Recommended Use of Body Weight 3/4 as the Default Method in Derivation of the Oral Reference Dose
Recommended Use of body weight ¾ as the Default Method in Derivation of the Oral Reference Dose presents body weight ¾ as the default methodology for interspecies dosimetric extrapolation for use in toxicological studies using animal data to assess effects on humans. The document lays out the scientific rationale for such an approach, the modifications to the application of interspecies uncertainty factors and provides the methods for computing the Dosimetric Adjustment Factor to determine the human equivalent dose. This document has undergone both internal (within EPA) and external peer review and public comment. The final document reflects the comments submitted through the review process.
Historically, EPA has applied a direct cross-species extrapolation based on body weight (body weight 1/1) for noncancer endpoints while applying a body weight ¾ extrapolation for cancer endpoints. By modifying the scaling to body weight ¾ for noncancer endpoints this document harmonizes the default methodology for assessing risks for cancer and noncancer endpoints.
Federal Register Notice
- Federal Register, Friday, Jun 5, 1992, Draft Report. A Cross-Species Scaling Factor for Carcinogen Risk Assessment Based on Equivalence of mg/kg ¾ Day (PDF)(24 pp, 1.8 MB, About PDF)
- Federal Register, Friday, Feb 25, 2011, Notice of Availability; Recommended Use of Body Weight3∕4 as the Default Method in Derivation of the Oral Reference Dose
Document Details and Links
This document promotes the use of body weight ¾ as a default method to convert data between species for both categories of endpoints. A hierarchy of methods for inter-species scaling is presented along with the rationale for selection of the scaling factor and guidance on how to conduct the conversion.