Uncertainties in interspecies extrapolations of carcinogenicity

The usual classification of results of animal carcinogenicity tests is positive or negative. Attempting to observe correlations between species using such results is complicated by differing test sensitivities. In these circumstances it is helpful to use models to represent the experimental data in a consistent way. Fitting the model parameters to the data allows computation of confidence limits and an assessment of concordance or discordance between different species in a way which accounts for differing test sensitivities. This paper describes this approach in detail for one class of models applied to the carcinogenicity test results of 187 of the NCI bioassay series, allowing comparison between B6C3F1 mice, Fischer 344 rats and Osborne Mendel rats. It is shown that the uncertainties in extrapolating between species are larger than generally acknowledged (a standard deviation of a factor of approximately 4.5), but that within these uncertainties there are few if any discordances.