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Toxicokinetics of captan and folpet biomarkers in dermally exposed volunteers
Author(s) -
Berthet Aurélie,
Bouchard Michèle,
Vernez David
Publication year - 2012
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.1659
Subject(s) - urine , phthalic acid , chemistry , toxicokinetics , captan , metabolite , half life , pharmacokinetics , biomonitoring , excretion , chromatography , toxicology , pharmacology , metabolism , biochemistry , fungicide , medicine , organic chemistry , biology , botany
To better assess biomonitoring data in workers exposed to captan and folpet, the kinetics of ring metabolites [tetrahydrophthalimide (THPI), phthalimide (PI) and phthalic acid] were determined in urine and plasma of dermally exposed volunteers. A 10 mg kg −1 dose of each fungicide was applied on 80 cm 2 of the forearm and left without occlusion or washing for 24 h. Blood samples were withdrawn at fixed time periods over the 72 h following application and complete urine voids were collected over 96 h post‐dosing, for metabolite analysis. In the hours following treatment, a progressive increase in plasma levels of THPI and PI was observed, with peak levels being reached at 24 h for THPI and 10 h for PI. The ensuing elimination phase appeared monophasic with a mean elimination half‐life ( t ½ ) of 24.7 and 29.7 h for THPI and PI, respectively. In urine, time courses PI and phthalic acid excretion rate rapidly evolved in parallel, and a mean elimination t ½ of 28.8 and 29.6 h, respectively, was calculated from these curves. THPI was eliminated slightly faster, with a mean t ½ of 18.7 h. Over the 96 h period post‐application, metabolites were almost completely excreted, and on average 0.02% of captan dose was recovered in urine as THPI while 1.8% of the folpet dose was excreted as phthalic acid and 0.002% as PI, suggesting a low dermal absorption fraction for both fungicides. This study showed the potential use of THPI, PI and phthalic acid as key biomarkers of exposure to captan and folpet. Copyright © 2011 John Wiley & Sons, Ltd.