title: Essential roles for animal models in understanding human toxicities.
abstract: Strong cases have been made that there are no viable alternatives to the use of animal models in toxicology and, indeed, that virtually every major advance in the biomedical sciences and technologies stems in whole or in part from research performed with animals. Basic to these assertions is the assumption that information gained from such research can be extrapolated to "analogous" human conditions. Analogies may involve modeling at levels of bio-organization from molecules to the behaviour of the total, integrated organism: toxicity of exposure to a chemical varies with the structure(s) or function(s) modeled. Important decisions by regulators are always influenced by trade-offs between biological limitations and social cost-benefits, much information about the former coming from research on animals. This places great importance on the validities of extrapolations from the animal data, which may be expected to satisfy a hierarchy of five criteria. These range from evidence of superficial similarity ("face validity") to demonstration that knowledge obtained from the model is related to predictable outcomes in humans ("predictive validity"). Given the nature of the problems to be solved, which drastically limits the use of humans as subjects, animal models play essential roles in the biomedical sciences and technologies provided that due precautions are taken in creating models and in generalizing from them.
authors.affiliation: Department of Pharmacology, School of Medicine, University of California, Los Angeles 90024.
authors.forename: R W
authors.initials: RW
authors.lastname: Russell
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D009462:Neurology / Q000379:methods*; D014116:Toxicology / Q000379:methods*