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Harmonization in Interspecies Extrapolation: Use of BW 3/4 as Default Method in Derivation of the Oral RfD (External Review Draft)

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Report Information

EPA has released for independent external peer review and a 60-day public comment period, a draft report entitled Harmonization in Interspecies Extrapolation: Use of BW3/4 as Default Method in Derivation of the Oral RfD. When data from experiments using laboratory animals are used for evaluating human health risks, an adjustment for differences among species, usually called an interspecies extrapolation, is made to determine a human equivalent exposure. For the inhalation route of exposure, this issue was addressed in the 1994 EPA document Methods for Derivation of Inhalation Reference Concentrations and Application of Inhalation Dosimetry. This draft report focuses on the oral route of exposure.

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Background

As part of EPA's efforts to harmonize cancer and non-cancer risk assessment methods for human health evaluations, a Risk Assessment Forum Technical Panel examined the use of a hierarchy of approaches (similar to that use for inhalation reference concentrations) to derive the human equivalent oral exposures from data from laboratory animals. This document recommends such a hierarchical approach for interspecies extrapolations when developing oral reference doses (RfDs). The preferred approach is physiologically based toxicokinetic modeling, intermediate approaches would include using some chemical-specific information, and when appropriate data are absent, body weight to the 3/4 power (BW3/4) would be used as a default. This approach is consistent with methods for interspecies extrapolations for inhalation exposures (reference concentration [RfC]), and the use of BW3/4 as a default value for interspecies extrapolation when evaluating risks from exposure to carcinogens as discussed in EPA's 2005 cancer guidelines.

History/Chronology

Mar 2005EPA published the EPA Cancer Guidelines (Final 2005)
Feb 2006EPA release the first External Peer Review Draft (ERD) for public comment.
Dec 2008EPA's RAF program moved this draft report to the Office of the Science Advisor's Web site at http://www.epa.gov/raf/publications/interspecies-extrapolation.htm.

Next Steps

A peer review teleconference to which the public is invited to attend as observers. A Federal Register notice will announce the date, call-in number, and other details; a short time for public comments will also be available during the teleconference.

Additional Information

Also attached for your information are the charge questions for this peer review. Also available from this page is a contractor's review of the relevant literature that is mentioned in the EPA report. This document (Rhomberg, 2004) was prepared under contract 3W-0477-NASX and does not represent policies or conclusions of the U.S. Environmental Protection Agency.

Citation

U.S. EPA. Harmonization in Interspecies Extrapolation: Use of BW 3/4 as Default Method in Derivation of the Oral RfD (External Review Draft). U.S. Environmental Protection Agency, Washington, D.C., EPA/630/R-06/001, 2006.

Downloads

This download(s) is distributed solely for the purpose of pre-dissemination peer review under applicable information quality guidelines. It has not been formally disseminated by EPA. It does not represent and should not be construed to represent any Agency determination or policy.

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