Teratogenic effects of valproate in the CD-1 mouse fetus.
Valproate sodium has been implicated in the production of spina bifida in humans; this article reports an animal model. Teratogenicity of valproate sodium was studied by oral administration of single doses of 225, 340, and 560 mg/kg to pregnant CD-1 mice on days 7 through 12 of gestation. All fetuses were examined on day 17. Treated fetuses demonstrated external malformations and a decrease in weight. The incidence of malformations was greater at the higher dosage levels of 340 mg/kg and 560 mg/kg, with a predominance of exencephaly, open eyelids, and gross skeletal defects. There was a significant increase in the resorption rate of the fetuses in the treated groups. There was also a significant increase in the malformations observed per litter and per live fetus population when compared with controls.
D000014:Abnormalities, Drug-Induced / Q000209:etiology* / Q000473:pathology; D000818:Animals; D001921:Brain / Q000002:abnormalities; D005260:Female; D005315:Fetal Diseases / Q000139:chemically induced* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D011247:Pregnancy; D012886:Skull / Q000002:abnormalities; D014635:Valproic Acid / Q000009:adverse effects*
D014635:Valproic Acid