Carcinogenicity results for 114 laboratory animal studies used to assess the predictivity of four in vitro genetic toxicity assays for rodent carcinogenicity.

Carcinogenicity results are presented for 114 long-term rodent studies carried out by the National Toxicology Program. Tumor rates are given for each positive or equivocal effect observed in 67 studies judged to show carcinogenic effects and in the 17 studies that show equivocal effects. The liver was found to be the most common site of carcinogenicity for both mice and rats; other frequent target sites included the lung, kidney, hematopoietic system, forestomach, thyroid gland, and mammary gland. The evaluative approach used in reaching decisions regarding the carcinogenicity of chemicals is discussed. No rigid statistical decision rules were employed, and biological as well as statistical factors were considered in the overall evaluation of the data. These long-term studies were utilized in a comprehensive evaluation of the ability of four in vitro genetic toxicity tests to predict rodent carcinogenicity. Details concerning these procedures and the results of this investigation are given elsewhere [Zeiger E, Haseman JK, Shelby MD, Margolin BH, Tennant RW 1990: Environ Mol Mutagen 16 (Supp. 18):1-14]. Interestingly, those chemicals evaluated at relatively low doses in the rodent experiments (because of the underlying toxicity of the chemicals) were far more likely to be positive in each of the four genetic toxicity assays than were "less toxic" chemicals evaluated in higher doses in the rodent studies.