Dissociation between maternal and fetal toxicity of methyl isocyanate in mice and rats.
The contribution of maternal hormonal changes and pulmonary damage on the fetal toxicity of methyl isocyanate (MIC) was studied in mice and rats. Exposure to MIC decreased maternal plasma progesterone levels in mice that lost but not in mice that retained pregnancy. Fetal toxicity of MIC was not related to changes in maternal plasma corticosterone levels. Neither chronic administration of progesterone nor the suppression of pulmonary edema with dexamethasone decreased fetal toxicity of MIC. Embryos exposed in utero or in vitro to MIC vapor exhibited a concentration-dependent decrease in growth in culture. An acute dose (3 mmol/kg) of the MIC metabolites (methylamine, dimethylamine, trimethylamine, dimethyl urea) did not exert fetal toxicity. These data suggest that the fetal toxicity of MIC is partly independent of maternal toxicity and may result from its transfer across the placenta and interaction with fetal tissues.
Varma
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DR
Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada.
Guest
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Smith
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Mulay
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D000280:Administration, Inhalation; D000818:Animals; D046508:Culture Techniques; D003485:Cyanates / Q000378:metabolism / Q000506:poisoning*; D003907:Dexamethasone / Q000494:pharmacology; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000187:drug effects*; D005740:Gases; D006728:Hormones / Q000097:blood; D017953:Isocyanates; D008431:Maternal-Fetal Exchange; D051379:Mice; D008815:Mice, Inbred Strains; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D003485:Cyanates; D005740:Gases; D006728:Hormones; D017953:Isocyanates; D011374:Progesterone; D003907:Dexamethasone; C008461:methyl isocyanate