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Methods for Identifying a Default Cross-Species Scaling Factor (Rhomsberg, 2004)

The goal of the present evaluation is to provide a rationale for selecting default cross-species extrapolation factors with which to scale oral doses across species for non-carcinogenic endpoints. Recognizing the importance of incorporating specific chemical data wherever appropriate, a second goal is to describe how chemical-specific data (e.g., metabolic or mechanistic data) can be incorporated into the dose extrapolation process.
This paper is focused primarily on oral doses and oral exposures, as these represent:
  1. the most common route of dosing used in toxicology studies
  2. the route least affected by factors (e.g., differences in respiratory physiology or skin thickness) which are unlikely to follow a clear relationship across species

The oral route is not the only exposure route for which cross-species scaling is of interest but, for the reasons just given, it is considered as the base case upon which further scaling relationships can be built to account for factors specific to other exposure routes.

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