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The use of average qualitative concordance between two bioassay endpoints is considered, with emphasis directed at agreement between rats and mice from results of long-term carcinogenicity studies. It is noted that concordance varies as a function of the underlying potency or toxicity of the chemicals over which the averaging is performed. Thus, the averaging process dilutes large observed concordances from potent chemicals, and possibly inflates lower observed concordances from weakly active chemicals. Stratification over some measure of potency is suggested as a method for taking these effects into account. Statistical simulations of concordance analyses limited to low-potency ranges are employed to examine the concordance measure in greater detail. It is seen that at low potencies, observed concordance is consistently underestimated, reaching maximum levels of only about 80%.

We consider animal bioassay experiments with variable dosing regimens in which groups of animals are dosed beginning at different ages and for varying durations. Two response models are discussed and then applied to data from an experiment on vinyl chloride exposure of F-344 rats, B6C3F1 and Swiss CD-1 mice, and Syrian Golden hamsters. The multistage model of Armitage and Doll, as extended by Whittemore, Day and Brown, and Crump and Howe, is used to estimate the dose effect on the ordered stages of tumor development. The data for all endpoints and species/strains examined consistently indicate a predominant effect on the first stage, suggesting that vinyl chloride is primarily a tumor initiator. This is consistent with evidence from two-stage experiments on this chemical. The second response model, new to this article, adjusts for survival nonparametrically. It is used to test for an age difference in susceptibility, to evaluate alternative exposure durations, and to compare the effectiveness of alternative dosing regimens for detecting carcinogenicity.

The TD50 (or tumorigenic dose rate 50) is a generally accepted measure of the carcinogenic potency of a chemical in a particular strain of animal. This paper discusses error in the estimation of the TD50 caused by intercurrent mortality and error resulting from consideration of only significant TD50's. Using computer simulations, we found that treatment-related toxicity had only a small effect on estimating the TD50, with errors seldom exceeding 5%. The TD50 is sensitive to changes in tumor lethality with errors ranging to as high as 50%. Many of these errors were significantly different from zero and the results suggest that potency estimation could be improved by basing the estimates upon the tumor incidence rate rather than upon the tumor death rate when an estimate of tumor lethality is obtainable.