Reproductive and teratogenic effects of nitrous oxide, isoflurane, and their combination in Sprague-Dawley rats

The reproductive and teratogenic effects of nitrous oxide (N2O), isoflurane, and their combination were studied in 130 timed-pregnant rats. Rats were exposed to either air, 0.35% isoflurane (1/4 MAC), 50% N2O (a known teratogenic concentration), or 50% N2O plus 0.35% isoflurane for 24 h on day 8 of pregnancy. On day 20 of pregnancy, cesarean sections were performed; a total of 1268 offspring were delivered and immediately examined for external abnormalities. They were subsequently examined microscopically either for visceral or skeletal abnormalities. N2O caused significantly higher incidences of early and late resorptions, and major visceral malformations. The addition of isoflurane to N2O prevented the majority of these adverse effects. These results cast doubt on the methionine synthase inhibition theory of N2O teratogenicity.