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A physiologically based pharmacokinetic model for the assessment of infant exposure to persistent organic pollutants

Marc-André Verner1, Pierre Ayotte, Gina Muckle

  • 1Département des sciences biologiques, Centre Toxen, Université du Québec à Montréal, and Centre de recherche du Hospitalier Universitaire de Québec, Montréal, Québec, Canada.

Environmental Health Perspectives
|April 2, 2009
PubMed

Insights

This study developed a physiologically based pharmacokinetic (PBPK) model to assess infant exposure to persistent organic pollutants (POPs). The validated model accurately predicts infant POP levels, reducing sampling needs for future research on child development.

Area of Science:

  • Environmental Health
  • Toxicology
  • Pharmacokinetics

Background:

  • Persistent organic pollutants (POPs) exposure in pregnancy may affect child neurodevelopment.
  • Current exposure assessment methods may not fully capture POP toxicokinetics.
  • Infant exposure assessment is crucial for understanding developmental effects.

Purpose of the Study:

  • To develop a generic physiologically based pharmacokinetic (PBPK) modeling framework for neutral POPs.
  • To assess infant toxicokinetic profiles using the PBPK model.
  • To validate the PBPK model with POP data from a Northern Québec Inuit population.

Main Methods:

  • An infant submodel was added to a pre-existing PBPK model.
  • Maternal blood POP levels were used to simulate infant blood, breast milk, and cord blood concentrations.
  • Simulated POP concentrations were compared to measured levels using Spearman correlation.

Main Results:

  • High correlations (r=0.83-0.96) were found for PCB-153, PCB-180, PCB-138, HCB, and p,p'-DDE.
  • Weaker correlations were observed for p,p'-DDT and beta-HCH due to low measured concentrations.
  • The PBPK model demonstrated good predictive performance for several key POPs.

Conclusions:

  • This is the first study to individually validate a PBPK model for POPs in infants.
  • The PBPK modeling approach can reduce the need for extensive biological sampling.
  • Individualized POP toxicokinetic profiles can enhance epidemiologic studies on POPs' effects on child development.
Abstract

Keywords:
epidemiologyexposure assessmentinfantspersistent organic pollutantsphysiologically based pharmacokinetic modeling

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