title: A physiologically based pharmacokinetic model for the assessment of infant exposure to persistent organic pollutants in epidemiologic studies.
abstract: BACKGROUND
  It has been suggested that pre- and postnatal exposure to persistent organic pollutants (POPs) can promote several adverse effects in children, such as altered neurodevelopment. Epidemiologic studies to date have relied on the analysis of biological samples drawn pre- or post-natally for exposure assessment, an approach that might not capture some key events in the toxicokinetics of POPs.
  
  
  OBJECTIVE
  We aimed to build a generic physiologically based pharmacokinetic (PBPK) modeling framework for neutral POPs to assess infant toxicokinetic profiles and to validate the model using data on POP levels measured in mothers and infants from a Northern Québec Inuit population.
  
  
  METHODS
  The PBPK model developed herein was based upon a previously published model to which an infant submodel was added. Using the model and maternal blood levels at the time of delivery, exposure to 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE), 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT), hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH), 2,2',3,4,4',5'-hexachlorobiphenyl (PCB-138), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153), and 2,2',3,4,4',5,5'-heptachlorobiphenyl (PCB-180) in mothers was estimated to subsequently simulate infant blood, breast milk, and cord blood POP concentration. Simulations were then compared with corresponding measured levels through Spearman correlation analyses.
  
  
  RESULTS
  Predictions were highly correlated with measured concentrations for PCB-153, PCB-180, PCB-138, HCB, and p,p'-DDE (r = 0.83-0.96). Weaker correlations were observed for p,p'-DDT and beta-HCH for which levels were near the limits of detection.
  
  
  CONCLUSIONS
  This is the first study to validate a PBPK model of POPs in infants on an individual basis. This approach will reduce sampling efforts and enable the use of individualized POP toxicokinetic profiles in the epidemiologic studies of POP adverse effects on child development.
authors.affiliation: Département des sciences biologiques, Centre Toxen, Université du Québec à Montréal, and Centre de recherche du Hospitalier Universitaire de Québec, Montréal, Québec, Canada.
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Verner
authors.forename: Pierre
authors.initials: P
authors.lastname: Ayotte
authors.forename: Gina
authors.initials: G
authors.lastname: Muckle
authors.forename: Michel
authors.initials: M
authors.lastname: Charbonneau
authors.forename: Sami
authors.initials: S
authors.lastname: Haddad