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The Sprague-Dawley rat was used to demonstrate the effect of nitrous oxide, with and without folinic pretreatment, on reproductive indices and fetal development. One of the objectives of the investigation was to test the hypothesis that at least some of the teratogenic effect of nitrous oxide is related to interference with folate metabolism. Groups of animals were exposed to 70-75% nitrous oxide on day 9 of pregnancy with or without folinic acid 0.1 mg i.p. 12 h before, and immediately before, exposure. Subsequent fetal development was compared with that of various control groups. There were no significant differences in fetal survival, but fetal weights were reduced in both groups exposed to nitrous oxide. Of the indices of skeletal maturity, the number of ossified sternebrae was reduced only in the nitrous oxide group not receiving folinic acid. The incidence of major skeletal abnormalities in the untreated nitrous oxide group was significantly increased to five times that of the control groups, whereas the incidence in the nitrous oxide group receiving folinic acid was not significantly different from control. It is concluded that pretreatment with folinic acid can at least partially reduce the teratogenic effects of nitrous oxide in the rat.
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