Effects of low concentrations of nitrous oxide on rat fetuses

The long-term inhalation of air polluted with nitrous oxide has been implicated in spontaneous abortions and fetal abnormalities in operating room personnel. Studies with 1% and 0.5% N2O in air have confirmed the adverse effects of dilute concentrations of N2O in pregnant rats. The present study was designed to determine the threshold concentration of nitrous oxide necessary to produce adverse responses in pregnant rats. Wistar albino rats were mated in an environmental chamber and conception confirmed by vaginal smears. Immediately thereafter, the rats were randomly divided into control and experimental groups. The control rats were exposed for 19 days to oil-free compressed air in an environmental chamber at a flow rate of 8.5 air changes per hour. Experimental animals were exposed continuously under identical conditions to concentrations of 0.0, 0.1%, 0.5%, or 0.025% N2O. On day 19 the gravid rats were killed. The corpora lutea of pregnancy were counted and related to the number of fetuses in the uterus. Fetuses were fixed, cleared, and their skeletons stained with alizarin red. Litter size, frequency of fetal resorption, and fetal crown rump measurements were significantly different following exposure to 0.1% N2O than they were in control rats or in rats exposed to 0.05% or 0.025% nitrous oxide, neither of which had any fetal effects. The suggested threshold level of 30 ppm (0.03%) N2O in humans may be unrealistically low.