NTP Technical Report on the toxicity studies of trans-1,2-dichloroethylene (CAS no. 156-60-5) administered in microcapsules in feed to F344/N rats and B6C3F(1) mice.
1,2-Dichloroethylene exists in two isomeric states: trans-1,2-dichloroethylene and cis-1,2-dichloroethylene. The trans isomer is used more widely in industry than the cis isomer. trans-1,2-Dichloroethylene is used as a solvent for waxes, resins, and acetylcellulose. It is also used in the extraction of rubber, as a refrigerant, and in the manufacture of pharmaceuticals and artificial pearls. F344/N rats and B6C3F1 mice were administered trans-1,2-dichloroethylene in microcapsules in feed for 14 weeks. Animals were evaluated for clinical pathology, reproductive system effects, and histopathology. Genetic toxicity studies were conducted in vitro in Salmonella typhimurium and Chinese hamster ovary (CHO) cells, and in vivo in mouse bone marrow cells and peripheral blood erythrocytes. In the 14-week feed studies, groups of 10 male and 10 female rats and mice were fed diets containing microcapsules with a chemical load of 45% trans-1,2-dichloroethylene. Dietary concentrations of 3,125, 6,250, 12,500, 25,000, and 50,000 ppm microencapsulated trans-1,2-dichloroethylene resulted in average daily doses of 190, 380, 770, 1,540, and 3,210 mg/kg for male rats; 190, 395, 780, 1,580, and 3,245 mg/kg for female rats; 480, 920, 1,900, 3,850, and 8,065 mg/kg for male mice; and 450, 915, 1,830, 3,760, and 7,925 mg/kg for female mice. Additional groups of 10 male and 10 female rats and mice served as untreated and vehicle controls. There were no exposure-related deaths of rats or mice. Mean body weights of male rats and male and female mice in the 50,000 ppm groups were significantly less than those of the vehicle controls. The mean body weight gains of female mice in the 12,500 and 25,000 ppm groups were also significantly less than that of the vehicle controls. On day 21 and at week 14, there were mild decreases in hematocrit values, hemoglobin concentrations, and erythrocyte counts in groups of male and female rats in the 25,000 and 50,000 ppm groups. At week 14, these effects were seen in male rats exposed to 6,250 and 12,500 ppm. There were no exposure-related alterations in clinical chemistry parameters in rats or mice. The liver weights of female rats exposed to 6,250 ppm or greater were significantly greater than those of the vehicle controls. The absolute kidney weights of male rats exposed to 25,000 or 50,000 ppm were significantly decreased. No gross or microscopic lesions were observed in rats or mice that could be attributed to trans-1,2-dichloroethylene exposure. Neither cis-, trans-, nor cis,trans-1,2-dichloroethylene was mutagenic in S. typhimurium strain TA97 (cis isomer only), TA98, TA100, TA1535, or TA1537, with or without S9 metabolic activation enzymes. In CHO cells in vitro, cis- 1,2-dichloroethylene induced sister chromatid exchanges (SCEs) in the absence of S9; with S9, the single trial that was performed yielded equivocal results. The cis,trans isomer induced significant increases in SCEs in cultured CHO cells with and without S9. In contrast to these positive results, trans-1,2-dichloroethylene gave negative results in the SCE test, with and without S9. Neither cis-, trans-, nor cis,trans-1,2-dichloroethylene induced chromosomal aberrations (Abs) in cultured CHO cells, with or without S9. In vivo, no induction of SCEs or Abs was noted in bone marrow cells of male mice administered cis- or trans-1,2-dichloroethylene by intraperitoneal injection once, with sampling performed 23 hours (for SCE analyses) or 17 hours (for Abs analyses) after injection. In addition, negative results were obtained in a peripheral blood micronucleus test in male and female mice administered trans- 1,2-dichloroethylene in microcapsules in feed for 14 weeks. Very little toxicity was associated with ingestion of microencapsulated trans-1-2-dichloroethylene. Histopathology and clinical chemistry data, combined with body and organ weight data, revealed that the maximum tolerated dose was not reached in these studies.
Ress
Nancy B
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National Toxicology Program, PO Box 12233, Research Triangle Park, NC 27709, USA.
D000818:Animals; D002214:Capsules; D015197:Carcinogenicity Tests; D004000:Dichloroethylenes / Q000008:administration & dosage / Q000633:toxicity*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D051379:Mice; D009152:Mutagenicity Tests; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344
D002214:Capsules; D004000:Dichloroethylenes; C035384:1,2-dichloroethylene