Ethylene dichloride: the influence of disulfiram or ethanol on oncogenicity, metabolism, and DNA covalent binding in rats.
Cheever-KL; Cholakis-JM; El-Hawari-AM; Kovatch-RM; Weisburger-EK
Fundam Appl Toxicol 1990 Feb; 14(2):243-261
An evaluation was conducted of the effects of disulfiram (97778) and ethanol (64175) on oncogenicity, metabolism and DNA covalent binding of ethylene-dichloride (107062) (EDC) in Sprague-Dawley-rats. Exposures were performed at 50 parts per million (ppm), the current occupational standard. The animals were exposed to EDC at 50ppm in air in 2.2 cubic meter chambers for 7 hours per day, 5 days per week for 24 months. The dose of disulfiram was given through addition to food at 0.05% and that of ethanol was given through addition to water at 5%. EDC metabolism and DNA binding were assessed after the 24 month study through the use of radiolabeled EDC. The animals were also exposed to a complete necropsy examination. Rats in either the disulfiram or EDC/disulfiram exposed group exhibited significant reductions in body weight throughout the investigation. The daily intake of disulfiram for female and male rats wase 7.0 to 7.1mg/kg and 10 to 10.6mg/kg, respectively. The ethanol doses were determined to be 2.4 to 2.6mg/kg and 2.3 to 2.4mg/kg for males and females, respectively. Overall mortality rates did not reveal any correlations with sex or exposure when compared to controls. It was determined that the overall tumor incidence for EDC/disulfiram exposed animals was increased with high levels of hepatic, testicular and mammary tumors. The levels of unchanged EDC observed in the blood of these animals after 7 hours of exposure was notably higher for disulfiram treated animals. Urinalysis revealed increased chloroacetic-acid in the urine of disulfiram and EDC/disulfiram exposed rats. Exposure related differences in DNA covalent binding were not observed for any of the exposure regimens. The authors conclude that only the EDC/disulfiram treatment caused higher tumor levels, with the EDC/ethanol, disulfiram, and ethanol exposure regimens demonstrating no increases in tumor formation.
NIOSH-Author; Tumorigenesis; Exposure-methods; Exposure-levels; Laboratory-animals; Metabolites; Oncogenesis; Occupational-exposure; Exposure-limits; Blood-analysis; In-vivo-study
97-77-8; 64-17-5; 107-06-2
Fundamental and Applied Toxicology