Metabolic and toxicologic studies with enflurane in Swiss/ICR mice

Swiss/ICR mice were tested to determine whether the volatile ether anesthetic, enflurane, causes induction of anesthetic defluorination and organ toxicity. Mice were exposed in utero and postnatally to 0.01, 0.1 and 1.0 volumes percent enflurane vapor. Body weight was measured at frequent intervals throughout the experiment. Animals were sacrificed at 73 days of age and liver microsomal cytochrome P-450 content and the rate of defluorination of enflurane, isoflurane, methoxyflurane ans sevoflurane were determined. In addition, the liver, kidney and testis were weighed and examined histologically for drug induced damage. The maximum tolerated dose of enflurane delivered over a twelve week period was determined to be 0.5 volumes percent for four hours a day, five days a week. Even at this high dose there was no evidence in either sex of liver, kidney or testicular damage. Following enflurane exposure, neither the liver microsomal cytochrome P-450 content nor the rate of anesthetic defluorination was increased. The rate of in vitro inorganic fluoride production per unit time was greatest for methoxyflurane, and approximately equal for enflurane, isoflurane and sevoflurane. Since there was no evidence of enzyme induction or specific organ toxicity, it was concluded that enflurane is a comparatively nontoxic volatile anesthetic under conditions of this study.