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Interaction between 1,2-dichloroethane and tetraethylthiuram disulfide (disulfiram) II. Hepatotoxic manifestations with possible mechanism of action.
Igwe OJ; Hee SS; Wagner WD
Toxicol Appl Pharmacol 1986 Nov; 86(2):286-297
Weanling male Sprague-Dawley-rats were exposed through their diets to disulfiram (97778) (DSF) while 1,2-dichloroethane (107062) (DCE) was administered subchronically by inhalation at 150, 300, or 450 parts per million. Clear evidence was obtained that the biochemical effects of DCE in the liver were changed by dietary DSF, including enhanced toxic responses verified through increased liver weight to body weight ratios, and increased serum activities of various enzymes. The authors suggest that the increased level of DCE toxicity in the presence of dietary DSF may be related to the observed reduction of hepatic cytochrome-P-450, as well as to the induction of cytosolic glutathione-S-transferase (GST) and increases in hepatic reduced glutathione (GSH). It is stated that these data support the assumption of in-vivo cytosolic metabolism of DCE and its importance when DSF is present. Decreased levels of cytochrome-P- 450, increased GSH levels in the tissues, and increased GST isoenzyme activities are considered to produce an enhanced potential for cytosol mediated metabolism of DCE. The authors suggest that the body may make a physiological attempt to maintain GSH homeostasis, thus causing an overcompensation resulting in the observed increase in liver GSH levels resulting from DCE and DSF exposure. It is suggested that there may be an increased risk of adverse effects resulting from DCE exposure for employees who are currently taking DSF therapy.
NIOSH-Author; Solvents; Rubber-workers; Rubber-manufacturing-industry; Tobacco-industry; Tobacco; Laboratory-animals; Inhalants; Hepatotoxicity; Pharmacodynamics; Drug-interaction; Hepatic-microsomal-enzymes
Issue of Publication
Toxicology and Applied Pharmacology
Page last reviewed: September 2, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division