As noted in our February 25, 2022 blog post, the U.S. Environmental Protection Agency (EPA) announced on February 25, 2022 the proposed TSCA (Toxic Substances Act) New Chemicals Collaborative Research Program. Control Act). 87 Fed. Reg. 10784. On March 10, 2022, the EPA released the draft document titled “Modernizing the Process and Bringing Innovative Science to Evaluate New Chemicals Under TSCA”. The Office of Chemical Safety and Pollution Prevention (OCSPP) proposes to develop and implement a multi-year collaborative research program focused on approaches to conducting risk assessments on new chemical substances within the framework of of the TSCA. EPA will hold a virtual public meeting April 20-21, 2022, to solicit an individual contribution. Written comments on the draft document are due April 26, 2022.

According to the draft document, prior to developing this research plan, the Office of Pollution Prevention and Toxic Substances (OPPT) developed the following problem formulation statement:

PROBLEM STATEMENT:

Using the best available science involves the OPPT’s use of methods, approaches, and tools to evaluate new chemicals before they enter the U.S. market, and to refine and update them as appropriate. applicable. Any changes should align with regulatory timelines, be operational in a data-poor environment, make effective use of new data sources and approaches, and be transparent to the extent possible given that TSCA [confidential business information (CBI)] can be used in the development of these approaches.

The draft document indicates that the following vision statement provides the fundamental concepts that must be included in research to resolve the problem statement.

VISION STATEMENT:

Continue to evolve OPPT’s use of new and existing methods, approaches, and tools to assess new chemicals under TSCA that typically lack specific information (that is to saylack of data) on risks to human health and the environment through the use of innovative science.

According to the draft document, the OPPT is working closely with the Center for Computational Toxicology and Exposure (CCTE) of the Office of Research and Development (ORD) and the Center for Public Health and Environmental Assessment (CPHEA) to develop and implement the research plan. In addition, EPA will consult with internal and external partners critical to the completion of the research plan for research input and contributions. The proposed research focuses on five areas. The EPA notes that some activities are already underway while others are new and have not yet started.

1. Update and refine chemical categories:

• Problem: Currently 56 TSCA categories, last updated 2010;
• Approach: Systematically define chemical categories and analogues for read-across using structural (and other) boundaries; physico-chemical properties; structural alerts for hazards, fate, exposure and/or functional uses; existing hazard data; and or in vitro mechanistic and toxicokinetic data from new approach methodologies (NAM); and
• Expected Result: This will increase the efficiency of new reviews of chemicals and promote the use of the best available data to protect human health and the environment.

2. Develop and develop databases containing TSCA chemical information:

• Problem: Existing TSCA information is not computationally accessible or easily searchable;
• Approach: Extract and store available information on the TSCA CBI study; continue the extraction and storage of information on physico-chemical properties, environmental fate, hazards and exposure (non-CBI) in the ORD databases; and mapping information from ORD databases to standardized reporting templates and storing it in a Uniform International Chemical Information Database (IUCLID); and
• Expected Result: TSCA CBI information will be combined with publicly available sources to expand the amount of information available, improve chemical reviews, and enable effective sharing of chemical information within the EPA. Safeguards for RCCs will be maintained as needed in this process.

3. Develop and refine quantitative structure-activity relationships (QSARs) and predictive models for physico-chemical properties, environmental fate/transport, hazard, exposure and toxicokinetics:

• Problem: Models currently in use are not always publicly available, easy to update with additional chemicals or best performing for all chemicals;
• Approach: Develop and update QSAR and predictive models using existing and curated data from Research Area 2; and evaluate the models to determine the best suite to be used by the OPPT for regulatory purposes; and
• Expected Result: Updated models that reflect the best available science, increased transparency, and a process for updating these models as science permits.

4. Explore ways to integrate and apply NAMs in new chemical assessments:

• Issue: Reduced use of vertebrate animals per TSCA Section 4(h); many Prefabrication Notice (PMN) submissions are data poor; and the amended TSCA requires an affirmative determination of unreasonable risk;
• Approach: Develop and evaluate a suite of in vitro NAM to inform new chemical assessments; and use mechanistic and toxicokinetic methods in vitro NAM to inform and refine chemical categories in Research Area 1; and
• Expected Result: A suite of NAMs that could be used by external stakeholders for TSCA testing and data submissions, as well as informing and expanding new chemical categories.

5. Develop a TSCA decision support tool on new chemicals to modernize the process:

• Problem: Researching, collecting and integrating data for new chemical assessments is inefficient and costly;
• Approach: Create a proof-of-concept software workflow that integrates all data streams into a new chemical risk decision context; and
• Expected result: A decision support tool that will effectively integrate all data streams (for example., chemistry, fate, exposures, hazards) in a final risk assessment and transparently document the decisions and assumptions made. This will facilitate the tracking of new chemicals program decisions over time and the assessment of consistency within and between chemicals.

Next steps

EPA will hold a virtual public meeting April 20-21, 2022, to solicit an individual contribution. Written comments on the draft document are due April 26, 2022. According to the draft document, later in 2022, the EPA plans to engage its Board of Science Advisors (BOSC), a federal advisory committee, for peer review. The EPA also intends to issue a Federal Register notice announcing the BOSC meeting and to open a file for public comment. The EPA states that it will seek additional peer review and public comment at several points during the development and implementation phases of the research. Although the peer review schedule may be adjusted if necessary in the future, at this time the OPPT anticipates the following:

EPA will publish data and approaches to research efforts in the open scientific literature. EPA will also implement outreach through appropriate mechanisms, including scientific societies, state and tribal communications, internationally through the Organization for Economic Co-operation and Development (OECD) and other mechanisms. EPA will hold public meetings to receive feedback and improve transparency.

Remark

The EPA is to be commended for initiating these areas of research. As the EPA’s own commentary notes, each of the five areas needs updating and modernization, and chemical innovation under TSCA will be advanced accordingly as desired results are achieved.