Determination of the proximate teratogen of the mouse fetal alcohol syndrome. 1. Teratogenicity of ethanol and acetaldehyde.

The proximate teratogen of the fetal alcohol syndrome is unknown. CD-1 mice were treated ip on Day 10 of gestation with 2, 4, 6, or 7 g/kg ethanol. The percentage of resorptions and malformed fetuses was increased and mean fetal weight was decreased in a dose-related manner. Treatment with 7 g/kg ethanol ip on one of gestational Days 7, 8, 9, 10, or 11 significantly increased the percentage of malformed fetuses and decreased fetal weight. In addition, treatment on Days 10 or 11 significantly increased the percentage of resorptions. Coadministration of 100 mg/kg of 4-methylpyrazole, an inhibitor of alcohol dehydrogenase, orally with 6 g/kg ethanol ip on Day 10 of gestation dramatically increased the embryotoxicity of ethanol. Five ip treatments of 200 mg/kg acetaldehyde at 2-hr intervals on Day 10 of gestation did not significantly increase the percentage of resorptions and malformed fetuses or decrease fetal weight. These data suggest that ethanol is the proximate teratogen of the fetal alcohol syndrome in CD-1 mice.