An appraisal of predictive tests for carcinogenicity

The history of the development of the DNA damage-induced somatic mutation theory of cancer induction, and of the development of predictive tests for carcinogenicity, is reviewed briefly. On the basis of present information, it is concluded that all predictive tests for carcinogenicity of chemicals should be based primarily on validation using established carcinogens and non-carcinogens. The validation studies reported frequently suffer from limitations in design. Predictive tests pass through three stages during validation. First, the developing tests have been subjected to limited validation but show sufficient promise to warrant further development. 10 such tests are identified from the 100 tests reported in the literature. The second stage test can be considered as developed, when adequate validation studies have been completed to enable the selection of a test for its particular performance criteria. Only 9 such tests were identified of which only 1 still requiring further development can be considered as a useful primary screening test. 2 further tests can be considered as confirmatory tests to be used as a back-up to bacterial mutation assays. Finally, the established tests have been validated on a large scale in several laboratories. At present there is only one established test, namely the Salmonella/microsome test (Ames test). A second assay, based on E. coli, may be considered in this category because of its similarity to the Salmonella test. In conclusion, some guidelines for using predictive tests for regulatory and other purposes are given.