Cancer bioassays short term tests

In the absence of definitive human data, risk assessment may have to depend on the results of cancer bioassays in laboratory animals, short-term tests, or other experimental methods. Hence the following issues must be addressed under such circumstances the ability of the test system to predict risks for man (quantitatively as well as qualitatively) the reproducibility of test results the influence of species differences in pharmacokinetics, metabolism, homeostasis, repair rates, life span, organ sensitivity, and baseline cancer rates extrapolation across dose and dose rates, and routes of exposure the significance of benign tumors fitting models to the data in order to characterize dose-incidence relationships and the significance of negative results. 

The cost and duration of the combined chronic/cancer bioassay has limited its conduct to small numbers of selected chemicals. As a result, several short-term methods aimed at increasing predictive accuracy to enable testing of larger numbers of chemicals have been developed in attempts to successfully correlate Iheir results with evidence of carcinogenicity (or lack of carcinogenicity). This includes investigation of potential to promote tumor development, several model systems in Irans-genic and knockout models, and consideration of the predictive potential of traditional toxicity endpoints in shorter-term studies. 

With pressures from the animal rights movement, an impetus has been generated for the development of in vitro and/or computer models to reduce the level of in vivo testing. In the seventies, the hope of the future was placed in what was then considered a potential replacement technique for the lifetime rodent bioassay for cancer assessment—the short-term mutagenicity tests, particularly the Ames Evaluation (16). Brusick (17) has shown that the correlation between a positive mouse bioassay and a positive rat bioassay for a selected group of materials is no better than the... 

U. Saffiotti, Validation of short-term bioassays as predictive screens for chemical carcinogens, in Screening Tests in Chemical Carcinogenesis (R. Montesano, H. Bartsch, and L. Tomatis, eds.), pp. 3-13, International Agency for Research on Cancer (lARC Scientific Publ. No. 12), Lyons, France (1976). 

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