Toxicokinetics of captan and folpet biomarkers in dermally exposed volunteers

Abstract

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fungicide was applied on 80 cm(2) of the forearm and left without occlusion or washing for 24 h. Blood samples were withdrawn at fixed time periods over the 72 h following application and complete urine voids were collected over 96 h post-dosing, for metabolite analysis.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.