Interaction between 1,2-Dichloroethane and Disulfiram: I. Toxicologic Effects

Interaction between 1,2-Dichioroethane and Disulfiram. 1. ToxicologicEffects. 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-Dawleyrats fed 0.15% disulfiram (tetraethylthiuram disulfide; Antabuse;DSF) in AIN-76 diet [approx. (79 ± 11) mg DSF/kg bodywt/day] resulted in the observation of a toxic interaction relativeto either agent alone. The combination treatment caused testicularatrophy and histopathology in the liver and testes at 1,2-DCEinhalation concentrations >300 ppm (an estimated dose of194 mg/kg body wt/day) administered 5 days/week for 30 daysor 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 weightgains appeared relative to exposure to the 1,2-DCE alone. Forthe ip study, a decrease in spleen weight also occurred. Testicularatrophy and liver pathology had previously been observed inrats exposed to 20 ppm of ethylene dibromide (EDB) and fed 0.05%DSF in rat chow diet; EDB or DSF alone did not elicit testicularatrophy. These toxic effects indicate that 1,2-DCE may interactwith DSF as does EDB, but at a much higher dose.