Dose-response studies with genetically homogeneous lines of mice as a teratology testing and risk-assessment procedure.
Current teratology testing procedures are mainly focused on qualitative considerations and, hence, largely ignore the variability in responsiveness to exogenous agents that may exist within species. An example is given of a test using genetically homogeneous lines of animals, which shows how extensive intraspecies variability can be. Pregnant females of six strains of mice were given single doses of 12.5 to 1200 mg/kg cortisone acetate by four routes on 4 days of gestation. The frequency of cleft palate and of fetal resorption were evaluated for their dose-response relations. The range of responses was extremely wide; in one series the malformation ED50 of the most responsive strain was about 16 times greater than that of the least responsive one. By indicating that a range of sensitivities may be possessed by species, and by approximating the limits of that range, inbred lines can reveal mild degrees of responsiveness that are frequently overlooked in using outbred stocks, and hence are of value in assessing risk.
D000014:Abnormalities, Drug-Induced / Q000453:epidemiology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains / Q000196:embryology* / Q000235:genetics; D011247:Pregnancy; D013045:Species Specificity; D013723:Teratogens / Q000494:pharmacology*
D013723:Teratogens