On April 24, 2023, the U.S. Environmental Protection Agency (EPA) held a virtual public preparatory meeting for the Science Advisory Committee on Chemicals (SACC) members, ad hoc reviewers, and the public to comment on and ask questions regarding the scope and clarity of the draft charge questions to be used for the May 8-11, 2023, review of two draft documents related to cumulative risk assessment (CRA) under the Toxic Substances Control Act (TSCA). As reported in our March 1, 2023, memorandum, earlier this year, EPA released for public comment and peer review a set of principles for evaluating cumulative risks under TSCA and an approach for applying those principles to the evaluation of the cumulative risk posed by certain phthalate chemicals undergoing TSCA Section 6 risk evaluation:

• Draft Proposed Principles of Cumulative Risk Assessment under the Toxic Substances Control Act (hereinafter the Draft Principles Document): The document discusses what CRA is and how it could be used in the scientific and regulatory context of TSCA. EPA notes that a CRA “will not always be the best approach, or possible to complete in the statutory timeframes provided for TSCA risk evaluations. But when chemicals are sufficiently similar toxicologically and are found to present co-exposures -- meaning people are . . . exposed to multiple chemicals at the same time -- a cumulative risk assessment may be appropriate.”

• Draft Proposed Approach for Cumulative Risk Assessment of High-Priority Phthalates and a Manufacturer-Requested Phthalate under the Toxic Substance Control Act (hereinafter the Draft Phthalates CRA Document): The document describes a proposed methodology for evaluating cumulative risk for the phthalate chemicals currently under review. EPA proposes in its approach submitted for public comment and peer review that di-ethylhexyl phthalate (DEHP), butyl benzyl phthalate (BBP), dibutyl phthalate (DBP), di-isobutyl phthalate (DIBP), dicyclohexyl phthalate (DCHP), and di-isononyl phthalate (DINP) (but not di-isodecyl phthalate (DIDP)) are toxicologically similar (and pose an additive hazard) and that the U.S. population is co-exposed to these phthalates. Therefore, EPA proposes to group these phthalates for CRA under TSCA as described in the Draft Phthalates CRA Document. EPA notes that this proposed approach “is not itself a cumulative risk assessment nor does it make a finding of risk, but rather is a methodology that EPA proposes to use and seeks public input about and peer review on.”

Anthony Luz provided an overview of the draft documents. As stated in the slides for the preparatory meeting, while TSCA does not explicitly require EPA to conduct CRAs, nothing in TSCA prohibits EPA from doing so. EPA noted that TSCA does require that EPA, when conducting TSCA risk evaluations, consider the reasonably available information, consistent with the best available science, and make decisions based on the weight of the scientific evidence. According to EPA, for some chemical substances, the best available science may indicate that “the development of a CRA is appropriate to ensure that any risks to human health are adequately characterized.” The Draft Principles Document:

• Outlines the proposed principles of CRA as potentially conducted in support of TSCA;

• Defines CRA within the regulatory requirements of TSCA as “an analysis, characterization, and possible quantification of the combined risks to health and/or the environment from multiple agents and/or stressors”;

• Focuses on cumulative risks from exposure to toxicologically similar chemical substances; and

• Builds off works by EPA’s Risk Assessment Forum and Office of Pesticide Programs, the Organization for Economic Cooperation and Development (OECD), the World Health Organization (WHO)/International Program on Chemical Safety (IPCS), and European Commission (EC).

The Draft Principles Document does not:

• Provide a framework or guidance on a process for conducting CRAs; or

• Address cumulative impacts. According to EPA, cumulative impacts “refers to the total burden -- positive, neutral, or negative -- from chemical and non-chemical stressors and their interactions that affect the health, well-being, and quality of life of an individual, community, or population at a given point in time or over a period of time.”

EPA stated that its Draft Phthalates CRA Document:

• Is an approach to evaluate several high-priority (DEHP, BBP, DBP, DIBP, DCHP) and manufacturer-requested phthalates (DINP, DIDP) for cumulative risk to human health;

• Adheres to many of the recommendations outlined by NRC; and

• Builds off the approaches used in previous phthalate CRAs conducted by the U.S. Consumer Product Safety Commission (CPSC), Health Canada, and other regulatory agencies.

EPA noted that its Draft Phthalates CRA Document is not:

• A risk evaluation, and no risk estimates are presented. EPA notes that it is currently conducting risk evaluations for individual phthalates (each will undergo peer-review); and

• A reflection of completed systematic review, hazard identification, dose-response assessment, or exposure assessment.

The SACC members asked for clarification of several of the charge questions. The first question asks the reviewers to identify any additional key methodology documents, but EPA stated in its summary that the Draft Principles Document concerns proposed principles and is not a required methodology. EPA responded that it would discuss clarifying the question. The second question states that EPA “is proposing to establish a cumulative chemical group for purposes of CRA using a weight of evidence approach that characterizes the strengths and uncertainties of the evidence of toxicological similarity and potential co-exposure for each chemical substance in the group.” EPA asks SACC to comment on the appropriateness of this approach, including on the strengths and uncertainties. A SACC member noted that EPA has provided a document that gets into the thought on the toxicology side, but there is nothing on exposure or special populations. EPA responded that it did so to keep it more broad in the Draft Principles Document, but that the Draft Phthalates CRA Document does get deeper.

The third charge question states that several additivity approaches can be used to evaluate multiple chemical substances for cumulative risk, including dose addition, response addition, and integrated addition and that EPA plans to rely upon a default assumption of dose addition when conducting CRAs for toxicologically similar chemical substances under TSCA, unless empirical evidence supports application of another approach. A SACC member asked if EPA wanted other approaches added that are variations on additivity. EPA stated that using the best available science supports using the available science, and that other approaches would be good to consider. Question five asks if there are any “additional notable phthalate CRAs” that may inform EPA’s Draft Phthalates CRA Document. A SACC member noted that the question appears to focus on information from regulatory bodies and asked if that is the only focus. EPA states that it focused on CRAs by other agencies because those CRAs had gone through both public comment and peer review. Question 21 concerns fenceline assessment and sources that EPA may consider for developing a cumulative fenceline assessment. A SACC member asked what EPA means by fenceline community. EPA responded that fenceline community is defined in the Draft Phthalates CRA Document and that it relied on the fenceline SACC.

Commentary

Bergeson & Campbell, P.C. (B&C^®) notes that the virtual public preparatory meeting was limited to receiving comment from the public and the SACC on the scope and clarity of the draft charge questions. The draft charge questions focused on receiving SACC’s comments on sections of the respective documents and EPA’s preliminary decisions. There was, however, a conspicuous difference between the draft charge questions on the Draft Principles Document and on the Draft Phthalates CRA Document, as discussed below.

The draft charge questions for the Draft Principles Document included a final request for the SACC to “Please comment on the overall clarity of EPA’s Draft Proposed Principles Document, including additional areas that EPA may consider for inclusion.” We note that the Draft Phthalates CRA Document did not contain a comparably open-ended request for overall comments from the SACC. This may have been an oversight on EPA’s part. Alternatively, EPA may have intentionally avoided adding an open-ended request on the Draft Phthalates CRA Document to avoid repetitious feedback from the SACC, which EPA received on its “first 10” final risk evaluations. Regardless, we mention this because the scope of the SACC’s review is guided by the charge questions. Therefore, interested persons may wish to comment on this point generally during the SACC’s peer review of the draft CRA documents, as discussed below.

B&C encourages interested persons to attend virtually the SACC peer-review meeting on the Draft Principles Document and the Draft Phthalates CRA Document on May 8-11, 2023. Unlike the virtual public preparatory meeting, the SACC peer-review meeting will provide interested persons with an opportunity to provide technical feedback to EPA, as part of oral comments, and to hear the perspectives of the SACC members on the merits of EPA’s decision-making and preliminary scientific conclusions on the Draft Principles Document and the Draft Phthalates CRA Document.

Companies with products that may be subject to a CRA approach are encouraged to participate. EPA and the SACC will be building the methodology with which EPA will conduct CRAs in the future. While the specific facts related to future CRAs will not be discussed, the criteria that inform whether a CRA is appropriate should be on the agenda and readers should take this opportunity to ensure that future CRAs are required to be grounded on sound science.