Determination of the proximate teratogen of the mouse fetal alcohol syndrome: 2. Pharmacokinetics of the placental transfer of ethanol and acetaldehyde |
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Authors: | Patricia M. Blakley William J. Scott |
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Affiliation: | 1. Children''s Hospital Research Foundation, University of Cincinnati College of Medicine, Cininnati, Ohio 45229 USA;2. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229 USA |
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Abstract: | 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. |
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Keywords: | To whom correspondence should be sent: Dr. William J. Scott Jr. Division of Teratology Children's Hospital Research Foundation Elland and Bethesda Avenues Cincinnati Ohio 45229. |
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