Variations in disease in inbred and outbred strains of rodents

Risk assessment from toxicity testing is difficult because of interanimal variability and high levels of spontaneous pathology in rodents. Genetically defined animals might improve risk assessment by reducing the effects of these two factors. Data is presented on disease patterns in mice from an outbred colony of Swiss albino Alpk:APfCD-1 mice, and inbred mouse strain C57Bl/10JfCD-1/Alpk, and an outbred rat colony Alpk:APfSD (Wistar derived). All of the strains have been bred, maintained and used continuously, in one laboratory, for 20 to 30 years. The data is derived from control animals in toxicity tests completed between 1960 and 1990, chiefly from oncogenicity studies. The results indicate that the major diseases, particularly the most common tumours in each strain, liver tumours in the outbred mouse, lymphomas in the inbred strain, and pituitary adenomas in the outbred rat, increase in incidence with time. Renal disease also increases in the outbred rat. This increase has been shown to be due to overnutrition. The effects of overnutrition can override the genetic characteristics of strain, and risk assessment is, therefore, unlikely to be improved by the use of genetically defined animals alone. The environmental conditions of toxicity experiments must also be defined and controlled.