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October 1985

Teratogenic Effects of Valproate in the CD-1 Mouse Fetus

Author Affiliations

From the Colleges of Dentistry (Dr R. Paulson) and Medicine (Drs Sucheston, Hayes, and G. Paulson), Ohio State University, Columbus.

Arch Neurol. 1985;42(10):980-983. doi:10.1001/archneur.1985.04060090062015

• 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.

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