Toxicity of low concentration long-term exposure to an airborne mixture of nitrous oxide and halothane

To evaluate experimentally the questions of reproductive, teratological, cytogenetic, and tumorigenic sequelae of long-term exposures to escape levels of halothane plus nitrous oxide (N2O), male and female rats were exposed either to air, to 1 ppm halothane plus 50 ppm N2O, or to 10 ppm halothane plus 500 ppm N2O for 7 hr/day, 5 days/wk for appropriate periods of time. In one experiment, young adult female rats were exposed for 60 days, then mated and reexposed either staring with Day 1 or Day 6 of gestation until Day 15. The former were permitted to deliver naturally while the latter were delivered by C-section on Day 20. The young adult males used in breeding were also exposed for 60 days prior to mating and then for a total of 52 weeks thereafter. At termination, bone marrow cell and spermatogonial metaphase preparations were made and assessed for cytogenetic abnormalities. The mated females were evaluated for ovulation, pre- and post-implantation loss, fetal growth, fetal abnormalities, and early post-natal development, as appropriate. In a parallel experiment, 50 male and 50 female weanling rats in each group were exposed for 104 weeks to the same levels and then evaluated for tumor development with emphasis on the reticuloendothelial system. The results indicated a significant reduction in ovulation and implantation efficiency from exposure to the higher levels and slightly retarded fetal development at both levels. No teratological or abortifacient effects were noted. No tumorogenic effects were observed. However, cytogenetic damage to both bone marrow and spermatogonial cells was seen at both levels.