PBPK modeling of the cis- and trans-permethrin isomers and their major urinary metabolites in rats

Toxicology and Applied Pharmacology
Marie-Emilie WilleminCéline Brochot

Abstract

Permethrin, a pyrethroid insecticide, is suspected to induce neuronal and hormonal disturbances in humans. The widespread exposure of the populations has been confirmed by the detection of the urinary metabolites of permethrin in biomonitoring studies. Permethrin is a chiral molecule presenting two forms, the cis and the trans isomers. Because in vitro studies indicated a metabolic interaction between the trans and cis isomers of permethrin, we adapted and calibrated a PBPK model for trans- and cis-permethrin separately in rats. The model also describes the toxicokinetics of three urinary metabolites, cis- and trans-3-(2,2 dichlorovinyl)-2,2-dimethyl-(1-cyclopropane) carboxylic acid (cis- and trans-DCCA), 3-phenoxybenzoic acid (3-PBA) and 4'OH-phenoxybenzoic acid (4'-OH-PBA). In vivo experiments performed in Sprague-Dawley rats were used to calibrate the PBPK model in a Bayesian framework. The model captured well the toxicokinetics of permethrin isomers and their metabolites including the rapid absorption, the accumulation in fat, the extensive metabolism of the parent compounds, and the rapid elimination of metabolites in urine. Average hepatic clearances in rats were estimated to be 2.4 and 5.7 L/h/kg for cis- and trans-perme...Continue Reading

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Citations

Nov 5, 2016·Toxicology and Applied Pharmacology·Virginia C MoserKatherine L McDaniel
Apr 27, 2017·Journal of Pharmaceutical Sciences·Manoj AmaraneniBrian S Cummings
Apr 17, 2018·Journal of Applied Toxicology : JAT·Rachid JellaliEric Leclerc
Dec 30, 2017·Journal of Exposure Science & Environmental Epidemiology·Jonathan Côté, Michèle Bouchard
Jun 30, 2019·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Pankaj SethiCatherine A White
Oct 9, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Pankajini MallickMiyoung Yoon
Dec 7, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jing PangJames V Bruckner
Jun 21, 2017·Critical Reviews in Toxicology·Marie-Emilie Willemin, Annie Lumen
Dec 14, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Tanzir B MortuzaJames V Bruckner
Mar 30, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Rachid JellaliEric Leclerc
Jul 4, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Marie VanackerAmélie Crépet

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