US EPA

EPA announced the availability of the final report, Considerations for Developing a Dosimetry-Based Cumulative Risk Assessment Approach for Mixtures of Environmental Contaminants. This report describes a process that can be used to determine the potential value of developing physiologically based pharmacokinetic (PBPK) modeling to support a cumulative risk assessment. It also addresses the justification for developing physiologically based pharmacokinetic (PBPK) models for cumulative risk assessment. Chemical interactions in the body can alter the response observed, but the likelihood of an interactions is often most dependent on exposure. Results from these models can explain the basis for chemical interactions and can predict their likelihood at low, environmental exposures. This report identifies some key points to be considered when deciding whether to use PBPK modeling in a cumulative risk assessment.

This report develops a framework to guide decisions whether to incorporate physiologically-based pharmacokinetic (PBPK) modeling into the cumulative risk assessment process. This approach stresses the importance of initial analysis to eliminate those situations that do not warrant a PBPK-based approach to cumulative risk assessment thereby reducing the unnecessary expenditure of resources.

The purpose of this final report is to serve as a learning tool for EPA scientists and risk assessors in choosing to embark on PBPK modeling for cumulative risk assessment. It is structured around the 10-step procedure developed by the Office of Pesticide programs for conducting a cumulative risk assessment and the foundations of mixtures and cumulative risk assessment as conducted by the U.S. EPA. The approach is conducted in two phases, with the initial phase devoted to deciphering chemical-specific information to group chemicals, and the second phase devoted to guiding the application of PBPK modeling and the interpretation of dosimetry results to better inform the likelihood of chemical interactions and provide insight as to the likelihood of those interactions at environmentally-relevant exposure levels.
This is the final report. Portions of this report may also be found published in the peer-reviewed literature.

This report develops a framework to guide decisions whether to incorporate physiologically-based pharmacokinetic (PBPK) modeling into the cumulative risk assessment process.

U.S. EPA. Considerations For Developing A Dosimetry-Based Cumulative Risk Assessment Approach For Mixtures of Environmental Contaminants (Final Report). U.S. Environmental Protection Agency, Washington, DC, EPA/600/R-07/064, 2007.