Application of the carcinogenicity prediction and battery selection (CPBS) method to the Gene-Tox data base

The carcinogenicity prediction and battery selection (CPBS) method (Chankong et al., 1985) utilizes the results of short-term tests to predict the carcinogenicity of chemicals and select batteries of tests that are capable of giving accurate predictions at reasonable costs. The CPBS method has been applied to the data compiled under the aegis of the Gene-Tox Program of the U.S. Environmental Protection Agency as a demonstration of the method on a typical data base. A number of batteries were selected by the methodology as having superior performance characteristics. The Bayesian predictions resulting from most of the selected 3-assay batteries were very good (greater than 90% of the carcinogens were correctly identified). It was also found that the 3-assay batteries of specified composition gave generally more accurate predictions than batteries of 4 or more assays of unspecified composition. A number of problems which may have affected our results have been identified: (1) the reliability of the sensitivities and specificities of the individual assays, (2) the prior probability that a chemical is a carcinogen was assumed to be 0.5, and (3) we have not (as yet) taken into account that some of the carcinogens are non-genotoxic and will produce false negative assays results. We are currently investigating approaches to take these factors into consideration. Our analysis also indicates that more testing of chemicals for carcinogenicity (especially probable non-carcinogens) is needed to further enhance the predictive capability of the CPBS method.