Effects of subchronic intermittent exposure to nitrous oxide in Swiss Webster mice

Swiss Webster mice were treated to determine whether the inhalational anesthetic, nitrous oxide (N2O), causes organ toxicity and enhances anesthetic defluorination. Two-hundred and sixteen young adult male and female mice were exposed to room air or to 5,000 (.5%), 50,000 (5%) or 500,000 (50%) N2O for four hours per day, five days per week for periods up to fourteen weeks. Body weight was measured twice weekly throughout the experiment. Liver, kidney, spleen and testis were weighed and examined histologically along with brain, stomach, seminal vesicle, and ovary for evidence of drug induced damage. Blood smears were examined microscopically and complete blood count, differential white cell count, and reticulocyte and platelet counts were performed. In addition, liver microsomal cytochrome P-450 content and the rates of defluorination of enflurane and methoxyflurane were determined. The maximum tolerated concentration of N2O was approximately 5000,000 ppm. Even at this high dose, there was no evidence of organ damage. Following N2O exposure, neither the hepatic microsomal cytochrome P-450 content nor the rates of anesthetic defluorination were increased; the rate of in vitro inorganic fluoride production was greater for methoxyflurane than for enflurane. Since there was no evidence of specific organ toxicity or of enzyme induction or inhibition, it was concluded that N2O is a comparatively nontoxic inhalational anesthetic under the conditions of this study.