Reproduction and fetal development in mice chronically exposed to enflurane

Reproductive indices and developmental toxicity were evaluated in Swiss/ICR mice chronically exposed to a subanesthetic (0.01 or 0.1 per cent) or an anesthetic (0.5/1.0 per cent) concentration of enflurane. Pregnant mice (443) and fetuses (4743) were examined. In one experiment, groups of females were exposed to 0.01, 0.1, or 0.5/1.0 per cent enflurane for 4 hours per day, 7 days per week for 3 weeks; they were then mated with unexposed males. Exposure of females was continued daily throughout pregnancy. No adverse effects on fertility were observed at any dosage. At the highest dosage, 1.0 per cent, minor developmental variations occurred (i.e., lumbar ribs and increased renal pelvic cavitation). In a second experiment, groups of mice were exposed to 0.01, 0.1 or 1.0 per cent enflurance only on days 6 through 15 of pregnancy for 4 hours per day, after having been mated with untreated males. Abnormalities (i.e., increased incidence of cleft palate, minor skeletal and visceral anomalies, and developmental variants) were again seen only at the highest dosage. In a third experiment, male mice were exposed to 0.01, 0.1 or 0.5/1.0 per cent enflurane for 11 weeks for 4 hours per day, 5 days per week, prior to mating with unexposed females; results of this experiment were negative. In general, enflurane treatments did not adversely affect reproductive indices. Effects on fetal development were minimal, being somewhat greater than those reported in previous experiments with methoxyflurane but less than those seen with halothane. The smallest exposure at which effects were seen was approximately 100 times greater than the level of human occupational exposure in unscavenged operating rooms.