US EPA

This report is not guidance but rather a presentation of concepts that could assist the development of guidance. It presents risk assessment approaches and information on a subset of issues that are identified in the 2003 Framework for Cumulative Risk Assessment. The sequence of procedural steps suggested in this report is designed to emphasize the links between the exposed population and the multiple factors being addressed. The audience for this report is anyone involved in chemical risk assessment who needs to address the joint impact of multiple chemicals, exposures and effects.

In EPA's 2003 Framework for Cumulative Risk Assessment, cumulative risk assessment is defined as the evaluation of risks from exposures to multiple chemicals and other stressors, and having a population focus rather than a source-to-receptor focus. Several reports and environmental justice concerns published over the past 11 years have highlighted the importance of estimating cumulative risks. EPA has published several guidance documents dealing with specific aspects of cumulative risk, such as chemical mixture risk assessment, planning and scoping, stakeholder involvement, and the toxicity from a mixture of pesticides sharing a common mode of action. This draft document is one contribution to EPA's efforts to address issues related to cumulative health risk assessment.

Existing EPA guidance addresses some of the aspects of cumulative risk, but none addresses all of the combinations of multiples included in this report, such as consideration of the composite impact of multiple health effects. Among the distinctive new approaches are:

• grouping chemicals based on exposure characteristics and toxic endpoints for use in applying chemical mixtures risk assessment methods,
• assessing multi-route exposure combinations using relative potency factors,
• integration of categorical regression modeling of multiple effects with additivity approaches, and
• emphasis on the iteration and collaboration between exposure assessment and dose-response assessment to ensure compatible and relevant information.

This draft report provides a set of approaches that deal with certain complications in cumulative risk assessment, specifically those caused by multiple chemicals, exposures and effects, including toxicological interactions and environmental transformations of mixture component chemicals. The report is also focused on the evaluation of health risks from exposures to multiple chemicals, including multiple exposure routes and times as well as multiple health endpoints. Major findings and conclusions in this document are as follows:

• Areas of cumulative health risk assessment emphasized in this report can often be performed with existing information.
• Exposure and toxicity characterizations of mixtures are strongly dependent on mixture composition (chemicals and concentrations) and timing of exposures and health effects.
• Qualitative and semiquantitative approaches provided can simplify the number of potential combinations of chemicals, exposures, and effects to make the cumulative health risk assessment more feasible.

This goal of this report is to present concepts that could assist in the development of guidance. It presents risk assessment approaches and information on a subset of issues that are identified in the 2003 Framework for Cumulative Risk Assessment.

NCEA will hold a public meeting in 2006 to receive scientific peer review and comments on this external review draft, Considerations for Developing Alternative Health Risk Assessment Approaches for Addressing Multiple Chemicals, Exposures and Effects. A Federal Register Notice will announce the date of the meeting and its location. EPA will then review any feedback and recommendations with plans to publish the final document by September 2006.

U.S. EPA. Considerations for Developing Alternative Health Risk Assessment Approaches for Addressing Multiple Chemicals, Exposures and Effect (External Review Draft). U.S. Environmental Protection Agency, Washington, D.C., EPA/600/R-06/014A, 2006.