Maternal toxicity, reproductive performance and developmental toxicology were evaluated in CD-1 mice following whole-body, inhalation exposures to 0 (filtered air), 40, 200 and 1000 ppm of 1,3-butadiene. The female mice, which had mated with unexposed males (day of detection of a copulation plug = 0 days of gestation), were exposed to the chemical for 6 hours/day on 6 through 15 dg and sacrificed on 18 dg.
Maternal animals were weighed prior to mating and on 0, 6, 11 and 18 dg; the mice were observed for mortality, morbidity and signs of toxicity during exposure and examined for gross tissue abnormalities at necropsy. Reproductive measures included 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.
For unknown reasons, the overall percentage of pregnant mice was low (60%), but no differences among treatments were detected in the number of pregnancies or implantation sites/dam. The incidence of early resorptions was higher in control mice than in animals exposed to 200 ppm, but no effect was observed on the percentage of total resorptions and live fetuses/litter.
Significant concentration-related decreases were detected in a number of maternal body weight measures (weight gains during the intervals encompassing the last 5 days of exposure and from the end of exposure to sacrifice, body weight at sacrifice, extragestational weight and weight gain, and weight of the gravid uterus). There was a significant concentration-related depression of fetal body weights and placental weights. Body weights of male fetuses of all exposed groups were significantly lower than values for control fetuses; weights of female fetuses were significantly depressed in the mice exposed to 200 and 1000 ppm. In the 200- and 1000-ppm exposure groups, weights of placentas of male fetuses were significantly decreased, but placental weights of female fetuses were significantly affected only in litters exposed to the highest 1,3-butadiene concentration. There were no significant differences among groups in the incidences of malformations. However, incidences of fetal variations (supernumerary ribs and reduced ossification of the sternebrae) were significantly increased in litters from mice exposed to 200 and 1000 ppm.
This exposure regimen produced significant signs of maternal toxicity at concentrations of 200 and 1000 1,3-butadiene. Fetal growth retardation, decreased placental weights, and increased incidences of morphologic variations were observed to occur in a concentration-related manner. Body weights of male fetuses of mice exposed to the lowest concentration of 1,3-butadiene (40) were significantly depressed, although no other signs of retarded fetal development or significant alterations in maternal indices were noted at this exposure level. These results may indicate that the fetus is more susceptible than the dam to 1,3-butadiene toxicity, but no evidence of teratogenicity was found in the offspring of dams exposed to 1,3-butadiene vapors on 6 through 15 dg.