Cargando…

Evaluation of Placental Transfer and Tissue Distribution of cis- and Trans-Permethrin in Pregnant Rats and Fetuses Using a Physiological-Based Pharmacokinetic Model

Biomonitoring studies have highlighted the exposure of pregnant women to pyrethroids based on the measurement of their metabolites in urine. Pyrethroids can cross the placental barrier and be distributed in the fetus as some pyrethroids were also measured in the meconium of newborns. Prenatal exposu...

Descripción completa

Detalles Bibliográficos
Autores principales: Personne, Stéphane, Brochot, Céline, Marcelo, Paulo, Corona, Aurélie, Desmots, Sophie, Robidel, Franck, Lecomte, Anthony, Bach, Véronique, Zeman, Florence
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495120/
https://www.ncbi.nlm.nih.gov/pubmed/34631627
http://dx.doi.org/10.3389/fped.2021.730383
_version_ 1784579468116885504
author Personne, Stéphane
Brochot, Céline
Marcelo, Paulo
Corona, Aurélie
Desmots, Sophie
Robidel, Franck
Lecomte, Anthony
Bach, Véronique
Zeman, Florence
author_facet Personne, Stéphane
Brochot, Céline
Marcelo, Paulo
Corona, Aurélie
Desmots, Sophie
Robidel, Franck
Lecomte, Anthony
Bach, Véronique
Zeman, Florence
author_sort Personne, Stéphane
collection PubMed
description Biomonitoring studies have highlighted the exposure of pregnant women to pyrethroids based on the measurement of their metabolites in urine. Pyrethroids can cross the placental barrier and be distributed in the fetus as some pyrethroids were also measured in the meconium of newborns. Prenatal exposure to pyrethroids is suspected to alter the neurodevelopment of children, and animal studies have shown that early life exposure to permethrin, one of the most commonly used pyrethroid in household applications, can alter the brain development. This study aimed to characterize the fetal permethrin exposure throughout gestation in rats. We developed a pregnancy physiologically based pharmacokinetic (pPBPK) model that describes the maternal and fetal kinetics of the cis- and trans- isomers of permethrin during the whole gestation period. Pregnant Sprague–Dawley rats were exposed daily to permethrin (50 mg/kg) by oral route from the start of gestation to day 20. Permethrin isomers were quantified in the feces, kidney, mammary gland, fat, and placenta in dams and in both maternal and fetal blood, brain, and liver. Cis- and trans-permethrin were quantified in fetal blood and tissues, with higher concentrations for the cis-isomer. The pPBPK model was fitted to the toxicokinetic maternal and fetal data in a Bayesian framework. Several parameters were adjusted, such as hepatic clearances, partition coefficients, and intestinal absorption. Our work allowed to estimate the prenatal exposure to permethrin in rats, especially in the fetal brain, and to quantitatively estimate the placental transfer. These transfers could be extrapolated to humans and be incorporated in a human pPBPK model to estimate the fetal exposure to permethrin from biomonitoring data.
format Online
Article
Text
id pubmed-8495120
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-84951202021-10-08 Evaluation of Placental Transfer and Tissue Distribution of cis- and Trans-Permethrin in Pregnant Rats and Fetuses Using a Physiological-Based Pharmacokinetic Model Personne, Stéphane Brochot, Céline Marcelo, Paulo Corona, Aurélie Desmots, Sophie Robidel, Franck Lecomte, Anthony Bach, Véronique Zeman, Florence Front Pediatr Pediatrics Biomonitoring studies have highlighted the exposure of pregnant women to pyrethroids based on the measurement of their metabolites in urine. Pyrethroids can cross the placental barrier and be distributed in the fetus as some pyrethroids were also measured in the meconium of newborns. Prenatal exposure to pyrethroids is suspected to alter the neurodevelopment of children, and animal studies have shown that early life exposure to permethrin, one of the most commonly used pyrethroid in household applications, can alter the brain development. This study aimed to characterize the fetal permethrin exposure throughout gestation in rats. We developed a pregnancy physiologically based pharmacokinetic (pPBPK) model that describes the maternal and fetal kinetics of the cis- and trans- isomers of permethrin during the whole gestation period. Pregnant Sprague–Dawley rats were exposed daily to permethrin (50 mg/kg) by oral route from the start of gestation to day 20. Permethrin isomers were quantified in the feces, kidney, mammary gland, fat, and placenta in dams and in both maternal and fetal blood, brain, and liver. Cis- and trans-permethrin were quantified in fetal blood and tissues, with higher concentrations for the cis-isomer. The pPBPK model was fitted to the toxicokinetic maternal and fetal data in a Bayesian framework. Several parameters were adjusted, such as hepatic clearances, partition coefficients, and intestinal absorption. Our work allowed to estimate the prenatal exposure to permethrin in rats, especially in the fetal brain, and to quantitatively estimate the placental transfer. These transfers could be extrapolated to humans and be incorporated in a human pPBPK model to estimate the fetal exposure to permethrin from biomonitoring data. Frontiers Media S.A. 2021-09-23 /pmc/articles/PMC8495120/ /pubmed/34631627 http://dx.doi.org/10.3389/fped.2021.730383 Text en Copyright © 2021 Personne, Brochot, Marcelo, Corona, Desmots, Robidel, Lecomte, Bach and Zeman. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pediatrics
Personne, Stéphane
Brochot, Céline
Marcelo, Paulo
Corona, Aurélie
Desmots, Sophie
Robidel, Franck
Lecomte, Anthony
Bach, Véronique
Zeman, Florence
Evaluation of Placental Transfer and Tissue Distribution of cis- and Trans-Permethrin in Pregnant Rats and Fetuses Using a Physiological-Based Pharmacokinetic Model
title Evaluation of Placental Transfer and Tissue Distribution of cis- and Trans-Permethrin in Pregnant Rats and Fetuses Using a Physiological-Based Pharmacokinetic Model
title_full Evaluation of Placental Transfer and Tissue Distribution of cis- and Trans-Permethrin in Pregnant Rats and Fetuses Using a Physiological-Based Pharmacokinetic Model
title_fullStr Evaluation of Placental Transfer and Tissue Distribution of cis- and Trans-Permethrin in Pregnant Rats and Fetuses Using a Physiological-Based Pharmacokinetic Model
title_full_unstemmed Evaluation of Placental Transfer and Tissue Distribution of cis- and Trans-Permethrin in Pregnant Rats and Fetuses Using a Physiological-Based Pharmacokinetic Model
title_short Evaluation of Placental Transfer and Tissue Distribution of cis- and Trans-Permethrin in Pregnant Rats and Fetuses Using a Physiological-Based Pharmacokinetic Model
title_sort evaluation of placental transfer and tissue distribution of cis- and trans-permethrin in pregnant rats and fetuses using a physiological-based pharmacokinetic model
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495120/
https://www.ncbi.nlm.nih.gov/pubmed/34631627
http://dx.doi.org/10.3389/fped.2021.730383
work_keys_str_mv AT personnestephane evaluationofplacentaltransferandtissuedistributionofcisandtranspermethrininpregnantratsandfetusesusingaphysiologicalbasedpharmacokineticmodel
AT brochotceline evaluationofplacentaltransferandtissuedistributionofcisandtranspermethrininpregnantratsandfetusesusingaphysiologicalbasedpharmacokineticmodel
AT marcelopaulo evaluationofplacentaltransferandtissuedistributionofcisandtranspermethrininpregnantratsandfetusesusingaphysiologicalbasedpharmacokineticmodel
AT coronaaurelie evaluationofplacentaltransferandtissuedistributionofcisandtranspermethrininpregnantratsandfetusesusingaphysiologicalbasedpharmacokineticmodel
AT desmotssophie evaluationofplacentaltransferandtissuedistributionofcisandtranspermethrininpregnantratsandfetusesusingaphysiologicalbasedpharmacokineticmodel
AT robidelfranck evaluationofplacentaltransferandtissuedistributionofcisandtranspermethrininpregnantratsandfetusesusingaphysiologicalbasedpharmacokineticmodel
AT lecomteanthony evaluationofplacentaltransferandtissuedistributionofcisandtranspermethrininpregnantratsandfetusesusingaphysiologicalbasedpharmacokineticmodel
AT bachveronique evaluationofplacentaltransferandtissuedistributionofcisandtranspermethrininpregnantratsandfetusesusingaphysiologicalbasedpharmacokineticmodel
AT zemanflorence evaluationofplacentaltransferandtissuedistributionofcisandtranspermethrininpregnantratsandfetusesusingaphysiologicalbasedpharmacokineticmodel