Identification of rodent carcinogens and noncarcinogens using genetic toxicity tests: Premises, promises, and performance

The basic premises that guide genetic toxicity testing for identifying carc inogens and to support administrative and regulatory decisions are: the Sal monella mutagenicity test is a necessary component of testing schemes; a ch romosome aberration test is needed in addition to a gene mutation test; a m ammalian cell mutagenicity test is needed in addition to the Salmonella tes t; in vivo tests are needed to confirm the results of in vitro tests; and t est batteries are more predictive than the individual tests of the battery. Results from the Salmonella mutagenicity, in vitro chromosome aberration, mutations in mouse lymphoma cells, rodent bone marrow micronucleus, and rod ent carcinogenicity tests, performed by the U.S. National Toxicology Progra m, were used to evaluate these premises. A positive Salmonella test was mos t predictive of carcinogenicity. However, the data do not support using the other tests in addition to Salmonella for predicting carcinogenicity. The genetic toxicity tests did not complement each other, and batteries or comb inations of the tests were no more predictive of carcinogenicity than Salmo nella alone. If a chemical is mutagenic in Salmonella it should be consider ed a potential rodent carcinogen, unless ancillary information suggests oth erwise. Positive responses in the other in vitro or in vivo tests do not in crease the probability that the chemical is a carcinogen, and negative resp onses in the other tests do not diminish the implications of the positive S almonella response.