The Fate ofN-Trichloro[14C]methylthio-4-cyclohexene-1,2-dicarboximide ([14C]Captan) in the Rat

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Abstract
1. Orally administered [14C]captan is rapidly metabolized and excreted by the rat. 50% of the oral dose was excreted within 9 h, but 50% excretion of an intraperitoneal dose was not achieved until 2 days after injection. 2. The final distribution of 14C 4 days after oral treatment with [14C]captan was: 51.8% (urine), 22.8% (expired air), 15.9% (faeces), and 0.6% (tissues). 3. Urinary metabolites of orally administered [14C]captan were identified as thiazolidine-2-thione-4-carboxylic acid (18.6%), a salt of dithiobis(methane-sulphonic acid) (54.0%), and the disulphide monoxide derivative of dithiobis-(methanesulphonic acid) (13.8%). The latter two metabolites were not detected in the urine of rats receiving [14C]captan by intraperitoneal injection. 14CO2 was identified in the expired air. 4. Radioactive thiazolidine-2-thione-4-carboxylic acid was detected in the urine of rats treated simultaneously with captan and either [U-14C]cystine or reduced [35S]glutathione. [35S]Dithiobis(methanesulphonic acid) was excreted in the urine of rats treated simultaneously with sodium [35S]sulphite and either captan or thiophosgene. 5. Metabolism of captan appears to involve evolution of thiophosgene, derived from the trichloromethylthio moiety. This thiophosgene is detoxified, at least in part, by three mechanisms: 1, oxidation and/or hydrolysis to CO2; 2, reaction with a cysteine moiety to yield thiazolidine-2-thione-4-carboxylic acid; 3, reaction with sulphite to produce dithiobis(methanesulphonic acid). Degradation in the gastrointestinal tract appears to play a major role in captan metabolism.