Statistical design of toxicity assays: role of genetic structure of test animal population.

This paper considers certain statistical aspects of the problem of among-strain differences in cancer susceptibilities and how these differences may affect the design of toxicity assays. First, in order to investigate the magnitude of within-study, between-strain differences in tumor induction, the data of Innes et al. (1969) were examined. It was found that although there was a very high overall association between mouse strains with respect to the induction of hepatomas, several compounds showed evidence of strain-to-strain variability. Next, a number of long-term carcinogenicity studies with DDT were considered, and among-strain differences in cancer susceptibility for this compound were noted. Finally, it was shown that if susceptible subgroups do exist and certain simplifying assumptions are made, then in many cases tumor increases can be detected more readily by using several inbred mouse strains for study rather than a single outbread stock.