Maternal toxicity, reproductive performance and developmental toxicology were evaluated in Sprague-Dawley-derived rats during and following 6 hours/day, whole-body, inhalation exposures to 0 (filtered air), 40, 200 and 1000 ppm of 1,3-butadiene. The female rats (Ns = 24 to 28), which had mated with unexposed males (day of sperm detection = 0 days of gestation; dg), were exposed to the chemical from 6 through 15 dg and sacrificed on 20 dg.
Maternal animals were weighed prior to mating and on 0, 6, 11, 16 and 20 dg; the rats were observed for mortality, morbidity and signs of toxicity during exposure and examined for gross tissue abnormalities at necropsy. Reproductive measures included the determination of numbers of implantation sites, resorptions and live and dead fetuses. Live fetuses were weighed and subjected to external, visceral and skeletal examinations to detect growth retardation and morphologic anomalies.
There were no significant differences among treatment groups in maternal body weights or extragestational weights of rats exposed to 1,3-butadiene concentrations of 40 or 200 ppm, but, in animals exposed to 1000 ppm, significantly depressed body weight gains were observed during the first 5 days of exposure and extragestational weight gains tended to be lower than control values. These results, and the absence of clinical signs of toxicity, were considered to indicate that there was no maternal toxicity at exposure levels of 200 ppm or lower. The percentage of pregnant animals and the number of litters with live fetuses were unaffected by treatment.
Placental weights, fetal body weights and sex ratios were unaffected by treatment. There were no significant differences among groups in incidences of fetal malformations. However, in the 200-ppm exposure group, a significant increase in the incidence of reduced sternebral ossification was detected when the analyses were based on the number of affected fetuses but not on the number of affected litters. This difference could not be correlated with fetal body weights or exposure regimens and was not considered to be treatment-related. There were also irregularities in the thoracic vertebrae, but the incidence of reduced ossification in fetuses of the control group was significantly higher than in fetuses of the 200- and 1000- ppm exposure groups.
Under the conditions of this exposure regimen, there was no evidence for a teratogenic response to 1,3-butadiene exposure.