PREDICTION OF RODENT CARCINOGENICITY FOR 44 CHEMICALS - RESULTS

Methods by which rodent carcinogenicity can be predicted have been pro spectively validated for 40 chemicals evaluated for carcinogenicity by the US National Toxicology Program. It is concluded that a chemical o f unknown carcinogenicity can be predicted to be in one of three possi ble categories-probably carcinogenic, probably non-carcinogenic or of uncertain activity. The last category is unlikely to contain genotoxic trans-species and/or multiple-site carcinogens. The component paramet ers of such predictions are one or more of several aspects of chemical structure, genotoxicity and rodent toxcity. Each of these parameters requires refinement but all are developed to the point that they can b e integrated to make assessment of possible carcinogenicity. Carcinoge nicity tends to be overpredicted by this integrated technique, each pa rt of which has already been simulated by computer modelling. Improvem ents in predictive methodology will now from three assumptions: (i) th at emphasis must be placed equally on the properties of the test chemi cal and the responses it elicits in tissues for which carcinogenicity is to be predicted, (ii) that the integration of different predictive techniques is preferrable to the exclusive use of a single technique, and (iii) that the general predictivity of any technique or combinatio n of techniques appears to be limited to less than or equal to 80%, im posed by inadequate knowledge, and uncertainties in the experimental e valuation and classification of carcinogenic responses for diverse che micals. This last statement does not preclude the attainment of higher accuracy within a congeneric series of chemicals. Foreknowledge of th e likely outcome of a rodent carcinogenicity bioassay is now possible and will contribute to the focusing of animal testing resources.