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Modélisation toxicocinétique de la perméthrine pour lier l’exposition aux biomarqueurs mesurés lors des campagnes de biosurveillance humaine

Abstract : Humans are largely exposed to pyrethroids, an insecticide family. In this project, we aimed at developing a PBPK model to link exposure to permethrin to the concentrations of metabolites in urine, used as biomarkers of exposure. A three steps strategy was followed. First, an analytical method (GC-MS/MS) was developed to measure simultaneously these compounds in the several biological matrices. A PBPK of permethrin was then developed for each isomer to describe the fate of permethrin and metabolites in rat. The toxicokinetic parameters were estimated in a Bayesian framework using in vivo experiments in rats. The PBPK model of permethrin was then validated on the kinetic data of a mixture of permethrin. Hepatic metabolism was quantified in humans in primary hepatocytes in optimal conditions for in vitro-in vivo extrapolation, by incubating the isomers separately and as a mixture. This work underlines that a general PBPK model for pyrethroids could be considered. The lack of interaction between isomers observed in in vitro experiments could simplify the characterization of the exposure to mixtures of pyrethroids.
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Céline Brochot. Modélisation toxicocinétique de la perméthrine pour lier l’exposition aux biomarqueurs mesurés lors des campagnes de biosurveillance humaine. Rapport Scientifique INERIS, 2016, 2015-2016, pp.54-55. ⟨ineris-01869630⟩

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