Toxicokinetics of captan and folpet biomarkers in orally exposed volunteers

Abstract

The time courses of key biomarkers of exposure to captan and folpet was assessed in accessible biological matrices of orally exposed volunteers. Ten volunteers ingested 1 mg kg(-1) body weight of captan or folpet. Blood samples were withdrawn at fixed time periods over the 72 h following ingestion and complete urine voids were collected over 96 h post-dosing. The tetrahydrophthalimide (THPI) metabolite of captan along with the phthalimide (PI) and phthalic acid metabolites of folpet were then quantified in these samples. Plasma levels of THPI and PI increased progressively after ingestion, reaching peak values ~10 and 6 h post-dosing, respectively; subsequent elimination phase appeared monophasic with a mean elimination half-life (t(½) ) of 15.7 and 31.5 h, respectively. In urine, elimination rate time courses of PI and phthalic acid evolved in parallel, with respective t(½) of 27.3 and 27.6 h; relatively faster elimination was found for THPI, with mean t(½) of 11.7 h. However, phthalic acid was present in urine in 1000-fold higher amounts than PI. In the 96 h period post-treatment, on average 25% of folpet dose was excreted in urine as phthalic acid as compared with only 0.02% as PI. The corresponding value for THPI was 3.5%. Overall, THPI and PI appear as interesting biomarkers of recent exposure, with relatively short half-lives; their sensitivity to assess exposure in field studies should be further verified. Although not a metabolite specific to folpet, the concomitant use of phthalic acid as a major biomarker of exposure to folpet should also be considered.

Toxicokinetics of captan and folpet biomarkers in dermally exposed volunteers

“…The urinary time course of THPI observed in this study following dermal application in volunteers can further be compared with that reported in Berthet et al (2011a) following an oral administration, again in the same volunteers. In accordance with the plasma profiles, the apparent elimination half-life of THPI calculated from urinary excretion rate time courses indicates a slightly slower elimination of THPI following dermal application than ingestion (average t ½ of 18.7 and 11.7 h, respectively).…”

Toxicokinetic modeling of folpet fungicide and its ring‐biomarkers of exposure in humans

“…The linear elimination of PI from blood observed in Berthet et al . () suggests the absence of a significant storage of folpet in the body, as either an accumulation in lipids or a binding to tissue proteins, and indicates that the whole body distribution of folpet ring metabolites can be described using a single compartment B ( t ) with first‐order elimination.…”

“…Model development was based on available published metabolism data (Gordon et al ., ) along with the human time‐course data newly collected in volunteers (Berthet et al ., , ). In this controlled experiment of Berthet et al .…”

“…In this controlled experiment of Berthet et al . (, ), healthy volunteers were exposed orally to 1 mg kg −1 of folpet or dermally to 10 mg kg −1 of folpet. The detailed time courses of PI in plasma and in urine were determined during a 96 h period post‐dosing.…”

Development of Specific Electrochemical Biosensor Based on Chitosan Modified Screen Printed Carbon Electrode for the Monitoring of Captan Fungicide

“…According to the postulation of captan reaction mechanism [14,15], this fungicide reacts extremely rapidly with thiol-containing compounds such as glutathione to produce THPI (1,2,3,6-tetrahydro-phthalimide) and reactive thiophosgene by the equation: Captan + GSH → Thiophosgene + THPI +HCl . The thiophosgene immediately undergoes further reaction with amino and thiol groups of the cysteine moiety contained in the tripeptide glutathione through a xenobiotic-GSH conjugation process by GST catalysis to form a thiazolidine-GSH complex which it is spontaneously transformed to an electroactive thiazolidine ring compound, thiazolidine-2-thione-4-carboxylic acid (TTCA).…”