The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings may not have been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. For more information, see the Explanation of Levels of Evidence for Developmental Toxicity. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.
Carbon disulfide, a widely used industrial chemical, was evaluated for toxic and teratogenic effects in timed-pregnant CD rats. CS (0, 100, 200, 400 and 600 mg/kg/day, po) in corn oil was administered in a volume of 5 ml per kilogram of body weight on gestational days 6 through 15. Females were weighed and observed during daily treatment and at 1 and 4 hours post-dosing for clinical signs of toxicity. At sacrifice on gd 20, a total of 22-27 confirmed-pregnant females per treatment group were evaluated. The gravid uterus for each dam was weighed and the number of implantation sites, and live, dead or resorbed fetuses were recorded. All live fetuses were weighed and examined for external, visceral and skeletal malformations. During CS treatment, dams exhibited clinical signs including rough or erect coat, lethargy, postural abnormalities, hind limb paralysis and weight loss; clinical signs were most frequent and severe in the 400 and 600 mg/kg/day groups. The maternal mortality rate was 4% (1/25) for the 400 mg/kg/day group and 0% for all other dose groups. On gd 11, 15 and 20 maternal body weight was decreased across treatment groups in a dose-related manner with 400 mg/kg/day CS dams exhibiting body weights significantly below vehicle controls on gd 15 and 20, and 600 mg/kg/day CS dams exhibiting body weights significantly below controls on gd 11, 15 and 20. Measures of maternal weight gain (i.e., weight gain during treatment weight gain during gestation and absolute weight gain) as well as gravid uterine weight were also decreased in a dose-related manner. Maternal weight gain during the treatment period was significantly below controls for dams treated with 200, 400 or 600 mg/kg/day CS. Absolute weight gain was significantly below controls for the 400 and 600 mg/kg/day CS groups. Gestational weight gain was below controls for all CS-treated groups. Relative maternal liver weight was increased in a dose-related manner with statistically significant increases above vehicle control observed in the 400 and 600 mg/kg/day CS groups; absolute maternal liver weight did not differ among treatment groups. The percentage per litter of resorbed, dead, nonlive (i.e., dead plus resorbed) or affected (i.e., nonlive plus malformed) fetuses did not differ among dose groups.
Among those litters containing live fetuses, there were no differences among dose groups in the number of live fetuses per live litter or in the proportion of males per live litter. Average fetal body weight per live litter was reduced in a dose-related manner, with CS 200, 400 and 600 mg/kg/day litters significantly below controls; males and females were equally affected on this measure. The percentage of fetuses malformed per litter, but not the proportion of litters with one or more malformed fetuses, differed significantly among treatment groups, but no clear dose-effect relationship was observed. In conclusion, CS (0, 100, 200, 400 or 600 mg/kg/day, po) administered on gd 6 through 15, produced dose-related maternal and fetal toxicity, but failed to increase the incidence of malformations in CD rats relative to vehicle control subjects.