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Science Advisor Programs

A Review of the Reference Dose and Reference Concentration Processes

This report, entitled, "A Review of the Reference Dose and Reference Concentration Processes," summarizes the review and deliberations of the Risk Assessment Forum's RfD/RfC Technical Panel and its recommendations for improvements in the process of deriving reference values, including setting less than lifetime as well as chronic reference values. It discusses revisions to the overall framework for the derivation of reference values that broaden and expand the information considered in setting reference values.

The document is a review, not guidance, and it evaluates the state-of-the-art for hazard characterization with a focus on protection of potentially sensitive subpopulations. The report makes a number of recommendations that should be considered in the implementation of changes in the current process and/or development of needed guidance. The Technical Panel views the RfD/RfC process as one that should be continually evolving as new information becomes available and as new scientific and risk assessment approaches are developed. This does not mean that current RfDs or RfCs are invalid, but these new scientific issues should be included in the process of re-evaluating current reference values.

As a follow-up to the recommendation for deriving less-than-lifetime reference values, the report includes a review of current testing guideline protocols to determine what data are collected that could be used in setting these reference values. The Technical Panel has provided specific recommendations for deriving reference values and the development of guidance in some cases and more general conclusions and recommendations in others. Case studies are included to illustrate the recommendations of the Technical Panel.

This document reflects information received during two Agency and interagency colloquia, a public comment period, an external peer review, and a Science Policy Council review.

Contact: Risk Assessment Forum Staff (, or 202-564-6483

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Additional Information

  • Minor corrections were made to Appendix B on March 26, 2003.


  • U.S. EPA. A Review of the Reference Dose and Reference Concentration Processes. U.S. Environmental Protection Agency, Risk Assessment Forum, Washington, DC, EPA/630/P-02/002F, 2002.