Examples of Alternative Use in Toxicology for Common Species

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The principle of refinement of animal usage in toxicology dictates that the appropriateness of a particular animal species for a particular protocol or experiment be thoroughly explored. Species are selected all too often on the basis of convenience or tradition. Rats are traditionally used for acute lethality testing and carcinogenicity testing. Dogs are traditionally used as a “nonrodent” species for general toxicity assessments. This review seeks to make the case that, for both scientific and economic reasons, other species can be appropriately substituted for rats or dogs for general toxicity assessment studies. These alternative species need not be totally exotic, but can, in fact, be species used in other areas of toxicology. Earthworms and fish are nonvertebrate animals used in environmental assessment studies. Earthworms could be used for lethality assessment in place of rodents, particularly for “QC batch” release or toxicity rating purposes. Fish could be used to further define hepatic carcinogenicity. Guinea pigs are frequently used for dermatologic studies, but rarely for other purposes. While a rodent, the guinea pig possesses many physiologic and metabolic characteristics that may make it more appropriate than rats for the chronic testing of certain classes of chemicals (NSAIDs, peroxisomal proliferators). Ferrets have been well studied in teratologic assessments, but have not gained wide acceptance as a “nonrodent” model. This review discusses in detail the available technology and published data that justifies the expanded and appropriate use of these “alternative” species. Special emphasis is given to xenobiotic metabolism, which is a major determinant in speciesrelated differences in toxicity.