title: Metabolism of a dithiocarbamate fungicide thiram to carbon disulfide in the rat and its hepatotoxic implications.
abstract: Thiram, tetramethylthiuram disulfide, is used extensively as an agricultural fungicide whose toxicity is largely dependent on its metabolism. The following experiments were carried out to investigate whether carbon disulfide (CS2) is a metabolic product of microsomal monooxygenase catalyzed metabolism of thiram in rats. Adult male Sprague-Dawley rats (160-200 g) were given thiram (60 mg/kg, b.wt.) in corn oil by intraperitoneal injection and placed individually in a metabolic apparatus. Concentration of CS2 in the breath was determined by drawing the expired air through a series of traps containing a CS2 complexing agent. Expiration of CS2 was almost complete within 5 hrs following thiram administration. The formation of CS2 from thiram was increased by pretreatment of rats with phenobarbital and decreased by SKF 525-A. Furthermore, measurement of the activities of hepatic microsomal and serum enzymes at 5 hrs and 24 hrs following thiram treatment indicated that thiram caused significant loss of cytochrome P-450 and benzphetamine N-demethylase activity only at 24 hrs interval whereas there was significant elevation of sorbitol dehydrogenase (SDH) and serum glutamic oxalacetic transaminase (SGOT) activity at 5 and 24 hrs after treatment. The data confirm that CS2 is an in vivo metabolite of thiram and may be, in part, responsible for the observed hepatotoxicity.
mesh_terms: D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002246:Carbon Disulfide / Q000378:metabolism*; D007064:L-Iditol 2-Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011335:Proadifen / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013859:Thiocarbamates / Q000378:metabolism*; D013893:Thiram / Q000378:metabolism* / Q000633:toxicity
chemical_list: D013859:Thiocarbamates; D013893:Thiram; D011335:Proadifen; D007064:L-Iditol 2-Dehydrogenase; D001219:Aspartate Aminotransferases; D002246:Carbon Disulfide