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

Joseph K. Haseman, Errol Zeiger, Michael D. Shelby, Barry H. Margolin and Raymond W. Tennant
Journal of the American Statistical Association
Vol. 85, No. 412 (Dec., 1990), pp. 964-971
DOI: 10.2307/2289593
Stable URL: http://www.jstor.org/stable/2289593
Page Count: 8
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Predicting Rodent Carcinogenicity From Four in Vitro Genetic Toxicity Assays: An Evaluation of 114 Chemicals Studied by the National Toxicology Program
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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 significant association with rodent carcinogenicity, but no significant correlation was observed for the sister chromatid exchange or mouse lymphoma assays. Positive results in the latter two assays were often associated with chemical toxicity. Our investigation confirmed the findings of Tennant et al. (1987) that for these particular chemicals there was no evidence of complementarity among the four assays, and no battery of tests constructed from these assays improved substantially the performance of the Salmonella assay.

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