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A study based on collection of AE 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

Post marketing surveillance, Post Marketing Surveillance (PMS), Post Marketing Surveillance

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 does QSAR stands for?

jzbn0226

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

Quantitative structure activity relationship, Quantitative Structure Activity relationship

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 Brozena@americanchemistrv.com 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 Brozena@americanchemistry.com 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

what is page 3 heading

kgpj0226

kgpj0226_p0, kgpj0226_p1, kgpj0226_p2

Memorandum of Meeting

me Mike - santed 7424 Certificate you this Antroberts Po Memorandum of Meeting Date: May 5, 1978 Between: Mr. William W. Goodrich, Institute of Shortening and Edible Oils, Inc. Mr. Robert J. Wager, American Bakers Association Mr. Thomas B. House, American Frozen Food Institute Mr. Richard Lyng, American Meat Institute Mr. George W. Koch, Grocery Manufacturers of America, Inc. Mr. Charles J. Carey, National Food Processors Association and Dr. Donald Kennedy, Commissioner, FDA Mr. Sherwin Gardner, Deputy Commissioner, FDA Mr. Thomas Grumbly, Executive Assistant to the Commissioner, FDA Ms. Ellen Williams, Associate Commissioner for Policy Coordination, FDA Mr. Thomas L. Hooker, Office of Policy Coordination, FDA Mr. J. P. Hile, Associate Commissioner for Regulatory Affairs, FDA Mr. Robert c. Wetherell, Jr., Office of Legislative Services, FDA Mr. Stuart Pape, Office of General Counsel, FDA Dr: Howard Roberts, Acting Director, BF/ Mr. Taylor Quinn, Associate Director for Compliance, BF Dr. Robert Schaffner, Associate Director for Technology, BF Mr. Joseph H. Prendergast, Executive Secretariat, 0C Time: 4:00 - 5:10 p.m. Place: Commissioner's FB#8 Conference Room Subject: Labeling Mr. Goodrich opened the meeting stating it was his desire and the desire of other visitors to participate in the discussion of possible labeling changes in the interest of FDA law. He cautioned the Commissioner not to get set on a fixed deadline to determine new labeling requirements-- to take as long as necessary to avoid controversy. Mr. Goodrich's opening remarks included the following: Source: https://www.industrydocuments.ucsf.edu/docs/kgpj0226 Page 2 - Memorandum of Meeting He is glad to see the scheduled public hearings on food labeling. That greater ingredient labeling may be a little oversold--that it may not deliver the expected benefits--that only 20% of consumers read labels. That if anything was unsafe in a product it wouldn't be there-- that something needs to be done to come up with a new technique for additive labeling--that this needs to be thought out. If a product is ingredient labeled with "Red 40" what will the consumer get out of it? Nutrition labeling is too complex--that the Commissioner should "try" anything we come up with prior to adopting it. He stated that percent labeling is of the same status. That he hopes that FDA is with him and his associates on national uniformity--that they are against preemption--that a State should not require different labeling--that we should prepare a means to update State laws. *e: Open date labeling: Mr Goodrich asked what the industry should be telling the consumers. Registration--should only be for where plants are-should not require routing records submission. There should be a method for people "at risk" to see FDA Establishment Inspection Reports. Mr. Goodrich ended his opening remarks with the observation that there must be some way that a person can challenge FDA when it chooses to enforce a procedure that someone is not in' favor of--that perhaps a challenge on constitutionality. The other visitors at the meeting then presented brief discussions of their opinion about labeling. Following are some of the general concerns raised. That there are unique problems in the baking industry--that they will have a label that only Ph.D's in chemistry will understand. The idea of greatly expanded labeling will come to an end no one expected. Source: https://www.industrydocuments.ucsf.edu/docs/kgpj0226 Page 3 - Memorandum of Meeting Strong feelings were expressed on uniformity--problom: with open dating. Dr. Kennedy commented that various factors such as the "safe and suitable" concept have resulted in a complex situation--tha we need to come up with what consumers will understand--that with such 2 great variety of views available, we must collect them all systematically He pointed out that our effort is not an effort to come up with legislation. Dr. Kennedy stated that he believed that our inquiries will lead us not merely to make more requirements, but will result in more intelligent regulations. That we are concentrating our efforts on a subset of problems and have decided to concentrate on standards and labeling first. Ms. Williams then gave a short discussion as to what her office is doing with respect to labeling. She stated that we are at the point of swinging into full gear for the public hearings on the subject of labeling. # That we have an interagency task force and that the hearing schedule has been established--thati it is hoped that each hearing will be one day in length. That we are preparing a series of in-depth issue papers that will have wide dissemination (topics such as safe and suitable, ingredient labeling, food fortification, substitute foods, etc.). An inventory of current regulations is also being prepared. That this effort is directed to trying to get out individual consumers. We are trying to find out what consumers really want--that there is some question if consumer groups really know. We are trying to get answers from people we don't usually hear from. Each hearing session will be chaired by FTC, USDA and FDA jointly. Ms. Williams announced the schedule of hearings. Tire visitors then remarked concerning two major issues of the meeting, national uniformity and open date labeling. Mr. Goodrich concluded that preemption without some provision for exemption would be unsalable--but he and his associates would like some Federal preemption. Source: :https://www.industrydocuments.ucsf.edu/docs/kgpj0226

Who gave a short discussion as to what her office is doing with respect to labeling?

kgpj0226

kgpj0226_p0, kgpj0226_p1, kgpj0226_p2

Ms. Williams

me Mike - santed 7424 Certificate you this Antroberts Po Memorandum of Meeting Date: May 5, 1978 Between: Mr. William W. Goodrich, Institute of Shortening and Edible Oils, Inc. Mr. Robert J. Wager, American Bakers Association Mr. Thomas B. House, American Frozen Food Institute Mr. Richard Lyng, American Meat Institute Mr. George W. Koch, Grocery Manufacturers of America, Inc. Mr. Charles J. Carey, National Food Processors Association and Dr. Donald Kennedy, Commissioner, FDA Mr. Sherwin Gardner, Deputy Commissioner, FDA Mr. Thomas Grumbly, Executive Assistant to the Commissioner, FDA Ms. Ellen Williams, Associate Commissioner for Policy Coordination, FDA Mr. Thomas L. Hooker, Office of Policy Coordination, FDA Mr. J. P. Hile, Associate Commissioner for Regulatory Affairs, FDA Mr. Robert c. Wetherell, Jr., Office of Legislative Services, FDA Mr. Stuart Pape, Office of General Counsel, FDA Dr: Howard Roberts, Acting Director, BF/ Mr. Taylor Quinn, Associate Director for Compliance, BF Dr. Robert Schaffner, Associate Director for Technology, BF Mr. Joseph H. Prendergast, Executive Secretariat, 0C Time: 4:00 - 5:10 p.m. Place: Commissioner's FB#8 Conference Room Subject: Labeling Mr. Goodrich opened the meeting stating it was his desire and the desire of other visitors to participate in the discussion of possible labeling changes in the interest of FDA law. He cautioned the Commissioner not to get set on a fixed deadline to determine new labeling requirements-- to take as long as necessary to avoid controversy. Mr. Goodrich's opening remarks included the following: Source: https://www.industrydocuments.ucsf.edu/docs/kgpj0226 Page 2 - Memorandum of Meeting He is glad to see the scheduled public hearings on food labeling. That greater ingredient labeling may be a little oversold--that it may not deliver the expected benefits--that only 20% of consumers read labels. That if anything was unsafe in a product it wouldn't be there-- that something needs to be done to come up with a new technique for additive labeling--that this needs to be thought out. If a product is ingredient labeled with "Red 40" what will the consumer get out of it? Nutrition labeling is too complex--that the Commissioner should "try" anything we come up with prior to adopting it. He stated that percent labeling is of the same status. That he hopes that FDA is with him and his associates on national uniformity--that they are against preemption--that a State should not require different labeling--that we should prepare a means to update State laws. *e: Open date labeling: Mr Goodrich asked what the industry should be telling the consumers. Registration--should only be for where plants are-should not require routing records submission. There should be a method for people "at risk" to see FDA Establishment Inspection Reports. Mr. Goodrich ended his opening remarks with the observation that there must be some way that a person can challenge FDA when it chooses to enforce a procedure that someone is not in' favor of--that perhaps a challenge on constitutionality. The other visitors at the meeting then presented brief discussions of their opinion about labeling. Following are some of the general concerns raised. That there are unique problems in the baking industry--that they will have a label that only Ph.D's in chemistry will understand. The idea of greatly expanded labeling will come to an end no one expected. Source: https://www.industrydocuments.ucsf.edu/docs/kgpj0226 Page 3 - Memorandum of Meeting Strong feelings were expressed on uniformity--problom: with open dating. Dr. Kennedy commented that various factors such as the "safe and suitable" concept have resulted in a complex situation--tha we need to come up with what consumers will understand--that with such 2 great variety of views available, we must collect them all systematically He pointed out that our effort is not an effort to come up with legislation. Dr. Kennedy stated that he believed that our inquiries will lead us not merely to make more requirements, but will result in more intelligent regulations. That we are concentrating our efforts on a subset of problems and have decided to concentrate on standards and labeling first. Ms. Williams then gave a short discussion as to what her office is doing with respect to labeling. She stated that we are at the point of swinging into full gear for the public hearings on the subject of labeling. # That we have an interagency task force and that the hearing schedule has been established--thati it is hoped that each hearing will be one day in length. That we are preparing a series of in-depth issue papers that will have wide dissemination (topics such as safe and suitable, ingredient labeling, food fortification, substitute foods, etc.). An inventory of current regulations is also being prepared. That this effort is directed to trying to get out individual consumers. We are trying to find out what consumers really want--that there is some question if consumer groups really know. We are trying to get answers from people we don't usually hear from. Each hearing session will be chaired by FTC, USDA and FDA jointly. Ms. Williams announced the schedule of hearings. Tire visitors then remarked concerning two major issues of the meeting, national uniformity and open date labeling. Mr. Goodrich concluded that preemption without some provision for exemption would be unsalable--but he and his associates would like some Federal preemption. Source: :https://www.industrydocuments.ucsf.edu/docs/kgpj0226

It is hoped that each hearing will be in what length

kgpj0226

kgpj0226_p0, kgpj0226_p1, kgpj0226_p2

one day, one day in length

me Mike - santed 7424 Certificate you this Antroberts Po Memorandum of Meeting Date: May 5, 1978 Between: Mr. William W. Goodrich, Institute of Shortening and Edible Oils, Inc. Mr. Robert J. Wager, American Bakers Association Mr. Thomas B. House, American Frozen Food Institute Mr. Richard Lyng, American Meat Institute Mr. George W. Koch, Grocery Manufacturers of America, Inc. Mr. Charles J. Carey, National Food Processors Association and Dr. Donald Kennedy, Commissioner, FDA Mr. Sherwin Gardner, Deputy Commissioner, FDA Mr. Thomas Grumbly, Executive Assistant to the Commissioner, FDA Ms. Ellen Williams, Associate Commissioner for Policy Coordination, FDA Mr. Thomas L. Hooker, Office of Policy Coordination, FDA Mr. J. P. Hile, Associate Commissioner for Regulatory Affairs, FDA Mr. Robert c. Wetherell, Jr., Office of Legislative Services, FDA Mr. Stuart Pape, Office of General Counsel, FDA Dr: Howard Roberts, Acting Director, BF/ Mr. Taylor Quinn, Associate Director for Compliance, BF Dr. Robert Schaffner, Associate Director for Technology, BF Mr. Joseph H. Prendergast, Executive Secretariat, 0C Time: 4:00 - 5:10 p.m. Place: Commissioner's FB#8 Conference Room Subject: Labeling Mr. Goodrich opened the meeting stating it was his desire and the desire of other visitors to participate in the discussion of possible labeling changes in the interest of FDA law. He cautioned the Commissioner not to get set on a fixed deadline to determine new labeling requirements-- to take as long as necessary to avoid controversy. Mr. Goodrich's opening remarks included the following: Source: https://www.industrydocuments.ucsf.edu/docs/kgpj0226 Page 2 - Memorandum of Meeting He is glad to see the scheduled public hearings on food labeling. That greater ingredient labeling may be a little oversold--that it may not deliver the expected benefits--that only 20% of consumers read labels. That if anything was unsafe in a product it wouldn't be there-- that something needs to be done to come up with a new technique for additive labeling--that this needs to be thought out. If a product is ingredient labeled with "Red 40" what will the consumer get out of it? Nutrition labeling is too complex--that the Commissioner should "try" anything we come up with prior to adopting it. He stated that percent labeling is of the same status. That he hopes that FDA is with him and his associates on national uniformity--that they are against preemption--that a State should not require different labeling--that we should prepare a means to update State laws. *e: Open date labeling: Mr Goodrich asked what the industry should be telling the consumers. Registration--should only be for where plants are-should not require routing records submission. There should be a method for people "at risk" to see FDA Establishment Inspection Reports. Mr. Goodrich ended his opening remarks with the observation that there must be some way that a person can challenge FDA when it chooses to enforce a procedure that someone is not in' favor of--that perhaps a challenge on constitutionality. The other visitors at the meeting then presented brief discussions of their opinion about labeling. Following are some of the general concerns raised. That there are unique problems in the baking industry--that they will have a label that only Ph.D's in chemistry will understand. The idea of greatly expanded labeling will come to an end no one expected. Source: https://www.industrydocuments.ucsf.edu/docs/kgpj0226 Page 3 - Memorandum of Meeting Strong feelings were expressed on uniformity--problom: with open dating. Dr. Kennedy commented that various factors such as the "safe and suitable" concept have resulted in a complex situation--tha we need to come up with what consumers will understand--that with such 2 great variety of views available, we must collect them all systematically He pointed out that our effort is not an effort to come up with legislation. Dr. Kennedy stated that he believed that our inquiries will lead us not merely to make more requirements, but will result in more intelligent regulations. That we are concentrating our efforts on a subset of problems and have decided to concentrate on standards and labeling first. Ms. Williams then gave a short discussion as to what her office is doing with respect to labeling. She stated that we are at the point of swinging into full gear for the public hearings on the subject of labeling. # That we have an interagency task force and that the hearing schedule has been established--thati it is hoped that each hearing will be one day in length. That we are preparing a series of in-depth issue papers that will have wide dissemination (topics such as safe and suitable, ingredient labeling, food fortification, substitute foods, etc.). An inventory of current regulations is also being prepared. That this effort is directed to trying to get out individual consumers. We are trying to find out what consumers really want--that there is some question if consumer groups really know. We are trying to get answers from people we don't usually hear from. Each hearing session will be chaired by FTC, USDA and FDA jointly. Ms. Williams announced the schedule of hearings. Tire visitors then remarked concerning two major issues of the meeting, national uniformity and open date labeling. Mr. Goodrich concluded that preemption without some provision for exemption would be unsalable--but he and his associates would like some Federal preemption. Source: :https://www.industrydocuments.ucsf.edu/docs/kgpj0226

who announced the schedule of hearings

kgpj0226

kgpj0226_p0, kgpj0226_p1, kgpj0226_p2

Ms williams, Ms. Williams

me Mike - santed 7424 Certificate you this Antroberts Po Memorandum of Meeting Date: May 5, 1978 Between: Mr. William W. Goodrich, Institute of Shortening and Edible Oils, Inc. Mr. Robert J. Wager, American Bakers Association Mr. Thomas B. House, American Frozen Food Institute Mr. Richard Lyng, American Meat Institute Mr. George W. Koch, Grocery Manufacturers of America, Inc. Mr. Charles J. Carey, National Food Processors Association and Dr. Donald Kennedy, Commissioner, FDA Mr. Sherwin Gardner, Deputy Commissioner, FDA Mr. Thomas Grumbly, Executive Assistant to the Commissioner, FDA Ms. Ellen Williams, Associate Commissioner for Policy Coordination, FDA Mr. Thomas L. Hooker, Office of Policy Coordination, FDA Mr. J. P. Hile, Associate Commissioner for Regulatory Affairs, FDA Mr. Robert c. Wetherell, Jr., Office of Legislative Services, FDA Mr. Stuart Pape, Office of General Counsel, FDA Dr: Howard Roberts, Acting Director, BF/ Mr. Taylor Quinn, Associate Director for Compliance, BF Dr. Robert Schaffner, Associate Director for Technology, BF Mr. Joseph H. Prendergast, Executive Secretariat, 0C Time: 4:00 - 5:10 p.m. Place: Commissioner's FB#8 Conference Room Subject: Labeling Mr. Goodrich opened the meeting stating it was his desire and the desire of other visitors to participate in the discussion of possible labeling changes in the interest of FDA law. He cautioned the Commissioner not to get set on a fixed deadline to determine new labeling requirements-- to take as long as necessary to avoid controversy. Mr. Goodrich's opening remarks included the following: Source: https://www.industrydocuments.ucsf.edu/docs/kgpj0226 Page 2 - Memorandum of Meeting He is glad to see the scheduled public hearings on food labeling. That greater ingredient labeling may be a little oversold--that it may not deliver the expected benefits--that only 20% of consumers read labels. That if anything was unsafe in a product it wouldn't be there-- that something needs to be done to come up with a new technique for additive labeling--that this needs to be thought out. If a product is ingredient labeled with "Red 40" what will the consumer get out of it? Nutrition labeling is too complex--that the Commissioner should "try" anything we come up with prior to adopting it. He stated that percent labeling is of the same status. That he hopes that FDA is with him and his associates on national uniformity--that they are against preemption--that a State should not require different labeling--that we should prepare a means to update State laws. *e: Open date labeling: Mr Goodrich asked what the industry should be telling the consumers. Registration--should only be for where plants are-should not require routing records submission. There should be a method for people "at risk" to see FDA Establishment Inspection Reports. Mr. Goodrich ended his opening remarks with the observation that there must be some way that a person can challenge FDA when it chooses to enforce a procedure that someone is not in' favor of--that perhaps a challenge on constitutionality. The other visitors at the meeting then presented brief discussions of their opinion about labeling. Following are some of the general concerns raised. That there are unique problems in the baking industry--that they will have a label that only Ph.D's in chemistry will understand. The idea of greatly expanded labeling will come to an end no one expected. Source: https://www.industrydocuments.ucsf.edu/docs/kgpj0226 Page 3 - Memorandum of Meeting Strong feelings were expressed on uniformity--problom: with open dating. Dr. Kennedy commented that various factors such as the "safe and suitable" concept have resulted in a complex situation--tha we need to come up with what consumers will understand--that with such 2 great variety of views available, we must collect them all systematically He pointed out that our effort is not an effort to come up with legislation. Dr. Kennedy stated that he believed that our inquiries will lead us not merely to make more requirements, but will result in more intelligent regulations. That we are concentrating our efforts on a subset of problems and have decided to concentrate on standards and labeling first. Ms. Williams then gave a short discussion as to what her office is doing with respect to labeling. She stated that we are at the point of swinging into full gear for the public hearings on the subject of labeling. # That we have an interagency task force and that the hearing schedule has been established--thati it is hoped that each hearing will be one day in length. That we are preparing a series of in-depth issue papers that will have wide dissemination (topics such as safe and suitable, ingredient labeling, food fortification, substitute foods, etc.). An inventory of current regulations is also being prepared. That this effort is directed to trying to get out individual consumers. We are trying to find out what consumers really want--that there is some question if consumer groups really know. We are trying to get answers from people we don't usually hear from. Each hearing session will be chaired by FTC, USDA and FDA jointly. Ms. Williams announced the schedule of hearings. Tire visitors then remarked concerning two major issues of the meeting, national uniformity and open date labeling. Mr. Goodrich concluded that preemption without some provision for exemption would be unsalable--but he and his associates would like some Federal preemption. Source: :https://www.industrydocuments.ucsf.edu/docs/kgpj0226

What is the heading

tljf0226

tljf0226_p0, tljf0226_p1, tljf0226_p2, tljf0226_p3, tljf0226_p4, tljf0226_p5, tljf0226_p6

Research & Development Organization Chart

Research & Development Organization Chart VP, Research & Development VP, Research & Development Dr. Claire Thom Masatake Kashiyae Admin. Admin. Jean Gragory Evelyn Simmons Last update OCT.2002 Confidential - Subject to Protective Order TAK-BAROND-00161941 Produced in MDL on 09/02/12 Roehel DEP. EX. NO 6 3-20-13, pu Research & Development Organization Chart VP, Research & Development Dr. Claire Thom & Masatake Kashiyae Clinical Research n=66 Dr. Claire Thom Leader, Clinical Research 12/02 n=12 n=14 VP. Clinical Research VP, Clinical Research Admin. Phase I Actosi MPDRAP IIIA Dr. Aziz Karim Dani Beckman Dr. Alfenso Parez Phase I Site Mgr. Pharmacekineticist Program Mgr. Program Mgr. Program Mgr., Actos DM Program Mgr., Actos CV Candy Columbia Dr. Dwain Tolbert Dawn Bradford 08/02 Stephen Cichy Brigit Isaacson Study Mgr. Study Manager Study Manger Study Manager Judi Johnson Maggle Krueger Penny Fleck Patrick Gallagher Study Manager Study Manager Study Manager Lisa Schwartz Study Manager Clement Popovici Patricia Schwartz Jennifer Ryan Study Manager Study Manager Study Manager Margaret Slater Amy Hagaman Jearme Mayer Study Manager Study Manager Todd Johnson Program Mgr., 135 Susen Weszt Ximora Alcaide Assoc. Study Study Manager Manager MCC-135 Mark Hogan Laurei Sindelar Contract Assoc. Study Mgr. Nancy Butler Program Mgr., 475 12/02 Last update OCT 2002 Confidential - Subject to Protective Order TAK-BAROND-00161942 Produced in MDL on 09/02/12 Source: https://www.indupovi's-g002ts.ucsf.edu/docs/tljf0226 Research & Development Organization Chart VP, Research & Development Dr. Claire Thom & Masafake Kashiyae Clinical Research n=66 Dr. Claire Thom Leader, Clinical Research 12/02 n=9 n°8 n=8 ne12 n=1 VP, Crinical Research VP, Cilnical Research VP, Clinical Research VP, Clinical Research MPDRAP I MPDRAP IIA MPDRAP IV, IIB MPDRAP IIB Sr. Word Processor Dr. David Recker Dr. Abebe Haregewoln Dr. Stephen Sainaú Dr. Charlene Stubbs Rudeen Grand Admin. Admin. Admin. Admin. Tiffany Mueller Robin Chrusnlak Kristy Beam Joel Rebinette Word Processor Program Mgr. 677 Program Mgr. 165 10/02 Betsy Gamlin Program Mgr. 715 Program Mgr. CRSD Ed Drower James Pedicano Laura Rodriguez A. Christensen (temp) n=1 Study Mgr. 677 DM Study Mgr. 165 Deborah Tyler Jalme Bayuk Program Mgr. 370 Program Mgr. 375 Julie Kohli Brenda Erickson Study Mgr. 677 Obesity Study Mgr. 185 08/02 08/02 Study Mgr. 370 Study Mgr. 375 Assee. Study Mgr. 677 Tamara Norman Sarah Tsymbalov Kristy Ramirez Program Mgr. -242 Susan Galvez Sludy Mgr. 370 Study Mgr. 375 Program Mgr. 559 10/02 Catharine Fields Diane Rammelsberg Program Mgr. 700 Study Mgr 375 Program Mgr. 428 128 Kumnan Palk Program Mgr. 1013 Heldi Rieckhoff Dr. Shorry Welgand 05/02 Assoc, Study Mgr.-375 Project Mgr. 220 Lynette Wright Study Mgr. 428/128 Study Mgr. 013 Michefe Wagner Nancy Fritz Nancy VanderNoot Study Mgr 375 Michael Dydo Study Mgr. 375 07/02 Program Mgr 070 David Kim Study Mgr. 070 Lolita Sweidan Last update OCT 2002 Confidential - Subject to Protective Order TAK-BAROND-00161943 Produced in MDL on 09/02/12 Source: https://www.indup0v5-00003ts.ucsf.edu/docs/tljf0226 Research & Development Organization Chart VP, Research & Development Dr. Claire Thom & Masatake Kashiyae Biometrics & Data Management n=50 Dr. Claire Thom Director, Biometrics a Data Management Dr. Bob Ahlbrandt n=17 n=3 n=23 Associate Directer Manager Associate Director Adroin Statistics Admin Jackie Gervai Programming Data Management Pam Leiter Dr. Shawn Yu Dr. Fima Gershteyn 08/02 Mgr. Phase I Lead Programmer Manager, Data Mgr. Database Manager, Data Statistics Mgr. Statistica Statistios Mgr. Phase Kathy Kasten Management Programming Management Phase II-IV II-IV Statistics Dr. Charlie Cag Charmairo Thomas Yun Oldshue suzanne Myatt Dr. Frank Ogrine 09/02 Sr. Programmer Sr. Data Analyst Clinical be Sr. Data Analyst Sr. Statistician Tina Nagrani Jie He Administrator ChrisVan Vieet Dr. Hung Lam Statistician Dr. Seleshi Sr. Statistician Ateny Veliz Sr. Stetistician Demissie: Dr. Zhan Ye Lead Programmer Yuan Zhou Data Analyst Clinical DB Data Analyst then Zhao Erika Wentworth Administrator 11/02 Nicholas Safow Project Lead Programmer Sr. Statistician Data Analyst Sr. Statistician Statistician Dr. Tony Tlan Data Analyst Clinicat DB Dr. Mahinda David Schwartz Dr. Anura Abeyrathe Jie Zhang Angelo Scarsella Administrator Karunaratne Sr. Programmer Andrea Bauer Shelly Yang Data Analyst Data Analyst Statistician Statistician Chris Santoro Clinical DB Penny Kedzorski Tomasz 08/02 Administrator Wojtkowski Sr. Statistician Sr. Programmer Data Analyst Thomas Coates Data Analyst Dr. Craig Wilson Yu Kie Kamia Taylor Aliza Durrani Clinical DB Statistician Administrator Data Analyst Data Analyst 09/02 Sr. Programmer Justin Weiler Michelle Powers Ethan Max Sr. Statistician Marie Uwera Dr. YinZhong TCI Oracle Chen Data Analyst Clinical Sr. Programmer Doug Coffman Contractor Jia Llu Mathew Lynes Contractor Programmer Alex Rubin Last update OCT 2002 Confidential - Subject to Protective Order TAK-BAROND-00161944 Produced in MDL on 09/02/12 Research & Development Organization Chart VP, Research & Development Dr. Claire Thom & Masatake Kashiyae Product Development & Planning n=42 Admin. Masetake Kashiyae Phylis Hujett na15 ***3 net Director Admin. Director, Pharmaceutical Director Sr. Manager Project Management Caroline Development & Supplies Non-Clinical Safety & Efficacy Product Evaluation Dr. Michael Ellsseou Winkler Dr. James Morfey Dr. David Baron Dr. Diane Workman Sr. Project Mgr. Sr. Project Mgr. MPDRAP III MPDRAP I Sr. Manager Manager, CMC St. Toxicologist Denise Dennie Mary Ramstack Clinical Supplies Steve Glenn Dr. Robert Weltman Gerry Flanagan Assoc. Project Assoc. Project Sr. Coordinator Assoc. Analytical Toxicologist Mgr. Mgr. Chemist Vickte Beson Clinical Supplies Christopher Durak Kären Kaluzny David Wingate Tram Nguyerd Coordinator Clinical Assoc. Analytical Project Mgr. Assoc. Project Supplies Chemist Mary Garcia Mgr. 08/02 Jason Studer Ellzabeth Cho Coordinator Clinical Sr. Analytical Chemist Assoc. Prolect Supplies Chris Rojewski Mgr. Project Mgr Eric Goll CRO Outsourcing n=4 08/02 Akira Salkawa Coordinator Clinical Masatake Kashiyae Analytical Chernist Supplies Jeremy Baumann 1 Contract Shan Rahmen Assoc. Director, Project Mgr. Coordinator Clinical CRO Outsourcing Sr. Project Mgr. 10/02 Supplies CMC Technician Jay Hansen MPDRAP IIA Mary Murphy Roopal Patel Rosemarie Green Coordinator Clinical Sr. Project Mgr. CRO Outsourcing Sr. CRO Supplies Phermaceutical MPDRAP IV, IIB Administrator Administrator Linda Fisher Scientist Assoc. Project Dr. ines Lauva Annemarie Vance Sheila Lapping 08/02 Mgr. Christine Clinical Supplies Administrative Bronson Operations Planner Assistant Project Mgr. Megan Huges Lena Harnden Project Mgr, Mary Conroy Kieran Corrado Project Mgr. David Aschenmenn Last update OCT 2002 Confidential - Subject to Protective Order TAK-BAROND-00161945 Produced in MDL on 09/02/12 Research & Development Organization Chart VP, Research & Development Dr. Ciaire Thom & Masatake Kashiyae Regulatory Affairs n=32 Dr. Claire Thom Director, Regulatory Affairs Admin. ingrid Hoos Marion Buforac n=16 n°4 n=16 Leader Sr. Mgr. Regulatory Promotion, Product Development Admin. Surveillance & Communication Sr. Mgr. Regulatory Operations Lesile Koohler Mary Lynn Dexter Elleen Vatenta Peter Noblin Mgr. MPDRAP 1 Mgr. MPDRAP III Manager RPS&C Supervisor Lead Submissions Specialist Gloria Harris Steve Daniefson Dr. Janet Lorenz Documents Documentum Brian Phillips Deborah Wigmore Coordinator Assoc Mgr. RPS&C Dana Hettinger Regulatory Assoc Sr. Regulatory Christine Ändersen Regulatory Affairs Assoc. Document Deborah Yarbrough Assistant 08/02 Specialist Documentum Michelle Pettry Contractor Jenniffer Assist, Regulatory Assoc Cindy Hale Anderson Keirre Craigen Regulatory Assoc. Tracy Dianis Kirsten Date Submissions Document Documentum Specialist Manager RPS&C 09/02 Specialist Bryn Assist, Sr. Regulatory Assoc Mary Jo Pritza Horton DeAuna White Mgr. Actos, Tracy Lynch MPDRAP IV, IIB Documentum Janet Haskins Correspondence Mgr. MPDRAP IIA) Assist. Clerk David Breines Gary Weber Sr. Regulatory Assoo Nancy Sheppler Pam Riggio Documentum Regulatory Assoc. Assist. Regulatory Assoc. Joanne Sambor Correspondence Ana Cortez Christie Wong Clerk Alissa Latham Regulatory Assoc. Documentum Regulatory Assoc. 08/02 Assistant 10/02 TEMP Document Onelda Rivera Specialist Karen Marks Last update OCT 2002 Confidential - Subject to Protective Order TAK-BAROND-00161946 Produced in MDL on 09/02/12 Research & Development Organization Chart VP, Research & Development Dr. Claire Thom & Masatake Kashiyae Safely n=25 Dr. Claire Thom Admin. Director, Safety Admin. Elleen Kusfer Dr. John Page Lori Muhlenbeck n=5 the nut n-7 Sr. Manager Sr. Manager Associale Director Supervisor Clinical Safety Post Mktg. Safety Medical Review Data Coordination & Logistics Dr. Connie Kasprzak Dr. Doug Joseph 10/02 Lisa Eck Sr. Cilinical Safety Sr, PM Safety Specialist Medical Safety Manager Specialist Data Coordinator Judly Mopper Dr. Mondira Bhattacharya 10/02 Awilda Colon Clinical Safety PM Safety Medical Safety Reviewer Specialist Specialist Dr. Larissa SirotovaRoya Data Coordinator Bonnie Blach Betty Rieckhoff Beverly Noonan Medical Safety Reviewer Clinical Safety PM Safaly Dr. Albert Dietz Data Coordinator Specialist Specialist Wande Mayfield Mary Ann Casseday Michael Kim Medical Safety Reviewer 11/02 PM Safety Data Coordinator Clinical Safety Speciallet Maria Esocobedo Specialist Mary Gegenhuber 10/02 Data Coordinator Lois MacAdam Data Coordinator Gloria Saldana Last update OCT 2002 Confidential - Subject to Protective Order TAK-BAROND-00161947 Produced in MDL on 09/02/12 Source: https://www.indupovis-o007ts.ucsf.edu/docs/tljf0226

who is VP, Research & Development

tljf0226

tljf0226_p0, tljf0226_p1, tljf0226_p2, tljf0226_p3, tljf0226_p4, tljf0226_p5, tljf0226_p6

Dr Claire Thom & Masatake Kashiyae, Dr. Claire Thom & Masatake Kashiyae

Research & Development Organization Chart VP, Research & Development VP, Research & Development Dr. Claire Thom Masatake Kashiyae Admin. Admin. Jean Gragory Evelyn Simmons Last update OCT.2002 Confidential - Subject to Protective Order TAK-BAROND-00161941 Produced in MDL on 09/02/12 Roehel DEP. EX. NO 6 3-20-13, pu Research & Development Organization Chart VP, Research & Development Dr. Claire Thom & Masatake Kashiyae Clinical Research n=66 Dr. Claire Thom Leader, Clinical Research 12/02 n=12 n=14 VP. Clinical Research VP, Clinical Research Admin. Phase I Actosi MPDRAP IIIA Dr. Aziz Karim Dani Beckman Dr. Alfenso Parez Phase I Site Mgr. Pharmacekineticist Program Mgr. Program Mgr. Program Mgr., Actos DM Program Mgr., Actos CV Candy Columbia Dr. Dwain Tolbert Dawn Bradford 08/02 Stephen Cichy Brigit Isaacson Study Mgr. Study Manager Study Manger Study Manager Judi Johnson Maggle Krueger Penny Fleck Patrick Gallagher Study Manager Study Manager Study Manager Lisa Schwartz Study Manager Clement Popovici Patricia Schwartz Jennifer Ryan Study Manager Study Manager Study Manager Margaret Slater Amy Hagaman Jearme Mayer Study Manager Study Manager Todd Johnson Program Mgr., 135 Susen Weszt Ximora Alcaide Assoc. Study Study Manager Manager MCC-135 Mark Hogan Laurei Sindelar Contract Assoc. Study Mgr. Nancy Butler Program Mgr., 475 12/02 Last update OCT 2002 Confidential - Subject to Protective Order TAK-BAROND-00161942 Produced in MDL on 09/02/12 Source: https://www.indupovi's-g002ts.ucsf.edu/docs/tljf0226 Research & Development Organization Chart VP, Research & Development Dr. Claire Thom & Masafake Kashiyae Clinical Research n=66 Dr. Claire Thom Leader, Clinical Research 12/02 n=9 n°8 n=8 ne12 n=1 VP, Crinical Research VP, Cilnical Research VP, Clinical Research VP, Clinical Research MPDRAP I MPDRAP IIA MPDRAP IV, IIB MPDRAP IIB Sr. Word Processor Dr. David Recker Dr. Abebe Haregewoln Dr. Stephen Sainaú Dr. Charlene Stubbs Rudeen Grand Admin. Admin. Admin. Admin. Tiffany Mueller Robin Chrusnlak Kristy Beam Joel Rebinette Word Processor Program Mgr. 677 Program Mgr. 165 10/02 Betsy Gamlin Program Mgr. 715 Program Mgr. CRSD Ed Drower James Pedicano Laura Rodriguez A. Christensen (temp) n=1 Study Mgr. 677 DM Study Mgr. 165 Deborah Tyler Jalme Bayuk Program Mgr. 370 Program Mgr. 375 Julie Kohli Brenda Erickson Study Mgr. 677 Obesity Study Mgr. 185 08/02 08/02 Study Mgr. 370 Study Mgr. 375 Assee. Study Mgr. 677 Tamara Norman Sarah Tsymbalov Kristy Ramirez Program Mgr. -242 Susan Galvez Sludy Mgr. 370 Study Mgr. 375 Program Mgr. 559 10/02 Catharine Fields Diane Rammelsberg Program Mgr. 700 Study Mgr 375 Program Mgr. 428 128 Kumnan Palk Program Mgr. 1013 Heldi Rieckhoff Dr. Shorry Welgand 05/02 Assoc, Study Mgr.-375 Project Mgr. 220 Lynette Wright Study Mgr. 428/128 Study Mgr. 013 Michefe Wagner Nancy Fritz Nancy VanderNoot Study Mgr 375 Michael Dydo Study Mgr. 375 07/02 Program Mgr 070 David Kim Study Mgr. 070 Lolita Sweidan Last update OCT 2002 Confidential - Subject to Protective Order TAK-BAROND-00161943 Produced in MDL on 09/02/12 Source: https://www.indup0v5-00003ts.ucsf.edu/docs/tljf0226 Research & Development Organization Chart VP, Research & Development Dr. Claire Thom & Masatake Kashiyae Biometrics & Data Management n=50 Dr. Claire Thom Director, Biometrics a Data Management Dr. Bob Ahlbrandt n=17 n=3 n=23 Associate Directer Manager Associate Director Adroin Statistics Admin Jackie Gervai Programming Data Management Pam Leiter Dr. Shawn Yu Dr. Fima Gershteyn 08/02 Mgr. Phase I Lead Programmer Manager, Data Mgr. Database Manager, Data Statistics Mgr. Statistica Statistios Mgr. Phase Kathy Kasten Management Programming Management Phase II-IV II-IV Statistics Dr. Charlie Cag Charmairo Thomas Yun Oldshue suzanne Myatt Dr. Frank Ogrine 09/02 Sr. Programmer Sr. Data Analyst Clinical be Sr. Data Analyst Sr. Statistician Tina Nagrani Jie He Administrator ChrisVan Vieet Dr. Hung Lam Statistician Dr. Seleshi Sr. Statistician Ateny Veliz Sr. Stetistician Demissie: Dr. Zhan Ye Lead Programmer Yuan Zhou Data Analyst Clinical DB Data Analyst then Zhao Erika Wentworth Administrator 11/02 Nicholas Safow Project Lead Programmer Sr. Statistician Data Analyst Sr. Statistician Statistician Dr. Tony Tlan Data Analyst Clinicat DB Dr. Mahinda David Schwartz Dr. Anura Abeyrathe Jie Zhang Angelo Scarsella Administrator Karunaratne Sr. Programmer Andrea Bauer Shelly Yang Data Analyst Data Analyst Statistician Statistician Chris Santoro Clinical DB Penny Kedzorski Tomasz 08/02 Administrator Wojtkowski Sr. Statistician Sr. Programmer Data Analyst Thomas Coates Data Analyst Dr. Craig Wilson Yu Kie Kamia Taylor Aliza Durrani Clinical DB Statistician Administrator Data Analyst Data Analyst 09/02 Sr. Programmer Justin Weiler Michelle Powers Ethan Max Sr. Statistician Marie Uwera Dr. YinZhong TCI Oracle Chen Data Analyst Clinical Sr. Programmer Doug Coffman Contractor Jia Llu Mathew Lynes Contractor Programmer Alex Rubin Last update OCT 2002 Confidential - Subject to Protective Order TAK-BAROND-00161944 Produced in MDL on 09/02/12 Research & Development Organization Chart VP, Research & Development Dr. Claire Thom & Masatake Kashiyae Product Development & Planning n=42 Admin. Masetake Kashiyae Phylis Hujett na15 ***3 net Director Admin. Director, Pharmaceutical Director Sr. Manager Project Management Caroline Development & Supplies Non-Clinical Safety & Efficacy Product Evaluation Dr. Michael Ellsseou Winkler Dr. James Morfey Dr. David Baron Dr. Diane Workman Sr. Project Mgr. Sr. Project Mgr. MPDRAP III MPDRAP I Sr. Manager Manager, CMC St. Toxicologist Denise Dennie Mary Ramstack Clinical Supplies Steve Glenn Dr. Robert Weltman Gerry Flanagan Assoc. Project Assoc. Project Sr. Coordinator Assoc. Analytical Toxicologist Mgr. Mgr. Chemist Vickte Beson Clinical Supplies Christopher Durak Kären Kaluzny David Wingate Tram Nguyerd Coordinator Clinical Assoc. Analytical Project Mgr. Assoc. Project Supplies Chemist Mary Garcia Mgr. 08/02 Jason Studer Ellzabeth Cho Coordinator Clinical Sr. Analytical Chemist Assoc. Prolect Supplies Chris Rojewski Mgr. Project Mgr Eric Goll CRO Outsourcing n=4 08/02 Akira Salkawa Coordinator Clinical Masatake Kashiyae Analytical Chernist Supplies Jeremy Baumann 1 Contract Shan Rahmen Assoc. Director, Project Mgr. Coordinator Clinical CRO Outsourcing Sr. Project Mgr. 10/02 Supplies CMC Technician Jay Hansen MPDRAP IIA Mary Murphy Roopal Patel Rosemarie Green Coordinator Clinical Sr. Project Mgr. CRO Outsourcing Sr. CRO Supplies Phermaceutical MPDRAP IV, IIB Administrator Administrator Linda Fisher Scientist Assoc. Project Dr. ines Lauva Annemarie Vance Sheila Lapping 08/02 Mgr. Christine Clinical Supplies Administrative Bronson Operations Planner Assistant Project Mgr. Megan Huges Lena Harnden Project Mgr, Mary Conroy Kieran Corrado Project Mgr. David Aschenmenn Last update OCT 2002 Confidential - Subject to Protective Order TAK-BAROND-00161945 Produced in MDL on 09/02/12 Research & Development Organization Chart VP, Research & Development Dr. Ciaire Thom & Masatake Kashiyae Regulatory Affairs n=32 Dr. Claire Thom Director, Regulatory Affairs Admin. ingrid Hoos Marion Buforac n=16 n°4 n=16 Leader Sr. Mgr. Regulatory Promotion, Product Development Admin. Surveillance & Communication Sr. Mgr. Regulatory Operations Lesile Koohler Mary Lynn Dexter Elleen Vatenta Peter Noblin Mgr. MPDRAP 1 Mgr. MPDRAP III Manager RPS&C Supervisor Lead Submissions Specialist Gloria Harris Steve Daniefson Dr. Janet Lorenz Documents Documentum Brian Phillips Deborah Wigmore Coordinator Assoc Mgr. RPS&C Dana Hettinger Regulatory Assoc Sr. Regulatory Christine Ändersen Regulatory Affairs Assoc. Document Deborah Yarbrough Assistant 08/02 Specialist Documentum Michelle Pettry Contractor Jenniffer Assist, Regulatory Assoc Cindy Hale Anderson Keirre Craigen Regulatory Assoc. Tracy Dianis Kirsten Date Submissions Document Documentum Specialist Manager RPS&C 09/02 Specialist Bryn Assist, Sr. Regulatory Assoc Mary Jo Pritza Horton DeAuna White Mgr. Actos, Tracy Lynch MPDRAP IV, IIB Documentum Janet Haskins Correspondence Mgr. MPDRAP IIA) Assist. Clerk David Breines Gary Weber Sr. Regulatory Assoo Nancy Sheppler Pam Riggio Documentum Regulatory Assoc. Assist. Regulatory Assoc. Joanne Sambor Correspondence Ana Cortez Christie Wong Clerk Alissa Latham Regulatory Assoc. Documentum Regulatory Assoc. 08/02 Assistant 10/02 TEMP Document Onelda Rivera Specialist Karen Marks Last update OCT 2002 Confidential - Subject to Protective Order TAK-BAROND-00161946 Produced in MDL on 09/02/12 Research & Development Organization Chart VP, Research & Development Dr. Claire Thom & Masatake Kashiyae Safely n=25 Dr. Claire Thom Admin. Director, Safety Admin. Elleen Kusfer Dr. John Page Lori Muhlenbeck n=5 the nut n-7 Sr. Manager Sr. Manager Associale Director Supervisor Clinical Safety Post Mktg. Safety Medical Review Data Coordination & Logistics Dr. Connie Kasprzak Dr. Doug Joseph 10/02 Lisa Eck Sr. Cilinical Safety Sr, PM Safety Specialist Medical Safety Manager Specialist Data Coordinator Judly Mopper Dr. Mondira Bhattacharya 10/02 Awilda Colon Clinical Safety PM Safety Medical Safety Reviewer Specialist Specialist Dr. Larissa SirotovaRoya Data Coordinator Bonnie Blach Betty Rieckhoff Beverly Noonan Medical Safety Reviewer Clinical Safety PM Safaly Dr. Albert Dietz Data Coordinator Specialist Specialist Wande Mayfield Mary Ann Casseday Michael Kim Medical Safety Reviewer 11/02 PM Safety Data Coordinator Clinical Safety Speciallet Maria Esocobedo Specialist Mary Gegenhuber 10/02 Data Coordinator Lois MacAdam Data Coordinator Gloria Saldana Last update OCT 2002 Confidential - Subject to Protective Order TAK-BAROND-00161947 Produced in MDL on 09/02/12 Source: https://www.indupovis-o007ts.ucsf.edu/docs/tljf0226

who is Director,Safety

tljf0226

tljf0226_p0, tljf0226_p1, tljf0226_p2, tljf0226_p3, tljf0226_p4, tljf0226_p5, tljf0226_p6

Dr. John Page, Dr John Page

Research & Development Organization Chart VP, Research & Development VP, Research & Development Dr. Claire Thom Masatake Kashiyae Admin. Admin. Jean Gragory Evelyn Simmons Last update OCT.2002 Confidential - Subject to Protective Order TAK-BAROND-00161941 Produced in MDL on 09/02/12 Roehel DEP. EX. NO 6 3-20-13, pu Research & Development Organization Chart VP, Research & Development Dr. Claire Thom & Masatake Kashiyae Clinical Research n=66 Dr. Claire Thom Leader, Clinical Research 12/02 n=12 n=14 VP. Clinical Research VP, Clinical Research Admin. Phase I Actosi MPDRAP IIIA Dr. Aziz Karim Dani Beckman Dr. Alfenso Parez Phase I Site Mgr. Pharmacekineticist Program Mgr. Program Mgr. Program Mgr., Actos DM Program Mgr., Actos CV Candy Columbia Dr. Dwain Tolbert Dawn Bradford 08/02 Stephen Cichy Brigit Isaacson Study Mgr. Study Manager Study Manger Study Manager Judi Johnson Maggle Krueger Penny Fleck Patrick Gallagher Study Manager Study Manager Study Manager Lisa Schwartz Study Manager Clement Popovici Patricia Schwartz Jennifer Ryan Study Manager Study Manager Study Manager Margaret Slater Amy Hagaman Jearme Mayer Study Manager Study Manager Todd Johnson Program Mgr., 135 Susen Weszt Ximora Alcaide Assoc. Study Study Manager Manager MCC-135 Mark Hogan Laurei Sindelar Contract Assoc. Study Mgr. Nancy Butler Program Mgr., 475 12/02 Last update OCT 2002 Confidential - Subject to Protective Order TAK-BAROND-00161942 Produced in MDL on 09/02/12 Source: https://www.indupovi's-g002ts.ucsf.edu/docs/tljf0226 Research & Development Organization Chart VP, Research & Development Dr. Claire Thom & Masafake Kashiyae Clinical Research n=66 Dr. Claire Thom Leader, Clinical Research 12/02 n=9 n°8 n=8 ne12 n=1 VP, Crinical Research VP, Cilnical Research VP, Clinical Research VP, Clinical Research MPDRAP I MPDRAP IIA MPDRAP IV, IIB MPDRAP IIB Sr. Word Processor Dr. David Recker Dr. Abebe Haregewoln Dr. Stephen Sainaú Dr. Charlene Stubbs Rudeen Grand Admin. Admin. Admin. Admin. Tiffany Mueller Robin Chrusnlak Kristy Beam Joel Rebinette Word Processor Program Mgr. 677 Program Mgr. 165 10/02 Betsy Gamlin Program Mgr. 715 Program Mgr. CRSD Ed Drower James Pedicano Laura Rodriguez A. Christensen (temp) n=1 Study Mgr. 677 DM Study Mgr. 165 Deborah Tyler Jalme Bayuk Program Mgr. 370 Program Mgr. 375 Julie Kohli Brenda Erickson Study Mgr. 677 Obesity Study Mgr. 185 08/02 08/02 Study Mgr. 370 Study Mgr. 375 Assee. Study Mgr. 677 Tamara Norman Sarah Tsymbalov Kristy Ramirez Program Mgr. -242 Susan Galvez Sludy Mgr. 370 Study Mgr. 375 Program Mgr. 559 10/02 Catharine Fields Diane Rammelsberg Program Mgr. 700 Study Mgr 375 Program Mgr. 428 128 Kumnan Palk Program Mgr. 1013 Heldi Rieckhoff Dr. Shorry Welgand 05/02 Assoc, Study Mgr.-375 Project Mgr. 220 Lynette Wright Study Mgr. 428/128 Study Mgr. 013 Michefe Wagner Nancy Fritz Nancy VanderNoot Study Mgr 375 Michael Dydo Study Mgr. 375 07/02 Program Mgr 070 David Kim Study Mgr. 070 Lolita Sweidan Last update OCT 2002 Confidential - Subject to Protective Order TAK-BAROND-00161943 Produced in MDL on 09/02/12 Source: https://www.indup0v5-00003ts.ucsf.edu/docs/tljf0226 Research & Development Organization Chart VP, Research & Development Dr. Claire Thom & Masatake Kashiyae Biometrics & Data Management n=50 Dr. Claire Thom Director, Biometrics a Data Management Dr. Bob Ahlbrandt n=17 n=3 n=23 Associate Directer Manager Associate Director Adroin Statistics Admin Jackie Gervai Programming Data Management Pam Leiter Dr. Shawn Yu Dr. Fima Gershteyn 08/02 Mgr. Phase I Lead Programmer Manager, Data Mgr. Database Manager, Data Statistics Mgr. Statistica Statistios Mgr. Phase Kathy Kasten Management Programming Management Phase II-IV II-IV Statistics Dr. Charlie Cag Charmairo Thomas Yun Oldshue suzanne Myatt Dr. Frank Ogrine 09/02 Sr. Programmer Sr. Data Analyst Clinical be Sr. Data Analyst Sr. Statistician Tina Nagrani Jie He Administrator ChrisVan Vieet Dr. Hung Lam Statistician Dr. Seleshi Sr. Statistician Ateny Veliz Sr. Stetistician Demissie: Dr. Zhan Ye Lead Programmer Yuan Zhou Data Analyst Clinical DB Data Analyst then Zhao Erika Wentworth Administrator 11/02 Nicholas Safow Project Lead Programmer Sr. Statistician Data Analyst Sr. Statistician Statistician Dr. Tony Tlan Data Analyst Clinicat DB Dr. Mahinda David Schwartz Dr. Anura Abeyrathe Jie Zhang Angelo Scarsella Administrator Karunaratne Sr. Programmer Andrea Bauer Shelly Yang Data Analyst Data Analyst Statistician Statistician Chris Santoro Clinical DB Penny Kedzorski Tomasz 08/02 Administrator Wojtkowski Sr. Statistician Sr. Programmer Data Analyst Thomas Coates Data Analyst Dr. Craig Wilson Yu Kie Kamia Taylor Aliza Durrani Clinical DB Statistician Administrator Data Analyst Data Analyst 09/02 Sr. Programmer Justin Weiler Michelle Powers Ethan Max Sr. Statistician Marie Uwera Dr. YinZhong TCI Oracle Chen Data Analyst Clinical Sr. Programmer Doug Coffman Contractor Jia Llu Mathew Lynes Contractor Programmer Alex Rubin Last update OCT 2002 Confidential - Subject to Protective Order TAK-BAROND-00161944 Produced in MDL on 09/02/12 Research & Development Organization Chart VP, Research & Development Dr. Claire Thom & Masatake Kashiyae Product Development & Planning n=42 Admin. Masetake Kashiyae Phylis Hujett na15 ***3 net Director Admin. Director, Pharmaceutical Director Sr. Manager Project Management Caroline Development & Supplies Non-Clinical Safety & Efficacy Product Evaluation Dr. Michael Ellsseou Winkler Dr. James Morfey Dr. David Baron Dr. Diane Workman Sr. Project Mgr. Sr. Project Mgr. MPDRAP III MPDRAP I Sr. Manager Manager, CMC St. Toxicologist Denise Dennie Mary Ramstack Clinical Supplies Steve Glenn Dr. Robert Weltman Gerry Flanagan Assoc. Project Assoc. Project Sr. Coordinator Assoc. Analytical Toxicologist Mgr. Mgr. Chemist Vickte Beson Clinical Supplies Christopher Durak Kären Kaluzny David Wingate Tram Nguyerd Coordinator Clinical Assoc. Analytical Project Mgr. Assoc. Project Supplies Chemist Mary Garcia Mgr. 08/02 Jason Studer Ellzabeth Cho Coordinator Clinical Sr. Analytical Chemist Assoc. Prolect Supplies Chris Rojewski Mgr. Project Mgr Eric Goll CRO Outsourcing n=4 08/02 Akira Salkawa Coordinator Clinical Masatake Kashiyae Analytical Chernist Supplies Jeremy Baumann 1 Contract Shan Rahmen Assoc. Director, Project Mgr. Coordinator Clinical CRO Outsourcing Sr. Project Mgr. 10/02 Supplies CMC Technician Jay Hansen MPDRAP IIA Mary Murphy Roopal Patel Rosemarie Green Coordinator Clinical Sr. Project Mgr. CRO Outsourcing Sr. CRO Supplies Phermaceutical MPDRAP IV, IIB Administrator Administrator Linda Fisher Scientist Assoc. Project Dr. ines Lauva Annemarie Vance Sheila Lapping 08/02 Mgr. Christine Clinical Supplies Administrative Bronson Operations Planner Assistant Project Mgr. Megan Huges Lena Harnden Project Mgr, Mary Conroy Kieran Corrado Project Mgr. David Aschenmenn Last update OCT 2002 Confidential - Subject to Protective Order TAK-BAROND-00161945 Produced in MDL on 09/02/12 Research & Development Organization Chart VP, Research & Development Dr. Ciaire Thom & Masatake Kashiyae Regulatory Affairs n=32 Dr. Claire Thom Director, Regulatory Affairs Admin. ingrid Hoos Marion Buforac n=16 n°4 n=16 Leader Sr. Mgr. Regulatory Promotion, Product Development Admin. Surveillance & Communication Sr. Mgr. Regulatory Operations Lesile Koohler Mary Lynn Dexter Elleen Vatenta Peter Noblin Mgr. MPDRAP 1 Mgr. MPDRAP III Manager RPS&C Supervisor Lead Submissions Specialist Gloria Harris Steve Daniefson Dr. Janet Lorenz Documents Documentum Brian Phillips Deborah Wigmore Coordinator Assoc Mgr. RPS&C Dana Hettinger Regulatory Assoc Sr. Regulatory Christine Ändersen Regulatory Affairs Assoc. Document Deborah Yarbrough Assistant 08/02 Specialist Documentum Michelle Pettry Contractor Jenniffer Assist, Regulatory Assoc Cindy Hale Anderson Keirre Craigen Regulatory Assoc. Tracy Dianis Kirsten Date Submissions Document Documentum Specialist Manager RPS&C 09/02 Specialist Bryn Assist, Sr. Regulatory Assoc Mary Jo Pritza Horton DeAuna White Mgr. Actos, Tracy Lynch MPDRAP IV, IIB Documentum Janet Haskins Correspondence Mgr. MPDRAP IIA) Assist. Clerk David Breines Gary Weber Sr. Regulatory Assoo Nancy Sheppler Pam Riggio Documentum Regulatory Assoc. Assist. Regulatory Assoc. Joanne Sambor Correspondence Ana Cortez Christie Wong Clerk Alissa Latham Regulatory Assoc. Documentum Regulatory Assoc. 08/02 Assistant 10/02 TEMP Document Onelda Rivera Specialist Karen Marks Last update OCT 2002 Confidential - Subject to Protective Order TAK-BAROND-00161946 Produced in MDL on 09/02/12 Research & Development Organization Chart VP, Research & Development Dr. Claire Thom & Masatake Kashiyae Safely n=25 Dr. Claire Thom Admin. Director, Safety Admin. Elleen Kusfer Dr. John Page Lori Muhlenbeck n=5 the nut n-7 Sr. Manager Sr. Manager Associale Director Supervisor Clinical Safety Post Mktg. Safety Medical Review Data Coordination & Logistics Dr. Connie Kasprzak Dr. Doug Joseph 10/02 Lisa Eck Sr. Cilinical Safety Sr, PM Safety Specialist Medical Safety Manager Specialist Data Coordinator Judly Mopper Dr. Mondira Bhattacharya 10/02 Awilda Colon Clinical Safety PM Safety Medical Safety Reviewer Specialist Specialist Dr. Larissa SirotovaRoya Data Coordinator Bonnie Blach Betty Rieckhoff Beverly Noonan Medical Safety Reviewer Clinical Safety PM Safaly Dr. Albert Dietz Data Coordinator Specialist Specialist Wande Mayfield Mary Ann Casseday Michael Kim Medical Safety Reviewer 11/02 PM Safety Data Coordinator Clinical Safety Speciallet Maria Esocobedo Specialist Mary Gegenhuber 10/02 Data Coordinator Lois MacAdam Data Coordinator Gloria Saldana Last update OCT 2002 Confidential - Subject to Protective Order TAK-BAROND-00161947 Produced in MDL on 09/02/12 Source: https://www.indupovis-o007ts.ucsf.edu/docs/tljf0226

From whom is this document

tqjf0226

tqjf0226_p0

tpna news on behalf of tpna news, TPNA News on behalf of tpna news

From: TPNA News on behalf of tpna news To: "Home Office Users; ***Field Users BCC: tpnanewssent@takedapharm.com EXHIBIT Sent: 9/17/2003 4:55:59 PM Subject: Important Takeda Legal Information Relating to Actos - 1st of 2 42 PLEASE READ THIS MESSAGE CAREFULLY As you know, Takeda is involved in a small number of lawsuits relating to ACTOS® (pioglitazone HCI). As a result of these lawsuits, all documents and materials that exist or continue to bei developed pertaining to ACTOS have been and continue to be subject to a litigation hold. This means that all documents, materials, and computer files (including e-mails, word processing documents, slides, etc.) falling into this category must continue to be maintained until you are informed otherwise, regardless of the typical document retention policy. This policy has been in place since the filing of the first lawsuit against Takeda pertaining to ACTOS®. For hard copy format document and materials recorded on disposable electronic storage media, such as documents, materials, information, paper, floppy discs, CDs, video or any other portable medium, you are reminded NOT to dispose of such material, and to continue to retain such material pursuant to your department's filing systems. For electronic management information, documents and materials in Takeda's electronic information management systems, including electronic records saved in your desktop computer, you are reminded that this material may NOT be deleted under any circumstances. To the extent that material exists both electronically and in any other format, all material is to be retained pursuant to your department's filing systems. Any records fitting the classifications set forth above that have been placed ínto storage are also not to be destroyed at any time. Although no new lawsuit has been filed for some time, it nonetheless seemed appropriate to remind all employees that you must continue to carefully maintain, and NOT throw away, all materials pertaining to ACTOS® until further notice. If you have any questions or need any assistance with respect to the retention of ACTOS related documents, please contact Arnold D' Angelo in the Law Department at 847-383-3450. Thank you for your continuing cooperation in this important matter. Source: https://www.indup3-00007ts.ucsf.edu/docs/tqjf0226

Who is the sender of this email?

tqjf0226

tqjf0226_p0

TPNA News on behalf of tpna news

From: TPNA News on behalf of tpna news To: "Home Office Users; ***Field Users BCC: tpnanewssent@takedapharm.com EXHIBIT Sent: 9/17/2003 4:55:59 PM Subject: Important Takeda Legal Information Relating to Actos - 1st of 2 42 PLEASE READ THIS MESSAGE CAREFULLY As you know, Takeda is involved in a small number of lawsuits relating to ACTOS® (pioglitazone HCI). As a result of these lawsuits, all documents and materials that exist or continue to bei developed pertaining to ACTOS have been and continue to be subject to a litigation hold. This means that all documents, materials, and computer files (including e-mails, word processing documents, slides, etc.) falling into this category must continue to be maintained until you are informed otherwise, regardless of the typical document retention policy. This policy has been in place since the filing of the first lawsuit against Takeda pertaining to ACTOS®. For hard copy format document and materials recorded on disposable electronic storage media, such as documents, materials, information, paper, floppy discs, CDs, video or any other portable medium, you are reminded NOT to dispose of such material, and to continue to retain such material pursuant to your department's filing systems. For electronic management information, documents and materials in Takeda's electronic information management systems, including electronic records saved in your desktop computer, you are reminded that this material may NOT be deleted under any circumstances. To the extent that material exists both electronically and in any other format, all material is to be retained pursuant to your department's filing systems. Any records fitting the classifications set forth above that have been placed ínto storage are also not to be destroyed at any time. Although no new lawsuit has been filed for some time, it nonetheless seemed appropriate to remind all employees that you must continue to carefully maintain, and NOT throw away, all materials pertaining to ACTOS® until further notice. If you have any questions or need any assistance with respect to the retention of ACTOS related documents, please contact Arnold D' Angelo in the Law Department at 847-383-3450. Thank you for your continuing cooperation in this important matter. Source: https://www.indup3-00007ts.ucsf.edu/docs/tqjf0226

What is the subject of this email?

tqjf0226

tqjf0226_p0

Important Takeda Legal Information Relating to Actos - 1st of 2

From: TPNA News on behalf of tpna news To: "Home Office Users; ***Field Users BCC: tpnanewssent@takedapharm.com EXHIBIT Sent: 9/17/2003 4:55:59 PM Subject: Important Takeda Legal Information Relating to Actos - 1st of 2 42 PLEASE READ THIS MESSAGE CAREFULLY As you know, Takeda is involved in a small number of lawsuits relating to ACTOS® (pioglitazone HCI). As a result of these lawsuits, all documents and materials that exist or continue to bei developed pertaining to ACTOS have been and continue to be subject to a litigation hold. This means that all documents, materials, and computer files (including e-mails, word processing documents, slides, etc.) falling into this category must continue to be maintained until you are informed otherwise, regardless of the typical document retention policy. This policy has been in place since the filing of the first lawsuit against Takeda pertaining to ACTOS®. For hard copy format document and materials recorded on disposable electronic storage media, such as documents, materials, information, paper, floppy discs, CDs, video or any other portable medium, you are reminded NOT to dispose of such material, and to continue to retain such material pursuant to your department's filing systems. For electronic management information, documents and materials in Takeda's electronic information management systems, including electronic records saved in your desktop computer, you are reminded that this material may NOT be deleted under any circumstances. To the extent that material exists both electronically and in any other format, all material is to be retained pursuant to your department's filing systems. Any records fitting the classifications set forth above that have been placed ínto storage are also not to be destroyed at any time. Although no new lawsuit has been filed for some time, it nonetheless seemed appropriate to remind all employees that you must continue to carefully maintain, and NOT throw away, all materials pertaining to ACTOS® until further notice. If you have any questions or need any assistance with respect to the retention of ACTOS related documents, please contact Arnold D' Angelo in the Law Department at 847-383-3450. Thank you for your continuing cooperation in this important matter. Source: https://www.indup3-00007ts.ucsf.edu/docs/tqjf0226

who is the sender of this email

ptjf0226

ptjf0226_p0

Jose F Caro/AM/LLY, Jose f caro/am/lly, Jose f caro

From: Jose F Caro/AM/LLY Sent: 1/3/2005 8:51:07 AM To: Steven M Paul/AM/LLY@Lilly CC: Jack R Tupman/AM/LLY@Lilly Vince Mihalik/AM/LLY@Lilly; William W Chin/AM/LLY@Lilly Subject: Re: Fw: I 12.20.04 | Eyetech gains $105M on Macugen approval; Pfizer pulls Celebrex ads Steve, The 3 PPARs that were in phase III have either died? (Takeda), are having difficulties (AstraZeneca), or have shown to be not better than the TZDs on body weight and edema (BMS's Muraglitazar). Naveglitazar is at the front now and has the potential of less increase in body weight than the TZDs. I like your idea of continuing the collaboration with Takeda on PPAR and have them help us to develop Naveglitazar. José Steven M Paul/AM/LLY To Jack R Tupman/AM/LLY@Lilly, Jose F Caro/AM/LLY@Lilly, Vince 12/20/2004 12:33 PM Mihalik/AM/LLY@Lilly, William W Chin/AM/LLY@Lilly CC Subject Fw: I 12.20.04 I Eyetech gains $105M on Macugen approval; Pfizer pulls Celebrex ads Wonder if we can extend the Actos deal -- in exchange for a PPAR collaboration around naveglitizar ? Seems like their phase PPAR has died ? Steve Steven M. Paul, M.D. Executive Vice President, Science and Technology President, Lilly Research Laboratories Eli Lilly and Company Lilly Corporate Center Indianapolis, IN 46285 Tel: (317)276-8799 Fax: (317)277-1125 Paul_Steven_M@Lilly.com Forwarded by Steven M Paul/AM/LLY on 12/20/2004 12:31 PM --- FierceBiotech <editors@fiercebiotech.com: To aul_steven_m@lilly.com 12/20/2004 12:18 PM cc Please respond to editors@fiercebiotech.com Subject I 12.20.04 | Eyetech gains $105M on Macugen approval; Pfizer pulls Celebrex ads EXHIBIT Hoven #33 5/1/13 ReD FierceBiotech December 20, 2004 Sign up for TH ******* free: www.fiercebiotech.com This week's sponsor is GoToMeeting. Online Meetings Made Easy Present, demo products and train online - in real time - with GoToMeeting. Reach clients and colleagues without leaving your office. You'll save time and money. Try it Free PLA-TAK-00020529

what algorithm is mentioned in Table 1 heading

qnjf0226

qnjf0226_p0, qnjf0226_p1, qnjf0226_p2, qnjf0226_p3, qnjf0226_p4, qnjf0226_p5, qnjf0226_p6, qnjf0226_p7, qnjf0226_p8, qnjf0226_p9

MGPS** data mining algorithm

From: Gerrits, Charles (TGRD) To: Van Troostenburg, Anne (TGRD); Bhattacharya, Mondira (TGRD) Sent: 10/28/2005 6:37:42 PM Subject: RE: disproportionality report Attachments: Disproportionality Analysis Actos.doo Anna, I am not sure what happened, but this is the updated report. I will have to do some additional checks, but I think the Table is fine now. 1 will be available tomorrow for a telecon, if deemed necessary regards, Charles Original Message From: Van Troostenburg, Anne (TGRD) Sent: Wednesday, October 26, 2005 10:15 AM To: Gerrits, Charles (TGRD) Subject: RE: disproportionality report Thanks Charles, - is it correct that the bladder cancer row is empty? Anna Original Message- From: Gerrits, Charles (TGRD) Sent: 26 October 2005 15:05 To: Bhattacharya, Mondira (TGRD); Van Troostenburg, Anne (TGRD) Subject: RE: disproportionality report Mondira and Anna, See attached an updated version of the disproportionality report. regards, Charles << File: Disproportionality Analysis Actos. doc >> Original Message From: Bhattacharya, Mondira (TGRD) Sent: Monday, October 24, 2005 3:27 PM To: Gerrits, Chartes (TGRD); Van Troostenburg, Anne (TGRD) Subject: RE: disproportionality report Dear Charles: Thanks again for this analysis, I just wanted to bring Anna up-to-date on my further request to you for additional refinement of the analysis which will now compare pla to other diabetic drugs (as a group) and to a all metformin- exposed and an all insulin-exposed group as well. Thanks again, Mondira Original Message- From: Gerrits, Charles (TGRD) Sent: Friday, October 21, 2005 5:52 PM To: Van Troastenburg, Anne (TGRD); Bhattacharya, Mondira (TGRD) Subject: disproportionality report Mondira and Anna, EXHIBIT See attached a first draft for the disproportionality analysis. 44 regards, Feisal Charles Confidential TAK-BHATTM-00117180 Produced in MDL on 09/14/12 << File: Disproportionality Analysis Actos.doc >> Confidential TAK-BHATTM-00117181 Produced in MDL on 09/14/12 Source: https://www.indupo33-00002.ucsf.edu/docs/qnjf0226 Disproportionality Analysis Confidential TAK-BHATTM-00117182 Produced in MDL on 09/14/12 Source: https://www.indup33-00003s.ucsf.edu/docs/qnjf0226 Table of Content 1.0. Introduction 3 2.0. Methods 3 3.0. Results 5 5.0. References 6 Confidential TAK-BHATTM-00117183 Produced in MDL on 09/14/12 Source: https://www.indu/03-00004s.ucsf.edu/docs/qnjf0226 1.0. Introduction At various stages of risk identification and assessment, looking systematically into the data by using computational signal detection algorithms, or so-called data mining algorithms (DMAs), can provide additional information about the existence, and/or characteristics of a signal, or lack thereof. By applying DMAs to large spontaneous reporting system (SRS) databases, like the FDA-AERS, or WHO database, a safety assessor may be able to identify unusual or unexpected drug-event combinations warranting further investigations. Importantly, because of the very nature of SRS databases, applying DMAs to these SRS databases can rarely be used for causal inference.[1,2,3,4] A number of approaches have merged in recent years that search SRS databases for interesting associations. Most such algorithms (e.g. Proportional Reporting Ratio [PRR], Gamma Poisson Shrinker [GPS], Multi-item Gamma Poisson Shrinker [MGPS], Bayesian Confidence Propagation Neural Network [BCPNN]) screen extremely large SRS databases for statistical dependencies between drugs and events in excess of what would be expected if the drug and event were independently distributed in the database (so-called *disproportionality analysis'). [2,3] Since a "signal" is usually considered to be more than just a statistical association, statistical associations found with DMAs are preferably called, signals of disproportionate reporting (SDRs) [5] when discussing statistical disproportionalities in SRS databases without clinical, pharmacological and/or (pharmaco)epidemiological context.[2 This terminology emphasizes that drug-event combinations indicate differential reporting of possible reactions, not necessarily indicative of differential occurrence.[2] 2.0. Methods For the purpose of this report, we analyzed the FDA-AERS database for pioglitazone. The proportional reporting of events coincident with pioglitazone use were compared to Confidential TAK-BHATTM-00117184 Produced in MDL on 09/14/12 Source: https://www.indus133-00005s.ucsf.edu/docs/qnjf0226 the entire FDA-AERS databases, as well as to all antidiabetic agents¹, insulin- preparations, metformin, sulfonylurea derivatives and rosiglitazone. The empirical Bayesian data-mining algorithm, MGPS (as well as its predecessor, GPS) places a prior distribution on the relative reporting ratio that encapsulates a prior belief that most relative reporting ratios are close to a value of "1", resulting in a shrinkage (thus the word "shrinker" in the name of certain algorithms) when the case count is low, thereby preventing overestimation of relative reporting ratio according to a number of papers.) Since some of the selected events had low case counts, we applied stratified MGPS to the FDA-AERS database through the first quarter 2005. Of note, this approach is inherently exploratory and may merely provide insights into the patterns of adverse events particular to a given product relative to other products in the same class or to all other products. As the FDA recommends in its Guidance document on Pharmacovigilance [4], caution should be exercised when making such comparisons, however, because voluntary adverse event reporting systems such as FDA-AERS are subject to a variety of reporting biases, and consequently, the observed SDRs could be due to the underlying indication (i.e., confounding by indication), co-morbid illnesses, protopathic bias, channeling bias and/or other reporting artifacts, inherent to SRS databases. [2,3] Reporting biases differ by product and change over time, and could change differently for different events; it is not possible to predict their impact on data mining scores. In the present study, commonly cited thresholds were used, i.e., a drug-event combination was considered an SDR when the EB05 > 2 - which is the fifth percentile of the posterior distribution, meaning that there is a 95% probability that the "true" RR exceeds the EB05.[2,6] For the purpose of this report, we analyzed merely the statistical association between use of pioglitazone and the reporting of congestive heart failure (CHF), edema, weight gain, neoplasia, liver, anemia, and rhabdomyolysis, as they compare to the reporting with all other drugs in the FDA-AERS database, as well as to all antidiabetic agents¹, insulin- preparations, metformin, sulfonylurea derivatives and rosiglitazone. The analyses were conducted with Qscan-FDA, version 3.1 (Reston, VA, USA). 1 Antidiabetic agents: Insuline-preparations, metformin, sulfonylurea-derivatives, and rosiglitazone Confidential TAK-BHATTM-00117185 Produced in MDL on 09/14/12 Source: 3.0. Results Table 1 shows the data mining results. It can be seen that compared to all other drugs in the database as well as compared to all antidiabetic agents², insulin-preparations, metformin and sulfonylurea derivatives, the empirical Bayesian DMA, highlights that CHF, edema and weight gain are disproportionally more reported for pioglitazone, However, these events do not seem to be disproportionally more reported with pioglitazone than with rosiglitazone. Additionally, hepatic events are more reported with pioglitazone according to this MGPS analysis compared to all other drugs in the database as well as compared to all antidiabetic drugs combined and insulin preparations separately. Relative to all other drugs in the FDA-AERS database, but not in comparison to all antidiabetic agents combined or separately, was bladder cancer disproportionally more reported. Non of the analyzed events were disproportionally more reported with pioglitazone relative to rosiglitazone. 4.0. Discussion A cross-sectional disproportionality analysis in the FDA-AERS database for pioglitazone has revealed that CHF, edema, and weight gain are reported disproportionally more with pioglitazone than compared to all other drugs in the FDA-AERS database, as well as compared to other antidiabetic drugs. However, the reporting of these events is not disproportionally more reported with pioglitazone than with other thiazolidinediones, such as rosiglitazone. Importantly, the observed SDRs are not necessarily indicative of a causal relationship, but could be due to the underlying disease (i.e., confounding by indication), co-morbid illnesses, protopathic bias, channeling bias and/or other reporting artifacts, inherent to SRS databases. Dependenti upon the quality and completeness of individual case reports, case-by-case analyses of these reports will be able to provide more information in this regard. Heart failure has recently been termed "the frequent, forgotten, and often fatal complication of diabetes"[7]. In a recent study Nichols et al. in the Kaiser Permanente 2 Antidiabetic agents: Insuline-preparations, metformin, sulfonylurea-derivatives, and rosiglitazone Confidential TAK-BHATTM-00117186 Produced in MDL on 09/14/12 Northwest (KPNW) database, calculated the incidence rate of CHF in a cohort of type II diabetes patients as 30.9 per 1,000 patient-years compared to 12,4 per 1,000 patient-years in an age-matched non-diabetic cohort [8], yielding a relative risk of 2.5. In addition, the severity of diabetes is an independent risk factor for CHF as was shown by Iribarren and co-workers who demonstrated that each 1% increase in baseline HbA1c was associated with an 8% (95% CI: 5% - 12%) increased risk of CHF. This could explain why compared to rosiglitazone - which is probably being prescribed to diabetes patients with more or less the same severity - the relative reporting of CHF does not seem to be disproportionally increased, while increased compared to the other backgrounds. Likewise, liver events have been associated with, not merely diabetes itself, but also with the severity of type II diabetes.[9] The MHA is currently conducting two large observational studies - a retrospective cohort study as well as a nested case-control study - to evaluate whether exposure to pioglitazone is associated with an increased risk of bladder cancer. The results from the retrospective follow-up study have not shown an increased risk of bladder cancer. 5.0. References 1 ALMENOFF J, TONNING JM, GOULD AL et al.: Perspectives on the use of data mining in plarmacovigilance. Drug "(2005) 28(11):981-1007. 2 HAUBEN M, MADIGAN D, GERRITS CM, WALSH L, VAN PULJENBROEK EP: The role of data mining in pharmacovigilance. Expert Opin Drug Saf(2005) 4(5):929-948. 3 HAUBEN M, PATADIA V, GERRITS C, WALSH L, REICH L: Data Mining in Pharmacovigilance: The Need for a Balanced Perspective. Drug Saf(2005) 28(in Press) 4 US-FDA. Guidance for Industry Good Pharmacovigilance Practicos and Pharmiacocpidemiologic Assessment. May, 2004; http://www.fda.gov/OHRMS/DOCKETS/98fr/04d-0189-gd10001- 5767dft.doc 5 HAUBEN M, REICH J: Communication of findings in pharmacovigilance: use of term "signal" and the need for precision in ils use. Eur J Clin Pharmacol (2005) 6 SZARFMAN A, MACHADO SG, O'NEILL RT: Use of screening algorithms and computer systems to efficiently signal ligher-than-expected combinations of drugs and events in the US FDA's spontaneous reports database. Drug Saf 25(6):381-392. Confidential TAK-BHATTM-00117187 Produced in MDL on 09/14/12 Source: 7 BELL DSH: Heart Failure: The frequent, forgotten, and often fatal complication of diabetes. Diabetes Care (2003) 26(8):2433-2441. 8 NICHOLS GA, GULLION CM, KORO CE, EPHROSS SA, BROWN JB: The Incidence of Congestive Heart Failure in Type 2 Diabetes: An opdate. Diabetes Care (2004)27(8):1879-1884. 9 EL-SERAG HB, TRAN T, EVERHART JB: Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterology (2004) 126(2):460-468. Confidential TAK-BHATTM-00117188 Produced in MDL on 09/14/12 Source: https://www.indupo33-00009.ucsf.edu/docs/qnjf0226 Table 1. Signaling Scores for selected events for Pioglitazone according to MGPS** data mining algortthm Multi-itern Gamma Poisson Shrinker (MGPS) all drug In FDA- all antidiabetics insulins Metformin AERS Sulfonylurea Rosiglifazione EB05 EB05 EB05 EB05 EB05 EB05 CHF 1.9 0.9 Edema 0.9 Weight Gain 0.8 Neoplasia (SOC) 1.5 1.4 1.5 1.1 1.2 1.2 - bladder cancer 29 1.8 1.4 1.2 1.3 0.9 Liver (TAK) 1.7 1.3 1.3 1.0 Anemia (TAK) 1.0 0.8 1.1 0,9 0.7 0.7 Rhabdemyalysis (SMQ) 1.7 1.0 1.2 0.7 0.9 1.0 SDR a Signal of Disproportional Reporting et MGRS: Mulit-Rem Gamma Poisson Sbrinken a signal score is representing en SDR when ESOS 2 2 ... Glicfazide; Gilmepiride; Glipizide; Glyburide; Totbutamide Antidiabetic agents: insuline-preparations, metformia, and rosiglitazons Confidential TAK-BHATTM-00117189 Produced in MDL on 09/14/12 Source: https://www.indusp/o3-0001.ucsf.edu/docs/qnjf0226

when will I be available for telecon if deemed necessary

qnjf0226

qnjf0226_p0, qnjf0226_p1, qnjf0226_p2, qnjf0226_p3, qnjf0226_p4, qnjf0226_p5, qnjf0226_p6, qnjf0226_p7, qnjf0226_p8, qnjf0226_p9

tomorrow

From: Gerrits, Charles (TGRD) To: Van Troostenburg, Anne (TGRD); Bhattacharya, Mondira (TGRD) Sent: 10/28/2005 6:37:42 PM Subject: RE: disproportionality report Attachments: Disproportionality Analysis Actos.doo Anna, I am not sure what happened, but this is the updated report. I will have to do some additional checks, but I think the Table is fine now. 1 will be available tomorrow for a telecon, if deemed necessary regards, Charles Original Message From: Van Troostenburg, Anne (TGRD) Sent: Wednesday, October 26, 2005 10:15 AM To: Gerrits, Charles (TGRD) Subject: RE: disproportionality report Thanks Charles, - is it correct that the bladder cancer row is empty? Anna Original Message- From: Gerrits, Charles (TGRD) Sent: 26 October 2005 15:05 To: Bhattacharya, Mondira (TGRD); Van Troostenburg, Anne (TGRD) Subject: RE: disproportionality report Mondira and Anna, See attached an updated version of the disproportionality report. regards, Charles << File: Disproportionality Analysis Actos. doc >> Original Message From: Bhattacharya, Mondira (TGRD) Sent: Monday, October 24, 2005 3:27 PM To: Gerrits, Chartes (TGRD); Van Troostenburg, Anne (TGRD) Subject: RE: disproportionality report Dear Charles: Thanks again for this analysis, I just wanted to bring Anna up-to-date on my further request to you for additional refinement of the analysis which will now compare pla to other diabetic drugs (as a group) and to a all metformin- exposed and an all insulin-exposed group as well. Thanks again, Mondira Original Message- From: Gerrits, Charles (TGRD) Sent: Friday, October 21, 2005 5:52 PM To: Van Troastenburg, Anne (TGRD); Bhattacharya, Mondira (TGRD) Subject: disproportionality report Mondira and Anna, EXHIBIT See attached a first draft for the disproportionality analysis. 44 regards, Feisal Charles Confidential TAK-BHATTM-00117180 Produced in MDL on 09/14/12 << File: Disproportionality Analysis Actos.doc >> Confidential TAK-BHATTM-00117181 Produced in MDL on 09/14/12 Source: https://www.indupo33-00002.ucsf.edu/docs/qnjf0226 Disproportionality Analysis Confidential TAK-BHATTM-00117182 Produced in MDL on 09/14/12 Source: https://www.indup33-00003s.ucsf.edu/docs/qnjf0226 Table of Content 1.0. Introduction 3 2.0. Methods 3 3.0. Results 5 5.0. References 6 Confidential TAK-BHATTM-00117183 Produced in MDL on 09/14/12 Source: https://www.indu/03-00004s.ucsf.edu/docs/qnjf0226 1.0. Introduction At various stages of risk identification and assessment, looking systematically into the data by using computational signal detection algorithms, or so-called data mining algorithms (DMAs), can provide additional information about the existence, and/or characteristics of a signal, or lack thereof. By applying DMAs to large spontaneous reporting system (SRS) databases, like the FDA-AERS, or WHO database, a safety assessor may be able to identify unusual or unexpected drug-event combinations warranting further investigations. Importantly, because of the very nature of SRS databases, applying DMAs to these SRS databases can rarely be used for causal inference.[1,2,3,4] A number of approaches have merged in recent years that search SRS databases for interesting associations. Most such algorithms (e.g. Proportional Reporting Ratio [PRR], Gamma Poisson Shrinker [GPS], Multi-item Gamma Poisson Shrinker [MGPS], Bayesian Confidence Propagation Neural Network [BCPNN]) screen extremely large SRS databases for statistical dependencies between drugs and events in excess of what would be expected if the drug and event were independently distributed in the database (so-called *disproportionality analysis'). [2,3] Since a "signal" is usually considered to be more than just a statistical association, statistical associations found with DMAs are preferably called, signals of disproportionate reporting (SDRs) [5] when discussing statistical disproportionalities in SRS databases without clinical, pharmacological and/or (pharmaco)epidemiological context.[2 This terminology emphasizes that drug-event combinations indicate differential reporting of possible reactions, not necessarily indicative of differential occurrence.[2] 2.0. Methods For the purpose of this report, we analyzed the FDA-AERS database for pioglitazone. The proportional reporting of events coincident with pioglitazone use were compared to Confidential TAK-BHATTM-00117184 Produced in MDL on 09/14/12 Source: https://www.indus133-00005s.ucsf.edu/docs/qnjf0226 the entire FDA-AERS databases, as well as to all antidiabetic agents¹, insulin- preparations, metformin, sulfonylurea derivatives and rosiglitazone. The empirical Bayesian data-mining algorithm, MGPS (as well as its predecessor, GPS) places a prior distribution on the relative reporting ratio that encapsulates a prior belief that most relative reporting ratios are close to a value of "1", resulting in a shrinkage (thus the word "shrinker" in the name of certain algorithms) when the case count is low, thereby preventing overestimation of relative reporting ratio according to a number of papers.) Since some of the selected events had low case counts, we applied stratified MGPS to the FDA-AERS database through the first quarter 2005. Of note, this approach is inherently exploratory and may merely provide insights into the patterns of adverse events particular to a given product relative to other products in the same class or to all other products. As the FDA recommends in its Guidance document on Pharmacovigilance [4], caution should be exercised when making such comparisons, however, because voluntary adverse event reporting systems such as FDA-AERS are subject to a variety of reporting biases, and consequently, the observed SDRs could be due to the underlying indication (i.e., confounding by indication), co-morbid illnesses, protopathic bias, channeling bias and/or other reporting artifacts, inherent to SRS databases. [2,3] Reporting biases differ by product and change over time, and could change differently for different events; it is not possible to predict their impact on data mining scores. In the present study, commonly cited thresholds were used, i.e., a drug-event combination was considered an SDR when the EB05 > 2 - which is the fifth percentile of the posterior distribution, meaning that there is a 95% probability that the "true" RR exceeds the EB05.[2,6] For the purpose of this report, we analyzed merely the statistical association between use of pioglitazone and the reporting of congestive heart failure (CHF), edema, weight gain, neoplasia, liver, anemia, and rhabdomyolysis, as they compare to the reporting with all other drugs in the FDA-AERS database, as well as to all antidiabetic agents¹, insulin- preparations, metformin, sulfonylurea derivatives and rosiglitazone. The analyses were conducted with Qscan-FDA, version 3.1 (Reston, VA, USA). 1 Antidiabetic agents: Insuline-preparations, metformin, sulfonylurea-derivatives, and rosiglitazone Confidential TAK-BHATTM-00117185 Produced in MDL on 09/14/12 Source: 3.0. Results Table 1 shows the data mining results. It can be seen that compared to all other drugs in the database as well as compared to all antidiabetic agents², insulin-preparations, metformin and sulfonylurea derivatives, the empirical Bayesian DMA, highlights that CHF, edema and weight gain are disproportionally more reported for pioglitazone, However, these events do not seem to be disproportionally more reported with pioglitazone than with rosiglitazone. Additionally, hepatic events are more reported with pioglitazone according to this MGPS analysis compared to all other drugs in the database as well as compared to all antidiabetic drugs combined and insulin preparations separately. Relative to all other drugs in the FDA-AERS database, but not in comparison to all antidiabetic agents combined or separately, was bladder cancer disproportionally more reported. Non of the analyzed events were disproportionally more reported with pioglitazone relative to rosiglitazone. 4.0. Discussion A cross-sectional disproportionality analysis in the FDA-AERS database for pioglitazone has revealed that CHF, edema, and weight gain are reported disproportionally more with pioglitazone than compared to all other drugs in the FDA-AERS database, as well as compared to other antidiabetic drugs. However, the reporting of these events is not disproportionally more reported with pioglitazone than with other thiazolidinediones, such as rosiglitazone. Importantly, the observed SDRs are not necessarily indicative of a causal relationship, but could be due to the underlying disease (i.e., confounding by indication), co-morbid illnesses, protopathic bias, channeling bias and/or other reporting artifacts, inherent to SRS databases. Dependenti upon the quality and completeness of individual case reports, case-by-case analyses of these reports will be able to provide more information in this regard. Heart failure has recently been termed "the frequent, forgotten, and often fatal complication of diabetes"[7]. In a recent study Nichols et al. in the Kaiser Permanente 2 Antidiabetic agents: Insuline-preparations, metformin, sulfonylurea-derivatives, and rosiglitazone Confidential TAK-BHATTM-00117186 Produced in MDL on 09/14/12 Northwest (KPNW) database, calculated the incidence rate of CHF in a cohort of type II diabetes patients as 30.9 per 1,000 patient-years compared to 12,4 per 1,000 patient-years in an age-matched non-diabetic cohort [8], yielding a relative risk of 2.5. In addition, the severity of diabetes is an independent risk factor for CHF as was shown by Iribarren and co-workers who demonstrated that each 1% increase in baseline HbA1c was associated with an 8% (95% CI: 5% - 12%) increased risk of CHF. This could explain why compared to rosiglitazone - which is probably being prescribed to diabetes patients with more or less the same severity - the relative reporting of CHF does not seem to be disproportionally increased, while increased compared to the other backgrounds. Likewise, liver events have been associated with, not merely diabetes itself, but also with the severity of type II diabetes.[9] The MHA is currently conducting two large observational studies - a retrospective cohort study as well as a nested case-control study - to evaluate whether exposure to pioglitazone is associated with an increased risk of bladder cancer. The results from the retrospective follow-up study have not shown an increased risk of bladder cancer. 5.0. References 1 ALMENOFF J, TONNING JM, GOULD AL et al.: Perspectives on the use of data mining in plarmacovigilance. Drug "(2005) 28(11):981-1007. 2 HAUBEN M, MADIGAN D, GERRITS CM, WALSH L, VAN PULJENBROEK EP: The role of data mining in pharmacovigilance. Expert Opin Drug Saf(2005) 4(5):929-948. 3 HAUBEN M, PATADIA V, GERRITS C, WALSH L, REICH L: Data Mining in Pharmacovigilance: The Need for a Balanced Perspective. Drug Saf(2005) 28(in Press) 4 US-FDA. Guidance for Industry Good Pharmacovigilance Practicos and Pharmiacocpidemiologic Assessment. May, 2004; http://www.fda.gov/OHRMS/DOCKETS/98fr/04d-0189-gd10001- 5767dft.doc 5 HAUBEN M, REICH J: Communication of findings in pharmacovigilance: use of term "signal" and the need for precision in ils use. Eur J Clin Pharmacol (2005) 6 SZARFMAN A, MACHADO SG, O'NEILL RT: Use of screening algorithms and computer systems to efficiently signal ligher-than-expected combinations of drugs and events in the US FDA's spontaneous reports database. Drug Saf 25(6):381-392. Confidential TAK-BHATTM-00117187 Produced in MDL on 09/14/12 Source: 7 BELL DSH: Heart Failure: The frequent, forgotten, and often fatal complication of diabetes. Diabetes Care (2003) 26(8):2433-2441. 8 NICHOLS GA, GULLION CM, KORO CE, EPHROSS SA, BROWN JB: The Incidence of Congestive Heart Failure in Type 2 Diabetes: An opdate. Diabetes Care (2004)27(8):1879-1884. 9 EL-SERAG HB, TRAN T, EVERHART JB: Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterology (2004) 126(2):460-468. Confidential TAK-BHATTM-00117188 Produced in MDL on 09/14/12 Source: https://www.indupo33-00009.ucsf.edu/docs/qnjf0226 Table 1. Signaling Scores for selected events for Pioglitazone according to MGPS** data mining algortthm Multi-itern Gamma Poisson Shrinker (MGPS) all drug In FDA- all antidiabetics insulins Metformin AERS Sulfonylurea Rosiglifazione EB05 EB05 EB05 EB05 EB05 EB05 CHF 1.9 0.9 Edema 0.9 Weight Gain 0.8 Neoplasia (SOC) 1.5 1.4 1.5 1.1 1.2 1.2 - bladder cancer 29 1.8 1.4 1.2 1.3 0.9 Liver (TAK) 1.7 1.3 1.3 1.0 Anemia (TAK) 1.0 0.8 1.1 0,9 0.7 0.7 Rhabdemyalysis (SMQ) 1.7 1.0 1.2 0.7 0.9 1.0 SDR a Signal of Disproportional Reporting et MGRS: Mulit-Rem Gamma Poisson Sbrinken a signal score is representing en SDR when ESOS 2 2 ... Glicfazide; Gilmepiride; Glipizide; Glyburide; Totbutamide Antidiabetic agents: insuline-preparations, metformia, and rosiglitazons Confidential TAK-BHATTM-00117189 Produced in MDL on 09/14/12 Source: https://www.indusp/o3-0001.ucsf.edu/docs/qnjf0226

which version of disproportionality report was attached

qnjf0226

qnjf0226_p0, qnjf0226_p1, qnjf0226_p2, qnjf0226_p3, qnjf0226_p4, qnjf0226_p5, qnjf0226_p6, qnjf0226_p7, qnjf0226_p8, qnjf0226_p9

updated, an updated version

From: Gerrits, Charles (TGRD) To: Van Troostenburg, Anne (TGRD); Bhattacharya, Mondira (TGRD) Sent: 10/28/2005 6:37:42 PM Subject: RE: disproportionality report Attachments: Disproportionality Analysis Actos.doo Anna, I am not sure what happened, but this is the updated report. I will have to do some additional checks, but I think the Table is fine now. 1 will be available tomorrow for a telecon, if deemed necessary regards, Charles Original Message From: Van Troostenburg, Anne (TGRD) Sent: Wednesday, October 26, 2005 10:15 AM To: Gerrits, Charles (TGRD) Subject: RE: disproportionality report Thanks Charles, - is it correct that the bladder cancer row is empty? Anna Original Message- From: Gerrits, Charles (TGRD) Sent: 26 October 2005 15:05 To: Bhattacharya, Mondira (TGRD); Van Troostenburg, Anne (TGRD) Subject: RE: disproportionality report Mondira and Anna, See attached an updated version of the disproportionality report. regards, Charles << File: Disproportionality Analysis Actos. doc >> Original Message From: Bhattacharya, Mondira (TGRD) Sent: Monday, October 24, 2005 3:27 PM To: Gerrits, Chartes (TGRD); Van Troostenburg, Anne (TGRD) Subject: RE: disproportionality report Dear Charles: Thanks again for this analysis, I just wanted to bring Anna up-to-date on my further request to you for additional refinement of the analysis which will now compare pla to other diabetic drugs (as a group) and to a all metformin- exposed and an all insulin-exposed group as well. Thanks again, Mondira Original Message- From: Gerrits, Charles (TGRD) Sent: Friday, October 21, 2005 5:52 PM To: Van Troastenburg, Anne (TGRD); Bhattacharya, Mondira (TGRD) Subject: disproportionality report Mondira and Anna, EXHIBIT See attached a first draft for the disproportionality analysis. 44 regards, Feisal Charles Confidential TAK-BHATTM-00117180 Produced in MDL on 09/14/12 << File: Disproportionality Analysis Actos.doc >> Confidential TAK-BHATTM-00117181 Produced in MDL on 09/14/12 Source: https://www.indupo33-00002.ucsf.edu/docs/qnjf0226 Disproportionality Analysis Confidential TAK-BHATTM-00117182 Produced in MDL on 09/14/12 Source: https://www.indup33-00003s.ucsf.edu/docs/qnjf0226 Table of Content 1.0. Introduction 3 2.0. Methods 3 3.0. Results 5 5.0. References 6 Confidential TAK-BHATTM-00117183 Produced in MDL on 09/14/12 Source: https://www.indu/03-00004s.ucsf.edu/docs/qnjf0226 1.0. Introduction At various stages of risk identification and assessment, looking systematically into the data by using computational signal detection algorithms, or so-called data mining algorithms (DMAs), can provide additional information about the existence, and/or characteristics of a signal, or lack thereof. By applying DMAs to large spontaneous reporting system (SRS) databases, like the FDA-AERS, or WHO database, a safety assessor may be able to identify unusual or unexpected drug-event combinations warranting further investigations. Importantly, because of the very nature of SRS databases, applying DMAs to these SRS databases can rarely be used for causal inference.[1,2,3,4] A number of approaches have merged in recent years that search SRS databases for interesting associations. Most such algorithms (e.g. Proportional Reporting Ratio [PRR], Gamma Poisson Shrinker [GPS], Multi-item Gamma Poisson Shrinker [MGPS], Bayesian Confidence Propagation Neural Network [BCPNN]) screen extremely large SRS databases for statistical dependencies between drugs and events in excess of what would be expected if the drug and event were independently distributed in the database (so-called *disproportionality analysis'). [2,3] Since a "signal" is usually considered to be more than just a statistical association, statistical associations found with DMAs are preferably called, signals of disproportionate reporting (SDRs) [5] when discussing statistical disproportionalities in SRS databases without clinical, pharmacological and/or (pharmaco)epidemiological context.[2 This terminology emphasizes that drug-event combinations indicate differential reporting of possible reactions, not necessarily indicative of differential occurrence.[2] 2.0. Methods For the purpose of this report, we analyzed the FDA-AERS database for pioglitazone. The proportional reporting of events coincident with pioglitazone use were compared to Confidential TAK-BHATTM-00117184 Produced in MDL on 09/14/12 Source: https://www.indus133-00005s.ucsf.edu/docs/qnjf0226 the entire FDA-AERS databases, as well as to all antidiabetic agents¹, insulin- preparations, metformin, sulfonylurea derivatives and rosiglitazone. The empirical Bayesian data-mining algorithm, MGPS (as well as its predecessor, GPS) places a prior distribution on the relative reporting ratio that encapsulates a prior belief that most relative reporting ratios are close to a value of "1", resulting in a shrinkage (thus the word "shrinker" in the name of certain algorithms) when the case count is low, thereby preventing overestimation of relative reporting ratio according to a number of papers.) Since some of the selected events had low case counts, we applied stratified MGPS to the FDA-AERS database through the first quarter 2005. Of note, this approach is inherently exploratory and may merely provide insights into the patterns of adverse events particular to a given product relative to other products in the same class or to all other products. As the FDA recommends in its Guidance document on Pharmacovigilance [4], caution should be exercised when making such comparisons, however, because voluntary adverse event reporting systems such as FDA-AERS are subject to a variety of reporting biases, and consequently, the observed SDRs could be due to the underlying indication (i.e., confounding by indication), co-morbid illnesses, protopathic bias, channeling bias and/or other reporting artifacts, inherent to SRS databases. [2,3] Reporting biases differ by product and change over time, and could change differently for different events; it is not possible to predict their impact on data mining scores. In the present study, commonly cited thresholds were used, i.e., a drug-event combination was considered an SDR when the EB05 > 2 - which is the fifth percentile of the posterior distribution, meaning that there is a 95% probability that the "true" RR exceeds the EB05.[2,6] For the purpose of this report, we analyzed merely the statistical association between use of pioglitazone and the reporting of congestive heart failure (CHF), edema, weight gain, neoplasia, liver, anemia, and rhabdomyolysis, as they compare to the reporting with all other drugs in the FDA-AERS database, as well as to all antidiabetic agents¹, insulin- preparations, metformin, sulfonylurea derivatives and rosiglitazone. The analyses were conducted with Qscan-FDA, version 3.1 (Reston, VA, USA). 1 Antidiabetic agents: Insuline-preparations, metformin, sulfonylurea-derivatives, and rosiglitazone Confidential TAK-BHATTM-00117185 Produced in MDL on 09/14/12 Source: 3.0. Results Table 1 shows the data mining results. It can be seen that compared to all other drugs in the database as well as compared to all antidiabetic agents², insulin-preparations, metformin and sulfonylurea derivatives, the empirical Bayesian DMA, highlights that CHF, edema and weight gain are disproportionally more reported for pioglitazone, However, these events do not seem to be disproportionally more reported with pioglitazone than with rosiglitazone. Additionally, hepatic events are more reported with pioglitazone according to this MGPS analysis compared to all other drugs in the database as well as compared to all antidiabetic drugs combined and insulin preparations separately. Relative to all other drugs in the FDA-AERS database, but not in comparison to all antidiabetic agents combined or separately, was bladder cancer disproportionally more reported. Non of the analyzed events were disproportionally more reported with pioglitazone relative to rosiglitazone. 4.0. Discussion A cross-sectional disproportionality analysis in the FDA-AERS database for pioglitazone has revealed that CHF, edema, and weight gain are reported disproportionally more with pioglitazone than compared to all other drugs in the FDA-AERS database, as well as compared to other antidiabetic drugs. However, the reporting of these events is not disproportionally more reported with pioglitazone than with other thiazolidinediones, such as rosiglitazone. Importantly, the observed SDRs are not necessarily indicative of a causal relationship, but could be due to the underlying disease (i.e., confounding by indication), co-morbid illnesses, protopathic bias, channeling bias and/or other reporting artifacts, inherent to SRS databases. Dependenti upon the quality and completeness of individual case reports, case-by-case analyses of these reports will be able to provide more information in this regard. Heart failure has recently been termed "the frequent, forgotten, and often fatal complication of diabetes"[7]. In a recent study Nichols et al. in the Kaiser Permanente 2 Antidiabetic agents: Insuline-preparations, metformin, sulfonylurea-derivatives, and rosiglitazone Confidential TAK-BHATTM-00117186 Produced in MDL on 09/14/12 Northwest (KPNW) database, calculated the incidence rate of CHF in a cohort of type II diabetes patients as 30.9 per 1,000 patient-years compared to 12,4 per 1,000 patient-years in an age-matched non-diabetic cohort [8], yielding a relative risk of 2.5. In addition, the severity of diabetes is an independent risk factor for CHF as was shown by Iribarren and co-workers who demonstrated that each 1% increase in baseline HbA1c was associated with an 8% (95% CI: 5% - 12%) increased risk of CHF. This could explain why compared to rosiglitazone - which is probably being prescribed to diabetes patients with more or less the same severity - the relative reporting of CHF does not seem to be disproportionally increased, while increased compared to the other backgrounds. Likewise, liver events have been associated with, not merely diabetes itself, but also with the severity of type II diabetes.[9] The MHA is currently conducting two large observational studies - a retrospective cohort study as well as a nested case-control study - to evaluate whether exposure to pioglitazone is associated with an increased risk of bladder cancer. The results from the retrospective follow-up study have not shown an increased risk of bladder cancer. 5.0. References 1 ALMENOFF J, TONNING JM, GOULD AL et al.: Perspectives on the use of data mining in plarmacovigilance. Drug "(2005) 28(11):981-1007. 2 HAUBEN M, MADIGAN D, GERRITS CM, WALSH L, VAN PULJENBROEK EP: The role of data mining in pharmacovigilance. Expert Opin Drug Saf(2005) 4(5):929-948. 3 HAUBEN M, PATADIA V, GERRITS C, WALSH L, REICH L: Data Mining in Pharmacovigilance: The Need for a Balanced Perspective. Drug Saf(2005) 28(in Press) 4 US-FDA. Guidance for Industry Good Pharmacovigilance Practicos and Pharmiacocpidemiologic Assessment. May, 2004; http://www.fda.gov/OHRMS/DOCKETS/98fr/04d-0189-gd10001- 5767dft.doc 5 HAUBEN M, REICH J: Communication of findings in pharmacovigilance: use of term "signal" and the need for precision in ils use. Eur J Clin Pharmacol (2005) 6 SZARFMAN A, MACHADO SG, O'NEILL RT: Use of screening algorithms and computer systems to efficiently signal ligher-than-expected combinations of drugs and events in the US FDA's spontaneous reports database. Drug Saf 25(6):381-392. Confidential TAK-BHATTM-00117187 Produced in MDL on 09/14/12 Source: 7 BELL DSH: Heart Failure: The frequent, forgotten, and often fatal complication of diabetes. Diabetes Care (2003) 26(8):2433-2441. 8 NICHOLS GA, GULLION CM, KORO CE, EPHROSS SA, BROWN JB: The Incidence of Congestive Heart Failure in Type 2 Diabetes: An opdate. Diabetes Care (2004)27(8):1879-1884. 9 EL-SERAG HB, TRAN T, EVERHART JB: Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterology (2004) 126(2):460-468. Confidential TAK-BHATTM-00117188 Produced in MDL on 09/14/12 Source: https://www.indupo33-00009.ucsf.edu/docs/qnjf0226 Table 1. Signaling Scores for selected events for Pioglitazone according to MGPS** data mining algortthm Multi-itern Gamma Poisson Shrinker (MGPS) all drug In FDA- all antidiabetics insulins Metformin AERS Sulfonylurea Rosiglifazione EB05 EB05 EB05 EB05 EB05 EB05 CHF 1.9 0.9 Edema 0.9 Weight Gain 0.8 Neoplasia (SOC) 1.5 1.4 1.5 1.1 1.2 1.2 - bladder cancer 29 1.8 1.4 1.2 1.3 0.9 Liver (TAK) 1.7 1.3 1.3 1.0 Anemia (TAK) 1.0 0.8 1.1 0,9 0.7 0.7 Rhabdemyalysis (SMQ) 1.7 1.0 1.2 0.7 0.9 1.0 SDR a Signal of Disproportional Reporting et MGRS: Mulit-Rem Gamma Poisson Sbrinken a signal score is representing en SDR when ESOS 2 2 ... Glicfazide; Gilmepiride; Glipizide; Glyburide; Totbutamide Antidiabetic agents: insuline-preparations, metformia, and rosiglitazons Confidential TAK-BHATTM-00117189 Produced in MDL on 09/14/12 Source: https://www.indusp/o3-0001.ucsf.edu/docs/qnjf0226

which report is mentioned in the subject

qnjf0226

qnjf0226_p0, qnjf0226_p1, qnjf0226_p2, qnjf0226_p3, qnjf0226_p4, qnjf0226_p5, qnjf0226_p6, qnjf0226_p7, qnjf0226_p8, qnjf0226_p9

disproportionality report

From: Gerrits, Charles (TGRD) To: Van Troostenburg, Anne (TGRD); Bhattacharya, Mondira (TGRD) Sent: 10/28/2005 6:37:42 PM Subject: RE: disproportionality report Attachments: Disproportionality Analysis Actos.doo Anna, I am not sure what happened, but this is the updated report. I will have to do some additional checks, but I think the Table is fine now. 1 will be available tomorrow for a telecon, if deemed necessary regards, Charles Original Message From: Van Troostenburg, Anne (TGRD) Sent: Wednesday, October 26, 2005 10:15 AM To: Gerrits, Charles (TGRD) Subject: RE: disproportionality report Thanks Charles, - is it correct that the bladder cancer row is empty? Anna Original Message- From: Gerrits, Charles (TGRD) Sent: 26 October 2005 15:05 To: Bhattacharya, Mondira (TGRD); Van Troostenburg, Anne (TGRD) Subject: RE: disproportionality report Mondira and Anna, See attached an updated version of the disproportionality report. regards, Charles << File: Disproportionality Analysis Actos. doc >> Original Message From: Bhattacharya, Mondira (TGRD) Sent: Monday, October 24, 2005 3:27 PM To: Gerrits, Chartes (TGRD); Van Troostenburg, Anne (TGRD) Subject: RE: disproportionality report Dear Charles: Thanks again for this analysis, I just wanted to bring Anna up-to-date on my further request to you for additional refinement of the analysis which will now compare pla to other diabetic drugs (as a group) and to a all metformin- exposed and an all insulin-exposed group as well. Thanks again, Mondira Original Message- From: Gerrits, Charles (TGRD) Sent: Friday, October 21, 2005 5:52 PM To: Van Troastenburg, Anne (TGRD); Bhattacharya, Mondira (TGRD) Subject: disproportionality report Mondira and Anna, EXHIBIT See attached a first draft for the disproportionality analysis. 44 regards, Feisal Charles Confidential TAK-BHATTM-00117180 Produced in MDL on 09/14/12 << File: Disproportionality Analysis Actos.doc >> Confidential TAK-BHATTM-00117181 Produced in MDL on 09/14/12 Source: https://www.indupo33-00002.ucsf.edu/docs/qnjf0226 Disproportionality Analysis Confidential TAK-BHATTM-00117182 Produced in MDL on 09/14/12 Source: https://www.indup33-00003s.ucsf.edu/docs/qnjf0226 Table of Content 1.0. Introduction 3 2.0. Methods 3 3.0. Results 5 5.0. References 6 Confidential TAK-BHATTM-00117183 Produced in MDL on 09/14/12 Source: https://www.indu/03-00004s.ucsf.edu/docs/qnjf0226 1.0. Introduction At various stages of risk identification and assessment, looking systematically into the data by using computational signal detection algorithms, or so-called data mining algorithms (DMAs), can provide additional information about the existence, and/or characteristics of a signal, or lack thereof. By applying DMAs to large spontaneous reporting system (SRS) databases, like the FDA-AERS, or WHO database, a safety assessor may be able to identify unusual or unexpected drug-event combinations warranting further investigations. Importantly, because of the very nature of SRS databases, applying DMAs to these SRS databases can rarely be used for causal inference.[1,2,3,4] A number of approaches have merged in recent years that search SRS databases for interesting associations. Most such algorithms (e.g. Proportional Reporting Ratio [PRR], Gamma Poisson Shrinker [GPS], Multi-item Gamma Poisson Shrinker [MGPS], Bayesian Confidence Propagation Neural Network [BCPNN]) screen extremely large SRS databases for statistical dependencies between drugs and events in excess of what would be expected if the drug and event were independently distributed in the database (so-called *disproportionality analysis'). [2,3] Since a "signal" is usually considered to be more than just a statistical association, statistical associations found with DMAs are preferably called, signals of disproportionate reporting (SDRs) [5] when discussing statistical disproportionalities in SRS databases without clinical, pharmacological and/or (pharmaco)epidemiological context.[2 This terminology emphasizes that drug-event combinations indicate differential reporting of possible reactions, not necessarily indicative of differential occurrence.[2] 2.0. Methods For the purpose of this report, we analyzed the FDA-AERS database for pioglitazone. The proportional reporting of events coincident with pioglitazone use were compared to Confidential TAK-BHATTM-00117184 Produced in MDL on 09/14/12 Source: https://www.indus133-00005s.ucsf.edu/docs/qnjf0226 the entire FDA-AERS databases, as well as to all antidiabetic agents¹, insulin- preparations, metformin, sulfonylurea derivatives and rosiglitazone. The empirical Bayesian data-mining algorithm, MGPS (as well as its predecessor, GPS) places a prior distribution on the relative reporting ratio that encapsulates a prior belief that most relative reporting ratios are close to a value of "1", resulting in a shrinkage (thus the word "shrinker" in the name of certain algorithms) when the case count is low, thereby preventing overestimation of relative reporting ratio according to a number of papers.) Since some of the selected events had low case counts, we applied stratified MGPS to the FDA-AERS database through the first quarter 2005. Of note, this approach is inherently exploratory and may merely provide insights into the patterns of adverse events particular to a given product relative to other products in the same class or to all other products. As the FDA recommends in its Guidance document on Pharmacovigilance [4], caution should be exercised when making such comparisons, however, because voluntary adverse event reporting systems such as FDA-AERS are subject to a variety of reporting biases, and consequently, the observed SDRs could be due to the underlying indication (i.e., confounding by indication), co-morbid illnesses, protopathic bias, channeling bias and/or other reporting artifacts, inherent to SRS databases. [2,3] Reporting biases differ by product and change over time, and could change differently for different events; it is not possible to predict their impact on data mining scores. In the present study, commonly cited thresholds were used, i.e., a drug-event combination was considered an SDR when the EB05 > 2 - which is the fifth percentile of the posterior distribution, meaning that there is a 95% probability that the "true" RR exceeds the EB05.[2,6] For the purpose of this report, we analyzed merely the statistical association between use of pioglitazone and the reporting of congestive heart failure (CHF), edema, weight gain, neoplasia, liver, anemia, and rhabdomyolysis, as they compare to the reporting with all other drugs in the FDA-AERS database, as well as to all antidiabetic agents¹, insulin- preparations, metformin, sulfonylurea derivatives and rosiglitazone. The analyses were conducted with Qscan-FDA, version 3.1 (Reston, VA, USA). 1 Antidiabetic agents: Insuline-preparations, metformin, sulfonylurea-derivatives, and rosiglitazone Confidential TAK-BHATTM-00117185 Produced in MDL on 09/14/12 Source: 3.0. Results Table 1 shows the data mining results. It can be seen that compared to all other drugs in the database as well as compared to all antidiabetic agents², insulin-preparations, metformin and sulfonylurea derivatives, the empirical Bayesian DMA, highlights that CHF, edema and weight gain are disproportionally more reported for pioglitazone, However, these events do not seem to be disproportionally more reported with pioglitazone than with rosiglitazone. Additionally, hepatic events are more reported with pioglitazone according to this MGPS analysis compared to all other drugs in the database as well as compared to all antidiabetic drugs combined and insulin preparations separately. Relative to all other drugs in the FDA-AERS database, but not in comparison to all antidiabetic agents combined or separately, was bladder cancer disproportionally more reported. Non of the analyzed events were disproportionally more reported with pioglitazone relative to rosiglitazone. 4.0. Discussion A cross-sectional disproportionality analysis in the FDA-AERS database for pioglitazone has revealed that CHF, edema, and weight gain are reported disproportionally more with pioglitazone than compared to all other drugs in the FDA-AERS database, as well as compared to other antidiabetic drugs. However, the reporting of these events is not disproportionally more reported with pioglitazone than with other thiazolidinediones, such as rosiglitazone. Importantly, the observed SDRs are not necessarily indicative of a causal relationship, but could be due to the underlying disease (i.e., confounding by indication), co-morbid illnesses, protopathic bias, channeling bias and/or other reporting artifacts, inherent to SRS databases. Dependenti upon the quality and completeness of individual case reports, case-by-case analyses of these reports will be able to provide more information in this regard. Heart failure has recently been termed "the frequent, forgotten, and often fatal complication of diabetes"[7]. In a recent study Nichols et al. in the Kaiser Permanente 2 Antidiabetic agents: Insuline-preparations, metformin, sulfonylurea-derivatives, and rosiglitazone Confidential TAK-BHATTM-00117186 Produced in MDL on 09/14/12 Northwest (KPNW) database, calculated the incidence rate of CHF in a cohort of type II diabetes patients as 30.9 per 1,000 patient-years compared to 12,4 per 1,000 patient-years in an age-matched non-diabetic cohort [8], yielding a relative risk of 2.5. In addition, the severity of diabetes is an independent risk factor for CHF as was shown by Iribarren and co-workers who demonstrated that each 1% increase in baseline HbA1c was associated with an 8% (95% CI: 5% - 12%) increased risk of CHF. This could explain why compared to rosiglitazone - which is probably being prescribed to diabetes patients with more or less the same severity - the relative reporting of CHF does not seem to be disproportionally increased, while increased compared to the other backgrounds. Likewise, liver events have been associated with, not merely diabetes itself, but also with the severity of type II diabetes.[9] The MHA is currently conducting two large observational studies - a retrospective cohort study as well as a nested case-control study - to evaluate whether exposure to pioglitazone is associated with an increased risk of bladder cancer. The results from the retrospective follow-up study have not shown an increased risk of bladder cancer. 5.0. References 1 ALMENOFF J, TONNING JM, GOULD AL et al.: Perspectives on the use of data mining in plarmacovigilance. Drug "(2005) 28(11):981-1007. 2 HAUBEN M, MADIGAN D, GERRITS CM, WALSH L, VAN PULJENBROEK EP: The role of data mining in pharmacovigilance. Expert Opin Drug Saf(2005) 4(5):929-948. 3 HAUBEN M, PATADIA V, GERRITS C, WALSH L, REICH L: Data Mining in Pharmacovigilance: The Need for a Balanced Perspective. Drug Saf(2005) 28(in Press) 4 US-FDA. Guidance for Industry Good Pharmacovigilance Practicos and Pharmiacocpidemiologic Assessment. May, 2004; http://www.fda.gov/OHRMS/DOCKETS/98fr/04d-0189-gd10001- 5767dft.doc 5 HAUBEN M, REICH J: Communication of findings in pharmacovigilance: use of term "signal" and the need for precision in ils use. Eur J Clin Pharmacol (2005) 6 SZARFMAN A, MACHADO SG, O'NEILL RT: Use of screening algorithms and computer systems to efficiently signal ligher-than-expected combinations of drugs and events in the US FDA's spontaneous reports database. Drug Saf 25(6):381-392. Confidential TAK-BHATTM-00117187 Produced in MDL on 09/14/12 Source: 7 BELL DSH: Heart Failure: The frequent, forgotten, and often fatal complication of diabetes. Diabetes Care (2003) 26(8):2433-2441. 8 NICHOLS GA, GULLION CM, KORO CE, EPHROSS SA, BROWN JB: The Incidence of Congestive Heart Failure in Type 2 Diabetes: An opdate. Diabetes Care (2004)27(8):1879-1884. 9 EL-SERAG HB, TRAN T, EVERHART JB: Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterology (2004) 126(2):460-468. Confidential TAK-BHATTM-00117188 Produced in MDL on 09/14/12 Source: https://www.indupo33-00009.ucsf.edu/docs/qnjf0226 Table 1. Signaling Scores for selected events for Pioglitazone according to MGPS** data mining algortthm Multi-itern Gamma Poisson Shrinker (MGPS) all drug In FDA- all antidiabetics insulins Metformin AERS Sulfonylurea Rosiglifazione EB05 EB05 EB05 EB05 EB05 EB05 CHF 1.9 0.9 Edema 0.9 Weight Gain 0.8 Neoplasia (SOC) 1.5 1.4 1.5 1.1 1.2 1.2 - bladder cancer 29 1.8 1.4 1.2 1.3 0.9 Liver (TAK) 1.7 1.3 1.3 1.0 Anemia (TAK) 1.0 0.8 1.1 0,9 0.7 0.7 Rhabdemyalysis (SMQ) 1.7 1.0 1.2 0.7 0.9 1.0 SDR a Signal of Disproportional Reporting et MGRS: Mulit-Rem Gamma Poisson Sbrinken a signal score is representing en SDR when ESOS 2 2 ... Glicfazide; Gilmepiride; Glipizide; Glyburide; Totbutamide Antidiabetic agents: insuline-preparations, metformia, and rosiglitazons Confidential TAK-BHATTM-00117189 Produced in MDL on 09/14/12 Source: https://www.indusp/o3-0001.ucsf.edu/docs/qnjf0226

who retained a professional translator

tfkf0226

tfkf0226_p0, tfkf0226_p1, tfkf0226_p2, tfkf0226_p3, tfkf0226_p4, tfkf0226_p5, tfkf0226_p6, tfkf0226_p7, tfkf0226_p8

International Litigation Services

From: Nishikata " Sent: Monday, December 04, 2006 9:05 AM To: Û^À Cc: Nakano " a." " Subject: RE: pioglitazone metaanalysis(Confidential) 7C80, itnox N tt o It OTLITETE. < E3L< to o The Original Message From: Wada Yasuhiko/ Sent: Monday, December 04, 2006 8 19 PM To: Nishikata Yukari/ Nakano Takayuki / Subject: RE: pioglitazone metaanalysis (Confidential) 75th CeriDith EEth Cochrane 32345th PediatricOPackagelttl L. Original Message From: Nishikata Yukari / G # Sent: Monday, December 04, 2006 10 : 01 AM To: Wada asuhiko/ Cc: Nakano Takayuki / It Subject: FW: pioglitazone metaanalysis (Confidential) 1-2 Ometa-analysiststeve Nissen02i 3 o Ctmeta- . t o . 16:30tist ti This Original Message Confidential - From: Nishikata Yukari, Sent: Saturday, December 02, 2006 2:15 PM To: Miyamoto Masaomi/;Nabulsi Azmi/ Cc: Niimi Mitsuhiro / E GM; Yates John/President.TGRD. TGRD. Subject: FW: pioglitazone metaanalysis (Confidential) Dear Dr. Miyamoto and Azmi, As I reported to you in Chicago, John originally planned to send a statement letter to the Cochrane library. According to his e-mail which I received yesterday and was copied to you, he changed the strategy and TGRD is going to publish our meta-analysis under the name of Steve Nissen and needs TPC' agreement urgently. Please refer to my previous e-mail to you and John's e-mail. As Azmi commented before, the meta-analysis is very important and I also think it should be published as soon as possible. After PDD's official approval is granted, I will make sure the draft will be reviewed by the relevant departments/divisions through SPPD according to the Corporate SOP for scientific publication. Since John will be in Osaka next week I would like to arrange a meeting with you. Kind regards, Yukari Original Message From: Yates John/President.TGRD. TGRD. Sent: Saturday, December 02, 2006 8:37 AM To: Perez Alfonso/VP Clin Rsrch. Clinical Research - MPDRAP IIIA. TGRD. ; Nishikata Yukari G Subject: RE : pioglitazone metaanalysis Confidential) Thanks Alfonso. I agree we need to expedite the meta-analysis publication. Yukari - we need buy in from TPC to move ahead very quickly to use Steve Nissen to author this publication. I will be coming to Osaka arriving Monday next week, so we can discuss there if that would be helpful. Thanks John From: Perez, Alfonso (TGRD) Confidential - Sent: Friday, December 01, 2006 5:29 PM To: Yates, John (TGRD) Subject: FW: pioglitazone metaanalysis (Confidential) John, ADOPT a 4 year trial comparing rosi vs. glyburide and vs. met formin will be publish shortly,looks another "nightmare" in CV events as Dream for rosi. This reinforce our urgent need for early publication of our metaanalysis : Regards, Alfonso From: Steven E. Nissen [mailto:nissens@ccf.org Sent: Friday, December 01, 2006 2:02 PM Perez, Alfonso (TGRD). Isaacson, Brigit (TGRD) Subject: Re: pioglitazone netaanalysis A DOPT is now available embargoed. Another bad CV result for rosiglitazone. Steve Nissen Confidential - Cleveland Clinic is ranked one of the top 3 hospitals in America by U.S.News & world Report. Visit us online at tp://www.clevelandclinic.org for a complete listing of our services, staff and locations. Confidentiality Note: This message is intended for use only by the individual or entity to which it is addressed and may contain information that is privileged, confidential, and exempt from disclosure inder applicable law. If the reader of this message is not the intended recipient or the employee or agent responsible for delivering the message to the intended recipient, you are hereby notified that any dissemination, distribution or copying of this communication is strictly prohibited. If you have received this communication in error, please contact the sender immediately and destroy the material in its entirety, whether electronic or hard copy. Thank you. ### This message is for the designated recipient only and may contain privileged or confidential information. If you have received it in error, please notify the sender immediately and delete the original. Any other use of the email by you is prohibited. ### - From: Nishikata i- i,fZà Sent: Monday, December 04, 2006 9:05 AM To: Wada Yasuhiko/`: ã-òSJ" Û'À io". Cc: Nakano i,f%- Subject: RE glitazone-metaanalysis(Confidential) Manager Wada, As you pointed out, before doing the presentation at the SAG conference, we already submitted it also to FDA, so if there is -even the slightest risk that contradictory results could be obtained, I think that we should publish the existing analysis results under Takeda's name, and not Nissen's. I intend to take the discussion in this direction on the 6th, so I will contact you with the outcome. I know I will be consulting with you more on Actos in the future, so I appreciate all your help. Nishikata Original Message From: Wada asuhiko/Pharmaceutical Development, international Safety information Manager Sent: Monday, December 04, 2006 8:19 PM To: Nishikata Yukari/Pharmaceutica Development, Strategic Development Promotion G, Principal Member Cc: Nakano Takayuki/Pharmace.utica Development, Strategic Development Dpt, Promotion G Acting Chief Subject: RE:pioglitazonemetaanalysis(confidential) Nishikata-san, On Wednesday, 12/6, in addition to Gerd and Ceri, I have a meeting with visitors from Aris-G, so I will not be able to attend. Looking at the email exchange, it appears that they are publishing as a response to Cochrane library, but these results will also be put into the package for pediatric, and the outline has already been submitted at the SAG conference with EMEA, so make sure there is no discrepancy with that. Wada Original Message From: Nishikata Vukari/Pharmaceutical Development, Strategic Development Promotion G, Principal Member Sent: Monday, December 04, 2006-10:01 AM To: Wada Yasuhiko/Pharmaceutical Development, International Safety information Manager Cc: Nakano Takayuki/Pharmaceutical Development, Strategic Development Dpt, Promotion G Acting Chief Subject: FWe-pioglitazone-metaanalysis(Confidential Manager Wada, As mentioned in the email below, TGRD is planning to publish the meta-analysis of Actos under Steve Nissen's name. I think there is no problem if the results of the meta-analysis as conducted by Takeda will be presented as-is, however, if Nessen (sic) is doing the analysis over again, I think we need to consider with caution. John will be visiting Japan this week to attend the Research HQ's yearly planning hearing, so I would like to secure a time to discuss this with him directly. I apologize for the last-minute notice, but we will have this meeting on 12/6 Wednesday from 16:30, at the 13th laboratory main tower, room 1114. This will be after the yearly planning hearing, so the starting time may get delayed a bit, but please do attend if time allows. Please decide within reason without pushing yourself too much, as you will have to come out all the way to the 13th laboratory. Nishikata Original Message Confidential - Subject to Protective Order TAK-NISHIY-00221506 TAK-NISHY-00221506P-000 From: Nishikata /ukari/Pharmaceutical Development, Strategic Development Department, Promotion G. Principal Member Sent: Saturday, December 02, 2006 2:15 PM To: Miyamoto Masaomi/Pharmaceutical Development Managing Director, Nabulsi Azmi/Pharmaceutical Development, Strategic Development Mgr Cc: Niimi Mitsuhiro/Pharmaceutica Development, Strategic Development Department, Promotion GM, Yates John/President.TGRD. TGRD Subject: FW: pioglitazone metaanalysis (Confidential) Dear Dr. Miyamoto and Azmi, As I reported to you in Chicago, John originally planned to send a statement letter to the Cochrane library. According to his -mail which I received yesterday and was copied to you, he changed the strategy and TGRD is going to publish our meta-analysis under the name of Steve Nissen and needs TPC's agreement urgently. Please refer to my previous e-mail to you and John's e-mail. As Azmi commented before, the meta-analysis is very important and I also think it should be published as soon as possible. After PDD's official approval is granted, I will make sure the draft will be reviewed by the relevant departments/divisions through SPPD according to the Corporate SOP for scientific publication. Since John will be in Osaka next week I would like to arrange a meeting with you. Kind regards, Yukari Original Message From: Yates John/President.TGRD. TGRD. Sent: Saturday, December 02, 2006 8:37 AM To: Perez Alfonso/VP Clin Rsrch.Clinical Research - MPDRAP IIIA. TGRD. ; Nishikata Yukari/Pharmaceutical Development, Strategic Development Department, Promotion G, Principal Member Subject: RE: pioglitazone metaanalysis(Confidential) Thanks Alfonso. II agree we-need to -expedite the -meta-analysis-publication Yukari -- we need buy in from TPC to move ahead very quickly to use Steve Nissen to author this publication. I will be coming to Osaka appiving Monday next week, so we can discuss there if that would be helpful. Thanks John From: Perez, Alfonso (TGRD) Confidential - Subject to Protective Order TAK-NISHIY-00221507 TAK-NISHY-00221506P-0002 Sent: Friday, December 01, 2006 5:29 PM To: Yates, John (TGRD) Subject: FW: pioglitazone metaanalysis(Confidential) John, ADOPT a 4 year trial comparing rosi vs glyburide and vs . met formin will be publish shortly, looks another "nightmare" in ev events as Dream for rosi. This reinforce our urgent need for early publication of our metaanalysis Regards, Alfonso From: Steven E. Nissen [mailto:nissens@ccf.org Sent: Friday, December 01, 2006 2:02 PM : Perez, Alfonso (TGRD) Isaacson,Brigit (TGRD) Subject: Re: pioglitazone metaanalysis ADOPT is now available embargoed. Another bad CV result for rosiglitazone. Steve Nissen Confidential - Subject to Protective Order TAK-NISHIY-00221508 TAK-NISHY-00221506P-000 Cleveland Clinic is ranked one of the top 3 hospitals in America by U.S. News & World Report. Visit us online at Ittp://www.clevelandclinic.org for a complete listing of our services, staff and locations. Confidentiality Note: This message is intended for use only by the individual or entity to which it is addressed and-may contain information that is privileged, confidential, and exempt from disclosure under applicable law. If the readen of this message is not the intended recipient or the employee or agent responsible for delivering the message to the intended recipient, you are hereby notified that any dissemination, distribution or copying of this communication is strictly prohibited. If you have received this communication in error, please contact the sender immediately and destroy the material in its entirety, whether electronic or hard copy. Thank you. ### This message is for the designated recipient only and may contain privileged or confidential information. If you have received it in error, please notify the sender immediately and delete the original. Any other use of the email by you is prohibited. ### Confidential - Subject to Protective Order TAK-NISHIY-00221509 TAK-NISHY-00221506P-000 its TM INTERNATIONAL LITIGATION SERVICES CERTIFICATION OF TRANSLATION International Litigation Services, a company specializing in international cases and foreign language document processing, certifies the following: International Litigation Services has retained a professional translator for the attached Japanese into English document. The document is referred to as: "TAK-NISHY-00221506P-0001" I affirm that such translation has been prepared by a duly qualified translator, who has confirmed that such translation is, to the best of his/her knowledge and belief, a true and accurate translation in English of the corresponding Japanese document. I declare under the penalty of perjury that the forgoing is true and correct. Notwithstanding the foregoing affirmations, no liability is assumed for errors and omissions in the translation of the attached document. Executed on this 19th day of February 2014, in Aliso Viejo, California. Josephore Joseph Thorpe Managing Director International Litigation Services, Inc. International Litigation Services, Inc. 8 65 Enterprise Aliso Viejo, California 92656 Phone: 888.313.4457 Fax: 213.674.4191 3 info@ilsteam.com NEW YORK Los ANGELES LAS VEGAS ORANGE COUNTY Source:

who is the managing director of international litigation services,Inc.

tfkf0226

tfkf0226_p0, tfkf0226_p1, tfkf0226_p2, tfkf0226_p3, tfkf0226_p4, tfkf0226_p5, tfkf0226_p6, tfkf0226_p7, tfkf0226_p8

Joseph Thorpe

From: Nishikata " Sent: Monday, December 04, 2006 9:05 AM To: Û^À Cc: Nakano " a." " Subject: RE: pioglitazone metaanalysis(Confidential) 7C80, itnox N tt o It OTLITETE. < E3L< to o The Original Message From: Wada Yasuhiko/ Sent: Monday, December 04, 2006 8 19 PM To: Nishikata Yukari/ Nakano Takayuki / Subject: RE: pioglitazone metaanalysis (Confidential) 75th CeriDith EEth Cochrane 32345th PediatricOPackagelttl L. Original Message From: Nishikata Yukari / G # Sent: Monday, December 04, 2006 10 : 01 AM To: Wada asuhiko/ Cc: Nakano Takayuki / It Subject: FW: pioglitazone metaanalysis (Confidential) 1-2 Ometa-analysiststeve Nissen02i 3 o Ctmeta- . t o . 16:30tist ti This Original Message Confidential - From: Nishikata Yukari, Sent: Saturday, December 02, 2006 2:15 PM To: Miyamoto Masaomi/;Nabulsi Azmi/ Cc: Niimi Mitsuhiro / E GM; Yates John/President.TGRD. TGRD. Subject: FW: pioglitazone metaanalysis (Confidential) Dear Dr. Miyamoto and Azmi, As I reported to you in Chicago, John originally planned to send a statement letter to the Cochrane library. According to his e-mail which I received yesterday and was copied to you, he changed the strategy and TGRD is going to publish our meta-analysis under the name of Steve Nissen and needs TPC' agreement urgently. Please refer to my previous e-mail to you and John's e-mail. As Azmi commented before, the meta-analysis is very important and I also think it should be published as soon as possible. After PDD's official approval is granted, I will make sure the draft will be reviewed by the relevant departments/divisions through SPPD according to the Corporate SOP for scientific publication. Since John will be in Osaka next week I would like to arrange a meeting with you. Kind regards, Yukari Original Message From: Yates John/President.TGRD. TGRD. Sent: Saturday, December 02, 2006 8:37 AM To: Perez Alfonso/VP Clin Rsrch. Clinical Research - MPDRAP IIIA. TGRD. ; Nishikata Yukari G Subject: RE : pioglitazone metaanalysis Confidential) Thanks Alfonso. I agree we need to expedite the meta-analysis publication. Yukari - we need buy in from TPC to move ahead very quickly to use Steve Nissen to author this publication. I will be coming to Osaka arriving Monday next week, so we can discuss there if that would be helpful. Thanks John From: Perez, Alfonso (TGRD) Confidential - Sent: Friday, December 01, 2006 5:29 PM To: Yates, John (TGRD) Subject: FW: pioglitazone metaanalysis (Confidential) John, ADOPT a 4 year trial comparing rosi vs. glyburide and vs. met formin will be publish shortly,looks another "nightmare" in CV events as Dream for rosi. This reinforce our urgent need for early publication of our metaanalysis : Regards, Alfonso From: Steven E. Nissen [mailto:nissens@ccf.org Sent: Friday, December 01, 2006 2:02 PM Perez, Alfonso (TGRD). Isaacson, Brigit (TGRD) Subject: Re: pioglitazone netaanalysis A DOPT is now available embargoed. Another bad CV result for rosiglitazone. Steve Nissen Confidential - Cleveland Clinic is ranked one of the top 3 hospitals in America by U.S.News & world Report. Visit us online at tp://www.clevelandclinic.org for a complete listing of our services, staff and locations. Confidentiality Note: This message is intended for use only by the individual or entity to which it is addressed and may contain information that is privileged, confidential, and exempt from disclosure inder applicable law. If the reader of this message is not the intended recipient or the employee or agent responsible for delivering the message to the intended recipient, you are hereby notified that any dissemination, distribution or copying of this communication is strictly prohibited. If you have received this communication in error, please contact the sender immediately and destroy the material in its entirety, whether electronic or hard copy. Thank you. ### This message is for the designated recipient only and may contain privileged or confidential information. If you have received it in error, please notify the sender immediately and delete the original. Any other use of the email by you is prohibited. ### - From: Nishikata i- i,fZà Sent: Monday, December 04, 2006 9:05 AM To: Wada Yasuhiko/`: ã-òSJ" Û'À io". Cc: Nakano i,f%- Subject: RE glitazone-metaanalysis(Confidential) Manager Wada, As you pointed out, before doing the presentation at the SAG conference, we already submitted it also to FDA, so if there is -even the slightest risk that contradictory results could be obtained, I think that we should publish the existing analysis results under Takeda's name, and not Nissen's. I intend to take the discussion in this direction on the 6th, so I will contact you with the outcome. I know I will be consulting with you more on Actos in the future, so I appreciate all your help. Nishikata Original Message From: Wada asuhiko/Pharmaceutical Development, international Safety information Manager Sent: Monday, December 04, 2006 8:19 PM To: Nishikata Yukari/Pharmaceutica Development, Strategic Development Promotion G, Principal Member Cc: Nakano Takayuki/Pharmace.utica Development, Strategic Development Dpt, Promotion G Acting Chief Subject: RE:pioglitazonemetaanalysis(confidential) Nishikata-san, On Wednesday, 12/6, in addition to Gerd and Ceri, I have a meeting with visitors from Aris-G, so I will not be able to attend. Looking at the email exchange, it appears that they are publishing as a response to Cochrane library, but these results will also be put into the package for pediatric, and the outline has already been submitted at the SAG conference with EMEA, so make sure there is no discrepancy with that. Wada Original Message From: Nishikata Vukari/Pharmaceutical Development, Strategic Development Promotion G, Principal Member Sent: Monday, December 04, 2006-10:01 AM To: Wada Yasuhiko/Pharmaceutical Development, International Safety information Manager Cc: Nakano Takayuki/Pharmaceutical Development, Strategic Development Dpt, Promotion G Acting Chief Subject: FWe-pioglitazone-metaanalysis(Confidential Manager Wada, As mentioned in the email below, TGRD is planning to publish the meta-analysis of Actos under Steve Nissen's name. I think there is no problem if the results of the meta-analysis as conducted by Takeda will be presented as-is, however, if Nessen (sic) is doing the analysis over again, I think we need to consider with caution. John will be visiting Japan this week to attend the Research HQ's yearly planning hearing, so I would like to secure a time to discuss this with him directly. I apologize for the last-minute notice, but we will have this meeting on 12/6 Wednesday from 16:30, at the 13th laboratory main tower, room 1114. This will be after the yearly planning hearing, so the starting time may get delayed a bit, but please do attend if time allows. Please decide within reason without pushing yourself too much, as you will have to come out all the way to the 13th laboratory. Nishikata Original Message Confidential - Subject to Protective Order TAK-NISHIY-00221506 TAK-NISHY-00221506P-000 From: Nishikata /ukari/Pharmaceutical Development, Strategic Development Department, Promotion G. Principal Member Sent: Saturday, December 02, 2006 2:15 PM To: Miyamoto Masaomi/Pharmaceutical Development Managing Director, Nabulsi Azmi/Pharmaceutical Development, Strategic Development Mgr Cc: Niimi Mitsuhiro/Pharmaceutica Development, Strategic Development Department, Promotion GM, Yates John/President.TGRD. TGRD Subject: FW: pioglitazone metaanalysis (Confidential) Dear Dr. Miyamoto and Azmi, As I reported to you in Chicago, John originally planned to send a statement letter to the Cochrane library. According to his -mail which I received yesterday and was copied to you, he changed the strategy and TGRD is going to publish our meta-analysis under the name of Steve Nissen and needs TPC's agreement urgently. Please refer to my previous e-mail to you and John's e-mail. As Azmi commented before, the meta-analysis is very important and I also think it should be published as soon as possible. After PDD's official approval is granted, I will make sure the draft will be reviewed by the relevant departments/divisions through SPPD according to the Corporate SOP for scientific publication. Since John will be in Osaka next week I would like to arrange a meeting with you. Kind regards, Yukari Original Message From: Yates John/President.TGRD. TGRD. Sent: Saturday, December 02, 2006 8:37 AM To: Perez Alfonso/VP Clin Rsrch.Clinical Research - MPDRAP IIIA. TGRD. ; Nishikata Yukari/Pharmaceutical Development, Strategic Development Department, Promotion G, Principal Member Subject: RE: pioglitazone metaanalysis(Confidential) Thanks Alfonso. II agree we-need to -expedite the -meta-analysis-publication Yukari -- we need buy in from TPC to move ahead very quickly to use Steve Nissen to author this publication. I will be coming to Osaka appiving Monday next week, so we can discuss there if that would be helpful. Thanks John From: Perez, Alfonso (TGRD) Confidential - Subject to Protective Order TAK-NISHIY-00221507 TAK-NISHY-00221506P-0002 Sent: Friday, December 01, 2006 5:29 PM To: Yates, John (TGRD) Subject: FW: pioglitazone metaanalysis(Confidential) John, ADOPT a 4 year trial comparing rosi vs glyburide and vs . met formin will be publish shortly, looks another "nightmare" in ev events as Dream for rosi. This reinforce our urgent need for early publication of our metaanalysis Regards, Alfonso From: Steven E. Nissen [mailto:nissens@ccf.org Sent: Friday, December 01, 2006 2:02 PM : Perez, Alfonso (TGRD) Isaacson,Brigit (TGRD) Subject: Re: pioglitazone metaanalysis ADOPT is now available embargoed. Another bad CV result for rosiglitazone. Steve Nissen Confidential - Subject to Protective Order TAK-NISHIY-00221508 TAK-NISHY-00221506P-000 Cleveland Clinic is ranked one of the top 3 hospitals in America by U.S. News & World Report. Visit us online at Ittp://www.clevelandclinic.org for a complete listing of our services, staff and locations. Confidentiality Note: This message is intended for use only by the individual or entity to which it is addressed and-may contain information that is privileged, confidential, and exempt from disclosure under applicable law. If the readen of this message is not the intended recipient or the employee or agent responsible for delivering the message to the intended recipient, you are hereby notified that any dissemination, distribution or copying of this communication is strictly prohibited. If you have received this communication in error, please contact the sender immediately and destroy the material in its entirety, whether electronic or hard copy. Thank you. ### This message is for the designated recipient only and may contain privileged or confidential information. If you have received it in error, please notify the sender immediately and delete the original. Any other use of the email by you is prohibited. ### Confidential - Subject to Protective Order TAK-NISHIY-00221509 TAK-NISHY-00221506P-000 its TM INTERNATIONAL LITIGATION SERVICES CERTIFICATION OF TRANSLATION International Litigation Services, a company specializing in international cases and foreign language document processing, certifies the following: International Litigation Services has retained a professional translator for the attached Japanese into English document. The document is referred to as: "TAK-NISHY-00221506P-0001" I affirm that such translation has been prepared by a duly qualified translator, who has confirmed that such translation is, to the best of his/her knowledge and belief, a true and accurate translation in English of the corresponding Japanese document. I declare under the penalty of perjury that the forgoing is true and correct. Notwithstanding the foregoing affirmations, no liability is assumed for errors and omissions in the translation of the attached document. Executed on this 19th day of February 2014, in Aliso Viejo, California. Josephore Joseph Thorpe Managing Director International Litigation Services, Inc. International Litigation Services, Inc. 8 65 Enterprise Aliso Viejo, California 92656 Phone: 888.313.4457 Fax: 213.674.4191 3 info@ilsteam.com NEW YORK Los ANGELES LAS VEGAS ORANGE COUNTY Source:

What is the fullform of ILS?

tfkf0226

tfkf0226_p0, tfkf0226_p1, tfkf0226_p2, tfkf0226_p3, tfkf0226_p4, tfkf0226_p5, tfkf0226_p6, tfkf0226_p7, tfkf0226_p8

INTERNATIONAL LITIGATION SERVICES

From: Nishikata " Sent: Monday, December 04, 2006 9:05 AM To: Û^À Cc: Nakano " a." " Subject: RE: pioglitazone metaanalysis(Confidential) 7C80, itnox N tt o It OTLITETE. < E3L< to o The Original Message From: Wada Yasuhiko/ Sent: Monday, December 04, 2006 8 19 PM To: Nishikata Yukari/ Nakano Takayuki / Subject: RE: pioglitazone metaanalysis (Confidential) 75th CeriDith EEth Cochrane 32345th PediatricOPackagelttl L. Original Message From: Nishikata Yukari / G # Sent: Monday, December 04, 2006 10 : 01 AM To: Wada asuhiko/ Cc: Nakano Takayuki / It Subject: FW: pioglitazone metaanalysis (Confidential) 1-2 Ometa-analysiststeve Nissen02i 3 o Ctmeta- . t o . 16:30tist ti This Original Message Confidential - From: Nishikata Yukari, Sent: Saturday, December 02, 2006 2:15 PM To: Miyamoto Masaomi/;Nabulsi Azmi/ Cc: Niimi Mitsuhiro / E GM; Yates John/President.TGRD. TGRD. Subject: FW: pioglitazone metaanalysis (Confidential) Dear Dr. Miyamoto and Azmi, As I reported to you in Chicago, John originally planned to send a statement letter to the Cochrane library. According to his e-mail which I received yesterday and was copied to you, he changed the strategy and TGRD is going to publish our meta-analysis under the name of Steve Nissen and needs TPC' agreement urgently. Please refer to my previous e-mail to you and John's e-mail. As Azmi commented before, the meta-analysis is very important and I also think it should be published as soon as possible. After PDD's official approval is granted, I will make sure the draft will be reviewed by the relevant departments/divisions through SPPD according to the Corporate SOP for scientific publication. Since John will be in Osaka next week I would like to arrange a meeting with you. Kind regards, Yukari Original Message From: Yates John/President.TGRD. TGRD. Sent: Saturday, December 02, 2006 8:37 AM To: Perez Alfonso/VP Clin Rsrch. Clinical Research - MPDRAP IIIA. TGRD. ; Nishikata Yukari G Subject: RE : pioglitazone metaanalysis Confidential) Thanks Alfonso. I agree we need to expedite the meta-analysis publication. Yukari - we need buy in from TPC to move ahead very quickly to use Steve Nissen to author this publication. I will be coming to Osaka arriving Monday next week, so we can discuss there if that would be helpful. Thanks John From: Perez, Alfonso (TGRD) Confidential - Sent: Friday, December 01, 2006 5:29 PM To: Yates, John (TGRD) Subject: FW: pioglitazone metaanalysis (Confidential) John, ADOPT a 4 year trial comparing rosi vs. glyburide and vs. met formin will be publish shortly,looks another "nightmare" in CV events as Dream for rosi. This reinforce our urgent need for early publication of our metaanalysis : Regards, Alfonso From: Steven E. Nissen [mailto:nissens@ccf.org Sent: Friday, December 01, 2006 2:02 PM Perez, Alfonso (TGRD). Isaacson, Brigit (TGRD) Subject: Re: pioglitazone netaanalysis A DOPT is now available embargoed. Another bad CV result for rosiglitazone. Steve Nissen Confidential - Cleveland Clinic is ranked one of the top 3 hospitals in America by U.S.News & world Report. Visit us online at tp://www.clevelandclinic.org for a complete listing of our services, staff and locations. Confidentiality Note: This message is intended for use only by the individual or entity to which it is addressed and may contain information that is privileged, confidential, and exempt from disclosure inder applicable law. If the reader of this message is not the intended recipient or the employee or agent responsible for delivering the message to the intended recipient, you are hereby notified that any dissemination, distribution or copying of this communication is strictly prohibited. If you have received this communication in error, please contact the sender immediately and destroy the material in its entirety, whether electronic or hard copy. Thank you. ### This message is for the designated recipient only and may contain privileged or confidential information. If you have received it in error, please notify the sender immediately and delete the original. Any other use of the email by you is prohibited. ### - From: Nishikata i- i,fZà Sent: Monday, December 04, 2006 9:05 AM To: Wada Yasuhiko/`: ã-òSJ" Û'À io". Cc: Nakano i,f%- Subject: RE glitazone-metaanalysis(Confidential) Manager Wada, As you pointed out, before doing the presentation at the SAG conference, we already submitted it also to FDA, so if there is -even the slightest risk that contradictory results could be obtained, I think that we should publish the existing analysis results under Takeda's name, and not Nissen's. I intend to take the discussion in this direction on the 6th, so I will contact you with the outcome. I know I will be consulting with you more on Actos in the future, so I appreciate all your help. Nishikata Original Message From: Wada asuhiko/Pharmaceutical Development, international Safety information Manager Sent: Monday, December 04, 2006 8:19 PM To: Nishikata Yukari/Pharmaceutica Development, Strategic Development Promotion G, Principal Member Cc: Nakano Takayuki/Pharmace.utica Development, Strategic Development Dpt, Promotion G Acting Chief Subject: RE:pioglitazonemetaanalysis(confidential) Nishikata-san, On Wednesday, 12/6, in addition to Gerd and Ceri, I have a meeting with visitors from Aris-G, so I will not be able to attend. Looking at the email exchange, it appears that they are publishing as a response to Cochrane library, but these results will also be put into the package for pediatric, and the outline has already been submitted at the SAG conference with EMEA, so make sure there is no discrepancy with that. Wada Original Message From: Nishikata Vukari/Pharmaceutical Development, Strategic Development Promotion G, Principal Member Sent: Monday, December 04, 2006-10:01 AM To: Wada Yasuhiko/Pharmaceutical Development, International Safety information Manager Cc: Nakano Takayuki/Pharmaceutical Development, Strategic Development Dpt, Promotion G Acting Chief Subject: FWe-pioglitazone-metaanalysis(Confidential Manager Wada, As mentioned in the email below, TGRD is planning to publish the meta-analysis of Actos under Steve Nissen's name. I think there is no problem if the results of the meta-analysis as conducted by Takeda will be presented as-is, however, if Nessen (sic) is doing the analysis over again, I think we need to consider with caution. John will be visiting Japan this week to attend the Research HQ's yearly planning hearing, so I would like to secure a time to discuss this with him directly. I apologize for the last-minute notice, but we will have this meeting on 12/6 Wednesday from 16:30, at the 13th laboratory main tower, room 1114. This will be after the yearly planning hearing, so the starting time may get delayed a bit, but please do attend if time allows. Please decide within reason without pushing yourself too much, as you will have to come out all the way to the 13th laboratory. Nishikata Original Message Confidential - Subject to Protective Order TAK-NISHIY-00221506 TAK-NISHY-00221506P-000 From: Nishikata /ukari/Pharmaceutical Development, Strategic Development Department, Promotion G. Principal Member Sent: Saturday, December 02, 2006 2:15 PM To: Miyamoto Masaomi/Pharmaceutical Development Managing Director, Nabulsi Azmi/Pharmaceutical Development, Strategic Development Mgr Cc: Niimi Mitsuhiro/Pharmaceutica Development, Strategic Development Department, Promotion GM, Yates John/President.TGRD. TGRD Subject: FW: pioglitazone metaanalysis (Confidential) Dear Dr. Miyamoto and Azmi, As I reported to you in Chicago, John originally planned to send a statement letter to the Cochrane library. According to his -mail which I received yesterday and was copied to you, he changed the strategy and TGRD is going to publish our meta-analysis under the name of Steve Nissen and needs TPC's agreement urgently. Please refer to my previous e-mail to you and John's e-mail. As Azmi commented before, the meta-analysis is very important and I also think it should be published as soon as possible. After PDD's official approval is granted, I will make sure the draft will be reviewed by the relevant departments/divisions through SPPD according to the Corporate SOP for scientific publication. Since John will be in Osaka next week I would like to arrange a meeting with you. Kind regards, Yukari Original Message From: Yates John/President.TGRD. TGRD. Sent: Saturday, December 02, 2006 8:37 AM To: Perez Alfonso/VP Clin Rsrch.Clinical Research - MPDRAP IIIA. TGRD. ; Nishikata Yukari/Pharmaceutical Development, Strategic Development Department, Promotion G, Principal Member Subject: RE: pioglitazone metaanalysis(Confidential) Thanks Alfonso. II agree we-need to -expedite the -meta-analysis-publication Yukari -- we need buy in from TPC to move ahead very quickly to use Steve Nissen to author this publication. I will be coming to Osaka appiving Monday next week, so we can discuss there if that would be helpful. Thanks John From: Perez, Alfonso (TGRD) Confidential - Subject to Protective Order TAK-NISHIY-00221507 TAK-NISHY-00221506P-0002 Sent: Friday, December 01, 2006 5:29 PM To: Yates, John (TGRD) Subject: FW: pioglitazone metaanalysis(Confidential) John, ADOPT a 4 year trial comparing rosi vs glyburide and vs . met formin will be publish shortly, looks another "nightmare" in ev events as Dream for rosi. This reinforce our urgent need for early publication of our metaanalysis Regards, Alfonso From: Steven E. Nissen [mailto:nissens@ccf.org Sent: Friday, December 01, 2006 2:02 PM : Perez, Alfonso (TGRD) Isaacson,Brigit (TGRD) Subject: Re: pioglitazone metaanalysis ADOPT is now available embargoed. Another bad CV result for rosiglitazone. Steve Nissen Confidential - Subject to Protective Order TAK-NISHIY-00221508 TAK-NISHY-00221506P-000 Cleveland Clinic is ranked one of the top 3 hospitals in America by U.S. News & World Report. Visit us online at Ittp://www.clevelandclinic.org for a complete listing of our services, staff and locations. Confidentiality Note: This message is intended for use only by the individual or entity to which it is addressed and-may contain information that is privileged, confidential, and exempt from disclosure under applicable law. If the readen of this message is not the intended recipient or the employee or agent responsible for delivering the message to the intended recipient, you are hereby notified that any dissemination, distribution or copying of this communication is strictly prohibited. If you have received this communication in error, please contact the sender immediately and destroy the material in its entirety, whether electronic or hard copy. Thank you. ### This message is for the designated recipient only and may contain privileged or confidential information. If you have received it in error, please notify the sender immediately and delete the original. Any other use of the email by you is prohibited. ### Confidential - Subject to Protective Order TAK-NISHIY-00221509 TAK-NISHY-00221506P-000 its TM INTERNATIONAL LITIGATION SERVICES CERTIFICATION OF TRANSLATION International Litigation Services, a company specializing in international cases and foreign language document processing, certifies the following: International Litigation Services has retained a professional translator for the attached Japanese into English document. The document is referred to as: "TAK-NISHY-00221506P-0001" I affirm that such translation has been prepared by a duly qualified translator, who has confirmed that such translation is, to the best of his/her knowledge and belief, a true and accurate translation in English of the corresponding Japanese document. I declare under the penalty of perjury that the forgoing is true and correct. Notwithstanding the foregoing affirmations, no liability is assumed for errors and omissions in the translation of the attached document. Executed on this 19th day of February 2014, in Aliso Viejo, California. Josephore Joseph Thorpe Managing Director International Litigation Services, Inc. International Litigation Services, Inc. 8 65 Enterprise Aliso Viejo, California 92656 Phone: 888.313.4457 Fax: 213.674.4191 3 info@ilsteam.com NEW YORK Los ANGELES LAS VEGAS ORANGE COUNTY Source:

What is the issued date of this letter?

klcn0226

klcn0226_p0, klcn0226_p1

June 15, 2006

American Chemistry Council Gand " Porsible Dr. Nancy Beck June 15, 2006 Office of Information and Regulatory Affairs Office of Management and Budget 725 17th Street, NW. New Executive Office Building Room 10201 Washington, DC 20503 Re: Comments on Proposed Risk Assessment Bulletin Dear Dr. Beck: The American Chemistry Council (ACC or the Council) is pleased to submit comments on the Office of Management and Budget's Proposed Risk Assessment Bulletin¹. The Council represents the leading companies engaged in the business of chemistry². ACC and its members make substantial, ongoing investments in research to support product development, health, safety and environmental protection, and to abide by product stewardship and regulatory policies. Chemistry is a science-based industry, and ACC has long sought to improve the quality of government science generally and risk assessment in particular. For example, in response to OMB's Draft 2003 Report to Congress on the Costs and Benefits of Federal Regulations, ACC filed an extensive set of comments (63 3 pages plus five appendices) that primarily focused on EPA's risk assessment practices. Appendix 5 to those comments provided 62 additional pages of examples of EPA risk assessments that overstated risks. ACC's comments were the principal drivers behind EPA's 2004 staff paper on the Agency's risk assessment principles and practices - a document which defended the appropriateness of many of the practices to which ACC objected. These controversies are still largely unresolved, and thus ACC has a substantial interest in the Bulletin. 1 Notice of availability at 71 Fed. Reg. 2600 (Jan. 17, 2006). 2 Council members apply the science of chemistry to make innovative products and services that make people's lives better, healthier and safer. The Council is committed to improved environmental, health and safety performance through Responsible R 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 $460 billion enterprise and a key element of the nation's economy. It is the nation's largest exporter, accounting for ten cents out of every dollar in U.S. exports. Chemistry companies invest more in research and development than any other business sector. 3 ACC, "Comments to the Office of Management & Budget; Draft 2003 Report to Congress on the Costs and Benefits of Federal Regulations," filed May 5, 2003. These comments and Appendix 5 are attached. 4 EPA Office of the Science Advisor Staff Paper, An Examination of EPA Risk Assessment Principles and Practices (EPA/100/B-04/001) (Feb. 2004). Responsible Care 1300 Wilson Boulevard, Arlington, VA 22209 Tel 703-741-5000 A Fax 703-741-6000 Source: https://www.industrydocuments.ucsf.edu/docs/klcn0226 Dr. Beck June 15, 2006 Page 2 ACC has strongly supported OMB's efforts - through its Information Quality Act (IQA) Guidelines, the 5 Peer Review Bulletin, 6 Circular A-4,7 and otherwise - to assure that the highest quality scientific work products are consistently and assiduously applied in support of regulatory policy. The proposed Risk Assessment Bulletin continues those efforts, and ACC applauds OMB for issuing it. We believe the Bulletin, once finalized, will improve the uneven performance of risk assessments at EPA and other federal agencies by setting a unified, upgraded standard. The attached comments highlight the strengths that we have identified in the document, and recommend a number of improvements that we believe are vital to its success. We understand that many important issues associated with the Bulletin will only become clear as it is implemented, and we look forward to a continuing dialogue with OMB before and after its final publication. Should you or other OMB staff have any questions on, or need clarification of, ACC comments, please don't hesitate to contact either of us at 703-741-5000. Sincerely, James W. Conrad, Jr. Richard A. Becker, Ph.D. DABT Assistant General Counsel Senior Toxicologist/Senior Director Attachment: Comments of the American Chemistry Council on the Proposed Risk Assessment Bulletin (released for public review and comment in January, 2006) 5 OMB, Guidelines for Ensuring and Maximizing the Quality, Objectivity, Utility, and Integrity of Information Disseminated by Federal Agencies, 67 Fed. Reg. 8452 (Feb. 22, 2002). 6 OMB, Final Information Quality Bulletin for Peer Review, 70 Fed. Reg. 2664 (Jan. 14, 2005). 7 OMB, Circular A-4 (Sept. 2003). Source: https://www.industrydocuments.ucsf.edu/docs/klcn0226

What is the subject of the letter?

klcn0226

klcn0226_p0, klcn0226_p1

Comments on proposed risk assessment bulletin, comments on proposed risk assessment bulletin

American Chemistry Council Gand " Porsible Dr. Nancy Beck June 15, 2006 Office of Information and Regulatory Affairs Office of Management and Budget 725 17th Street, NW. New Executive Office Building Room 10201 Washington, DC 20503 Re: Comments on Proposed Risk Assessment Bulletin Dear Dr. Beck: The American Chemistry Council (ACC or the Council) is pleased to submit comments on the Office of Management and Budget's Proposed Risk Assessment Bulletin¹. The Council represents the leading companies engaged in the business of chemistry². ACC and its members make substantial, ongoing investments in research to support product development, health, safety and environmental protection, and to abide by product stewardship and regulatory policies. Chemistry is a science-based industry, and ACC has long sought to improve the quality of government science generally and risk assessment in particular. For example, in response to OMB's Draft 2003 Report to Congress on the Costs and Benefits of Federal Regulations, ACC filed an extensive set of comments (63 3 pages plus five appendices) that primarily focused on EPA's risk assessment practices. Appendix 5 to those comments provided 62 additional pages of examples of EPA risk assessments that overstated risks. ACC's comments were the principal drivers behind EPA's 2004 staff paper on the Agency's risk assessment principles and practices - a document which defended the appropriateness of many of the practices to which ACC objected. These controversies are still largely unresolved, and thus ACC has a substantial interest in the Bulletin. 1 Notice of availability at 71 Fed. Reg. 2600 (Jan. 17, 2006). 2 Council members apply the science of chemistry to make innovative products and services that make people's lives better, healthier and safer. The Council is committed to improved environmental, health and safety performance through Responsible R 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 $460 billion enterprise and a key element of the nation's economy. It is the nation's largest exporter, accounting for ten cents out of every dollar in U.S. exports. Chemistry companies invest more in research and development than any other business sector. 3 ACC, "Comments to the Office of Management & Budget; Draft 2003 Report to Congress on the Costs and Benefits of Federal Regulations," filed May 5, 2003. These comments and Appendix 5 are attached. 4 EPA Office of the Science Advisor Staff Paper, An Examination of EPA Risk Assessment Principles and Practices (EPA/100/B-04/001) (Feb. 2004). Responsible Care 1300 Wilson Boulevard, Arlington, VA 22209 Tel 703-741-5000 A Fax 703-741-6000 Source: https://www.industrydocuments.ucsf.edu/docs/klcn0226 Dr. Beck June 15, 2006 Page 2 ACC has strongly supported OMB's efforts - through its Information Quality Act (IQA) Guidelines, the 5 Peer Review Bulletin, 6 Circular A-4,7 and otherwise - to assure that the highest quality scientific work products are consistently and assiduously applied in support of regulatory policy. The proposed Risk Assessment Bulletin continues those efforts, and ACC applauds OMB for issuing it. We believe the Bulletin, once finalized, will improve the uneven performance of risk assessments at EPA and other federal agencies by setting a unified, upgraded standard. The attached comments highlight the strengths that we have identified in the document, and recommend a number of improvements that we believe are vital to its success. We understand that many important issues associated with the Bulletin will only become clear as it is implemented, and we look forward to a continuing dialogue with OMB before and after its final publication. Should you or other OMB staff have any questions on, or need clarification of, ACC comments, please don't hesitate to contact either of us at 703-741-5000. Sincerely, James W. Conrad, Jr. Richard A. Becker, Ph.D. DABT Assistant General Counsel Senior Toxicologist/Senior Director Attachment: Comments of the American Chemistry Council on the Proposed Risk Assessment Bulletin (released for public review and comment in January, 2006) 5 OMB, Guidelines for Ensuring and Maximizing the Quality, Objectivity, Utility, and Integrity of Information Disseminated by Federal Agencies, 67 Fed. Reg. 8452 (Feb. 22, 2002). 6 OMB, Final Information Quality Bulletin for Peer Review, 70 Fed. Reg. 2664 (Jan. 14, 2005). 7 OMB, Circular A-4 (Sept. 2003). Source: https://www.industrydocuments.ucsf.edu/docs/klcn0226

What is ACC stands for?

klcn0226

klcn0226_p0, klcn0226_p1

American Chemistry council, American Chemistry Council

American Chemistry Council Gand " Porsible Dr. Nancy Beck June 15, 2006 Office of Information and Regulatory Affairs Office of Management and Budget 725 17th Street, NW. New Executive Office Building Room 10201 Washington, DC 20503 Re: Comments on Proposed Risk Assessment Bulletin Dear Dr. Beck: The American Chemistry Council (ACC or the Council) is pleased to submit comments on the Office of Management and Budget's Proposed Risk Assessment Bulletin¹. The Council represents the leading companies engaged in the business of chemistry². ACC and its members make substantial, ongoing investments in research to support product development, health, safety and environmental protection, and to abide by product stewardship and regulatory policies. Chemistry is a science-based industry, and ACC has long sought to improve the quality of government science generally and risk assessment in particular. For example, in response to OMB's Draft 2003 Report to Congress on the Costs and Benefits of Federal Regulations, ACC filed an extensive set of comments (63 3 pages plus five appendices) that primarily focused on EPA's risk assessment practices. Appendix 5 to those comments provided 62 additional pages of examples of EPA risk assessments that overstated risks. ACC's comments were the principal drivers behind EPA's 2004 staff paper on the Agency's risk assessment principles and practices - a document which defended the appropriateness of many of the practices to which ACC objected. These controversies are still largely unresolved, and thus ACC has a substantial interest in the Bulletin. 1 Notice of availability at 71 Fed. Reg. 2600 (Jan. 17, 2006). 2 Council members apply the science of chemistry to make innovative products and services that make people's lives better, healthier and safer. The Council is committed to improved environmental, health and safety performance through Responsible R 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 $460 billion enterprise and a key element of the nation's economy. It is the nation's largest exporter, accounting for ten cents out of every dollar in U.S. exports. Chemistry companies invest more in research and development than any other business sector. 3 ACC, "Comments to the Office of Management & Budget; Draft 2003 Report to Congress on the Costs and Benefits of Federal Regulations," filed May 5, 2003. These comments and Appendix 5 are attached. 4 EPA Office of the Science Advisor Staff Paper, An Examination of EPA Risk Assessment Principles and Practices (EPA/100/B-04/001) (Feb. 2004). Responsible Care 1300 Wilson Boulevard, Arlington, VA 22209 Tel 703-741-5000 A Fax 703-741-6000 Source: https://www.industrydocuments.ucsf.edu/docs/klcn0226 Dr. Beck June 15, 2006 Page 2 ACC has strongly supported OMB's efforts - through its Information Quality Act (IQA) Guidelines, the 5 Peer Review Bulletin, 6 Circular A-4,7 and otherwise - to assure that the highest quality scientific work products are consistently and assiduously applied in support of regulatory policy. The proposed Risk Assessment Bulletin continues those efforts, and ACC applauds OMB for issuing it. We believe the Bulletin, once finalized, will improve the uneven performance of risk assessments at EPA and other federal agencies by setting a unified, upgraded standard. The attached comments highlight the strengths that we have identified in the document, and recommend a number of improvements that we believe are vital to its success. We understand that many important issues associated with the Bulletin will only become clear as it is implemented, and we look forward to a continuing dialogue with OMB before and after its final publication. Should you or other OMB staff have any questions on, or need clarification of, ACC comments, please don't hesitate to contact either of us at 703-741-5000. Sincerely, James W. Conrad, Jr. Richard A. Becker, Ph.D. DABT Assistant General Counsel Senior Toxicologist/Senior Director Attachment: Comments of the American Chemistry Council on the Proposed Risk Assessment Bulletin (released for public review and comment in January, 2006) 5 OMB, Guidelines for Ensuring and Maximizing the Quality, Objectivity, Utility, and Integrity of Information Disseminated by Federal Agencies, 67 Fed. Reg. 8452 (Feb. 22, 2002). 6 OMB, Final Information Quality Bulletin for Peer Review, 70 Fed. Reg. 2664 (Jan. 14, 2005). 7 OMB, Circular A-4 (Sept. 2003). Source: https://www.industrydocuments.ucsf.edu/docs/klcn0226

What is Task A?

qrbn0226

qrbn0226_p0, qrbn0226_p1, qrbn0226_p2, qrbn0226_p3, qrbn0226_p4

Fabricate Replica Baby Monitors

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; info@troitzsch.com 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 White@americanchemistry.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 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 does the Figure 3 show?

qrbn0226

qrbn0226_p0, qrbn0226_p1, qrbn0226_p2, qrbn0226_p3, qrbn0226_p4

Makerbot flammability warning video, Makerbot Flammability warning video

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; info@troitzsch.com 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 White@americanchemistry.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 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 date mentioned?

qrbn0226

qrbn0226_p0, qrbn0226_p1, qrbn0226_p2, qrbn0226_p3, qrbn0226_p4

August 3, 2016

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; info@troitzsch.com 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 White@americanchemistry.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 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

How many steps Prioritization Process is shown?

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

Two-step, Two-Step

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 the Second Tier the Ranking Ordering are within which 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, Priority Groups, Priority groups

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

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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

Risk-Based Prioritization Matrix

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 alternative given for Biomonitoring?

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

Environmental Monitoring

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 heading of the document?

ngcn0226

ngcn0226_p0

American Chemistry council, American Chemistry Council

American' Chemistry Council January 28, 2013 John Cowden, Ph.D. Janice Lee, Ph.D. U.S. EPA National Center for Environmental Assessment Mail Code: B243-01 109 T.W. Alexander Drive, Durham, N.C, 27711 Submitted via email to: Docket ORD@epa.gov; cowden.john@epa.gov;lee.janices@epa.gov Regarding: Submission to docket EPA-HQ-ORD-2012-0830; comments on the Planning and Scoping Summary for the Toxicological Review of Inorganic Arsenic. Dear Drs. Cowden and Lee: The American Chemistry Council (ACC¹ and its Center for Advancing Risk Assessment Science and Policy (ARASP)2 appreciate the opportunity to provide comments to the Environmental Protection Agency (EPA) on the draft Planning and Scoping Summary for the Toxicological Review of Inorganic Arsenic (hereinafter referred to as draft Scope). We applaud EPA for holding a two-day stakeholder workshop to begin addressing important scientific issues that will inform the toxicological review as well as the National Academies review of inorganic arsenic. ACC participated remotely via webinar and we found the technology to be easily accessible and generally user-friendly. While there were some small glitches, we are confident that EPA will work to improve them in the future. To further improve transparency, it would be very helpful if EPA could share the presentations with the meeting participants in advance of the meeting or in real-time via email. While we understand that web posting may take longer, it is unfortunate that this delays active participation from engaged stakeholders. 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 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 $760 billion enterprise and a key element of the nation's economy. It is the largest exporting sector in the U.S., accounting for 12 percent of 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 threats to the nation's critical infrastructure. 2 Within ACC, the Center for Advancing Risk Assessment Science and Policy (ARASP) is a coalition of independent groups and associations that promotes the development and application of up-to-date, scientifically sound methods for conducting chemical assessments. americanchemistry.com 700 Second St., NE I Washington, DC 20002 I (202)249.7000 Source: https://www.industrydocuments.ucsf.edu/docs/ngcn0226

What is the date mentioned?

ngcn0226

ngcn0226_p0

January 28, 2013, january 28, 2013

American' Chemistry Council January 28, 2013 John Cowden, Ph.D. Janice Lee, Ph.D. U.S. EPA National Center for Environmental Assessment Mail Code: B243-01 109 T.W. Alexander Drive, Durham, N.C, 27711 Submitted via email to: Docket ORD@epa.gov; cowden.john@epa.gov;lee.janices@epa.gov Regarding: Submission to docket EPA-HQ-ORD-2012-0830; comments on the Planning and Scoping Summary for the Toxicological Review of Inorganic Arsenic. Dear Drs. Cowden and Lee: The American Chemistry Council (ACC¹ and its Center for Advancing Risk Assessment Science and Policy (ARASP)2 appreciate the opportunity to provide comments to the Environmental Protection Agency (EPA) on the draft Planning and Scoping Summary for the Toxicological Review of Inorganic Arsenic (hereinafter referred to as draft Scope). We applaud EPA for holding a two-day stakeholder workshop to begin addressing important scientific issues that will inform the toxicological review as well as the National Academies review of inorganic arsenic. ACC participated remotely via webinar and we found the technology to be easily accessible and generally user-friendly. While there were some small glitches, we are confident that EPA will work to improve them in the future. To further improve transparency, it would be very helpful if EPA could share the presentations with the meeting participants in advance of the meeting or in real-time via email. While we understand that web posting may take longer, it is unfortunate that this delays active participation from engaged stakeholders. 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 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 $760 billion enterprise and a key element of the nation's economy. It is the largest exporting sector in the U.S., accounting for 12 percent of 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 threats to the nation's critical infrastructure. 2 Within ACC, the Center for Advancing Risk Assessment Science and Policy (ARASP) is a coalition of independent groups and associations that promotes the development and application of up-to-date, scientifically sound methods for conducting chemical assessments. americanchemistry.com 700 Second St., NE I Washington, DC 20002 I (202)249.7000 Source: https://www.industrydocuments.ucsf.edu/docs/ngcn0226

To whom is this email addressed?

ngcn0226

ngcn0226_p0

Drs. Cowden and Lee, John Cowden, Ph.D., Docket_ORD@epa.gov; cowden.john@epa.gov; lee.janices@epagov

American' Chemistry Council January 28, 2013 John Cowden, Ph.D. Janice Lee, Ph.D. U.S. EPA National Center for Environmental Assessment Mail Code: B243-01 109 T.W. Alexander Drive, Durham, N.C, 27711 Submitted via email to: Docket ORD@epa.gov; cowden.john@epa.gov;lee.janices@epa.gov Regarding: Submission to docket EPA-HQ-ORD-2012-0830; comments on the Planning and Scoping Summary for the Toxicological Review of Inorganic Arsenic. Dear Drs. Cowden and Lee: The American Chemistry Council (ACC¹ and its Center for Advancing Risk Assessment Science and Policy (ARASP)2 appreciate the opportunity to provide comments to the Environmental Protection Agency (EPA) on the draft Planning and Scoping Summary for the Toxicological Review of Inorganic Arsenic (hereinafter referred to as draft Scope). We applaud EPA for holding a two-day stakeholder workshop to begin addressing important scientific issues that will inform the toxicological review as well as the National Academies review of inorganic arsenic. ACC participated remotely via webinar and we found the technology to be easily accessible and generally user-friendly. While there were some small glitches, we are confident that EPA will work to improve them in the future. To further improve transparency, it would be very helpful if EPA could share the presentations with the meeting participants in advance of the meeting or in real-time via email. While we understand that web posting may take longer, it is unfortunate that this delays active participation from engaged stakeholders. 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 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 $760 billion enterprise and a key element of the nation's economy. It is the largest exporting sector in the U.S., accounting for 12 percent of 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 threats to the nation's critical infrastructure. 2 Within ACC, the Center for Advancing Risk Assessment Science and Policy (ARASP) is a coalition of independent groups and associations that promotes the development and application of up-to-date, scientifically sound methods for conducting chemical assessments. americanchemistry.com 700 Second St., NE I Washington, DC 20002 I (202)249.7000 Source: https://www.industrydocuments.ucsf.edu/docs/ngcn0226

What is the full form ACC?

ngcn0226

ngcn0226_p0

American Chemistry council, American Chemistry Council

American' Chemistry Council January 28, 2013 John Cowden, Ph.D. Janice Lee, Ph.D. U.S. EPA National Center for Environmental Assessment Mail Code: B243-01 109 T.W. Alexander Drive, Durham, N.C, 27711 Submitted via email to: Docket ORD@epa.gov; cowden.john@epa.gov;lee.janices@epa.gov Regarding: Submission to docket EPA-HQ-ORD-2012-0830; comments on the Planning and Scoping Summary for the Toxicological Review of Inorganic Arsenic. Dear Drs. Cowden and Lee: The American Chemistry Council (ACC¹ and its Center for Advancing Risk Assessment Science and Policy (ARASP)2 appreciate the opportunity to provide comments to the Environmental Protection Agency (EPA) on the draft Planning and Scoping Summary for the Toxicological Review of Inorganic Arsenic (hereinafter referred to as draft Scope). We applaud EPA for holding a two-day stakeholder workshop to begin addressing important scientific issues that will inform the toxicological review as well as the National Academies review of inorganic arsenic. ACC participated remotely via webinar and we found the technology to be easily accessible and generally user-friendly. While there were some small glitches, we are confident that EPA will work to improve them in the future. To further improve transparency, it would be very helpful if EPA could share the presentations with the meeting participants in advance of the meeting or in real-time via email. While we understand that web posting may take longer, it is unfortunate that this delays active participation from engaged stakeholders. 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 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 $760 billion enterprise and a key element of the nation's economy. It is the largest exporting sector in the U.S., accounting for 12 percent of 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 threats to the nation's critical infrastructure. 2 Within ACC, the Center for Advancing Risk Assessment Science and Policy (ARASP) is a coalition of independent groups and associations that promotes the development and application of up-to-date, scientifically sound methods for conducting chemical assessments. americanchemistry.com 700 Second St., NE I Washington, DC 20002 I (202)249.7000 Source: https://www.industrydocuments.ucsf.edu/docs/ngcn0226

By whom is this ethics agreement written?

llcn0226

llcn0226_p0, llcn0226_p1

Michael L. Dourson

July 11, 2017 Mr. Kevin S. Minoli Designated Agency Ethics Official U.S. EPA (2310A) 1200 Pennsylvania Avenue, NW Washington, DC 20460 Dear Mr. Minoli: The purpose of this letter is to describe the steps that I will take to avoid any actual or apparent conflict of interest in the event that I am confirmed for the position of Assistant Administrator for the Office of Chemical Safety and Pollution Prevention of the United States Environmental Protection Agency. As required by 18 U.S.C. § 208(a), I will not participate personally and substantially in any particular matter in which I know that I have a financial interest directly and predictably affected by the matter, or in which I know that a person whose interests are imputed to me has a financial interest directly and predictably affected by the matter, unless I first obtain a written waiver, pursuant to 18 U.S.C. § 208(b)(1), or qualify for a regulatory exemption, pursuant to 18 U.S.C. § 208(b)(2). I understand that the interests of the following persons are imputed to me: any spouse or minor child of mine; any general partner of a partnership in which I am a limited or general partner; any organization in which I serve as officer, director, trustee, general partner or employee; and any person or organization with which I am negotiating or have an arrangement concerning prospective employment. Upon confirmation, I will resign from my positions with the following entities: University of Cincinnati, and the Toxicology Education Foundation. I resigned from my position with the North American Flame Retardant Alliance, and the Toxicology Forum in June 2017. For a period of one year after my resignation from each of these entities, I will not participate personally and substantially in any particular matter involving specific parties in which I know that entity is a party or represents a party, unless I am first authorized to participate, pursuant to 5 C.F.R. § 2635.502(d) Upon confirmation, I also will resign from my position with the Environmental Protection Agency's Science Advisory Board. Upon confirmation, I will resign from my position as general partner of Dourson, Dourson and Fowler, a partnership that owns undeveloped land in Stanton, KY, and I will transfer my financial interest in this entity to my adult son. I will not participate personally and substantially in any particular matter that to my knowledge has a direct and predictable effect on the financial interests of this entity until I have transferred it, unless I first obtain a written waiver, pursuant to 18 U.S.C. § 208(b)(1), or qualify for a regulatory exemption, pursuant to 18 U.S.C. § 208(b)(2). For a period of one year after my resignation, I will not participate personally and substantially in any particular matter involving specific parties in which I know Dourson, Dourson, and Fowler is a party or represents a party, unless I am first authorized to Source: https://www.industrydocuments.ucsf.edu/docs//lcn0226 participate, pursuant to 5 C.F.R. § 2635.502(d). My spouse is a sole proprietor of her law firm, which does business as Martha C. Dourson, LLC. For as long as my spouse continues to have her law practice, I will not participate personally and substantially in any particular matter that to my knowledge has a direct and predictable effect on the financial interests of the firm, unless I first obtain a written waiver, pursuant to 18 U.S.C. § 208(b)(1). I also will not participate personally and substantially in any particular matter involving specific parties in which I know a client of my spouse is a party or represents a party, unless I am first authorized to participate, pursuant to 5 C.F.R. § 2635.502(d). I receive royalties from CreateSpace Independent Publishing Platform for sales of my three books: Messiah's Star (Evidence for Faith) (Volume 1); The Beginning: Let there be light (Evidence of Faith) (Volume 2); and "The Linen Cloths: Jesus left behind (Evidence of Faith) (Volume 3). I will not participate personally and substantially in any particular matter involving specific parties in which I know CreateSpace Independent Publishing Platform is a party or represents a party, unless I am first authorized to participate, pursuant to 5 C.F.R. § 2635.502(d). If I have a managed account or otherwise use the services of an investment professional during my appointment, I will ensure that the account manager or investment professional obtains my prior approval on a case-by-case basis for the purchase of any assets other than cash, cash equivalents, investment funds that qualify for the exemption at 5 C.F.R. § 2640.201(a), obligations of the United States, or municipal bonds. I will meet in person with you during the first week of my service in the position of Assistant Administrator in order to complete the initial ethics briefing required under 5 C.F.R. § 2638.305. Within 90 days of my confirmation, I will document my compliance with this ethics agreement by notifying you in writing when I have completed the steps described in this ethics agreement. I understand that as an appointee I will be required to sign the Ethics Pledge (Exec. Order No. 13770) and that I will be bound by the requirements and restrictions therein in addition to the commitments I have made in this ethics agreement. I have been advised that this ethics agreement will be posted publicly, consistent with 5 U.S.C. § 552, on the website of the U.S. Office of Government Ethics with ethics agreements of other Presidential nominees who file public financial disclosure reports. Sincerely yours, intentioned Michael L. Dourson Source: https://www.industrydocuments.ucsf.edu/docs/llcn0226

From which Publishing Platform did the author receive royalties for sales of his three books?

llcn0226

llcn0226_p0, llcn0226_p1

CreateSpace Independent Publishing Platform

July 11, 2017 Mr. Kevin S. Minoli Designated Agency Ethics Official U.S. EPA (2310A) 1200 Pennsylvania Avenue, NW Washington, DC 20460 Dear Mr. Minoli: The purpose of this letter is to describe the steps that I will take to avoid any actual or apparent conflict of interest in the event that I am confirmed for the position of Assistant Administrator for the Office of Chemical Safety and Pollution Prevention of the United States Environmental Protection Agency. As required by 18 U.S.C. § 208(a), I will not participate personally and substantially in any particular matter in which I know that I have a financial interest directly and predictably affected by the matter, or in which I know that a person whose interests are imputed to me has a financial interest directly and predictably affected by the matter, unless I first obtain a written waiver, pursuant to 18 U.S.C. § 208(b)(1), or qualify for a regulatory exemption, pursuant to 18 U.S.C. § 208(b)(2). I understand that the interests of the following persons are imputed to me: any spouse or minor child of mine; any general partner of a partnership in which I am a limited or general partner; any organization in which I serve as officer, director, trustee, general partner or employee; and any person or organization with which I am negotiating or have an arrangement concerning prospective employment. Upon confirmation, I will resign from my positions with the following entities: University of Cincinnati, and the Toxicology Education Foundation. I resigned from my position with the North American Flame Retardant Alliance, and the Toxicology Forum in June 2017. For a period of one year after my resignation from each of these entities, I will not participate personally and substantially in any particular matter involving specific parties in which I know that entity is a party or represents a party, unless I am first authorized to participate, pursuant to 5 C.F.R. § 2635.502(d) Upon confirmation, I also will resign from my position with the Environmental Protection Agency's Science Advisory Board. Upon confirmation, I will resign from my position as general partner of Dourson, Dourson and Fowler, a partnership that owns undeveloped land in Stanton, KY, and I will transfer my financial interest in this entity to my adult son. I will not participate personally and substantially in any particular matter that to my knowledge has a direct and predictable effect on the financial interests of this entity until I have transferred it, unless I first obtain a written waiver, pursuant to 18 U.S.C. § 208(b)(1), or qualify for a regulatory exemption, pursuant to 18 U.S.C. § 208(b)(2). For a period of one year after my resignation, I will not participate personally and substantially in any particular matter involving specific parties in which I know Dourson, Dourson, and Fowler is a party or represents a party, unless I am first authorized to Source: https://www.industrydocuments.ucsf.edu/docs//lcn0226 participate, pursuant to 5 C.F.R. § 2635.502(d). My spouse is a sole proprietor of her law firm, which does business as Martha C. Dourson, LLC. For as long as my spouse continues to have her law practice, I will not participate personally and substantially in any particular matter that to my knowledge has a direct and predictable effect on the financial interests of the firm, unless I first obtain a written waiver, pursuant to 18 U.S.C. § 208(b)(1). I also will not participate personally and substantially in any particular matter involving specific parties in which I know a client of my spouse is a party or represents a party, unless I am first authorized to participate, pursuant to 5 C.F.R. § 2635.502(d). I receive royalties from CreateSpace Independent Publishing Platform for sales of my three books: Messiah's Star (Evidence for Faith) (Volume 1); The Beginning: Let there be light (Evidence of Faith) (Volume 2); and "The Linen Cloths: Jesus left behind (Evidence of Faith) (Volume 3). I will not participate personally and substantially in any particular matter involving specific parties in which I know CreateSpace Independent Publishing Platform is a party or represents a party, unless I am first authorized to participate, pursuant to 5 C.F.R. § 2635.502(d). If I have a managed account or otherwise use the services of an investment professional during my appointment, I will ensure that the account manager or investment professional obtains my prior approval on a case-by-case basis for the purchase of any assets other than cash, cash equivalents, investment funds that qualify for the exemption at 5 C.F.R. § 2640.201(a), obligations of the United States, or municipal bonds. I will meet in person with you during the first week of my service in the position of Assistant Administrator in order to complete the initial ethics briefing required under 5 C.F.R. § 2638.305. Within 90 days of my confirmation, I will document my compliance with this ethics agreement by notifying you in writing when I have completed the steps described in this ethics agreement. I understand that as an appointee I will be required to sign the Ethics Pledge (Exec. Order No. 13770) and that I will be bound by the requirements and restrictions therein in addition to the commitments I have made in this ethics agreement. I have been advised that this ethics agreement will be posted publicly, consistent with 5 U.S.C. § 552, on the website of the U.S. Office of Government Ethics with ethics agreements of other Presidential nominees who file public financial disclosure reports. Sincerely yours, intentioned Michael L. Dourson Source: https://www.industrydocuments.ucsf.edu/docs/llcn0226

The authors wife is a sole proprietor of which firm?

llcn0226

llcn0226_p0, llcn0226_p1

law firm, her law firm, Martha C. Dourson, LLC.

July 11, 2017 Mr. Kevin S. Minoli Designated Agency Ethics Official U.S. EPA (2310A) 1200 Pennsylvania Avenue, NW Washington, DC 20460 Dear Mr. Minoli: The purpose of this letter is to describe the steps that I will take to avoid any actual or apparent conflict of interest in the event that I am confirmed for the position of Assistant Administrator for the Office of Chemical Safety and Pollution Prevention of the United States Environmental Protection Agency. As required by 18 U.S.C. § 208(a), I will not participate personally and substantially in any particular matter in which I know that I have a financial interest directly and predictably affected by the matter, or in which I know that a person whose interests are imputed to me has a financial interest directly and predictably affected by the matter, unless I first obtain a written waiver, pursuant to 18 U.S.C. § 208(b)(1), or qualify for a regulatory exemption, pursuant to 18 U.S.C. § 208(b)(2). I understand that the interests of the following persons are imputed to me: any spouse or minor child of mine; any general partner of a partnership in which I am a limited or general partner; any organization in which I serve as officer, director, trustee, general partner or employee; and any person or organization with which I am negotiating or have an arrangement concerning prospective employment. Upon confirmation, I will resign from my positions with the following entities: University of Cincinnati, and the Toxicology Education Foundation. I resigned from my position with the North American Flame Retardant Alliance, and the Toxicology Forum in June 2017. For a period of one year after my resignation from each of these entities, I will not participate personally and substantially in any particular matter involving specific parties in which I know that entity is a party or represents a party, unless I am first authorized to participate, pursuant to 5 C.F.R. § 2635.502(d) Upon confirmation, I also will resign from my position with the Environmental Protection Agency's Science Advisory Board. Upon confirmation, I will resign from my position as general partner of Dourson, Dourson and Fowler, a partnership that owns undeveloped land in Stanton, KY, and I will transfer my financial interest in this entity to my adult son. I will not participate personally and substantially in any particular matter that to my knowledge has a direct and predictable effect on the financial interests of this entity until I have transferred it, unless I first obtain a written waiver, pursuant to 18 U.S.C. § 208(b)(1), or qualify for a regulatory exemption, pursuant to 18 U.S.C. § 208(b)(2). For a period of one year after my resignation, I will not participate personally and substantially in any particular matter involving specific parties in which I know Dourson, Dourson, and Fowler is a party or represents a party, unless I am first authorized to Source: https://www.industrydocuments.ucsf.edu/docs//lcn0226 participate, pursuant to 5 C.F.R. § 2635.502(d). My spouse is a sole proprietor of her law firm, which does business as Martha C. Dourson, LLC. For as long as my spouse continues to have her law practice, I will not participate personally and substantially in any particular matter that to my knowledge has a direct and predictable effect on the financial interests of the firm, unless I first obtain a written waiver, pursuant to 18 U.S.C. § 208(b)(1). I also will not participate personally and substantially in any particular matter involving specific parties in which I know a client of my spouse is a party or represents a party, unless I am first authorized to participate, pursuant to 5 C.F.R. § 2635.502(d). I receive royalties from CreateSpace Independent Publishing Platform for sales of my three books: Messiah's Star (Evidence for Faith) (Volume 1); The Beginning: Let there be light (Evidence of Faith) (Volume 2); and "The Linen Cloths: Jesus left behind (Evidence of Faith) (Volume 3). I will not participate personally and substantially in any particular matter involving specific parties in which I know CreateSpace Independent Publishing Platform is a party or represents a party, unless I am first authorized to participate, pursuant to 5 C.F.R. § 2635.502(d). If I have a managed account or otherwise use the services of an investment professional during my appointment, I will ensure that the account manager or investment professional obtains my prior approval on a case-by-case basis for the purchase of any assets other than cash, cash equivalents, investment funds that qualify for the exemption at 5 C.F.R. § 2640.201(a), obligations of the United States, or municipal bonds. I will meet in person with you during the first week of my service in the position of Assistant Administrator in order to complete the initial ethics briefing required under 5 C.F.R. § 2638.305. Within 90 days of my confirmation, I will document my compliance with this ethics agreement by notifying you in writing when I have completed the steps described in this ethics agreement. I understand that as an appointee I will be required to sign the Ethics Pledge (Exec. Order No. 13770) and that I will be bound by the requirements and restrictions therein in addition to the commitments I have made in this ethics agreement. I have been advised that this ethics agreement will be posted publicly, consistent with 5 U.S.C. § 552, on the website of the U.S. Office of Government Ethics with ethics agreements of other Presidential nominees who file public financial disclosure reports. Sincerely yours, intentioned Michael L. Dourson Source: https://www.industrydocuments.ucsf.edu/docs/llcn0226

Name the first book written by the author among the three?

llcn0226

llcn0226_p0, llcn0226_p1

"Messiahs Star (Evidence for Faith) (Volume 1)"

July 11, 2017 Mr. Kevin S. Minoli Designated Agency Ethics Official U.S. EPA (2310A) 1200 Pennsylvania Avenue, NW Washington, DC 20460 Dear Mr. Minoli: The purpose of this letter is to describe the steps that I will take to avoid any actual or apparent conflict of interest in the event that I am confirmed for the position of Assistant Administrator for the Office of Chemical Safety and Pollution Prevention of the United States Environmental Protection Agency. As required by 18 U.S.C. § 208(a), I will not participate personally and substantially in any particular matter in which I know that I have a financial interest directly and predictably affected by the matter, or in which I know that a person whose interests are imputed to me has a financial interest directly and predictably affected by the matter, unless I first obtain a written waiver, pursuant to 18 U.S.C. § 208(b)(1), or qualify for a regulatory exemption, pursuant to 18 U.S.C. § 208(b)(2). I understand that the interests of the following persons are imputed to me: any spouse or minor child of mine; any general partner of a partnership in which I am a limited or general partner; any organization in which I serve as officer, director, trustee, general partner or employee; and any person or organization with which I am negotiating or have an arrangement concerning prospective employment. Upon confirmation, I will resign from my positions with the following entities: University of Cincinnati, and the Toxicology Education Foundation. I resigned from my position with the North American Flame Retardant Alliance, and the Toxicology Forum in June 2017. For a period of one year after my resignation from each of these entities, I will not participate personally and substantially in any particular matter involving specific parties in which I know that entity is a party or represents a party, unless I am first authorized to participate, pursuant to 5 C.F.R. § 2635.502(d) Upon confirmation, I also will resign from my position with the Environmental Protection Agency's Science Advisory Board. Upon confirmation, I will resign from my position as general partner of Dourson, Dourson and Fowler, a partnership that owns undeveloped land in Stanton, KY, and I will transfer my financial interest in this entity to my adult son. I will not participate personally and substantially in any particular matter that to my knowledge has a direct and predictable effect on the financial interests of this entity until I have transferred it, unless I first obtain a written waiver, pursuant to 18 U.S.C. § 208(b)(1), or qualify for a regulatory exemption, pursuant to 18 U.S.C. § 208(b)(2). For a period of one year after my resignation, I will not participate personally and substantially in any particular matter involving specific parties in which I know Dourson, Dourson, and Fowler is a party or represents a party, unless I am first authorized to Source: https://www.industrydocuments.ucsf.edu/docs//lcn0226 participate, pursuant to 5 C.F.R. § 2635.502(d). My spouse is a sole proprietor of her law firm, which does business as Martha C. Dourson, LLC. For as long as my spouse continues to have her law practice, I will not participate personally and substantially in any particular matter that to my knowledge has a direct and predictable effect on the financial interests of the firm, unless I first obtain a written waiver, pursuant to 18 U.S.C. § 208(b)(1). I also will not participate personally and substantially in any particular matter involving specific parties in which I know a client of my spouse is a party or represents a party, unless I am first authorized to participate, pursuant to 5 C.F.R. § 2635.502(d). I receive royalties from CreateSpace Independent Publishing Platform for sales of my three books: Messiah's Star (Evidence for Faith) (Volume 1); The Beginning: Let there be light (Evidence of Faith) (Volume 2); and "The Linen Cloths: Jesus left behind (Evidence of Faith) (Volume 3). I will not participate personally and substantially in any particular matter involving specific parties in which I know CreateSpace Independent Publishing Platform is a party or represents a party, unless I am first authorized to participate, pursuant to 5 C.F.R. § 2635.502(d). If I have a managed account or otherwise use the services of an investment professional during my appointment, I will ensure that the account manager or investment professional obtains my prior approval on a case-by-case basis for the purchase of any assets other than cash, cash equivalents, investment funds that qualify for the exemption at 5 C.F.R. § 2640.201(a), obligations of the United States, or municipal bonds. I will meet in person with you during the first week of my service in the position of Assistant Administrator in order to complete the initial ethics briefing required under 5 C.F.R. § 2638.305. Within 90 days of my confirmation, I will document my compliance with this ethics agreement by notifying you in writing when I have completed the steps described in this ethics agreement. I understand that as an appointee I will be required to sign the Ethics Pledge (Exec. Order No. 13770) and that I will be bound by the requirements and restrictions therein in addition to the commitments I have made in this ethics agreement. I have been advised that this ethics agreement will be posted publicly, consistent with 5 U.S.C. § 552, on the website of the U.S. Office of Government Ethics with ethics agreements of other Presidential nominees who file public financial disclosure reports. Sincerely yours, intentioned Michael L. Dourson Source: https://www.industrydocuments.ucsf.edu/docs/llcn0226

What two are the degree of independent verification and peer review?

kzbn0226

kzbn0226_p19, kzbn0226_p20, kzbn0226_p21

variability, uncertainty

variability, uncertainty, the degree of independent verification and peer review. In proposing this definition, ACC has drawn language directly from the 1996 SDWA amendments29 and from section 26(h) of the LCSA. EPA has already adopted the language from the SDWA amendments in the EPA Information Quality Guidelines. In addition, the concept 30 of evaluating data based on strengths and limitations is consistent with the definition provided in 31 the Senate Congressional Record for LCSA. To ensure a greater level transparency that forces EPA to "show its work," as was envisioned by the authors of the LCSA, 32 this definition covers not only what EPA must consider and evaluate, but also requires that important descriptions and documentation be including in EPA work products developed under Sections 4-6 of TSCA. ii. Weight of the Evidence (WoE). ACC suggests the following definition: Weight of the evidence means a systematic review method that uses a pre- established protocol to comprehensively, objectively, transparently, and consistently, identify and evaluate each stream of evidence, including strengths, limitations, and relevance of each study and to integrate evidence as necessary and appropriate based upon strengths, limitations, and relevance. ACC agrees that the term WoE has meant different things to different groups. In fact, different NAS studies contradict themselves regarding the use of this term and inconsistently define its meaning. As such, it is critically important that EPA clearly explain what this term means to the Agency. This term cannot and should not be avoided or discounted as Section 26(i) of the LCSA codifies the requirement for EPA to use a WoE approach. As such, a clear and transparent definition is critical. ACC is recommending the use of the definition that is in the June 7, 2016 Senate Congressional Record. This is the definition we have provided above. This definition is also consistent with 33 the June 2015 House Report Language. 34 While other definitions exist, using the definition associated with LCSA makes the most sense and is a straightforward approach that is clearly linked to the intent of Congress. Without a clear definition, WoE will continue to mean different things to different experts and stakeholders. An example illustrates that EPA very recently has not interpreted WoE in the same way Congress now intends. In the draft risk assessment of 1-bromopropane (released prior to enactment of LCSA), EPA does not provide information regarding the quality of the individual 29 Id. 30 See generally, EPA Information Quality Guidelines. 31 Senate Congressional Record, June 7, 2016 at S3518. 32 Id. at S3522. 33 Id at S3518. 34 See House Report, at 33, available at 15/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 studies. Although the assessment identified some quality considerations, EPA did not provide 35,36 any information regarding its own findings from its quality review of the individual studies. 37 Additionally, no information was provided to describe how quality, relevance, and reliability considerations were applied and what constitutes a study of "high quality" or "good quality.' EPA simply chose the value that provided the lowest point of departure and thus would be most health protective. While EPA staff stated that they followed a WoE approach, 38 picking the lowest point of departure, without an explicit consideration of study quality, is not consistent with a WoE approach. Until there is one clear definition, confusion such as this will likely continue and this confusion will stifle the scientific dialogue. iii. Sufficiency of Information. ACC suggests the following definition: Sufficiency of information means that, taking into account the importance of the determination, the Agency has appropriately relied on the best available science, considering the weight of the scientific evidence to make a reasoned and transparent fit-for-purpose determination. This definition is important as EPA uses this term repeatedly in the preamble of the proposed rule to describe scientific information. We have provided a definition that ties this information directly to the best available science and weight of the evidence standards required in Section 26 of the LCSA. If no definition is provided, stakeholders are left guessing as to what standards will define sufficient information. In the preamble of the proposed rule, EPA uses related terms including "scientifically valid information" and "sufficient quality.' These terms must also be defined. ACC suggests the following: Scientifically valid information means information that the agency has considered the quality, reliability, and relevance of the information for the decision being made. Consistent with the Agency Assessment Factors Guidance (2003) evaluation of information will include the consideration of the soundness, applicability and utility, clarity and completeness, uncertainty and variability and evaluation and review of the information. 35 See Comments of the American Chemistry Council on the TSCA Work Plan Chemical Draft Risk Assessment of 1-Bromopropane, Docket No. EPA-HQ-OPPT-2015-0084, May 9, 2016. 36 See Chemical Safety Advisory Committee Minutes No. 2016-02, at 41, available at the Agency indicates that the literature was thoroughly reviewed for robustness, adequacy, etc., the Committee found that it is not clear what exact methodology was used to systematically rate, rank, and select studies to inform sections of the risk assessment. For example, was a quantitative ranking system developed for study quality?") 37 See TSCA Work Plan Chemical Risk Assessment Peer Review Draft, at Appendix M, available at and appendices final.pdf. 38 See Chemical Safety Advisory Committee Meeting Transcript, at 130, available at ittps://www.regulations.gov/documentD=BPA-HQ-OPPT-2015-0805-0027. 16/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 Sufficient quality means that the Agency has relied on scientifically valid information to make the determination. These definitions are consistent with existing Agency guidance. However, to improve transparency and consistency, it is important that EPA clearly define these terms in the final rulemaking. iv. Unreasonable Risk. ACC agrees with EPA that a single definition of unreasonable risk is not workable due to the variety of factors that are necessary to consider when making an unreasonable risk finding. However, the risk evaluation rule should list the considerations that must be taken into account in making that finding. More importantly, EPA should commit to describing and transparently presenting how each of these considerations impacted the unreasonable risk finding. The descriptions that support the unreasonable risk finding should be presented in the draft and final risk evaluation documents. ACC suggests the following description be included in the preamble to final rule: Unreasonable risk means that the Administrator has considered relevant factors, including the effects of the chemical substance on health and the magnitude of human exposure to such substance under the conditions of use; the effects of the chemical substance on the environment; and the magnitude of environmental exposure to such substance under the conditions of use. Factors considered to reach this risk-based determination may include: characterization of cancer and non-cancer risks (including margins of exposure for non-cancer risks and mode of action analyses for cancer risks), characterization of environmental risk, the population exposed (including any susceptible populations), the severity of hazard (the nature of the hazard), the irreversibility of hazard, and uncertainties associated with the analyses and data. This description is generally consistent with the considerations EPA has provided in the proposed rule, and adds a consideration to ensure that environmental risk findings are also considered. Notably, however, EPA inappropriately includes cumulative exposure in its list of considerations. This should be removed. LCSA does not require the consideration of 39 cumulative exposure in the risk evaluation process. Further, there is no generally accepted approach to inform the scientific methods, inputs and tools to evaluate cumulative risk. While EPA and other agencies continue to work on guidance in this area, scientifically robust draft frameworks for the evaluation of cumulative exposure risks are non-existent. V. Reasonably Available Information. ACC supports a clear definition of "reasonably available information;" however, we offer specific suggestions (shown in strikethrough and underline) to improve the definition EPA has provided: 39 82 Fed. Reg. at 7566. 17/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226

Who agrees that the term WoE has meant different things to different groups?

kzbn0226

kzbn0226_p19, kzbn0226_p20, kzbn0226_p21

ACC

variability, uncertainty, the degree of independent verification and peer review. In proposing this definition, ACC has drawn language directly from the 1996 SDWA amendments29 and from section 26(h) of the LCSA. EPA has already adopted the language from the SDWA amendments in the EPA Information Quality Guidelines. In addition, the concept 30 of evaluating data based on strengths and limitations is consistent with the definition provided in 31 the Senate Congressional Record for LCSA. To ensure a greater level transparency that forces EPA to "show its work," as was envisioned by the authors of the LCSA, 32 this definition covers not only what EPA must consider and evaluate, but also requires that important descriptions and documentation be including in EPA work products developed under Sections 4-6 of TSCA. ii. Weight of the Evidence (WoE). ACC suggests the following definition: Weight of the evidence means a systematic review method that uses a pre- established protocol to comprehensively, objectively, transparently, and consistently, identify and evaluate each stream of evidence, including strengths, limitations, and relevance of each study and to integrate evidence as necessary and appropriate based upon strengths, limitations, and relevance. ACC agrees that the term WoE has meant different things to different groups. In fact, different NAS studies contradict themselves regarding the use of this term and inconsistently define its meaning. As such, it is critically important that EPA clearly explain what this term means to the Agency. This term cannot and should not be avoided or discounted as Section 26(i) of the LCSA codifies the requirement for EPA to use a WoE approach. As such, a clear and transparent definition is critical. ACC is recommending the use of the definition that is in the June 7, 2016 Senate Congressional Record. This is the definition we have provided above. This definition is also consistent with 33 the June 2015 House Report Language. 34 While other definitions exist, using the definition associated with LCSA makes the most sense and is a straightforward approach that is clearly linked to the intent of Congress. Without a clear definition, WoE will continue to mean different things to different experts and stakeholders. An example illustrates that EPA very recently has not interpreted WoE in the same way Congress now intends. In the draft risk assessment of 1-bromopropane (released prior to enactment of LCSA), EPA does not provide information regarding the quality of the individual 29 Id. 30 See generally, EPA Information Quality Guidelines. 31 Senate Congressional Record, June 7, 2016 at S3518. 32 Id. at S3522. 33 Id at S3518. 34 See House Report, at 33, available at 15/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 studies. Although the assessment identified some quality considerations, EPA did not provide 35,36 any information regarding its own findings from its quality review of the individual studies. 37 Additionally, no information was provided to describe how quality, relevance, and reliability considerations were applied and what constitutes a study of "high quality" or "good quality.' EPA simply chose the value that provided the lowest point of departure and thus would be most health protective. While EPA staff stated that they followed a WoE approach, 38 picking the lowest point of departure, without an explicit consideration of study quality, is not consistent with a WoE approach. Until there is one clear definition, confusion such as this will likely continue and this confusion will stifle the scientific dialogue. iii. Sufficiency of Information. ACC suggests the following definition: Sufficiency of information means that, taking into account the importance of the determination, the Agency has appropriately relied on the best available science, considering the weight of the scientific evidence to make a reasoned and transparent fit-for-purpose determination. This definition is important as EPA uses this term repeatedly in the preamble of the proposed rule to describe scientific information. We have provided a definition that ties this information directly to the best available science and weight of the evidence standards required in Section 26 of the LCSA. If no definition is provided, stakeholders are left guessing as to what standards will define sufficient information. In the preamble of the proposed rule, EPA uses related terms including "scientifically valid information" and "sufficient quality.' These terms must also be defined. ACC suggests the following: Scientifically valid information means information that the agency has considered the quality, reliability, and relevance of the information for the decision being made. Consistent with the Agency Assessment Factors Guidance (2003) evaluation of information will include the consideration of the soundness, applicability and utility, clarity and completeness, uncertainty and variability and evaluation and review of the information. 35 See Comments of the American Chemistry Council on the TSCA Work Plan Chemical Draft Risk Assessment of 1-Bromopropane, Docket No. EPA-HQ-OPPT-2015-0084, May 9, 2016. 36 See Chemical Safety Advisory Committee Minutes No. 2016-02, at 41, available at the Agency indicates that the literature was thoroughly reviewed for robustness, adequacy, etc., the Committee found that it is not clear what exact methodology was used to systematically rate, rank, and select studies to inform sections of the risk assessment. For example, was a quantitative ranking system developed for study quality?") 37 See TSCA Work Plan Chemical Risk Assessment Peer Review Draft, at Appendix M, available at and appendices final.pdf. 38 See Chemical Safety Advisory Committee Meeting Transcript, at 130, available at ittps://www.regulations.gov/documentD=BPA-HQ-OPPT-2015-0805-0027. 16/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 Sufficient quality means that the Agency has relied on scientifically valid information to make the determination. These definitions are consistent with existing Agency guidance. However, to improve transparency and consistency, it is important that EPA clearly define these terms in the final rulemaking. iv. Unreasonable Risk. ACC agrees with EPA that a single definition of unreasonable risk is not workable due to the variety of factors that are necessary to consider when making an unreasonable risk finding. However, the risk evaluation rule should list the considerations that must be taken into account in making that finding. More importantly, EPA should commit to describing and transparently presenting how each of these considerations impacted the unreasonable risk finding. The descriptions that support the unreasonable risk finding should be presented in the draft and final risk evaluation documents. ACC suggests the following description be included in the preamble to final rule: Unreasonable risk means that the Administrator has considered relevant factors, including the effects of the chemical substance on health and the magnitude of human exposure to such substance under the conditions of use; the effects of the chemical substance on the environment; and the magnitude of environmental exposure to such substance under the conditions of use. Factors considered to reach this risk-based determination may include: characterization of cancer and non-cancer risks (including margins of exposure for non-cancer risks and mode of action analyses for cancer risks), characterization of environmental risk, the population exposed (including any susceptible populations), the severity of hazard (the nature of the hazard), the irreversibility of hazard, and uncertainties associated with the analyses and data. This description is generally consistent with the considerations EPA has provided in the proposed rule, and adds a consideration to ensure that environmental risk findings are also considered. Notably, however, EPA inappropriately includes cumulative exposure in its list of considerations. This should be removed. LCSA does not require the consideration of 39 cumulative exposure in the risk evaluation process. Further, there is no generally accepted approach to inform the scientific methods, inputs and tools to evaluate cumulative risk. While EPA and other agencies continue to work on guidance in this area, scientifically robust draft frameworks for the evaluation of cumulative exposure risks are non-existent. V. Reasonably Available Information. ACC supports a clear definition of "reasonably available information;" however, we offer specific suggestions (shown in strikethrough and underline) to improve the definition EPA has provided: 39 82 Fed. Reg. at 7566. 17/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226

Who does not provide information regarding the quality of the individual?

kzbn0226

kzbn0226_p19, kzbn0226_p20, kzbn0226_p21

EPA

variability, uncertainty, the degree of independent verification and peer review. In proposing this definition, ACC has drawn language directly from the 1996 SDWA amendments29 and from section 26(h) of the LCSA. EPA has already adopted the language from the SDWA amendments in the EPA Information Quality Guidelines. In addition, the concept 30 of evaluating data based on strengths and limitations is consistent with the definition provided in 31 the Senate Congressional Record for LCSA. To ensure a greater level transparency that forces EPA to "show its work," as was envisioned by the authors of the LCSA, 32 this definition covers not only what EPA must consider and evaluate, but also requires that important descriptions and documentation be including in EPA work products developed under Sections 4-6 of TSCA. ii. Weight of the Evidence (WoE). ACC suggests the following definition: Weight of the evidence means a systematic review method that uses a pre- established protocol to comprehensively, objectively, transparently, and consistently, identify and evaluate each stream of evidence, including strengths, limitations, and relevance of each study and to integrate evidence as necessary and appropriate based upon strengths, limitations, and relevance. ACC agrees that the term WoE has meant different things to different groups. In fact, different NAS studies contradict themselves regarding the use of this term and inconsistently define its meaning. As such, it is critically important that EPA clearly explain what this term means to the Agency. This term cannot and should not be avoided or discounted as Section 26(i) of the LCSA codifies the requirement for EPA to use a WoE approach. As such, a clear and transparent definition is critical. ACC is recommending the use of the definition that is in the June 7, 2016 Senate Congressional Record. This is the definition we have provided above. This definition is also consistent with 33 the June 2015 House Report Language. 34 While other definitions exist, using the definition associated with LCSA makes the most sense and is a straightforward approach that is clearly linked to the intent of Congress. Without a clear definition, WoE will continue to mean different things to different experts and stakeholders. An example illustrates that EPA very recently has not interpreted WoE in the same way Congress now intends. In the draft risk assessment of 1-bromopropane (released prior to enactment of LCSA), EPA does not provide information regarding the quality of the individual 29 Id. 30 See generally, EPA Information Quality Guidelines. 31 Senate Congressional Record, June 7, 2016 at S3518. 32 Id. at S3522. 33 Id at S3518. 34 See House Report, at 33, available at 15/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 studies. Although the assessment identified some quality considerations, EPA did not provide 35,36 any information regarding its own findings from its quality review of the individual studies. 37 Additionally, no information was provided to describe how quality, relevance, and reliability considerations were applied and what constitutes a study of "high quality" or "good quality.' EPA simply chose the value that provided the lowest point of departure and thus would be most health protective. While EPA staff stated that they followed a WoE approach, 38 picking the lowest point of departure, without an explicit consideration of study quality, is not consistent with a WoE approach. Until there is one clear definition, confusion such as this will likely continue and this confusion will stifle the scientific dialogue. iii. Sufficiency of Information. ACC suggests the following definition: Sufficiency of information means that, taking into account the importance of the determination, the Agency has appropriately relied on the best available science, considering the weight of the scientific evidence to make a reasoned and transparent fit-for-purpose determination. This definition is important as EPA uses this term repeatedly in the preamble of the proposed rule to describe scientific information. We have provided a definition that ties this information directly to the best available science and weight of the evidence standards required in Section 26 of the LCSA. If no definition is provided, stakeholders are left guessing as to what standards will define sufficient information. In the preamble of the proposed rule, EPA uses related terms including "scientifically valid information" and "sufficient quality.' These terms must also be defined. ACC suggests the following: Scientifically valid information means information that the agency has considered the quality, reliability, and relevance of the information for the decision being made. Consistent with the Agency Assessment Factors Guidance (2003) evaluation of information will include the consideration of the soundness, applicability and utility, clarity and completeness, uncertainty and variability and evaluation and review of the information. 35 See Comments of the American Chemistry Council on the TSCA Work Plan Chemical Draft Risk Assessment of 1-Bromopropane, Docket No. EPA-HQ-OPPT-2015-0084, May 9, 2016. 36 See Chemical Safety Advisory Committee Minutes No. 2016-02, at 41, available at the Agency indicates that the literature was thoroughly reviewed for robustness, adequacy, etc., the Committee found that it is not clear what exact methodology was used to systematically rate, rank, and select studies to inform sections of the risk assessment. For example, was a quantitative ranking system developed for study quality?") 37 See TSCA Work Plan Chemical Risk Assessment Peer Review Draft, at Appendix M, available at and appendices final.pdf. 38 See Chemical Safety Advisory Committee Meeting Transcript, at 130, available at ittps://www.regulations.gov/documentD=BPA-HQ-OPPT-2015-0805-0027. 16/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 Sufficient quality means that the Agency has relied on scientifically valid information to make the determination. These definitions are consistent with existing Agency guidance. However, to improve transparency and consistency, it is important that EPA clearly define these terms in the final rulemaking. iv. Unreasonable Risk. ACC agrees with EPA that a single definition of unreasonable risk is not workable due to the variety of factors that are necessary to consider when making an unreasonable risk finding. However, the risk evaluation rule should list the considerations that must be taken into account in making that finding. More importantly, EPA should commit to describing and transparently presenting how each of these considerations impacted the unreasonable risk finding. The descriptions that support the unreasonable risk finding should be presented in the draft and final risk evaluation documents. ACC suggests the following description be included in the preamble to final rule: Unreasonable risk means that the Administrator has considered relevant factors, including the effects of the chemical substance on health and the magnitude of human exposure to such substance under the conditions of use; the effects of the chemical substance on the environment; and the magnitude of environmental exposure to such substance under the conditions of use. Factors considered to reach this risk-based determination may include: characterization of cancer and non-cancer risks (including margins of exposure for non-cancer risks and mode of action analyses for cancer risks), characterization of environmental risk, the population exposed (including any susceptible populations), the severity of hazard (the nature of the hazard), the irreversibility of hazard, and uncertainties associated with the analyses and data. This description is generally consistent with the considerations EPA has provided in the proposed rule, and adds a consideration to ensure that environmental risk findings are also considered. Notably, however, EPA inappropriately includes cumulative exposure in its list of considerations. This should be removed. LCSA does not require the consideration of 39 cumulative exposure in the risk evaluation process. Further, there is no generally accepted approach to inform the scientific methods, inputs and tools to evaluate cumulative risk. While EPA and other agencies continue to work on guidance in this area, scientifically robust draft frameworks for the evaluation of cumulative exposure risks are non-existent. V. Reasonably Available Information. ACC supports a clear definition of "reasonably available information;" however, we offer specific suggestions (shown in strikethrough and underline) to improve the definition EPA has provided: 39 82 Fed. Reg. at 7566. 17/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226

What is the name of the second point?

kzbn0226

kzbn0226_p19, kzbn0226_p20, kzbn0226_p21

Weight of the Evidence (WoE)

variability, uncertainty, the degree of independent verification and peer review. In proposing this definition, ACC has drawn language directly from the 1996 SDWA amendments29 and from section 26(h) of the LCSA. EPA has already adopted the language from the SDWA amendments in the EPA Information Quality Guidelines. In addition, the concept 30 of evaluating data based on strengths and limitations is consistent with the definition provided in 31 the Senate Congressional Record for LCSA. To ensure a greater level transparency that forces EPA to "show its work," as was envisioned by the authors of the LCSA, 32 this definition covers not only what EPA must consider and evaluate, but also requires that important descriptions and documentation be including in EPA work products developed under Sections 4-6 of TSCA. ii. Weight of the Evidence (WoE). ACC suggests the following definition: Weight of the evidence means a systematic review method that uses a pre- established protocol to comprehensively, objectively, transparently, and consistently, identify and evaluate each stream of evidence, including strengths, limitations, and relevance of each study and to integrate evidence as necessary and appropriate based upon strengths, limitations, and relevance. ACC agrees that the term WoE has meant different things to different groups. In fact, different NAS studies contradict themselves regarding the use of this term and inconsistently define its meaning. As such, it is critically important that EPA clearly explain what this term means to the Agency. This term cannot and should not be avoided or discounted as Section 26(i) of the LCSA codifies the requirement for EPA to use a WoE approach. As such, a clear and transparent definition is critical. ACC is recommending the use of the definition that is in the June 7, 2016 Senate Congressional Record. This is the definition we have provided above. This definition is also consistent with 33 the June 2015 House Report Language. 34 While other definitions exist, using the definition associated with LCSA makes the most sense and is a straightforward approach that is clearly linked to the intent of Congress. Without a clear definition, WoE will continue to mean different things to different experts and stakeholders. An example illustrates that EPA very recently has not interpreted WoE in the same way Congress now intends. In the draft risk assessment of 1-bromopropane (released prior to enactment of LCSA), EPA does not provide information regarding the quality of the individual 29 Id. 30 See generally, EPA Information Quality Guidelines. 31 Senate Congressional Record, June 7, 2016 at S3518. 32 Id. at S3522. 33 Id at S3518. 34 See House Report, at 33, available at 15/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 studies. Although the assessment identified some quality considerations, EPA did not provide 35,36 any information regarding its own findings from its quality review of the individual studies. 37 Additionally, no information was provided to describe how quality, relevance, and reliability considerations were applied and what constitutes a study of "high quality" or "good quality.' EPA simply chose the value that provided the lowest point of departure and thus would be most health protective. While EPA staff stated that they followed a WoE approach, 38 picking the lowest point of departure, without an explicit consideration of study quality, is not consistent with a WoE approach. Until there is one clear definition, confusion such as this will likely continue and this confusion will stifle the scientific dialogue. iii. Sufficiency of Information. ACC suggests the following definition: Sufficiency of information means that, taking into account the importance of the determination, the Agency has appropriately relied on the best available science, considering the weight of the scientific evidence to make a reasoned and transparent fit-for-purpose determination. This definition is important as EPA uses this term repeatedly in the preamble of the proposed rule to describe scientific information. We have provided a definition that ties this information directly to the best available science and weight of the evidence standards required in Section 26 of the LCSA. If no definition is provided, stakeholders are left guessing as to what standards will define sufficient information. In the preamble of the proposed rule, EPA uses related terms including "scientifically valid information" and "sufficient quality.' These terms must also be defined. ACC suggests the following: Scientifically valid information means information that the agency has considered the quality, reliability, and relevance of the information for the decision being made. Consistent with the Agency Assessment Factors Guidance (2003) evaluation of information will include the consideration of the soundness, applicability and utility, clarity and completeness, uncertainty and variability and evaluation and review of the information. 35 See Comments of the American Chemistry Council on the TSCA Work Plan Chemical Draft Risk Assessment of 1-Bromopropane, Docket No. EPA-HQ-OPPT-2015-0084, May 9, 2016. 36 See Chemical Safety Advisory Committee Minutes No. 2016-02, at 41, available at the Agency indicates that the literature was thoroughly reviewed for robustness, adequacy, etc., the Committee found that it is not clear what exact methodology was used to systematically rate, rank, and select studies to inform sections of the risk assessment. For example, was a quantitative ranking system developed for study quality?") 37 See TSCA Work Plan Chemical Risk Assessment Peer Review Draft, at Appendix M, available at and appendices final.pdf. 38 See Chemical Safety Advisory Committee Meeting Transcript, at 130, available at ittps://www.regulations.gov/documentD=BPA-HQ-OPPT-2015-0805-0027. 16/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 Sufficient quality means that the Agency has relied on scientifically valid information to make the determination. These definitions are consistent with existing Agency guidance. However, to improve transparency and consistency, it is important that EPA clearly define these terms in the final rulemaking. iv. Unreasonable Risk. ACC agrees with EPA that a single definition of unreasonable risk is not workable due to the variety of factors that are necessary to consider when making an unreasonable risk finding. However, the risk evaluation rule should list the considerations that must be taken into account in making that finding. More importantly, EPA should commit to describing and transparently presenting how each of these considerations impacted the unreasonable risk finding. The descriptions that support the unreasonable risk finding should be presented in the draft and final risk evaluation documents. ACC suggests the following description be included in the preamble to final rule: Unreasonable risk means that the Administrator has considered relevant factors, including the effects of the chemical substance on health and the magnitude of human exposure to such substance under the conditions of use; the effects of the chemical substance on the environment; and the magnitude of environmental exposure to such substance under the conditions of use. Factors considered to reach this risk-based determination may include: characterization of cancer and non-cancer risks (including margins of exposure for non-cancer risks and mode of action analyses for cancer risks), characterization of environmental risk, the population exposed (including any susceptible populations), the severity of hazard (the nature of the hazard), the irreversibility of hazard, and uncertainties associated with the analyses and data. This description is generally consistent with the considerations EPA has provided in the proposed rule, and adds a consideration to ensure that environmental risk findings are also considered. Notably, however, EPA inappropriately includes cumulative exposure in its list of considerations. This should be removed. LCSA does not require the consideration of 39 cumulative exposure in the risk evaluation process. Further, there is no generally accepted approach to inform the scientific methods, inputs and tools to evaluate cumulative risk. While EPA and other agencies continue to work on guidance in this area, scientifically robust draft frameworks for the evaluation of cumulative exposure risks are non-existent. V. Reasonably Available Information. ACC supports a clear definition of "reasonably available information;" however, we offer specific suggestions (shown in strikethrough and underline) to improve the definition EPA has provided: 39 82 Fed. Reg. at 7566. 17/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226

What is the date mentioned in the bottom?

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

August 29, 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

What is the heading of the point B?

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

Exposure Potential Ranking

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

Together how many elements are used to make rank exposure potential?

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

3 elements, 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

The proposed approach applies the most to which year's TSCA Inventory Update Reporting rule?

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

2006

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 fullform of ACC?

jzbn0226

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

The American Chemistry Council, American Chemistry Council

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 Brozena@americanchemistrv.com 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 Brozena@americanchemistry.com 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

what does acc stands for?

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american chemistry council, The American Chemistry Council, American Chemistry Council

American° Chemistry Council March 20, 2017 Document Control Office (7407M) Office of Pollution Prevention and Toxics Environmental Protection Agency 1200 Pennsylvania Ave. NW Washington, DC 20460-0001 Submitted electronically via www.regulations.gov Re: Comments of the American Chemistry Council on EPA's Proposed Rule: Procedures for Chemical Risk Evaluation under the Amended Toxic Substances Control Act, 82 Fed. Reg. 7562 (January 19, 2017); EPA-HQ-OPPT-2016-0654 Dear Docket Clerk: The American Chemistry Council (ACC¹ is pleased to submit the attached comments on the Environmental Protection Agency, Office of Pollution Prevention and Toxics Proposed Rule, Procedures for Chemical Risk Evaluation under the Amended Toxic Substances Control Act. These comments align with our separately filed comments on the proposed rules describing the processes for inventory reset and prioritization for risk evaluation, and for the development of the scopes for risk evaluation of the first 10 chemicals selected from the TSCA work plan. All comments should be considered together. Please feel free to contact me with any questions at 202-249-6130 or karyn schmidu@americanchemistrv.com Sincerely, families Karyn M. Schmidt Senior Director, Regulatory and Technical Affairs American Chemistry Council cc: Jeffery Morris, Director, OPPT Wendy Cleland-Hamnett, OPPT Tala Henry, Director, Risk Assessment Division, OPPT Susanna Blair, Office of Chemical Safety and Pollution Prevention 1 ACC represents the leading companies engaged in the business of chemistry. More information about ACC is presented in the body of our comments. Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226

In which year, EPA held a Stakeholder Dialogue on prioritization?

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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 Brozena@americanchemistrv.com 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 Brozena@americanchemistry.com 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

What is the date mentioned?

pfcn0226

pfcn0226_p0, pfcn0226_p1

June 9, 2017

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

What is the subject of the memorandum?

pfcn0226

pfcn0226_p0, pfcn0226_p1

Recusal Statement

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

Why ACC developed a two-step quantitative and qualitative tool?

jzbn0226

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

to "proof test" our prioritization principles (attachement B), to "proof test" our prioritization principles

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 Brozena@americanchemistrv.com 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 Brozena@americanchemistry.com 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

What is the heading of the letter?

jzbn0226

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

American Chemistry Council

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 Brozena@americanchemistrv.com 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 Brozena@americanchemistry.com 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 Brozena@americanchemistrv.com 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 Brozena@americanchemistry.com 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

By whom is this letter written?

jzbn0226

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 Brozena@americanchemistrv.com 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 Brozena@americanchemistry.com 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

What is the abbreviation of Toxic Substances Control Act?

jzbn0226

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

TSCA

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 Brozena@americanchemistrv.com 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 Brozena@americanchemistry.com 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

Where is The National Academic Press located?

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Washington, D.C.

Scientific Review of the Proposed Risk Assessment Bulletin from the Office of Management and Budget http://www.nap.edu/catalog/11811.html PREPUBLICATION COPY Scientific Review of the Proposed Risk Assessment Bulletin from the Office of Management and Budget Committee to Review the OMB Risk Assessment Bulletin Board on Environmental Studies and Toxicology Division on Earth and Life Studies NATIONAL RESEARCH COUNCIL OF THE NATIONAL ACADEMIES THE NATIONAL ACADEMIES PRESS Washington, D.C. www.nap.edu Scientific Review of the Proposed Risk Assessment Bulletin from the Office of Management and Budget http://www.nap.edu/catalog/11811.htm COMMITTEE TO REVIEW THE OMB RISK ASSESSMENT BULLETIN Members JOHN F. AHEARNE (Chair), Sigma Xi, Research Triangle Park, NC GEORGE V. ALEXEEFF, California Environmental Protection Agency, Oakland GREGORY B. BAECHER, University of Maryland, College Park A. JOHN BAILER, Miami University, Oxford, OH ROGER M. COOKE, Resources for the Future, Washington, DC CHARLES E. FEIGLEY, University of South Carolina, Columbia BARUCH FISCHHOFF, Carnegie Mellon University, Pittsburgh, PA CHARLES P. GERBA, University of Arizona, Tucson ROSE H. GOLDMAN, Harvard Medical School, Cambridge, MA ROBERT HAVEMAN, University of Wisconsin-Madison Madison WILLIAM E. KASTENBERG, University of California, Berkeley SALLY KATZEN, George Mason University Law School, Arlington, VA EDUARDO MIRANDA, Stanford University, Stanford, CA MICHAEL NEWMAN, The College of William and Mary, Gloucester Point, VA DOROTHY E. PATTON, Retired, Chicago, IL CHARLES POOLE, University of North Carolina, Chapel Hill DANNY D. REIBLE, University of Texas at Austin JOSEPH V. RODRICKS, ENVIRON International Corporation, Arlington, VA Staff ELLEN K. MANTUS, Project Director JENNIFER SAUNDERS, Associate Program Officer NORMAN GROSSBLATT, Senior Editor MIRSADA KARALIC-LONCAREVIC, Research Associate JOHN BROWN, Program Associate Sponsors U.S. ENVIRONMENTAL PROTECTION AGENCY U.S. DEPARTMENT OF AGRICULTURE U.S. DEPARTMENT OF DEFENSE U.S. DEPARTMENT OF ENERGY U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES U.S. DEPARTMENT OF LABOR NATIONAL AERONAUTICS AND SPACE ADMINISTRATION PREPUBLICATION COPY V

What did ACC strongly supported?

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

"Congresss efforts to update and reform TSCA", "supported Congresss efforts to update & reform TSCA"

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 Brozena@americanchemistrv.com 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 Brozena@americanchemistry.com 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

what is the regulation for amended toxic substances control act?

kzbn0226

kzbn0226_p0

7562

American° Chemistry Council March 20, 2017 Document Control Office (7407M) Office of Pollution Prevention and Toxics Environmental Protection Agency 1200 Pennsylvania Ave. NW Washington, DC 20460-0001 Submitted electronically via www.regulations.gov Re: Comments of the American Chemistry Council on EPA's Proposed Rule: Procedures for Chemical Risk Evaluation under the Amended Toxic Substances Control Act, 82 Fed. Reg. 7562 (January 19, 2017); EPA-HQ-OPPT-2016-0654 Dear Docket Clerk: The American Chemistry Council (ACC¹ is pleased to submit the attached comments on the Environmental Protection Agency, Office of Pollution Prevention and Toxics Proposed Rule, Procedures for Chemical Risk Evaluation under the Amended Toxic Substances Control Act. These comments align with our separately filed comments on the proposed rules describing the processes for inventory reset and prioritization for risk evaluation, and for the development of the scopes for risk evaluation of the first 10 chemicals selected from the TSCA work plan. All comments should be considered together. Please feel free to contact me with any questions at 202-249-6130 or karyn schmidu@americanchemistrv.com Sincerely, families Karyn M. Schmidt Senior Director, Regulatory and Technical Affairs American Chemistry Council cc: Jeffery Morris, Director, OPPT Wendy Cleland-Hamnett, OPPT Tala Henry, Director, Risk Assessment Division, OPPT Susanna Blair, Office of Chemical Safety and Pollution Prevention 1 ACC represents the leading companies engaged in the business of chemistry. More information about ACC is presented in the body of our comments. Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226

Why is it neccessary to consider IUR information within a particular priority grouping?

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

for Second Tier rank ordering, for second tier rank ordering

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 number should Karyn M. Schmidt be contacted?

kzbn0226

kzbn0226_p0

202-249-6130

American° Chemistry Council March 20, 2017 Document Control Office (7407M) Office of Pollution Prevention and Toxics Environmental Protection Agency 1200 Pennsylvania Ave. NW Washington, DC 20460-0001 Submitted electronically via www.regulations.gov Re: Comments of the American Chemistry Council on EPA's Proposed Rule: Procedures for Chemical Risk Evaluation under the Amended Toxic Substances Control Act, 82 Fed. Reg. 7562 (January 19, 2017); EPA-HQ-OPPT-2016-0654 Dear Docket Clerk: The American Chemistry Council (ACC¹ is pleased to submit the attached comments on the Environmental Protection Agency, Office of Pollution Prevention and Toxics Proposed Rule, Procedures for Chemical Risk Evaluation under the Amended Toxic Substances Control Act. These comments align with our separately filed comments on the proposed rules describing the processes for inventory reset and prioritization for risk evaluation, and for the development of the scopes for risk evaluation of the first 10 chemicals selected from the TSCA work plan. All comments should be considered together. Please feel free to contact me with any questions at 202-249-6130 or karyn schmidu@americanchemistrv.com Sincerely, families Karyn M. Schmidt Senior Director, Regulatory and Technical Affairs American Chemistry Council cc: Jeffery Morris, Director, OPPT Wendy Cleland-Hamnett, OPPT Tala Henry, Director, Risk Assessment Division, OPPT Susanna Blair, Office of Chemical Safety and Pollution Prevention 1 ACC represents the leading companies engaged in the business of chemistry. More information about ACC is presented in the body of our comments. Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226

Which age group foes the IUR definition target?

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

targets children age 14 and younger, age 14 and younger, children age 14 and younger

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 would have de minimis exposure potential by definition?

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

non-isolated system intermediates

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

On what basis, an initial screening approach for chemical prioritization is done?

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based upon consistent application of specific hazard and exposure science elements that define risk potential., based upon consistent application of specific hazard and exposure science elements that define risk potential, consistent application of specific hazard and exposure science elements that define risk potential

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 Section 26(h) set out?

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scientific standards that apply to every "decision based on science"

Data quality assurance to confirm identified conditions of use should occur before the scope is released, and certainly must occur before the scope is published as final. It is essential to the quality and integrity of the risk evaluation itself. Use of poor quality or outdated information to "identify" conditions of use taints the ultimate science-based decisions required in the risk evaluation and undermines the statutorily-required application of best available science to exposure assessment. EPA should describe the process it uses to identify conditions of use in the scope of the risk evaluation, including: - The source of the information about a condition of use; - The reliability of the source of information (e.g., whether the information is a first- party, anecdotal report (blog, social media post, product comment or review) or reported to a government or credible third party); - A description of the Agency's assessment of whether the identity of the source of information is known and verified; - A description of how the information source has been verified and validated, if appropriate; and - Whether the information is current. I. EPA Should Not "Lock Down" Conditions of Use at the Time of Scoping. The Agency simultaneously insists that it must consider "all conditions of use" in the scope of the risk evaluation, but that it will then not actually consider "all" conditions of use through use of a "lock down" procedure, freezing the conditions of use at the time of scoping. In other words, if a new condition of use is discovered or emerges after the scope is published, EPA will not include it in the risk evaluation, regardless of impact. EPA proposes this "lock down" to help the Agency meet its statutory deadlines.17 We think the Agency has this backwards. To stay on its statutory schedule - or to move more quickly - the best tool EPA has available is scoping (the ability to scope its risk evaluations in a flexible manner to focus on the conditions posing the greatest potential risk). EPA should propose a process that allows the Agency to take full advantage of this important tool on a case- by-case basis. EPA should be able to select the conditions of use that it believes are most relevant and meaningful to human health and environmental risk and proceed accordingly. Likewise, EPA should not commit to "locking" conditions of use at the time of scoping. If EPA has discretion to select the conditions of use that it will include in the scope of a risk evaluation - which it does - then EPA should have the companion ability to remove or add a condition of use 18 as circumstances warrant. For example, following scoping EPA might determine that reports of an isolated use were wrong - and that the condition of use does not actually exist. It would 17 This proposal leaves in limbo the regulatory status of conditions of use that are excluded from the review. If EPA were to implement this approach, it would also need to clarify that excluded conditions of use go back to the prioritization process, and would also need to clarify that they do not have a high priority designation. This approach is also completely inconsistent with EPA's approach taken for manufacturer-requested evaluations. 18 Similarly, EPA has a companion ability to redesignate low priorities or high priorities as warranted. 10/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 make little sense to continue evaluating that condition of use in the risk evaluation. Otherwise, EPA's final risk evaluation would be of suspect quality, integrity, and reliability. A better approach would be for EPA to articulate in the rule that after a scope is published, EPA retains discretion to modify it upon a showing of substantial need or changed circumstances, or is otherwise warranted because the addition or removal of a condition of use, properly substantiated, will significantly affect the conduct of the risk evaluation. J. EPA Must Remove the Comment-or-Waive (Issue Exhaustion) Proposal. EPA further proposes that it can keep risk evaluations on schedule, notwithstanding its proposal to include "all conditions of use" in every scope, by "providing opportunity for comment on the scoping document and specifying that any objections to the draft scope document are waived if not raised during this process. ",99 We urge the Agency to remove this issue exhaustion (waiver) requirement for several reasons. First, it places an unfair burden on the regulated community. A particular company may not be aware, or otherwise in a position to verify, particular end uses that the company does not support (i.e., a downstream value chain to which it does not sell). A company likewise may not be able to verify occurrences of a chemical from natural sources or the actions of third parties through combustion, spills and discharges, disposal, manufacturing practices or incidents, and the like. When EPA insists on including "all conditions of use" in the scope of a risk evaluation, it moves well past the "major" uses of a chemical and "major" sources of exposure to include fleeting, incidental, minor, isolated, or exceptional cases. Information about these "minor" sources of exposure may be well outside the first-hand knowledge of a manufacturer or processor, making it difficult or impossible to offer meaningful comment during the scoping period. Second, participation in notice and comment rulemaking is governed by the Administrative Procedure Act (APA) and the judicial review provisions of Section 19 of TSCA. Issue exhaustion requirements can be imposed by statute. Notably, there are only a few statutory issue exhaustion provisions in environmental statutes, the most notable of which is in Section 307(d)(7)(b) of the Clean Air Act. There are none in TSCA. Congress had the opportunity to impose an issue exhaustion requirement for the scope of a risk evaluation in LCSA amendment - and declined to do so. EPA cannot, by regulation, impose an issue exhaustion requirement that trumps the statutory rights and obligations of stakeholders under the APA and TSCA Section 19.20 Indeed, ACC believes a waiver provision such as that proposed by EPA may not meet Constitutional muster. Third, the proposal does not rationally advance its claimed purpose - to meet statutory risk evaluation deadlines. An issue exhaustion requirement is supposed to serve two purposes: it 19 82 Fed. Reg. at 7566. 20 Administrative issue exhaustion requirements are largely creatures of statute, and here we have no such statutory construct. While some agency regulations set out issue exhaustion requirements without a statutory mandate, these tend to be in administrative appeal situations or proceedings that are analogs to adversarial litigation. Notably, the LCSA amendment removed a procedure for formal TSCA hearings. 11/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 protects administrative agency authority and promotes judicial efficiency. But here, by 21 requiring inclusion of "all conditions of use" in scopes, the agency impairs the ability of industry to meaningfully comment in the limited time available. EPA seems to be of the view that it would rather include "too much" in a scope than inadvertently omit a condition of use and include "too little," but it is the overly broad, unrefined scope that expands the scale and cost of risk evaluations and slows them. EPA then ties its own hands by proposing to "lock down" overly broad scopes, impeding its ability to update or modify them later in the process. This does not advance efficiency or transparency in the regulatory process. EPA can avoid these inefficiencies by offering a simple process to identify those major, important conditions of use that are most relevant and meaningful to a high-quality risk evaluation - and to use flexibility in designing the scope accordingly. EPA should offer a rationale of why it selected the uses it did in the scope itself. II. EPA Must Describe How and When it Will Apply Section 26 Requirements to Risk Evaluations. Section 26(h) sets out scientific standards that apply to every "decision based on science" while EPA carries out risk evaluation under Section 6 [emphasis added]. Section 26(i) requires EPA to "make decisions" under Section 6 based on the weight of the scientific evidence [emphasis added]. A decision would include any judicially reviewable determination, but also any other decision that requires application of science or scientific judgment by the Agency. EPA should articulate in the risk evaluation rule, at a minimum, the key decision points that will require compliance with Section 26 requirements. These should include, but are not limited to: - The proposed scope and final scope for risk evaluation - Hazard assessment, including, where applicable, the likely operable mode of action - Exposure assessment - Selection and evaluation of technical procedures, measures, methods, protocols, methodologies, and models - Basis for scientific assumptions - Selection and evaluation of quality assurance procedures - Decisions regarding variability and uncertainty - Statistical methods - The draft and final risk evaluation EPA should document how it applied Section 26(h) and 26(i) requirements for each decision. 21 The issue exhaustion proposal does not advance judicial economy either. Determinations of no unreasonable risk, made by the Agency following the completion of the risk evaluation process, are judicially reviewable - but as a practical matter this means that a judicial challenge to such a determination would be unlikely to occur until years after the scope was published (and the risk evaluation completed). Changes to conditions of use, or errors in their identification and inclusion, may not all be evident at the time the scope is originally prepared and published, so applying issue exhaustion at this step makes little sense. 12/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226

Under which section, EPA carries out risk evaluation?

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section 6, under Section 6

Data quality assurance to confirm identified conditions of use should occur before the scope is released, and certainly must occur before the scope is published as final. It is essential to the quality and integrity of the risk evaluation itself. Use of poor quality or outdated information to "identify" conditions of use taints the ultimate science-based decisions required in the risk evaluation and undermines the statutorily-required application of best available science to exposure assessment. EPA should describe the process it uses to identify conditions of use in the scope of the risk evaluation, including: - The source of the information about a condition of use; - The reliability of the source of information (e.g., whether the information is a first- party, anecdotal report (blog, social media post, product comment or review) or reported to a government or credible third party); - A description of the Agency's assessment of whether the identity of the source of information is known and verified; - A description of how the information source has been verified and validated, if appropriate; and - Whether the information is current. I. EPA Should Not "Lock Down" Conditions of Use at the Time of Scoping. The Agency simultaneously insists that it must consider "all conditions of use" in the scope of the risk evaluation, but that it will then not actually consider "all" conditions of use through use of a "lock down" procedure, freezing the conditions of use at the time of scoping. In other words, if a new condition of use is discovered or emerges after the scope is published, EPA will not include it in the risk evaluation, regardless of impact. EPA proposes this "lock down" to help the Agency meet its statutory deadlines.17 We think the Agency has this backwards. To stay on its statutory schedule - or to move more quickly - the best tool EPA has available is scoping (the ability to scope its risk evaluations in a flexible manner to focus on the conditions posing the greatest potential risk). EPA should propose a process that allows the Agency to take full advantage of this important tool on a case- by-case basis. EPA should be able to select the conditions of use that it believes are most relevant and meaningful to human health and environmental risk and proceed accordingly. Likewise, EPA should not commit to "locking" conditions of use at the time of scoping. If EPA has discretion to select the conditions of use that it will include in the scope of a risk evaluation - which it does - then EPA should have the companion ability to remove or add a condition of use 18 as circumstances warrant. For example, following scoping EPA might determine that reports of an isolated use were wrong - and that the condition of use does not actually exist. It would 17 This proposal leaves in limbo the regulatory status of conditions of use that are excluded from the review. If EPA were to implement this approach, it would also need to clarify that excluded conditions of use go back to the prioritization process, and would also need to clarify that they do not have a high priority designation. This approach is also completely inconsistent with EPA's approach taken for manufacturer-requested evaluations. 18 Similarly, EPA has a companion ability to redesignate low priorities or high priorities as warranted. 10/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 make little sense to continue evaluating that condition of use in the risk evaluation. Otherwise, EPA's final risk evaluation would be of suspect quality, integrity, and reliability. A better approach would be for EPA to articulate in the rule that after a scope is published, EPA retains discretion to modify it upon a showing of substantial need or changed circumstances, or is otherwise warranted because the addition or removal of a condition of use, properly substantiated, will significantly affect the conduct of the risk evaluation. J. EPA Must Remove the Comment-or-Waive (Issue Exhaustion) Proposal. EPA further proposes that it can keep risk evaluations on schedule, notwithstanding its proposal to include "all conditions of use" in every scope, by "providing opportunity for comment on the scoping document and specifying that any objections to the draft scope document are waived if not raised during this process. ",99 We urge the Agency to remove this issue exhaustion (waiver) requirement for several reasons. First, it places an unfair burden on the regulated community. A particular company may not be aware, or otherwise in a position to verify, particular end uses that the company does not support (i.e., a downstream value chain to which it does not sell). A company likewise may not be able to verify occurrences of a chemical from natural sources or the actions of third parties through combustion, spills and discharges, disposal, manufacturing practices or incidents, and the like. When EPA insists on including "all conditions of use" in the scope of a risk evaluation, it moves well past the "major" uses of a chemical and "major" sources of exposure to include fleeting, incidental, minor, isolated, or exceptional cases. Information about these "minor" sources of exposure may be well outside the first-hand knowledge of a manufacturer or processor, making it difficult or impossible to offer meaningful comment during the scoping period. Second, participation in notice and comment rulemaking is governed by the Administrative Procedure Act (APA) and the judicial review provisions of Section 19 of TSCA. Issue exhaustion requirements can be imposed by statute. Notably, there are only a few statutory issue exhaustion provisions in environmental statutes, the most notable of which is in Section 307(d)(7)(b) of the Clean Air Act. There are none in TSCA. Congress had the opportunity to impose an issue exhaustion requirement for the scope of a risk evaluation in LCSA amendment - and declined to do so. EPA cannot, by regulation, impose an issue exhaustion requirement that trumps the statutory rights and obligations of stakeholders under the APA and TSCA Section 19.20 Indeed, ACC believes a waiver provision such as that proposed by EPA may not meet Constitutional muster. Third, the proposal does not rationally advance its claimed purpose - to meet statutory risk evaluation deadlines. An issue exhaustion requirement is supposed to serve two purposes: it 19 82 Fed. Reg. at 7566. 20 Administrative issue exhaustion requirements are largely creatures of statute, and here we have no such statutory construct. While some agency regulations set out issue exhaustion requirements without a statutory mandate, these tend to be in administrative appeal situations or proceedings that are analogs to adversarial litigation. Notably, the LCSA amendment removed a procedure for formal TSCA hearings. 11/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 protects administrative agency authority and promotes judicial efficiency. But here, by 21 requiring inclusion of "all conditions of use" in scopes, the agency impairs the ability of industry to meaningfully comment in the limited time available. EPA seems to be of the view that it would rather include "too much" in a scope than inadvertently omit a condition of use and include "too little," but it is the overly broad, unrefined scope that expands the scale and cost of risk evaluations and slows them. EPA then ties its own hands by proposing to "lock down" overly broad scopes, impeding its ability to update or modify them later in the process. This does not advance efficiency or transparency in the regulatory process. EPA can avoid these inefficiencies by offering a simple process to identify those major, important conditions of use that are most relevant and meaningful to a high-quality risk evaluation - and to use flexibility in designing the scope accordingly. EPA should offer a rationale of why it selected the uses it did in the scope itself. II. EPA Must Describe How and When it Will Apply Section 26 Requirements to Risk Evaluations. Section 26(h) sets out scientific standards that apply to every "decision based on science" while EPA carries out risk evaluation under Section 6 [emphasis added]. Section 26(i) requires EPA to "make decisions" under Section 6 based on the weight of the scientific evidence [emphasis added]. A decision would include any judicially reviewable determination, but also any other decision that requires application of science or scientific judgment by the Agency. EPA should articulate in the risk evaluation rule, at a minimum, the key decision points that will require compliance with Section 26 requirements. These should include, but are not limited to: - The proposed scope and final scope for risk evaluation - Hazard assessment, including, where applicable, the likely operable mode of action - Exposure assessment - Selection and evaluation of technical procedures, measures, methods, protocols, methodologies, and models - Basis for scientific assumptions - Selection and evaluation of quality assurance procedures - Decisions regarding variability and uncertainty - Statistical methods - The draft and final risk evaluation EPA should document how it applied Section 26(h) and 26(i) requirements for each decision. 21 The issue exhaustion proposal does not advance judicial economy either. Determinations of no unreasonable risk, made by the Agency following the completion of the risk evaluation process, are judicially reviewable - but as a practical matter this means that a judicial challenge to such a determination would be unlikely to occur until years after the scope was published (and the risk evaluation completed). Changes to conditions of use, or errors in their identification and inclusion, may not all be evident at the time the scope is originally prepared and published, so applying issue exhaustion at this step makes little sense. 12/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226

What is the fullform of SCIL?

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Safer Chemicals Ingredients List

ACC is well aware that information about potential hazards and potential uses and exposures of a chemical is critical to sound decision-making by EPA - for both prioritization and risk evaluation decisions. ACC is also well aware of the aggressive timeframes within which both prioritization and risk evaluations must be conducted. ACC strongly believes that both prioritization and risk evaluation processes are more efficient if they use iterative and tiered processes and that these processes help ensure science-based decision-making. ACC recommends therefore that EPA clearly distinguish in the prioritization process rule those elements that are specific to gathering of reasonably available information and those elements relating to the development of existing or new information through TSCA Sections 8 and 4. For example, information gathering about candidate chemicals for high and low priority designations should be clearly sequential and iterative. EPA should first gather reasonably available information about potential hazards, uses and potential exposures of a candidate chemical and integrate that information. Sources of such information could include: QSAR and read-across information; information from the Chemical Data Reporting (CDR) and from EPA's Dashboard; information from the TSCA Work Plan Chemicals program as well as from other EPA efforts to develop and assess chemicals such as EPA's High Production Volume (HPV) Challenge Program, its Voluntary Children's Chemical Evaluation Program (VCCEP) and its Chemical Assessment and Management Program (ChAMP); exposure scenario information - -both actual or estimated from exposure models; information from Canada's Chemical Management Program (CMP) and from the European Chemical Agency's (ECHA) robust study summaries developed for REACH; and REACH use scenarios (though EPA must be cognizant of potential differences in EU and U.S. use scenarios and address these through U.S.-centric use mapping). As EPA is gathering reasonably available information, it could also request voluntary submission of information about a candidate chemical's potential hazards, uses and exposure from manufacturers, processors, distributors and users of candidate chemicals. It should invite discussions with manufacturers, processors, distributors and downstream users of a candidate chemical. If EPA concludes after it has implemented those initial information gathering steps that it still needs more information to prioritize, it should then turn to its Section 8(a) and 8(d) rule authority to seek additional existing information. Only if after using its Section 8 authority EPA determines that new information is necessary to prioritize should EPA then consider using its Section 4 test rule/order or consent agreement authorities to develop that information. Section 4 imposes limitations on when EPA can develop new information for prioritization. Congress generally expected EPA to base prioritization decisions on reasonably available information. EPA should acknowledge these limitations in the final rule - both in the preamble and the rule itself. Once EPA can make a preliminary determination that it has sufficient, integrated hazard, use and exposure information to designate a candidate chemical as a low or high priority, EPA should use a "bridging" step for chemicals being considered as high priority candidates before prioritization is actually initiated. At this "bridging" step, the Agency could consider whether it has sufficient information to "scope" a risk evaluation of the chemical. In this step, EPA might conduct a screening review of the candidate chemical to ascertain what additional hazard, use and exposure information might be needed to scope a risk evaluation of a high priority candidate. If information is identified as needed, and could be gathered/developed at this stage, the Agency could seek to obtain it. EPA's expectation that it can obtain all the information it needs to conduct a risk evaluation at the "pre-prioritization" stage, however, is unrealistic. EPA will have to consider other approaches to efficiently meet the risk evaluation process's statutory deadlines. 13 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 To address preliminary "insufficient" information findings, an additional "iterative" step might also be useful. Such a step might allow the Agency time to pursue different avenues for information before automatically defaulting to a high priority designation based on a finding of "insufficient" information to designate a candidate as a low priority. EPA's preamble discussion of the sufficiency or insufficiency of information to designate high or low priorities for risk evaluations is conclusory at best. EPA provides little indication how it will decide whether the available information it has 18 or can gather is sufficient or not; and what it will take to be considered "sufficient." EPA must provide greater clarity here, as well as for purposes of EPA's determination of the need for new information and its use of Section 4 in priority setting. ACC's comments on the proposed risk evaluation rule provide a definition of "sufficiency of information" that might be adaptable to the 19 prioritization context. ACC urges EPA to better explain the application of this concept more fully in the prioritization process rule. Finally, the Section 4 "statement of needs" requirement must be met if EPA concludes it can't prioritize without the development of new information. Overall, information gathering and information development at any stage in the prioritization process should use tiered and iterative processes for greater efficiencies, for meeting animal welfare requirements, and for meeting statutory deadlines. Integration of hazard, use and exposure information in a risk-based screen is also essential to prioritization which Congress intended would be a risk-based screening process, not a risk evaluation. RECOMMENDATION: EPA should use tiered, iterative approaches to information gathering/development in the prioritization process rule. EPA should also carefully delineate the requirements imposed on EPA to make determinations of need for new information in prioritization and statements of need for risk evaluations, as required by Section 4 of TSCA. EPA must also integrate hazard, use and exposure information in its prioritization risk based screening process. C. The Importance of Transparency in Prioritization Cannot Be Over-Emphasized As discussed above, there are many questions that the Agency must answer in its final rule concerning the specific steps of the prioritization process. Many of these steps also raise transparency issues. One of the most fundamental transparency issues that the Agency needs to address in the prioritization process is adequate notice to manufacturers and processors at critical points in the process. While it may be obvious that EPA would provide notice and request for comment/input once a chemical is in a "pool" or narrowed to be included in a "batch" to be prioritized, the Agency should also provide earlier notice about what groups of active chemicals in commerce from which it plans to identify potential candidates for prioritization. The Agency should also explain the methodology it will use to narrow and refine the pool of candidates. With each pool of candidates, the Agency should explain how it applied its methodology to narrow that pool and how it plans to "batch" them for efficient prioritization screening. The Agency should be clear about the number of chemicals it will address in each "batch" and how much time it will provide to gather information about a chemical in a batch. 18 Id. at 4830 and 4831. 19 Sufficiency of information means that, taking into account the importance of the determination, the Agency has appropriately relied on the best available science, considering the weight of the scientific evidence to make a reasoned and transparent fit-for-purpose determination. 14 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Transparency in the prioritization process is critical to enable the regulated community to understand the Agency's methodologies, criteria and processes and to better plan how they should prepare in advance. In addition, transparency is critical to instill public trust and confidence in the determinations ultimately made by EPA. Much of the pre-prioritization process is opaque as proposed. Without more transparency, the rule establishing the prioritization process risks being unduly vague and EPA's actions under it both arbitrary and capricious. RECOMMENDATION: Greater transparency is a central tenet of the LCSA. EPA must provide as much early notice as possible in the prioritization process, including about the methodology, criteria and processes it will use to select a "pool" of candidates for potential prioritization, to narrow and "batch" these pools, and its anticipated timing for announcing pools and narrowing batches, and about requiring information to be gathered, etc. 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 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. Under the LCSA, EPA must designate chemicals as high or low priority for risk evaluations. The key criteria by which EPA must determine whether a chemical is a high or low priority, however, are its hazard potential and exposure potential under its conditions of use and significant changes in the conditions of use. EPA's proposed prioritization process rule allows high priority chemicals to be designated as such based on a single condition of use, but requires all low priority designations to be based on "all conditions of use." This requirement for low priority designations is not mandated by the LCSA and was not intended by Congress. EPA concludes that the standard for a low priority chemical "effectively requires EPA to determine that under no conditions of use does the chemical meet the high priority substance standard."20 This proposed standard for designating low priority chemicals is such a high hurdle even EPA admits "it will be more difficult to support such designations."2 EPA bases its reasoning for its proposed approach to low priority designations on a cramped reading of the LCSA Sections 6(b)(1)(B)(i) and (ii) provisions on identification of high priority and low-priority substances and on its broad interpretation of the term "conditions of use" throughout its proposed implementation of the LCSA to mean "all" conditions of use. ACC discusses this same EPA interpretation of "conditions of use" in depth in ACC's comments on EPA's proposed risk evaluation process rule.22 In the preamble to the proposed prioritization process rule, EPA first emphasizes that Section 6(b)(1)(B)(ii)'s provision for designating a substance as a low priority must have "information sufficient" to establish that a substance does not meet the (B)(i) standard for designating a chemical as a high priority chemical. EPA discusses its rationale for concluding it can designate high priority 20 82 Fed. Reg. at 4830. 21 Id. 22 American Chemistry Council Comments on the Procedures for Chemical Risk Evaluation under the Amended Toxic Substances Control Act (RIN 2070- AK20). 15 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 chemicals under "a single condition of use, provided the hazard and exposure potential associated with that single use support such a designation."23 But EPA then creates a "converse" construct of the high priority designation standard to support its position on low priority designations. EPA concludes that since it can designate a chemical as a high priority because of the Section 6(b)(1)(B)(i) language, "a potential hazard and a potential route of exposure under the conditions of use, that low priorities can be so designated only if they don't meet this high priority standard ,,24 under all conditions of use. This argument in the "converse" coupled with EPA's interpretation of "the" conditions of use to mean "all" conditions of use is strained and counter to Congressional intent. A better interpretation is that a chemical could be designated low priority if it does not meet the "may present an unreasonable risk" high priority standard for "a" potential hazard or "a" potential route of exposure under a, some, or all conditions of use. EPA has flexibility here that it needs to apply, given the 6(b)(1) requirement for EPA to designate chemicals as low priority and the important policy objectives for low priority designations. 25 EPA's strained reading of the phrase "conditions of use" in designating low priority chemicals is wholly at odds with congressional intent to help the Agency focus its risk evaluation resources on high priority chemicals and conditions of use that raise the greatest potential for risk. Further, EPA's reference to its Safer 26 Chemicals Ingredients List (SCIL)27 as a starting point for identifying low priority chemicals is disingenuous since the SCIL list does not represent all conditions of use of those chemicals. A chemical under certain conditions of use may warrant a risk evaluation while that same chemical under other conditions of use may not warrant a risk evaluation at all. EPA should not have to scope a risk evaluation or conduct risk evaluations on most chemicals under all conditions of use before it can conclude that a certain use is not likely to present an unreasonable risk. EPA should be able to set aside chemicals for certain conditions of use through low priority designations where EPA concludes that the chemical does not meet the "may" present standard for those conditions of use. Designating low priorities for risk evaluations based on less than "all" conditions of use will help EPA meet its deadlines for scoping risk evaluations, will conserve resources, and will enable EPA to focus its risk evaluation efforts on chemicals that meet the high priority criteria under certain conditions of use. EPA has authority to determine that certain conditions of use of a chemical are likely to have low potential for risk and can be designated as "low priority" for risk evaluation. EPA should use this authority to help it focus its risk evaluations on chemicals designated as high priority under certain conditions of use. B. EPA's Abuse of Discretion Argument EPA provides as its rationale for addressing all conditions of use in the low priority designation process that EPA "considers that it would be an abuse of that discretion to simply disregard known, 23 82 Fed. Reg.at 4830. 24 15 U.S.C. 2605(b)(1)(B)(i) (emphasis added). 25 82 Fed. Reg. at 4829, Section IIIA notes "conserving resources" and giving "the public notice of chemical substances for which potential risks are likely low or nonexistent," as important policy objectives. 26 See Senate Congressional Record, June 7, 2016, at page 3519, in which Senator Vitter states: "The language of the compromise makes clear that EPA has to make a determination on all conditions of use considered in the scope but the Agency is given the discretion to determine the conditions of use that the Agency will address in its evaluation of the priority chemical. This assures that the Agency's focus on priority chemicals is on conditions of use that raise the greatest potential for risk. This also assures that the Agency can effectively assess and control priority chemicals and meet the new law's deadlines. Without this discretion to focus chemical risk assessments on certain conditions of use, the Agency's job would be more difficult." htps://www.congress.goy/crec/2016/06/07/CREC-2016-06-07-pu1-PgS3511.pdf 27 82 Fed. Reg. at 4830. 16 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0228

Which agency can designate a chemical as a high priority?

jzbn0226

jzbn0226_p14, jzbn0226_p15, jzbn0226_p16, jzbn0226_p17

EPA

ACC is well aware that information about potential hazards and potential uses and exposures of a chemical is critical to sound decision-making by EPA - for both prioritization and risk evaluation decisions. ACC is also well aware of the aggressive timeframes within which both prioritization and risk evaluations must be conducted. ACC strongly believes that both prioritization and risk evaluation processes are more efficient if they use iterative and tiered processes and that these processes help ensure science-based decision-making. ACC recommends therefore that EPA clearly distinguish in the prioritization process rule those elements that are specific to gathering of reasonably available information and those elements relating to the development of existing or new information through TSCA Sections 8 and 4. For example, information gathering about candidate chemicals for high and low priority designations should be clearly sequential and iterative. EPA should first gather reasonably available information about potential hazards, uses and potential exposures of a candidate chemical and integrate that information. Sources of such information could include: QSAR and read-across information; information from the Chemical Data Reporting (CDR) and from EPA's Dashboard; information from the TSCA Work Plan Chemicals program as well as from other EPA efforts to develop and assess chemicals such as EPA's High Production Volume (HPV) Challenge Program, its Voluntary Children's Chemical Evaluation Program (VCCEP) and its Chemical Assessment and Management Program (ChAMP); exposure scenario information - -both actual or estimated from exposure models; information from Canada's Chemical Management Program (CMP) and from the European Chemical Agency's (ECHA) robust study summaries developed for REACH; and REACH use scenarios (though EPA must be cognizant of potential differences in EU and U.S. use scenarios and address these through U.S.-centric use mapping). As EPA is gathering reasonably available information, it could also request voluntary submission of information about a candidate chemical's potential hazards, uses and exposure from manufacturers, processors, distributors and users of candidate chemicals. It should invite discussions with manufacturers, processors, distributors and downstream users of a candidate chemical. If EPA concludes after it has implemented those initial information gathering steps that it still needs more information to prioritize, it should then turn to its Section 8(a) and 8(d) rule authority to seek additional existing information. Only if after using its Section 8 authority EPA determines that new information is necessary to prioritize should EPA then consider using its Section 4 test rule/order or consent agreement authorities to develop that information. Section 4 imposes limitations on when EPA can develop new information for prioritization. Congress generally expected EPA to base prioritization decisions on reasonably available information. EPA should acknowledge these limitations in the final rule - both in the preamble and the rule itself. Once EPA can make a preliminary determination that it has sufficient, integrated hazard, use and exposure information to designate a candidate chemical as a low or high priority, EPA should use a "bridging" step for chemicals being considered as high priority candidates before prioritization is actually initiated. At this "bridging" step, the Agency could consider whether it has sufficient information to "scope" a risk evaluation of the chemical. In this step, EPA might conduct a screening review of the candidate chemical to ascertain what additional hazard, use and exposure information might be needed to scope a risk evaluation of a high priority candidate. If information is identified as needed, and could be gathered/developed at this stage, the Agency could seek to obtain it. EPA's expectation that it can obtain all the information it needs to conduct a risk evaluation at the "pre-prioritization" stage, however, is unrealistic. EPA will have to consider other approaches to efficiently meet the risk evaluation process's statutory deadlines. 13 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 To address preliminary "insufficient" information findings, an additional "iterative" step might also be useful. Such a step might allow the Agency time to pursue different avenues for information before automatically defaulting to a high priority designation based on a finding of "insufficient" information to designate a candidate as a low priority. EPA's preamble discussion of the sufficiency or insufficiency of information to designate high or low priorities for risk evaluations is conclusory at best. EPA provides little indication how it will decide whether the available information it has 18 or can gather is sufficient or not; and what it will take to be considered "sufficient." EPA must provide greater clarity here, as well as for purposes of EPA's determination of the need for new information and its use of Section 4 in priority setting. ACC's comments on the proposed risk evaluation rule provide a definition of "sufficiency of information" that might be adaptable to the 19 prioritization context. ACC urges EPA to better explain the application of this concept more fully in the prioritization process rule. Finally, the Section 4 "statement of needs" requirement must be met if EPA concludes it can't prioritize without the development of new information. Overall, information gathering and information development at any stage in the prioritization process should use tiered and iterative processes for greater efficiencies, for meeting animal welfare requirements, and for meeting statutory deadlines. Integration of hazard, use and exposure information in a risk-based screen is also essential to prioritization which Congress intended would be a risk-based screening process, not a risk evaluation. RECOMMENDATION: EPA should use tiered, iterative approaches to information gathering/development in the prioritization process rule. EPA should also carefully delineate the requirements imposed on EPA to make determinations of need for new information in prioritization and statements of need for risk evaluations, as required by Section 4 of TSCA. EPA must also integrate hazard, use and exposure information in its prioritization risk based screening process. C. The Importance of Transparency in Prioritization Cannot Be Over-Emphasized As discussed above, there are many questions that the Agency must answer in its final rule concerning the specific steps of the prioritization process. Many of these steps also raise transparency issues. One of the most fundamental transparency issues that the Agency needs to address in the prioritization process is adequate notice to manufacturers and processors at critical points in the process. While it may be obvious that EPA would provide notice and request for comment/input once a chemical is in a "pool" or narrowed to be included in a "batch" to be prioritized, the Agency should also provide earlier notice about what groups of active chemicals in commerce from which it plans to identify potential candidates for prioritization. The Agency should also explain the methodology it will use to narrow and refine the pool of candidates. With each pool of candidates, the Agency should explain how it applied its methodology to narrow that pool and how it plans to "batch" them for efficient prioritization screening. The Agency should be clear about the number of chemicals it will address in each "batch" and how much time it will provide to gather information about a chemical in a batch. 18 Id. at 4830 and 4831. 19 Sufficiency of information means that, taking into account the importance of the determination, the Agency has appropriately relied on the best available science, considering the weight of the scientific evidence to make a reasoned and transparent fit-for-purpose determination. 14 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 Transparency in the prioritization process is critical to enable the regulated community to understand the Agency's methodologies, criteria and processes and to better plan how they should prepare in advance. In addition, transparency is critical to instill public trust and confidence in the determinations ultimately made by EPA. Much of the pre-prioritization process is opaque as proposed. Without more transparency, the rule establishing the prioritization process risks being unduly vague and EPA's actions under it both arbitrary and capricious. RECOMMENDATION: Greater transparency is a central tenet of the LCSA. EPA must provide as much early notice as possible in the prioritization process, including about the methodology, criteria and processes it will use to select a "pool" of candidates for potential prioritization, to narrow and "batch" these pools, and its anticipated timing for announcing pools and narrowing batches, and about requiring information to be gathered, etc. 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 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. Under the LCSA, EPA must designate chemicals as high or low priority for risk evaluations. The key criteria by which EPA must determine whether a chemical is a high or low priority, however, are its hazard potential and exposure potential under its conditions of use and significant changes in the conditions of use. EPA's proposed prioritization process rule allows high priority chemicals to be designated as such based on a single condition of use, but requires all low priority designations to be based on "all conditions of use." This requirement for low priority designations is not mandated by the LCSA and was not intended by Congress. EPA concludes that the standard for a low priority chemical "effectively requires EPA to determine that under no conditions of use does the chemical meet the high priority substance standard."20 This proposed standard for designating low priority chemicals is such a high hurdle even EPA admits "it will be more difficult to support such designations."2 EPA bases its reasoning for its proposed approach to low priority designations on a cramped reading of the LCSA Sections 6(b)(1)(B)(i) and (ii) provisions on identification of high priority and low-priority substances and on its broad interpretation of the term "conditions of use" throughout its proposed implementation of the LCSA to mean "all" conditions of use. ACC discusses this same EPA interpretation of "conditions of use" in depth in ACC's comments on EPA's proposed risk evaluation process rule.22 In the preamble to the proposed prioritization process rule, EPA first emphasizes that Section 6(b)(1)(B)(ii)'s provision for designating a substance as a low priority must have "information sufficient" to establish that a substance does not meet the (B)(i) standard for designating a chemical as a high priority chemical. EPA discusses its rationale for concluding it can designate high priority 20 82 Fed. Reg. at 4830. 21 Id. 22 American Chemistry Council Comments on the Procedures for Chemical Risk Evaluation under the Amended Toxic Substances Control Act (RIN 2070- AK20). 15 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 chemicals under "a single condition of use, provided the hazard and exposure potential associated with that single use support such a designation."23 But EPA then creates a "converse" construct of the high priority designation standard to support its position on low priority designations. EPA concludes that since it can designate a chemical as a high priority because of the Section 6(b)(1)(B)(i) language, "a potential hazard and a potential route of exposure under the conditions of use, that low priorities can be so designated only if they don't meet this high priority standard ,,24 under all conditions of use. This argument in the "converse" coupled with EPA's interpretation of "the" conditions of use to mean "all" conditions of use is strained and counter to Congressional intent. A better interpretation is that a chemical could be designated low priority if it does not meet the "may present an unreasonable risk" high priority standard for "a" potential hazard or "a" potential route of exposure under a, some, or all conditions of use. EPA has flexibility here that it needs to apply, given the 6(b)(1) requirement for EPA to designate chemicals as low priority and the important policy objectives for low priority designations. 25 EPA's strained reading of the phrase "conditions of use" in designating low priority chemicals is wholly at odds with congressional intent to help the Agency focus its risk evaluation resources on high priority chemicals and conditions of use that raise the greatest potential for risk. Further, EPA's reference to its Safer 26 Chemicals Ingredients List (SCIL)27 as a starting point for identifying low priority chemicals is disingenuous since the SCIL list does not represent all conditions of use of those chemicals. A chemical under certain conditions of use may warrant a risk evaluation while that same chemical under other conditions of use may not warrant a risk evaluation at all. EPA should not have to scope a risk evaluation or conduct risk evaluations on most chemicals under all conditions of use before it can conclude that a certain use is not likely to present an unreasonable risk. EPA should be able to set aside chemicals for certain conditions of use through low priority designations where EPA concludes that the chemical does not meet the "may" present standard for those conditions of use. Designating low priorities for risk evaluations based on less than "all" conditions of use will help EPA meet its deadlines for scoping risk evaluations, will conserve resources, and will enable EPA to focus its risk evaluation efforts on chemicals that meet the high priority criteria under certain conditions of use. EPA has authority to determine that certain conditions of use of a chemical are likely to have low potential for risk and can be designated as "low priority" for risk evaluation. EPA should use this authority to help it focus its risk evaluations on chemicals designated as high priority under certain conditions of use. B. EPA's Abuse of Discretion Argument EPA provides as its rationale for addressing all conditions of use in the low priority designation process that EPA "considers that it would be an abuse of that discretion to simply disregard known, 23 82 Fed. Reg.at 4830. 24 15 U.S.C. 2605(b)(1)(B)(i) (emphasis added). 25 82 Fed. Reg. at 4829, Section IIIA notes "conserving resources" and giving "the public notice of chemical substances for which potential risks are likely low or nonexistent," as important policy objectives. 26 See Senate Congressional Record, June 7, 2016, at page 3519, in which Senator Vitter states: "The language of the compromise makes clear that EPA has to make a determination on all conditions of use considered in the scope but the Agency is given the discretion to determine the conditions of use that the Agency will address in its evaluation of the priority chemical. This assures that the Agency's focus on priority chemicals is on conditions of use that raise the greatest potential for risk. This also assures that the Agency can effectively assess and control priority chemicals and meet the new law's deadlines. Without this discretion to focus chemical risk assessments on certain conditions of use, the Agency's job would be more difficult." htps://www.congress.goy/crec/2016/06/07/CREC-2016-06-07-pu1-PgS3511.pdf 27 82 Fed. Reg. at 4830. 16 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0228

What is the page no mentioned in this document?

nlcn0226

nlcn0226_p15

16

4. Please provide the pub lic withanestimate ofthe ad ditionalcostseach agency will inc ur annua ly to produce risk a sse ssments under the Risk Asse ssment Bulle tin and an estimate of the corresponding benefits in te rms of improve d risk analysis. Comments prepared by: Je nnife r Sass, Ph.D. Se nio r SC ie ntist, He a lth and Environment Na tura 1 Re so urc es Defense Council 1200 Ne W Yo rk Avenue, NW, Suite 400, Wa shing ton, DC, 20005 te l: 202-289-2362, emailjjass@nrdc.org NRDC on OMBRA Bulle tin June 2006 16 Source: :ttps://www.industrydocuments.ucsf.edu/docs/nlcn0226

What is the date mentioned in this document?

nlcn0226

nlcn0226_p15

June 2006

4. Please provide the pub lic withanestimate ofthe ad ditionalcostseach agency will inc ur annua ly to produce risk a sse ssments under the Risk Asse ssment Bulle tin and an estimate of the corresponding benefits in te rms of improve d risk analysis. Comments prepared by: Je nnife r Sass, Ph.D. Se nio r SC ie ntist, He a lth and Environment Na tura 1 Re so urc es Defense Council 1200 Ne W Yo rk Avenue, NW, Suite 400, Wa shing ton, DC, 20005 te l: 202-289-2362, emailjjass@nrdc.org NRDC on OMBRA Bulle tin June 2006 16 Source: :ttps://www.industrydocuments.ucsf.edu/docs/nlcn0226

Who prepared the comments for this document?

nlcn0226

nlcn0226_p15

Je nnife r Sa ss, Ph.D., Jennifer Sass , Je nnife r Sa ss

4. Please provide the pub lic withanestimate ofthe ad ditionalcostseach agency will inc ur annua ly to produce risk a sse ssments under the Risk Asse ssment Bulle tin and an estimate of the corresponding benefits in te rms of improve d risk analysis. Comments prepared by: Je nnife r Sass, Ph.D. Se nio r SC ie ntist, He a lth and Environment Na tura 1 Re so urc es Defense Council 1200 Ne W Yo rk Avenue, NW, Suite 400, Wa shing ton, DC, 20005 te l: 202-289-2362, emailjjass@nrdc.org NRDC on OMBRA Bulle tin June 2006 16 Source: :ttps://www.industrydocuments.ucsf.edu/docs/nlcn0226

What is the name of the council?

nlcn0226

nlcn0226_p15

Natura l Re so urc e s De fe nse Co unc il, Natural Resources Defense Council

4. Please provide the pub lic withanestimate ofthe ad ditionalcostseach agency will inc ur annua ly to produce risk a sse ssments under the Risk Asse ssment Bulle tin and an estimate of the corresponding benefits in te rms of improve d risk analysis. Comments prepared by: Je nnife r Sass, Ph.D. Se nio r SC ie ntist, He a lth and Environment Na tura 1 Re so urc es Defense Council 1200 Ne W Yo rk Avenue, NW, Suite 400, Wa shing ton, DC, 20005 te l: 202-289-2362, emailjjass@nrdc.org NRDC on OMBRA Bulle tin June 2006 16 Source: :ttps://www.industrydocuments.ucsf.edu/docs/nlcn0226

What is the issued date of this document?

nlcn0226

nlcn0226_p0

June 15, 2006

NRDC NATURAL Resovaces Derense Couves Noss June 15, 2006 FILED ELEC'RRONICALLY OMB RAbulletin@omb.eop.goy Dr. Nancy Be c k Office of Information and Regulato ry Affairs Offic e of Managementand Budget 725 17th Stre et, N.W. Ne W Exe c utive Office Building, Room 10201 Washington, D, 20503 Re: NRDC Comments on the OMB Proposed Risk Assessme nt Bulle tin DearDr. Bec k: The Natura 1 Re so urc es De fe nse Counc il (NRDC), a na tio nalnon-pro fit public interest rg aniza tio n, o ffe rs the se comments in re sponse to the Offic e of Management and Budge t's (OMB) Proposed Risk Assessment Bulle tin, re le a se on January 9, 2006,1 whic h will be peer-reviewed by the Na tionalAc ademie S of Science. The vie WS expresse d he re in are presented on behalf of NRDC' sover1 millio n members and ac tivists, who he lp us pro tectournatio n' lic health, safety, and environmental fe uards. Such safeguardswere bomfrom a deliberative pub lic process, and a ltho ug h these protectionsmaycome atsome cost, they delivertremendousbenefits from decreased risksofcancer, to safer automobiles, and increased energy savings. Thus, we believe those who wish to change these safeguards shot engage in the same deliberative processused to create them. 1 Offic e of Info. & Reg Affs., OMB, Propose Risk Asse ssme nt Bulle tin (Jan. 2006), available at www.whiteho use.gov/omb/inforeg/propose risk a sse ssme nt bulle tin 010906.pd 2 Na tio nalAc a demies. Review of the OMB Risk Asse ssm nt Bulle tin. BEST-K-06-02-A (E Mantus) www8.nationalacademies.org/cp/proj tvie w.asp x? ke y=34282 Source:https://www.industrydocuments.ucsf.edu/docs/nlcn0226

Who is the addressee of this letter?

nlcn0226

nlcn0226_p0

Dr. Beck, Dr. Nancy Beck

NRDC NATURAL Resovaces Derense Couves Noss June 15, 2006 FILED ELEC'RRONICALLY OMB RAbulletin@omb.eop.goy Dr. Nancy Be c k Office of Information and Regulato ry Affairs Offic e of Managementand Budget 725 17th Stre et, N.W. Ne W Exe c utive Office Building, Room 10201 Washington, D, 20503 Re: NRDC Comments on the OMB Proposed Risk Assessme nt Bulle tin DearDr. Bec k: The Natura 1 Re so urc es De fe nse Counc il (NRDC), a na tio nalnon-pro fit public interest rg aniza tio n, o ffe rs the se comments in re sponse to the Offic e of Management and Budge t's (OMB) Proposed Risk Assessment Bulle tin, re le a se on January 9, 2006,1 whic h will be peer-reviewed by the Na tionalAc ademie S of Science. The vie WS expresse d he re in are presented on behalf of NRDC' sover1 millio n members and ac tivists, who he lp us pro tectournatio n' lic health, safety, and environmental fe uards. Such safeguardswere bomfrom a deliberative pub lic process, and a ltho ug h these protectionsmaycome atsome cost, they delivertremendousbenefits from decreased risksofcancer, to safer automobiles, and increased energy savings. Thus, we believe those who wish to change these safeguards shot engage in the same deliberative processused to create them. 1 Offic e of Info. & Reg Affs., OMB, Propose Risk Asse ssme nt Bulle tin (Jan. 2006), available at www.whiteho use.gov/omb/inforeg/propose risk a sse ssme nt bulle tin 010906.pd 2 Na tio nalAc a demies. Review of the OMB Risk Asse ssm nt Bulle tin. BEST-K-06-02-A (E Mantus) www8.nationalacademies.org/cp/proj tvie w.asp x? ke y=34282 Source:https://www.industrydocuments.ucsf.edu/docs/nlcn0226

What is the fullform of NRDC?

nlcn0226

nlcn0226_p0

Natural Resources Defense Council

NRDC NATURAL Resovaces Derense Couves Noss June 15, 2006 FILED ELEC'RRONICALLY OMB RAbulletin@omb.eop.goy Dr. Nancy Be c k Office of Information and Regulato ry Affairs Offic e of Managementand Budget 725 17th Stre et, N.W. Ne W Exe c utive Office Building, Room 10201 Washington, D, 20503 Re: NRDC Comments on the OMB Proposed Risk Assessme nt Bulle tin DearDr. Bec k: The Natura 1 Re so urc es De fe nse Counc il (NRDC), a na tio nalnon-pro fit public interest rg aniza tio n, o ffe rs the se comments in re sponse to the Offic e of Management and Budge t's (OMB) Proposed Risk Assessment Bulle tin, re le a se on January 9, 2006,1 whic h will be peer-reviewed by the Na tionalAc ademie S of Science. The vie WS expresse d he re in are presented on behalf of NRDC' sover1 millio n members and ac tivists, who he lp us pro tectournatio n' lic health, safety, and environmental fe uards. Such safeguardswere bomfrom a deliberative pub lic process, and a ltho ug h these protectionsmaycome atsome cost, they delivertremendousbenefits from decreased risksofcancer, to safer automobiles, and increased energy savings. Thus, we believe those who wish to change these safeguards shot engage in the same deliberative processused to create them. 1 Offic e of Info. & Reg Affs., OMB, Propose Risk Asse ssme nt Bulle tin (Jan. 2006), available at www.whiteho use.gov/omb/inforeg/propose risk a sse ssme nt bulle tin 010906.pd 2 Na tio nalAc a demies. Review of the OMB Risk Asse ssm nt Bulle tin. BEST-K-06-02-A (E Mantus) www8.nationalacademies.org/cp/proj tvie w.asp x? ke y=34282 Source:https://www.industrydocuments.ucsf.edu/docs/nlcn0226

What kind of organization is NRDC?

nlcn0226

nlcn0226_p0

a national non-profit public interest organization

NRDC NATURAL Resovaces Derense Couves Noss June 15, 2006 FILED ELEC'RRONICALLY OMB RAbulletin@omb.eop.goy Dr. Nancy Be c k Office of Information and Regulato ry Affairs Offic e of Managementand Budget 725 17th Stre et, N.W. Ne W Exe c utive Office Building, Room 10201 Washington, D, 20503 Re: NRDC Comments on the OMB Proposed Risk Assessme nt Bulle tin DearDr. Bec k: The Natura 1 Re so urc es De fe nse Counc il (NRDC), a na tio nalnon-pro fit public interest rg aniza tio n, o ffe rs the se comments in re sponse to the Offic e of Management and Budge t's (OMB) Proposed Risk Assessment Bulle tin, re le a se on January 9, 2006,1 whic h will be peer-reviewed by the Na tionalAc ademie S of Science. The vie WS expresse d he re in are presented on behalf of NRDC' sover1 millio n members and ac tivists, who he lp us pro tectournatio n' lic health, safety, and environmental fe uards. Such safeguardswere bomfrom a deliberative pub lic process, and a ltho ug h these protectionsmaycome atsome cost, they delivertremendousbenefits from decreased risksofcancer, to safer automobiles, and increased energy savings. Thus, we believe those who wish to change these safeguards shot engage in the same deliberative processused to create them. 1 Offic e of Info. & Reg Affs., OMB, Propose Risk Asse ssme nt Bulle tin (Jan. 2006), available at www.whiteho use.gov/omb/inforeg/propose risk a sse ssme nt bulle tin 010906.pd 2 Na tio nalAc a demies. Review of the OMB Risk Asse ssm nt Bulle tin. BEST-K-06-02-A (E Mantus) www8.nationalacademies.org/cp/proj tvie w.asp x? ke y=34282 Source:https://www.industrydocuments.ucsf.edu/docs/nlcn0226

What is the subject line of this letter?

nlcn0226

nlcn0226_p0

Re: NRDC Comments on the OMB Proposed Risk Assessment Bulletin

NRDC NATURAL Resovaces Derense Couves Noss June 15, 2006 FILED ELEC'RRONICALLY OMB RAbulletin@omb.eop.goy Dr. Nancy Be c k Office of Information and Regulato ry Affairs Offic e of Managementand Budget 725 17th Stre et, N.W. Ne W Exe c utive Office Building, Room 10201 Washington, D, 20503 Re: NRDC Comments on the OMB Proposed Risk Assessme nt Bulle tin DearDr. Bec k: The Natura 1 Re so urc es De fe nse Counc il (NRDC), a na tio nalnon-pro fit public interest rg aniza tio n, o ffe rs the se comments in re sponse to the Offic e of Management and Budge t's (OMB) Proposed Risk Assessment Bulle tin, re le a se on January 9, 2006,1 whic h will be peer-reviewed by the Na tionalAc ademie S of Science. The vie WS expresse d he re in are presented on behalf of NRDC' sover1 millio n members and ac tivists, who he lp us pro tectournatio n' lic health, safety, and environmental fe uards. Such safeguardswere bomfrom a deliberative pub lic process, and a ltho ug h these protectionsmaycome atsome cost, they delivertremendousbenefits from decreased risksofcancer, to safer automobiles, and increased energy savings. Thus, we believe those who wish to change these safeguards shot engage in the same deliberative processused to create them. 1 Offic e of Info. & Reg Affs., OMB, Propose Risk Asse ssme nt Bulle tin (Jan. 2006), available at www.whiteho use.gov/omb/inforeg/propose risk a sse ssme nt bulle tin 010906.pd 2 Na tio nalAc a demies. Review of the OMB Risk Asse ssm nt Bulle tin. BEST-K-06-02-A (E Mantus) www8.nationalacademies.org/cp/proj tvie w.asp x? ke y=34282 Source:https://www.industrydocuments.ucsf.edu/docs/nlcn0226

which contact number is provided in this letter?

kzbn0226

kzbn0226_p0

202-249-6130

American° Chemistry Council March 20, 2017 Document Control Office (7407M) Office of Pollution Prevention and Toxics Environmental Protection Agency 1200 Pennsylvania Ave. NW Washington, DC 20460-0001 Submitted electronically via www.regulations.gov Re: Comments of the American Chemistry Council on EPA's Proposed Rule: Procedures for Chemical Risk Evaluation under the Amended Toxic Substances Control Act, 82 Fed. Reg. 7562 (January 19, 2017); EPA-HQ-OPPT-2016-0654 Dear Docket Clerk: The American Chemistry Council (ACC¹ is pleased to submit the attached comments on the Environmental Protection Agency, Office of Pollution Prevention and Toxics Proposed Rule, Procedures for Chemical Risk Evaluation under the Amended Toxic Substances Control Act. These comments align with our separately filed comments on the proposed rules describing the processes for inventory reset and prioritization for risk evaluation, and for the development of the scopes for risk evaluation of the first 10 chemicals selected from the TSCA work plan. All comments should be considered together. Please feel free to contact me with any questions at 202-249-6130 or karyn schmidu@americanchemistrv.com Sincerely, families Karyn M. Schmidt Senior Director, Regulatory and Technical Affairs American Chemistry Council cc: Jeffery Morris, Director, OPPT Wendy Cleland-Hamnett, OPPT Tala Henry, Director, Risk Assessment Division, OPPT Susanna Blair, Office of Chemical Safety and Pollution Prevention 1 ACC represents the leading companies engaged in the business of chemistry. More information about ACC is presented in the body of our comments. Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226

who is senior director for regulatory and technical affairs american chemistry council?

kzbn0226

kzbn0226_p0

Karyn M. Schmidt, karyn m. schmidt

American° Chemistry Council March 20, 2017 Document Control Office (7407M) Office of Pollution Prevention and Toxics Environmental Protection Agency 1200 Pennsylvania Ave. NW Washington, DC 20460-0001 Submitted electronically via www.regulations.gov Re: Comments of the American Chemistry Council on EPA's Proposed Rule: Procedures for Chemical Risk Evaluation under the Amended Toxic Substances Control Act, 82 Fed. Reg. 7562 (January 19, 2017); EPA-HQ-OPPT-2016-0654 Dear Docket Clerk: The American Chemistry Council (ACC¹ is pleased to submit the attached comments on the Environmental Protection Agency, Office of Pollution Prevention and Toxics Proposed Rule, Procedures for Chemical Risk Evaluation under the Amended Toxic Substances Control Act. These comments align with our separately filed comments on the proposed rules describing the processes for inventory reset and prioritization for risk evaluation, and for the development of the scopes for risk evaluation of the first 10 chemicals selected from the TSCA work plan. All comments should be considered together. Please feel free to contact me with any questions at 202-249-6130 or karyn schmidu@americanchemistrv.com Sincerely, families Karyn M. Schmidt Senior Director, Regulatory and Technical Affairs American Chemistry Council cc: Jeffery Morris, Director, OPPT Wendy Cleland-Hamnett, OPPT Tala Henry, Director, Risk Assessment Division, OPPT Susanna Blair, Office of Chemical Safety and Pollution Prevention 1 ACC represents the leading companies engaged in the business of chemistry. More information about ACC is presented in the body of our comments. Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226

What is commonly used in the environmental toxicology field?

kzbn0226

kzbn0226_p41, kzbn0226_p42, kzbn0226_p43, kzbn0226_p44, kzbn0226_p45, kzbn0226_p46

it is common to use the 95th percentile under average exposure conditions., 95th percentile under average exposure conditions

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

Which field does not use the "plausible maximum exposure" ?

kzbn0226

kzbn0226_p41, kzbn0226_p42, kzbn0226_p43, kzbn0226_p44, kzbn0226_p45, kzbn0226_p46

environmental toxicology field

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 does EPA cites as the source?

kzbn0226

kzbn0226_p41, kzbn0226_p42, kzbn0226_p43, kzbn0226_p44, kzbn0226_p45, kzbn0226_p46

"cites EPAs 2014 Human Health Risk Assessment Framework as the source."

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 would be the EPA's final risk evaluation?

kzbn0226

kzbn0226_p14, kzbn0226_p15, kzbn0226_p16

suspect quality, integrity, and reliability

Data quality assurance to confirm identified conditions of use should occur before the scope is released, and certainly must occur before the scope is published as final. It is essential to the quality and integrity of the risk evaluation itself. Use of poor quality or outdated information to "identify" conditions of use taints the ultimate science-based decisions required in the risk evaluation and undermines the statutorily-required application of best available science to exposure assessment. EPA should describe the process it uses to identify conditions of use in the scope of the risk evaluation, including: - The source of the information about a condition of use; - The reliability of the source of information (e.g., whether the information is a first- party, anecdotal report (blog, social media post, product comment or review) or reported to a government or credible third party); - A description of the Agency's assessment of whether the identity of the source of information is known and verified; - A description of how the information source has been verified and validated, if appropriate; and - Whether the information is current. I. EPA Should Not "Lock Down" Conditions of Use at the Time of Scoping. The Agency simultaneously insists that it must consider "all conditions of use" in the scope of the risk evaluation, but that it will then not actually consider "all" conditions of use through use of a "lock down" procedure, freezing the conditions of use at the time of scoping. In other words, if a new condition of use is discovered or emerges after the scope is published, EPA will not include it in the risk evaluation, regardless of impact. EPA proposes this "lock down" to help the Agency meet its statutory deadlines.17 We think the Agency has this backwards. To stay on its statutory schedule - or to move more quickly - the best tool EPA has available is scoping (the ability to scope its risk evaluations in a flexible manner to focus on the conditions posing the greatest potential risk). EPA should propose a process that allows the Agency to take full advantage of this important tool on a case- by-case basis. EPA should be able to select the conditions of use that it believes are most relevant and meaningful to human health and environmental risk and proceed accordingly. Likewise, EPA should not commit to "locking" conditions of use at the time of scoping. If EPA has discretion to select the conditions of use that it will include in the scope of a risk evaluation - which it does - then EPA should have the companion ability to remove or add a condition of use 18 as circumstances warrant. For example, following scoping EPA might determine that reports of an isolated use were wrong - and that the condition of use does not actually exist. It would 17 This proposal leaves in limbo the regulatory status of conditions of use that are excluded from the review. If EPA were to implement this approach, it would also need to clarify that excluded conditions of use go back to the prioritization process, and would also need to clarify that they do not have a high priority designation. This approach is also completely inconsistent with EPA's approach taken for manufacturer-requested evaluations. 18 Similarly, EPA has a companion ability to redesignate low priorities or high priorities as warranted. 10/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 make little sense to continue evaluating that condition of use in the risk evaluation. Otherwise, EPA's final risk evaluation would be of suspect quality, integrity, and reliability. A better approach would be for EPA to articulate in the rule that after a scope is published, EPA retains discretion to modify it upon a showing of substantial need or changed circumstances, or is otherwise warranted because the addition or removal of a condition of use, properly substantiated, will significantly affect the conduct of the risk evaluation. J. EPA Must Remove the Comment-or-Waive (Issue Exhaustion) Proposal. EPA further proposes that it can keep risk evaluations on schedule, notwithstanding its proposal to include "all conditions of use" in every scope, by "providing opportunity for comment on the scoping document and specifying that any objections to the draft scope document are waived if not raised during this process. ",99 We urge the Agency to remove this issue exhaustion (waiver) requirement for several reasons. First, it places an unfair burden on the regulated community. A particular company may not be aware, or otherwise in a position to verify, particular end uses that the company does not support (i.e., a downstream value chain to which it does not sell). A company likewise may not be able to verify occurrences of a chemical from natural sources or the actions of third parties through combustion, spills and discharges, disposal, manufacturing practices or incidents, and the like. When EPA insists on including "all conditions of use" in the scope of a risk evaluation, it moves well past the "major" uses of a chemical and "major" sources of exposure to include fleeting, incidental, minor, isolated, or exceptional cases. Information about these "minor" sources of exposure may be well outside the first-hand knowledge of a manufacturer or processor, making it difficult or impossible to offer meaningful comment during the scoping period. Second, participation in notice and comment rulemaking is governed by the Administrative Procedure Act (APA) and the judicial review provisions of Section 19 of TSCA. Issue exhaustion requirements can be imposed by statute. Notably, there are only a few statutory issue exhaustion provisions in environmental statutes, the most notable of which is in Section 307(d)(7)(b) of the Clean Air Act. There are none in TSCA. Congress had the opportunity to impose an issue exhaustion requirement for the scope of a risk evaluation in LCSA amendment - and declined to do so. EPA cannot, by regulation, impose an issue exhaustion requirement that trumps the statutory rights and obligations of stakeholders under the APA and TSCA Section 19.20 Indeed, ACC believes a waiver provision such as that proposed by EPA may not meet Constitutional muster. Third, the proposal does not rationally advance its claimed purpose - to meet statutory risk evaluation deadlines. An issue exhaustion requirement is supposed to serve two purposes: it 19 82 Fed. Reg. at 7566. 20 Administrative issue exhaustion requirements are largely creatures of statute, and here we have no such statutory construct. While some agency regulations set out issue exhaustion requirements without a statutory mandate, these tend to be in administrative appeal situations or proceedings that are analogs to adversarial litigation. Notably, the LCSA amendment removed a procedure for formal TSCA hearings. 11/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 protects administrative agency authority and promotes judicial efficiency. But here, by 21 requiring inclusion of "all conditions of use" in scopes, the agency impairs the ability of industry to meaningfully comment in the limited time available. EPA seems to be of the view that it would rather include "too much" in a scope than inadvertently omit a condition of use and include "too little," but it is the overly broad, unrefined scope that expands the scale and cost of risk evaluations and slows them. EPA then ties its own hands by proposing to "lock down" overly broad scopes, impeding its ability to update or modify them later in the process. This does not advance efficiency or transparency in the regulatory process. EPA can avoid these inefficiencies by offering a simple process to identify those major, important conditions of use that are most relevant and meaningful to a high-quality risk evaluation - and to use flexibility in designing the scope accordingly. EPA should offer a rationale of why it selected the uses it did in the scope itself. II. EPA Must Describe How and When it Will Apply Section 26 Requirements to Risk Evaluations. Section 26(h) sets out scientific standards that apply to every "decision based on science" while EPA carries out risk evaluation under Section 6 [emphasis added]. Section 26(i) requires EPA to "make decisions" under Section 6 based on the weight of the scientific evidence [emphasis added]. A decision would include any judicially reviewable determination, but also any other decision that requires application of science or scientific judgment by the Agency. EPA should articulate in the risk evaluation rule, at a minimum, the key decision points that will require compliance with Section 26 requirements. These should include, but are not limited to: - The proposed scope and final scope for risk evaluation - Hazard assessment, including, where applicable, the likely operable mode of action - Exposure assessment - Selection and evaluation of technical procedures, measures, methods, protocols, methodologies, and models - Basis for scientific assumptions - Selection and evaluation of quality assurance procedures - Decisions regarding variability and uncertainty - Statistical methods - The draft and final risk evaluation EPA should document how it applied Section 26(h) and 26(i) requirements for each decision. 21 The issue exhaustion proposal does not advance judicial economy either. Determinations of no unreasonable risk, made by the Agency following the completion of the risk evaluation process, are judicially reviewable - but as a practical matter this means that a judicial challenge to such a determination would be unlikely to occur until years after the scope was published (and the risk evaluation completed). Changes to conditions of use, or errors in their identification and inclusion, may not all be evident at the time the scope is originally prepared and published, so applying issue exhaustion at this step makes little sense. 12/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226

Which law is signed by President Obama?

ylcn0226

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

the Frank R. Launtenberg Chemical Safety for 21st Century 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 beck@americanchemistry.com 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 fullform of TSCA?

ylcn0226

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

Toxic Substances Control 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 beck@americanchemistry.com 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

When did president Obama amends the TSCA?

ylcn0226

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On June 22, 2016

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 beck@americanchemistry.com 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 was the Mandatory requirement for EPA?

ylcn0226

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

to evaluate existing chemicals with clear and enforceable deadlines

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 beck@americanchemistry.com 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 abbreviation for Chemical Safety Advisory Committee?

kzbn0226

kzbn0226_p32, kzbn0226_p33, kzbn0226_p34, kzbn0226_p35, kzbn0226_p36, kzbn0226_p37, kzbn0226_p38, kzbn0226_p39

CSAC

screening level quantitative risk analysis in the scope phase. 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. Examples of low risk conditions of use could include occupational uses already regulated under OSHA, de minimis uses, or feedstock uses where the use is already regulated, as discussed above in Sections I(D)- I(F) 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. This tiered, iterative approach is consistent with EPA's exposure assessment practices, where screening level tools, which are "protective by design," may be used initially, and then if needed, higher tier tools, which are "more complex and allow for more realistic exposure assessments" can later be employed. 69 i 10 Workplan High-Quality Refined Risk Evaluation High Priority Chemicals & DRAFT Chemicais Manufacturer Risk Evaluation Requested EXPOSUNE HAZARO ASSESSMENE Evaluation incorporating Sections 6 and 26 of the Lautenberg Chemical Safety Act (LCSA): Scope/Screening Level Risk Evaluation Scientifio Standards FINAL Susceptible Weight of Scientific Evidence Evaluations Risk Evaluation Exposures Maxands CONDITIONS or USE Certain Conditions of Use Present Do not present an unreasonable risk an unreasonable risk Refined No further risk evaluation risk evaluation No further action; needed RULEMAKING PROCESS COMPLETE Figure 1. A Two-Step Process for Conducting Risk Evaluations Note this is a simplified version of the process, see text for more detail i. Conditions of Use Requiring No Further Evaluation Once the draft scope is complete, there will likely be conditions of use which will not require any further evaluation as they are unlikely to present an unreasonable 69 28/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 risk to human health or the environment. After EPA takes comment on these findings and finalizes the scope document, EPA should formally announce the conditions of use that "do not present an unreasonable risk." While EPA may make additional findings of "does not present unreasonable risk" after the refined risk evaluation is complete, for those conditions of use that do not require further evaluation after scoping, there is no reason for EPA to wait the 3 to 3.5 years to complete the refined risk evaluation before announcing these findings. Once announced, the determination of "does not present unreasonable risk" for the specific condition(s) of use should be considered final agency action. ii. Ensuring Sufficient Information to Conduct a Refined Risk Evaluation While EPA intends to only conduct risk evaluations on those chemicals for which sufficient information exists, there will likely be a few cases where, once a screening level evaluation is complete, EPA will realize that certain data needs preclude conducting a refined risk evaluation. In such cases, where EPA may need to use test rules, orders or consent agreements to gather existing or new information, EPA should pause the risk evaluation process. This pause will allow the needed data to be generated in a scientifically robust manner. When this is necessary, EPA should announce this pause and its expected length in the Federal Register. EPA should also use the Federal Register to notify the public when the pause ends and the risk evaluation commences. ACC expects that EPA will not need to pause assessments frequently, but EPA should be aware that there may be cases that necessitate the use of a pause. As ACC discusses in our comments on the Prioritization Framework, during the prioritization process, it is not appropriate for EPA to collect data to conduct full risk evaluations.70 B. Refined Risk Evaluation The additional steps of the risk evaluation process include hazard assessment, exposure assessment, risk characterization, public comment, and peer review. Further details regarding the specific elements that should be in different sections of the risk evaluation are included in the appendices of ACC's August 24, 2016 comments. 71 As they were clearly presented to the Agency and are in the public docket, while they are still relevant, we will not reiterate them here. While previously emphasized in these comments, ACC reiterates that it will be important throughout the refined risk evaluation process that EPA always rely on the best available science and follow a WoE approach that incorporates systematic review processes. 70 See ACC comments on the Prioritization Framework Rule, submitted on March 20, 2017. 71 See ACC comments, at Appendices B-E, available at: butps//www.regulations.gos/document?D=EPA-HQ-OPPT 2016-0400-0028. 29/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 Comments on the sections of the risk evaluation process that have not been previously addressed above are presented in this section. i. Hazard Assessment When conducting refined hazard assessments for human health or environmental endpoints, EPA must rely on the data (reasonably available information that is scientifically valid, as defined in Section IV of these comments) first and foremost. When additional data are needed, EPA may rely on models and extrapolations. All assumptions and uncertainties associated with these models and extrapolations must be transparently discussed. When EPA is faced with conflicting data or data that could be interpreted in multiple scientifically plausible ways, EPA should strive to present the full range of scientifically supportable analyses for consideration. As the types of data that will be available for the agency to consider will vary for each chemical and as science advances (e.g., high throughput screening tools), EPA should not specifically mandate the types of data that will be used. There will likely be cases where these data do not exist or are not of sufficient quality. In addition, EPA states that it will evaluate, as appropriate, "acute, subchronic, and chronic effects during various stages of reproduction or life stage."72 We urge EPA to ensure that these evaluations are necessary for the relevant conditions of use. Otherwise the Agency will spend too much time focusing on subpopulations or durations that are not relevant or critical to the refined risk evaluation. EPA must also verify that scientifically valid information exists to inform each of these scenarios and that consistent with WoE and systematic review practices, data are evaluated based on their strengths and limitations. The criteria that will be used to evaluate the strengths and limitations of studies from different streams (epidemiologic, toxicologic, mechanistic), should be presented in the protocol that is released with the scope document. EPA states that dose-response assessments will be included where possible. 73 EPA should describe transparent criteria that will be used throughout the risk evaluation process to determine if the data are of sufficient quality for dose-response assessment. Conducting dose-response assessment on data of inadequate quality will likely lead to misleading and unreliable findings in the risk characterization step. For environmental hazard assessment, EPA notes that the agency may rely on 74 incident data. ACC cautions EPA on this approach as incident data is very situational specific, requires a deep understanding of the particular situation and may not be of sufficient quality for use in other situations. Therefore, EPA should 72 See 82 Fed. Reg. at 7579. 73 Id. at 7571. 74 Id. at 7579. 30/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 judiciously use this information and must be extremely transparent regarding all assumptions and uncertainties when incident data are used. Similarly, EPA states that the Agency may also consider ecological field data. 75 ACC appreciates that EPA will consider using these data over modeling data as this is consistent with EPA's data preference hierarchy. 76 Consistent with this hierarchy, EPA must ensure that the data are valid, reliable and relevant for the decision being made. ii. Exposure Assessment For refined exposure assessment, above all else, EPA must ensure that it is using high quality representative data that are reflective of current uses for the conditions of use that are of concern. Similar to the necessity to clarify how the strengths and limitations of hazard information will be evaluated, EPA should also clearly present the approach that will be used to evaluation exposure information. As data and models permit, EPA must strive to use probabilistic exposure analyses.77 iii. Risk Characterization To ensure that risk characterization is robust and consistent with not only EPA's 2000 Risk Characterization Handbook and EPA Information Quality Guidelines, 78 we recommend that EPA include the following description in the regulatory text, which is consistent with those documents: In the risk characterization, particularly when there are findings that a chemical presents an unreasonable risk, for each condition of use evaluated, EPA will present (i) each population addressed by any estimate of applicable human health risk or each risk assessment endpoint, including populations if applicable, addressed by any estimate of applicable ecological risk; (ii) the expected risk or central estimate of risk of the human health risk for the specific populations affected or the ecological assessment endpoints, including populations if applicable; (iii) each appropriate upper-bound or lower-bound estimate of risk; (iv) each significant uncertainty identified in the process of the assessment of risk and the studies that would assist in resolving the uncertainty; and (v) peer- reviewed studies known to the Agency that support, are directly relevant to, or fail to support any estimate of risk and the methodology used to reconcile inconsistencies in the scientific data. 75 Id. at 7571. 76 See 77 This recommendation is consistent with the comments from the CSAC on the 1-bromopropane review, see Chemical Safety Advisory Committee Minutes No. 2016-02, at 13. 78 See EPA Risk Characterization Handbook, available at bitps:/www.epa.gov/sites/production/files/2015. 10/documents/osp risk characterization bandbook 2000.pdf. 31/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 In addition, the risk characterization summary should be consistent with the Section 26 science standards. As such, EPA should also include the following language at $702.41 in the regulatory text: This summary will include, as appropriate, a discussion of (1) the extent to which the scientific information, technical procedures, measures, methods, protocols, methodologies, or models employed to generate the information are reasonable for and consistent with the intended use of the information; (2) the extent to which the information is relevant for the Administrator's use in making a decision about a chemical substance or mixture; (3) the degree of clarity and completeness with which the data, assumptions, methods, quality assurance, and analyses employed to generate the information are documented; (4) the extent to which the variability and uncertainty in the information, or in the procedures, measures, methods, protocols, methodologies, or models, are evaluated and characterized; and (5) the extent of independent verification or peer review of the information or of the procedures, measures, methods, protocols, methodologies, or models. EPA notes, in particular, that the Agency may exercise its discretion to include discussion of any alternative interpretation of results. 79 This statement should be clarified. To resolve differences of scientific opinion, when reasonable judgments may lead to different interpretations or alternative methods (e.g., linear and non- linear cancer modeling), the Agency should always err on the side of presenting all scientifically valid approaches. Presentation of alternatives should be the norm, not the exception. For environmental evaluations, EPA notes that the Agency may consider "effects at the individual, species and community level Environmental assessments are ,,80 typically focused on protecting populations, not necessarily individual environmental organisms. EPA must clearly justify any environmental 81 assessments that are conducted at the individual level. Finally, risk characterization should strive to present what is commonly termed a "reality check.' EPA should ensure that its final estimate of risk is reasonable and is scientifically sound considering what is widely known about the chemical and its condition(s) of use. A good example of this can be found in a few earlier assessments that EPA conducted. 82 79 See 82 Fed. Reg. at 7571. 80 Id. 81 See EPA's Ecological Risk Assessment Guidance for Superfund: Process for Designing and Conducting Ecological Risk Assessments, 1997, available at hups:/isemspub.epa.gov/work/HQ/15794Lpdi 82 See for example EPA's 1985 Mutagenicity and Carcinogenicity Assessment of 1,3-Butadiene, at 6-70 and 6-71 available at 32/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 C. Publicly Available Information Consistent with Section 26(j) of the LCSA, EPA commits to making information available to the public. ACC concurs with this approach and has a few suggested additions for what should be made available. Consistent with our comments on peer review, EPA should ensure that there is an opportunity for the public to provide comments to peer review panels on key areas of the assessments that warrant detailed review, and the peer reviewers should subsequently provide responses to substantive scientific public comments that they receive. These public comments and the peer reviewer responses should be included in the final peer review report that is placed in the public docket. In addition to providing a response to public comments received on the draft risk evaluation, EPA should provide a similar response to public comments received on the draft scope document. Both sets of agency responses should be in the public docket. To ensure that CBI is appropriately used in the risk evaluation process, EPA should use an appropriate third party to review this information. The report from this review should also be placed in the public docket, safeguarding all CBI. This approach will help to facilitate the agencies use of CBI in the risk evaluation process, as appropriate. D. Reassessment 83 EPA states that the Agency may reassess a final unreasonable risk determination at any time. EPA should clarify that EPA may reassess a finding of "no unreasonable risk" or a finding of "unreasonable risk" based on a review of available information. There is no justification for reassessment to apply only to findings of "no unreasonable risk.' The requirements for reassessment must be applied equally to both positive and negative risk findings. EPA should put in place a transparent petition process that will allow the public to comment on chemicals and conditions of use that may require reassessment. In addition, ACC recommends that when a determination is made to reassess a chemical substance, the Agency begin with prioritization before proceeding to risk evaluation. E. Third Party Assessments While EPA has not yet released guidance to assist persons interested in developing and submitting draft risk evaluations which shall be considered by the Administrator, EPA should expect to receive some risk evaluations from third parties for consideration in the process. The ANONYMOUS&Passwordeanonymous&SortMethodmh%70.- y=135. 83 See 82 Fed. Reg. at 7580. 33/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 final rulemaking should describe the process the Agency will use for internally reviewing these risk evaluations and for moving them to peer review expeditiously. When submitted evaluations follow the same policies and procedures that will be described in the final risk evaluation rule, EPA should commit to reviewing draft risk evaluations within 90 days. This timeframe is consistent with the period of time ACC proposes that EPA allow for public comment on risk evaluations developed by the Agency. ACC also recommends that public comment be simultaneous with internal EPA review. Once the review process is complete, these assessments should move to peer review. VII. Additional Definitions The proposed rule discusses other important definitions. Some are new, while others are redefinitions of existing terms. Below ACC provides recommendations to inform EPA's use and interpretation of a few of these definitions. A. Aggregate Exposure While EPA provides an appropriate definition of aggregate exposure, consistent with the definition in the EPA Exposure Factors Handbook, ACC is concerned that when considering aggregate exposures, EPA may go beyond the intended scope of what should be in a risk evaluation under the LCSA. Risk evaluations conducted under the LCSA should be consistent with the scope of the LCSA. For instance, the LCSA does not cover the evaluation of pesticides, foods, food additives, drugs, cosmetics, tobacco products, etc. As such, it would be inappropriate for consideration of aggregate exposure to lead to a risk evaluation of non-LCSA products. If EPA felt it necessary to consider such products, any assessment conducted should be done only on a case specific basis and in consultation with the appropriate Agency or program with the statutory authority for the review and assessment of that product. EPA should commit to including relevant authorities and experts when there are such cases. We expect the need to conduct these consultations to be the exception rather than the norm. B. Categories of Chemical Substances The term "category of chemical substances" is clearly defined in Section 26(c) of the LCSA. In the proposed rule, EPA specifically notes that, where appropriate, a risk evaluation may be conducted on a category of chemical substances. ACC supports this approach. EPA explicitly seeks comment on areas where additional transparency, public accountability, and opportunities for public comment can be improved.84 To be consistent with cross-cutting requirements in Section 26(h), and to be consistent with EPA's general commitment to transparency and public accountability, when EPA finds that it is appropriate to consider a category of chemical substances, this finding should be clearly explained. The justification should include all the factors and considerations which led to the determination that a category approach was appropriate. When such an approach is taken, before EPA begins their risk evaluation, EPA should solicit public comment on its determination that it is appropriate. 84 See 82 Fed. Reg. at 7565. 34/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 C. Potentially Exposed and Susceptible Populations This term is clearly described in the statute. There is no need for EPA to reinterpret it or broaden the definition. The edits below bring the proposed definition in the regulatory text in line with the statutory definition: Potentially exposed or susceptible subpopulation means a group of individuals within the general population identified by the Agency who, due to either greater susceptibility or greater exposure, may be at greater risk than the general population of adverse health effects from exposure to a chemical substance or mixture, including but not limited to, as infants, children, pregnant women, workers, or the elderly. EPA may identify a susceptible subpopulation in an individual risk evaluation upon consideration of various intrinsic (e.g., life stage, reproductive status, age, gender, genetic traits) or acquired (e.g. pre existing disease, geography, workplace) characteristics that may affect exposure or modify the risk of illness or disease. EPA has suggested modifying the statutory definition for two stated reasons: to clarify that EPA may identify additional populations where warranted, and to include specific authorization for EPA to consider broader factors (e.g., consideration of various intrinsic or acquired factors) when identifying this population. The term "such as" is sufficiently clear to allow EPA to 85 identify additional subpopulations when needed. Had Congress intended to explicitly include other subpopulations, Congress would have chosen different language. Similarly, if Congress felt the need to explicitly define what factors EPA must consider (e.g., intrinsic and extrinsic factors), these factors would have been included in the definition. This is not an area in need of clarification in the regulatory definition. Similarly, EPA broadens the definition to include explicit consideration of those with illness or disease. While such considerations may very well be appropriate in case-by-case situations for particular conditions of use, had Congress intended this consideration for each condition of use evaluated under the LCSA, the language would have been included in the statute. EPA's proposed revision is clearly intended to broaden the scope of EPA's evaluation. Congress did not support such a broad scope, nor does ACC. We recommend that EPA finalize the definition provided in the statute. D. Sentinel Exposure EPA provides a definition for sentinel exposure and notes that while it is not a novel way of characterizing exposure, it is a new term for EPA. 86 EPA does not identify the source for its definition. ACC is concerned that EPA's proposed definition does not reflect a fundamental understanding of how the concept of sentinel exposure has been used by other national authorities, such as Health Canada or the European Union (EU). In fact the term and use of sentinel exposures is not new in either jurisdiction; as such, it is not new to U.S. chemical manufacturers. The concept of 85 Id. at 7576. 86 Id. at 7658. 35/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226

what does APA stands for?

kzbn0226

kzbn0226_p14, kzbn0226_p15, kzbn0226_p16

Administrative Procedure Act

Data quality assurance to confirm identified conditions of use should occur before the scope is released, and certainly must occur before the scope is published as final. It is essential to the quality and integrity of the risk evaluation itself. Use of poor quality or outdated information to "identify" conditions of use taints the ultimate science-based decisions required in the risk evaluation and undermines the statutorily-required application of best available science to exposure assessment. EPA should describe the process it uses to identify conditions of use in the scope of the risk evaluation, including: - The source of the information about a condition of use; - The reliability of the source of information (e.g., whether the information is a first- party, anecdotal report (blog, social media post, product comment or review) or reported to a government or credible third party); - A description of the Agency's assessment of whether the identity of the source of information is known and verified; - A description of how the information source has been verified and validated, if appropriate; and - Whether the information is current. I. EPA Should Not "Lock Down" Conditions of Use at the Time of Scoping. The Agency simultaneously insists that it must consider "all conditions of use" in the scope of the risk evaluation, but that it will then not actually consider "all" conditions of use through use of a "lock down" procedure, freezing the conditions of use at the time of scoping. In other words, if a new condition of use is discovered or emerges after the scope is published, EPA will not include it in the risk evaluation, regardless of impact. EPA proposes this "lock down" to help the Agency meet its statutory deadlines.17 We think the Agency has this backwards. To stay on its statutory schedule - or to move more quickly - the best tool EPA has available is scoping (the ability to scope its risk evaluations in a flexible manner to focus on the conditions posing the greatest potential risk). EPA should propose a process that allows the Agency to take full advantage of this important tool on a case- by-case basis. EPA should be able to select the conditions of use that it believes are most relevant and meaningful to human health and environmental risk and proceed accordingly. Likewise, EPA should not commit to "locking" conditions of use at the time of scoping. If EPA has discretion to select the conditions of use that it will include in the scope of a risk evaluation - which it does - then EPA should have the companion ability to remove or add a condition of use 18 as circumstances warrant. For example, following scoping EPA might determine that reports of an isolated use were wrong - and that the condition of use does not actually exist. It would 17 This proposal leaves in limbo the regulatory status of conditions of use that are excluded from the review. If EPA were to implement this approach, it would also need to clarify that excluded conditions of use go back to the prioritization process, and would also need to clarify that they do not have a high priority designation. This approach is also completely inconsistent with EPA's approach taken for manufacturer-requested evaluations. 18 Similarly, EPA has a companion ability to redesignate low priorities or high priorities as warranted. 10/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 make little sense to continue evaluating that condition of use in the risk evaluation. Otherwise, EPA's final risk evaluation would be of suspect quality, integrity, and reliability. A better approach would be for EPA to articulate in the rule that after a scope is published, EPA retains discretion to modify it upon a showing of substantial need or changed circumstances, or is otherwise warranted because the addition or removal of a condition of use, properly substantiated, will significantly affect the conduct of the risk evaluation. J. EPA Must Remove the Comment-or-Waive (Issue Exhaustion) Proposal. EPA further proposes that it can keep risk evaluations on schedule, notwithstanding its proposal to include "all conditions of use" in every scope, by "providing opportunity for comment on the scoping document and specifying that any objections to the draft scope document are waived if not raised during this process. ",99 We urge the Agency to remove this issue exhaustion (waiver) requirement for several reasons. First, it places an unfair burden on the regulated community. A particular company may not be aware, or otherwise in a position to verify, particular end uses that the company does not support (i.e., a downstream value chain to which it does not sell). A company likewise may not be able to verify occurrences of a chemical from natural sources or the actions of third parties through combustion, spills and discharges, disposal, manufacturing practices or incidents, and the like. When EPA insists on including "all conditions of use" in the scope of a risk evaluation, it moves well past the "major" uses of a chemical and "major" sources of exposure to include fleeting, incidental, minor, isolated, or exceptional cases. Information about these "minor" sources of exposure may be well outside the first-hand knowledge of a manufacturer or processor, making it difficult or impossible to offer meaningful comment during the scoping period. Second, participation in notice and comment rulemaking is governed by the Administrative Procedure Act (APA) and the judicial review provisions of Section 19 of TSCA. Issue exhaustion requirements can be imposed by statute. Notably, there are only a few statutory issue exhaustion provisions in environmental statutes, the most notable of which is in Section 307(d)(7)(b) of the Clean Air Act. There are none in TSCA. Congress had the opportunity to impose an issue exhaustion requirement for the scope of a risk evaluation in LCSA amendment - and declined to do so. EPA cannot, by regulation, impose an issue exhaustion requirement that trumps the statutory rights and obligations of stakeholders under the APA and TSCA Section 19.20 Indeed, ACC believes a waiver provision such as that proposed by EPA may not meet Constitutional muster. Third, the proposal does not rationally advance its claimed purpose - to meet statutory risk evaluation deadlines. An issue exhaustion requirement is supposed to serve two purposes: it 19 82 Fed. Reg. at 7566. 20 Administrative issue exhaustion requirements are largely creatures of statute, and here we have no such statutory construct. While some agency regulations set out issue exhaustion requirements without a statutory mandate, these tend to be in administrative appeal situations or proceedings that are analogs to adversarial litigation. Notably, the LCSA amendment removed a procedure for formal TSCA hearings. 11/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 protects administrative agency authority and promotes judicial efficiency. But here, by 21 requiring inclusion of "all conditions of use" in scopes, the agency impairs the ability of industry to meaningfully comment in the limited time available. EPA seems to be of the view that it would rather include "too much" in a scope than inadvertently omit a condition of use and include "too little," but it is the overly broad, unrefined scope that expands the scale and cost of risk evaluations and slows them. EPA then ties its own hands by proposing to "lock down" overly broad scopes, impeding its ability to update or modify them later in the process. This does not advance efficiency or transparency in the regulatory process. EPA can avoid these inefficiencies by offering a simple process to identify those major, important conditions of use that are most relevant and meaningful to a high-quality risk evaluation - and to use flexibility in designing the scope accordingly. EPA should offer a rationale of why it selected the uses it did in the scope itself. II. EPA Must Describe How and When it Will Apply Section 26 Requirements to Risk Evaluations. Section 26(h) sets out scientific standards that apply to every "decision based on science" while EPA carries out risk evaluation under Section 6 [emphasis added]. Section 26(i) requires EPA to "make decisions" under Section 6 based on the weight of the scientific evidence [emphasis added]. A decision would include any judicially reviewable determination, but also any other decision that requires application of science or scientific judgment by the Agency. EPA should articulate in the risk evaluation rule, at a minimum, the key decision points that will require compliance with Section 26 requirements. These should include, but are not limited to: - The proposed scope and final scope for risk evaluation - Hazard assessment, including, where applicable, the likely operable mode of action - Exposure assessment - Selection and evaluation of technical procedures, measures, methods, protocols, methodologies, and models - Basis for scientific assumptions - Selection and evaluation of quality assurance procedures - Decisions regarding variability and uncertainty - Statistical methods - The draft and final risk evaluation EPA should document how it applied Section 26(h) and 26(i) requirements for each decision. 21 The issue exhaustion proposal does not advance judicial economy either. Determinations of no unreasonable risk, made by the Agency following the completion of the risk evaluation process, are judicially reviewable - but as a practical matter this means that a judicial challenge to such a determination would be unlikely to occur until years after the scope was published (and the risk evaluation completed). Changes to conditions of use, or errors in their identification and inclusion, may not all be evident at the time the scope is originally prepared and published, so applying issue exhaustion at this step makes little sense. 12/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226

Which component is used for the last completed draft TSCA Workplan RIsk Evaluation?

kzbn0226

kzbn0226_p24, kzbn0226_p25, kzbn0226_p26, kzbn0226_p27, kzbn0226_p28, kzbn0226_p29

1-bromopropane

review reliability is reduced and it cannot be referred to as systematic It is unhelpful to classify "narrative reviews" as systematic reviews. 48 EPA states that it has included systematic reviews in the past; however, it is not clear what exactly it has done and where these reviews can be found. 49 The last completed draft TSCA Work Plan risk evaluation was for 1-bromopropane. The executive summary of the peer review report of this draft evaluation, dated August 22, 2016, states: Committee members agreed that the 1-BP risk assessment (and other TSCA chemical assessments to be presented in the future) would benefit by adoption of systematic review practices to increase the transparency of how studies were selected and evaluated. For example, the Committee recommended that it should be explicitly stated what criteria were used to determine "the monitoring was adequate and of acceptable quality" (risk assessment document, page 44). The Committee also noted that it would be useful to reference studies that were evaluated but did not meet baseline criteria to inform the exposure estimates. 50 In addition, the peer review committee could not determine "what exact methodology was used to systematically rate, rank, and select studies to inform sections of the risk assessment. ",151 Peer 52 reviewers also could not find any ranking system developed for study quality. It is critically important that systematic review mean the same thing to all engaged stakeholders, including Agency staff and peer reviewers. ACC cannot envision any situation where a definition of systematic review would unduly restrict the specific science that can be used to conduct a risk evaluation. A systematic review process will allow EPA to be flexible and to adapt with changing science, assuming that the new science meets the necessary high quality standards that are required by the LCSA. Including a regulatory definition for systematic review is fully consistent with EPA's policy objectives. 53 As such, ACC recommends the following definition be included in the final rule: Systematic review means that the evidence has been evaluated using a predefined, transparent, and reproducible process to identify, appraise, and synthesize the available body of evidence to answer a specific question. To ensure transparency, systematic reviews should include a Protocol that describes the specific question(s) that will be answered, the literature search strategy and plans for data collection, the methods for evaluating the quality and relevance of the data 48 Id. at 4. 49 See 82 Fed. Reg. at 7572. 50 See Chemical Safety Advisory Committee Minutes No. 2016-02, at 1. 51 See id. at 41. 52 Id. at 42. 53 See 82 Fed. Reg. at 7567 ("Due to the rapid advancement of the science of risk evaluation and the science and technology that inform risk evaluation, this proposed rule seeks to balance the need for the risk evaluation procedures to be transparent, without unduly restricting the specific science that will be used to conduct the evaluations, allowing the Agency flexibility to adapt and keep current with changing science as it conducts TSCA evaluations into the future." 20/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 (including the specific criteria that will be used), the approach for data analysis and integration and also the plans for peer review. Question 4. Manufacturer Requests EPA seeks comment on approaches to using its information gathering authorities (such as Section 8(a) or (d) authorities) to ensure that EPA has the most complete information to make its risk determination for a manufacturer requested evaluation. ACC urges EPA to appropriately use its authority. In its proposal, EPA indicates that it will not accept a manufacturer request where any of the relevant data is not in the possession of the manufacturer but is "with" another entity. EPA also requires a commitment that manufacturers provide all reasonably available information on hazard and exposure for all conditions of use, even if it is not publicly available. These 54 requirements will make it extraordinarily difficult, if not impossible, for a manufacturer to submit a request acceptable to EPA. ACC believes it is inappropriate for EPA to require that a single manufacturer contact and extract information outside its possession and control - and for which it has no legal authority to obtain - to be able to initiate a manufacturer requested risk evaluation. It is more appropriate that EPA use its Section 8 authority judiciously to collect information to be able to review and make a determination on a manufacturer requested risk evaluation. There are also instances where other governments (e.g., U.S. state or locality, U.S. government agency), universities, non-profits, or other entities may have information that the manufacturer is unable to obtain. There may even be cases where EPA itself has relevant information to inform a risk evaluation, and a manufacturer is incapable of obtaining it, providing it, or referencing it to EPA. These circumstances should not bar a manufacturer from initiating a request. Manufacturer requested evaluation are further discussed at Section VIII. Question 5. Peer Review EPA requests public comment on whether there are circumstances where peer review might not be warranted. When risk evaluations will lead to findings of unreasonable risk, which will then trigger risk management actions, the draft risk evaluation should always be peer reviewed. As conclusions of "no unreasonable risk" for specific conditions of use may likely be part of the risk evaluation, the science supporting these determinations should also be reviewed to ensure public confidence. Certainly for the first few years of LCSA implementation, as EPA applies new statutory requirements including the Section 26 scientific standards, risk evaluations will be highly influential. For highly influential scientific assessments, the most robust peer review standards 54 82 Fed. Reg. at 7569. 21/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 should be followed, including the need for panel review that strives to reach consensus. When the panel review is structured to provide individual opinions in a report to EPA, it resembles a letter review, which is appropriate when a draft document covers only one discipline. As the 55 draft risk evaluations developed under the LCSA will be complex multidisciplinary assessments which integrate both hazard and exposure information, robust expertise will be needed and a more rigorous review process is appropriate. 56 The EPA Science Advisory Board (SAB) strives 57 to reach consensus when conducting panel reviews. Reports in which only non-consensus opinions are provided will not be sufficiently helpful to the agency. They will not reflect scientific consensus and this will undermine both stakeholder and risk manager confidence, subsequently impacting the confidence in future risk management rulemakings. Thus we highly recommend that peer review reports to EPA should provide consensus opinions where possible, with the understanding that non-consensus opinions be included in the rare cases where consensus cannot be reached in a timely manner. ACC agrees with EPA's approach to release peer review plans along with the draft scoping documents. These peer review plans, which will be subject to public comment, should commit the agency to conducting panel reviews which strive to reach consensus. In addition, the peer review plan should confirm EPA's intent to share a draft charge with the public for comment and input. The peer review plan should also ensure that as part of the process the peer review panel will provide responses to the substantive scientific comments that are received from the public. Question 6. Reliance on Existing Guidance and Procedures for Conducting Risk Evaluations EPA is seeking input on its proposal to not "codify" any specific guidance, method or model in the regulatory text. As noted above, ACC believes that EPA must, at a minimum, include the definitions for WoE and systematic review in the regulatory text itself. The uses of these evaluation approaches (or methods) should be required for risk evaluations; these are cross- cutting approaches to evaluating evidence. While the type and quality of evidence available will change and evolve over time, what constitutes a good scientific approach has not changed over time and is not likely to change at any pace which could be characterized as "rapid." With respect to guidance, it is important that EPA not codify in the rule EPA's guidance documents, many of which are outdated. Much of what is in existing guidance includes default approaches that may be outdated (see discussion below) and many of the recommendations in guidance documents are situation-specific and cannot be universally applied. 58 Due to these limitations, neither should EPA cite a list of guidance documents in scoping documents. 55 See Office of Management and Budget (OMB), Final Information Quality Bulletin on Peer Review, 70 Fed. Reg. 2664 (Jan. 14, 2005). 56 See id. for further details on this distinction. 57 See EPA SAB, Advisory Committee Meetings and Report Development: Process for Public Involvement, available ("Ideally, the deliberative process should converge on some sort of consensus conclusion."). 58 For instance, EPA's 1991 Guidelines for Developmental Toxicity, available at: state, at 38, "for developmental toxic effects, a primary assumption is that a single exposure at a critical time in development may produce an adverse developmental effect, i.e., repeated exposure is not a necessary prerequisite for developmental toxicity to be manifested." This is an assumption that does not put the science first. If EPA were to invoke this guidance, risk 22/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 For instance, simply stating that EPA will follow the 2005 Guidelines for Carcinogen Risk Assessment (Cancer Guidelines) or other EPA guidelines does not provide the public with a sufficient level of specificity or granularity to understand what scientific approach and "accepted science policies" will be followed. As has been documented from years of peer review of some EPA hazard assessments (e.g., IRIS assessments), interpretation of even EPA's Cancer Guidelines can vary from expert to expert. For example, EPA's Cancer Guidelines invoke a linear extrapolation approach as a default in the absence of sufficient scientifically justifiable mode of action information, but there has been considerable variability in both EPA's and experts' determinations of when sufficient information exists to require non-linear modeling. For example, for 1,4-dioxane, Health Canada determined that a threshold approach is appropriate to use for characterizing risks to human health, 59 but, in evaluating essentially the same dataset, 60 EPA IRIS program discounted this mode of action and adopted a liner, no-threshold method. In addition, there are very few "accepted science policies" that all stakeholders can agree upon. For example: EPA's Cancer Guidelines specifically state that data should be used ahead of defaults; however, the members of the 2009 NAS Science and Decisions committee supported defaults as adequate and appropriate. EPA's Cancer Guidelines recommend using mode of action in a risk assessment; however, the members of the 2009 NAS Science and Decisions committee suggested that one of three dose-response approaches is typically going to be appropriate for use. This default approach recommended by these NAS committee members conflicts with EPA's own guidelines. Rather than merely point to guidance documents, EPA must be more specific with respsed to its process in the rule itself. In the appendices of ACC's August 24, 2016 comments to EPA to inform EPA's proposed risk evaluation framework rule, ACC provides detailed comments on the elements of specific and important steps within the risk evaluation process (e.g., hazard 61 identification, dose-response, risk characterization, peer review). EPA's scoping document should provide a level of specificity that addresses each of these elements. Just providing a list of EPA guidance documents or NAS reports is not only woefully inadequate, it is not sufficiently transparent for stakeholders to understand the actual scientific approach EPA intends to take to evaluate, analyze data and information, and then integrate all the evidence from mechanistic studies, animal toxicity tests, and human epidemiological investigations for WoE decision making. EPA also seeks input on whether current guidance documents are sufficient or if additional guidance documents that already exist, but are not noted on a particular EPA website, should be evaluations would not be consistent with best available science, which puts actual data and information ahead of default approaches. We also note that this is an example of a guidance document which should be updated. 59 See en.pdf. 60 61 See ACC comments, at Appendices B-E, available 2016-0400-0028. 23/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 added. 62 EPA's question is too narrow. EPA should ask the more important question regarding whether or not existing guidance is sufficient. Many of the guidance documents on the cited EPA website are extremely outdated, particularly considering the evolution of the science. For instance, EPA's Guidelines for Mutagenicity were last updated in 1986 and Guidelines for Developmental Toxicity are from 1991. These documents, and others, are over 20 years old and the science has evolved considerably over the last 20-30 years. In addition, when these documents were written they put in place policies which were driven by default assumptions based on a lack of data and a lack of understanding at that time of molecular biology, dosimetry, mode of action pathways, and toxicity mechanisms. Many of these "policies" are essentially default approaches that should be replaced by data and up-to-date 215 century knowledge. There are areas where current guidance is simply lacking. For instance, EPA's 2006 Framework for Assessing Health Risk of Environmental Exposures to Children states "the integration of toxicity data and children's exposure estimates is an area for which no guidance exists but is needed. As there will likely be cases where children are a susceptible population of concern, ,,63 this is certainly an area where guidance is needed. EPA states "EPA may also develop additional guidance(s) for risk evaluation in the future.">4 This statement is inadequate. Section 26(1) of the LCSA requires that by June 22, 2018 EPA develop any policies, procedures, and guidance necessary to carry out LCSA. This section also 65 requires that not later than June 22, 2021, and not less frequently than once every five years thereafter, EPA review the adequacy of policies, procedures and guidance. EPA should immediately begin to engage the public, in an official stakeholder process, to begin identifying areas where guidance should be developed. ACC also urges EPA to begin the process of evaluating all existing risk assessment related guidance documents for accuracy and relevance. Guidance documents that need to be updated should be identified and prioritized. There will likely be a significant amount of guidance that will need to be created and updated within the next two to five years. Assessments that are being started now should be consistent with these new and updated guidance documents. It is in the interest of all stakeholders that EPA's guidance be updated to reflect current science and that all assessments initiated after the enactment of LCSA be developed in compliance with updated guidance. Question 7. Interagency Collaboration As discussed in more detail in section I(E) of these comments and consistent with TSCA § 9, EPA is obligated to consult and coordinate with OSHA. EPA must describe the process it uses to consult with OSHA and the basis for EPA's findings in the scope of the risk evaluation. Ensuring appropriate collaboration with other agencies is as important as it is with OSHA. While EPA notes that it is committed to ensuring engagement and dialogue with interagency 62 See 82 Fed. Reg. at 7573. 63 See EPA 2006 Framework for Assessing Health Risk of Environmental Exposures to Children, at 6-2, available at 64 See 82 Fed. Reg. at 7570. 65 See TSCA Section 26(1). 24/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 experts, EPA is reluctant to provide a general description of the process and timing it will use. 66 EPA states that codifying a process in the regulation may limit potential interagency collaboration. ACC does not agree. Offering a general description of the interagency collaboration process in the rule would set a baseline which EPA would be free to exceed; it would not limit collaboration. More importantly, it helps explain to stakeholders which 67 agencies will be consulted and when. This transparency helps stakeholders understand what to expect, and it also helps them ensure that relevant information is shared among agencies. EPA should commit to ensuring an interagency coordination process as soon as a chemical is designated a high priority. At this early stage, interagency coordination should be used to inform the development of the scope document and then to review the scope document. In addition to including OSHA and the National Institute for Occupational Safety and Health (NIOSH) if workplace exposures may be considered, EPA should also include relevant agencies such as the Small Business Administration (SBA) Office of Advocacy and any other agencies that may be impacted by a particular condition of use (e.g., Department of Defense (DOD), Department of Energy (DOE), and the National Aeronautics and Space Administration (NASA)). EPA should also include other agencies that are members of the National Science and Technology Council's Committee on Environment, Natural Resources, and Sustainability's new Toxicity Assessment Committee. These agencies may likely have chemical-specific knowledge which may inform EPA's risk evaluation. Note, however, ACC does not support the use of the existing OSHA-MSHA-NIOSH-NIEHS-EPA (OMNE) committee. Use of this committee alone excludes important agencies with not only relevant expertise but also potential experience as users of chemicals, such as DOD, DOE, NASA and the SBA Office of Advocacy. Once the scoping step is complete, the full interagency group should be afforded an opportunity to review and comment on draft risk evaluations before they are released for public comment and before the assessment is finalized. While a risk evaluation is not a regulation, it is an influential science document that will inform regulatory activities, potentially at multiple agencies. As such, interagency review coordinated by OMB may be appropriate. With this approach, a neutral arbiter would be coordinating the review and ensuring that all interagency concerns are voiced and appropriately addressed. SPECIFIC RECOMMENDATIONS V. Timelines for Public Comment The proposed rule describes a risk evaluation process that has three opportunities for public comment. These include a period for comment on draft scoping evaluations, a period for comment on draft risk evaluations, and period to comment on manufacturer submitted requests for risk evaluations. ACC supports these public comment opportunities; however, longer 66 82 Fed. Reg. at 7573. 67 This is to be distinguished from a detailed recitation of when and how agency consultation will occur, which is not necessary. 25/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226

which section is for judicial review provisions of TSCA?

kzbn0226

kzbn0226_p14, kzbn0226_p15, kzbn0226_p16

Section 19

Data quality assurance to confirm identified conditions of use should occur before the scope is released, and certainly must occur before the scope is published as final. It is essential to the quality and integrity of the risk evaluation itself. Use of poor quality or outdated information to "identify" conditions of use taints the ultimate science-based decisions required in the risk evaluation and undermines the statutorily-required application of best available science to exposure assessment. EPA should describe the process it uses to identify conditions of use in the scope of the risk evaluation, including: - The source of the information about a condition of use; - The reliability of the source of information (e.g., whether the information is a first- party, anecdotal report (blog, social media post, product comment or review) or reported to a government or credible third party); - A description of the Agency's assessment of whether the identity of the source of information is known and verified; - A description of how the information source has been verified and validated, if appropriate; and - Whether the information is current. I. EPA Should Not "Lock Down" Conditions of Use at the Time of Scoping. The Agency simultaneously insists that it must consider "all conditions of use" in the scope of the risk evaluation, but that it will then not actually consider "all" conditions of use through use of a "lock down" procedure, freezing the conditions of use at the time of scoping. In other words, if a new condition of use is discovered or emerges after the scope is published, EPA will not include it in the risk evaluation, regardless of impact. EPA proposes this "lock down" to help the Agency meet its statutory deadlines.17 We think the Agency has this backwards. To stay on its statutory schedule - or to move more quickly - the best tool EPA has available is scoping (the ability to scope its risk evaluations in a flexible manner to focus on the conditions posing the greatest potential risk). EPA should propose a process that allows the Agency to take full advantage of this important tool on a case- by-case basis. EPA should be able to select the conditions of use that it believes are most relevant and meaningful to human health and environmental risk and proceed accordingly. Likewise, EPA should not commit to "locking" conditions of use at the time of scoping. If EPA has discretion to select the conditions of use that it will include in the scope of a risk evaluation - which it does - then EPA should have the companion ability to remove or add a condition of use 18 as circumstances warrant. For example, following scoping EPA might determine that reports of an isolated use were wrong - and that the condition of use does not actually exist. It would 17 This proposal leaves in limbo the regulatory status of conditions of use that are excluded from the review. If EPA were to implement this approach, it would also need to clarify that excluded conditions of use go back to the prioritization process, and would also need to clarify that they do not have a high priority designation. This approach is also completely inconsistent with EPA's approach taken for manufacturer-requested evaluations. 18 Similarly, EPA has a companion ability to redesignate low priorities or high priorities as warranted. 10/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 make little sense to continue evaluating that condition of use in the risk evaluation. Otherwise, EPA's final risk evaluation would be of suspect quality, integrity, and reliability. A better approach would be for EPA to articulate in the rule that after a scope is published, EPA retains discretion to modify it upon a showing of substantial need or changed circumstances, or is otherwise warranted because the addition or removal of a condition of use, properly substantiated, will significantly affect the conduct of the risk evaluation. J. EPA Must Remove the Comment-or-Waive (Issue Exhaustion) Proposal. EPA further proposes that it can keep risk evaluations on schedule, notwithstanding its proposal to include "all conditions of use" in every scope, by "providing opportunity for comment on the scoping document and specifying that any objections to the draft scope document are waived if not raised during this process. ",99 We urge the Agency to remove this issue exhaustion (waiver) requirement for several reasons. First, it places an unfair burden on the regulated community. A particular company may not be aware, or otherwise in a position to verify, particular end uses that the company does not support (i.e., a downstream value chain to which it does not sell). A company likewise may not be able to verify occurrences of a chemical from natural sources or the actions of third parties through combustion, spills and discharges, disposal, manufacturing practices or incidents, and the like. When EPA insists on including "all conditions of use" in the scope of a risk evaluation, it moves well past the "major" uses of a chemical and "major" sources of exposure to include fleeting, incidental, minor, isolated, or exceptional cases. Information about these "minor" sources of exposure may be well outside the first-hand knowledge of a manufacturer or processor, making it difficult or impossible to offer meaningful comment during the scoping period. Second, participation in notice and comment rulemaking is governed by the Administrative Procedure Act (APA) and the judicial review provisions of Section 19 of TSCA. Issue exhaustion requirements can be imposed by statute. Notably, there are only a few statutory issue exhaustion provisions in environmental statutes, the most notable of which is in Section 307(d)(7)(b) of the Clean Air Act. There are none in TSCA. Congress had the opportunity to impose an issue exhaustion requirement for the scope of a risk evaluation in LCSA amendment - and declined to do so. EPA cannot, by regulation, impose an issue exhaustion requirement that trumps the statutory rights and obligations of stakeholders under the APA and TSCA Section 19.20 Indeed, ACC believes a waiver provision such as that proposed by EPA may not meet Constitutional muster. Third, the proposal does not rationally advance its claimed purpose - to meet statutory risk evaluation deadlines. An issue exhaustion requirement is supposed to serve two purposes: it 19 82 Fed. Reg. at 7566. 20 Administrative issue exhaustion requirements are largely creatures of statute, and here we have no such statutory construct. While some agency regulations set out issue exhaustion requirements without a statutory mandate, these tend to be in administrative appeal situations or proceedings that are analogs to adversarial litigation. Notably, the LCSA amendment removed a procedure for formal TSCA hearings. 11/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 protects administrative agency authority and promotes judicial efficiency. But here, by 21 requiring inclusion of "all conditions of use" in scopes, the agency impairs the ability of industry to meaningfully comment in the limited time available. EPA seems to be of the view that it would rather include "too much" in a scope than inadvertently omit a condition of use and include "too little," but it is the overly broad, unrefined scope that expands the scale and cost of risk evaluations and slows them. EPA then ties its own hands by proposing to "lock down" overly broad scopes, impeding its ability to update or modify them later in the process. This does not advance efficiency or transparency in the regulatory process. EPA can avoid these inefficiencies by offering a simple process to identify those major, important conditions of use that are most relevant and meaningful to a high-quality risk evaluation - and to use flexibility in designing the scope accordingly. EPA should offer a rationale of why it selected the uses it did in the scope itself. II. EPA Must Describe How and When it Will Apply Section 26 Requirements to Risk Evaluations. Section 26(h) sets out scientific standards that apply to every "decision based on science" while EPA carries out risk evaluation under Section 6 [emphasis added]. Section 26(i) requires EPA to "make decisions" under Section 6 based on the weight of the scientific evidence [emphasis added]. A decision would include any judicially reviewable determination, but also any other decision that requires application of science or scientific judgment by the Agency. EPA should articulate in the risk evaluation rule, at a minimum, the key decision points that will require compliance with Section 26 requirements. These should include, but are not limited to: - The proposed scope and final scope for risk evaluation - Hazard assessment, including, where applicable, the likely operable mode of action - Exposure assessment - Selection and evaluation of technical procedures, measures, methods, protocols, methodologies, and models - Basis for scientific assumptions - Selection and evaluation of quality assurance procedures - Decisions regarding variability and uncertainty - Statistical methods - The draft and final risk evaluation EPA should document how it applied Section 26(h) and 26(i) requirements for each decision. 21 The issue exhaustion proposal does not advance judicial economy either. Determinations of no unreasonable risk, made by the Agency following the completion of the risk evaluation process, are judicially reviewable - but as a practical matter this means that a judicial challenge to such a determination would be unlikely to occur until years after the scope was published (and the risk evaluation completed). Changes to conditions of use, or errors in their identification and inclusion, may not all be evident at the time the scope is originally prepared and published, so applying issue exhaustion at this step makes little sense. 12/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226

When was the peer review report of this draft evaluation dated?

kzbn0226

kzbn0226_p24, kzbn0226_p25, kzbn0226_p26, kzbn0226_p27, kzbn0226_p28, kzbn0226_p29

August 22, 2016

review reliability is reduced and it cannot be referred to as systematic It is unhelpful to classify "narrative reviews" as systematic reviews. 48 EPA states that it has included systematic reviews in the past; however, it is not clear what exactly it has done and where these reviews can be found. 49 The last completed draft TSCA Work Plan risk evaluation was for 1-bromopropane. The executive summary of the peer review report of this draft evaluation, dated August 22, 2016, states: Committee members agreed that the 1-BP risk assessment (and other TSCA chemical assessments to be presented in the future) would benefit by adoption of systematic review practices to increase the transparency of how studies were selected and evaluated. For example, the Committee recommended that it should be explicitly stated what criteria were used to determine "the monitoring was adequate and of acceptable quality" (risk assessment document, page 44). The Committee also noted that it would be useful to reference studies that were evaluated but did not meet baseline criteria to inform the exposure estimates. 50 In addition, the peer review committee could not determine "what exact methodology was used to systematically rate, rank, and select studies to inform sections of the risk assessment. ",151 Peer 52 reviewers also could not find any ranking system developed for study quality. It is critically important that systematic review mean the same thing to all engaged stakeholders, including Agency staff and peer reviewers. ACC cannot envision any situation where a definition of systematic review would unduly restrict the specific science that can be used to conduct a risk evaluation. A systematic review process will allow EPA to be flexible and to adapt with changing science, assuming that the new science meets the necessary high quality standards that are required by the LCSA. Including a regulatory definition for systematic review is fully consistent with EPA's policy objectives. 53 As such, ACC recommends the following definition be included in the final rule: Systematic review means that the evidence has been evaluated using a predefined, transparent, and reproducible process to identify, appraise, and synthesize the available body of evidence to answer a specific question. To ensure transparency, systematic reviews should include a Protocol that describes the specific question(s) that will be answered, the literature search strategy and plans for data collection, the methods for evaluating the quality and relevance of the data 48 Id. at 4. 49 See 82 Fed. Reg. at 7572. 50 See Chemical Safety Advisory Committee Minutes No. 2016-02, at 1. 51 See id. at 41. 52 Id. at 42. 53 See 82 Fed. Reg. at 7567 ("Due to the rapid advancement of the science of risk evaluation and the science and technology that inform risk evaluation, this proposed rule seeks to balance the need for the risk evaluation procedures to be transparent, without unduly restricting the specific science that will be used to conduct the evaluations, allowing the Agency flexibility to adapt and keep current with changing science as it conducts TSCA evaluations into the future." 20/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 (including the specific criteria that will be used), the approach for data analysis and integration and also the plans for peer review. Question 4. Manufacturer Requests EPA seeks comment on approaches to using its information gathering authorities (such as Section 8(a) or (d) authorities) to ensure that EPA has the most complete information to make its risk determination for a manufacturer requested evaluation. ACC urges EPA to appropriately use its authority. In its proposal, EPA indicates that it will not accept a manufacturer request where any of the relevant data is not in the possession of the manufacturer but is "with" another entity. EPA also requires a commitment that manufacturers provide all reasonably available information on hazard and exposure for all conditions of use, even if it is not publicly available. These 54 requirements will make it extraordinarily difficult, if not impossible, for a manufacturer to submit a request acceptable to EPA. ACC believes it is inappropriate for EPA to require that a single manufacturer contact and extract information outside its possession and control - and for which it has no legal authority to obtain - to be able to initiate a manufacturer requested risk evaluation. It is more appropriate that EPA use its Section 8 authority judiciously to collect information to be able to review and make a determination on a manufacturer requested risk evaluation. There are also instances where other governments (e.g., U.S. state or locality, U.S. government agency), universities, non-profits, or other entities may have information that the manufacturer is unable to obtain. There may even be cases where EPA itself has relevant information to inform a risk evaluation, and a manufacturer is incapable of obtaining it, providing it, or referencing it to EPA. These circumstances should not bar a manufacturer from initiating a request. Manufacturer requested evaluation are further discussed at Section VIII. Question 5. Peer Review EPA requests public comment on whether there are circumstances where peer review might not be warranted. When risk evaluations will lead to findings of unreasonable risk, which will then trigger risk management actions, the draft risk evaluation should always be peer reviewed. As conclusions of "no unreasonable risk" for specific conditions of use may likely be part of the risk evaluation, the science supporting these determinations should also be reviewed to ensure public confidence. Certainly for the first few years of LCSA implementation, as EPA applies new statutory requirements including the Section 26 scientific standards, risk evaluations will be highly influential. For highly influential scientific assessments, the most robust peer review standards 54 82 Fed. Reg. at 7569. 21/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 should be followed, including the need for panel review that strives to reach consensus. When the panel review is structured to provide individual opinions in a report to EPA, it resembles a letter review, which is appropriate when a draft document covers only one discipline. As the 55 draft risk evaluations developed under the LCSA will be complex multidisciplinary assessments which integrate both hazard and exposure information, robust expertise will be needed and a more rigorous review process is appropriate. 56 The EPA Science Advisory Board (SAB) strives 57 to reach consensus when conducting panel reviews. Reports in which only non-consensus opinions are provided will not be sufficiently helpful to the agency. They will not reflect scientific consensus and this will undermine both stakeholder and risk manager confidence, subsequently impacting the confidence in future risk management rulemakings. Thus we highly recommend that peer review reports to EPA should provide consensus opinions where possible, with the understanding that non-consensus opinions be included in the rare cases where consensus cannot be reached in a timely manner. ACC agrees with EPA's approach to release peer review plans along with the draft scoping documents. These peer review plans, which will be subject to public comment, should commit the agency to conducting panel reviews which strive to reach consensus. In addition, the peer review plan should confirm EPA's intent to share a draft charge with the public for comment and input. The peer review plan should also ensure that as part of the process the peer review panel will provide responses to the substantive scientific comments that are received from the public. Question 6. Reliance on Existing Guidance and Procedures for Conducting Risk Evaluations EPA is seeking input on its proposal to not "codify" any specific guidance, method or model in the regulatory text. As noted above, ACC believes that EPA must, at a minimum, include the definitions for WoE and systematic review in the regulatory text itself. The uses of these evaluation approaches (or methods) should be required for risk evaluations; these are cross- cutting approaches to evaluating evidence. While the type and quality of evidence available will change and evolve over time, what constitutes a good scientific approach has not changed over time and is not likely to change at any pace which could be characterized as "rapid." With respect to guidance, it is important that EPA not codify in the rule EPA's guidance documents, many of which are outdated. Much of what is in existing guidance includes default approaches that may be outdated (see discussion below) and many of the recommendations in guidance documents are situation-specific and cannot be universally applied. 58 Due to these limitations, neither should EPA cite a list of guidance documents in scoping documents. 55 See Office of Management and Budget (OMB), Final Information Quality Bulletin on Peer Review, 70 Fed. Reg. 2664 (Jan. 14, 2005). 56 See id. for further details on this distinction. 57 See EPA SAB, Advisory Committee Meetings and Report Development: Process for Public Involvement, available ("Ideally, the deliberative process should converge on some sort of consensus conclusion."). 58 For instance, EPA's 1991 Guidelines for Developmental Toxicity, available at: state, at 38, "for developmental toxic effects, a primary assumption is that a single exposure at a critical time in development may produce an adverse developmental effect, i.e., repeated exposure is not a necessary prerequisite for developmental toxicity to be manifested." This is an assumption that does not put the science first. If EPA were to invoke this guidance, risk 22/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 For instance, simply stating that EPA will follow the 2005 Guidelines for Carcinogen Risk Assessment (Cancer Guidelines) or other EPA guidelines does not provide the public with a sufficient level of specificity or granularity to understand what scientific approach and "accepted science policies" will be followed. As has been documented from years of peer review of some EPA hazard assessments (e.g., IRIS assessments), interpretation of even EPA's Cancer Guidelines can vary from expert to expert. For example, EPA's Cancer Guidelines invoke a linear extrapolation approach as a default in the absence of sufficient scientifically justifiable mode of action information, but there has been considerable variability in both EPA's and experts' determinations of when sufficient information exists to require non-linear modeling. For example, for 1,4-dioxane, Health Canada determined that a threshold approach is appropriate to use for characterizing risks to human health, 59 but, in evaluating essentially the same dataset, 60 EPA IRIS program discounted this mode of action and adopted a liner, no-threshold method. In addition, there are very few "accepted science policies" that all stakeholders can agree upon. For example: EPA's Cancer Guidelines specifically state that data should be used ahead of defaults; however, the members of the 2009 NAS Science and Decisions committee supported defaults as adequate and appropriate. EPA's Cancer Guidelines recommend using mode of action in a risk assessment; however, the members of the 2009 NAS Science and Decisions committee suggested that one of three dose-response approaches is typically going to be appropriate for use. This default approach recommended by these NAS committee members conflicts with EPA's own guidelines. Rather than merely point to guidance documents, EPA must be more specific with respsed to its process in the rule itself. In the appendices of ACC's August 24, 2016 comments to EPA to inform EPA's proposed risk evaluation framework rule, ACC provides detailed comments on the elements of specific and important steps within the risk evaluation process (e.g., hazard 61 identification, dose-response, risk characterization, peer review). EPA's scoping document should provide a level of specificity that addresses each of these elements. Just providing a list of EPA guidance documents or NAS reports is not only woefully inadequate, it is not sufficiently transparent for stakeholders to understand the actual scientific approach EPA intends to take to evaluate, analyze data and information, and then integrate all the evidence from mechanistic studies, animal toxicity tests, and human epidemiological investigations for WoE decision making. EPA also seeks input on whether current guidance documents are sufficient or if additional guidance documents that already exist, but are not noted on a particular EPA website, should be evaluations would not be consistent with best available science, which puts actual data and information ahead of default approaches. We also note that this is an example of a guidance document which should be updated. 59 See en.pdf. 60 61 See ACC comments, at Appendices B-E, available 2016-0400-0028. 23/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 added. 62 EPA's question is too narrow. EPA should ask the more important question regarding whether or not existing guidance is sufficient. Many of the guidance documents on the cited EPA website are extremely outdated, particularly considering the evolution of the science. For instance, EPA's Guidelines for Mutagenicity were last updated in 1986 and Guidelines for Developmental Toxicity are from 1991. These documents, and others, are over 20 years old and the science has evolved considerably over the last 20-30 years. In addition, when these documents were written they put in place policies which were driven by default assumptions based on a lack of data and a lack of understanding at that time of molecular biology, dosimetry, mode of action pathways, and toxicity mechanisms. Many of these "policies" are essentially default approaches that should be replaced by data and up-to-date 215 century knowledge. There are areas where current guidance is simply lacking. For instance, EPA's 2006 Framework for Assessing Health Risk of Environmental Exposures to Children states "the integration of toxicity data and children's exposure estimates is an area for which no guidance exists but is needed. As there will likely be cases where children are a susceptible population of concern, ,,63 this is certainly an area where guidance is needed. EPA states "EPA may also develop additional guidance(s) for risk evaluation in the future.">4 This statement is inadequate. Section 26(1) of the LCSA requires that by June 22, 2018 EPA develop any policies, procedures, and guidance necessary to carry out LCSA. This section also 65 requires that not later than June 22, 2021, and not less frequently than once every five years thereafter, EPA review the adequacy of policies, procedures and guidance. EPA should immediately begin to engage the public, in an official stakeholder process, to begin identifying areas where guidance should be developed. ACC also urges EPA to begin the process of evaluating all existing risk assessment related guidance documents for accuracy and relevance. Guidance documents that need to be updated should be identified and prioritized. There will likely be a significant amount of guidance that will need to be created and updated within the next two to five years. Assessments that are being started now should be consistent with these new and updated guidance documents. It is in the interest of all stakeholders that EPA's guidance be updated to reflect current science and that all assessments initiated after the enactment of LCSA be developed in compliance with updated guidance. Question 7. Interagency Collaboration As discussed in more detail in section I(E) of these comments and consistent with TSCA § 9, EPA is obligated to consult and coordinate with OSHA. EPA must describe the process it uses to consult with OSHA and the basis for EPA's findings in the scope of the risk evaluation. Ensuring appropriate collaboration with other agencies is as important as it is with OSHA. While EPA notes that it is committed to ensuring engagement and dialogue with interagency 62 See 82 Fed. Reg. at 7573. 63 See EPA 2006 Framework for Assessing Health Risk of Environmental Exposures to Children, at 6-2, available at 64 See 82 Fed. Reg. at 7570. 65 See TSCA Section 26(1). 24/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 experts, EPA is reluctant to provide a general description of the process and timing it will use. 66 EPA states that codifying a process in the regulation may limit potential interagency collaboration. ACC does not agree. Offering a general description of the interagency collaboration process in the rule would set a baseline which EPA would be free to exceed; it would not limit collaboration. More importantly, it helps explain to stakeholders which 67 agencies will be consulted and when. This transparency helps stakeholders understand what to expect, and it also helps them ensure that relevant information is shared among agencies. EPA should commit to ensuring an interagency coordination process as soon as a chemical is designated a high priority. At this early stage, interagency coordination should be used to inform the development of the scope document and then to review the scope document. In addition to including OSHA and the National Institute for Occupational Safety and Health (NIOSH) if workplace exposures may be considered, EPA should also include relevant agencies such as the Small Business Administration (SBA) Office of Advocacy and any other agencies that may be impacted by a particular condition of use (e.g., Department of Defense (DOD), Department of Energy (DOE), and the National Aeronautics and Space Administration (NASA)). EPA should also include other agencies that are members of the National Science and Technology Council's Committee on Environment, Natural Resources, and Sustainability's new Toxicity Assessment Committee. These agencies may likely have chemical-specific knowledge which may inform EPA's risk evaluation. Note, however, ACC does not support the use of the existing OSHA-MSHA-NIOSH-NIEHS-EPA (OMNE) committee. Use of this committee alone excludes important agencies with not only relevant expertise but also potential experience as users of chemicals, such as DOD, DOE, NASA and the SBA Office of Advocacy. Once the scoping step is complete, the full interagency group should be afforded an opportunity to review and comment on draft risk evaluations before they are released for public comment and before the assessment is finalized. While a risk evaluation is not a regulation, it is an influential science document that will inform regulatory activities, potentially at multiple agencies. As such, interagency review coordinated by OMB may be appropriate. With this approach, a neutral arbiter would be coordinating the review and ensuring that all interagency concerns are voiced and appropriately addressed. SPECIFIC RECOMMENDATIONS V. Timelines for Public Comment The proposed rule describes a risk evaluation process that has three opportunities for public comment. These include a period for comment on draft scoping evaluations, a period for comment on draft risk evaluations, and period to comment on manufacturer submitted requests for risk evaluations. ACC supports these public comment opportunities; however, longer 66 82 Fed. Reg. at 7573. 67 This is to be distinguished from a detailed recitation of when and how agency consultation will occur, which is not necessary. 25/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226

Which section is for issue exhaustion provisions in environmentional statues?

kzbn0226

kzbn0226_p14, kzbn0226_p15, kzbn0226_p16

Section 307(d)(7)(b), Section 307(d)(7)(b) of the Clean Air Act

Data quality assurance to confirm identified conditions of use should occur before the scope is released, and certainly must occur before the scope is published as final. It is essential to the quality and integrity of the risk evaluation itself. Use of poor quality or outdated information to "identify" conditions of use taints the ultimate science-based decisions required in the risk evaluation and undermines the statutorily-required application of best available science to exposure assessment. EPA should describe the process it uses to identify conditions of use in the scope of the risk evaluation, including: - The source of the information about a condition of use; - The reliability of the source of information (e.g., whether the information is a first- party, anecdotal report (blog, social media post, product comment or review) or reported to a government or credible third party); - A description of the Agency's assessment of whether the identity of the source of information is known and verified; - A description of how the information source has been verified and validated, if appropriate; and - Whether the information is current. I. EPA Should Not "Lock Down" Conditions of Use at the Time of Scoping. The Agency simultaneously insists that it must consider "all conditions of use" in the scope of the risk evaluation, but that it will then not actually consider "all" conditions of use through use of a "lock down" procedure, freezing the conditions of use at the time of scoping. In other words, if a new condition of use is discovered or emerges after the scope is published, EPA will not include it in the risk evaluation, regardless of impact. EPA proposes this "lock down" to help the Agency meet its statutory deadlines.17 We think the Agency has this backwards. To stay on its statutory schedule - or to move more quickly - the best tool EPA has available is scoping (the ability to scope its risk evaluations in a flexible manner to focus on the conditions posing the greatest potential risk). EPA should propose a process that allows the Agency to take full advantage of this important tool on a case- by-case basis. EPA should be able to select the conditions of use that it believes are most relevant and meaningful to human health and environmental risk and proceed accordingly. Likewise, EPA should not commit to "locking" conditions of use at the time of scoping. If EPA has discretion to select the conditions of use that it will include in the scope of a risk evaluation - which it does - then EPA should have the companion ability to remove or add a condition of use 18 as circumstances warrant. For example, following scoping EPA might determine that reports of an isolated use were wrong - and that the condition of use does not actually exist. It would 17 This proposal leaves in limbo the regulatory status of conditions of use that are excluded from the review. If EPA were to implement this approach, it would also need to clarify that excluded conditions of use go back to the prioritization process, and would also need to clarify that they do not have a high priority designation. This approach is also completely inconsistent with EPA's approach taken for manufacturer-requested evaluations. 18 Similarly, EPA has a companion ability to redesignate low priorities or high priorities as warranted. 10/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 make little sense to continue evaluating that condition of use in the risk evaluation. Otherwise, EPA's final risk evaluation would be of suspect quality, integrity, and reliability. A better approach would be for EPA to articulate in the rule that after a scope is published, EPA retains discretion to modify it upon a showing of substantial need or changed circumstances, or is otherwise warranted because the addition or removal of a condition of use, properly substantiated, will significantly affect the conduct of the risk evaluation. J. EPA Must Remove the Comment-or-Waive (Issue Exhaustion) Proposal. EPA further proposes that it can keep risk evaluations on schedule, notwithstanding its proposal to include "all conditions of use" in every scope, by "providing opportunity for comment on the scoping document and specifying that any objections to the draft scope document are waived if not raised during this process. ",99 We urge the Agency to remove this issue exhaustion (waiver) requirement for several reasons. First, it places an unfair burden on the regulated community. A particular company may not be aware, or otherwise in a position to verify, particular end uses that the company does not support (i.e., a downstream value chain to which it does not sell). A company likewise may not be able to verify occurrences of a chemical from natural sources or the actions of third parties through combustion, spills and discharges, disposal, manufacturing practices or incidents, and the like. When EPA insists on including "all conditions of use" in the scope of a risk evaluation, it moves well past the "major" uses of a chemical and "major" sources of exposure to include fleeting, incidental, minor, isolated, or exceptional cases. Information about these "minor" sources of exposure may be well outside the first-hand knowledge of a manufacturer or processor, making it difficult or impossible to offer meaningful comment during the scoping period. Second, participation in notice and comment rulemaking is governed by the Administrative Procedure Act (APA) and the judicial review provisions of Section 19 of TSCA. Issue exhaustion requirements can be imposed by statute. Notably, there are only a few statutory issue exhaustion provisions in environmental statutes, the most notable of which is in Section 307(d)(7)(b) of the Clean Air Act. There are none in TSCA. Congress had the opportunity to impose an issue exhaustion requirement for the scope of a risk evaluation in LCSA amendment - and declined to do so. EPA cannot, by regulation, impose an issue exhaustion requirement that trumps the statutory rights and obligations of stakeholders under the APA and TSCA Section 19.20 Indeed, ACC believes a waiver provision such as that proposed by EPA may not meet Constitutional muster. Third, the proposal does not rationally advance its claimed purpose - to meet statutory risk evaluation deadlines. An issue exhaustion requirement is supposed to serve two purposes: it 19 82 Fed. Reg. at 7566. 20 Administrative issue exhaustion requirements are largely creatures of statute, and here we have no such statutory construct. While some agency regulations set out issue exhaustion requirements without a statutory mandate, these tend to be in administrative appeal situations or proceedings that are analogs to adversarial litigation. Notably, the LCSA amendment removed a procedure for formal TSCA hearings. 11/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 protects administrative agency authority and promotes judicial efficiency. But here, by 21 requiring inclusion of "all conditions of use" in scopes, the agency impairs the ability of industry to meaningfully comment in the limited time available. EPA seems to be of the view that it would rather include "too much" in a scope than inadvertently omit a condition of use and include "too little," but it is the overly broad, unrefined scope that expands the scale and cost of risk evaluations and slows them. EPA then ties its own hands by proposing to "lock down" overly broad scopes, impeding its ability to update or modify them later in the process. This does not advance efficiency or transparency in the regulatory process. EPA can avoid these inefficiencies by offering a simple process to identify those major, important conditions of use that are most relevant and meaningful to a high-quality risk evaluation - and to use flexibility in designing the scope accordingly. EPA should offer a rationale of why it selected the uses it did in the scope itself. II. EPA Must Describe How and When it Will Apply Section 26 Requirements to Risk Evaluations. Section 26(h) sets out scientific standards that apply to every "decision based on science" while EPA carries out risk evaluation under Section 6 [emphasis added]. Section 26(i) requires EPA to "make decisions" under Section 6 based on the weight of the scientific evidence [emphasis added]. A decision would include any judicially reviewable determination, but also any other decision that requires application of science or scientific judgment by the Agency. EPA should articulate in the risk evaluation rule, at a minimum, the key decision points that will require compliance with Section 26 requirements. These should include, but are not limited to: - The proposed scope and final scope for risk evaluation - Hazard assessment, including, where applicable, the likely operable mode of action - Exposure assessment - Selection and evaluation of technical procedures, measures, methods, protocols, methodologies, and models - Basis for scientific assumptions - Selection and evaluation of quality assurance procedures - Decisions regarding variability and uncertainty - Statistical methods - The draft and final risk evaluation EPA should document how it applied Section 26(h) and 26(i) requirements for each decision. 21 The issue exhaustion proposal does not advance judicial economy either. Determinations of no unreasonable risk, made by the Agency following the completion of the risk evaluation process, are judicially reviewable - but as a practical matter this means that a judicial challenge to such a determination would be unlikely to occur until years after the scope was published (and the risk evaluation completed). Changes to conditions of use, or errors in their identification and inclusion, may not all be evident at the time the scope is originally prepared and published, so applying issue exhaustion at this step makes little sense. 12/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226

Define Foreseeability.

kzbn0226

kzbn0226_p8, kzbn0226_p9, kzbn0226_p10, kzbn0226_p11, kzbn0226_p12

is "the determinant for the limits of duty under a conventional risk analysis"

At the same time, risk evaluations must meet Section 26 quality requirements, using best available science and weight of the evidence review. To achieve the throughput and quality requirements for risk evaluation, Congress designed a process to allow chemicals to be systematically prioritized and evaluated. This design is apparent throughout LCSA. It begins with a reset of the TSCA Inventory -- the full catalog of chemicals in commerce. LCSA requires that the TSCA Inventory be sorted, so that chemicals that are currently active in commerce are separated from those not currently used. This sorting enables EPA to identify only those chemicals that are active in commerce for prioritization and risk evaluation. This statutory design makes eminent sense: it allows EPA to focus resources for its multi-year, time- and resource-intensive risk evaluations on chemicals that are actually being used. From this initial focusing step, LCSA repeatedly requires EPA to further refine its focus throughout prioritization and risk evaluation. EPA must next implement a prioritization process, which further refines the active chemicals in commerce to those that are high priority for risk evaluation. These chemicals must then undergo a scoping exercise to further focus on the conditions of use that will be the subject of the risk evaluation. In implementing LCSA, EPA has indicated that it intends to identify and consider all conditions of use of a chemical in all risk evaluations, all the time. This interpretation cannot be reconciled with EPA's statutory directive to achieve throughput and quality in risk evaluations. It is inconsistent with the design of the statute; inconsistent with congressional intent to give EPA the flexibility to make case-by-case scoping decisions; and undermines statutory purposes and the effective function of the statute itself. A. There is No Statutory Mandate to Include All Conditions of Use in the Scope of Every Risk Evaluation Under TSCA § 6(b). EPA notes in the preamble that, prior to enactment of LCSA, the Agency was "free to and did" conduct risk assessments on selected uses of chemical substances, but that it now interprets the amended statute as "requiring that risk evaluations encompass all manufacture, processing, distribution in commerce, use, and disposal activities [t]hat is to say, a risk evaluation must encompass all known, intended, and reasonably foreseen activities associated with the subject chemical substance" [emphasis added]. ACC strongly disagrees with this interpretation -- EPA 3 is reading a mandate into the statute where none exists. Rather, Congress equipped EPA with the tools to scope risk evaluations in order to achieve statutory purposes, and EPA should use those tools accordingly. The statute does not require EPA to include "all" conditions of use in any particular risk evaluation, or in each and every risk evaluation. Nowhere in the statute does Congress modify "conditions of use" with "all." EPA has the discretion to interpret the term. It cannot apply this discretion in such a manner, however, as to undercut the operation of the statute or to make it impossible for EPA to meet its statutory objectives of throughput and quality. 3 82 Fed. Reg. at 7565. 4/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 B. Scoping Necessarily Requires EPA to Select Relevant Conditions of Use for Inclusion, and Scope Accordingly. LCSA requires EPA to conduct risk evaluations to determine whether a chemical substance presents an unreasonable risk of injury to health or the environment under certain circumstances called "conditions of use. ,,4 Conditions of use are defined as "the circumstances, as determined by [EPA], under which a chemical substance is intended, known, or reasonably foreseen to be manufactured, processed, distributed in commerce, used, or disposed of." The legislative text did not direct EPA to include "all" conditions of use. The statute creates a scoping process that precedes the risk evaluation itself. For a scoping process to have any reasonable meaning, it must actually "scope" -- on a case by case basis, it must determine which conditions of use are appropriate for inclusion because they are relevant and meaningful to the risk evaluation process. EPA's plan to universally include "all conditions of use" all the time in every risk evaluation is contrary to common sense, conflicts with and undermines the statutory design of TSCA as amended by LCSA, and would lead to an absurd result. 5 EPA's preamble acknowledges the value of scoping (also called problem formulation) in citing the National Academy of Sciences (NAS) National Research Council (NRC) Science and Decisions Report. The NAS report recommended that EPA focus on the "important roles of scoping or problem formulation so that a risk assessment will serve a specific and documented purpose" [emphasis added]. The preamble cites an additional NAS recommendation to EPA 6 that the Agency "develop risk assessments that are well-tailored to the problems and decisions at hand so that they can inform the decision-making process in the most meaningful way." We agree, and urge the agency to apply these recommendations to the scoping process. C. The Legislative Text Acknowledges that What EPA Will Consider and Include in a Given Scope Necessarily Varies. The scoping provision requires identification of those conditions EPA "expects to consider," a clause that would be unnecessary if EPA were directed to simply include "all" conditions of use in a risk evaluation. The future tense also acknowledges that EPA might subsequently change 8 4 TSCA § 6(b)(4)(A). 5 See Massachusetts v. EPA, 549 U.S. 497, 531, 535 (2007) addressing EPA's application of its Chevron deference to particular statutory constructions: EPA not required to regulate "all" greenhouse gases as "air pollutants" everywhere that term appears in the statute; EPA must ground its reasons for action or inaction in the statute; agency regulation cannot conflict with statutory design, and law cannot be read to compel EPA to regulate in a manner contrary to "common sense." 6 82 Fed. Reg. at 7265. 7 TSCA § 6(b)(3)(D). 8 Before LCSA was enacted, EPA had published multiple problem formulations under the TSCA Work Plan. EPA explained that its problem formulations served as a means for explaining the scope of a risk assessment: "A problem formulation and initial assessment document will serve to inform the public and other interested stakeholders about EPA's initial scoping of findings and plan for any further risk assessment. Problem formulation and initial assessment is the analytical phase of the assessment in which the purpose for the assessment is articulated, the problem defined and a plan for analyzing and characterizing risk is determined." Many of those completed problem formulations were for limited conditions of use. Like other aspects of the TSCA Work Plan, Congress 5/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 its position with respect to what conditions of use to include or exclude. Notably, this construction affords EPA the discretion to include all conditions of use where necessary. This is consistent with congressional intent. Speaking about the compromise bill that was signed into law, Senator Vitter said that EPA "is given the discretion to determine the conditions of use that the Agency will address in its evaluation of the priority chemical." This discretion and flexibility "assures that the Agency's focus is on conditions of use that raise the greatest potential for risk" particularly given that "many TSCA chemicals have multiple uses - industrial, commercial and consumer uses" and EPA is "well aware that some categories of uses pose greater potential for exposure than others and that the risks from many categories of uses are deemed negligible or already well controlled."9 D. EPA Should Expressly Exclude Substances that Are Not Regulated Under TSCA from the Scope of Risk Evaluations. TSCA excludes a number of chemical categories from its statutory scope. LCSA did not change these; accordingly, these categories should not be considered for inclusion in any risk evaluation undertaken pursuant to Section 6: (i) [a]ny mixture, (ii) any pesticide (as defined in the Federal Insecticide, Fungicide, and Rodenticide Act) when manufactured, processed, or distributed in commerce for use as a pesticide; (iii) tobacco or any tobacco product, (iv) any source material, special nuclear material, or byproduct material (as such terms are defined in the Atomic Energy Act of 1954 and regulations issued under such Act), (v) any article the sale of which is subject to the tax imposed by section 4181 of the Internal Revenue Code of 1986 [i.e., firearms and ammunition] (vi) any food, food additive, drug, cosmetic, or device (as such terms are defined in section 201 of the Federal Food, Drug, and Cosmetic Act) when manufactured, processed, or distributed in commerce for use as a food, food additive, drug, cosmetic, or device. The risk evaluation rule should expressly clarify that because these categories are excluded from the definition of "chemical substance" under TSCA, and they are outside EPA's legislative authority to regulate, they therefore excluded from the scope of risk evaluations under Section 6. contemplated that problem formulations from the TSCA Work Plan would serve as the model for EPA actions under the amended TSCA. In this case, the problem formulations were to be the model for the scoping exercise under Section 6(b)(4)(D). This is a strong indication that Congress authorized EPA to determine which conditions of use it would evaluate in a risk evaluation by defining the scope appropriately. 9 Senate Congressional Record, June 7, 2016, at S3519; available at also clarifies that unreasonable risk/no unreasonable risk determinations made pursuant to the risk evaluation are made use-by-use: "[T]o be clear, every condition of use identified by the Administrator in the scope of the risk evaluation must, and will be either found to present or not present an unreasonable risk." Id. at S3520. 6/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 Likewise, the rule should clarify that chemical uses within these exclusions are "conditions of use" that are outside the scope of any Section 6 risk evaluation. In addition to TSCA, which was modernized by the passage of LCSA in 2016, there is a network of statutes in place regulating the safety of chemicals in various venues and applications. Several other federal statutes are in place to regulate chemicals in products and during activities such as workplace manufacturing. Notably, the Consumer Protection Act, Consumer Product Safety Improvement Act, and the Federal Hazardous Substances Act regulate chemicals in a suite of consumer products, including children's products and toys, and the Occupational Safety and Health Act (OSH Act) regulates chemicals in the workplace. Chemicals in uses regulated by other federal laws and agencies are often referred to as "non- TSCA" uses. EPA should not include these uses in its risk evaluations under TSCA. In rare cases where inclusion might be justified, the Agency should establish criteria to justify including non-TSCA uses in its risk evaluations and should articulate the steps it will follow to ensure adequate interagency consultation and review at the scoping stage. We discuss this topic in more detail below. E. EPA Should Generally Exclude OSHA-Regulated Uses from the Scopes of TSCA Risk Evaluations. Although LCSA specifically includes "workers" as a possible category of "potentially exposed or susceptible subpopulation," it does not designate "workers" as a default category. Any consideration of worker exposure must begin with the recognition that worker exposures are regulated under the OSH Act. Given that Occupational Safety and Health Administration (OSHA) standards are in place for the very purpose of regulating risk to worker populations, it should be the unusual case where unreasonable risk may present to a worker population under conditions of use (e.g., use of personal protective equipment). Importantly, although Congress recognizes under LCSA that it may be appropriate, under particular circumstances, for EPA to designate workers as a potentially exposed or susceptible subpopulation under TSCA, and to regulate workplace exposures, Congress did not amend the OSH Act at the same time that it amended TSCA. Congress also left Section 9(d) of TSCA intact. This section requires EPA to consult and coordinate with OSHA "for the purpose of achieving the maximum enforcement of [TSCA] while imposing the least burdens of duplicative requirements on those subject to [TSCA] and for other purposes.' EPA should ensure that this consultation occurs before risk evaluations are scoped; in cases where worker exposures do not present a significant risk of health impairment under current conditions of use, EPA should decline to include worker populations within the scope of the risk assessment as unduly burdensome and duplicative. This process will help focus risk evaluations and reduce the resource cost to the Agency. Following this consultation, if OSHA agrees that EPA-led risk evaluation considering worker exposures is necessary (and not otherwise duplicative), EPA should describe the process it used to consult with OSHA and the basis for its findings in the scope of the risk evaluation. 7/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 F. EPA Should Generally Exclude Low Exposure Conditions of Use from the Scopes of TSCA Risk Evaluations. In the prioritization process, certain scenarios may emerge that are low- - to no-exposure. An example is a closed system, intermediate chemical manufacture or processing at an industrial site, where worker exposure is well documented and controlled, and does not present a significant risk. A second example would be de minimis levels of an impurity in a consumer product, where the levels and variability are well documented and well understood, and exposures are so low as not to present a significant risk. In such cases, it should be apparent in the prioritization process or before scoping that these use scenarios can readily be excluded from the scope of the risk evaluation. G. EPA Should Apply the "Reasonably Foreseen" Provision as a Focusing Tool to Help Tailor the Scope of Risk Evaluations - Not to Expand Them. The statutory definition of "conditions of use" is "the circumstances, as determined by the Administrator, under which a chemical substances is intended, known, or reasonably foreseen to be manufactured, processed, distributed in commerce, used or disposed of.">10 The phrase "intended, known, or reasonably foreseen" limits the conditions of use that may be identified and included in a scope. Clearly, if a particular use is not intended, known, or reasonably foreseen, it is not a statutory "condition of use" and may not be included within the scope of a risk evaluation. The term "intended" is generally well understood to mean intended by the manufacturer or processor. Intention can be demonstrated through express (e.g., a statement to that effect in a premanufacture notice) or implied evidence (e.g., marketing materials that imply a potential application for the chemical). The term "known" is often considered a backstop for the term "intended," in that manufacturers or processors may not "intend" or support a particular downstream use for a chemical but may have actual or imputed knowledge that a chemical is being used in that application. The definition of "conditions of use" also includes the term "reasonably foreseen." The concept of reasonable foreseeability is well understood in American and western11 tort law. Foreseeability is "the determinant for the limits of duty under a conventional risk analysis" [emphasis added]. Foreseeability is modified by "reasonably," which makes clear that not 12 every conceivable or speculative use is included. Product misuses and illegal uses, and manufacturing that disregards legal and industrial hygiene requirements, are not "reasonable" and thus not "reasonably foreseen." 10 TSCA §3(4). 11 See, e.g., ANNEXURE T, The Concept of Limited Liability, Existing Law and Rationale (Australia), referring to the limiting tests of reasonable foreseeability and proximity, available at htp:/lwww.dpc.nsw.gov.au data/assets/odf.file/0012/11406/T.pdi 12 Tyrus V. Dahl Jr., Strict Products Liability: The Irrelevance of Foreseeability and Related Negligence Concepts, 14 Tulsa L. J. 338, 343 (1978). 8/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226

which act is for section 307(d)(7)(b)?

kzbn0226

kzbn0226_p14, kzbn0226_p15, kzbn0226_p16

the clean air act, Clean Air Act

Data quality assurance to confirm identified conditions of use should occur before the scope is released, and certainly must occur before the scope is published as final. It is essential to the quality and integrity of the risk evaluation itself. Use of poor quality or outdated information to "identify" conditions of use taints the ultimate science-based decisions required in the risk evaluation and undermines the statutorily-required application of best available science to exposure assessment. EPA should describe the process it uses to identify conditions of use in the scope of the risk evaluation, including: - The source of the information about a condition of use; - The reliability of the source of information (e.g., whether the information is a first- party, anecdotal report (blog, social media post, product comment or review) or reported to a government or credible third party); - A description of the Agency's assessment of whether the identity of the source of information is known and verified; - A description of how the information source has been verified and validated, if appropriate; and - Whether the information is current. I. EPA Should Not "Lock Down" Conditions of Use at the Time of Scoping. The Agency simultaneously insists that it must consider "all conditions of use" in the scope of the risk evaluation, but that it will then not actually consider "all" conditions of use through use of a "lock down" procedure, freezing the conditions of use at the time of scoping. In other words, if a new condition of use is discovered or emerges after the scope is published, EPA will not include it in the risk evaluation, regardless of impact. EPA proposes this "lock down" to help the Agency meet its statutory deadlines.17 We think the Agency has this backwards. To stay on its statutory schedule - or to move more quickly - the best tool EPA has available is scoping (the ability to scope its risk evaluations in a flexible manner to focus on the conditions posing the greatest potential risk). EPA should propose a process that allows the Agency to take full advantage of this important tool on a case- by-case basis. EPA should be able to select the conditions of use that it believes are most relevant and meaningful to human health and environmental risk and proceed accordingly. Likewise, EPA should not commit to "locking" conditions of use at the time of scoping. If EPA has discretion to select the conditions of use that it will include in the scope of a risk evaluation - which it does - then EPA should have the companion ability to remove or add a condition of use 18 as circumstances warrant. For example, following scoping EPA might determine that reports of an isolated use were wrong - and that the condition of use does not actually exist. It would 17 This proposal leaves in limbo the regulatory status of conditions of use that are excluded from the review. If EPA were to implement this approach, it would also need to clarify that excluded conditions of use go back to the prioritization process, and would also need to clarify that they do not have a high priority designation. This approach is also completely inconsistent with EPA's approach taken for manufacturer-requested evaluations. 18 Similarly, EPA has a companion ability to redesignate low priorities or high priorities as warranted. 10/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 make little sense to continue evaluating that condition of use in the risk evaluation. Otherwise, EPA's final risk evaluation would be of suspect quality, integrity, and reliability. A better approach would be for EPA to articulate in the rule that after a scope is published, EPA retains discretion to modify it upon a showing of substantial need or changed circumstances, or is otherwise warranted because the addition or removal of a condition of use, properly substantiated, will significantly affect the conduct of the risk evaluation. J. EPA Must Remove the Comment-or-Waive (Issue Exhaustion) Proposal. EPA further proposes that it can keep risk evaluations on schedule, notwithstanding its proposal to include "all conditions of use" in every scope, by "providing opportunity for comment on the scoping document and specifying that any objections to the draft scope document are waived if not raised during this process. ",99 We urge the Agency to remove this issue exhaustion (waiver) requirement for several reasons. First, it places an unfair burden on the regulated community. A particular company may not be aware, or otherwise in a position to verify, particular end uses that the company does not support (i.e., a downstream value chain to which it does not sell). A company likewise may not be able to verify occurrences of a chemical from natural sources or the actions of third parties through combustion, spills and discharges, disposal, manufacturing practices or incidents, and the like. When EPA insists on including "all conditions of use" in the scope of a risk evaluation, it moves well past the "major" uses of a chemical and "major" sources of exposure to include fleeting, incidental, minor, isolated, or exceptional cases. Information about these "minor" sources of exposure may be well outside the first-hand knowledge of a manufacturer or processor, making it difficult or impossible to offer meaningful comment during the scoping period. Second, participation in notice and comment rulemaking is governed by the Administrative Procedure Act (APA) and the judicial review provisions of Section 19 of TSCA. Issue exhaustion requirements can be imposed by statute. Notably, there are only a few statutory issue exhaustion provisions in environmental statutes, the most notable of which is in Section 307(d)(7)(b) of the Clean Air Act. There are none in TSCA. Congress had the opportunity to impose an issue exhaustion requirement for the scope of a risk evaluation in LCSA amendment - and declined to do so. EPA cannot, by regulation, impose an issue exhaustion requirement that trumps the statutory rights and obligations of stakeholders under the APA and TSCA Section 19.20 Indeed, ACC believes a waiver provision such as that proposed by EPA may not meet Constitutional muster. Third, the proposal does not rationally advance its claimed purpose - to meet statutory risk evaluation deadlines. An issue exhaustion requirement is supposed to serve two purposes: it 19 82 Fed. Reg. at 7566. 20 Administrative issue exhaustion requirements are largely creatures of statute, and here we have no such statutory construct. While some agency regulations set out issue exhaustion requirements without a statutory mandate, these tend to be in administrative appeal situations or proceedings that are analogs to adversarial litigation. Notably, the LCSA amendment removed a procedure for formal TSCA hearings. 11/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 protects administrative agency authority and promotes judicial efficiency. But here, by 21 requiring inclusion of "all conditions of use" in scopes, the agency impairs the ability of industry to meaningfully comment in the limited time available. EPA seems to be of the view that it would rather include "too much" in a scope than inadvertently omit a condition of use and include "too little," but it is the overly broad, unrefined scope that expands the scale and cost of risk evaluations and slows them. EPA then ties its own hands by proposing to "lock down" overly broad scopes, impeding its ability to update or modify them later in the process. This does not advance efficiency or transparency in the regulatory process. EPA can avoid these inefficiencies by offering a simple process to identify those major, important conditions of use that are most relevant and meaningful to a high-quality risk evaluation - and to use flexibility in designing the scope accordingly. EPA should offer a rationale of why it selected the uses it did in the scope itself. II. EPA Must Describe How and When it Will Apply Section 26 Requirements to Risk Evaluations. Section 26(h) sets out scientific standards that apply to every "decision based on science" while EPA carries out risk evaluation under Section 6 [emphasis added]. Section 26(i) requires EPA to "make decisions" under Section 6 based on the weight of the scientific evidence [emphasis added]. A decision would include any judicially reviewable determination, but also any other decision that requires application of science or scientific judgment by the Agency. EPA should articulate in the risk evaluation rule, at a minimum, the key decision points that will require compliance with Section 26 requirements. These should include, but are not limited to: - The proposed scope and final scope for risk evaluation - Hazard assessment, including, where applicable, the likely operable mode of action - Exposure assessment - Selection and evaluation of technical procedures, measures, methods, protocols, methodologies, and models - Basis for scientific assumptions - Selection and evaluation of quality assurance procedures - Decisions regarding variability and uncertainty - Statistical methods - The draft and final risk evaluation EPA should document how it applied Section 26(h) and 26(i) requirements for each decision. 21 The issue exhaustion proposal does not advance judicial economy either. Determinations of no unreasonable risk, made by the Agency following the completion of the risk evaluation process, are judicially reviewable - but as a practical matter this means that a judicial challenge to such a determination would be unlikely to occur until years after the scope was published (and the risk evaluation completed). Changes to conditions of use, or errors in their identification and inclusion, may not all be evident at the time the scope is originally prepared and published, so applying issue exhaustion at this step makes little sense. 12/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226

What should EPA exclude from the Scopes of TSCA Risk Evaluations?

kzbn0226

kzbn0226_p8, kzbn0226_p9, kzbn0226_p10, kzbn0226_p11, kzbn0226_p12

Low Exposure Conditions of use, Exclude Low Exposure Conditions of Use

At the same time, risk evaluations must meet Section 26 quality requirements, using best available science and weight of the evidence review. To achieve the throughput and quality requirements for risk evaluation, Congress designed a process to allow chemicals to be systematically prioritized and evaluated. This design is apparent throughout LCSA. It begins with a reset of the TSCA Inventory -- the full catalog of chemicals in commerce. LCSA requires that the TSCA Inventory be sorted, so that chemicals that are currently active in commerce are separated from those not currently used. This sorting enables EPA to identify only those chemicals that are active in commerce for prioritization and risk evaluation. This statutory design makes eminent sense: it allows EPA to focus resources for its multi-year, time- and resource-intensive risk evaluations on chemicals that are actually being used. From this initial focusing step, LCSA repeatedly requires EPA to further refine its focus throughout prioritization and risk evaluation. EPA must next implement a prioritization process, which further refines the active chemicals in commerce to those that are high priority for risk evaluation. These chemicals must then undergo a scoping exercise to further focus on the conditions of use that will be the subject of the risk evaluation. In implementing LCSA, EPA has indicated that it intends to identify and consider all conditions of use of a chemical in all risk evaluations, all the time. This interpretation cannot be reconciled with EPA's statutory directive to achieve throughput and quality in risk evaluations. It is inconsistent with the design of the statute; inconsistent with congressional intent to give EPA the flexibility to make case-by-case scoping decisions; and undermines statutory purposes and the effective function of the statute itself. A. There is No Statutory Mandate to Include All Conditions of Use in the Scope of Every Risk Evaluation Under TSCA § 6(b). EPA notes in the preamble that, prior to enactment of LCSA, the Agency was "free to and did" conduct risk assessments on selected uses of chemical substances, but that it now interprets the amended statute as "requiring that risk evaluations encompass all manufacture, processing, distribution in commerce, use, and disposal activities [t]hat is to say, a risk evaluation must encompass all known, intended, and reasonably foreseen activities associated with the subject chemical substance" [emphasis added]. ACC strongly disagrees with this interpretation -- EPA 3 is reading a mandate into the statute where none exists. Rather, Congress equipped EPA with the tools to scope risk evaluations in order to achieve statutory purposes, and EPA should use those tools accordingly. The statute does not require EPA to include "all" conditions of use in any particular risk evaluation, or in each and every risk evaluation. Nowhere in the statute does Congress modify "conditions of use" with "all." EPA has the discretion to interpret the term. It cannot apply this discretion in such a manner, however, as to undercut the operation of the statute or to make it impossible for EPA to meet its statutory objectives of throughput and quality. 3 82 Fed. Reg. at 7565. 4/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 B. Scoping Necessarily Requires EPA to Select Relevant Conditions of Use for Inclusion, and Scope Accordingly. LCSA requires EPA to conduct risk evaluations to determine whether a chemical substance presents an unreasonable risk of injury to health or the environment under certain circumstances called "conditions of use. ,,4 Conditions of use are defined as "the circumstances, as determined by [EPA], under which a chemical substance is intended, known, or reasonably foreseen to be manufactured, processed, distributed in commerce, used, or disposed of." The legislative text did not direct EPA to include "all" conditions of use. The statute creates a scoping process that precedes the risk evaluation itself. For a scoping process to have any reasonable meaning, it must actually "scope" -- on a case by case basis, it must determine which conditions of use are appropriate for inclusion because they are relevant and meaningful to the risk evaluation process. EPA's plan to universally include "all conditions of use" all the time in every risk evaluation is contrary to common sense, conflicts with and undermines the statutory design of TSCA as amended by LCSA, and would lead to an absurd result. 5 EPA's preamble acknowledges the value of scoping (also called problem formulation) in citing the National Academy of Sciences (NAS) National Research Council (NRC) Science and Decisions Report. The NAS report recommended that EPA focus on the "important roles of scoping or problem formulation so that a risk assessment will serve a specific and documented purpose" [emphasis added]. The preamble cites an additional NAS recommendation to EPA 6 that the Agency "develop risk assessments that are well-tailored to the problems and decisions at hand so that they can inform the decision-making process in the most meaningful way." We agree, and urge the agency to apply these recommendations to the scoping process. C. The Legislative Text Acknowledges that What EPA Will Consider and Include in a Given Scope Necessarily Varies. The scoping provision requires identification of those conditions EPA "expects to consider," a clause that would be unnecessary if EPA were directed to simply include "all" conditions of use in a risk evaluation. The future tense also acknowledges that EPA might subsequently change 8 4 TSCA § 6(b)(4)(A). 5 See Massachusetts v. EPA, 549 U.S. 497, 531, 535 (2007) addressing EPA's application of its Chevron deference to particular statutory constructions: EPA not required to regulate "all" greenhouse gases as "air pollutants" everywhere that term appears in the statute; EPA must ground its reasons for action or inaction in the statute; agency regulation cannot conflict with statutory design, and law cannot be read to compel EPA to regulate in a manner contrary to "common sense." 6 82 Fed. Reg. at 7265. 7 TSCA § 6(b)(3)(D). 8 Before LCSA was enacted, EPA had published multiple problem formulations under the TSCA Work Plan. EPA explained that its problem formulations served as a means for explaining the scope of a risk assessment: "A problem formulation and initial assessment document will serve to inform the public and other interested stakeholders about EPA's initial scoping of findings and plan for any further risk assessment. Problem formulation and initial assessment is the analytical phase of the assessment in which the purpose for the assessment is articulated, the problem defined and a plan for analyzing and characterizing risk is determined." Many of those completed problem formulations were for limited conditions of use. Like other aspects of the TSCA Work Plan, Congress 5/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 its position with respect to what conditions of use to include or exclude. Notably, this construction affords EPA the discretion to include all conditions of use where necessary. This is consistent with congressional intent. Speaking about the compromise bill that was signed into law, Senator Vitter said that EPA "is given the discretion to determine the conditions of use that the Agency will address in its evaluation of the priority chemical." This discretion and flexibility "assures that the Agency's focus is on conditions of use that raise the greatest potential for risk" particularly given that "many TSCA chemicals have multiple uses - industrial, commercial and consumer uses" and EPA is "well aware that some categories of uses pose greater potential for exposure than others and that the risks from many categories of uses are deemed negligible or already well controlled."9 D. EPA Should Expressly Exclude Substances that Are Not Regulated Under TSCA from the Scope of Risk Evaluations. TSCA excludes a number of chemical categories from its statutory scope. LCSA did not change these; accordingly, these categories should not be considered for inclusion in any risk evaluation undertaken pursuant to Section 6: (i) [a]ny mixture, (ii) any pesticide (as defined in the Federal Insecticide, Fungicide, and Rodenticide Act) when manufactured, processed, or distributed in commerce for use as a pesticide; (iii) tobacco or any tobacco product, (iv) any source material, special nuclear material, or byproduct material (as such terms are defined in the Atomic Energy Act of 1954 and regulations issued under such Act), (v) any article the sale of which is subject to the tax imposed by section 4181 of the Internal Revenue Code of 1986 [i.e., firearms and ammunition] (vi) any food, food additive, drug, cosmetic, or device (as such terms are defined in section 201 of the Federal Food, Drug, and Cosmetic Act) when manufactured, processed, or distributed in commerce for use as a food, food additive, drug, cosmetic, or device. The risk evaluation rule should expressly clarify that because these categories are excluded from the definition of "chemical substance" under TSCA, and they are outside EPA's legislative authority to regulate, they therefore excluded from the scope of risk evaluations under Section 6. contemplated that problem formulations from the TSCA Work Plan would serve as the model for EPA actions under the amended TSCA. In this case, the problem formulations were to be the model for the scoping exercise under Section 6(b)(4)(D). This is a strong indication that Congress authorized EPA to determine which conditions of use it would evaluate in a risk evaluation by defining the scope appropriately. 9 Senate Congressional Record, June 7, 2016, at S3519; available at also clarifies that unreasonable risk/no unreasonable risk determinations made pursuant to the risk evaluation are made use-by-use: "[T]o be clear, every condition of use identified by the Administrator in the scope of the risk evaluation must, and will be either found to present or not present an unreasonable risk." Id. at S3520. 6/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 Likewise, the rule should clarify that chemical uses within these exclusions are "conditions of use" that are outside the scope of any Section 6 risk evaluation. In addition to TSCA, which was modernized by the passage of LCSA in 2016, there is a network of statutes in place regulating the safety of chemicals in various venues and applications. Several other federal statutes are in place to regulate chemicals in products and during activities such as workplace manufacturing. Notably, the Consumer Protection Act, Consumer Product Safety Improvement Act, and the Federal Hazardous Substances Act regulate chemicals in a suite of consumer products, including children's products and toys, and the Occupational Safety and Health Act (OSH Act) regulates chemicals in the workplace. Chemicals in uses regulated by other federal laws and agencies are often referred to as "non- TSCA" uses. EPA should not include these uses in its risk evaluations under TSCA. In rare cases where inclusion might be justified, the Agency should establish criteria to justify including non-TSCA uses in its risk evaluations and should articulate the steps it will follow to ensure adequate interagency consultation and review at the scoping stage. We discuss this topic in more detail below. E. EPA Should Generally Exclude OSHA-Regulated Uses from the Scopes of TSCA Risk Evaluations. Although LCSA specifically includes "workers" as a possible category of "potentially exposed or susceptible subpopulation," it does not designate "workers" as a default category. Any consideration of worker exposure must begin with the recognition that worker exposures are regulated under the OSH Act. Given that Occupational Safety and Health Administration (OSHA) standards are in place for the very purpose of regulating risk to worker populations, it should be the unusual case where unreasonable risk may present to a worker population under conditions of use (e.g., use of personal protective equipment). Importantly, although Congress recognizes under LCSA that it may be appropriate, under particular circumstances, for EPA to designate workers as a potentially exposed or susceptible subpopulation under TSCA, and to regulate workplace exposures, Congress did not amend the OSH Act at the same time that it amended TSCA. Congress also left Section 9(d) of TSCA intact. This section requires EPA to consult and coordinate with OSHA "for the purpose of achieving the maximum enforcement of [TSCA] while imposing the least burdens of duplicative requirements on those subject to [TSCA] and for other purposes.' EPA should ensure that this consultation occurs before risk evaluations are scoped; in cases where worker exposures do not present a significant risk of health impairment under current conditions of use, EPA should decline to include worker populations within the scope of the risk assessment as unduly burdensome and duplicative. This process will help focus risk evaluations and reduce the resource cost to the Agency. Following this consultation, if OSHA agrees that EPA-led risk evaluation considering worker exposures is necessary (and not otherwise duplicative), EPA should describe the process it used to consult with OSHA and the basis for its findings in the scope of the risk evaluation. 7/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 F. EPA Should Generally Exclude Low Exposure Conditions of Use from the Scopes of TSCA Risk Evaluations. In the prioritization process, certain scenarios may emerge that are low- - to no-exposure. An example is a closed system, intermediate chemical manufacture or processing at an industrial site, where worker exposure is well documented and controlled, and does not present a significant risk. A second example would be de minimis levels of an impurity in a consumer product, where the levels and variability are well documented and well understood, and exposures are so low as not to present a significant risk. In such cases, it should be apparent in the prioritization process or before scoping that these use scenarios can readily be excluded from the scope of the risk evaluation. G. EPA Should Apply the "Reasonably Foreseen" Provision as a Focusing Tool to Help Tailor the Scope of Risk Evaluations - Not to Expand Them. The statutory definition of "conditions of use" is "the circumstances, as determined by the Administrator, under which a chemical substances is intended, known, or reasonably foreseen to be manufactured, processed, distributed in commerce, used or disposed of.">10 The phrase "intended, known, or reasonably foreseen" limits the conditions of use that may be identified and included in a scope. Clearly, if a particular use is not intended, known, or reasonably foreseen, it is not a statutory "condition of use" and may not be included within the scope of a risk evaluation. The term "intended" is generally well understood to mean intended by the manufacturer or processor. Intention can be demonstrated through express (e.g., a statement to that effect in a premanufacture notice) or implied evidence (e.g., marketing materials that imply a potential application for the chemical). The term "known" is often considered a backstop for the term "intended," in that manufacturers or processors may not "intend" or support a particular downstream use for a chemical but may have actual or imputed knowledge that a chemical is being used in that application. The definition of "conditions of use" also includes the term "reasonably foreseen." The concept of reasonable foreseeability is well understood in American and western11 tort law. Foreseeability is "the determinant for the limits of duty under a conventional risk analysis" [emphasis added]. Foreseeability is modified by "reasonably," which makes clear that not 12 every conceivable or speculative use is included. Product misuses and illegal uses, and manufacturing that disregards legal and industrial hygiene requirements, are not "reasonable" and thus not "reasonably foreseen." 10 TSCA §3(4). 11 See, e.g., ANNEXURE T, The Concept of Limited Liability, Existing Law and Rationale (Australia), referring to the limiting tests of reasonable foreseeability and proximity, available at htp:/lwww.dpc.nsw.gov.au data/assets/odf.file/0012/11406/T.pdi 12 Tyrus V. Dahl Jr., Strict Products Liability: The Irrelevance of Foreseeability and Related Negligence Concepts, 14 Tulsa L. J. 338, 343 (1978). 8/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226

Which Provision should be applied as a focusing tool by EPA?

kzbn0226

kzbn0226_p8, kzbn0226_p9, kzbn0226_p10, kzbn0226_p11, kzbn0226_p12

EPA Should Apply the "Reasonably Foreseen" Provision., the "Reasonably Foreseen" Provision

At the same time, risk evaluations must meet Section 26 quality requirements, using best available science and weight of the evidence review. To achieve the throughput and quality requirements for risk evaluation, Congress designed a process to allow chemicals to be systematically prioritized and evaluated. This design is apparent throughout LCSA. It begins with a reset of the TSCA Inventory -- the full catalog of chemicals in commerce. LCSA requires that the TSCA Inventory be sorted, so that chemicals that are currently active in commerce are separated from those not currently used. This sorting enables EPA to identify only those chemicals that are active in commerce for prioritization and risk evaluation. This statutory design makes eminent sense: it allows EPA to focus resources for its multi-year, time- and resource-intensive risk evaluations on chemicals that are actually being used. From this initial focusing step, LCSA repeatedly requires EPA to further refine its focus throughout prioritization and risk evaluation. EPA must next implement a prioritization process, which further refines the active chemicals in commerce to those that are high priority for risk evaluation. These chemicals must then undergo a scoping exercise to further focus on the conditions of use that will be the subject of the risk evaluation. In implementing LCSA, EPA has indicated that it intends to identify and consider all conditions of use of a chemical in all risk evaluations, all the time. This interpretation cannot be reconciled with EPA's statutory directive to achieve throughput and quality in risk evaluations. It is inconsistent with the design of the statute; inconsistent with congressional intent to give EPA the flexibility to make case-by-case scoping decisions; and undermines statutory purposes and the effective function of the statute itself. A. There is No Statutory Mandate to Include All Conditions of Use in the Scope of Every Risk Evaluation Under TSCA § 6(b). EPA notes in the preamble that, prior to enactment of LCSA, the Agency was "free to and did" conduct risk assessments on selected uses of chemical substances, but that it now interprets the amended statute as "requiring that risk evaluations encompass all manufacture, processing, distribution in commerce, use, and disposal activities [t]hat is to say, a risk evaluation must encompass all known, intended, and reasonably foreseen activities associated with the subject chemical substance" [emphasis added]. ACC strongly disagrees with this interpretation -- EPA 3 is reading a mandate into the statute where none exists. Rather, Congress equipped EPA with the tools to scope risk evaluations in order to achieve statutory purposes, and EPA should use those tools accordingly. The statute does not require EPA to include "all" conditions of use in any particular risk evaluation, or in each and every risk evaluation. Nowhere in the statute does Congress modify "conditions of use" with "all." EPA has the discretion to interpret the term. It cannot apply this discretion in such a manner, however, as to undercut the operation of the statute or to make it impossible for EPA to meet its statutory objectives of throughput and quality. 3 82 Fed. Reg. at 7565. 4/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 B. Scoping Necessarily Requires EPA to Select Relevant Conditions of Use for Inclusion, and Scope Accordingly. LCSA requires EPA to conduct risk evaluations to determine whether a chemical substance presents an unreasonable risk of injury to health or the environment under certain circumstances called "conditions of use. ,,4 Conditions of use are defined as "the circumstances, as determined by [EPA], under which a chemical substance is intended, known, or reasonably foreseen to be manufactured, processed, distributed in commerce, used, or disposed of." The legislative text did not direct EPA to include "all" conditions of use. The statute creates a scoping process that precedes the risk evaluation itself. For a scoping process to have any reasonable meaning, it must actually "scope" -- on a case by case basis, it must determine which conditions of use are appropriate for inclusion because they are relevant and meaningful to the risk evaluation process. EPA's plan to universally include "all conditions of use" all the time in every risk evaluation is contrary to common sense, conflicts with and undermines the statutory design of TSCA as amended by LCSA, and would lead to an absurd result. 5 EPA's preamble acknowledges the value of scoping (also called problem formulation) in citing the National Academy of Sciences (NAS) National Research Council (NRC) Science and Decisions Report. The NAS report recommended that EPA focus on the "important roles of scoping or problem formulation so that a risk assessment will serve a specific and documented purpose" [emphasis added]. The preamble cites an additional NAS recommendation to EPA 6 that the Agency "develop risk assessments that are well-tailored to the problems and decisions at hand so that they can inform the decision-making process in the most meaningful way." We agree, and urge the agency to apply these recommendations to the scoping process. C. The Legislative Text Acknowledges that What EPA Will Consider and Include in a Given Scope Necessarily Varies. The scoping provision requires identification of those conditions EPA "expects to consider," a clause that would be unnecessary if EPA were directed to simply include "all" conditions of use in a risk evaluation. The future tense also acknowledges that EPA might subsequently change 8 4 TSCA § 6(b)(4)(A). 5 See Massachusetts v. EPA, 549 U.S. 497, 531, 535 (2007) addressing EPA's application of its Chevron deference to particular statutory constructions: EPA not required to regulate "all" greenhouse gases as "air pollutants" everywhere that term appears in the statute; EPA must ground its reasons for action or inaction in the statute; agency regulation cannot conflict with statutory design, and law cannot be read to compel EPA to regulate in a manner contrary to "common sense." 6 82 Fed. Reg. at 7265. 7 TSCA § 6(b)(3)(D). 8 Before LCSA was enacted, EPA had published multiple problem formulations under the TSCA Work Plan. EPA explained that its problem formulations served as a means for explaining the scope of a risk assessment: "A problem formulation and initial assessment document will serve to inform the public and other interested stakeholders about EPA's initial scoping of findings and plan for any further risk assessment. Problem formulation and initial assessment is the analytical phase of the assessment in which the purpose for the assessment is articulated, the problem defined and a plan for analyzing and characterizing risk is determined." Many of those completed problem formulations were for limited conditions of use. Like other aspects of the TSCA Work Plan, Congress 5/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 its position with respect to what conditions of use to include or exclude. Notably, this construction affords EPA the discretion to include all conditions of use where necessary. This is consistent with congressional intent. Speaking about the compromise bill that was signed into law, Senator Vitter said that EPA "is given the discretion to determine the conditions of use that the Agency will address in its evaluation of the priority chemical." This discretion and flexibility "assures that the Agency's focus is on conditions of use that raise the greatest potential for risk" particularly given that "many TSCA chemicals have multiple uses - industrial, commercial and consumer uses" and EPA is "well aware that some categories of uses pose greater potential for exposure than others and that the risks from many categories of uses are deemed negligible or already well controlled."9 D. EPA Should Expressly Exclude Substances that Are Not Regulated Under TSCA from the Scope of Risk Evaluations. TSCA excludes a number of chemical categories from its statutory scope. LCSA did not change these; accordingly, these categories should not be considered for inclusion in any risk evaluation undertaken pursuant to Section 6: (i) [a]ny mixture, (ii) any pesticide (as defined in the Federal Insecticide, Fungicide, and Rodenticide Act) when manufactured, processed, or distributed in commerce for use as a pesticide; (iii) tobacco or any tobacco product, (iv) any source material, special nuclear material, or byproduct material (as such terms are defined in the Atomic Energy Act of 1954 and regulations issued under such Act), (v) any article the sale of which is subject to the tax imposed by section 4181 of the Internal Revenue Code of 1986 [i.e., firearms and ammunition] (vi) any food, food additive, drug, cosmetic, or device (as such terms are defined in section 201 of the Federal Food, Drug, and Cosmetic Act) when manufactured, processed, or distributed in commerce for use as a food, food additive, drug, cosmetic, or device. The risk evaluation rule should expressly clarify that because these categories are excluded from the definition of "chemical substance" under TSCA, and they are outside EPA's legislative authority to regulate, they therefore excluded from the scope of risk evaluations under Section 6. contemplated that problem formulations from the TSCA Work Plan would serve as the model for EPA actions under the amended TSCA. In this case, the problem formulations were to be the model for the scoping exercise under Section 6(b)(4)(D). This is a strong indication that Congress authorized EPA to determine which conditions of use it would evaluate in a risk evaluation by defining the scope appropriately. 9 Senate Congressional Record, June 7, 2016, at S3519; available at also clarifies that unreasonable risk/no unreasonable risk determinations made pursuant to the risk evaluation are made use-by-use: "[T]o be clear, every condition of use identified by the Administrator in the scope of the risk evaluation must, and will be either found to present or not present an unreasonable risk." Id. at S3520. 6/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 Likewise, the rule should clarify that chemical uses within these exclusions are "conditions of use" that are outside the scope of any Section 6 risk evaluation. In addition to TSCA, which was modernized by the passage of LCSA in 2016, there is a network of statutes in place regulating the safety of chemicals in various venues and applications. Several other federal statutes are in place to regulate chemicals in products and during activities such as workplace manufacturing. Notably, the Consumer Protection Act, Consumer Product Safety Improvement Act, and the Federal Hazardous Substances Act regulate chemicals in a suite of consumer products, including children's products and toys, and the Occupational Safety and Health Act (OSH Act) regulates chemicals in the workplace. Chemicals in uses regulated by other federal laws and agencies are often referred to as "non- TSCA" uses. EPA should not include these uses in its risk evaluations under TSCA. In rare cases where inclusion might be justified, the Agency should establish criteria to justify including non-TSCA uses in its risk evaluations and should articulate the steps it will follow to ensure adequate interagency consultation and review at the scoping stage. We discuss this topic in more detail below. E. EPA Should Generally Exclude OSHA-Regulated Uses from the Scopes of TSCA Risk Evaluations. Although LCSA specifically includes "workers" as a possible category of "potentially exposed or susceptible subpopulation," it does not designate "workers" as a default category. Any consideration of worker exposure must begin with the recognition that worker exposures are regulated under the OSH Act. Given that Occupational Safety and Health Administration (OSHA) standards are in place for the very purpose of regulating risk to worker populations, it should be the unusual case where unreasonable risk may present to a worker population under conditions of use (e.g., use of personal protective equipment). Importantly, although Congress recognizes under LCSA that it may be appropriate, under particular circumstances, for EPA to designate workers as a potentially exposed or susceptible subpopulation under TSCA, and to regulate workplace exposures, Congress did not amend the OSH Act at the same time that it amended TSCA. Congress also left Section 9(d) of TSCA intact. This section requires EPA to consult and coordinate with OSHA "for the purpose of achieving the maximum enforcement of [TSCA] while imposing the least burdens of duplicative requirements on those subject to [TSCA] and for other purposes.' EPA should ensure that this consultation occurs before risk evaluations are scoped; in cases where worker exposures do not present a significant risk of health impairment under current conditions of use, EPA should decline to include worker populations within the scope of the risk assessment as unduly burdensome and duplicative. This process will help focus risk evaluations and reduce the resource cost to the Agency. Following this consultation, if OSHA agrees that EPA-led risk evaluation considering worker exposures is necessary (and not otherwise duplicative), EPA should describe the process it used to consult with OSHA and the basis for its findings in the scope of the risk evaluation. 7/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226 F. EPA Should Generally Exclude Low Exposure Conditions of Use from the Scopes of TSCA Risk Evaluations. In the prioritization process, certain scenarios may emerge that are low- - to no-exposure. An example is a closed system, intermediate chemical manufacture or processing at an industrial site, where worker exposure is well documented and controlled, and does not present a significant risk. A second example would be de minimis levels of an impurity in a consumer product, where the levels and variability are well documented and well understood, and exposures are so low as not to present a significant risk. In such cases, it should be apparent in the prioritization process or before scoping that these use scenarios can readily be excluded from the scope of the risk evaluation. G. EPA Should Apply the "Reasonably Foreseen" Provision as a Focusing Tool to Help Tailor the Scope of Risk Evaluations - Not to Expand Them. The statutory definition of "conditions of use" is "the circumstances, as determined by the Administrator, under which a chemical substances is intended, known, or reasonably foreseen to be manufactured, processed, distributed in commerce, used or disposed of.">10 The phrase "intended, known, or reasonably foreseen" limits the conditions of use that may be identified and included in a scope. Clearly, if a particular use is not intended, known, or reasonably foreseen, it is not a statutory "condition of use" and may not be included within the scope of a risk evaluation. The term "intended" is generally well understood to mean intended by the manufacturer or processor. Intention can be demonstrated through express (e.g., a statement to that effect in a premanufacture notice) or implied evidence (e.g., marketing materials that imply a potential application for the chemical). The term "known" is often considered a backstop for the term "intended," in that manufacturers or processors may not "intend" or support a particular downstream use for a chemical but may have actual or imputed knowledge that a chemical is being used in that application. The definition of "conditions of use" also includes the term "reasonably foreseen." The concept of reasonable foreseeability is well understood in American and western11 tort law. Foreseeability is "the determinant for the limits of duty under a conventional risk analysis" [emphasis added]. Foreseeability is modified by "reasonably," which makes clear that not 12 every conceivable or speculative use is included. Product misuses and illegal uses, and manufacturing that disregards legal and industrial hygiene requirements, are not "reasonable" and thus not "reasonably foreseen." 10 TSCA §3(4). 11 See, e.g., ANNEXURE T, The Concept of Limited Liability, Existing Law and Rationale (Australia), referring to the limiting tests of reasonable foreseeability and proximity, available at htp:/lwww.dpc.nsw.gov.au data/assets/odf.file/0012/11406/T.pdi 12 Tyrus V. Dahl Jr., Strict Products Liability: The Irrelevance of Foreseeability and Related Negligence Concepts, 14 Tulsa L. J. 338, 343 (1978). 8/Page Source: https://www.industrydocuments.ucsf.edu/docs/kzbn0226

why industry should be provided an opportunity ?

jzbn0226

jzbn0226_p24, jzbn0226_p25, jzbn0226_p26

to provide EPA additional data/information., to provide EPA additional data/information

C. Waivers EPA has proposed that all comments that could be raised on issues in a proposed low priority designation be presented during the comment period, and that any issues not raised then be considered to have been waived. Waived issues could not form the basis of an objection or challenge in any subsequent administrative or judicial proceeding on the designation of the substance as a low priority substance (which is subject to judicial review). EPA points to the statutory deadlines in the prioritization process as the policy justification for this proposal. 38 ACC urges EPA to remove this waiver requirement from the prioritization rule. First, it is inconsistent with Congress's intent that the prioritization process be iterative and science-based. Low priority designations should be able to be modified - expanded or contracted - based on new information that is brought to the Agency's attention after the designation. This new information might not have been known during the public comment period on the low priority designation. It would be bad public policy to consider new information waived because that could discourage stakeholders from gathering or developing relevant information about a chemical. Second, participation in the notice and comment rulemaking process of prioritization is governed by statute - through the Administrative Procedures Act (APA) and the judicial review provisions of Section 19 of TSCA. There are no issue exhaustion provisions in TSCA. EPA cannot by regulation, impose an issue exhaustion requirement that trumps the statutory rights and obligations of stakeholders under the APA and TSCA Section 19.39 D. Definitions As an addendum to ACC's recommendations for EPA to reference the Section 26 science standards in the prioritization process rule, ACC offers the following definitions for EPA's consideration: Best available science means information that has been evaluated based on its strengths, limitations and relevance and the Agency is relying on the highest quality information. In evaluating best available science the Agency will also consider the peer review of the science, whether the study was conducted in accordance with sound and objective practices, and if the data were collected by accepted methods or best available methods. To ensure transparency regarding best available science the Agency will describe and document any assumptions and methods used, and address variability, uncertainty, the degree of independent verification and peer review. Weight of the evidence means a systematic review method that uses a pre-established protocol to comprehensively, objectively, transparently, and consistently, identify and evaluate each stream of evidence, including strengths, limitations, and relevance of each study and to integrate evidence as necessary and appropriate based upon strengths, limitations, and relevance. 38 Id. at 4833. 39 See ACC Comments on EPA's Proposed Rule: Procedures for Chemical Risk Evaluation under the Amended Toxic Substances Control Act (RIN 2070- AK20) for additional discussion of the waiver/lock down/issue exhaustion issue. 23 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 E. Repopulation of High Priority Substances EPA's preamble discussion of the "repopulation" of high priority substances40 presents a reasonable approach by which the Agency could meet the LCSA obligation to finalize the designation of one new high priority substance upon completion of a risk evaluation for another substance. The one-for-one approach makes sense as this program gets underway. ACC suggests, however, that EPA consider a placeholder in its rule to anticipate changes in the rate at which EPA might be able to conduct risk evaluations over time (based on use of 21st Century tools and methods) and hence potentially change the rate at which EPA may need to designate high priorities for risk evaluation. VIII. Summary of ACC's Recommendations: Throughout these comments, ACC has included many specific recommendations for EPA to consider as it develops its final prioritization process rule to address ACC's concerns about the proposed rule. These recommendations urge EPA to direct its authority on what it is mandated to do under the LCSA - designate high priority and low priority chemicals for risk evaluations in accordance with both the criteria in LCSA Section 6 and the LCSA Section 26 science based standards. To help the regulated community provide EPA the information the Agency will need to prioritize chemicals for risk evaluations, EPA must clarify the prioritization process as a whole and develop an efficient and focused prioritization process rule that meets the LCSA mandate and Congressional intent. ACC strongly urges EPA to amend its proposal to include these suggested recommendations and seek public comment before finalizing the prioritization process rule. Alternatively, EPA should propose a supplemental rule providing more detail and clarifications on the prioritization process steps involved and finalize it prior to the Agency's first application of the prioritization process . To help foster the submission of information needed to prioritize chemicals for risk evaluations, EPA must ultimately develop an efficient and focused prioritization process rule that clearly lays out the major steps for meeting its mandate. 40 82 Fed. Reg. at 4833. 24 Source: :ttps://www.industrydocuments.ucsf.edu/docs/jzbn0226 Attachment A ACC's General Principles on Prioritization (Developed for EPA Dialogue 7-2011) EPA should systematically prioritize chemicals for purposes of safe use determinations. As a general matter, prioritization should be based on existing hazard and exposure data and information (including models, read across, QSAR, etc.) and industry should be responsible for providing EPA with this data and information. Chemicals lacking adequate hazard and exposure information should be considered a higher priority (until relevant information is provided that suggests otherwise). Industry should be provided an opportunity to provide EPA additional data/information. (Timing is an issue, however. And the format in which the information is provided to EPA must be useable/digestible by EPA, e.g. robust summaries.) Hazard, use and exposure based criteria should be integrated to form the basis for EPA's prioritization decisions. Prioritization should not be based on either hazard-only or exposure-only information. The prioritization process and science based criteria that EPA uses to prioritize chemicals must be transparent. Prioritization should be a dynamic, iterative process. Re-examination of priorities should occur as new information becomes available and as new chemicals are approved for manufacturing. For prioritization to be successful, it must include three critical elements: reliable and up- to- date chemical data and information; evaluation criteria that consider both hazard and exposure information together; and established cutoffs to make priority decisions. EPA's communication about priority chemicals must be clear about what the list is and what it is not, to avoid unintended consequences of product de-selection purely on the basis of listing. Transparency; consistent, scientific criteria; intersection of both hazard and exposure information; dynamic process so new information can be incorporated as it is made available and so if priorities are initially "wrong" they can be corrected. 25 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226

What is the fullform of MCSA?

ylcn0226

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

Motor Carrier 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 beck@americanchemistry.com 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

how should be prioritization process ?

jzbn0226

jzbn0226_p24, jzbn0226_p25, jzbn0226_p26

dynamic, iterative process, a dynamic, iterative process.

C. Waivers EPA has proposed that all comments that could be raised on issues in a proposed low priority designation be presented during the comment period, and that any issues not raised then be considered to have been waived. Waived issues could not form the basis of an objection or challenge in any subsequent administrative or judicial proceeding on the designation of the substance as a low priority substance (which is subject to judicial review). EPA points to the statutory deadlines in the prioritization process as the policy justification for this proposal. 38 ACC urges EPA to remove this waiver requirement from the prioritization rule. First, it is inconsistent with Congress's intent that the prioritization process be iterative and science-based. Low priority designations should be able to be modified - expanded or contracted - based on new information that is brought to the Agency's attention after the designation. This new information might not have been known during the public comment period on the low priority designation. It would be bad public policy to consider new information waived because that could discourage stakeholders from gathering or developing relevant information about a chemical. Second, participation in the notice and comment rulemaking process of prioritization is governed by statute - through the Administrative Procedures Act (APA) and the judicial review provisions of Section 19 of TSCA. There are no issue exhaustion provisions in TSCA. EPA cannot by regulation, impose an issue exhaustion requirement that trumps the statutory rights and obligations of stakeholders under the APA and TSCA Section 19.39 D. Definitions As an addendum to ACC's recommendations for EPA to reference the Section 26 science standards in the prioritization process rule, ACC offers the following definitions for EPA's consideration: Best available science means information that has been evaluated based on its strengths, limitations and relevance and the Agency is relying on the highest quality information. In evaluating best available science the Agency will also consider the peer review of the science, whether the study was conducted in accordance with sound and objective practices, and if the data were collected by accepted methods or best available methods. To ensure transparency regarding best available science the Agency will describe and document any assumptions and methods used, and address variability, uncertainty, the degree of independent verification and peer review. Weight of the evidence means a systematic review method that uses a pre-established protocol to comprehensively, objectively, transparently, and consistently, identify and evaluate each stream of evidence, including strengths, limitations, and relevance of each study and to integrate evidence as necessary and appropriate based upon strengths, limitations, and relevance. 38 Id. at 4833. 39 See ACC Comments on EPA's Proposed Rule: Procedures for Chemical Risk Evaluation under the Amended Toxic Substances Control Act (RIN 2070- AK20) for additional discussion of the waiver/lock down/issue exhaustion issue. 23 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226 E. Repopulation of High Priority Substances EPA's preamble discussion of the "repopulation" of high priority substances40 presents a reasonable approach by which the Agency could meet the LCSA obligation to finalize the designation of one new high priority substance upon completion of a risk evaluation for another substance. The one-for-one approach makes sense as this program gets underway. ACC suggests, however, that EPA consider a placeholder in its rule to anticipate changes in the rate at which EPA might be able to conduct risk evaluations over time (based on use of 21st Century tools and methods) and hence potentially change the rate at which EPA may need to designate high priorities for risk evaluation. VIII. Summary of ACC's Recommendations: Throughout these comments, ACC has included many specific recommendations for EPA to consider as it develops its final prioritization process rule to address ACC's concerns about the proposed rule. These recommendations urge EPA to direct its authority on what it is mandated to do under the LCSA - designate high priority and low priority chemicals for risk evaluations in accordance with both the criteria in LCSA Section 6 and the LCSA Section 26 science based standards. To help the regulated community provide EPA the information the Agency will need to prioritize chemicals for risk evaluations, EPA must clarify the prioritization process as a whole and develop an efficient and focused prioritization process rule that meets the LCSA mandate and Congressional intent. ACC strongly urges EPA to amend its proposal to include these suggested recommendations and seek public comment before finalizing the prioritization process rule. Alternatively, EPA should propose a supplemental rule providing more detail and clarifications on the prioritization process steps involved and finalize it prior to the Agency's first application of the prioritization process . To help foster the submission of information needed to prioritize chemicals for risk evaluations, EPA must ultimately develop an efficient and focused prioritization process rule that clearly lays out the major steps for meeting its mandate. 40 82 Fed. Reg. at 4833. 24 Source: :ttps://www.industrydocuments.ucsf.edu/docs/jzbn0226 Attachment A ACC's General Principles on Prioritization (Developed for EPA Dialogue 7-2011) EPA should systematically prioritize chemicals for purposes of safe use determinations. As a general matter, prioritization should be based on existing hazard and exposure data and information (including models, read across, QSAR, etc.) and industry should be responsible for providing EPA with this data and information. Chemicals lacking adequate hazard and exposure information should be considered a higher priority (until relevant information is provided that suggests otherwise). Industry should be provided an opportunity to provide EPA additional data/information. (Timing is an issue, however. And the format in which the information is provided to EPA must be useable/digestible by EPA, e.g. robust summaries.) Hazard, use and exposure based criteria should be integrated to form the basis for EPA's prioritization decisions. Prioritization should not be based on either hazard-only or exposure-only information. The prioritization process and science based criteria that EPA uses to prioritize chemicals must be transparent. Prioritization should be a dynamic, iterative process. Re-examination of priorities should occur as new information becomes available and as new chemicals are approved for manufacturing. For prioritization to be successful, it must include three critical elements: reliable and up- to- date chemical data and information; evaluation criteria that consider both hazard and exposure information together; and established cutoffs to make priority decisions. EPA's communication about priority chemicals must be clear about what the list is and what it is not, to avoid unintended consequences of product de-selection purely on the basis of listing. Transparency; consistent, scientific criteria; intersection of both hazard and exposure information; dynamic process so new information can be incorporated as it is made available and so if priorities are initially "wrong" they can be corrected. 25 Source: https://www.industrydocuments.ucsf.edu/docs/jzbn0226