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Prediction of maternal and foetal exposures to perfluoroalkyl compounds in a Spanish birth cohort using toxicokinetic modelling.

Authors
  • Brochot, Céline1
  • Casas, Maribel2
  • Manzano-Salgado, Cyntia2
  • Zeman, Florence A3
  • Schettgen, Thomas4
  • Vrijheid, Martine2
  • Bois, Frédéric Y3
  • 1 Institut National de l'Environnement Industriel et des Risques (INERIS), Unité Modèles pour l'Ecotoxicologie et la Toxicologie (METO), Parc ALATA BP2, 60550 Verneuil en Halatte, France. Electronic address: [email protected] , (France)
  • 2 ISGlobal, Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; CIBER Epidemiologa y Salud Pública (CIBERESP), Madrid, Spain. , (Spain)
  • 3 Institut National de l'Environnement Industriel et des Risques (INERIS), Unité Modèles pour l'Ecotoxicologie et la Toxicologie (METO), Parc ALATA BP2, 60550 Verneuil en Halatte, France. , (France)
  • 4 Institute for Occupational Medicine, RWTH Aachen University, Aachen, Germany. , (Germany)
Type
Published Article
Journal
Toxicology and Applied Pharmacology
Publisher
Elsevier
Publication Date
Jun 26, 2019
Volume
379
Pages
114640–114640
Identifiers
DOI: 10.1016/j.taap.2019.114640
PMID: 31251942
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Prenatal exposures to perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) have been associated with child health outcomes, but many of these associations remain poorly characterized. The aim of this work was to provide new indicators of foetal exposure for the Spanish INMA birth cohort. First, a pregnancy and lactation physiologically based pharmacokinetic (PBPK) model was calibrated in a population framework to provide quantitative estimates for the PFOA and PFOS placental transfers in humans. The estimated distributions indicated that PFOA crosses the placental barrier at a rate three times higher than PFOS and shows a higher variability between mothers. The PBPK model was then used to back-calculate the time-varying daily intakes of the INMA mothers corrected for their individual history from a spot maternal concentration. We showed the importance of accounting for the mothers' history as different dietary intakes can result in similar measured concentrations at one time point. Finally, the foetal exposure was simulated in target organs over pregnancy using the PBPK model and the estimated maternal intakes. We showed that the pattern of PFOA and PFOS exposures varies greatly among the foetuses. About a third has levels of either one compound always higher than the levels of the other compound. The other two thirds showed different ranking of PFOA and PFOS in terms of concentrations in the target organs. Our simulated foetal exposures bring additional information to the measured maternal spot concentrations and can help to better characterize the prenatal exposure in target organs during windows of susceptibility. Copyright © 2019 Elsevier Inc. All rights reserved.

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