Teratogenic effects of valproate in the CD-1 mouse fetus
R. B. Paulson, M. E. Sucheston, T. G. Hayes and G. W. Paulson
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.
