Biological basis for extrapolation across mammalian species

The rationale for extrapolation or "scaling" across species is founded in the commonality of anatomic characteristics and the universality of physiologic functions and biochemical reactions. The development of the allometric equation, Y = aWn, relating species body size (W) with various morphological, physiological, biochemical, pharmacological, and toxicological characteristics, as the fundamental basis for extrapolation of biological data from laboratory animals to man is outlined. The familiar methods of extrapolation on the basis of "milligrams per kilogram body weight" and "body surface area" are simply examples, W1.0 and W0.67, respectively, of this equation. The experimental observations used to support these two, and other extrapolation bases, are reviewed. Criteria for the selection of an appropriate base for transfer of specific biologic data from laboratory animals to man, and the expected reliability of the extrapolation, are discussed with the enunciation of four guiding principles. The application of these principles to the extrapolation to man of dose-tumor incidence data from carcinogenicity bioassays of laboratory animals is discussed. The components are identified, and illustrative examples are given.