Extrapolation of animal toxicity data to man.
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. Allometry, defined as the study of size and its consequences, is considered. There is still controversy whether there is an allometric relationship for energy metabolism. Allometry offers, among others, the concept that not all of the mass of the animal is equally involved in metabolism. 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.
Vocci
F
F
Environmental Protection Agency, Office of Pesticides Program, Washington, DC 20460.
Farber
T
T
D000280:Administration, Inhalation; D000818:Animals; D001835:Body Weight; D004195:Disease Models, Animal; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D010599:Pharmacokinetics; D013045:Species Specificity