Teratology studies of lewisite and sulfur mustard agents: Effects of lewisite in rats and rabbits: Final report: Part 2, Appendices

Lewisite was administered to rats and rabbits by intragastric intubation. Maternal animals were weighed periodically, and, at necropsy (20 dg (days of gestation) in rats and 30 dg in rabbits), were examined for gross lesions of major organs and reproductive performances; live fetuses were weighed and examined for external, internal and skeletal defects. In rats, a dose level of 1.5 mg/kg did not induce toxic or teratogenic responses in maternal animals or their fetuses. At 2.0 mg/kg, 10% maternal mortality, trends in decreased maternal and fetal body weights and a significant reduction in the number of viable fetuses were evident. In rabbit studies, maternal mortality occured in all but one of the lewisite treatment groups and range from 13% to 100% at dose levels of 0.07 and 1.5 mg/kg, respectively. This mortality rate limited the sample size and impaired the detection of statistical significance among treatments. However, at the lowest dose level of the teratology study (0.07 mg/kg), maternal mortality was the only indicator of lewisite toxicity; at the highest dose (0.6 mg/kg), significant findings included 86% maternal mortality, a decrease in maternal body weight gains and an increase in the incidence of fetal stunting, although only a tendency in decreased fetal body weights was observed. These results suggest that maternal mortality was the most important factor in predicting the induction of maternal and fetal effects and, therefore, a ''no observable effect level'' in maternal animals and their fetuses would be between 1.5 and 2.0 mg/kg in rats and less than 0.07 mg/kg in rabbits. Part 2 contains 6 appendices

Dominant lethal study in CD-1 mice following inhalation exposure to 1,3-butadiene: Final technical report

The effects of whole-body inhalation exposures to 1,3-butadiene on the reproductive system was evaluated. The results of dominant lethality in CD-1 male mice that were exposed to 1,3-butadiene are described. Subsequent to exposure, males were mated with two unexposed females. Mating was continued for 8 weeks with replacement of two females each week. Gravid uteri were removed, and the total number, position and status of implantations were determined. The mice were weighed prior to exposure and at 0, 1, 2, 3, 4, 5, 6, 7, and 8 weeks after exposure and at sacrifice. The animals were observed for mortality, morbidity and signs of toxicity throughout the study. 19 refs., 5 figs., 9 tabs

Inhalation developmental toxicology studies: Teratology study of 1,3-butadiene in mice: Final report

Maternal toxicity, reproductive performance and developmental toxicology were evaluated in CD-1 mice following whole-body, inhalation exposures to 0, 40, 200 and 1000 ppM of 1,3-butadiene. The female mice, which had mated with unexposed males 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. Live fetuses were weighed and subjected to external, visceral and skeletal examinations to detect growth retardation and morphologic anomalies. Significant concentration-related decreases were detected in a number of maternal body weight measures. 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. This exposure regimen produced significant signs of maternal toxicity at concentrations of 200 and 1000 ppM 1,3-butadiene