Reproductive and Teratogenic Effects of Nitrous Oxide, Halothane, Isoflurane, and Enflurane in Sprague-Dawley Rats

A total of 305 timed-pregnant Sprague-Dawley rats were exposed for 6 h a day on each of three consecutive days in one of three periods, i.e., pregnancy days 14-16, 11-13, or 8-10, either to 0.55 times the minimum alveolar concentration (MAC) of nitrous oxide (75%) or to 0.75 MAC of halothane (0.8%), isoflurane (1.05%) or enflurane (1.65%); an additional 232 positive-control (retinoic acid) and air control rats were studied. Reproductive indices were determined, and the 5178 offspring delivered at cesarean section were examined for external, internal, and skeletal abnormalities. There were no major or minor teratologic effects in anesthetic treated groups, although several developmental variants were observed in halothane- and enflurane-treated groups. Nitrous oxide exposure on days 14-16 resulted in a three-fold increase in fetal resorptions. The results suggest that the volatile anesthetics are not teratogenic and confirm that nitrous oxide may be associated with increased reproductive loss.