Influence of genetic population structure on the results of chronic toxicity studies

The importance of the genetic makeup of animals used for toxicological testing has been recognized, although there are few data regarding this. In the study discussed here offspring from a BALB/cStCrlfC3Hf/Nctr male and C57BL/6jfC3Hf/Nctr female cross were used to produce a homogeneous (F1) strain, and brother-sister mating of the F1 population was used to produce a heterogeneous (F2) strain of mice, both having essentially the same gene pool but with different distributions. The end points of mortality and body weights were used to demonstrate relative variability about a mean resulting from genetic constitution when the mice were exposed to benzidine dihydrochloride. This life-span study demonstrated that genetic constitution in research animals should be an important consideration in toxicological research. There were significant differences in body weight and mortality between the two populations, with the F2 mice exhibiting wider body weight ranges and greater susceptibility to the test chemical.