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A series of studies to further evaluate the developmental and reproductive toxicity of inhaled 1,3-butadiene was sponsored by the National Toxicology Program. Pregnant Sprague-Dawley rats (24-28/group) and Swiss (CD-1) mice (18-22/group) were exposed to atmospheric concentrations of 0, 40, 200, or 1000 ppm 1,3-butadiene for 6 hr/day on days 6 through 15 of gestation (dg) and killed on dg 18 (mice) or dg 20 (rats). Subsequently, the uterine contents were evaluated; individual fetal body weights were recorded; and external, visceral, and skeletal examinations were performed. In rats, maternal toxicity was observed in the 1000-ppm group in the form of reduced extragestational weight gain and, during the first week of treatment, decreased body weight gain. Under these conditions, there was no evidence of developmental toxicity in rats. In contrast, results of the mouse developmental toxicity study indicated that the fetus may be more susceptible than the dam to inhaled 1,3-butadiene. Maternal toxicity was observed in mice at the 200- and 1000-ppm 1,3-butadiene exposure levels, whereas 40 ppm and higher concentrations of 1,3-butadiene caused significant exposure-related reductions in the mean body weights of male fetuses. Mean body weights of female fetuses were also reduced at the 200- and 1000-ppm exposure levels. No increased incidence of malformations was observed in either study. Other studies addressing male reproductive and mutagenesis end points were performed with B6C3F1 mice (sperm-head morphology) and Swiss (CD-1) mice (dominant lethal study).(ABSTRACT TRUNCATED AT 250 WORDS)

Ethylene oxide (CAS no 75-21-8), propylene oxide (CAS no 75-56-9), butylene oxide (CAS no 106-88-7), and styrene oxide (CAS no 96-09-3) were tested for teratogenic activity by inhalation exposure of rats and rabbits. Ethylene oxide and propylene oxide were tested at only one concentration in both species (150 ppm for ethylene oxide and 500 ppm for propylene oxide). Butylene oxide was tested at 250 and 1,000 ppm in both species, while styrene oxide was tested at 100 ppm in rats and 15 and 50 ppm in rabbits. For each of these four epoxides, the acute toxicity was similar for pregnant and nonpregnant rats. Styrene oxide was the most toxic in both species, and rabbits were more sensitive than rats. Rats exposed to propylene oxide for 7 h/d, 5 d/week for three weeks before breeding had a significant reduction in the number of corpora lutea. Fetal mortality was not increased, but significantly fewer mated rats were found pregnant following gestational exposure to styrene oxide, a finding suggesting preimplantation loss. In rabbits exposed to styrene oxide, the number of resorptions per litter was increased in concentration related manner, but differences were not statistically significant. Fetal examination revealed evidence of fetotoxicity with all four epoxides. There was no overt teratogenic activity, but a number of minor morphologic aberrations were detected.