Quantitative prediction of human cancer risk from rodent carcinogenic potencies: A closer look at the epidemiological evidence for some chemicals not definitively carcinogenic in humans

Abstract

The existence of rodent carcinogens for which at least one epidemiological study found no evidence of human carcinogenicity has been claimed to provide evidence of the poor predictivity of rodent bioassays ( F. K. Ennever, T. J. Noonan, and H. S. Rosenkranz (1987). Mutagenesis, 2, 73–78). We have performed quantitative comparisons of the rodent and human carcinogenic potencies for these same chemicals. Starting with the rodent TD 50 at the most sensitive site, we derived a predicted human incidence for the degree of exposure and duration of follow-up corresponding to the most comprehensive epidemiological study available, and then we compared the predicted incidence with the observed incidence. If a chemical produced no statistically significant increase in cancer at any site in the exposed population, consistency with rodent results is inferred if the minimum rodent TD 50 is sufficiently high that no attributable cases would have been expected under the actual conditions of human exposure and follow-up. For 18 of the 22 chemicals examined, the human evidence is consistent with the predictions based on the rodent bioassay results. For two chemicals, dichlorobenzidine and ethylene thiourea, there is not enough epidemiological information to make a useful comparison with rodent bioassay data. For the two remaining chemicals, actinomycin D and vinylidene chloride, the human evidence is inconsistent with the predictions. But the conditions of the rodent bioassay of actinomycin D were inappropriate for the comparison, and for vinylidene chloride the human exposure dose and duration were uncertain; either chemical might yet demonstrate consistency with the rodent results in future epidemiological studies.