© 1986 Oxford University Press
research-article |
Interaction between 1,2-Dichloroethane and Disulfiram
I. Toxicologic Effects
*Department of Environmental Health, University of Cincinnati Medical Center 3223 Eden Avenue, Cincinnati. Ohio 45267-0056
tNational Institute for Occupational Safety and Health, Robert A. Taft Center 4676 Columbia Parkway, Cincinnati, Ohio 45226
Interaction between 1,2-Dichioroethane and Disulfiram. 1. Toxicologic Effects. IGWE, O. J., QUE HEE, S. S., AND WAGNER, W. D. (1986). Fundam Appl. Toxicol. 6, 733–746. Inhalation and intraperitoneal (ip) studies with 1,2-dichloroethane (1,2-DCE) using Sprague-Dawley rats fed 0.15% disulfiram (tetraethylthiuram disulfide; Antabuse; DSF) in AIN-76 diet [approx. (79 ± 11) mg DSF/kg body wt/day] resulted in the observation of a toxic interaction relative to either agent alone. The combination treatment caused testicular atrophy and histopathology in the liver and testes at 1,2-DCE inhalation concentrations >300 ppm (an estimated dose of 194 mg/kg body wt/day) administered 5 days/week for 30 days or at ip doses of 150 mg 1,2-DCE/kg body wt/day over 30 days, 7 days/week. DSF lowered the 1,2-DCE dose at which liver enlargement, decreased liver/body weight ratios, and decreased body weight gains appeared relative to exposure to the 1,2-DCE alone. For the ip study, a decrease in spleen weight also occurred. Testicular atrophy and liver pathology had previously been observed in rats exposed to 20 ppm of ethylene dibromide (EDB) and fed 0.05% DSF in rat chow diet; EDB or DSF alone did not elicit testicular atrophy. These toxic effects indicate that 1,2-DCE may interact with DSF as does EDB, but at a much higher dose.