email: [email protected] Phone: 484-433-4072 Dan Silvestri, 9-1-1 Safety (PA) Email: [email protected] Liaison Contacts Phone: Pierre Carlotti, Ministry of Interior & Liaison for ISO TC92/SC3 (France) Email: [email protected] Phone: Eric Guillaume, Efectis & Liaison for ISO TC92/SC3 (France) Email: [email protected] Phone: Bill Haskell, NIOSH NPPTL (MA) Email: [email protected] Phone: James Hoar, Boston Fire Department (MA) Email: [email protected] Phone: 631-242-0621 Steve King, Chair NFPA 1851 (NY) Email: [email protected] Phone: +33(0)1.55.76.26.18 Fanny Rieunier, Ministry of Interior & Liaison for ISO TC92/SC3 (France) Email: [email protected] Phone: 612-247-6429 Marni Schmid, Fortunes Collide & Secretariat NFPA 1851 (MI) Email: [email protected] Page 2 of 3 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Core Research Team Phone: 607-758-6537 Cell: 607-423-5617 Jason Allen, Intertek (NY) Email: [email protected] Phone: 304-285-6076 Daniel Farcas, NIOSH HELD (WV) Email: [email protected] Phone: Crystal Forester, NIOSH NPPTL (WV) Email: [email protected] Phone: 617-984-7284 Cell: 617-659-1159 Casey Grant, Fire Protection Research Foundation (MA) Email: [email protected] Phone: Lee Greenawald, NIOSH NPPTL (WV) Email: [email protected] Phone: Bill Lindsley, NIOSH HELD (WV) Email: [email protected] Phone: Stephen Martin, NIOSH DRDS (WV) Email: [email protected] Phone: John Noti, NIOSH HELD (WV) Email: [email protected] Phone: Deborah Sbarra, NIOSH NPPTL (WV) Email: [email protected] Phone: 512-288-8272 cell: 512-623-9558 Jeff Stull, International Personal Protection (TX) Email: [email protected] Phone: 304-285-5858 cell: 681-209-2571 Jay Tarley, NIOSH NPPTL (WV) Email: [email protected] Additional Research Team Contacts Phone: 304-285-5884 Francoise Blachere, NIOSH HELD (WV) Email: [email protected] Phone: Renee Dotson, NIOSH HELD (WV) Email: [email protected] Phone: James Harris, NIOSH NPPTL (WV) Email: [email protected] Phone: Ryan Lebouf, NIOSH DRDS (WV) Email: [email protected] Phone: 617-984-7281 Eric Peterson, Fire Protection Research Foundation (MA) Email: [email protected] Phone: John Powers, NIOSH (WV) Email: [email protected] Phone: 412-386-4621 Cell: 412-463-9561 Heather Reed, NIOSH NPPTL (PA) Email: [email protected] Page 3 of 3 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION PPE Cleaning Validation Validation of Cleaning Procedures for Fire Fighter Personal Protective Equipment (PPE) (for more information see www.nfpa.org/PPECleaning) PROJECT SUMMARY Last updated: 5 February 2016 Background: Fire fighter exposure to personal protective equipment (PPE) that is dirty, soiled, and contaminated is an increasing concern for long-term fire fighter health. This exposure to persistent harmful contaminants in PPE is an extremely serious problem both on the fireground to highly toxic substances including a variety of carcinogens, and more insidiously to an increasing range of infectious pathogens that are encountered in patient care and different emergency operations. Fire fighter PPE becomes contaminated during these exposures and there are no industry standards that conclusively and reliably show that clothing is being adequately cleaned. While general cleaning procedures have been established in NFPA 1851, Standard on Selection, Care, and Maintenance of Protective Ensembles for Structural Fire Fighting and Proximity Fire Fighting, there are no procedures or requirements to demonstrate whether current cleaning practices, including those specified in NFPA 1851, will remove contaminants from fire fighter protective clothing. This project is intended to establish clear and definitive guidance to the fire service for applying cleaning and decontamination procedures that effectively remove both chemical and biological contaminants. Research Goal and Objectives, and Conceptual Approach: The overall goal of this project is to improve fire fighter safety and health by reducing continuing exposure to harmful contaminants in unclean or inadequately cleaned PPE. The objectives to achieve this goal are twofold: (1) To characterize fireground and emergency scene contamination leading to these exposures and develop the methodology for the consistent measurement of cleaning effectiveness; and (2) determine implementable cleaning, decontamination, and disinfection strategies that effectively reduce fire fighter exposures to persistent contaminants. The approach taken by this project is illustrated in Figure 1: Project Conceptual Approach. - Ensure Identify Devise Validate lab - - chemical and methods to methods - at biologicat conteminate againet field ses target clothing in contaminants laboratory exposures acceptance Project Direction Figure 1: Project Conceptual Approach 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7281 Fax: +1.617.984.7010 Email: [email protected] www.NFPA.org/Foundation Source: :ttps://www.industrydocuments.ucsf.edu/docs/hlcn0226 Project Phases and Tasks: This project involves the following four key phases of activity: 1) Identification of Contaminants: Confirm identification and ability to characterize persistent chemical and biological contaminants in fire fighter PPE through target substances and microorganisms. 2) Establishment of Soil and Chemical Contamination/Decontamination Procedures: Develop and validate specific procedures that determine the effectiveness of laundering and other cleaning methods in removing specific soils and chemical contaminants. 3) Establishment of Biological Contamination/Disinfection or Sanitization Procedures: Develop and validate specific procedures that determine the effectiveness of laundering or disinfection/sanitization processes that remove/deactivate biologically-based contaminants. 4) Creation of Overall Fire Service Guidance: Prepare clear and definitive information for the fire service industry (fire fighters, fire departments, clothing manufacturers, material suppliers, cleaning/care organizations, and cleaning agent or equipment manufacturers) on appropriate approaches for properly cleaning fire fighter protective clothing and equipment. The specific tasks of this project are based on these four phases of the project, and these are illustrated in Figure 2: Project Tasks. PHASE 2 PHASEZ Task 2.4 Task 2.5 Task 1.1 Task 2.1 Validate testsat Refine test Appoint Technical Select cleaning selected ISPS methodology Review Panel methods/agents (chemical) (chemical) PHASE $ Task 4.1 Task 1.2 Task 2.2 Write qualification Review Prigr Put together test plan methods studies/literature (chemical) Task 2.3 Task 4.2 Task 1.3 PHASE 3 Perform laboratory Establish cleaning Setup analytical chemical Task 3.3 acceptance criteria capabilities decontaminant Put together test plan testing (biological) Task 4.3 Task 1.4 Perform Task 3.4 Prepare public inputs for NFPA 1851 demonstration tests Task 3.1 Perform laboratory Task 3.6 Select study biological Refine test microorganisms decontaminant methodology Task 1.5 testing (biological) Task 4.4 Refine biological Prepare industry decontamination Task 3.2 Task 3.5 guidance document scope Select biological Validate testsat cleaning methods selected ISPs (biological) Task 1.6 Task 4,5 Establish cleanliness Prepare project final metrics report Figure 2: Project Tasks Implementation and Schedule: This three year project is due to be completed no later than " August 2018, and is funded through an AFG Fire Prevention & Safety Grant from the U.S. Department of Homeland Security / Federal Emergency Management Agency. The Research Foundation will lead a unique research team partnership composed of the FPRF, National Institute for Occupational Safety and Health (NIOSH), International Personal Protection (IPP), and Intertek. The research team, along with several Independent Service Providers (ISPs), will work with the fire service partners and others to validate and optimize fire fighter PPE cleaning validation methods. For more information see www.nfpa.org/PPECleaning. Page 2 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 RESEARCH FOUNDATION NFPA RESEARCH FOR THE NFPA MISSION Fire Fighter Cancer Cohort Study Full Title: The Firefighter Multicenter Cancer Cohort Study: Framework Development and Testing PROJECT SUMMARY Last Updated: 20 September 2016 Background: Cancer is a leading cause of fire service morbidity and mortality. Firefighter exposure to carcinogens occurs through skin contamination and through inhalation when respiratory protection is not worn when combustion products are present such as during overhaul, standby, and operation of apparatus, as well as through off-gassing of equipment and exposures in the fire station. However, we currently do not understand which exposures are responsible for cancer in firefighters, the mechanisms by which firefighter exposures cause cancer, nor the most effective means of reducing exposures. Since cancer has a long latency period, biomarkers are also needed that can measure the toxicological effects of carcinogen exposure well before the development of cancer, when interventions to prevent disease could be effective. Development of a large (>10,000 firefighter) multicenter firefighter cancer prospective cohort study will address these needs, but the framework for such a study needs to be first developed and tested among a smaller initial set of fire service partners. Implementation and Schedule: This research project is led by University of Arizona with collaborative support from multiple other research partners, including the University of Miami, National Institute for Occupational Safety and Health; National Fallen Firefighter Foundation, Fire Protection Research Foundation, and others. Initial funding for this project is through a 3-year DHS/FEMA Assistance to Fire Fighter (AFG) Fire Grant, with the intention to identify and obtain additional funding for the duration of the 30 year effort. The project start date is August 2016. The Principal Investigator for this project is: Jefferey L. Burgess, MD, MS, MPH, University of Arizona, email: [email protected]. Project Goal and Aims: The goal of the initial 3-year effort of this overall project is to develop and test a framework for establishing a long-term fire fighter multicenter prospective cohort study focused on carcinogenic exposures and effects. The specific aims are to: 1) Establish an oversight and planning board to provide study oversight, foster communication among fire organizations and help develop a long-term funding plan; 2) Create and test a cohort study data coordinating center and harmonized survey data protocols; 3) Develop and validate a firefighter carcinogen exposure matrix and data collection system; and 4) Create a biomarker assessment center and evaluate the association between cumulative firefighter exposures and epigenetic effects. For more information, contact: Casey Grant, Fire Protection Research Foundation 1 Batterymarch Park, Quincy, MA 02169-7471 Telephone: +1.617.984.7284 Fax: +1.617.984.7010 Email: [email protected] Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226 Project Methodology: This study will harmonize and build on recent and developing firefighter cancer prevention studies in Arizona, Florida and Massachusetts, adding volunteer fire departments. An oversight and planning board will be established by the Fire Protection Research Foundation (FPRF) in association with the National Fallen Firefighter Foundation (NFFF) Fire Service Occupational Cancer Alliance (FSOCA) to provide oversight of the study through collaboration among fire service organizations, academia, and government agencies, and develop a long-term funding and sustainability plan. A data coordination center team will design, develop and evaluate a framework for a multicenter prospective cohort study of firefighters and cancer risk, including standardized participant survey data collection tools and analysis protocols sufficient to address the short- and long-term study objectives as well as linkage with long-term outcome data including cancer development. An exposure assessment center team will develop a carcinogen exposure matrix and data collection system to provide improved occupational exposure data for comparison with epigenetic outcomes and eventual cancer outcomes. Carcinogen exposures associated with specific fire types will be evaluated across fire departments through industrial hygiene monitoring and analysis of urine for absorbed contaminants, supplementing existing FEMA-funded and other studies of firefighter exposures and allowing for participating fire departments to design interventions to reduce current exposures. Expansion of the National Fire Operations Reporting System (NFORS) will be explored as one option to uniformly collect incident and exposure data. Blood and buccal cells will be collected during annual medical surveillance evaluations, including both new recruits and incumbent firefighters. Pilot studies of epigenetic markers of cancer effect and cancer risk will be analyzed comparing municipal firefighters with high chronic exposures, volunteer firefighters with low chronic exposures, and non- firefighter friends of the municipal firefighters (serving as controls). Project Deliverables: The anticipated outcomes from this 3-year effort is to establish and test the framework necessary for the subsequent development of a large multicenter cohort study of cancer in the fire service. Page 2 of 2 Source: https://www.industrydocuments.ucsf.edu/docs/hlcn0226

What does ICMJE stand for?

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lzbn0226_p2

International Committee of Medical Journal Editors

ICMJE INITERNATIONAL COMMITTEE of MEDICAL JOURNAL EDITORS ICMJE Form for Disclosure of Potential Conflicts of Interest Section 5. Relationships not covered above Are there other relationships or activities that readers could perceive to have influenced, or that give the appearance of potentially influencing, what you wrote in the submitted work? Yes, the following relationships/conditions/circumstance are present (explain below): No other relationships/conditions/circumstances that present a potential conflict of interest At the time of manuscript acceptance, journals will ask authors to confirm and, if necessary, update their disclosure statements. On occasion, journals may ask authors to disclose further information about reported relationships. Section 6. Disclosure Statement Based on the above disclosures, this form will automatically generate a disclosure statement, which will appear in the box below. Dr. Dourson reports funding for this project was provided by from Hamp, Mathews & Associates, Inc., PPG Corporation, Waste Management, and the University of Cincinnati during the conduct of the analysis. Evaluation and Feedback Please visit http://www.icmje.org/cgi-bin/feedback to provide feedback on your experience with completing this form. Dourson 3 Source: https://www.industrydocuments.ucsf.edu/docs/lzbn0226

What is Section 5 ?

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Relationships not covered above

ICMJE INITERNATIONAL COMMITTEE of MEDICAL JOURNAL EDITORS ICMJE Form for Disclosure of Potential Conflicts of Interest Section 5. Relationships not covered above Are there other relationships or activities that readers could perceive to have influenced, or that give the appearance of potentially influencing, what you wrote in the submitted work? Yes, the following relationships/conditions/circumstance are present (explain below): No other relationships/conditions/circumstances that present a potential conflict of interest At the time of manuscript acceptance, journals will ask authors to confirm and, if necessary, update their disclosure statements. On occasion, journals may ask authors to disclose further information about reported relationships. Section 6. Disclosure Statement Based on the above disclosures, this form will automatically generate a disclosure statement, which will appear in the box below. Dr. Dourson reports funding for this project was provided by from Hamp, Mathews & Associates, Inc., PPG Corporation, Waste Management, and the University of Cincinnati during the conduct of the analysis. Evaluation and Feedback Please visit http://www.icmje.org/cgi-bin/feedback to provide feedback on your experience with completing this form. Dourson 3 Source: https://www.industrydocuments.ucsf.edu/docs/lzbn0226

What is Section 6?

lzbn0226

lzbn0226_p2

Disclosure statement, Disclosure Statement

ICMJE INITERNATIONAL COMMITTEE of MEDICAL JOURNAL EDITORS ICMJE Form for Disclosure of Potential Conflicts of Interest Section 5. Relationships not covered above Are there other relationships or activities that readers could perceive to have influenced, or that give the appearance of potentially influencing, what you wrote in the submitted work? Yes, the following relationships/conditions/circumstance are present (explain below): No other relationships/conditions/circumstances that present a potential conflict of interest At the time of manuscript acceptance, journals will ask authors to confirm and, if necessary, update their disclosure statements. On occasion, journals may ask authors to disclose further information about reported relationships. Section 6. Disclosure Statement Based on the above disclosures, this form will automatically generate a disclosure statement, which will appear in the box below. Dr. Dourson reports funding for this project was provided by from Hamp, Mathews & Associates, Inc., PPG Corporation, Waste Management, and the University of Cincinnati during the conduct of the analysis. Evaluation and Feedback Please visit http://www.icmje.org/cgi-bin/feedback to provide feedback on your experience with completing this form. Dourson 3 Source: https://www.industrydocuments.ucsf.edu/docs/lzbn0226

How many days are the people granted to submit relevant information about that chemical?

jzbn0226

jzbn0226_p0, jzbn0226_p1, jzbn0226_p2, jzbn0226_p3, jzbn0226_p4, jzbn0226_p5, jzbn0226_p6, jzbn0226_p7, jzbn0226_p8

90 days

American° Chemistry Council March 20, 2017 Docket Control Office (7407M) Office of Pollution Prevention and Toxics (OPPT) U.S. Environmental Protection Agency 1200 Pennsylvania Ave., NW Washington, DC 20460-0001 Sent electronically to www.regulations.gov Docket ID# EPA-HQ-OPPT-2016-0636 Re: ACC Comments on EPA's Proposed Procedures for Prioritization of Chemicals for Risk Evaluation under the Toxic Substances Control Act as amended by the Lautenberg Chemical Safety Act Dear Sir/Madam: The American Chemistry Council (ACC¹ appreciates the opportunity to provide written comments to the Office of Chemical Safety and Pollution Prevention to inform the Agency's development of a prioritization process rule under the Toxic Substances Control Act (TSCA), as amended by the Lautenberg Chemical Safety Act (LCSA). ACC is committed to being a constructive stakeholder in the effective implementation of the LCSA and we provide these comments to assist the Agency in its development of a chemical evaluation and management program that is efficient, science-based, and consistent with the legal requirements of the LCSA. Prioritization is the first step in the LCSA's framework for evaluating active chemicals in commerce and the prioritization process rule must establish a risk-based screening process and criteria to identify high and low priority substances for risk evaluations under the LCSA. If you have any questions, please contact me at: 202-249-6403 or Sarah [email protected] Sincerely, Saraht. Brance Sarah Brozena Senior Director, Regulatory & Technical Affairs Cc: Jeffrey Morris, Director, OPPT Wendy Cleland Hamnett, OCSPP Ryan Schmit, OCSPP 1 The American Chemistry Council (ACC) represents the leading companies engaged in the business of chemistry. ACC members apply the science of chemistry to make innovative products and services that make people's lives better, healthier and safer. ACC is committed to improved environmental, health and safety performance through Responsible CareR, common sense advocacy designed to address major public policy issues, and health and environmental research and product testing. The business of chemistry is a $797 billion enterprise and a key element of the nation's economy. It is one of the nation's largest exporters, accounting for ten cents out of every dollar in U.S. exports. Chemistry companies are among the largest investors in research and development. Safety and security have always been primary concerns of ACC members, and they have intensified their efforts, working closely with government agencies to improve security and to defend against any threat to the nation's critical infrastructure. americanchemistry.com" 700 Second St., NE I Washington, DC 20002 I (202) 249.7000 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 American Chemistry Council American Chemistry Council Comments on EPA's Proposed Procedures for Prioritization of Chemicals for Risk Evaluation under the Toxic Substances Control Act as amended by the Lautenberg Chemical Safety Act Docket ID# EPA-HQ-OPPT-2016-0636 March 20, 2017 Sarah Brozena Senior Director, Regulatory & Technical Affairs American Chemistry Council 700 2nd Street, NE Washington DC 2002 (202) 249-6403 Sarah [email protected] americanchemistry.com 700 Second St., NE I Washington, DC 20002 I (202)249.7000 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Table of Contents EXECUTIVE SUMMARY 2 INTRODUCTION 4 I. ACC's Vision for a TSCA Prioritization Process Consistent with the LCSA 5 II. Overview of LCSA Prioritization Process Requirements 9 III. EPA Should Clarify Pre-Prioritization Step in Final Rule or Alternatively in Supplemental Rule 10 A. EPA Should Update Its TSCA Work Plan Criteria Before Using Them in Pre-Prioritization of Non-Work Plan Chemicals and Should Begin Planning to Integrate 21st Century Tools 11 B. EPA's Proposed Use of the Pre-Prioritization Step to Gather Information for Risk Evaluations Needs to Be Better Supported and Articulated 12 C. The Importance of Transparency in Prioritization Cannot Be Over-Emphasized 14 IV. EPA's Interpretation of Its Authority to Designate Low Priority Substances Is Short- Sighted, Contrary to Congressional Intent, Inconsistent with Best Available Science and Must Be Revised 15 A. EPA's Interpretation of Conditions of Use in the Prioritization Context Is a Strained Reading of the Statute and Contrary to Congressional Intent and Policy Objectives. 15 B. EPA's Abuse of Discretion Argument 16 C. EPA's Default to High Priority Designations Is Flawed Due to EPA's All Conditions of Use Interpretation. 17 D. Congress Authorized Ongoing Designations of Low Priority Chemicals 18 E. Best Available Risk-Based Scientific Procedures Enable EPA to Designate Low Priority Chemicals 18 V. Scientific Standards Must Be Referenced in the Prioritization Process Rule 19 A. Prioritization Decisions Must Be Based on Section 26 Standards for Best Available Science, Weight of the Scientific Evidence, and Transparency 19 B. EPA Should Address Other LCSA Science-Based Requirements in the Rule (Such As Tiered Testing and Animal Welfare Requirements). EPA Should Also Include a "Reserved" Placeholder in the Prioritization Rule for Incorporation of 21st Century Methods for Prioritization. 20 VI. Responses to EPA's Questions 20 A. Animal welfare requirements and scientific standards 20 B. EPA requests comments on its proposed process for prioritization overall. 21 C. Public input at pre-prioritization step 21 D. Consideration of substitutes in pre-prioritization 21 VII. Additional Specific Comments 22 A. Category of Chemical Substances 22 B. Inactive chemicals and new chemicals 22 C. Waivers 23 D. Definitions 23 E. Repopulation of High Priority Substances 24 VIII. Summary of ACC's Recommendations: 24 Attachment A 25 Attachment B 26 Attachment C 39 1 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 EXECUTIVE SUMMARY EPA has suggested four steps in its proposed rule to implement the prioritization requirements of Section 6(b) of the Toxic Substances Control Act (TSCA), as amended by the Frank R. Lautenberg Chemical Safety for the 21st Century Act: "Pre-prioritization" to narrow the pool of potential candidate substances Initiation of the prioritization process by identifying candidate substances and soliciting public comment Proposed priority designation, including an opportunity for public comment Priority designation The American Chemistry Council (ACC) has three major concerns with EPA's proposed prioritization process rule. Our concerns relate to the proposed pre-prioritization step, the treatment of low priority designations, and EPA's failure to address the LCSA Section 26 science standards in the rule. ACC's comments include specific recommendations to address these concerns. EPA's proposed prioritization process hinges on the "pre-prioritization" step. EPA does not fully and clearly describe this step, its statutory authority or limitations. Pre-prioritization is not mentioned in TSCA section 6(b) as amended. EPA asserts that the statute leaves it "broad discretion" to choose which chemicals on the TSCA Inventory to put into the prioritization process. However, EPA must exercise its discretion in a reasonable manner and is required to describe the statutory authorities for its exercise of discretion. EPA has not done so here. EPA intends the pre-prioritization step to inform prioritization decisions and the risk evaluation process, without regard to other relevant provisions of the statute. Because EPA asserts that it may need additional time to gather or develop information for risk evaluations, it has proposed to use the pre-prioritization step to gather information on substances with "insufficient information" for risk evaluation. ACC acknowledges that the statute imposes time constraints on the Agency once the prioritization process is triggered, but we believe that EPA has other tools available to address information needs in both the prioritization and risk evaluation stages in a timely, efficient manner. For example, in its pre-prioritization step EPA does not address the important relevant testing requirements of Section 4(a)(2)(A) or (B), the statement of need requirements of Section 4(a)(3) or the tiered testing requirements of Section 4(a)(4). As proposed, the pre-prioritization step conflates the prioritization and risk evaluation processes in ways that are confusing to the regulated community. Importantly, the pre-prioritization step appears contrary to congressional intent. In prioritization, it is very important that all substances be treated consistently, by the same transparent criteria, and that the process is replicable. Other than noting the statutory obligation to designate as high priorities the Work Plan chemicals that meet certain "preference" criteria, the proposed rule does not define the criteria or tools by which EPA will choose Work Plan and other chemicals from the active TSCA Inventory for the pre-prioritization or candidate "pool." EPA did not seek any stakeholder input on this question. EPA has not explained how many chemicals it proposes to include in the pre-prioritization or prioritization pool, or whether and how it will 2 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 "batch" chemicals to move them forward into the "initiation of prioritization" step. Although EPA has identified the nine criteria by which it proposes to narrow the pool into a list of candidates for prioritization, EPA does not define the criteria and or discuss the methodology by which these criteria will be applied. EPA proposes no timeframe for the pre-prioritization step, and provides little guidance on the status of chemicals included in pre-prioritization but excluded from prioritization. EPA's treatment of low priority chemicals raises significant concerns. EPA's proposal to require that low priority designations be based upon "all" conditions of use is a gross misinterpretation of the statute. This flawed interpretation of EPA's authority will cause the Agency to designate most chemicals in commerce as high priorities, and the Agency states as much in the preamble to the proposed rule. Congress did not intend this result. Low priority designations were seen as one mechanism to enhance public confidence in the safety of a chemical substance under its conditions of use, short of a full risk assessment. EPA has continuing authority to revise priority designations at any time based on new information. EPA has failed to include the LCSA Section 26 science standards in the prioritization process rule itself. EPA continues to assert that, while relevant to prioritization, EPA is not obliged to include these standards in the rule. ACC respectfully but strongly disagrees with EPA's reasoning. ACC's comments include a series of recommendations to address the shortcomings of the proposed prioritization process rule. Our recommendations describe: A transparent process for pooling and batching active chemicals in commerce for prioritization screening. A process to gather available information needed to reach a decision. A "bridging" step to permit EPA to assess the sufficiency of information for anticipated priority designations of candidate chemicals, which will inform the risk evaluation scoping process (should it be necessary). Revisions that recognize EPA's discretion to designate a low priority substance based on one, some or all conditions of use Identification of science-based criteria, tools and standards that apply in the prioritization process. 3 Source: :ttps://www.industrydocuments.ucsf.edu/docs/jzbn0226 American Chemistry Council Comments to U.S. Environmental Protection Agency on Its Proposed Procedures for Prioritization of Chemicals for Risk Evaluation under the Toxic Substances Control Act INTRODUCTION The American Chemistry Council (ACC) is pleased to provide the U.S. Environmental Protection Agency (EPA) these comments on the Agency's proposed procedures for prioritization of chemicals for risk evaluation under the Toxic Substances Control Act (TSCA) as amended by the Lautenberg Chemical Safety Act (LCSA). The LCSA requires EPA to establish, by rule, a risk-based screening process to identify high and low priority substances for risk evaluations under the LCSA. ACC strongly supported Congress's efforts to update and reform TSCA. One of ACC's principles for modernizing TSCA called on EPA to systematically prioritize chemicals for purposes of risk evaluations. Without a scientifically based prioritization process, EPA would not be able to meet efficiently the other requirements of the LCSA and achieve the objectives of TSCA reform that Congress intended. As discussed in more detail below, EPA's proposed prioritization process falls short. Congress designed the LCSA to allow chemicals to be systematically prioritized and then to evaluate those substances presenting the greatest potential risk. This design is apparent in every part of the LCSA. It begins with a reclassification of the full catalog of chemistries in U.S. commerce, the TSCA Inventory. The LCSA requires that the TSCA Inventory be sorted, so that chemicals that are currently active in commerce are separated from those no longer manufactured, imported or used; only chemicals that are active in commerce are subject to the prioritization and risk evaluation. This enables EPA to focus resources for its multi-year, time-and-resource intensive risk evaluations on chemicals that are actually in current use. EPA must next undertake a prioritization process, to inform the sequence of chemicals that will undergo risk evaluation. EPA must then undertake a formal scoping process, to define the conditions of use (and potentially exposed sub-populations relevant to the use) that will be included in the scope of the risk evaluation of the chemical. Prioritization of chemicals for various purposes is not new to the Agency. In 2011, EPA held a Stakeholder Dialogue on Prioritization and established a Discussion Blog for additional input on the topic. In our comments to that discussion blog, ACC identified several general principles for prioritization (Attachment A). We believe these principles are reflected in the LCSA requirements, in particular the LCSA's recognition that prioritization is a risk based screening process that integrates information on both hazard and exposure potential. In 2011, ACC developed a two-step quantitative and qualitative tool to "proof test" our prioritization principles (Attachment B). We presented our principles and our prioritization tool to EPA in 2011, as well as to other industry and NGO stakeholders at the time. In 2012, EPA published its methodology to identify chemicals for its TSCA Work 4 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Plan for Chemical Assessment (TSCA Work Plan) program. I. ACC's Vision for a TSCA Prioritization Process Consistent with the LCSA The LCSA requires EPA, by rule, to establish a risk-based screening process to designate chemicals as high or low priorities for risk evaluations. The LCSA includes criteria and considerations by which EPA must make these priority designations. To ensure EPA consistently has risk evaluations underway, the LCSA requires EPA to identify at least one new high priority for every risk evaluation that is completed. EPA's ability to designate additional priorities for 2 evaluation is limited only by the Agency's ability to complete risk evaluations in accordance with the deadlines established by Congress. Thus, Congress requires EPA to carefully choreograph the 3 identification of high priority substances for risk evaluations, in order to ensure that appropriate resources are available to complete the evaluations with the established deadlines. This implies a framework that efficiently coordinates EPA's prioritization process with EPA's risk evaluation process. ACC's vision for the prioritization process is one that enables EPA to meet all the requirements of the LCSA and congressional intent. Prioritization must be a risk based screening process in which EPA integrates hazard, use and exposure information to designate chemicals or categories of chemicals as either high or low priority for risk evaluations based on the criteria in Section 6. Information used to make prioritization decisions must be reasonably available; new information should be required through Section 4 tools only if EPA makes a determination pursuant to Section 4(a)(2)(B) that new information is necessary for prioritization. Prioritization designations must be based upon the science standards of LCSA Section 26, particularly best available science and weight of the scientific evidence. The basis for prioritization designations must be transparent and EPA's decisions must be communicated objectively and in neutral terms. ACC's vision of a prioritization process that meets these requirements includes six steps (see discussion below and the flowchart illustrating these steps on the next page and in Attachment C). ACC recommends that EPA clarify the needed timelines, criteria, tools, approaches and processes for these six steps, publish them for comment and include them in the final rule. Alternatively, EPA should propose these clarifications in a supplemental rule prior to the Agency's first application of the prioritization process. ACC's recommended six steps for the prioritization process are as follows: 1. Pool and Batch: EPA must "pool" active chemicals in commerce as candidates for designation as high or low priority for risk evaluation, based on transparent criteria/methods/approaches/tools and processes. EPA should then "batch" these candidates for information gathering. As EPA acknowledges in the "re-population" discussion of the preamble to the proposed rule4, the pace of EPA's completion of risk evaluations factors into the finalization of EPA's prioritization decisions. As a result, ACC expects that the number of candidates per "batch" for information gathering should be relatively small, at least in the early years of LCSA implementation. EPA's development of pools and batches should be subject to 2 15 U.S.C 1.2605(b)(3)(C) 3 15 U.S.C. 2605 (b)(2)(C) 4 82 Fed.Reg. 4825, 4833 (January 17, 2017). 5 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 estimated timeframes. 2. Information Gathering: Because Congress intended prioritization decisions to be based on reasonably available information, EPA should take a sequenced approach to information gathering on chemicals that EPA "batches" for prioritization. The sequenced steps should begin with EPA gathering reasonably available information about potential hazards, uses and potential exposure by relying upon sources such as read across/Quantitative Structure Activity Relationship (QSAR) information; Chemical Data Reporting (CDR) reports; EPA's CompTox Dashboard; High Production Volume (HPV) Challenge program; exposure information/models; EPA's Chemical Assessment and Management program (ChAMP); EPA's Voluntary Children's Chemical Evaluation Program (VCCEP); Canada's Chemical Management Program (CMP); OECD's eChemPortal; and robust study summaries developed under the EU's Registration, Evaluation, and Assessment of Chemicals (REACH). If this information is insufficient to designate the priority of a batched chemical, EPA should issue a notice in the Federal Register for voluntary call-ins of the type of information needed for prioritization and request discussions with manufacturers and processors of the chemicals. If voluntary information is still inadequate to prioritize, EPA should consider issuing TSCA Section 8(a) or 8(d) rules to require manufacturers/processors to collect existing information needed to prioritize. Finally, if EPA makes a determination subject to Section 4 requirements that new information is necessary to prioritize (and explaining why), EPA may issue Section 4 rules, orders or consent agreements. EPA should also be held accountable to using that information. The testing/exposure information EPA requires to be developed through Section 4 must be tiered. Finally, throughout the information gathering step, EPA should be asking whether it needs to "iterate" the information gathering process for prioritization, i.e., ask itself whether additional information should be gathered to designate a chemical as a high or low priority and if so to obtain it through the information gathering step process. 3. Sufficient Information to Designate: If EPA concludes it has sufficient information to designate the priority of a substance it can move that substance to the "Initiation of prioritization" step. If EPA concludes it has sufficient information to designate a substance as a high priority chemical, it should conduct a "pre-screening" review to identify potential data/information needs for scoping the risk evaluation (a bridging step between prioritization and scoping). If information on the chemical is deemed sufficient for scoping, the high priority chemical can then be put into the queue for "initiation" of the prioritization process at the appropriate time. If information is determined not sufficient for scoping, EPA should begin to collect/develop necessary information to scope the risk evaluation. This information screening "bridge" step should help EPA meet the 6-month statutory deadline for scoping a risk evaluation. However, this step would not replace either scoping itself or the anticipated need for EPA to collect other information during scoping. Further, it is not anticipated that this 6 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 step will develop all the information it will need for risk evaluation. EPA will not necessarily know what information it may need for risk evaluation until it actually conducts it. 4. Initiate the Priority Designation: EPA must announce a candidate for prioritization and request "relevant information" about that chemical and provide 90 days for persons to submit that information to EPA. The LCSA deadlines for priority setting (no less than 9 months; no more than 12 months) begin at this step. EPA will "pace" its priority designations to be ready when risk evaluations are near completion and ready to be replaced with a new priority. 5. Propose Priority Designation: EPA must propose a designation of a chemical as a high or low priority, including the basis for its proposal, and provide a 90 day public comment period. 6. Finalize the Designation of High Priority or Low Priority Chemical: EPA must finalize its designation of the chemical as either a high or low priority within the statutory deadlines (no less than 9 months; no more than 12 months). Low priority chemical designations are final agency action, subject to judicial review. EPA must communicate final designations of high priority chemicals very carefully to prevent the creation of "red-lists" of chemicals and other mis-interpretations by states or the marketplace. To help EPA understand ACC's vision of the prioritization process, we have attempted to capture a simplified version of it in the flowchart below. (See comments' text for more details.) 7 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226

Who must propose a designation of a chemical as a high or low priority?

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jzbn0226_p0, jzbn0226_p1, jzbn0226_p2, jzbn0226_p3, jzbn0226_p4, jzbn0226_p5, jzbn0226_p6, jzbn0226_p7, jzbn0226_p8

EPA, The EPA

American° Chemistry Council March 20, 2017 Docket Control Office (7407M) Office of Pollution Prevention and Toxics (OPPT) U.S. Environmental Protection Agency 1200 Pennsylvania Ave., NW Washington, DC 20460-0001 Sent electronically to www.regulations.gov Docket ID# EPA-HQ-OPPT-2016-0636 Re: ACC Comments on EPA's Proposed Procedures for Prioritization of Chemicals for Risk Evaluation under the Toxic Substances Control Act as amended by the Lautenberg Chemical Safety Act Dear Sir/Madam: The American Chemistry Council (ACC¹ appreciates the opportunity to provide written comments to the Office of Chemical Safety and Pollution Prevention to inform the Agency's development of a prioritization process rule under the Toxic Substances Control Act (TSCA), as amended by the Lautenberg Chemical Safety Act (LCSA). ACC is committed to being a constructive stakeholder in the effective implementation of the LCSA and we provide these comments to assist the Agency in its development of a chemical evaluation and management program that is efficient, science-based, and consistent with the legal requirements of the LCSA. Prioritization is the first step in the LCSA's framework for evaluating active chemicals in commerce and the prioritization process rule must establish a risk-based screening process and criteria to identify high and low priority substances for risk evaluations under the LCSA. If you have any questions, please contact me at: 202-249-6403 or Sarah [email protected] Sincerely, Saraht. Brance Sarah Brozena Senior Director, Regulatory & Technical Affairs Cc: Jeffrey Morris, Director, OPPT Wendy Cleland Hamnett, OCSPP Ryan Schmit, OCSPP 1 The American Chemistry Council (ACC) represents the leading companies engaged in the business of chemistry. ACC members apply the science of chemistry to make innovative products and services that make people's lives better, healthier and safer. ACC is committed to improved environmental, health and safety performance through Responsible CareR, common sense advocacy designed to address major public policy issues, and health and environmental research and product testing. The business of chemistry is a $797 billion enterprise and a key element of the nation's economy. It is one of the nation's largest exporters, accounting for ten cents out of every dollar in U.S. exports. Chemistry companies are among the largest investors in research and development. Safety and security have always been primary concerns of ACC members, and they have intensified their efforts, working closely with government agencies to improve security and to defend against any threat to the nation's critical infrastructure. americanchemistry.com" 700 Second St., NE I Washington, DC 20002 I (202) 249.7000 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 American Chemistry Council American Chemistry Council Comments on EPA's Proposed Procedures for Prioritization of Chemicals for Risk Evaluation under the Toxic Substances Control Act as amended by the Lautenberg Chemical Safety Act Docket ID# EPA-HQ-OPPT-2016-0636 March 20, 2017 Sarah Brozena Senior Director, Regulatory & Technical Affairs American Chemistry Council 700 2nd Street, NE Washington DC 2002 (202) 249-6403 Sarah [email protected] americanchemistry.com 700 Second St., NE I Washington, DC 20002 I (202)249.7000 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Table of Contents EXECUTIVE SUMMARY 2 INTRODUCTION 4 I. ACC's Vision for a TSCA Prioritization Process Consistent with the LCSA 5 II. Overview of LCSA Prioritization Process Requirements 9 III. EPA Should Clarify Pre-Prioritization Step in Final Rule or Alternatively in Supplemental Rule 10 A. EPA Should Update Its TSCA Work Plan Criteria Before Using Them in Pre-Prioritization of Non-Work Plan Chemicals and Should Begin Planning to Integrate 21st Century Tools 11 B. EPA's Proposed Use of the Pre-Prioritization Step to Gather Information for Risk Evaluations Needs to Be Better Supported and Articulated 12 C. The Importance of Transparency in Prioritization Cannot Be Over-Emphasized 14 IV. EPA's Interpretation of Its Authority to Designate Low Priority Substances Is Short- Sighted, Contrary to Congressional Intent, Inconsistent with Best Available Science and Must Be Revised 15 A. EPA's Interpretation of Conditions of Use in the Prioritization Context Is a Strained Reading of the Statute and Contrary to Congressional Intent and Policy Objectives. 15 B. EPA's Abuse of Discretion Argument 16 C. EPA's Default to High Priority Designations Is Flawed Due to EPA's All Conditions of Use Interpretation. 17 D. Congress Authorized Ongoing Designations of Low Priority Chemicals 18 E. Best Available Risk-Based Scientific Procedures Enable EPA to Designate Low Priority Chemicals 18 V. Scientific Standards Must Be Referenced in the Prioritization Process Rule 19 A. Prioritization Decisions Must Be Based on Section 26 Standards for Best Available Science, Weight of the Scientific Evidence, and Transparency 19 B. EPA Should Address Other LCSA Science-Based Requirements in the Rule (Such As Tiered Testing and Animal Welfare Requirements). EPA Should Also Include a "Reserved" Placeholder in the Prioritization Rule for Incorporation of 21st Century Methods for Prioritization. 20 VI. Responses to EPA's Questions 20 A. Animal welfare requirements and scientific standards 20 B. EPA requests comments on its proposed process for prioritization overall. 21 C. Public input at pre-prioritization step 21 D. Consideration of substitutes in pre-prioritization 21 VII. Additional Specific Comments 22 A. Category of Chemical Substances 22 B. Inactive chemicals and new chemicals 22 C. Waivers 23 D. Definitions 23 E. Repopulation of High Priority Substances 24 VIII. Summary of ACC's Recommendations: 24 Attachment A 25 Attachment B 26 Attachment C 39 1 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 EXECUTIVE SUMMARY EPA has suggested four steps in its proposed rule to implement the prioritization requirements of Section 6(b) of the Toxic Substances Control Act (TSCA), as amended by the Frank R. Lautenberg Chemical Safety for the 21st Century Act: "Pre-prioritization" to narrow the pool of potential candidate substances Initiation of the prioritization process by identifying candidate substances and soliciting public comment Proposed priority designation, including an opportunity for public comment Priority designation The American Chemistry Council (ACC) has three major concerns with EPA's proposed prioritization process rule. Our concerns relate to the proposed pre-prioritization step, the treatment of low priority designations, and EPA's failure to address the LCSA Section 26 science standards in the rule. ACC's comments include specific recommendations to address these concerns. EPA's proposed prioritization process hinges on the "pre-prioritization" step. EPA does not fully and clearly describe this step, its statutory authority or limitations. Pre-prioritization is not mentioned in TSCA section 6(b) as amended. EPA asserts that the statute leaves it "broad discretion" to choose which chemicals on the TSCA Inventory to put into the prioritization process. However, EPA must exercise its discretion in a reasonable manner and is required to describe the statutory authorities for its exercise of discretion. EPA has not done so here. EPA intends the pre-prioritization step to inform prioritization decisions and the risk evaluation process, without regard to other relevant provisions of the statute. Because EPA asserts that it may need additional time to gather or develop information for risk evaluations, it has proposed to use the pre-prioritization step to gather information on substances with "insufficient information" for risk evaluation. ACC acknowledges that the statute imposes time constraints on the Agency once the prioritization process is triggered, but we believe that EPA has other tools available to address information needs in both the prioritization and risk evaluation stages in a timely, efficient manner. For example, in its pre-prioritization step EPA does not address the important relevant testing requirements of Section 4(a)(2)(A) or (B), the statement of need requirements of Section 4(a)(3) or the tiered testing requirements of Section 4(a)(4). As proposed, the pre-prioritization step conflates the prioritization and risk evaluation processes in ways that are confusing to the regulated community. Importantly, the pre-prioritization step appears contrary to congressional intent. In prioritization, it is very important that all substances be treated consistently, by the same transparent criteria, and that the process is replicable. Other than noting the statutory obligation to designate as high priorities the Work Plan chemicals that meet certain "preference" criteria, the proposed rule does not define the criteria or tools by which EPA will choose Work Plan and other chemicals from the active TSCA Inventory for the pre-prioritization or candidate "pool." EPA did not seek any stakeholder input on this question. EPA has not explained how many chemicals it proposes to include in the pre-prioritization or prioritization pool, or whether and how it will 2 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 "batch" chemicals to move them forward into the "initiation of prioritization" step. Although EPA has identified the nine criteria by which it proposes to narrow the pool into a list of candidates for prioritization, EPA does not define the criteria and or discuss the methodology by which these criteria will be applied. EPA proposes no timeframe for the pre-prioritization step, and provides little guidance on the status of chemicals included in pre-prioritization but excluded from prioritization. EPA's treatment of low priority chemicals raises significant concerns. EPA's proposal to require that low priority designations be based upon "all" conditions of use is a gross misinterpretation of the statute. This flawed interpretation of EPA's authority will cause the Agency to designate most chemicals in commerce as high priorities, and the Agency states as much in the preamble to the proposed rule. Congress did not intend this result. Low priority designations were seen as one mechanism to enhance public confidence in the safety of a chemical substance under its conditions of use, short of a full risk assessment. EPA has continuing authority to revise priority designations at any time based on new information. EPA has failed to include the LCSA Section 26 science standards in the prioritization process rule itself. EPA continues to assert that, while relevant to prioritization, EPA is not obliged to include these standards in the rule. ACC respectfully but strongly disagrees with EPA's reasoning. ACC's comments include a series of recommendations to address the shortcomings of the proposed prioritization process rule. Our recommendations describe: A transparent process for pooling and batching active chemicals in commerce for prioritization screening. A process to gather available information needed to reach a decision. A "bridging" step to permit EPA to assess the sufficiency of information for anticipated priority designations of candidate chemicals, which will inform the risk evaluation scoping process (should it be necessary). Revisions that recognize EPA's discretion to designate a low priority substance based on one, some or all conditions of use Identification of science-based criteria, tools and standards that apply in the prioritization process. 3 Source: :ttps://www.industrydocuments.ucsf.edu/docs/jzbn0226 American Chemistry Council Comments to U.S. Environmental Protection Agency on Its Proposed Procedures for Prioritization of Chemicals for Risk Evaluation under the Toxic Substances Control Act INTRODUCTION The American Chemistry Council (ACC) is pleased to provide the U.S. Environmental Protection Agency (EPA) these comments on the Agency's proposed procedures for prioritization of chemicals for risk evaluation under the Toxic Substances Control Act (TSCA) as amended by the Lautenberg Chemical Safety Act (LCSA). The LCSA requires EPA to establish, by rule, a risk-based screening process to identify high and low priority substances for risk evaluations under the LCSA. ACC strongly supported Congress's efforts to update and reform TSCA. One of ACC's principles for modernizing TSCA called on EPA to systematically prioritize chemicals for purposes of risk evaluations. Without a scientifically based prioritization process, EPA would not be able to meet efficiently the other requirements of the LCSA and achieve the objectives of TSCA reform that Congress intended. As discussed in more detail below, EPA's proposed prioritization process falls short. Congress designed the LCSA to allow chemicals to be systematically prioritized and then to evaluate those substances presenting the greatest potential risk. This design is apparent in every part of the LCSA. It begins with a reclassification of the full catalog of chemistries in U.S. commerce, the TSCA Inventory. The LCSA requires that the TSCA Inventory be sorted, so that chemicals that are currently active in commerce are separated from those no longer manufactured, imported or used; only chemicals that are active in commerce are subject to the prioritization and risk evaluation. This enables EPA to focus resources for its multi-year, time-and-resource intensive risk evaluations on chemicals that are actually in current use. EPA must next undertake a prioritization process, to inform the sequence of chemicals that will undergo risk evaluation. EPA must then undertake a formal scoping process, to define the conditions of use (and potentially exposed sub-populations relevant to the use) that will be included in the scope of the risk evaluation of the chemical. Prioritization of chemicals for various purposes is not new to the Agency. In 2011, EPA held a Stakeholder Dialogue on Prioritization and established a Discussion Blog for additional input on the topic. In our comments to that discussion blog, ACC identified several general principles for prioritization (Attachment A). We believe these principles are reflected in the LCSA requirements, in particular the LCSA's recognition that prioritization is a risk based screening process that integrates information on both hazard and exposure potential. In 2011, ACC developed a two-step quantitative and qualitative tool to "proof test" our prioritization principles (Attachment B). We presented our principles and our prioritization tool to EPA in 2011, as well as to other industry and NGO stakeholders at the time. In 2012, EPA published its methodology to identify chemicals for its TSCA Work 4 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Plan for Chemical Assessment (TSCA Work Plan) program. I. ACC's Vision for a TSCA Prioritization Process Consistent with the LCSA The LCSA requires EPA, by rule, to establish a risk-based screening process to designate chemicals as high or low priorities for risk evaluations. The LCSA includes criteria and considerations by which EPA must make these priority designations. To ensure EPA consistently has risk evaluations underway, the LCSA requires EPA to identify at least one new high priority for every risk evaluation that is completed. EPA's ability to designate additional priorities for 2 evaluation is limited only by the Agency's ability to complete risk evaluations in accordance with the deadlines established by Congress. Thus, Congress requires EPA to carefully choreograph the 3 identification of high priority substances for risk evaluations, in order to ensure that appropriate resources are available to complete the evaluations with the established deadlines. This implies a framework that efficiently coordinates EPA's prioritization process with EPA's risk evaluation process. ACC's vision for the prioritization process is one that enables EPA to meet all the requirements of the LCSA and congressional intent. Prioritization must be a risk based screening process in which EPA integrates hazard, use and exposure information to designate chemicals or categories of chemicals as either high or low priority for risk evaluations based on the criteria in Section 6. Information used to make prioritization decisions must be reasonably available; new information should be required through Section 4 tools only if EPA makes a determination pursuant to Section 4(a)(2)(B) that new information is necessary for prioritization. Prioritization designations must be based upon the science standards of LCSA Section 26, particularly best available science and weight of the scientific evidence. The basis for prioritization designations must be transparent and EPA's decisions must be communicated objectively and in neutral terms. ACC's vision of a prioritization process that meets these requirements includes six steps (see discussion below and the flowchart illustrating these steps on the next page and in Attachment C). ACC recommends that EPA clarify the needed timelines, criteria, tools, approaches and processes for these six steps, publish them for comment and include them in the final rule. Alternatively, EPA should propose these clarifications in a supplemental rule prior to the Agency's first application of the prioritization process. ACC's recommended six steps for the prioritization process are as follows: 1. Pool and Batch: EPA must "pool" active chemicals in commerce as candidates for designation as high or low priority for risk evaluation, based on transparent criteria/methods/approaches/tools and processes. EPA should then "batch" these candidates for information gathering. As EPA acknowledges in the "re-population" discussion of the preamble to the proposed rule4, the pace of EPA's completion of risk evaluations factors into the finalization of EPA's prioritization decisions. As a result, ACC expects that the number of candidates per "batch" for information gathering should be relatively small, at least in the early years of LCSA implementation. EPA's development of pools and batches should be subject to 2 15 U.S.C 1.2605(b)(3)(C) 3 15 U.S.C. 2605 (b)(2)(C) 4 82 Fed.Reg. 4825, 4833 (January 17, 2017). 5 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 estimated timeframes. 2. Information Gathering: Because Congress intended prioritization decisions to be based on reasonably available information, EPA should take a sequenced approach to information gathering on chemicals that EPA "batches" for prioritization. The sequenced steps should begin with EPA gathering reasonably available information about potential hazards, uses and potential exposure by relying upon sources such as read across/Quantitative Structure Activity Relationship (QSAR) information; Chemical Data Reporting (CDR) reports; EPA's CompTox Dashboard; High Production Volume (HPV) Challenge program; exposure information/models; EPA's Chemical Assessment and Management program (ChAMP); EPA's Voluntary Children's Chemical Evaluation Program (VCCEP); Canada's Chemical Management Program (CMP); OECD's eChemPortal; and robust study summaries developed under the EU's Registration, Evaluation, and Assessment of Chemicals (REACH). If this information is insufficient to designate the priority of a batched chemical, EPA should issue a notice in the Federal Register for voluntary call-ins of the type of information needed for prioritization and request discussions with manufacturers and processors of the chemicals. If voluntary information is still inadequate to prioritize, EPA should consider issuing TSCA Section 8(a) or 8(d) rules to require manufacturers/processors to collect existing information needed to prioritize. Finally, if EPA makes a determination subject to Section 4 requirements that new information is necessary to prioritize (and explaining why), EPA may issue Section 4 rules, orders or consent agreements. EPA should also be held accountable to using that information. The testing/exposure information EPA requires to be developed through Section 4 must be tiered. Finally, throughout the information gathering step, EPA should be asking whether it needs to "iterate" the information gathering process for prioritization, i.e., ask itself whether additional information should be gathered to designate a chemical as a high or low priority and if so to obtain it through the information gathering step process. 3. Sufficient Information to Designate: If EPA concludes it has sufficient information to designate the priority of a substance it can move that substance to the "Initiation of prioritization" step. If EPA concludes it has sufficient information to designate a substance as a high priority chemical, it should conduct a "pre-screening" review to identify potential data/information needs for scoping the risk evaluation (a bridging step between prioritization and scoping). If information on the chemical is deemed sufficient for scoping, the high priority chemical can then be put into the queue for "initiation" of the prioritization process at the appropriate time. If information is determined not sufficient for scoping, EPA should begin to collect/develop necessary information to scope the risk evaluation. This information screening "bridge" step should help EPA meet the 6-month statutory deadline for scoping a risk evaluation. However, this step would not replace either scoping itself or the anticipated need for EPA to collect other information during scoping. Further, it is not anticipated that this 6 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 step will develop all the information it will need for risk evaluation. EPA will not necessarily know what information it may need for risk evaluation until it actually conducts it. 4. Initiate the Priority Designation: EPA must announce a candidate for prioritization and request "relevant information" about that chemical and provide 90 days for persons to submit that information to EPA. The LCSA deadlines for priority setting (no less than 9 months; no more than 12 months) begin at this step. EPA will "pace" its priority designations to be ready when risk evaluations are near completion and ready to be replaced with a new priority. 5. Propose Priority Designation: EPA must propose a designation of a chemical as a high or low priority, including the basis for its proposal, and provide a 90 day public comment period. 6. Finalize the Designation of High Priority or Low Priority Chemical: EPA must finalize its designation of the chemical as either a high or low priority within the statutory deadlines (no less than 9 months; no more than 12 months). Low priority chemical designations are final agency action, subject to judicial review. EPA must communicate final designations of high priority chemicals very carefully to prevent the creation of "red-lists" of chemicals and other mis-interpretations by states or the marketplace. To help EPA understand ACC's vision of the prioritization process, we have attempted to capture a simplified version of it in the flowchart below. (See comments' text for more details.) 7 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226

Who initiates priority designation?

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jzbn0226_p0, jzbn0226_p1, jzbn0226_p2, jzbn0226_p3, jzbn0226_p4, jzbn0226_p5, jzbn0226_p6, jzbn0226_p7, jzbn0226_p8

EPA

American° Chemistry Council March 20, 2017 Docket Control Office (7407M) Office of Pollution Prevention and Toxics (OPPT) U.S. Environmental Protection Agency 1200 Pennsylvania Ave., NW Washington, DC 20460-0001 Sent electronically to www.regulations.gov Docket ID# EPA-HQ-OPPT-2016-0636 Re: ACC Comments on EPA's Proposed Procedures for Prioritization of Chemicals for Risk Evaluation under the Toxic Substances Control Act as amended by the Lautenberg Chemical Safety Act Dear Sir/Madam: The American Chemistry Council (ACC¹ appreciates the opportunity to provide written comments to the Office of Chemical Safety and Pollution Prevention to inform the Agency's development of a prioritization process rule under the Toxic Substances Control Act (TSCA), as amended by the Lautenberg Chemical Safety Act (LCSA). ACC is committed to being a constructive stakeholder in the effective implementation of the LCSA and we provide these comments to assist the Agency in its development of a chemical evaluation and management program that is efficient, science-based, and consistent with the legal requirements of the LCSA. Prioritization is the first step in the LCSA's framework for evaluating active chemicals in commerce and the prioritization process rule must establish a risk-based screening process and criteria to identify high and low priority substances for risk evaluations under the LCSA. If you have any questions, please contact me at: 202-249-6403 or Sarah [email protected] Sincerely, Saraht. Brance Sarah Brozena Senior Director, Regulatory & Technical Affairs Cc: Jeffrey Morris, Director, OPPT Wendy Cleland Hamnett, OCSPP Ryan Schmit, OCSPP 1 The American Chemistry Council (ACC) represents the leading companies engaged in the business of chemistry. ACC members apply the science of chemistry to make innovative products and services that make people's lives better, healthier and safer. ACC is committed to improved environmental, health and safety performance through Responsible CareR, common sense advocacy designed to address major public policy issues, and health and environmental research and product testing. The business of chemistry is a $797 billion enterprise and a key element of the nation's economy. It is one of the nation's largest exporters, accounting for ten cents out of every dollar in U.S. exports. Chemistry companies are among the largest investors in research and development. Safety and security have always been primary concerns of ACC members, and they have intensified their efforts, working closely with government agencies to improve security and to defend against any threat to the nation's critical infrastructure. americanchemistry.com" 700 Second St., NE I Washington, DC 20002 I (202) 249.7000 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 American Chemistry Council American Chemistry Council Comments on EPA's Proposed Procedures for Prioritization of Chemicals for Risk Evaluation under the Toxic Substances Control Act as amended by the Lautenberg Chemical Safety Act Docket ID# EPA-HQ-OPPT-2016-0636 March 20, 2017 Sarah Brozena Senior Director, Regulatory & Technical Affairs American Chemistry Council 700 2nd Street, NE Washington DC 2002 (202) 249-6403 Sarah [email protected] americanchemistry.com 700 Second St., NE I Washington, DC 20002 I (202)249.7000 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Table of Contents EXECUTIVE SUMMARY 2 INTRODUCTION 4 I. ACC's Vision for a TSCA Prioritization Process Consistent with the LCSA 5 II. Overview of LCSA Prioritization Process Requirements 9 III. EPA Should Clarify Pre-Prioritization Step in Final Rule or Alternatively in Supplemental Rule 10 A. EPA Should Update Its TSCA Work Plan Criteria Before Using Them in Pre-Prioritization of Non-Work Plan Chemicals and Should Begin Planning to Integrate 21st Century Tools 11 B. EPA's Proposed Use of the Pre-Prioritization Step to Gather Information for Risk Evaluations Needs to Be Better Supported and Articulated 12 C. The Importance of Transparency in Prioritization Cannot Be Over-Emphasized 14 IV. EPA's Interpretation of Its Authority to Designate Low Priority Substances Is Short- Sighted, Contrary to Congressional Intent, Inconsistent with Best Available Science and Must Be Revised 15 A. EPA's Interpretation of Conditions of Use in the Prioritization Context Is a Strained Reading of the Statute and Contrary to Congressional Intent and Policy Objectives. 15 B. EPA's Abuse of Discretion Argument 16 C. EPA's Default to High Priority Designations Is Flawed Due to EPA's All Conditions of Use Interpretation. 17 D. Congress Authorized Ongoing Designations of Low Priority Chemicals 18 E. Best Available Risk-Based Scientific Procedures Enable EPA to Designate Low Priority Chemicals 18 V. Scientific Standards Must Be Referenced in the Prioritization Process Rule 19 A. Prioritization Decisions Must Be Based on Section 26 Standards for Best Available Science, Weight of the Scientific Evidence, and Transparency 19 B. EPA Should Address Other LCSA Science-Based Requirements in the Rule (Such As Tiered Testing and Animal Welfare Requirements). EPA Should Also Include a "Reserved" Placeholder in the Prioritization Rule for Incorporation of 21st Century Methods for Prioritization. 20 VI. Responses to EPA's Questions 20 A. Animal welfare requirements and scientific standards 20 B. EPA requests comments on its proposed process for prioritization overall. 21 C. Public input at pre-prioritization step 21 D. Consideration of substitutes in pre-prioritization 21 VII. Additional Specific Comments 22 A. Category of Chemical Substances 22 B. Inactive chemicals and new chemicals 22 C. Waivers 23 D. Definitions 23 E. Repopulation of High Priority Substances 24 VIII. Summary of ACC's Recommendations: 24 Attachment A 25 Attachment B 26 Attachment C 39 1 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 EXECUTIVE SUMMARY EPA has suggested four steps in its proposed rule to implement the prioritization requirements of Section 6(b) of the Toxic Substances Control Act (TSCA), as amended by the Frank R. Lautenberg Chemical Safety for the 21st Century Act: "Pre-prioritization" to narrow the pool of potential candidate substances Initiation of the prioritization process by identifying candidate substances and soliciting public comment Proposed priority designation, including an opportunity for public comment Priority designation The American Chemistry Council (ACC) has three major concerns with EPA's proposed prioritization process rule. Our concerns relate to the proposed pre-prioritization step, the treatment of low priority designations, and EPA's failure to address the LCSA Section 26 science standards in the rule. ACC's comments include specific recommendations to address these concerns. EPA's proposed prioritization process hinges on the "pre-prioritization" step. EPA does not fully and clearly describe this step, its statutory authority or limitations. Pre-prioritization is not mentioned in TSCA section 6(b) as amended. EPA asserts that the statute leaves it "broad discretion" to choose which chemicals on the TSCA Inventory to put into the prioritization process. However, EPA must exercise its discretion in a reasonable manner and is required to describe the statutory authorities for its exercise of discretion. EPA has not done so here. EPA intends the pre-prioritization step to inform prioritization decisions and the risk evaluation process, without regard to other relevant provisions of the statute. Because EPA asserts that it may need additional time to gather or develop information for risk evaluations, it has proposed to use the pre-prioritization step to gather information on substances with "insufficient information" for risk evaluation. ACC acknowledges that the statute imposes time constraints on the Agency once the prioritization process is triggered, but we believe that EPA has other tools available to address information needs in both the prioritization and risk evaluation stages in a timely, efficient manner. For example, in its pre-prioritization step EPA does not address the important relevant testing requirements of Section 4(a)(2)(A) or (B), the statement of need requirements of Section 4(a)(3) or the tiered testing requirements of Section 4(a)(4). As proposed, the pre-prioritization step conflates the prioritization and risk evaluation processes in ways that are confusing to the regulated community. Importantly, the pre-prioritization step appears contrary to congressional intent. In prioritization, it is very important that all substances be treated consistently, by the same transparent criteria, and that the process is replicable. Other than noting the statutory obligation to designate as high priorities the Work Plan chemicals that meet certain "preference" criteria, the proposed rule does not define the criteria or tools by which EPA will choose Work Plan and other chemicals from the active TSCA Inventory for the pre-prioritization or candidate "pool." EPA did not seek any stakeholder input on this question. EPA has not explained how many chemicals it proposes to include in the pre-prioritization or prioritization pool, or whether and how it will 2 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 "batch" chemicals to move them forward into the "initiation of prioritization" step. Although EPA has identified the nine criteria by which it proposes to narrow the pool into a list of candidates for prioritization, EPA does not define the criteria and or discuss the methodology by which these criteria will be applied. EPA proposes no timeframe for the pre-prioritization step, and provides little guidance on the status of chemicals included in pre-prioritization but excluded from prioritization. EPA's treatment of low priority chemicals raises significant concerns. EPA's proposal to require that low priority designations be based upon "all" conditions of use is a gross misinterpretation of the statute. This flawed interpretation of EPA's authority will cause the Agency to designate most chemicals in commerce as high priorities, and the Agency states as much in the preamble to the proposed rule. Congress did not intend this result. Low priority designations were seen as one mechanism to enhance public confidence in the safety of a chemical substance under its conditions of use, short of a full risk assessment. EPA has continuing authority to revise priority designations at any time based on new information. EPA has failed to include the LCSA Section 26 science standards in the prioritization process rule itself. EPA continues to assert that, while relevant to prioritization, EPA is not obliged to include these standards in the rule. ACC respectfully but strongly disagrees with EPA's reasoning. ACC's comments include a series of recommendations to address the shortcomings of the proposed prioritization process rule. Our recommendations describe: A transparent process for pooling and batching active chemicals in commerce for prioritization screening. A process to gather available information needed to reach a decision. A "bridging" step to permit EPA to assess the sufficiency of information for anticipated priority designations of candidate chemicals, which will inform the risk evaluation scoping process (should it be necessary). Revisions that recognize EPA's discretion to designate a low priority substance based on one, some or all conditions of use Identification of science-based criteria, tools and standards that apply in the prioritization process. 3 Source: :ttps://www.industrydocuments.ucsf.edu/docs/jzbn0226 American Chemistry Council Comments to U.S. Environmental Protection Agency on Its Proposed Procedures for Prioritization of Chemicals for Risk Evaluation under the Toxic Substances Control Act INTRODUCTION The American Chemistry Council (ACC) is pleased to provide the U.S. Environmental Protection Agency (EPA) these comments on the Agency's proposed procedures for prioritization of chemicals for risk evaluation under the Toxic Substances Control Act (TSCA) as amended by the Lautenberg Chemical Safety Act (LCSA). The LCSA requires EPA to establish, by rule, a risk-based screening process to identify high and low priority substances for risk evaluations under the LCSA. ACC strongly supported Congress's efforts to update and reform TSCA. One of ACC's principles for modernizing TSCA called on EPA to systematically prioritize chemicals for purposes of risk evaluations. Without a scientifically based prioritization process, EPA would not be able to meet efficiently the other requirements of the LCSA and achieve the objectives of TSCA reform that Congress intended. As discussed in more detail below, EPA's proposed prioritization process falls short. Congress designed the LCSA to allow chemicals to be systematically prioritized and then to evaluate those substances presenting the greatest potential risk. This design is apparent in every part of the LCSA. It begins with a reclassification of the full catalog of chemistries in U.S. commerce, the TSCA Inventory. The LCSA requires that the TSCA Inventory be sorted, so that chemicals that are currently active in commerce are separated from those no longer manufactured, imported or used; only chemicals that are active in commerce are subject to the prioritization and risk evaluation. This enables EPA to focus resources for its multi-year, time-and-resource intensive risk evaluations on chemicals that are actually in current use. EPA must next undertake a prioritization process, to inform the sequence of chemicals that will undergo risk evaluation. EPA must then undertake a formal scoping process, to define the conditions of use (and potentially exposed sub-populations relevant to the use) that will be included in the scope of the risk evaluation of the chemical. Prioritization of chemicals for various purposes is not new to the Agency. In 2011, EPA held a Stakeholder Dialogue on Prioritization and established a Discussion Blog for additional input on the topic. In our comments to that discussion blog, ACC identified several general principles for prioritization (Attachment A). We believe these principles are reflected in the LCSA requirements, in particular the LCSA's recognition that prioritization is a risk based screening process that integrates information on both hazard and exposure potential. In 2011, ACC developed a two-step quantitative and qualitative tool to "proof test" our prioritization principles (Attachment B). We presented our principles and our prioritization tool to EPA in 2011, as well as to other industry and NGO stakeholders at the time. In 2012, EPA published its methodology to identify chemicals for its TSCA Work 4 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Plan for Chemical Assessment (TSCA Work Plan) program. I. ACC's Vision for a TSCA Prioritization Process Consistent with the LCSA The LCSA requires EPA, by rule, to establish a risk-based screening process to designate chemicals as high or low priorities for risk evaluations. The LCSA includes criteria and considerations by which EPA must make these priority designations. To ensure EPA consistently has risk evaluations underway, the LCSA requires EPA to identify at least one new high priority for every risk evaluation that is completed. EPA's ability to designate additional priorities for 2 evaluation is limited only by the Agency's ability to complete risk evaluations in accordance with the deadlines established by Congress. Thus, Congress requires EPA to carefully choreograph the 3 identification of high priority substances for risk evaluations, in order to ensure that appropriate resources are available to complete the evaluations with the established deadlines. This implies a framework that efficiently coordinates EPA's prioritization process with EPA's risk evaluation process. ACC's vision for the prioritization process is one that enables EPA to meet all the requirements of the LCSA and congressional intent. Prioritization must be a risk based screening process in which EPA integrates hazard, use and exposure information to designate chemicals or categories of chemicals as either high or low priority for risk evaluations based on the criteria in Section 6. Information used to make prioritization decisions must be reasonably available; new information should be required through Section 4 tools only if EPA makes a determination pursuant to Section 4(a)(2)(B) that new information is necessary for prioritization. Prioritization designations must be based upon the science standards of LCSA Section 26, particularly best available science and weight of the scientific evidence. The basis for prioritization designations must be transparent and EPA's decisions must be communicated objectively and in neutral terms. ACC's vision of a prioritization process that meets these requirements includes six steps (see discussion below and the flowchart illustrating these steps on the next page and in Attachment C). ACC recommends that EPA clarify the needed timelines, criteria, tools, approaches and processes for these six steps, publish them for comment and include them in the final rule. Alternatively, EPA should propose these clarifications in a supplemental rule prior to the Agency's first application of the prioritization process. ACC's recommended six steps for the prioritization process are as follows: 1. Pool and Batch: EPA must "pool" active chemicals in commerce as candidates for designation as high or low priority for risk evaluation, based on transparent criteria/methods/approaches/tools and processes. EPA should then "batch" these candidates for information gathering. As EPA acknowledges in the "re-population" discussion of the preamble to the proposed rule4, the pace of EPA's completion of risk evaluations factors into the finalization of EPA's prioritization decisions. As a result, ACC expects that the number of candidates per "batch" for information gathering should be relatively small, at least in the early years of LCSA implementation. EPA's development of pools and batches should be subject to 2 15 U.S.C 1.2605(b)(3)(C) 3 15 U.S.C. 2605 (b)(2)(C) 4 82 Fed.Reg. 4825, 4833 (January 17, 2017). 5 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 estimated timeframes. 2. Information Gathering: Because Congress intended prioritization decisions to be based on reasonably available information, EPA should take a sequenced approach to information gathering on chemicals that EPA "batches" for prioritization. The sequenced steps should begin with EPA gathering reasonably available information about potential hazards, uses and potential exposure by relying upon sources such as read across/Quantitative Structure Activity Relationship (QSAR) information; Chemical Data Reporting (CDR) reports; EPA's CompTox Dashboard; High Production Volume (HPV) Challenge program; exposure information/models; EPA's Chemical Assessment and Management program (ChAMP); EPA's Voluntary Children's Chemical Evaluation Program (VCCEP); Canada's Chemical Management Program (CMP); OECD's eChemPortal; and robust study summaries developed under the EU's Registration, Evaluation, and Assessment of Chemicals (REACH). If this information is insufficient to designate the priority of a batched chemical, EPA should issue a notice in the Federal Register for voluntary call-ins of the type of information needed for prioritization and request discussions with manufacturers and processors of the chemicals. If voluntary information is still inadequate to prioritize, EPA should consider issuing TSCA Section 8(a) or 8(d) rules to require manufacturers/processors to collect existing information needed to prioritize. Finally, if EPA makes a determination subject to Section 4 requirements that new information is necessary to prioritize (and explaining why), EPA may issue Section 4 rules, orders or consent agreements. EPA should also be held accountable to using that information. The testing/exposure information EPA requires to be developed through Section 4 must be tiered. Finally, throughout the information gathering step, EPA should be asking whether it needs to "iterate" the information gathering process for prioritization, i.e., ask itself whether additional information should be gathered to designate a chemical as a high or low priority and if so to obtain it through the information gathering step process. 3. Sufficient Information to Designate: If EPA concludes it has sufficient information to designate the priority of a substance it can move that substance to the "Initiation of prioritization" step. If EPA concludes it has sufficient information to designate a substance as a high priority chemical, it should conduct a "pre-screening" review to identify potential data/information needs for scoping the risk evaluation (a bridging step between prioritization and scoping). If information on the chemical is deemed sufficient for scoping, the high priority chemical can then be put into the queue for "initiation" of the prioritization process at the appropriate time. If information is determined not sufficient for scoping, EPA should begin to collect/develop necessary information to scope the risk evaluation. This information screening "bridge" step should help EPA meet the 6-month statutory deadline for scoping a risk evaluation. However, this step would not replace either scoping itself or the anticipated need for EPA to collect other information during scoping. Further, it is not anticipated that this 6 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 step will develop all the information it will need for risk evaluation. EPA will not necessarily know what information it may need for risk evaluation until it actually conducts it. 4. Initiate the Priority Designation: EPA must announce a candidate for prioritization and request "relevant information" about that chemical and provide 90 days for persons to submit that information to EPA. The LCSA deadlines for priority setting (no less than 9 months; no more than 12 months) begin at this step. EPA will "pace" its priority designations to be ready when risk evaluations are near completion and ready to be replaced with a new priority. 5. Propose Priority Designation: EPA must propose a designation of a chemical as a high or low priority, including the basis for its proposal, and provide a 90 day public comment period. 6. Finalize the Designation of High Priority or Low Priority Chemical: EPA must finalize its designation of the chemical as either a high or low priority within the statutory deadlines (no less than 9 months; no more than 12 months). Low priority chemical designations are final agency action, subject to judicial review. EPA must communicate final designations of high priority chemicals very carefully to prevent the creation of "red-lists" of chemicals and other mis-interpretations by states or the marketplace. To help EPA understand ACC's vision of the prioritization process, we have attempted to capture a simplified version of it in the flowchart below. (See comments' text for more details.) 7 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226

How long is the public comment period?

jzbn0226

jzbn0226_p0, jzbn0226_p1, jzbn0226_p2, jzbn0226_p3, jzbn0226_p4, jzbn0226_p5, jzbn0226_p6, jzbn0226_p7, jzbn0226_p8

90 day, 90 day public comment period

American° Chemistry Council March 20, 2017 Docket Control Office (7407M) Office of Pollution Prevention and Toxics (OPPT) U.S. Environmental Protection Agency 1200 Pennsylvania Ave., NW Washington, DC 20460-0001 Sent electronically to www.regulations.gov Docket ID# EPA-HQ-OPPT-2016-0636 Re: ACC Comments on EPA's Proposed Procedures for Prioritization of Chemicals for Risk Evaluation under the Toxic Substances Control Act as amended by the Lautenberg Chemical Safety Act Dear Sir/Madam: The American Chemistry Council (ACC¹ appreciates the opportunity to provide written comments to the Office of Chemical Safety and Pollution Prevention to inform the Agency's development of a prioritization process rule under the Toxic Substances Control Act (TSCA), as amended by the Lautenberg Chemical Safety Act (LCSA). ACC is committed to being a constructive stakeholder in the effective implementation of the LCSA and we provide these comments to assist the Agency in its development of a chemical evaluation and management program that is efficient, science-based, and consistent with the legal requirements of the LCSA. Prioritization is the first step in the LCSA's framework for evaluating active chemicals in commerce and the prioritization process rule must establish a risk-based screening process and criteria to identify high and low priority substances for risk evaluations under the LCSA. If you have any questions, please contact me at: 202-249-6403 or Sarah [email protected] Sincerely, Saraht. Brance Sarah Brozena Senior Director, Regulatory & Technical Affairs Cc: Jeffrey Morris, Director, OPPT Wendy Cleland Hamnett, OCSPP Ryan Schmit, OCSPP 1 The American Chemistry Council (ACC) represents the leading companies engaged in the business of chemistry. ACC members apply the science of chemistry to make innovative products and services that make people's lives better, healthier and safer. ACC is committed to improved environmental, health and safety performance through Responsible CareR, common sense advocacy designed to address major public policy issues, and health and environmental research and product testing. The business of chemistry is a $797 billion enterprise and a key element of the nation's economy. It is one of the nation's largest exporters, accounting for ten cents out of every dollar in U.S. exports. Chemistry companies are among the largest investors in research and development. Safety and security have always been primary concerns of ACC members, and they have intensified their efforts, working closely with government agencies to improve security and to defend against any threat to the nation's critical infrastructure. americanchemistry.com" 700 Second St., NE I Washington, DC 20002 I (202) 249.7000 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 American Chemistry Council American Chemistry Council Comments on EPA's Proposed Procedures for Prioritization of Chemicals for Risk Evaluation under the Toxic Substances Control Act as amended by the Lautenberg Chemical Safety Act Docket ID# EPA-HQ-OPPT-2016-0636 March 20, 2017 Sarah Brozena Senior Director, Regulatory & Technical Affairs American Chemistry Council 700 2nd Street, NE Washington DC 2002 (202) 249-6403 Sarah [email protected] americanchemistry.com 700 Second St., NE I Washington, DC 20002 I (202)249.7000 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Table of Contents EXECUTIVE SUMMARY 2 INTRODUCTION 4 I. ACC's Vision for a TSCA Prioritization Process Consistent with the LCSA 5 II. Overview of LCSA Prioritization Process Requirements 9 III. EPA Should Clarify Pre-Prioritization Step in Final Rule or Alternatively in Supplemental Rule 10 A. EPA Should Update Its TSCA Work Plan Criteria Before Using Them in Pre-Prioritization of Non-Work Plan Chemicals and Should Begin Planning to Integrate 21st Century Tools 11 B. EPA's Proposed Use of the Pre-Prioritization Step to Gather Information for Risk Evaluations Needs to Be Better Supported and Articulated 12 C. The Importance of Transparency in Prioritization Cannot Be Over-Emphasized 14 IV. EPA's Interpretation of Its Authority to Designate Low Priority Substances Is Short- Sighted, Contrary to Congressional Intent, Inconsistent with Best Available Science and Must Be Revised 15 A. EPA's Interpretation of Conditions of Use in the Prioritization Context Is a Strained Reading of the Statute and Contrary to Congressional Intent and Policy Objectives. 15 B. EPA's Abuse of Discretion Argument 16 C. EPA's Default to High Priority Designations Is Flawed Due to EPA's All Conditions of Use Interpretation. 17 D. Congress Authorized Ongoing Designations of Low Priority Chemicals 18 E. Best Available Risk-Based Scientific Procedures Enable EPA to Designate Low Priority Chemicals 18 V. Scientific Standards Must Be Referenced in the Prioritization Process Rule 19 A. Prioritization Decisions Must Be Based on Section 26 Standards for Best Available Science, Weight of the Scientific Evidence, and Transparency 19 B. EPA Should Address Other LCSA Science-Based Requirements in the Rule (Such As Tiered Testing and Animal Welfare Requirements). EPA Should Also Include a "Reserved" Placeholder in the Prioritization Rule for Incorporation of 21st Century Methods for Prioritization. 20 VI. Responses to EPA's Questions 20 A. Animal welfare requirements and scientific standards 20 B. EPA requests comments on its proposed process for prioritization overall. 21 C. Public input at pre-prioritization step 21 D. Consideration of substitutes in pre-prioritization 21 VII. Additional Specific Comments 22 A. Category of Chemical Substances 22 B. Inactive chemicals and new chemicals 22 C. Waivers 23 D. Definitions 23 E. Repopulation of High Priority Substances 24 VIII. Summary of ACC's Recommendations: 24 Attachment A 25 Attachment B 26 Attachment C 39 1 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 EXECUTIVE SUMMARY EPA has suggested four steps in its proposed rule to implement the prioritization requirements of Section 6(b) of the Toxic Substances Control Act (TSCA), as amended by the Frank R. Lautenberg Chemical Safety for the 21st Century Act: "Pre-prioritization" to narrow the pool of potential candidate substances Initiation of the prioritization process by identifying candidate substances and soliciting public comment Proposed priority designation, including an opportunity for public comment Priority designation The American Chemistry Council (ACC) has three major concerns with EPA's proposed prioritization process rule. Our concerns relate to the proposed pre-prioritization step, the treatment of low priority designations, and EPA's failure to address the LCSA Section 26 science standards in the rule. ACC's comments include specific recommendations to address these concerns. EPA's proposed prioritization process hinges on the "pre-prioritization" step. EPA does not fully and clearly describe this step, its statutory authority or limitations. Pre-prioritization is not mentioned in TSCA section 6(b) as amended. EPA asserts that the statute leaves it "broad discretion" to choose which chemicals on the TSCA Inventory to put into the prioritization process. However, EPA must exercise its discretion in a reasonable manner and is required to describe the statutory authorities for its exercise of discretion. EPA has not done so here. EPA intends the pre-prioritization step to inform prioritization decisions and the risk evaluation process, without regard to other relevant provisions of the statute. Because EPA asserts that it may need additional time to gather or develop information for risk evaluations, it has proposed to use the pre-prioritization step to gather information on substances with "insufficient information" for risk evaluation. ACC acknowledges that the statute imposes time constraints on the Agency once the prioritization process is triggered, but we believe that EPA has other tools available to address information needs in both the prioritization and risk evaluation stages in a timely, efficient manner. For example, in its pre-prioritization step EPA does not address the important relevant testing requirements of Section 4(a)(2)(A) or (B), the statement of need requirements of Section 4(a)(3) or the tiered testing requirements of Section 4(a)(4). As proposed, the pre-prioritization step conflates the prioritization and risk evaluation processes in ways that are confusing to the regulated community. Importantly, the pre-prioritization step appears contrary to congressional intent. In prioritization, it is very important that all substances be treated consistently, by the same transparent criteria, and that the process is replicable. Other than noting the statutory obligation to designate as high priorities the Work Plan chemicals that meet certain "preference" criteria, the proposed rule does not define the criteria or tools by which EPA will choose Work Plan and other chemicals from the active TSCA Inventory for the pre-prioritization or candidate "pool." EPA did not seek any stakeholder input on this question. EPA has not explained how many chemicals it proposes to include in the pre-prioritization or prioritization pool, or whether and how it will 2 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 "batch" chemicals to move them forward into the "initiation of prioritization" step. Although EPA has identified the nine criteria by which it proposes to narrow the pool into a list of candidates for prioritization, EPA does not define the criteria and or discuss the methodology by which these criteria will be applied. EPA proposes no timeframe for the pre-prioritization step, and provides little guidance on the status of chemicals included in pre-prioritization but excluded from prioritization. EPA's treatment of low priority chemicals raises significant concerns. EPA's proposal to require that low priority designations be based upon "all" conditions of use is a gross misinterpretation of the statute. This flawed interpretation of EPA's authority will cause the Agency to designate most chemicals in commerce as high priorities, and the Agency states as much in the preamble to the proposed rule. Congress did not intend this result. Low priority designations were seen as one mechanism to enhance public confidence in the safety of a chemical substance under its conditions of use, short of a full risk assessment. EPA has continuing authority to revise priority designations at any time based on new information. EPA has failed to include the LCSA Section 26 science standards in the prioritization process rule itself. EPA continues to assert that, while relevant to prioritization, EPA is not obliged to include these standards in the rule. ACC respectfully but strongly disagrees with EPA's reasoning. ACC's comments include a series of recommendations to address the shortcomings of the proposed prioritization process rule. Our recommendations describe: A transparent process for pooling and batching active chemicals in commerce for prioritization screening. A process to gather available information needed to reach a decision. A "bridging" step to permit EPA to assess the sufficiency of information for anticipated priority designations of candidate chemicals, which will inform the risk evaluation scoping process (should it be necessary). Revisions that recognize EPA's discretion to designate a low priority substance based on one, some or all conditions of use Identification of science-based criteria, tools and standards that apply in the prioritization process. 3 Source: :ttps://www.industrydocuments.ucsf.edu/docs/jzbn0226 American Chemistry Council Comments to U.S. Environmental Protection Agency on Its Proposed Procedures for Prioritization of Chemicals for Risk Evaluation under the Toxic Substances Control Act INTRODUCTION The American Chemistry Council (ACC) is pleased to provide the U.S. Environmental Protection Agency (EPA) these comments on the Agency's proposed procedures for prioritization of chemicals for risk evaluation under the Toxic Substances Control Act (TSCA) as amended by the Lautenberg Chemical Safety Act (LCSA). The LCSA requires EPA to establish, by rule, a risk-based screening process to identify high and low priority substances for risk evaluations under the LCSA. ACC strongly supported Congress's efforts to update and reform TSCA. One of ACC's principles for modernizing TSCA called on EPA to systematically prioritize chemicals for purposes of risk evaluations. Without a scientifically based prioritization process, EPA would not be able to meet efficiently the other requirements of the LCSA and achieve the objectives of TSCA reform that Congress intended. As discussed in more detail below, EPA's proposed prioritization process falls short. Congress designed the LCSA to allow chemicals to be systematically prioritized and then to evaluate those substances presenting the greatest potential risk. This design is apparent in every part of the LCSA. It begins with a reclassification of the full catalog of chemistries in U.S. commerce, the TSCA Inventory. The LCSA requires that the TSCA Inventory be sorted, so that chemicals that are currently active in commerce are separated from those no longer manufactured, imported or used; only chemicals that are active in commerce are subject to the prioritization and risk evaluation. This enables EPA to focus resources for its multi-year, time-and-resource intensive risk evaluations on chemicals that are actually in current use. EPA must next undertake a prioritization process, to inform the sequence of chemicals that will undergo risk evaluation. EPA must then undertake a formal scoping process, to define the conditions of use (and potentially exposed sub-populations relevant to the use) that will be included in the scope of the risk evaluation of the chemical. Prioritization of chemicals for various purposes is not new to the Agency. In 2011, EPA held a Stakeholder Dialogue on Prioritization and established a Discussion Blog for additional input on the topic. In our comments to that discussion blog, ACC identified several general principles for prioritization (Attachment A). We believe these principles are reflected in the LCSA requirements, in particular the LCSA's recognition that prioritization is a risk based screening process that integrates information on both hazard and exposure potential. In 2011, ACC developed a two-step quantitative and qualitative tool to "proof test" our prioritization principles (Attachment B). We presented our principles and our prioritization tool to EPA in 2011, as well as to other industry and NGO stakeholders at the time. In 2012, EPA published its methodology to identify chemicals for its TSCA Work 4 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Plan for Chemical Assessment (TSCA Work Plan) program. I. ACC's Vision for a TSCA Prioritization Process Consistent with the LCSA The LCSA requires EPA, by rule, to establish a risk-based screening process to designate chemicals as high or low priorities for risk evaluations. The LCSA includes criteria and considerations by which EPA must make these priority designations. To ensure EPA consistently has risk evaluations underway, the LCSA requires EPA to identify at least one new high priority for every risk evaluation that is completed. EPA's ability to designate additional priorities for 2 evaluation is limited only by the Agency's ability to complete risk evaluations in accordance with the deadlines established by Congress. Thus, Congress requires EPA to carefully choreograph the 3 identification of high priority substances for risk evaluations, in order to ensure that appropriate resources are available to complete the evaluations with the established deadlines. This implies a framework that efficiently coordinates EPA's prioritization process with EPA's risk evaluation process. ACC's vision for the prioritization process is one that enables EPA to meet all the requirements of the LCSA and congressional intent. Prioritization must be a risk based screening process in which EPA integrates hazard, use and exposure information to designate chemicals or categories of chemicals as either high or low priority for risk evaluations based on the criteria in Section 6. Information used to make prioritization decisions must be reasonably available; new information should be required through Section 4 tools only if EPA makes a determination pursuant to Section 4(a)(2)(B) that new information is necessary for prioritization. Prioritization designations must be based upon the science standards of LCSA Section 26, particularly best available science and weight of the scientific evidence. The basis for prioritization designations must be transparent and EPA's decisions must be communicated objectively and in neutral terms. ACC's vision of a prioritization process that meets these requirements includes six steps (see discussion below and the flowchart illustrating these steps on the next page and in Attachment C). ACC recommends that EPA clarify the needed timelines, criteria, tools, approaches and processes for these six steps, publish them for comment and include them in the final rule. Alternatively, EPA should propose these clarifications in a supplemental rule prior to the Agency's first application of the prioritization process. ACC's recommended six steps for the prioritization process are as follows: 1. Pool and Batch: EPA must "pool" active chemicals in commerce as candidates for designation as high or low priority for risk evaluation, based on transparent criteria/methods/approaches/tools and processes. EPA should then "batch" these candidates for information gathering. As EPA acknowledges in the "re-population" discussion of the preamble to the proposed rule4, the pace of EPA's completion of risk evaluations factors into the finalization of EPA's prioritization decisions. As a result, ACC expects that the number of candidates per "batch" for information gathering should be relatively small, at least in the early years of LCSA implementation. EPA's development of pools and batches should be subject to 2 15 U.S.C 1.2605(b)(3)(C) 3 15 U.S.C. 2605 (b)(2)(C) 4 82 Fed.Reg. 4825, 4833 (January 17, 2017). 5 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 estimated timeframes. 2. Information Gathering: Because Congress intended prioritization decisions to be based on reasonably available information, EPA should take a sequenced approach to information gathering on chemicals that EPA "batches" for prioritization. The sequenced steps should begin with EPA gathering reasonably available information about potential hazards, uses and potential exposure by relying upon sources such as read across/Quantitative Structure Activity Relationship (QSAR) information; Chemical Data Reporting (CDR) reports; EPA's CompTox Dashboard; High Production Volume (HPV) Challenge program; exposure information/models; EPA's Chemical Assessment and Management program (ChAMP); EPA's Voluntary Children's Chemical Evaluation Program (VCCEP); Canada's Chemical Management Program (CMP); OECD's eChemPortal; and robust study summaries developed under the EU's Registration, Evaluation, and Assessment of Chemicals (REACH). If this information is insufficient to designate the priority of a batched chemical, EPA should issue a notice in the Federal Register for voluntary call-ins of the type of information needed for prioritization and request discussions with manufacturers and processors of the chemicals. If voluntary information is still inadequate to prioritize, EPA should consider issuing TSCA Section 8(a) or 8(d) rules to require manufacturers/processors to collect existing information needed to prioritize. Finally, if EPA makes a determination subject to Section 4 requirements that new information is necessary to prioritize (and explaining why), EPA may issue Section 4 rules, orders or consent agreements. EPA should also be held accountable to using that information. The testing/exposure information EPA requires to be developed through Section 4 must be tiered. Finally, throughout the information gathering step, EPA should be asking whether it needs to "iterate" the information gathering process for prioritization, i.e., ask itself whether additional information should be gathered to designate a chemical as a high or low priority and if so to obtain it through the information gathering step process. 3. Sufficient Information to Designate: If EPA concludes it has sufficient information to designate the priority of a substance it can move that substance to the "Initiation of prioritization" step. If EPA concludes it has sufficient information to designate a substance as a high priority chemical, it should conduct a "pre-screening" review to identify potential data/information needs for scoping the risk evaluation (a bridging step between prioritization and scoping). If information on the chemical is deemed sufficient for scoping, the high priority chemical can then be put into the queue for "initiation" of the prioritization process at the appropriate time. If information is determined not sufficient for scoping, EPA should begin to collect/develop necessary information to scope the risk evaluation. This information screening "bridge" step should help EPA meet the 6-month statutory deadline for scoping a risk evaluation. However, this step would not replace either scoping itself or the anticipated need for EPA to collect other information during scoping. Further, it is not anticipated that this 6 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 step will develop all the information it will need for risk evaluation. EPA will not necessarily know what information it may need for risk evaluation until it actually conducts it. 4. Initiate the Priority Designation: EPA must announce a candidate for prioritization and request "relevant information" about that chemical and provide 90 days for persons to submit that information to EPA. The LCSA deadlines for priority setting (no less than 9 months; no more than 12 months) begin at this step. EPA will "pace" its priority designations to be ready when risk evaluations are near completion and ready to be replaced with a new priority. 5. Propose Priority Designation: EPA must propose a designation of a chemical as a high or low priority, including the basis for its proposal, and provide a 90 day public comment period. 6. Finalize the Designation of High Priority or Low Priority Chemical: EPA must finalize its designation of the chemical as either a high or low priority within the statutory deadlines (no less than 9 months; no more than 12 months). Low priority chemical designations are final agency action, subject to judicial review. EPA must communicate final designations of high priority chemicals very carefully to prevent the creation of "red-lists" of chemicals and other mis-interpretations by states or the marketplace. To help EPA understand ACC's vision of the prioritization process, we have attempted to capture a simplified version of it in the flowchart below. (See comments' text for more details.) 7 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226

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American° Chemistry Council March 20, 2017 Docket Control Office (7407M) Office of Pollution Prevention and Toxics (OPPT) U.S. Environmental Protection Agency 1200 Pennsylvania Ave., NW Washington, DC 20460-0001 Sent electronically to www.regulations.gov Docket ID# EPA-HQ-OPPT-2016-0636 Re: ACC Comments on EPA's Proposed Procedures for Prioritization of Chemicals for Risk Evaluation under the Toxic Substances Control Act as amended by the Lautenberg Chemical Safety Act Dear Sir/Madam: The American Chemistry Council (ACC¹ appreciates the opportunity to provide written comments to the Office of Chemical Safety and Pollution Prevention to inform the Agency's development of a prioritization process rule under the Toxic Substances Control Act (TSCA), as amended by the Lautenberg Chemical Safety Act (LCSA). ACC is committed to being a constructive stakeholder in the effective implementation of the LCSA and we provide these comments to assist the Agency in its development of a chemical evaluation and management program that is efficient, science-based, and consistent with the legal requirements of the LCSA. Prioritization is the first step in the LCSA's framework for evaluating active chemicals in commerce and the prioritization process rule must establish a risk-based screening process and criteria to identify high and low priority substances for risk evaluations under the LCSA. If you have any questions, please contact me at: 202-249-6403 or Sarah [email protected] Sincerely, Saraht. Brance Sarah Brozena Senior Director, Regulatory & Technical Affairs Cc: Jeffrey Morris, Director, OPPT Wendy Cleland Hamnett, OCSPP Ryan Schmit, OCSPP 1 The American Chemistry Council (ACC) represents the leading companies engaged in the business of chemistry. ACC members apply the science of chemistry to make innovative products and services that make people's lives better, healthier and safer. ACC is committed to improved environmental, health and safety performance through Responsible CareR, common sense advocacy designed to address major public policy issues, and health and environmental research and product testing. The business of chemistry is a $797 billion enterprise and a key element of the nation's economy. It is one of the nation's largest exporters, accounting for ten cents out of every dollar in U.S. exports. Chemistry companies are among the largest investors in research and development. Safety and security have always been primary concerns of ACC members, and they have intensified their efforts, working closely with government agencies to improve security and to defend against any threat to the nation's critical infrastructure. americanchemistry.com" 700 Second St., NE I Washington, DC 20002 I (202) 249.7000 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 American Chemistry Council American Chemistry Council Comments on EPA's Proposed Procedures for Prioritization of Chemicals for Risk Evaluation under the Toxic Substances Control Act as amended by the Lautenberg Chemical Safety Act Docket ID# EPA-HQ-OPPT-2016-0636 March 20, 2017 Sarah Brozena Senior Director, Regulatory & Technical Affairs American Chemistry Council 700 2nd Street, NE Washington DC 2002 (202) 249-6403 Sarah [email protected] americanchemistry.com 700 Second St., NE I Washington, DC 20002 I (202)249.7000 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Table of Contents EXECUTIVE SUMMARY 2 INTRODUCTION 4 I. ACC's Vision for a TSCA Prioritization Process Consistent with the LCSA 5 II. Overview of LCSA Prioritization Process Requirements 9 III. EPA Should Clarify Pre-Prioritization Step in Final Rule or Alternatively in Supplemental Rule 10 A. EPA Should Update Its TSCA Work Plan Criteria Before Using Them in Pre-Prioritization of Non-Work Plan Chemicals and Should Begin Planning to Integrate 21st Century Tools 11 B. EPA's Proposed Use of the Pre-Prioritization Step to Gather Information for Risk Evaluations Needs to Be Better Supported and Articulated 12 C. The Importance of Transparency in Prioritization Cannot Be Over-Emphasized 14 IV. EPA's Interpretation of Its Authority to Designate Low Priority Substances Is Short- Sighted, Contrary to Congressional Intent, Inconsistent with Best Available Science and Must Be Revised 15 A. EPA's Interpretation of Conditions of Use in the Prioritization Context Is a Strained Reading of the Statute and Contrary to Congressional Intent and Policy Objectives. 15 B. EPA's Abuse of Discretion Argument 16 C. EPA's Default to High Priority Designations Is Flawed Due to EPA's All Conditions of Use Interpretation. 17 D. Congress Authorized Ongoing Designations of Low Priority Chemicals 18 E. Best Available Risk-Based Scientific Procedures Enable EPA to Designate Low Priority Chemicals 18 V. Scientific Standards Must Be Referenced in the Prioritization Process Rule 19 A. Prioritization Decisions Must Be Based on Section 26 Standards for Best Available Science, Weight of the Scientific Evidence, and Transparency 19 B. EPA Should Address Other LCSA Science-Based Requirements in the Rule (Such As Tiered Testing and Animal Welfare Requirements). EPA Should Also Include a "Reserved" Placeholder in the Prioritization Rule for Incorporation of 21st Century Methods for Prioritization. 20 VI. Responses to EPA's Questions 20 A. Animal welfare requirements and scientific standards 20 B. EPA requests comments on its proposed process for prioritization overall. 21 C. Public input at pre-prioritization step 21 D. Consideration of substitutes in pre-prioritization 21 VII. Additional Specific Comments 22 A. Category of Chemical Substances 22 B. Inactive chemicals and new chemicals 22 C. Waivers 23 D. Definitions 23 E. Repopulation of High Priority Substances 24 VIII. Summary of ACC's Recommendations: 24 Attachment A 25 Attachment B 26 Attachment C 39 1 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 EXECUTIVE SUMMARY EPA has suggested four steps in its proposed rule to implement the prioritization requirements of Section 6(b) of the Toxic Substances Control Act (TSCA), as amended by the Frank R. Lautenberg Chemical Safety for the 21st Century Act: "Pre-prioritization" to narrow the pool of potential candidate substances Initiation of the prioritization process by identifying candidate substances and soliciting public comment Proposed priority designation, including an opportunity for public comment Priority designation The American Chemistry Council (ACC) has three major concerns with EPA's proposed prioritization process rule. Our concerns relate to the proposed pre-prioritization step, the treatment of low priority designations, and EPA's failure to address the LCSA Section 26 science standards in the rule. ACC's comments include specific recommendations to address these concerns. EPA's proposed prioritization process hinges on the "pre-prioritization" step. EPA does not fully and clearly describe this step, its statutory authority or limitations. Pre-prioritization is not mentioned in TSCA section 6(b) as amended. EPA asserts that the statute leaves it "broad discretion" to choose which chemicals on the TSCA Inventory to put into the prioritization process. However, EPA must exercise its discretion in a reasonable manner and is required to describe the statutory authorities for its exercise of discretion. EPA has not done so here. EPA intends the pre-prioritization step to inform prioritization decisions and the risk evaluation process, without regard to other relevant provisions of the statute. Because EPA asserts that it may need additional time to gather or develop information for risk evaluations, it has proposed to use the pre-prioritization step to gather information on substances with "insufficient information" for risk evaluation. ACC acknowledges that the statute imposes time constraints on the Agency once the prioritization process is triggered, but we believe that EPA has other tools available to address information needs in both the prioritization and risk evaluation stages in a timely, efficient manner. For example, in its pre-prioritization step EPA does not address the important relevant testing requirements of Section 4(a)(2)(A) or (B), the statement of need requirements of Section 4(a)(3) or the tiered testing requirements of Section 4(a)(4). As proposed, the pre-prioritization step conflates the prioritization and risk evaluation processes in ways that are confusing to the regulated community. Importantly, the pre-prioritization step appears contrary to congressional intent. In prioritization, it is very important that all substances be treated consistently, by the same transparent criteria, and that the process is replicable. Other than noting the statutory obligation to designate as high priorities the Work Plan chemicals that meet certain "preference" criteria, the proposed rule does not define the criteria or tools by which EPA will choose Work Plan and other chemicals from the active TSCA Inventory for the pre-prioritization or candidate "pool." EPA did not seek any stakeholder input on this question. EPA has not explained how many chemicals it proposes to include in the pre-prioritization or prioritization pool, or whether and how it will 2 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 "batch" chemicals to move them forward into the "initiation of prioritization" step. Although EPA has identified the nine criteria by which it proposes to narrow the pool into a list of candidates for prioritization, EPA does not define the criteria and or discuss the methodology by which these criteria will be applied. EPA proposes no timeframe for the pre-prioritization step, and provides little guidance on the status of chemicals included in pre-prioritization but excluded from prioritization. EPA's treatment of low priority chemicals raises significant concerns. EPA's proposal to require that low priority designations be based upon "all" conditions of use is a gross misinterpretation of the statute. This flawed interpretation of EPA's authority will cause the Agency to designate most chemicals in commerce as high priorities, and the Agency states as much in the preamble to the proposed rule. Congress did not intend this result. Low priority designations were seen as one mechanism to enhance public confidence in the safety of a chemical substance under its conditions of use, short of a full risk assessment. EPA has continuing authority to revise priority designations at any time based on new information. EPA has failed to include the LCSA Section 26 science standards in the prioritization process rule itself. EPA continues to assert that, while relevant to prioritization, EPA is not obliged to include these standards in the rule. ACC respectfully but strongly disagrees with EPA's reasoning. ACC's comments include a series of recommendations to address the shortcomings of the proposed prioritization process rule. Our recommendations describe: A transparent process for pooling and batching active chemicals in commerce for prioritization screening. A process to gather available information needed to reach a decision. A "bridging" step to permit EPA to assess the sufficiency of information for anticipated priority designations of candidate chemicals, which will inform the risk evaluation scoping process (should it be necessary). Revisions that recognize EPA's discretion to designate a low priority substance based on one, some or all conditions of use Identification of science-based criteria, tools and standards that apply in the prioritization process. 3 Source: :ttps://www.industrydocuments.ucsf.edu/docs/jzbn0226 American Chemistry Council Comments to U.S. Environmental Protection Agency on Its Proposed Procedures for Prioritization of Chemicals for Risk Evaluation under the Toxic Substances Control Act INTRODUCTION The American Chemistry Council (ACC) is pleased to provide the U.S. Environmental Protection Agency (EPA) these comments on the Agency's proposed procedures for prioritization of chemicals for risk evaluation under the Toxic Substances Control Act (TSCA) as amended by the Lautenberg Chemical Safety Act (LCSA). The LCSA requires EPA to establish, by rule, a risk-based screening process to identify high and low priority substances for risk evaluations under the LCSA. ACC strongly supported Congress's efforts to update and reform TSCA. One of ACC's principles for modernizing TSCA called on EPA to systematically prioritize chemicals for purposes of risk evaluations. Without a scientifically based prioritization process, EPA would not be able to meet efficiently the other requirements of the LCSA and achieve the objectives of TSCA reform that Congress intended. As discussed in more detail below, EPA's proposed prioritization process falls short. Congress designed the LCSA to allow chemicals to be systematically prioritized and then to evaluate those substances presenting the greatest potential risk. This design is apparent in every part of the LCSA. It begins with a reclassification of the full catalog of chemistries in U.S. commerce, the TSCA Inventory. The LCSA requires that the TSCA Inventory be sorted, so that chemicals that are currently active in commerce are separated from those no longer manufactured, imported or used; only chemicals that are active in commerce are subject to the prioritization and risk evaluation. This enables EPA to focus resources for its multi-year, time-and-resource intensive risk evaluations on chemicals that are actually in current use. EPA must next undertake a prioritization process, to inform the sequence of chemicals that will undergo risk evaluation. EPA must then undertake a formal scoping process, to define the conditions of use (and potentially exposed sub-populations relevant to the use) that will be included in the scope of the risk evaluation of the chemical. Prioritization of chemicals for various purposes is not new to the Agency. In 2011, EPA held a Stakeholder Dialogue on Prioritization and established a Discussion Blog for additional input on the topic. In our comments to that discussion blog, ACC identified several general principles for prioritization (Attachment A). We believe these principles are reflected in the LCSA requirements, in particular the LCSA's recognition that prioritization is a risk based screening process that integrates information on both hazard and exposure potential. In 2011, ACC developed a two-step quantitative and qualitative tool to "proof test" our prioritization principles (Attachment B). We presented our principles and our prioritization tool to EPA in 2011, as well as to other industry and NGO stakeholders at the time. In 2012, EPA published its methodology to identify chemicals for its TSCA Work 4 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Plan for Chemical Assessment (TSCA Work Plan) program. I. ACC's Vision for a TSCA Prioritization Process Consistent with the LCSA The LCSA requires EPA, by rule, to establish a risk-based screening process to designate chemicals as high or low priorities for risk evaluations. The LCSA includes criteria and considerations by which EPA must make these priority designations. To ensure EPA consistently has risk evaluations underway, the LCSA requires EPA to identify at least one new high priority for every risk evaluation that is completed. EPA's ability to designate additional priorities for 2 evaluation is limited only by the Agency's ability to complete risk evaluations in accordance with the deadlines established by Congress. Thus, Congress requires EPA to carefully choreograph the 3 identification of high priority substances for risk evaluations, in order to ensure that appropriate resources are available to complete the evaluations with the established deadlines. This implies a framework that efficiently coordinates EPA's prioritization process with EPA's risk evaluation process. ACC's vision for the prioritization process is one that enables EPA to meet all the requirements of the LCSA and congressional intent. Prioritization must be a risk based screening process in which EPA integrates hazard, use and exposure information to designate chemicals or categories of chemicals as either high or low priority for risk evaluations based on the criteria in Section 6. Information used to make prioritization decisions must be reasonably available; new information should be required through Section 4 tools only if EPA makes a determination pursuant to Section 4(a)(2)(B) that new information is necessary for prioritization. Prioritization designations must be based upon the science standards of LCSA Section 26, particularly best available science and weight of the scientific evidence. The basis for prioritization designations must be transparent and EPA's decisions must be communicated objectively and in neutral terms. ACC's vision of a prioritization process that meets these requirements includes six steps (see discussion below and the flowchart illustrating these steps on the next page and in Attachment C). ACC recommends that EPA clarify the needed timelines, criteria, tools, approaches and processes for these six steps, publish them for comment and include them in the final rule. Alternatively, EPA should propose these clarifications in a supplemental rule prior to the Agency's first application of the prioritization process. ACC's recommended six steps for the prioritization process are as follows: 1. Pool and Batch: EPA must "pool" active chemicals in commerce as candidates for designation as high or low priority for risk evaluation, based on transparent criteria/methods/approaches/tools and processes. EPA should then "batch" these candidates for information gathering. As EPA acknowledges in the "re-population" discussion of the preamble to the proposed rule4, the pace of EPA's completion of risk evaluations factors into the finalization of EPA's prioritization decisions. As a result, ACC expects that the number of candidates per "batch" for information gathering should be relatively small, at least in the early years of LCSA implementation. EPA's development of pools and batches should be subject to 2 15 U.S.C 1.2605(b)(3)(C) 3 15 U.S.C. 2605 (b)(2)(C) 4 82 Fed.Reg. 4825, 4833 (January 17, 2017). 5 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 estimated timeframes. 2. Information Gathering: Because Congress intended prioritization decisions to be based on reasonably available information, EPA should take a sequenced approach to information gathering on chemicals that EPA "batches" for prioritization. The sequenced steps should begin with EPA gathering reasonably available information about potential hazards, uses and potential exposure by relying upon sources such as read across/Quantitative Structure Activity Relationship (QSAR) information; Chemical Data Reporting (CDR) reports; EPA's CompTox Dashboard; High Production Volume (HPV) Challenge program; exposure information/models; EPA's Chemical Assessment and Management program (ChAMP); EPA's Voluntary Children's Chemical Evaluation Program (VCCEP); Canada's Chemical Management Program (CMP); OECD's eChemPortal; and robust study summaries developed under the EU's Registration, Evaluation, and Assessment of Chemicals (REACH). If this information is insufficient to designate the priority of a batched chemical, EPA should issue a notice in the Federal Register for voluntary call-ins of the type of information needed for prioritization and request discussions with manufacturers and processors of the chemicals. If voluntary information is still inadequate to prioritize, EPA should consider issuing TSCA Section 8(a) or 8(d) rules to require manufacturers/processors to collect existing information needed to prioritize. Finally, if EPA makes a determination subject to Section 4 requirements that new information is necessary to prioritize (and explaining why), EPA may issue Section 4 rules, orders or consent agreements. EPA should also be held accountable to using that information. The testing/exposure information EPA requires to be developed through Section 4 must be tiered. Finally, throughout the information gathering step, EPA should be asking whether it needs to "iterate" the information gathering process for prioritization, i.e., ask itself whether additional information should be gathered to designate a chemical as a high or low priority and if so to obtain it through the information gathering step process. 3. Sufficient Information to Designate: If EPA concludes it has sufficient information to designate the priority of a substance it can move that substance to the "Initiation of prioritization" step. If EPA concludes it has sufficient information to designate a substance as a high priority chemical, it should conduct a "pre-screening" review to identify potential data/information needs for scoping the risk evaluation (a bridging step between prioritization and scoping). If information on the chemical is deemed sufficient for scoping, the high priority chemical can then be put into the queue for "initiation" of the prioritization process at the appropriate time. If information is determined not sufficient for scoping, EPA should begin to collect/develop necessary information to scope the risk evaluation. This information screening "bridge" step should help EPA meet the 6-month statutory deadline for scoping a risk evaluation. However, this step would not replace either scoping itself or the anticipated need for EPA to collect other information during scoping. Further, it is not anticipated that this 6 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 step will develop all the information it will need for risk evaluation. EPA will not necessarily know what information it may need for risk evaluation until it actually conducts it. 4. Initiate the Priority Designation: EPA must announce a candidate for prioritization and request "relevant information" about that chemical and provide 90 days for persons to submit that information to EPA. The LCSA deadlines for priority setting (no less than 9 months; no more than 12 months) begin at this step. EPA will "pace" its priority designations to be ready when risk evaluations are near completion and ready to be replaced with a new priority. 5. Propose Priority Designation: EPA must propose a designation of a chemical as a high or low priority, including the basis for its proposal, and provide a 90 day public comment period. 6. Finalize the Designation of High Priority or Low Priority Chemical: EPA must finalize its designation of the chemical as either a high or low priority within the statutory deadlines (no less than 9 months; no more than 12 months). Low priority chemical designations are final agency action, subject to judicial review. EPA must communicate final designations of high priority chemicals very carefully to prevent the creation of "red-lists" of chemicals and other mis-interpretations by states or the marketplace. To help EPA understand ACC's vision of the prioritization process, we have attempted to capture a simplified version of it in the flowchart below. (See comments' text for more details.) 7 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226

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jzbn0226_p0, jzbn0226_p1, jzbn0226_p2, jzbn0226_p3, jzbn0226_p4, jzbn0226_p5, jzbn0226_p6, jzbn0226_p7, jzbn0226_p8

Senior director, regulatory and technical affairs

American° Chemistry Council March 20, 2017 Docket Control Office (7407M) Office of Pollution Prevention and Toxics (OPPT) U.S. Environmental Protection Agency 1200 Pennsylvania Ave., NW Washington, DC 20460-0001 Sent electronically to www.regulations.gov Docket ID# EPA-HQ-OPPT-2016-0636 Re: ACC Comments on EPA's Proposed Procedures for Prioritization of Chemicals for Risk Evaluation under the Toxic Substances Control Act as amended by the Lautenberg Chemical Safety Act Dear Sir/Madam: The American Chemistry Council (ACC¹ appreciates the opportunity to provide written comments to the Office of Chemical Safety and Pollution Prevention to inform the Agency's development of a prioritization process rule under the Toxic Substances Control Act (TSCA), as amended by the Lautenberg Chemical Safety Act (LCSA). ACC is committed to being a constructive stakeholder in the effective implementation of the LCSA and we provide these comments to assist the Agency in its development of a chemical evaluation and management program that is efficient, science-based, and consistent with the legal requirements of the LCSA. Prioritization is the first step in the LCSA's framework for evaluating active chemicals in commerce and the prioritization process rule must establish a risk-based screening process and criteria to identify high and low priority substances for risk evaluations under the LCSA. If you have any questions, please contact me at: 202-249-6403 or Sarah [email protected] Sincerely, Saraht. Brance Sarah Brozena Senior Director, Regulatory & Technical Affairs Cc: Jeffrey Morris, Director, OPPT Wendy Cleland Hamnett, OCSPP Ryan Schmit, OCSPP 1 The American Chemistry Council (ACC) represents the leading companies engaged in the business of chemistry. ACC members apply the science of chemistry to make innovative products and services that make people's lives better, healthier and safer. ACC is committed to improved environmental, health and safety performance through Responsible CareR, common sense advocacy designed to address major public policy issues, and health and environmental research and product testing. The business of chemistry is a $797 billion enterprise and a key element of the nation's economy. It is one of the nation's largest exporters, accounting for ten cents out of every dollar in U.S. exports. Chemistry companies are among the largest investors in research and development. Safety and security have always been primary concerns of ACC members, and they have intensified their efforts, working closely with government agencies to improve security and to defend against any threat to the nation's critical infrastructure. americanchemistry.com" 700 Second St., NE I Washington, DC 20002 I (202) 249.7000 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 American Chemistry Council American Chemistry Council Comments on EPA's Proposed Procedures for Prioritization of Chemicals for Risk Evaluation under the Toxic Substances Control Act as amended by the Lautenberg Chemical Safety Act Docket ID# EPA-HQ-OPPT-2016-0636 March 20, 2017 Sarah Brozena Senior Director, Regulatory & Technical Affairs American Chemistry Council 700 2nd Street, NE Washington DC 2002 (202) 249-6403 Sarah [email protected] americanchemistry.com 700 Second St., NE I Washington, DC 20002 I (202)249.7000 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Table of Contents EXECUTIVE SUMMARY 2 INTRODUCTION 4 I. ACC's Vision for a TSCA Prioritization Process Consistent with the LCSA 5 II. Overview of LCSA Prioritization Process Requirements 9 III. EPA Should Clarify Pre-Prioritization Step in Final Rule or Alternatively in Supplemental Rule 10 A. EPA Should Update Its TSCA Work Plan Criteria Before Using Them in Pre-Prioritization of Non-Work Plan Chemicals and Should Begin Planning to Integrate 21st Century Tools 11 B. EPA's Proposed Use of the Pre-Prioritization Step to Gather Information for Risk Evaluations Needs to Be Better Supported and Articulated 12 C. The Importance of Transparency in Prioritization Cannot Be Over-Emphasized 14 IV. EPA's Interpretation of Its Authority to Designate Low Priority Substances Is Short- Sighted, Contrary to Congressional Intent, Inconsistent with Best Available Science and Must Be Revised 15 A. EPA's Interpretation of Conditions of Use in the Prioritization Context Is a Strained Reading of the Statute and Contrary to Congressional Intent and Policy Objectives. 15 B. EPA's Abuse of Discretion Argument 16 C. EPA's Default to High Priority Designations Is Flawed Due to EPA's All Conditions of Use Interpretation. 17 D. Congress Authorized Ongoing Designations of Low Priority Chemicals 18 E. Best Available Risk-Based Scientific Procedures Enable EPA to Designate Low Priority Chemicals 18 V. Scientific Standards Must Be Referenced in the Prioritization Process Rule 19 A. Prioritization Decisions Must Be Based on Section 26 Standards for Best Available Science, Weight of the Scientific Evidence, and Transparency 19 B. EPA Should Address Other LCSA Science-Based Requirements in the Rule (Such As Tiered Testing and Animal Welfare Requirements). EPA Should Also Include a "Reserved" Placeholder in the Prioritization Rule for Incorporation of 21st Century Methods for Prioritization. 20 VI. Responses to EPA's Questions 20 A. Animal welfare requirements and scientific standards 20 B. EPA requests comments on its proposed process for prioritization overall. 21 C. Public input at pre-prioritization step 21 D. Consideration of substitutes in pre-prioritization 21 VII. Additional Specific Comments 22 A. Category of Chemical Substances 22 B. Inactive chemicals and new chemicals 22 C. Waivers 23 D. Definitions 23 E. Repopulation of High Priority Substances 24 VIII. Summary of ACC's Recommendations: 24 Attachment A 25 Attachment B 26 Attachment C 39 1 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 EXECUTIVE SUMMARY EPA has suggested four steps in its proposed rule to implement the prioritization requirements of Section 6(b) of the Toxic Substances Control Act (TSCA), as amended by the Frank R. Lautenberg Chemical Safety for the 21st Century Act: "Pre-prioritization" to narrow the pool of potential candidate substances Initiation of the prioritization process by identifying candidate substances and soliciting public comment Proposed priority designation, including an opportunity for public comment Priority designation The American Chemistry Council (ACC) has three major concerns with EPA's proposed prioritization process rule. Our concerns relate to the proposed pre-prioritization step, the treatment of low priority designations, and EPA's failure to address the LCSA Section 26 science standards in the rule. ACC's comments include specific recommendations to address these concerns. EPA's proposed prioritization process hinges on the "pre-prioritization" step. EPA does not fully and clearly describe this step, its statutory authority or limitations. Pre-prioritization is not mentioned in TSCA section 6(b) as amended. EPA asserts that the statute leaves it "broad discretion" to choose which chemicals on the TSCA Inventory to put into the prioritization process. However, EPA must exercise its discretion in a reasonable manner and is required to describe the statutory authorities for its exercise of discretion. EPA has not done so here. EPA intends the pre-prioritization step to inform prioritization decisions and the risk evaluation process, without regard to other relevant provisions of the statute. Because EPA asserts that it may need additional time to gather or develop information for risk evaluations, it has proposed to use the pre-prioritization step to gather information on substances with "insufficient information" for risk evaluation. ACC acknowledges that the statute imposes time constraints on the Agency once the prioritization process is triggered, but we believe that EPA has other tools available to address information needs in both the prioritization and risk evaluation stages in a timely, efficient manner. For example, in its pre-prioritization step EPA does not address the important relevant testing requirements of Section 4(a)(2)(A) or (B), the statement of need requirements of Section 4(a)(3) or the tiered testing requirements of Section 4(a)(4). As proposed, the pre-prioritization step conflates the prioritization and risk evaluation processes in ways that are confusing to the regulated community. Importantly, the pre-prioritization step appears contrary to congressional intent. In prioritization, it is very important that all substances be treated consistently, by the same transparent criteria, and that the process is replicable. Other than noting the statutory obligation to designate as high priorities the Work Plan chemicals that meet certain "preference" criteria, the proposed rule does not define the criteria or tools by which EPA will choose Work Plan and other chemicals from the active TSCA Inventory for the pre-prioritization or candidate "pool." EPA did not seek any stakeholder input on this question. EPA has not explained how many chemicals it proposes to include in the pre-prioritization or prioritization pool, or whether and how it will 2 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 "batch" chemicals to move them forward into the "initiation of prioritization" step. Although EPA has identified the nine criteria by which it proposes to narrow the pool into a list of candidates for prioritization, EPA does not define the criteria and or discuss the methodology by which these criteria will be applied. EPA proposes no timeframe for the pre-prioritization step, and provides little guidance on the status of chemicals included in pre-prioritization but excluded from prioritization. EPA's treatment of low priority chemicals raises significant concerns. EPA's proposal to require that low priority designations be based upon "all" conditions of use is a gross misinterpretation of the statute. This flawed interpretation of EPA's authority will cause the Agency to designate most chemicals in commerce as high priorities, and the Agency states as much in the preamble to the proposed rule. Congress did not intend this result. Low priority designations were seen as one mechanism to enhance public confidence in the safety of a chemical substance under its conditions of use, short of a full risk assessment. EPA has continuing authority to revise priority designations at any time based on new information. EPA has failed to include the LCSA Section 26 science standards in the prioritization process rule itself. EPA continues to assert that, while relevant to prioritization, EPA is not obliged to include these standards in the rule. ACC respectfully but strongly disagrees with EPA's reasoning. ACC's comments include a series of recommendations to address the shortcomings of the proposed prioritization process rule. Our recommendations describe: A transparent process for pooling and batching active chemicals in commerce for prioritization screening. A process to gather available information needed to reach a decision. A "bridging" step to permit EPA to assess the sufficiency of information for anticipated priority designations of candidate chemicals, which will inform the risk evaluation scoping process (should it be necessary). Revisions that recognize EPA's discretion to designate a low priority substance based on one, some or all conditions of use Identification of science-based criteria, tools and standards that apply in the prioritization process. 3 Source: :ttps://www.industrydocuments.ucsf.edu/docs/jzbn0226 American Chemistry Council Comments to U.S. Environmental Protection Agency on Its Proposed Procedures for Prioritization of Chemicals for Risk Evaluation under the Toxic Substances Control Act INTRODUCTION The American Chemistry Council (ACC) is pleased to provide the U.S. Environmental Protection Agency (EPA) these comments on the Agency's proposed procedures for prioritization of chemicals for risk evaluation under the Toxic Substances Control Act (TSCA) as amended by the Lautenberg Chemical Safety Act (LCSA). The LCSA requires EPA to establish, by rule, a risk-based screening process to identify high and low priority substances for risk evaluations under the LCSA. ACC strongly supported Congress's efforts to update and reform TSCA. One of ACC's principles for modernizing TSCA called on EPA to systematically prioritize chemicals for purposes of risk evaluations. Without a scientifically based prioritization process, EPA would not be able to meet efficiently the other requirements of the LCSA and achieve the objectives of TSCA reform that Congress intended. As discussed in more detail below, EPA's proposed prioritization process falls short. Congress designed the LCSA to allow chemicals to be systematically prioritized and then to evaluate those substances presenting the greatest potential risk. This design is apparent in every part of the LCSA. It begins with a reclassification of the full catalog of chemistries in U.S. commerce, the TSCA Inventory. The LCSA requires that the TSCA Inventory be sorted, so that chemicals that are currently active in commerce are separated from those no longer manufactured, imported or used; only chemicals that are active in commerce are subject to the prioritization and risk evaluation. This enables EPA to focus resources for its multi-year, time-and-resource intensive risk evaluations on chemicals that are actually in current use. EPA must next undertake a prioritization process, to inform the sequence of chemicals that will undergo risk evaluation. EPA must then undertake a formal scoping process, to define the conditions of use (and potentially exposed sub-populations relevant to the use) that will be included in the scope of the risk evaluation of the chemical. Prioritization of chemicals for various purposes is not new to the Agency. In 2011, EPA held a Stakeholder Dialogue on Prioritization and established a Discussion Blog for additional input on the topic. In our comments to that discussion blog, ACC identified several general principles for prioritization (Attachment A). We believe these principles are reflected in the LCSA requirements, in particular the LCSA's recognition that prioritization is a risk based screening process that integrates information on both hazard and exposure potential. In 2011, ACC developed a two-step quantitative and qualitative tool to "proof test" our prioritization principles (Attachment B). We presented our principles and our prioritization tool to EPA in 2011, as well as to other industry and NGO stakeholders at the time. In 2012, EPA published its methodology to identify chemicals for its TSCA Work 4 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Plan for Chemical Assessment (TSCA Work Plan) program. I. ACC's Vision for a TSCA Prioritization Process Consistent with the LCSA The LCSA requires EPA, by rule, to establish a risk-based screening process to designate chemicals as high or low priorities for risk evaluations. The LCSA includes criteria and considerations by which EPA must make these priority designations. To ensure EPA consistently has risk evaluations underway, the LCSA requires EPA to identify at least one new high priority for every risk evaluation that is completed. EPA's ability to designate additional priorities for 2 evaluation is limited only by the Agency's ability to complete risk evaluations in accordance with the deadlines established by Congress. Thus, Congress requires EPA to carefully choreograph the 3 identification of high priority substances for risk evaluations, in order to ensure that appropriate resources are available to complete the evaluations with the established deadlines. This implies a framework that efficiently coordinates EPA's prioritization process with EPA's risk evaluation process. ACC's vision for the prioritization process is one that enables EPA to meet all the requirements of the LCSA and congressional intent. Prioritization must be a risk based screening process in which EPA integrates hazard, use and exposure information to designate chemicals or categories of chemicals as either high or low priority for risk evaluations based on the criteria in Section 6. Information used to make prioritization decisions must be reasonably available; new information should be required through Section 4 tools only if EPA makes a determination pursuant to Section 4(a)(2)(B) that new information is necessary for prioritization. Prioritization designations must be based upon the science standards of LCSA Section 26, particularly best available science and weight of the scientific evidence. The basis for prioritization designations must be transparent and EPA's decisions must be communicated objectively and in neutral terms. ACC's vision of a prioritization process that meets these requirements includes six steps (see discussion below and the flowchart illustrating these steps on the next page and in Attachment C). ACC recommends that EPA clarify the needed timelines, criteria, tools, approaches and processes for these six steps, publish them for comment and include them in the final rule. Alternatively, EPA should propose these clarifications in a supplemental rule prior to the Agency's first application of the prioritization process. ACC's recommended six steps for the prioritization process are as follows: 1. Pool and Batch: EPA must "pool" active chemicals in commerce as candidates for designation as high or low priority for risk evaluation, based on transparent criteria/methods/approaches/tools and processes. EPA should then "batch" these candidates for information gathering. As EPA acknowledges in the "re-population" discussion of the preamble to the proposed rule4, the pace of EPA's completion of risk evaluations factors into the finalization of EPA's prioritization decisions. As a result, ACC expects that the number of candidates per "batch" for information gathering should be relatively small, at least in the early years of LCSA implementation. EPA's development of pools and batches should be subject to 2 15 U.S.C 1.2605(b)(3)(C) 3 15 U.S.C. 2605 (b)(2)(C) 4 82 Fed.Reg. 4825, 4833 (January 17, 2017). 5 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 estimated timeframes. 2. Information Gathering: Because Congress intended prioritization decisions to be based on reasonably available information, EPA should take a sequenced approach to information gathering on chemicals that EPA "batches" for prioritization. The sequenced steps should begin with EPA gathering reasonably available information about potential hazards, uses and potential exposure by relying upon sources such as read across/Quantitative Structure Activity Relationship (QSAR) information; Chemical Data Reporting (CDR) reports; EPA's CompTox Dashboard; High Production Volume (HPV) Challenge program; exposure information/models; EPA's Chemical Assessment and Management program (ChAMP); EPA's Voluntary Children's Chemical Evaluation Program (VCCEP); Canada's Chemical Management Program (CMP); OECD's eChemPortal; and robust study summaries developed under the EU's Registration, Evaluation, and Assessment of Chemicals (REACH). If this information is insufficient to designate the priority of a batched chemical, EPA should issue a notice in the Federal Register for voluntary call-ins of the type of information needed for prioritization and request discussions with manufacturers and processors of the chemicals. If voluntary information is still inadequate to prioritize, EPA should consider issuing TSCA Section 8(a) or 8(d) rules to require manufacturers/processors to collect existing information needed to prioritize. Finally, if EPA makes a determination subject to Section 4 requirements that new information is necessary to prioritize (and explaining why), EPA may issue Section 4 rules, orders or consent agreements. EPA should also be held accountable to using that information. The testing/exposure information EPA requires to be developed through Section 4 must be tiered. Finally, throughout the information gathering step, EPA should be asking whether it needs to "iterate" the information gathering process for prioritization, i.e., ask itself whether additional information should be gathered to designate a chemical as a high or low priority and if so to obtain it through the information gathering step process. 3. Sufficient Information to Designate: If EPA concludes it has sufficient information to designate the priority of a substance it can move that substance to the "Initiation of prioritization" step. If EPA concludes it has sufficient information to designate a substance as a high priority chemical, it should conduct a "pre-screening" review to identify potential data/information needs for scoping the risk evaluation (a bridging step between prioritization and scoping). If information on the chemical is deemed sufficient for scoping, the high priority chemical can then be put into the queue for "initiation" of the prioritization process at the appropriate time. If information is determined not sufficient for scoping, EPA should begin to collect/develop necessary information to scope the risk evaluation. This information screening "bridge" step should help EPA meet the 6-month statutory deadline for scoping a risk evaluation. However, this step would not replace either scoping itself or the anticipated need for EPA to collect other information during scoping. Further, it is not anticipated that this 6 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 step will develop all the information it will need for risk evaluation. EPA will not necessarily know what information it may need for risk evaluation until it actually conducts it. 4. Initiate the Priority Designation: EPA must announce a candidate for prioritization and request "relevant information" about that chemical and provide 90 days for persons to submit that information to EPA. The LCSA deadlines for priority setting (no less than 9 months; no more than 12 months) begin at this step. EPA will "pace" its priority designations to be ready when risk evaluations are near completion and ready to be replaced with a new priority. 5. Propose Priority Designation: EPA must propose a designation of a chemical as a high or low priority, including the basis for its proposal, and provide a 90 day public comment period. 6. Finalize the Designation of High Priority or Low Priority Chemical: EPA must finalize its designation of the chemical as either a high or low priority within the statutory deadlines (no less than 9 months; no more than 12 months). Low priority chemical designations are final agency action, subject to judicial review. EPA must communicate final designations of high priority chemicals very carefully to prevent the creation of "red-lists" of chemicals and other mis-interpretations by states or the marketplace. To help EPA understand ACC's vision of the prioritization process, we have attempted to capture a simplified version of it in the flowchart below. (See comments' text for more details.) 7 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226

Who is the Senior director, regulatory and technical affairs at American chemistry council?

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jzbn0226_p0, jzbn0226_p1, jzbn0226_p2, jzbn0226_p3, jzbn0226_p4, jzbn0226_p5, jzbn0226_p6, jzbn0226_p7, jzbn0226_p8

Sarah Brozena

American° Chemistry Council March 20, 2017 Docket Control Office (7407M) Office of Pollution Prevention and Toxics (OPPT) U.S. Environmental Protection Agency 1200 Pennsylvania Ave., NW Washington, DC 20460-0001 Sent electronically to www.regulations.gov Docket ID# EPA-HQ-OPPT-2016-0636 Re: ACC Comments on EPA's Proposed Procedures for Prioritization of Chemicals for Risk Evaluation under the Toxic Substances Control Act as amended by the Lautenberg Chemical Safety Act Dear Sir/Madam: The American Chemistry Council (ACC¹ appreciates the opportunity to provide written comments to the Office of Chemical Safety and Pollution Prevention to inform the Agency's development of a prioritization process rule under the Toxic Substances Control Act (TSCA), as amended by the Lautenberg Chemical Safety Act (LCSA). ACC is committed to being a constructive stakeholder in the effective implementation of the LCSA and we provide these comments to assist the Agency in its development of a chemical evaluation and management program that is efficient, science-based, and consistent with the legal requirements of the LCSA. Prioritization is the first step in the LCSA's framework for evaluating active chemicals in commerce and the prioritization process rule must establish a risk-based screening process and criteria to identify high and low priority substances for risk evaluations under the LCSA. If you have any questions, please contact me at: 202-249-6403 or Sarah [email protected] Sincerely, Saraht. Brance Sarah Brozena Senior Director, Regulatory & Technical Affairs Cc: Jeffrey Morris, Director, OPPT Wendy Cleland Hamnett, OCSPP Ryan Schmit, OCSPP 1 The American Chemistry Council (ACC) represents the leading companies engaged in the business of chemistry. ACC members apply the science of chemistry to make innovative products and services that make people's lives better, healthier and safer. ACC is committed to improved environmental, health and safety performance through Responsible CareR, common sense advocacy designed to address major public policy issues, and health and environmental research and product testing. The business of chemistry is a $797 billion enterprise and a key element of the nation's economy. It is one of the nation's largest exporters, accounting for ten cents out of every dollar in U.S. exports. Chemistry companies are among the largest investors in research and development. Safety and security have always been primary concerns of ACC members, and they have intensified their efforts, working closely with government agencies to improve security and to defend against any threat to the nation's critical infrastructure. americanchemistry.com" 700 Second St., NE I Washington, DC 20002 I (202) 249.7000 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 American Chemistry Council American Chemistry Council Comments on EPA's Proposed Procedures for Prioritization of Chemicals for Risk Evaluation under the Toxic Substances Control Act as amended by the Lautenberg Chemical Safety Act Docket ID# EPA-HQ-OPPT-2016-0636 March 20, 2017 Sarah Brozena Senior Director, Regulatory & Technical Affairs American Chemistry Council 700 2nd Street, NE Washington DC 2002 (202) 249-6403 Sarah [email protected] americanchemistry.com 700 Second St., NE I Washington, DC 20002 I (202)249.7000 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Table of Contents EXECUTIVE SUMMARY 2 INTRODUCTION 4 I. ACC's Vision for a TSCA Prioritization Process Consistent with the LCSA 5 II. Overview of LCSA Prioritization Process Requirements 9 III. EPA Should Clarify Pre-Prioritization Step in Final Rule or Alternatively in Supplemental Rule 10 A. EPA Should Update Its TSCA Work Plan Criteria Before Using Them in Pre-Prioritization of Non-Work Plan Chemicals and Should Begin Planning to Integrate 21st Century Tools 11 B. EPA's Proposed Use of the Pre-Prioritization Step to Gather Information for Risk Evaluations Needs to Be Better Supported and Articulated 12 C. The Importance of Transparency in Prioritization Cannot Be Over-Emphasized 14 IV. EPA's Interpretation of Its Authority to Designate Low Priority Substances Is Short- Sighted, Contrary to Congressional Intent, Inconsistent with Best Available Science and Must Be Revised 15 A. EPA's Interpretation of Conditions of Use in the Prioritization Context Is a Strained Reading of the Statute and Contrary to Congressional Intent and Policy Objectives. 15 B. EPA's Abuse of Discretion Argument 16 C. EPA's Default to High Priority Designations Is Flawed Due to EPA's All Conditions of Use Interpretation. 17 D. Congress Authorized Ongoing Designations of Low Priority Chemicals 18 E. Best Available Risk-Based Scientific Procedures Enable EPA to Designate Low Priority Chemicals 18 V. Scientific Standards Must Be Referenced in the Prioritization Process Rule 19 A. Prioritization Decisions Must Be Based on Section 26 Standards for Best Available Science, Weight of the Scientific Evidence, and Transparency 19 B. EPA Should Address Other LCSA Science-Based Requirements in the Rule (Such As Tiered Testing and Animal Welfare Requirements). EPA Should Also Include a "Reserved" Placeholder in the Prioritization Rule for Incorporation of 21st Century Methods for Prioritization. 20 VI. Responses to EPA's Questions 20 A. Animal welfare requirements and scientific standards 20 B. EPA requests comments on its proposed process for prioritization overall. 21 C. Public input at pre-prioritization step 21 D. Consideration of substitutes in pre-prioritization 21 VII. Additional Specific Comments 22 A. Category of Chemical Substances 22 B. Inactive chemicals and new chemicals 22 C. Waivers 23 D. Definitions 23 E. Repopulation of High Priority Substances 24 VIII. Summary of ACC's Recommendations: 24 Attachment A 25 Attachment B 26 Attachment C 39 1 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 EXECUTIVE SUMMARY EPA has suggested four steps in its proposed rule to implement the prioritization requirements of Section 6(b) of the Toxic Substances Control Act (TSCA), as amended by the Frank R. Lautenberg Chemical Safety for the 21st Century Act: "Pre-prioritization" to narrow the pool of potential candidate substances Initiation of the prioritization process by identifying candidate substances and soliciting public comment Proposed priority designation, including an opportunity for public comment Priority designation The American Chemistry Council (ACC) has three major concerns with EPA's proposed prioritization process rule. Our concerns relate to the proposed pre-prioritization step, the treatment of low priority designations, and EPA's failure to address the LCSA Section 26 science standards in the rule. ACC's comments include specific recommendations to address these concerns. EPA's proposed prioritization process hinges on the "pre-prioritization" step. EPA does not fully and clearly describe this step, its statutory authority or limitations. Pre-prioritization is not mentioned in TSCA section 6(b) as amended. EPA asserts that the statute leaves it "broad discretion" to choose which chemicals on the TSCA Inventory to put into the prioritization process. However, EPA must exercise its discretion in a reasonable manner and is required to describe the statutory authorities for its exercise of discretion. EPA has not done so here. EPA intends the pre-prioritization step to inform prioritization decisions and the risk evaluation process, without regard to other relevant provisions of the statute. Because EPA asserts that it may need additional time to gather or develop information for risk evaluations, it has proposed to use the pre-prioritization step to gather information on substances with "insufficient information" for risk evaluation. ACC acknowledges that the statute imposes time constraints on the Agency once the prioritization process is triggered, but we believe that EPA has other tools available to address information needs in both the prioritization and risk evaluation stages in a timely, efficient manner. For example, in its pre-prioritization step EPA does not address the important relevant testing requirements of Section 4(a)(2)(A) or (B), the statement of need requirements of Section 4(a)(3) or the tiered testing requirements of Section 4(a)(4). As proposed, the pre-prioritization step conflates the prioritization and risk evaluation processes in ways that are confusing to the regulated community. Importantly, the pre-prioritization step appears contrary to congressional intent. In prioritization, it is very important that all substances be treated consistently, by the same transparent criteria, and that the process is replicable. Other than noting the statutory obligation to designate as high priorities the Work Plan chemicals that meet certain "preference" criteria, the proposed rule does not define the criteria or tools by which EPA will choose Work Plan and other chemicals from the active TSCA Inventory for the pre-prioritization or candidate "pool." EPA did not seek any stakeholder input on this question. EPA has not explained how many chemicals it proposes to include in the pre-prioritization or prioritization pool, or whether and how it will 2 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 "batch" chemicals to move them forward into the "initiation of prioritization" step. Although EPA has identified the nine criteria by which it proposes to narrow the pool into a list of candidates for prioritization, EPA does not define the criteria and or discuss the methodology by which these criteria will be applied. EPA proposes no timeframe for the pre-prioritization step, and provides little guidance on the status of chemicals included in pre-prioritization but excluded from prioritization. EPA's treatment of low priority chemicals raises significant concerns. EPA's proposal to require that low priority designations be based upon "all" conditions of use is a gross misinterpretation of the statute. This flawed interpretation of EPA's authority will cause the Agency to designate most chemicals in commerce as high priorities, and the Agency states as much in the preamble to the proposed rule. Congress did not intend this result. Low priority designations were seen as one mechanism to enhance public confidence in the safety of a chemical substance under its conditions of use, short of a full risk assessment. EPA has continuing authority to revise priority designations at any time based on new information. EPA has failed to include the LCSA Section 26 science standards in the prioritization process rule itself. EPA continues to assert that, while relevant to prioritization, EPA is not obliged to include these standards in the rule. ACC respectfully but strongly disagrees with EPA's reasoning. ACC's comments include a series of recommendations to address the shortcomings of the proposed prioritization process rule. Our recommendations describe: A transparent process for pooling and batching active chemicals in commerce for prioritization screening. A process to gather available information needed to reach a decision. A "bridging" step to permit EPA to assess the sufficiency of information for anticipated priority designations of candidate chemicals, which will inform the risk evaluation scoping process (should it be necessary). Revisions that recognize EPA's discretion to designate a low priority substance based on one, some or all conditions of use Identification of science-based criteria, tools and standards that apply in the prioritization process. 3 Source: :ttps://www.industrydocuments.ucsf.edu/docs/jzbn0226 American Chemistry Council Comments to U.S. Environmental Protection Agency on Its Proposed Procedures for Prioritization of Chemicals for Risk Evaluation under the Toxic Substances Control Act INTRODUCTION The American Chemistry Council (ACC) is pleased to provide the U.S. Environmental Protection Agency (EPA) these comments on the Agency's proposed procedures for prioritization of chemicals for risk evaluation under the Toxic Substances Control Act (TSCA) as amended by the Lautenberg Chemical Safety Act (LCSA). The LCSA requires EPA to establish, by rule, a risk-based screening process to identify high and low priority substances for risk evaluations under the LCSA. ACC strongly supported Congress's efforts to update and reform TSCA. One of ACC's principles for modernizing TSCA called on EPA to systematically prioritize chemicals for purposes of risk evaluations. Without a scientifically based prioritization process, EPA would not be able to meet efficiently the other requirements of the LCSA and achieve the objectives of TSCA reform that Congress intended. As discussed in more detail below, EPA's proposed prioritization process falls short. Congress designed the LCSA to allow chemicals to be systematically prioritized and then to evaluate those substances presenting the greatest potential risk. This design is apparent in every part of the LCSA. It begins with a reclassification of the full catalog of chemistries in U.S. commerce, the TSCA Inventory. The LCSA requires that the TSCA Inventory be sorted, so that chemicals that are currently active in commerce are separated from those no longer manufactured, imported or used; only chemicals that are active in commerce are subject to the prioritization and risk evaluation. This enables EPA to focus resources for its multi-year, time-and-resource intensive risk evaluations on chemicals that are actually in current use. EPA must next undertake a prioritization process, to inform the sequence of chemicals that will undergo risk evaluation. EPA must then undertake a formal scoping process, to define the conditions of use (and potentially exposed sub-populations relevant to the use) that will be included in the scope of the risk evaluation of the chemical. Prioritization of chemicals for various purposes is not new to the Agency. In 2011, EPA held a Stakeholder Dialogue on Prioritization and established a Discussion Blog for additional input on the topic. In our comments to that discussion blog, ACC identified several general principles for prioritization (Attachment A). We believe these principles are reflected in the LCSA requirements, in particular the LCSA's recognition that prioritization is a risk based screening process that integrates information on both hazard and exposure potential. In 2011, ACC developed a two-step quantitative and qualitative tool to "proof test" our prioritization principles (Attachment B). We presented our principles and our prioritization tool to EPA in 2011, as well as to other industry and NGO stakeholders at the time. In 2012, EPA published its methodology to identify chemicals for its TSCA Work 4 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Plan for Chemical Assessment (TSCA Work Plan) program. I. ACC's Vision for a TSCA Prioritization Process Consistent with the LCSA The LCSA requires EPA, by rule, to establish a risk-based screening process to designate chemicals as high or low priorities for risk evaluations. The LCSA includes criteria and considerations by which EPA must make these priority designations. To ensure EPA consistently has risk evaluations underway, the LCSA requires EPA to identify at least one new high priority for every risk evaluation that is completed. EPA's ability to designate additional priorities for 2 evaluation is limited only by the Agency's ability to complete risk evaluations in accordance with the deadlines established by Congress. Thus, Congress requires EPA to carefully choreograph the 3 identification of high priority substances for risk evaluations, in order to ensure that appropriate resources are available to complete the evaluations with the established deadlines. This implies a framework that efficiently coordinates EPA's prioritization process with EPA's risk evaluation process. ACC's vision for the prioritization process is one that enables EPA to meet all the requirements of the LCSA and congressional intent. Prioritization must be a risk based screening process in which EPA integrates hazard, use and exposure information to designate chemicals or categories of chemicals as either high or low priority for risk evaluations based on the criteria in Section 6. Information used to make prioritization decisions must be reasonably available; new information should be required through Section 4 tools only if EPA makes a determination pursuant to Section 4(a)(2)(B) that new information is necessary for prioritization. Prioritization designations must be based upon the science standards of LCSA Section 26, particularly best available science and weight of the scientific evidence. The basis for prioritization designations must be transparent and EPA's decisions must be communicated objectively and in neutral terms. ACC's vision of a prioritization process that meets these requirements includes six steps (see discussion below and the flowchart illustrating these steps on the next page and in Attachment C). ACC recommends that EPA clarify the needed timelines, criteria, tools, approaches and processes for these six steps, publish them for comment and include them in the final rule. Alternatively, EPA should propose these clarifications in a supplemental rule prior to the Agency's first application of the prioritization process. ACC's recommended six steps for the prioritization process are as follows: 1. Pool and Batch: EPA must "pool" active chemicals in commerce as candidates for designation as high or low priority for risk evaluation, based on transparent criteria/methods/approaches/tools and processes. EPA should then "batch" these candidates for information gathering. As EPA acknowledges in the "re-population" discussion of the preamble to the proposed rule4, the pace of EPA's completion of risk evaluations factors into the finalization of EPA's prioritization decisions. As a result, ACC expects that the number of candidates per "batch" for information gathering should be relatively small, at least in the early years of LCSA implementation. EPA's development of pools and batches should be subject to 2 15 U.S.C 1.2605(b)(3)(C) 3 15 U.S.C. 2605 (b)(2)(C) 4 82 Fed.Reg. 4825, 4833 (January 17, 2017). 5 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 estimated timeframes. 2. Information Gathering: Because Congress intended prioritization decisions to be based on reasonably available information, EPA should take a sequenced approach to information gathering on chemicals that EPA "batches" for prioritization. The sequenced steps should begin with EPA gathering reasonably available information about potential hazards, uses and potential exposure by relying upon sources such as read across/Quantitative Structure Activity Relationship (QSAR) information; Chemical Data Reporting (CDR) reports; EPA's CompTox Dashboard; High Production Volume (HPV) Challenge program; exposure information/models; EPA's Chemical Assessment and Management program (ChAMP); EPA's Voluntary Children's Chemical Evaluation Program (VCCEP); Canada's Chemical Management Program (CMP); OECD's eChemPortal; and robust study summaries developed under the EU's Registration, Evaluation, and Assessment of Chemicals (REACH). If this information is insufficient to designate the priority of a batched chemical, EPA should issue a notice in the Federal Register for voluntary call-ins of the type of information needed for prioritization and request discussions with manufacturers and processors of the chemicals. If voluntary information is still inadequate to prioritize, EPA should consider issuing TSCA Section 8(a) or 8(d) rules to require manufacturers/processors to collect existing information needed to prioritize. Finally, if EPA makes a determination subject to Section 4 requirements that new information is necessary to prioritize (and explaining why), EPA may issue Section 4 rules, orders or consent agreements. EPA should also be held accountable to using that information. The testing/exposure information EPA requires to be developed through Section 4 must be tiered. Finally, throughout the information gathering step, EPA should be asking whether it needs to "iterate" the information gathering process for prioritization, i.e., ask itself whether additional information should be gathered to designate a chemical as a high or low priority and if so to obtain it through the information gathering step process. 3. Sufficient Information to Designate: If EPA concludes it has sufficient information to designate the priority of a substance it can move that substance to the "Initiation of prioritization" step. If EPA concludes it has sufficient information to designate a substance as a high priority chemical, it should conduct a "pre-screening" review to identify potential data/information needs for scoping the risk evaluation (a bridging step between prioritization and scoping). If information on the chemical is deemed sufficient for scoping, the high priority chemical can then be put into the queue for "initiation" of the prioritization process at the appropriate time. If information is determined not sufficient for scoping, EPA should begin to collect/develop necessary information to scope the risk evaluation. This information screening "bridge" step should help EPA meet the 6-month statutory deadline for scoping a risk evaluation. However, this step would not replace either scoping itself or the anticipated need for EPA to collect other information during scoping. Further, it is not anticipated that this 6 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 step will develop all the information it will need for risk evaluation. EPA will not necessarily know what information it may need for risk evaluation until it actually conducts it. 4. Initiate the Priority Designation: EPA must announce a candidate for prioritization and request "relevant information" about that chemical and provide 90 days for persons to submit that information to EPA. The LCSA deadlines for priority setting (no less than 9 months; no more than 12 months) begin at this step. EPA will "pace" its priority designations to be ready when risk evaluations are near completion and ready to be replaced with a new priority. 5. Propose Priority Designation: EPA must propose a designation of a chemical as a high or low priority, including the basis for its proposal, and provide a 90 day public comment period. 6. Finalize the Designation of High Priority or Low Priority Chemical: EPA must finalize its designation of the chemical as either a high or low priority within the statutory deadlines (no less than 9 months; no more than 12 months). Low priority chemical designations are final agency action, subject to judicial review. EPA must communicate final designations of high priority chemicals very carefully to prevent the creation of "red-lists" of chemicals and other mis-interpretations by states or the marketplace. To help EPA understand ACC's vision of the prioritization process, we have attempted to capture a simplified version of it in the flowchart below. (See comments' text for more details.) 7 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226

Post marketing surveillance(PMS) affiliates to which region?

fzjf0226

fzjf0226_p0, fzjf0226_p1, fzjf0226_p2, fzjf0226_p3, fzjf0226_p4, fzjf0226_p5, fzjf0226_p6, fzjf0226_p7, fzjf0226_p8, fzjf0226_p9, fzjf0226_p10, fzjf0226_p11, fzjf0226_p12, fzjf0226_p13, fzjf0226_p14, fzjf0226_p15

Spain

PLA-TAK-00053920 PLA-TAK-00053921 Source: :ttps://www.indupt340-00002ts.ucsf.edu/docs/fzjf0226 Clinical Plan supporting Marketing Objectives Marketing Objective : Grow the customer base who differentiate and prefer ACTOS versus Avandia because of the lipid profile by Q3 2003 Strategic Clinical Study Target Date Action Plan Objective Database Locked Demonstrate significant GLAI Q4'02-Q2'03 Publication lipid differences versus Abstracts Avandia Update slide series Symposia Speaker Training Demonstrate Possible IIT (US) TBD Abstracts improvement in Publication postprandial lipidemia 9/18/2013 Company Confidential 3 Copyright © 2000 Eli Lilly and Company PLA-TAK-00053922 Source: https://www.indupt340-00003ts.ucsf.edu/docs/fzjf0226 PLA-TAK-00053923 Source: https://www.indupt340-00004ts.ucsf.edu/docs/fzjf0226 Clinical Plan supporting Marketing Objectives Marketing Objective : Create perception of ACTOS reducing risk of cardiovascular complications starting in 2003 Strategic Clinical Study Target Date Action Plan Objective Database Locked Demonstrate GLAE Q2'02-Q1'02 Included in symposia improvement in Update slide series SBP/DBP Demonstrate GLAC reduction in C- GLAI Q4'02-Q2'03 Reactive Protein Demonstrate effects GLAI Q4'02-Q2'03 on PAI-1 Demonstrate TL-OPI-516 Q3'03? Publication to be planned prevention of Abstracts to be submitted Secondary MI after Symposia first MI Prevention of PROactive Q3'05 Takeda to submit for Cardiovascular EC-444 label change outcomes Publication to be planned Symposia Focus 9/18/2013 Company Confidential 5 Copyright © 2000 Eli Lilly and Company PLA-TAK-00053924 Source: https://www.indup5340-00005ts.ucsf.edu/docs/fzjf0226 Clinical Plan supporting Marketing Objectives Marketing Objective : Create perception of ACTOS reducing risk of cardiovascular complications starting in 2003 Strategic Clinical Study Target Date Action Plan Objective Database Locked Show effects in LDL GLAI -Q4'02-Q2'03 Update slides particle size Incorporate into articles on diabetes dyslipidemia Effects on plaque TL-OPI-516 Q3'03? Symposia topic biology/endothelium US IIT - Fronseca TBD Publication Abstract 9/18/2013 Company Confidential 6 Copyright C 2000 Eli Lilly and Company PLA-TAK-00053925 Source: https://www.indup6340-00006ts.ucsf.edu/docs/fzjf0226 PROactive Objective: Demonstrate that pioglitazone reduces total mortality and macrovascular morbidity in high-risk patients with type 2 diabetes mellitus Number of patients: 5,000 Countries: Austria, Belgium, Czech Republic, Denmark, Estonia, Finland, France, Germany, Hungary, Italy, Latvia, Lithuania, Netherlands, Norway, Poland, Sweden, Switzerland, UK FPV: June 2001 LPV: Q2 2005 Primary Endpoints: All-cause mortality, non-fatal MI, acute coronary syndrome, cardiac intervention, stroke, major leg amputation, bypass surgery, or revascularisation in the leg Secondary Endpoints: Cardiovascular mortality 9/18/2013 Company Confidential 7 Copyright 2000 Eli Lilly and Company PLA-TAK-00053926 Source: https://www.indupe340-00007ts.ucsf.edu/docs/fzjf0226 Clinical Data to Support CV Risk Reduction PROactive 2005 EC 409 EC 410 TL-OPI-503 2004 GLAI EC 404 GLAG 2003 GLAL Evident 2002 2001 9/18/2013 Company Confidential 8 Copyright 2000 Eli Lilly and Company PLA-TAK-00053927 Source: https://www.indup340-00008ts.ucsf.edu/docs/fzjf0226 Clinical Plan supporting Marketing Objectives Marketing Objective : Ensure access and reimbursement of ACTOS in maximize markets Strategic Clinical Study Target Date Action Plan Objective Database Locked Expand European EC 404 Q2'02 Takeda to submit for Label to include EC 405/GLAG label expansion monotherapy Submit abstract in 2003 ADA/EASD/IDF Expand the European PNFP-341 - SU Q2'02 Takeda to submit for label to include 45 mg, PNFP-342 - Met label change Utilize 45 mg EC 409 / GLAP Q3'04-Q3'02 (1 Year) Production forecasts to combination in US EC 410 / GLAQ Q3'04-Q3'02 (1 Year) be modified Expand European PNFP-343 Q2'02 Takeda to submit for Label to include Insulin comb. trial for Q4'04 Q2'04 label change Combination with efficacy and Guidelines/algorithm Insulin European safety-not- developed on yet funded- decreases in suggested insulin? Establish safety in TL-OPI-504 (II-III) Q1'02 Takeda to submit for Class I, II and III CHF TL-OP-520 (I) Q1'03- Q2'03 label modification in Europe Update slide series 9/18/2013 Company Confidential 9 Copyright 2000 Eli Lilly and Company PLA-TAK-00053928 Source: https://www.indupt340-00009ts.ucsf.edu/docs/fzjf0226 PLA-TAK-00053929 Source: https://www.indupe340-00070ts.ucsf.edu/docs/fzjf0226 Clinical Plan supporting Marketing Objectives Strategic Clinical Study Target Date Action Plan Objective Database Locked Reduction/Removal of TL-OPI-506 Q2'04 Discussions need to the liver monitoring continue with the FDA to requirements establish clear safety milestones Demonstrate lack of TL-OPI-509 ? Publication(s) to be Drug-Drug (Cyclosporine B) planned Interactions TL-OPI-510 Q2'01 Abstracts to be submitted (Theophylline) on each study TL-OPI-511 Q2'01 (Atorvastatin) Adolescent data/use TL-OPI-507 TBD 9/18/2013 Company Confidential 11 Copyright © 2000 Eli Lilly and Company PLA-TAK-00053930 PLA-TAK-00053931 Source: https://www.indup5340-0002ts.ucsf.edu/docs/fzjf0226 Possible Suggested Topics for IITs Blood Pressure effects Onset of Action Metformin VS Actos Mechanism of Action Post-Prandial lipids Weight Management Beta-cell Protection (preclinical studies to support theory) 9/18/2013 Company Confidential 13 Copyright © 2000 Eli Lilly and Company PLA-TAK-00053932 Source: https://www.indup6340-00013ts.ucsf.edu/docs/fzjf0226 PLA-TAK-00053933 Source: https://www.indupt340-00094ts.ucsf.edu/docs/fzjf0226 Clinical Experience Programs Program Description Affiliates Investigator Initiated A trial/study initiated by Recommended for all Trials (IITs) investigator(s) not Maximize Affiliates Or study (IIS) affiliated with Lilly Observational Studies A study based on US "Evident" collection of data from patient charts Physician Experience Provide free products Mexico, Canada, Programs (PEPs) for specified time Australia frames to physicians for them to gain experience Post Marketing A study based on Spain Surveillance (PMS) collection of AE data from patient charts 9/18/2013 Company Confidential 15 Copyright © 2000 Eli Lilly and Company PLA-TAK-00053934 Source: https://www.indup340-00095ts.ucsf.edu/docs/fzjf0226 PLA-TAK-00053935 Source: https://www.indup6340-00076ts.ucsf.edu/docs/fzjf0226

The study based on collection of data from patient charts

fzjf0226

fzjf0226_p0, fzjf0226_p1, fzjf0226_p2, fzjf0226_p3, fzjf0226_p4, fzjf0226_p5, fzjf0226_p6, fzjf0226_p7, fzjf0226_p8, fzjf0226_p9, fzjf0226_p10, fzjf0226_p11, fzjf0226_p12, fzjf0226_p13, fzjf0226_p14, fzjf0226_p15

Observational Studies

PLA-TAK-00053920 PLA-TAK-00053921 Source: :ttps://www.indupt340-00002ts.ucsf.edu/docs/fzjf0226 Clinical Plan supporting Marketing Objectives Marketing Objective : Grow the customer base who differentiate and prefer ACTOS versus Avandia because of the lipid profile by Q3 2003 Strategic Clinical Study Target Date Action Plan Objective Database Locked Demonstrate significant GLAI Q4'02-Q2'03 Publication lipid differences versus Abstracts Avandia Update slide series Symposia Speaker Training Demonstrate Possible IIT (US) TBD Abstracts improvement in Publication postprandial lipidemia 9/18/2013 Company Confidential 3 Copyright © 2000 Eli Lilly and Company PLA-TAK-00053922 Source: https://www.indupt340-00003ts.ucsf.edu/docs/fzjf0226 PLA-TAK-00053923 Source: https://www.indupt340-00004ts.ucsf.edu/docs/fzjf0226 Clinical Plan supporting Marketing Objectives Marketing Objective : Create perception of ACTOS reducing risk of cardiovascular complications starting in 2003 Strategic Clinical Study Target Date Action Plan Objective Database Locked Demonstrate GLAE Q2'02-Q1'02 Included in symposia improvement in Update slide series SBP/DBP Demonstrate GLAC reduction in C- GLAI Q4'02-Q2'03 Reactive Protein Demonstrate effects GLAI Q4'02-Q2'03 on PAI-1 Demonstrate TL-OPI-516 Q3'03? Publication to be planned prevention of Abstracts to be submitted Secondary MI after Symposia first MI Prevention of PROactive Q3'05 Takeda to submit for Cardiovascular EC-444 label change outcomes Publication to be planned Symposia Focus 9/18/2013 Company Confidential 5 Copyright © 2000 Eli Lilly and Company PLA-TAK-00053924 Source: https://www.indup5340-00005ts.ucsf.edu/docs/fzjf0226 Clinical Plan supporting Marketing Objectives Marketing Objective : Create perception of ACTOS reducing risk of cardiovascular complications starting in 2003 Strategic Clinical Study Target Date Action Plan Objective Database Locked Show effects in LDL GLAI -Q4'02-Q2'03 Update slides particle size Incorporate into articles on diabetes dyslipidemia Effects on plaque TL-OPI-516 Q3'03? Symposia topic biology/endothelium US IIT - Fronseca TBD Publication Abstract 9/18/2013 Company Confidential 6 Copyright C 2000 Eli Lilly and Company PLA-TAK-00053925 Source: https://www.indup6340-00006ts.ucsf.edu/docs/fzjf0226 PROactive Objective: Demonstrate that pioglitazone reduces total mortality and macrovascular morbidity in high-risk patients with type 2 diabetes mellitus Number of patients: 5,000 Countries: Austria, Belgium, Czech Republic, Denmark, Estonia, Finland, France, Germany, Hungary, Italy, Latvia, Lithuania, Netherlands, Norway, Poland, Sweden, Switzerland, UK FPV: June 2001 LPV: Q2 2005 Primary Endpoints: All-cause mortality, non-fatal MI, acute coronary syndrome, cardiac intervention, stroke, major leg amputation, bypass surgery, or revascularisation in the leg Secondary Endpoints: Cardiovascular mortality 9/18/2013 Company Confidential 7 Copyright 2000 Eli Lilly and Company PLA-TAK-00053926 Source: https://www.indupe340-00007ts.ucsf.edu/docs/fzjf0226 Clinical Data to Support CV Risk Reduction PROactive 2005 EC 409 EC 410 TL-OPI-503 2004 GLAI EC 404 GLAG 2003 GLAL Evident 2002 2001 9/18/2013 Company Confidential 8 Copyright 2000 Eli Lilly and Company PLA-TAK-00053927 Source: https://www.indup340-00008ts.ucsf.edu/docs/fzjf0226 Clinical Plan supporting Marketing Objectives Marketing Objective : Ensure access and reimbursement of ACTOS in maximize markets Strategic Clinical Study Target Date Action Plan Objective Database Locked Expand European EC 404 Q2'02 Takeda to submit for Label to include EC 405/GLAG label expansion monotherapy Submit abstract in 2003 ADA/EASD/IDF Expand the European PNFP-341 - SU Q2'02 Takeda to submit for label to include 45 mg, PNFP-342 - Met label change Utilize 45 mg EC 409 / GLAP Q3'04-Q3'02 (1 Year) Production forecasts to combination in US EC 410 / GLAQ Q3'04-Q3'02 (1 Year) be modified Expand European PNFP-343 Q2'02 Takeda to submit for Label to include Insulin comb. trial for Q4'04 Q2'04 label change Combination with efficacy and Guidelines/algorithm Insulin European safety-not- developed on yet funded- decreases in suggested insulin? Establish safety in TL-OPI-504 (II-III) Q1'02 Takeda to submit for Class I, II and III CHF TL-OP-520 (I) Q1'03- Q2'03 label modification in Europe Update slide series 9/18/2013 Company Confidential 9 Copyright 2000 Eli Lilly and Company PLA-TAK-00053928 Source: https://www.indupt340-00009ts.ucsf.edu/docs/fzjf0226 PLA-TAK-00053929 Source: https://www.indupe340-00070ts.ucsf.edu/docs/fzjf0226 Clinical Plan supporting Marketing Objectives Strategic Clinical Study Target Date Action Plan Objective Database Locked Reduction/Removal of TL-OPI-506 Q2'04 Discussions need to the liver monitoring continue with the FDA to requirements establish clear safety milestones Demonstrate lack of TL-OPI-509 ? Publication(s) to be Drug-Drug (Cyclosporine B) planned Interactions TL-OPI-510 Q2'01 Abstracts to be submitted (Theophylline) on each study TL-OPI-511 Q2'01 (Atorvastatin) Adolescent data/use TL-OPI-507 TBD 9/18/2013 Company Confidential 11 Copyright © 2000 Eli Lilly and Company PLA-TAK-00053930 PLA-TAK-00053931 Source: https://www.indup5340-0002ts.ucsf.edu/docs/fzjf0226 Possible Suggested Topics for IITs Blood Pressure effects Onset of Action Metformin VS Actos Mechanism of Action Post-Prandial lipids Weight Management Beta-cell Protection (preclinical studies to support theory) 9/18/2013 Company Confidential 13 Copyright © 2000 Eli Lilly and Company PLA-TAK-00053932 Source: https://www.indup6340-00013ts.ucsf.edu/docs/fzjf0226 PLA-TAK-00053933 Source: https://www.indupt340-00094ts.ucsf.edu/docs/fzjf0226 Clinical Experience Programs Program Description Affiliates Investigator Initiated A trial/study initiated by Recommended for all Trials (IITs) investigator(s) not Maximize Affiliates Or study (IIS) affiliated with Lilly Observational Studies A study based on US "Evident" collection of data from patient charts Physician Experience Provide free products Mexico, Canada, Programs (PEPs) for specified time Australia frames to physicians for them to gain experience Post Marketing A study based on Spain Surveillance (PMS) collection of AE data from patient charts 9/18/2013 Company Confidential 15 Copyright © 2000 Eli Lilly and Company PLA-TAK-00053934 Source: https://www.indup340-00095ts.ucsf.edu/docs/fzjf0226 PLA-TAK-00053935 Source: https://www.indup6340-00076ts.ucsf.edu/docs/fzjf0226

IITs stands for?

fzjf0226

fzjf0226_p0, fzjf0226_p1, fzjf0226_p2, fzjf0226_p3, fzjf0226_p4, fzjf0226_p5, fzjf0226_p6, fzjf0226_p7, fzjf0226_p8, fzjf0226_p9, fzjf0226_p10, fzjf0226_p11, fzjf0226_p12, fzjf0226_p13, fzjf0226_p14, fzjf0226_p15

Investigator Initiated Trials

PLA-TAK-00053920 PLA-TAK-00053921 Source: :ttps://www.indupt340-00002ts.ucsf.edu/docs/fzjf0226 Clinical Plan supporting Marketing Objectives Marketing Objective : Grow the customer base who differentiate and prefer ACTOS versus Avandia because of the lipid profile by Q3 2003 Strategic Clinical Study Target Date Action Plan Objective Database Locked Demonstrate significant GLAI Q4'02-Q2'03 Publication lipid differences versus Abstracts Avandia Update slide series Symposia Speaker Training Demonstrate Possible IIT (US) TBD Abstracts improvement in Publication postprandial lipidemia 9/18/2013 Company Confidential 3 Copyright © 2000 Eli Lilly and Company PLA-TAK-00053922 Source: https://www.indupt340-00003ts.ucsf.edu/docs/fzjf0226 PLA-TAK-00053923 Source: https://www.indupt340-00004ts.ucsf.edu/docs/fzjf0226 Clinical Plan supporting Marketing Objectives Marketing Objective : Create perception of ACTOS reducing risk of cardiovascular complications starting in 2003 Strategic Clinical Study Target Date Action Plan Objective Database Locked Demonstrate GLAE Q2'02-Q1'02 Included in symposia improvement in Update slide series SBP/DBP Demonstrate GLAC reduction in C- GLAI Q4'02-Q2'03 Reactive Protein Demonstrate effects GLAI Q4'02-Q2'03 on PAI-1 Demonstrate TL-OPI-516 Q3'03? Publication to be planned prevention of Abstracts to be submitted Secondary MI after Symposia first MI Prevention of PROactive Q3'05 Takeda to submit for Cardiovascular EC-444 label change outcomes Publication to be planned Symposia Focus 9/18/2013 Company Confidential 5 Copyright © 2000 Eli Lilly and Company PLA-TAK-00053924 Source: https://www.indup5340-00005ts.ucsf.edu/docs/fzjf0226 Clinical Plan supporting Marketing Objectives Marketing Objective : Create perception of ACTOS reducing risk of cardiovascular complications starting in 2003 Strategic Clinical Study Target Date Action Plan Objective Database Locked Show effects in LDL GLAI -Q4'02-Q2'03 Update slides particle size Incorporate into articles on diabetes dyslipidemia Effects on plaque TL-OPI-516 Q3'03? Symposia topic biology/endothelium US IIT - Fronseca TBD Publication Abstract 9/18/2013 Company Confidential 6 Copyright C 2000 Eli Lilly and Company PLA-TAK-00053925 Source: https://www.indup6340-00006ts.ucsf.edu/docs/fzjf0226 PROactive Objective: Demonstrate that pioglitazone reduces total mortality and macrovascular morbidity in high-risk patients with type 2 diabetes mellitus Number of patients: 5,000 Countries: Austria, Belgium, Czech Republic, Denmark, Estonia, Finland, France, Germany, Hungary, Italy, Latvia, Lithuania, Netherlands, Norway, Poland, Sweden, Switzerland, UK FPV: June 2001 LPV: Q2 2005 Primary Endpoints: All-cause mortality, non-fatal MI, acute coronary syndrome, cardiac intervention, stroke, major leg amputation, bypass surgery, or revascularisation in the leg Secondary Endpoints: Cardiovascular mortality 9/18/2013 Company Confidential 7 Copyright 2000 Eli Lilly and Company PLA-TAK-00053926 Source: https://www.indupe340-00007ts.ucsf.edu/docs/fzjf0226 Clinical Data to Support CV Risk Reduction PROactive 2005 EC 409 EC 410 TL-OPI-503 2004 GLAI EC 404 GLAG 2003 GLAL Evident 2002 2001 9/18/2013 Company Confidential 8 Copyright 2000 Eli Lilly and Company PLA-TAK-00053927 Source: https://www.indup340-00008ts.ucsf.edu/docs/fzjf0226 Clinical Plan supporting Marketing Objectives Marketing Objective : Ensure access and reimbursement of ACTOS in maximize markets Strategic Clinical Study Target Date Action Plan Objective Database Locked Expand European EC 404 Q2'02 Takeda to submit for Label to include EC 405/GLAG label expansion monotherapy Submit abstract in 2003 ADA/EASD/IDF Expand the European PNFP-341 - SU Q2'02 Takeda to submit for label to include 45 mg, PNFP-342 - Met label change Utilize 45 mg EC 409 / GLAP Q3'04-Q3'02 (1 Year) Production forecasts to combination in US EC 410 / GLAQ Q3'04-Q3'02 (1 Year) be modified Expand European PNFP-343 Q2'02 Takeda to submit for Label to include Insulin comb. trial for Q4'04 Q2'04 label change Combination with efficacy and Guidelines/algorithm Insulin European safety-not- developed on yet funded- decreases in suggested insulin? Establish safety in TL-OPI-504 (II-III) Q1'02 Takeda to submit for Class I, II and III CHF TL-OP-520 (I) Q1'03- Q2'03 label modification in Europe Update slide series 9/18/2013 Company Confidential 9 Copyright 2000 Eli Lilly and Company PLA-TAK-00053928 Source: https://www.indupt340-00009ts.ucsf.edu/docs/fzjf0226 PLA-TAK-00053929 Source: https://www.indupe340-00070ts.ucsf.edu/docs/fzjf0226 Clinical Plan supporting Marketing Objectives Strategic Clinical Study Target Date Action Plan Objective Database Locked Reduction/Removal of TL-OPI-506 Q2'04 Discussions need to the liver monitoring continue with the FDA to requirements establish clear safety milestones Demonstrate lack of TL-OPI-509 ? Publication(s) to be Drug-Drug (Cyclosporine B) planned Interactions TL-OPI-510 Q2'01 Abstracts to be submitted (Theophylline) on each study TL-OPI-511 Q2'01 (Atorvastatin) Adolescent data/use TL-OPI-507 TBD 9/18/2013 Company Confidential 11 Copyright © 2000 Eli Lilly and Company PLA-TAK-00053930 PLA-TAK-00053931 Source: https://www.indup5340-0002ts.ucsf.edu/docs/fzjf0226 Possible Suggested Topics for IITs Blood Pressure effects Onset of Action Metformin VS Actos Mechanism of Action Post-Prandial lipids Weight Management Beta-cell Protection (preclinical studies to support theory) 9/18/2013 Company Confidential 13 Copyright © 2000 Eli Lilly and Company PLA-TAK-00053932 Source: https://www.indup6340-00013ts.ucsf.edu/docs/fzjf0226 PLA-TAK-00053933 Source: https://www.indupt340-00094ts.ucsf.edu/docs/fzjf0226 Clinical Experience Programs Program Description Affiliates Investigator Initiated A trial/study initiated by Recommended for all Trials (IITs) investigator(s) not Maximize Affiliates Or study (IIS) affiliated with Lilly Observational Studies A study based on US "Evident" collection of data from patient charts Physician Experience Provide free products Mexico, Canada, Programs (PEPs) for specified time Australia frames to physicians for them to gain experience Post Marketing A study based on Spain Surveillance (PMS) collection of AE data from patient charts 9/18/2013 Company Confidential 15 Copyright © 2000 Eli Lilly and Company PLA-TAK-00053934 Source: https://www.indup340-00095ts.ucsf.edu/docs/fzjf0226 PLA-TAK-00053935 Source: https://www.indup6340-00076ts.ucsf.edu/docs/fzjf0226

What is the fullform of ICR?

kzbn0226

kzbn0226_p4, kzbn0226_p5, kzbn0226_p6

Information Collection Request

D. EPA Should Not Require Submission of "All" Prior Risk Assessments by Manufacturers as a Precondition to Accepting a Manufacturer Request 39 E. EPA Should Limit Public Comments Accepted on a Manufacturer Request to the Expected Scope of the Risk Evaluation. 40 F. EPA Should Remove the Certification Requirement for Manufacturer- Requested Risk Evaluations 40 IX. Information Collection Request (ICR) Burden Estimates 41 Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 EXECUTIVE SUMMARY Under the Toxic Substances Control Act (TSCA), as amended by the Frank R. Lautenberg Chemical Safety for the 21st Century Act (LCSA), EPA must complete risk evaluations under statutory deadlines and using robust scientific standards. To achieve this goal, EPA must be flexible in its scoping of risk evaluations so it can maintain both pace and quality, and to inform the regulatory decision-making process in the most meaningful way. EPA should conduct its scoping to include conditions of use that are relevant and meaningful to a fit-for-purpose risk evaluation, and well-tailored to the problems and decisions at hand. EPA must incorporate Section 26 science standards throughout the risk evaluation process. ACC recommends that EPA apply a tiered approach throughout the risk evaluation process. This approach will allow EPA to identify and consider the most relevant and highest risk conditions of use in an efficient and practical manner. The figure below depicts ACC's suggested approach, which is discussed in further detail in Section VI of these comments. in 10 Workplan High-Quality Refined Risk Evaluation High Priority Chemicals & DRAFT Chemicals Manufactures Risk Evaluation Requestes ASSESSMENTI ASSESEMENT Evaluation incorporating Sections is and 26 of the Lautenberg Chemical Safety Act (LOSAL Scope/Screening Level Risk Evaluation Scientific Standards FINAL Susceprible Weight of Scientific Exidence Evaluations Risk Evaluation Exposures Macards Pooulations CONDITI Certain Conditions of Use Present Do not present an unreasonable risk an unreasonable risk Refined No further risk evaluation risk evaluation needed RULEMAKING No further action, PROCESS COMPLETE - These comments offer overarching comments, specific comments responding to EPA's questions set out in the preamble, and additional specific recommendations for the conduct of risk evaluations under the amended statute. Key observations are: EPA must flexibly scope risk evaluations to focus on the most relevant, greatest potential for risk conditions of use. 1/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 EPA should apply a tiered approach throughout risk evaluation, including when identifying and considering relevant conditions of use. It is essential that Section 26 science standards are applied to science-based decisions throughout the entire risk evaluation process. These requirements are so central to the function of LSCA risk evaluations that they must be described fully and defined in the regulation so they are applied consistently and stakeholders have adequate notice to participate in the development of the risk evaluations. EPA must revise criteria for manufacturer-requested evaluations to align them procedurally with EPA-initiated ones to incentivize their use as contemplated by statute and to make information and certification requests reasonable. The rule must ensure that peer reviews strive to provide consensus reports. EPA must articulate, with specificity, the scientific approaches and methods it will use in the risk evaluation, rather than simply pointing to Agency guidance which is often outdated, inconsistently interpreted, and inconsistently applied. EPA must describe procedures to ensure robust interagency collaborations that include all knowledgeable and potentially affected agencies, and timelines for public comment must be sufficiently robust to allow for a thorough review of EPA analyses. 2/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226

The program which provides free products for specified time frames to physicians to gain experience

fzjf0226

fzjf0226_p0, fzjf0226_p1, fzjf0226_p2, fzjf0226_p3, fzjf0226_p4, fzjf0226_p5, fzjf0226_p6, fzjf0226_p7, fzjf0226_p8, fzjf0226_p9, fzjf0226_p10, fzjf0226_p11, fzjf0226_p12, fzjf0226_p13, fzjf0226_p14, fzjf0226_p15

Physician Experience Programs, Physician Experience Programs (PEPs)

PLA-TAK-00053920 PLA-TAK-00053921 Source: :ttps://www.indupt340-00002ts.ucsf.edu/docs/fzjf0226 Clinical Plan supporting Marketing Objectives Marketing Objective : Grow the customer base who differentiate and prefer ACTOS versus Avandia because of the lipid profile by Q3 2003 Strategic Clinical Study Target Date Action Plan Objective Database Locked Demonstrate significant GLAI Q4'02-Q2'03 Publication lipid differences versus Abstracts Avandia Update slide series Symposia Speaker Training Demonstrate Possible IIT (US) TBD Abstracts improvement in Publication postprandial lipidemia 9/18/2013 Company Confidential 3 Copyright © 2000 Eli Lilly and Company PLA-TAK-00053922 Source: https://www.indupt340-00003ts.ucsf.edu/docs/fzjf0226 PLA-TAK-00053923 Source: https://www.indupt340-00004ts.ucsf.edu/docs/fzjf0226 Clinical Plan supporting Marketing Objectives Marketing Objective : Create perception of ACTOS reducing risk of cardiovascular complications starting in 2003 Strategic Clinical Study Target Date Action Plan Objective Database Locked Demonstrate GLAE Q2'02-Q1'02 Included in symposia improvement in Update slide series SBP/DBP Demonstrate GLAC reduction in C- GLAI Q4'02-Q2'03 Reactive Protein Demonstrate effects GLAI Q4'02-Q2'03 on PAI-1 Demonstrate TL-OPI-516 Q3'03? Publication to be planned prevention of Abstracts to be submitted Secondary MI after Symposia first MI Prevention of PROactive Q3'05 Takeda to submit for Cardiovascular EC-444 label change outcomes Publication to be planned Symposia Focus 9/18/2013 Company Confidential 5 Copyright © 2000 Eli Lilly and Company PLA-TAK-00053924 Source: https://www.indup5340-00005ts.ucsf.edu/docs/fzjf0226 Clinical Plan supporting Marketing Objectives Marketing Objective : Create perception of ACTOS reducing risk of cardiovascular complications starting in 2003 Strategic Clinical Study Target Date Action Plan Objective Database Locked Show effects in LDL GLAI -Q4'02-Q2'03 Update slides particle size Incorporate into articles on diabetes dyslipidemia Effects on plaque TL-OPI-516 Q3'03? Symposia topic biology/endothelium US IIT - Fronseca TBD Publication Abstract 9/18/2013 Company Confidential 6 Copyright C 2000 Eli Lilly and Company PLA-TAK-00053925 Source: https://www.indup6340-00006ts.ucsf.edu/docs/fzjf0226 PROactive Objective: Demonstrate that pioglitazone reduces total mortality and macrovascular morbidity in high-risk patients with type 2 diabetes mellitus Number of patients: 5,000 Countries: Austria, Belgium, Czech Republic, Denmark, Estonia, Finland, France, Germany, Hungary, Italy, Latvia, Lithuania, Netherlands, Norway, Poland, Sweden, Switzerland, UK FPV: June 2001 LPV: Q2 2005 Primary Endpoints: All-cause mortality, non-fatal MI, acute coronary syndrome, cardiac intervention, stroke, major leg amputation, bypass surgery, or revascularisation in the leg Secondary Endpoints: Cardiovascular mortality 9/18/2013 Company Confidential 7 Copyright 2000 Eli Lilly and Company PLA-TAK-00053926 Source: https://www.indupe340-00007ts.ucsf.edu/docs/fzjf0226 Clinical Data to Support CV Risk Reduction PROactive 2005 EC 409 EC 410 TL-OPI-503 2004 GLAI EC 404 GLAG 2003 GLAL Evident 2002 2001 9/18/2013 Company Confidential 8 Copyright 2000 Eli Lilly and Company PLA-TAK-00053927 Source: https://www.indup340-00008ts.ucsf.edu/docs/fzjf0226 Clinical Plan supporting Marketing Objectives Marketing Objective : Ensure access and reimbursement of ACTOS in maximize markets Strategic Clinical Study Target Date Action Plan Objective Database Locked Expand European EC 404 Q2'02 Takeda to submit for Label to include EC 405/GLAG label expansion monotherapy Submit abstract in 2003 ADA/EASD/IDF Expand the European PNFP-341 - SU Q2'02 Takeda to submit for label to include 45 mg, PNFP-342 - Met label change Utilize 45 mg EC 409 / GLAP Q3'04-Q3'02 (1 Year) Production forecasts to combination in US EC 410 / GLAQ Q3'04-Q3'02 (1 Year) be modified Expand European PNFP-343 Q2'02 Takeda to submit for Label to include Insulin comb. trial for Q4'04 Q2'04 label change Combination with efficacy and Guidelines/algorithm Insulin European safety-not- developed on yet funded- decreases in suggested insulin? Establish safety in TL-OPI-504 (II-III) Q1'02 Takeda to submit for Class I, II and III CHF TL-OP-520 (I) Q1'03- Q2'03 label modification in Europe Update slide series 9/18/2013 Company Confidential 9 Copyright 2000 Eli Lilly and Company PLA-TAK-00053928 Source: https://www.indupt340-00009ts.ucsf.edu/docs/fzjf0226 PLA-TAK-00053929 Source: https://www.indupe340-00070ts.ucsf.edu/docs/fzjf0226 Clinical Plan supporting Marketing Objectives Strategic Clinical Study Target Date Action Plan Objective Database Locked Reduction/Removal of TL-OPI-506 Q2'04 Discussions need to the liver monitoring continue with the FDA to requirements establish clear safety milestones Demonstrate lack of TL-OPI-509 ? Publication(s) to be Drug-Drug (Cyclosporine B) planned Interactions TL-OPI-510 Q2'01 Abstracts to be submitted (Theophylline) on each study TL-OPI-511 Q2'01 (Atorvastatin) Adolescent data/use TL-OPI-507 TBD 9/18/2013 Company Confidential 11 Copyright © 2000 Eli Lilly and Company PLA-TAK-00053930 PLA-TAK-00053931 Source: https://www.indup5340-0002ts.ucsf.edu/docs/fzjf0226 Possible Suggested Topics for IITs Blood Pressure effects Onset of Action Metformin VS Actos Mechanism of Action Post-Prandial lipids Weight Management Beta-cell Protection (preclinical studies to support theory) 9/18/2013 Company Confidential 13 Copyright © 2000 Eli Lilly and Company PLA-TAK-00053932 Source: https://www.indup6340-00013ts.ucsf.edu/docs/fzjf0226 PLA-TAK-00053933 Source: https://www.indupt340-00094ts.ucsf.edu/docs/fzjf0226 Clinical Experience Programs Program Description Affiliates Investigator Initiated A trial/study initiated by Recommended for all Trials (IITs) investigator(s) not Maximize Affiliates Or study (IIS) affiliated with Lilly Observational Studies A study based on US "Evident" collection of data from patient charts Physician Experience Provide free products Mexico, Canada, Programs (PEPs) for specified time Australia frames to physicians for them to gain experience Post Marketing A study based on Spain Surveillance (PMS) collection of AE data from patient charts 9/18/2013 Company Confidential 15 Copyright © 2000 Eli Lilly and Company PLA-TAK-00053934 Source: https://www.indup340-00095ts.ucsf.edu/docs/fzjf0226 PLA-TAK-00053935 Source: https://www.indup6340-00076ts.ucsf.edu/docs/fzjf0226