Validation of an in vivo developmental toxicity screen in the mouse.
A test system for identifying toxicity, including potential teratogenicity has been developed that is based on growth and viability of embryonic, fetal, and postnatal mice (J Toxicol Environ Health 10:541-550, 1982). To test the utility of this assay, a series of 55 compounds was administered to timed-pregnant ICR/SIM mice during organogenesis. The test compounds included known teratogens, known nonteratogens, and equivocal teratogens. They represented a wide variety of classes including pesticides, organic solvents, metals, steroids, nutrients, food additives, antimetabolites, alkylating agents, and pharmaceutical agents. A single dose level, at or near the level producing overt maternal toxicity in preliminary range-finding studies, was administered by gavage on gestation days 8 through 12. Females were allowed to deliver; litter size and weight on the day of birth and 2 days postpartum were recorded, and stillborns were examined. Dams that had not given birth by gestation days 21 or 22 were killed and their uteri were examined. The results confirmed a strong correlation between reported teratogenic activity and embryo/fetal viability, and/or postnatal growth and viability. The results indicate that this test system is an effective, cost-efficient means of prioritizing compounds for more detailed teratogenicity testing.
D000818:Animals; D001724:Birth Weight / Q000187:drug effects; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D005328:Fetal Viability / Q000187:drug effects; D008098:Litter Size / Q000187:drug effects; D008722:Methods; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D013723:Teratogens / Q000633:toxicity*
D013723:Teratogens