Determination of the proximate teratogen of the mouse fetal alcohol syndrome. 2. Pharmacokinetics of the placental transfer of ethanol and acetaldehyde.
CD-1 mice were treated ip on Day 10 of gestation with 4, 6, or 7 g/kg ethanol. Maternal and embryonic tissues were analyzed for ethanol and acetaldehyde levels by head-space gas chromatography 5 min to 24 hr after treatment. Dose-dependent ethanol concentrations were observed in maternal blood and liver. Ethanol rapidly crossed the placenta and appeared in the embryo 5 min after treatment. Acetaldehyde was detectable in maternal blood following all treatments and in maternal liver and embryos following treatment with 7 g/kg ethanol. Coadministration of 100 mg/kg 4-methylpyrazole, an alcohol dehydrogenase inhibitor, with 4 or 6 g/kg ethanol on Day 10 of gestation significantly reduced the rate of ethanol elimination in all tissues examined. This reduction was manifested as a prolongation in the half-life of ethanol detectable in maternal and embryonic tissues but not in an increase in maximum ethanol concentrations. Within 5 min of maternal ip treatment with 200 mg/kg acetaldehyde on Day 10 of gestation, acetaldehyde was detectable in the embryo. These data suggest that both ethanol and acetaldehyde are accessible to the embryo during a critical period of development.
D000079:Acetaldehyde / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D000431:Ethanol / Q000378:metabolism* / Q000633:toxicity; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000378:metabolism*; D005312:Fetal Blood / Q000032:analysis; D000077604:Fomepizole; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D051379:Mice; D011247:Pregnancy; D011720:Pyrazoles / Q000494:pharmacology
D011720:Pyrazoles; D000431:Ethanol; D000077604:Fomepizole; D000079:Acetaldehyde