Regulatory toxicology and pharmacology : RTP
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Laboratory animals are used as models for humans in toxicity studies. This use is based on the assumption that extrapolation of biological data from animals to humans is valid. Three methods of extrapolation are considered: the use of body mass equivalence, caloric scaling across species, and the use of the surface area equivalence. ⋯ In recent years the principles of pharmacokinetics have been applied to interspecies scaling; pharmacokinetic short-term studies can be used to determine whether allometric scaling is justified. Considerations, however, should be given to (pharmacokinetic) differences in the same species and to species variability. It would be useful to develop a set of criteria for deciding when the pharmacokinetic model is needed and when simpler models will suffice.
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Regul. Toxicol. Pharmacol. · Sep 1986
Comparative StudyBiological 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. ⋯ 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.