Considerations For Developing A Dosimetry-Based Cumulative Risk Assessment Approach For Mixtures of Environmental Contaminants (Final Report)
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Overview
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.
Citation
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.
Background
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.
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.
History/Chronology
| Date | Description |
|---|---|
| 2003 | EPA award releases a solicitation for a contract to develop a report for the Method of Analysis to Perform a Tissue-Based Cumulative Risk Assessment for Mixtures of Chemicals. |
| 2004 | A draft document is circulated for internal review. |
| 2005 | A draft document is subjected to an external panel review. |
| Sep 2007 | EPA finalized the report. |
| Apr 2009 | EPA released the final report. |
Download(s)
This document has been reviewed in accordance with U.S. Environmental Protection Agency policy and approved for publication. Mention of trade names or commercial products does not constitute endorsement or recommendation for use.
- U.S. EPA/Considerations for Developing a Dosimetry-Based Cumulative Risk Assessment Approach for Mixtures of Environmental Contaminants (Final Report) (PDF) (77 pp, 595.7 KB, about PDF)
- Appendix A: PHYSIOLOGICALLY-BASED PHARMACOKINETIC/PHARMACODYNAMIC (PBPK/PD) MODELING REFERENCE (PDF) (16 pp, 515.6 KB, about PDF)
- Appendix B: HOW TO INCORPORATE CREDIBLE HUMAN ENZYME STUDIES INTO THE PHYSIOLOGICALLY-BASED PHARMACOKINETIC (PBPK) MODELING AND RISK ASSESSMENT PROCESS Reference (PDF) (19 pp, 1.2 MB, about PDF)
- Appendix C: INFORMATION ON CHEMICAL MIXTURES AND THEIR COMPONENT CHEMICALS (PDF) (86 pp, 994.1 KB, about PDF)
- Appendix D: Method of Analysis to Perform a Tissue-Based Cumulative Risk Assessment for Mixtures of Chemicals (PDF) (22 pp, 252.9 KB, about PDF)
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Document Related Link(s)
- EPA Guidance on Cumulative Risk Assessment of Pesticide Chemicals that Have a Common Mechanism of Toxicity
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WHO. 2010. Characterization and Application of PBPK Models in Risk Assessment (Final Report)
- Supplementary Guidance for Conducting Health Risk Assessment of Chemical Mixtures
- Guidelines for the Health Risk Assessment of Chemical Mixtures (Final Report, 1986)
- Health Risk Assessment of Chemical Mixtures
- Approaches For the Application of Physiologically Based Pharmacokinetic (PBPK) Models and Supporting Data In Risk Assessment (Final Report)