By Lynn L. Bergeson and Carla N. Hutton
 
The U.S. Environmental Protection Agency (EPA) announced on December 7, 2022, that the final video recording, slide deck, and case study worksheets from the CompTox Chemicals Dashboard virtual training are now available. EPA also announced that the Dashboard recently released a new version (v2.1.1). New features include:

• A new link to an updated set of Help Pages containing new information;
• Ability to visualize structures in Batch Search;
• Ability to filter out chemicals that are structures;
• Moving the chemistry-related data tabs under a single tab;
• reCAPTCHA implementation to ensure continued functionality;
• Updating the Production Volume data;
• Updating the ADME > IVIVE table using the latest HTTK R-package v2.2.1 algorithm; and
• Several bug fixes.

EPA suggests that if users do not see these updates to try clearing the cache.

The recordings and slides from the October 12-13, 2022, EPA New Approach Methods (NAM) Conference are available on the conference web page. Conference topics included:

• Variability and Relevance of Traditional Toxicity Tests;
• Evolution of Validation and Scientific Confidence Frameworks to Incorporate 21st Century Science; and
• Breakout groups discussing Variability of Traditional Toxicity Tests, Relevance of Traditional Toxicity Tests, and Feedback on EPA Scientific Confidence Framework.

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By Lynn L. Bergeson and Carla N. Hutton
 
The U.S. Environmental Protection Agency (EPA) will hold a webinar on October 27, 2022, in its Computational Toxicology and Exposure Communities of Practice (CompTox Communities of Practice) series on “Analysis of High-Throughput Profiling Assays in Chemical Safety Screening.” The abstract for the webinar states that recent technological advancements have led to the development of new high-throughput profiling methods, such as transcriptomics, that can be used to screen rapidly chemicals for potential hazards. Decreasing costs have made it feasible to profile all protein-coding genes across thousands of samples, allowing for broad evaluation of many target pathways and modes of action in a single screening assay. Similarly, it is now possible to apply high-content imaging across many different chemical exposures to capture a variety of changes in cell morphology. According to the abstract, such methods have been applied to in vitro chemical screening studies, including screening studies at EPA that were recently released on the CompTox Chemicals Dashboard. These types of data can be used for both hazard prediction and potency estimation, thereby informing risk assessments and prioritizing chemicals for further testing.
 
The abstract notes that assessing the reliability and reproducibility of these screening platforms is critical to their utility in regulatory applications. While these platforms often have lower signal-to-noise ratios compared to individual targeted assays, the resulting data are also high-dimensional, allowing for the analysis of consistent trends across many molecular endpoints. The webinar will provide an overview of computational methods and best practices for reliable analysis of high-throughput profiling data in a variety of use cases and will highlight the recent data release on the CompTox Chemicals Dashboard. Registration is open.

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By Lynn L. Bergeson and Carla N. Hutton

The U.S. Environmental Protection Agency (EPA) has posted two new resource documents for recipients of test orders under Section 4 of the Toxic Substances Control Act (TSCA). The August 5, 2022, policy document entitled “Policies Regarding Manufacturers and Processors Subject to TSCA Section 4(a) Testing” provides two policies:

• Policy 1: Companies engaged in manufacturing activities for a chemical substance during the five years prior to the projected signature date or effective date of a Section 4(a) action (i.e., a rule, consent agreement, or order) will generally be included in the scope of the action. EPA may apply a longer or shorter period of time when appropriate in specific cases, however. EPA states that “[w]here (1) a five-year period fails to identify a sufficient number of manufacturers, (2) fairness reasons warrant inclusion of a manufacturer, especially a high-volume manufacturer, of the chemical substance with less recent manufacturing, (3) a chemical substance has persistence and/or bioaccumulative properties that warrant inclusion of companies that contributed to potential exposures associated with such substance, or (4) where warranted for other reasons, which the Agency would explain as part of the Section 4(a) action, EPA will consider a longer manufacturing period than five years for the identification of companies as manufacturers subject to TSCA Section 4 testing obligations for a given chemical substance.” According to EPA, an example of where it may not include a company that has manufactured in the past five years as a manufacturer subject to testing requirements in a specific Section 4(a) action would be a company that “may have gone into bankruptcy and be in the hands of receivers who do not seek to continue the company’s manufacturing activities involving the chemical substance subject to the testing requirements.”
• Policy 2: Section 4 actions will not include an option to cease manufacturing as a means to satisfy the requirements of the action. Test orders issued in January 2021 included this option. EPA removed this response option to ensure that a sufficient number of entities remained subject to an order (e.g., for one 2021 order, no manufacturers identified by the order remained available to conduct the testing due to their use of the cease manufacture response option). According to EPA, were all entities subject to the testing requirements able to exit the market to forgo producing the required data, EPA would be unable to seek and obtain data under Section 4(a) to support better its assessments and action. EPA states that where it is conducting a risk evaluation on chemical substances that have conditions of use that “are not currently ongoing but are reasonably foreseen to reoccur or for which the effects and exposures are ongoing, EPA generally believes it is appropriate to include companies responsible for those activities in testing obligations.”

The August 5, 2022, policy document entitled “Removal of Certain Companies from Seven TSCA Section 4(a)(2) Orders Issued in 2022” states that although EPA’s policy is that it will no longer provide a “cease manufacture” response option for a company to cease its manufacture of a chemical substance to satisfy the requirements of an order, EPA recognizes that a company that ceased its manufacture of a chemical substance in response to a 2021 order “forewent a business opportunity in reliance upon EPA’s representation that testing on the chemical substance would not be required by the company.” EPA will remove from a 2022 order on a chemical substance any company that made successful use of the cease manufacture response option for a 2021 order on that same chemical substance, “provided the company has not, and does not, recommence its manufacture of the chemical substance while testing obligations remain in effect for that chemical substance under the applicable 2021 Order and/or 2022 Order.” According to EPA, removal of such companies due to EPA’s approval of the “cease manufacture” response option provided in the 2021 order applies only to the 2022 orders issued for the eight subject chemical substances. EPA notes that any future Section 4 action involving the applicable chemical substance will include manufacturers and/or processors as EPA deems to be appropriate upon any final future action (e.g., should such companies resume their manufacturing and/or processing of the chemical substance following the completion of the testing requirements in the 2021 and 2022 orders).

EPA states in each document that the policy document is not intended to bind EPA or members of the public. EPA “may revisit and depart from these policies based on reasoned consideration as it deems appropriate in the future.”

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By Lynn L. Bergeson and Carla N. Hutton
 
On May 23, 2022, the Vinyl Institute, Inc. (VI) filed suit in the U.S. Court of Appeals for the District of Columbia against the U.S. Environmental Protection Agency (EPA), seeking review of EPA’s March 2022 test order for 1,1,2-trichloroethane issued under Section 4(a)(2) of the Toxic Substances Control Act (TSCA). As reported in our March 25, 2022, blog item, EPA announced on March 24, 2022, that it issued a second round of test orders under TSCA Section 4 to obtain additional data on eight of the next 20 chemicals undergoing risk evaluation. The VI seeks judicial review of the test order under federal law, including but not limited to the Administrative Procedure Act (APA), TSCA, and EPA’s regulations promulgated thereunder. The VI seeks a determination that, inter alia, the test order violates these authorities; is arbitrary, capricious, an abuse of discretion, and otherwise not in accordance with the law; is in excess of statutory jurisdiction, authority, or limitations, or short of statutory right; is without observance of procedure required by law; is unsupported by substantial evidence; and is otherwise contrary to law. The VI asks that the court hold unlawful, vacate, enjoin, set aside, and remand the test order.

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By Lynn L. Bergeson and Carla N. Hutton
 
As reported in our March 25, 2022, blog item, the U.S. Environmental Protection Agency (EPA) announced on March 24, 2022, that it issued a second round of test orders under Section 4 of the Toxic Substances Control Act (TSCA) to obtain additional data on eight of the next 20 chemicals undergoing risk evaluation. In April 2022, EPA issued corrections to the following test orders:

• 1,1,2-Trichloroethane: EPA amended Appendix D -- Order Recipient Selection. According to EPA, Appendix D referred to p-dichlorobenzene, although it should have referred to 1,1,2-trichloroethane. Appendix D only explains the process for identifying order recipients. EPA states that this correction does not change the obligations that apply to manufacturers and processors of 1,1,2-trichloroethane, pursuant to TSCA Section 4(a)(2). EPA identified the recipients of the order through those sources related to manufacturers and processors of 1,1,2-trichloroethane.
   
• 1,2-Dichloroethane: EPA amended Appendix D -- Order Recipient Selection. According to EPA, Appendix D referred to p-dichlorobenzene, although it should have referred to 1,2-dichloroethane. Appendix D only explains the process for identifying order recipients. EPA states that the correction does not change the obligations that apply to manufacturers and processors of 1,2-dichloroethane, pursuant to TSCA Section 4(a)(2). EPA identified the recipients of the order through those sources related to manufacturers and processors of 1,2-dichloroethane.
   
• 1,2-Dichloropropane: EPA amended Appendix D -- Order Recipient Selection. Appendix D referred to p-dichlorobenzene, although it should have referred to 1,2-dichloropropane. Appendix D only explains the process for identifying order recipients. The correction does not change the obligations that apply to manufacturers and processors of 1,2-dichloropropane, pursuant to TSCA Section 4(a)(2). EPA identified the recipients of the order through those sources related to manufacturers and processors of 1,2-dichloropropane.
   
• 4,4'-(1-Methylethylidene)bis[2,6-dibromophenol] (TBBPA): EPA states that it amended the list of recipients to replace INEOS USA LLC with INEOS Enterprises US Holdco LLC. The effective date for INEOS Enterprises US Holdco LLC is five days after April 20, 2022, the date the memorandum was signed. The effective date for the companies listed in the original order issued on March 24, 2022, will remain March 29, 2022. EPA amended Appendix D -- Order Recipient Selection. Appendix D referred to p-dichlorobenzene, although it should have referred to TBBPA. Appendix D only explains the process for identifying order recipients. The correction does not change the obligations that apply to manufacturers and processors of TBBPA, pursuant to TSCA Section 4(a)(2). EPA identified the recipients of the order through those sources related to manufacturers and processors of TBBPA.
   
• o-Dichlorobenzene: EPA amended Appendix D -- Order Recipient Selection. EPA states that Appendix D referred to p-dichlorobenzene, although it should have referred to o-dichlorobenzene. Appendix D only explains the process for identifying order recipients. The correction does not change the obligations that apply to manufacturers and processors of o-dichlorobenzene, pursuant to TSCA Section 4(a)(2). EPA identified the recipients of the order through those sources related to manufacturers and processors of o-dichlorobenzene.
   
• Phosphoric acid, triphenyl ester (TPP): EPA amended the list of recipients to replace Axalta Coating Systems LLC with ChemSpec Ltd. The effective date for ChemSpec Ltd is five days after April 20, 2022, the date the memorandum was signed. The effective date for the companies listed in the original order issued on March 24, 2022, will remain as March 29, 2022. EPA also amended Appendix D -- Order Recipient Selection. According to EPA, Appendix D referred to p-dichlorobenzene, although it should have referred to TPP. Appendix D only explains the process for identifying order recipients. The correction does not change the obligations that apply to manufacturers and processors of TPP, pursuant to TSCA Section 4(a)(2). EPA identified the recipients of the order through those sources related to manufacturers and processors of TPP.
   
• Trans-1,2-dichloroethylene: EPA amended the list of recipients to add the companies listed below. The effective date for the order for these companies will be five days after April 20, 2022, when the modification was signed. The effective date of the order for the companies listed in the March 24, 2022, order will also have the effective date of five days from April 20, 2022, when the modification was signed (i.e., both the companies listed below and the companies in the order signed on March 24, 2022, for trans-1,2-dichloroethylene will have an effective date five days after April 20, 2022, the date the memorandum was signed):
  • Chemical Compounding Co;
  • Dow Inc;
  • MicroCare LLC;
  • Occidental Chemical Holding Corp;
  • Olin Corp; and
  • Versum Materials Inc.

EPA amended Appendix D -- Order Recipient Selection. Appendix D referred to p-dichlorobenzene, although it should have referred to trans-1,2-dichloroethylene. Appendix D only explains the process for identifying order recipients. EPA states that the correction does not change the obligations that apply to manufacturers and processors of trans-1,2- dichloroethylene, pursuant to TSCA Section 4(a)(2). EPA identified the recipients of the order through those sources related to manufacturers and processors of trans-1,2-dichloroethylene.

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By Lynn L. Bergeson and Carla N. Hutton
 
The U.S. Environmental Protection Agency (EPA) announced on April 18, 2022, that it will hold a webinar on May 11, 2022, entitled “Data-Driven Solutions to Reducing Animal Use in Ecotoxicity.” Speakers will include:

• Carlie LaLone, Ph.D., EPA Office of Research and Development (ORD), on “The Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) Tool: Extrapolating Knowledge Computationally.” EPA states that regulatory decision-making for chemical safety relies upon toxicity data generated from laboratory test species for the protection of wildlife in the environment. Typically, ecological risk assessments integrate safety factors to account for interspecies variability. According to EPA, the SeqAPASS tool is a more informed way to extrapolate knowledge from model species to other species that does not require the use of animals in toxicity testing and instead uses existing protein sequence knowledge. LaLone will describe EPA’s SeqAPASS tool and its applications for cross-species extrapolation relative to understanding conservation of biology and predicting chemical susceptibility.
   
• Michael Lowit, Ph.D., EPA Office of Pesticide Programs (OPP), on “Exploring Potential Reductions in Fish Testing in a Regulatory Context.” According to EPA, as part of its commitment to reducing animal testing, OPP is conducting retrospective analyses of existing data to evaluate critically which EPA guideline studies form the basis of regulatory decisions. EPA states that the results from these analyses can inform if reductions can be made to the number of animals used without reducing the quality of ecological risk assessments. EPA is currently conducting a retrospective analysis for fish acute toxicity tests, which are used by OPP to assess potential risk to fish species from pesticides. For each pesticide, EPA typically requires in vivo testing of three different fish species. Lowit will focus on the relative sensitivity among species subjected to in vivo fish acute toxicity studies. The results of this analysis will inform whether there is a basis for reducing the number of species while providing sufficient information to support pesticide registration decisions.

The webinar is co-organized by the People for the Ethical Treatment of Animals (PETA) Science Consortium International, EPA, and the Physicians Committee for Responsible Medicine (PCRM). EPA notes that it does not necessarily endorse the views of the speakers. Registration is now open.

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By Lynn L. Bergeson and Carla N. Hutton
 
The U.S. Environmental Protection Agency (EPA) announced on March 24, 2022, that it has issued a second round of test orders under Section 4 of the Toxic Substances Control Act (TSCA) to obtain additional data on eight of the next 20 chemicals undergoing risk evaluation. EPA states that after reviewing reasonably available data on these chemicals, it determined additional data are needed and is using its TSCA test order authority to require companies to develop and submit information on avian and aquatic environmental hazard and consumer exposure. The chemicals are:

• Chlorinated Solvents:
  • 1,1,2-Trichloroethane;
  • 1,2-Dichloroethane;
  • 1,2-Dichloropropane;
  • Trans-1,2-Dichloroethylene;
  • o-Dichlorobenzene; and
  • p-Dichlorobenzene;
• Flame Retardants:
  • 4,4ʹ-(1-Methylethylidene)bis[2,6-dibromophenol] (TBBPA); and
  • Phosphoric acid, triphenyl ester (TPP).

According to EPA, this is the third time it has used its new authority to issue test orders under Section 4 of amended TSCA. As reported in our January 15, 2021, blog item, in January 2021, EPA issued test orders for nine chemicals -- the eight chemicals above plus 1,1-dichloroethane -- requiring testing on aquatic environmental hazard and inhalation and dermal exposures for workers. EPA states that the information obtained through the orders will help ensure that its risk evaluations are “robust, credible, and use the best available data.”
 
EPA has posted a document describing the process of developing, drafting, and issuing Section 4 test orders. Companies subject to test orders may provide EPA with existing data, if available, or may conduct new tests. EPA states that companies are “encouraged to form consortia to consolidate costs and burden and avoid unnecessary duplication of testing.”

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By Lynn L. Bergeson and Carla N. Hutton
 
The U.S. Environmental Protection Agency (EPA) announced on March 4, 2022, the availability of the latest Toxic Substances Control Act (TSCA) Inventory. EPA states that the biannual update to the public TSCA Inventory is part of its regular posting of non-confidential TSCA Inventory data. EPA plans the next regular update of the Inventory for summer 2022. According to EPA, the Inventory contains 86,631 chemicals, of which 42,039 are active in U.S commerce. Other updates include new chemical substance additions, commercial activity data and regulatory flags, such as polymer exemptions, TSCA Section 4 test orders, and TSCA Section 5 significant new use rules (SNUR). EPA notes that on October 15, 2021, it announced a list of 377 specific chemical identities that were expected to lose their confidential status and move to the public portion of the Inventory. According to EPA, these 377 are listed in this public Inventory posting by their specific chemical identities.

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By Lynn L. Bergeson and Carla N. Hutton

The U.S. Environmental Protection Agency (EPA) announced on December 28, 2021, it is granting a petition from six North Carolina public health and environmental justice organizations filed under Section 21 of the Toxic Substances Control Act (TSCA) to compel companies to conduct testing of certain per- and polyfluoroalkyl substances (PFAS). The previous Administration denied the petition on January 22, 2021. 86 Fed. Reg. 6602. The petition sought issuance of a rule or order under TSCA Section 4 compelling The Chemours Company to fund and carry out this testing under the direction of a panel of independent scientists. The petitioners requested that EPA reconsider its denial in March 2021, which EPA agreed to do in September 2021, in light of the change in Administration and attendant change in policy priorities concerning PFAS. As reported in our October 19, 2021, memorandum, EPA published a National PFAS Testing Strategy (Testing Strategy) that identifies priority substances for the first of several described phases of an iterative testing approach based on grouping of chemicals by chemistry features and available toxicity data. EPA states that these substances include many of the chemicals identified in the petition, as well as additional PFAS that will inform a wider universe of categories of PFAS where key data are lacking. For example, according to EPA, the first phase of testing on 24 PFAS is expected to provide data that can be extrapolated to 2,950 PFAS that belong to the same categories as the 24 individual substances.

EPA states that it has granted the petition and will use its TSCA Section 4 order authority to require PFAS manufacturers to conduct and fund the following studies that will provide toxicity data and information on categories of PFAS:

• Near-Term Testing Covers 30 of 54 Petition Chemicals -- Under the Testing Strategy, EPA’s first test orders for 24 categories of PFAS about which the least is known will provide human health hazard data that cover 30 of the 54 petition chemicals;
• Subsequent Testing May Cover Nine of 54 Petition Chemicals -- An additional nine PFAS identified in the petition belong to one other category included in the Testing Strategy. EPA is conducting more in-depth analyses of the sufficiency of the existing data, which will inform later phases of testing;
• Remaining 15 of 54 Petition Chemicals -- According to EPA, 15 chemicals identified in the petition do not fit the definition of PFAS used in developing the Testing Strategy. EPA has determined that there are robust data on some of them available to it. EPA is conducting more in-depth analyses of the existing data, which will inform later phases of testing;
• Mixtures Studies -- EPA will address PFAS mixtures by using the toxicity of the individual substances to predict the toxicity of the mixture, an approach which is consistent with the current state-of-science on PFAS. EPA is proceeding with development and peer review of these methods as specifically applied to PFAS;
• Human Studies -- EPA is contributing to and reviewing numerous existing ongoing human studies, including studies on potentially exposed workers and communities in North Carolina, and is evaluating how to advance and expand on these efforts further. These include studies of health outcomes for people in communities impacted by industrial PFAS releases, as well studies that explore the connection between chronic health outcomes and PFAS exposures in North Carolina; and
• Analytical Standards -- EPA does not believe it is appropriate to require the development or submission of analytical standards with the initial test orders that will be issued under the Testing Strategy and lacks the ability to order the submission of all analytical standards in the manner requested. Nonetheless, EPA has requested comment on whether to require the submission of existing analytical methods for PFAS under a separate rulemaking that the Agency expects to issue in final next year.

Commentary

EPA’s reversal is hardly surprising. The Biden Administration’s commitment to obtaining information on PFAS is clear and has been reinforced in many contexts. In her remarks before the Committee on Energy and Commerce on October 27, 2021, for example, Assistant Administrator Freedhoff stated that EPA is “scouring all sources of information to identify important gaps in existing data and to select representative chemicals within identified categories or additional testing.” Reconsidering the prior Administration’s denial of the Section 21 petition seems like a no-brainer.

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By Lynn L. Bergeson and Carla N. Hutton
 
The U.S. Environmental Protection Agency (EPA) announced on August 31, 2021, the availability of the latest Toxic Substances Control Act (TSCA) Inventory. EPA states that the biannual update to the public TSCA Inventory is part of its regular posting of non-confidential TSCA Inventory data. EPA plans the next regular update of the Inventory for winter 2022. According to EPA, the Inventory contains 86,607 chemicals of which 41,953 are active in U.S commerce. Other updates to the TSCA Inventory include new chemical substance additions, commercial activity data and regulatory flags, such as polymer exemptions, TSCA Section 4 test orders, and TSCA Section 5 significant new use rules (SNUR). In April 2021, EPA released a list of 390 chemicals expected to lose their confidential status and move to the public portion of the Inventory. EPA states that it continues to work on final declassifications for these chemicals and plans to include them in the next public posting of the TSCA Inventory.

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