The Influence of Disulfiram or Ethanol on 1,2-Dichloroethane Carcinogenicity, Metabolism, and DNA Binding.
Cheever KL; Cholakis JM; El-hawari AM; Kovatch RM; Weisbruger EK
The interaction of 1,2-dichloroethane (107062) (EDC) with disulfiram (97778) (DS) or ethanol (64175) was investigated in rats. Sprague- Dawley-rats were exposed for 24 months to 50 parts per million (ppm) concentrations of EDC in an inhalation study while at the same time being exposed to 0.05 percent DS in the diet and/or 5 percent ethanol in the drinking water. A high incidence of intrahepatic bile duct cholangiomas were reported in both sexes receiving EDC and DS, 18 percent incidence among males and 34 percent among females. Male rats also registered 12 percent incidence of hepatocellular adenomas, 22 percent incidence for interstitial cell tumors in the testes, 20 percent subcutis fibroma, and 25 percent mammary adenocarcinomas in females. The expected rates for these disorders would have been 0, 4, 4, and 8 percent, respectively. A slight increase in neoplastic nodules occurred in males receiving EDC and ethanol, 8 percent versus 0 percent expected. The DNA binding by EDC was not altered by DS treatment, and the metabolism of EDC was qualitatively the same as in corresponding controls. However, the combined treatment of EDC and DS did reduce the rate of elimination of EDC, and sustained the blood concentration levels of unchanged EDC, which may be related to the increased carcinogenic effect of the combination.
NIOSH-Contract; Contract-200-82-2508; NIOSH-Author; Laboratory-animals; Metabolic-study; Organic-solvents; Carcinogens; Nucleic-acids; Liver-tumors;
107-06-2; 97-77-8; 64-17-5;
Proceedings of the Fourth NCI/EPA/NIOSH Collaborative Workshop: Progress on Joint Environmental and Occupational Cancer Studies, April 22-23, 1986, Rockville, Maryland, NIH Publication No. 88-2960, NIOSH Contract No. 200-82-2508