Interaction between 1,2-dichloroethane and disulfiram. I. Toxicologic effects.
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 greater than 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.
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D000336:Aerosols; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004221:Disulfiram / Q000008:administration & dosage / Q000633:toxicity*; D004347:Drug Interactions; D005025:Ethylene Dichlorides / Q000008:administration & dosage / Q000633:toxicity*; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013737:Testis / Q000187:drug effects* / Q000473:pathology; D014835:Volatilization
D000336:Aerosols; D005025:Ethylene Dichlorides; D006843:Hydrocarbons, Chlorinated; C024565:ethylene dichloride; D004221:Disulfiram