Chronic Exposure to Low Concentrations of Halothane-Nitrous Oxide: Reproductive and Cytogenetic Effects in the Rat

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To determine whether prolonged exposure to low-concentration combinations of halothane and nitrous oxide would adversely affect fertility, gestation, or fetal development or damage chromosomes in vivo, adult male and female rats were exposed for 60 days prior to mating either to halothane, 1 ppm, and nitrous oxide (N2O), 50 ppm, or to these agents at 10 and 500 ppm, respectively, for seven hours/day, five days/week. Inseminated females were either exposed seven hours/day from Day 1 through Day 15 or from Day 6 through Day 15 of their putative gestation. The former were allowed to deliver normally; fetuses of the latter were delivered by cesarean section on Day 10. The males were exposed for an additional 40 weeks (after the three-week mating period), after which bone marrow and spermatogonial cells were harvested for cytogenetic analysis.

Exposure to halothane, 10 ppm, plus N2O, 500 ppm, resulted in decreased ovulation and implantation efficiency and in slightly retarded fetal development (also seen at the lower level exposure). No major teratologic effect or unequivocal abortifacient effect of exposure of pregnant females during organogenesis or prior exposure of males was observed. However, cytogenetic damage to both bone marrow and spermatogonial cells was found at both levels of exposure.

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