2-thioxo-4-thiazolidinecarboxylic-acid and tetrahydrophthalimide

Captan fungicide (N-(trichloromethylthio)-4-cyclohexene-1,2-dicarboximide) metabolism in two human volunteers rapidly yields THPI (tetrahydrophthalimide) and TTCA (thiazolidine-2-thione-4-carboxylic acid). The work was done to evaluate usefulness of TTCA and THPI as biomarkers of occupational exposure and to compare human and rat dermal absorption and metabolism. THPI in 12h urine ranged from MDL (5 ppb) to 640 ppb and was stable for at least one year. TTCA was also a stable metabolite, but the MDL was 50 ppb. THPI was detectable in urine for 72 hours following oral dosages of 1 mg/kg, but most was eliminated 0-24 h. No THPI was detectable in urine following application of a chloroform solution to hands, forearms, or inguinal region. Dermal absorption and metabolism of captan are substantially different in humans and rats.

Topics: Administration, Cutaneous; Administration, Oral; Adult; Biomarkers; Biotransformation; Captan; Dose-Response Relationship, Drug; Humans; Male; Phthalimides; Thiazoles; Thiazolidines

Capillary gas chromatographic (GC) methods using sulphur and mass selective detection for the qualitative and quantitative determination of tetrahydrophtalimide (THPI) and 2-thiothiazolidine-4-carboxylic acid (TTCA), urinary metabolites of the fungicide captan in rat and humans, were developed. Urinary detection limits were 2.7 micrograms/l for THPI and 110 micrograms/l for TTCA. Intraperitoneal and oral administration of captan to rats resulted in a 48-h cumulative urinary excretion of THPI of 1%-2% and 3%-9% of the dose, respectively. Cumulative urinary excretion of TTCA over 48 h ranged from 2% to 5% of the captan dose for the respective routes of administration. In urine of non-exposed human subjects, neither THPI nor TTCA could be detected. In urine of fruit-growers who were occupationally exposed to captan, both THPI and TTCA could be detected. Based on these results, THPI and TTCA are proposed as promising parameters for the biological monitoring of occupational exposure to captan.

Topics: Agriculture; Animals; Captan; Chromatography, Gas; Environmental Monitoring; Humans; Male; Occupational Exposure; Phthalimides; Rats; Rats, Inbred Strains; Sulfur; Thiazoles; Thiazolidines