The U.S. Environmental Protection Agency (EPA) announced on June 16, 2023, a 60-day public comment period on the draft Guidelines for Cumulative Risk Assessment Planning and Problem Formulation (draft CRA Guidelines). 88 Fed. Reg. 39424. According to EPA, the draft CRA Guidelines describe steps for the planning and problem formulation of CRAs and offer guidelines for when CRAs could be appropriate. Planning defines both the process for conducting the risk assessment and its general scope, while problem formulation identifies major factors considered in a specific assessment to inform its technical approach. EPA notes that the draft CRA Guidelines “are not final, and do not represent, and should not be construed to represent, Agency policy or views.” Comments are due August 15, 2023.

The draft CRA Guidelines provide methods and procedures for CRA planning, “a necessary step in the advancement of CRA from a concept to a decision-relevant tool.” The draft CRA Guidelines comprise three sections:

• An introduction;

• A second section on CRA planning and scoping: The scoping step in the planning phase identifies the significant factors in the assessment and should determine if CRA is the right approach for conducting the assessment. The steps for scoping the assessment presume a risk management question suited to CRA; and

• A third section on CRA problem formulation: The problem formulation section describes steps for developing the conceptual model that provides initial understanding of relationships among factors in the assessment. The problem formulation statement provides a precise description of how the proposed risk assessment serves the risk management decision. Problem formulation results in an analysis plan, which describes the methods necessary to conduct the needed analysis.

According to the draft CRA Guidelines, although it defines steps sequentially for ease of communication, the process can involve simultaneous steps or a different sequence. Steps also might be repeated in an iterative approach. The draft CRA Guidelines state that the scoping and problem formulation phases “are mutually informative, as greater detail and more information advance the assessment.” The draft CRA Guidelines provide factors considered to be important for consideration in bulleted form or listed in many of the sections. Strategic questions associated with some sections are highlighted in green.

The draft CRA Guidelines recommend a tiered and/or phased process for matching the design of CRA to the level of risk management need. The intent of tiering or phasing the analysis is “to tailor the level of effort to be commensurate with the purpose of the risk assessment.” According to the draft CRA Guidelines, “[t]he incremental process of gathering information typical of tiering and phasing reinforces the recursive process between problem formulation and the other steps in planning of the CRA.”

The draft CRA Guidelines identify eight milestones that segment important stages of the CRA planning process, and at which time the CRA Team “should pause to formalize understanding of the progress in planning the CRA”:

1. Initiating factors;

2. Identification of stakeholders;

3. Statement of purpose;

4. Evaluation of the fit for purpose;

5. Scoping summary statement;

6. Conceptual model;

7. Weight of evidence evaluation; and

8. Analysis plan.

According to the draft CRA Guidelines, “[e]ach milestone is an appropriate point at which the CRA Team may confirm its planning progress and consider reiteration of earlier steps based on collection of new information, insights from evaluation, or indication that additional data or information may be required to complete the CRA.”

Commentary

EPA is to be commended for tackling CRA, and stakeholders are grateful for EPA’s efforts. The plan, however, will pose some significant scientific challenges for EPA. It may be the case that EPA will face instances in which there is limited opportunity to evaluate cumulative toxicity (e.g., phthalate syndrome) or instances in which the mechanism is so common that it will be difficult to limit the scope of a CRA (e.g., lung surfactancy, sensitization, corrosion, or lung overload). For location-specific CRA analyses, EPA will be challenged to identify the non-chemical factors that lead to cumulative risk.

Commenters may wish to focus on how EPA defines the categories to be evaluated for cumulative risk.