US EPA

EPA announced the availability of the final report, Concepts, Methods, and Data Sources for Cumulative Health Risk Assessment of Multiple Chemicals, Exposures and Effects: A Resource Document. This report provides the concepts, methods and data sources needed to assist in the conduct of a multi-chemical, population-focused cumulative risk assessment. It is not guidance, but rather a presentation of information that could assist in the development of future guidance on cumulative risk assessment. It addresses a subset of issues related to chemical mixtures risk assessment that are identified in the 2003 Framework for Cumulative Risk Assessment. This report focuses on two areas:

1. initiating factors for a cumulative risk assessment, with procedures for data collection and organization, and
2. technical approaches for assessing human health risks associated with a multiple chemicals, exposures and effects.

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 includes anyone involved in cumulative 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 Agency reports on cumulative risk assessment planning and scoping and on environmental justice concerns have highlighted the importance of estimating cumulative risks. EPA has published 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 new document 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. Innovations include the following:

• Procedures for population characterization, data collection and data organization based on the initiating factors for a cumulative risk assessment
• A chemical grouping method to scope analyses into manageable pieces to be assessed as multiple chemicals with co-occurring exposures and common toxicity
• Approaches and data sources for evaluating the timing of exposures, including discussions of chemical degradation over time in the environment and of kinetics and dynamics
• Integration of internal dose measurements to account for multiple route exposures
• Estimation of mixture risks for multiple route exposures by calculating route-specific risks using the Relative Potency Factor (RPF) approach and then summing the route-specific RPF-based risks across routes
• Integration of output from multiple effects modeling (illustrated using a categorical regression model) with the Hazard Index (HI) and response addition models to express risks for multiple health effects
• Detail on the cumulative HI approach, including impacts for risk characterization
• Refinement of the interaction-based HI method to account for toxicological interactions
• A method for cumulative risk characterization that considers factors unique to the conduct of a cumulative risk assessment, including uncertainties in cumulative dose-response and exposure assessment
• A general emphasis on integrating exposure and dose-response analysis
• A Risk Assessment Toolbox (Appendix A) that provides numerous sources of data and tools for use in conducting a cumulative risk assessment.

This goal of this report is to present concepts that could assist in the development of future Cumulative Risk guidance.

U.S. EPA. Concepts, Methods, and Data Sources For Cumulative Health Risk Assessment of Multiple Chemicals, Exposures and Effects: A Resource Document (Final Report, 2008). U.S. Environmental Protection Agency, Washington, DC, EPA/600/R-06/013F, 2007.