Journal
TOXICOLOGY AND APPLIED PHARMACOLOGY
Volume 379, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2019.114640
Keywords
PBPK model; PFAS; Reverse dosimetry; In utero; Exposure assessment; Pregnancy
Categories
Funding
- European Community [308333]
- French Ministry of Ecology and Sustainable Development [Program 190]
- Instituto de Salud Carlos III [Red INMA G03/176, PI12/01890]
- Generalitat de Catalunya-CIRIT [1999SGR 00241]
- Instituto de Salud Carlos III (Ministry of Economy and Competitiveness) [MS16/00128, FI14/00099]
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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.
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