title: A Simple Pharmacokinetic Model of Prenatal and Postnatal Exposure to Perfluoroalkyl Substances (PFASs).
abstract: Most children are exposed to perfluoroalkyl substances (PFASs) through placental transfer, breastfeeding, and other environmental sources. To date, there are no validated tools to estimate exposure and body burden during infancy and childhood. In this study, we aimed to (i) develop a two-generation pharmacokinetic model of prenatal and postnatal exposure to perfluorooctanoic acid (PFOA), perfluorooctanesulfonate (PFOS), and perfluorohexanesulfonate (PFHxS); and to (ii) evaluate it against measured children's levels in two studies. We developed a pharmacokinetic model consisting of a maternal and a child compartment to simulate lifetime exposure in women and transfer to the child across the placenta and through breastfeeding. To evaluate the model, we performed simulations for each mother-child dyad from two studies in which maternal PFAS levels at delivery and children's PFAS levels were available. Model predictions based on maternal PFAS levels, sex of child, body weight, and duration of breastfeeding explained between 52% and 60% of the variability in measured children's levels at 6 months of age and between 52% and 62% at 36 months. Monte Carlo simulations showed that the daily intake through breastfeeding and resulting internal PFAS levels can be much higher in nursing infants than in mothers. This pharmacokinetic model shows potential for postnatal exposure assessment in the context of epidemiological studies and risk assessment.
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Verner
authors.forename: Gérard
authors.initials: G
authors.lastname: Ngueta
authors.affiliation: National Institute of Environmental Health Sciences, National Institutes of Health , Department of Health and Human Services, Research Triangle Park, North Carolina 27709, United States.|Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest University School of Medicine , Winston-Salem, North Carolina 27157, United States.
authors.forename: Elizabeth T
authors.initials: ET
authors.lastname: Jensen
authors.affiliation: Department of Chemical Safety and Toxicology, Bavarian Health and Food Safety Authority , D-80538 Munich, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Fromme
authors.affiliation: Department of Chemical Safety and Toxicology, Bavarian Health and Food Safety Authority , D-80538 Munich, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Völkel
authors.affiliation: Division of Environmental Medicine, Norwegian Institute of Public Health , PO Box 4404 Nydalen, 0403 Oslo, Norway.
authors.forename: Unni Cecilie
authors.initials: UC
authors.lastname: Nygaard
authors.affiliation: Division of Environmental Medicine, Norwegian Institute of Public Health , PO Box 4404 Nydalen, 0403 Oslo, Norway.
authors.forename: Berit
authors.initials: B
authors.lastname: Granum
authors.affiliation: National Institute of Environmental Health Sciences, National Institutes of Health , Department of Health and Human Services, Research Triangle Park, North Carolina 27709, United States.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Longnecker
mesh_terms: D000328:Adult; D017738:Alkanesulfonic Acids / Q000009:adverse effects / Q000493:pharmacokinetics; D001942:Breast Feeding; D002210:Caprylates / Q000009:adverse effects / Q000493:pharmacokinetics; D002648:Child; D002675:Child, Preschool; D004781:Environmental Exposure / Q000009:adverse effects*; D004785:Environmental Pollutants / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D005466:Fluorocarbons / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008962:Models, Theoretical; D009010:Monte Carlo Method; D009035:Mothers; D010920:Placenta / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D013451:Sulfonic Acids / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D017738:Alkanesulfonic Acids; D002210:Caprylates; D004785:Environmental Pollutants; D005466:Fluorocarbons; D013451:Sulfonic Acids; C471071:perfluorohexanesulfonic acid; C023036:perfluorooctanoic acid; C076994:perfluorooctane sulfonic acid