The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings were not evaluated in accordance with the levels of evidence for reproductive or developmental criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.
Trichloroethylene (TCE), a common industrial solvent and dry cleaning agent, was tested for its effects on reproduction and fertility in Swiss CD-1 mice using the RACB protocol. TCE was microencapsulated in a gelatin/sorbitol shell, and added to the diet. Data from a two week dose-range-finding study (Task 1) were used to set exposure concentrations for the Task 2 continuous cohabitation study at 0.15, 0.30, and 0.60% w/w. Based on the results of the analysis of feed formulations and an average daily feed consumption of nearly equal to 5.0g, the daily TCE dosages were nearly equal to 100, 300, and 700 mg/kg/d.
TCE exposure was associated with no adverse clinical signs, and post-partum dam weights during the Task 2 cohabitation phase were not reduced by TCE. The only adverse reproductive change noted during Task 2 was a 4% reduction in pup weight adjusted for litter size at the high dose.
The last litter from the control and high dose groups was reared to weaning, for subsequent evaluation of second generation fertility. Maternal TCE exposure during lactation was associated with a significant increase in perinatal mortality: the 28% mortality rate in control litters is significantly less than the 61% mortality rats in the high dose TCE group. After weaning, mortality rates were comparable between the two groups.
After the F1 pups were weaned, the F0 control and high dose mice were killed and necropsied. Male body weight was not changed, while absolute testis weight was reduced by 4%, adjusted liver weight was increased by nearly equal to 34%, and adjusted prostate weight was reduced by nearly equal to 16%. Sperm motility was reduced by nearly equal to 45% in the high dose TCE treated animals; no other sperm or reproductive changes were noted. In females, body weight was unchanged while adjusted liver weight was increased by nearly equal to 30%. No histologically-visible changes in vaginal epithelium were noted. Treated mice had a greater incidence of centrilobular hypertrophy, and renal tubular degeneration and corticomedullary epithelial karyomegaly. Males were generally more affected than females.
The second generation mice from the control and high dose groups were cohabited at nearly equal to pnd 74. No reproductive endpoint was altered by TCE exposure. After evaluation of the F2 pups, the F1 adults were killed and necropsied. Male body weight was unchanged, but adjusted liver weight was increased by nearly equal to 60%, adjusted kidney weight was increased by nearly equal to 9%, and adjusted epididymis weight increased by nearly equal to 9%. The % motile sperm was reduced by nearly equal to 20%, while the proportion of abnormal sperm was increased from a control value of 8%, to 10% in the treated mice. TCE-treated female body weights were not different from controls, while adjusted liver weight and kidney weight were increased by nearly equal to 30% and 16%, respectively. Hepatic and renal microscopic lesions were similar to those noted for the F0 mice. Histologic evaluation of the vaginal epithelium indicated cycling in both groups, but cycles were not assessed in vivo.In summary, TCE exposure to mice via the diet produced significant hepatic and renal toxicity (increased weights and microscopic lesions), reduced sperm motility in both generations, and produced greater lactational mortality in the high dose group. These data suggest that the hepatic/renal/lactational toxicities were more severe than the relatively moderate reductions in sperm motility.