Predicting Rodent Carcinogenicity from Four in vitro Genetic Toxicity Assays: An Evaluation of 114 Chemicals Studied by the National Toxicology Program

Abstract

Abstract Four widely used in vitro assays for genetic toxicity were investigated for their ability to predict the carcinogenicity of chemicals evaluated in long-term rodent studies by the National Toxicology Program (NTP). These assays were mutagenesis in Salmonella typhimurium and in mouse lymphoma cells and chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells. Our evaluation compared results previously reported for 73 chemicals (Tennant et al. 1987) with results of similar analyses carried out for 41 additional chemicals tested subsequently by the NTP (Zeiger, Haseman, Shelby, Margolin, and Tennant, in press). For the combined data, Salmonella performed best, achieving a 66% (75/114) concordance, an 89% (32/36) positive predictivity, and a 55% (43/78) negative predictivity with regard to rodent carcinogenicity. The predictivity of Salmonella was even higher when attention was restricted to the multisite and/or two-species carcinogens. Chromosome aberrations also showed a ...