Reproduction and Fetal Development in Mice Chronically Exposed to Enflurane

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Abstract
Reproductive indices and developmental toxicity were evaluated in Swiss/ICR mice chronically exposed to a subanesthetic (0.01 or 0.1%) or an anesthetic (0.5/1.0%) concentration of enflurane. Pregnant mice (443) and fetuses (4743) were examined. In 1 experiment, groups of females were exposed to 0.01, 0.1 or 0.5/1.0% enflurane for 4 h/day, 7 days/wk for 3 wk; 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%, minor developmental variations occurred, (lumbar ribs and increased renal pelvic cavitation). In a 2nd experiment, groups of mice were exposed to 0.01, 0.1 or 1.0% enflurane only on days 6-15 of pregnancy for 4 h/day, after having been mated with untreated males. Abnormalities (increased incidence of cleft palate, minor skeletal and visceral anomalies and developmental variants) were seen only at the highest dosage. In a 3rd experiment, male mice were exposed to 0.01, 0.1 or 0.5/1.0% enflurane for 11 wk for 4 h/day, 5 days/wk, prior to mating with unexposed females; results of this experiment were negative. Enflurane treatments did not adversely affect reproductive indices. Effects on fetal development were minimal, being 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 .apprx. 100 times greater than the level of human occupational exposure in unscavenged operating rooms.