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Marc-André Verner,¹ Pierre Ayotte,² Gina Muckle,² Michel Charbonneau,³ and Sami Haddad¹

¹Département des sciences biologiques, Centre Toxen, Université du Québec à Montréal, Montréal, Québec, Canada; ²Centre de recherche du Centre Hospitalier Universitaire de Québec – Centre Hospitalier de l'Université Laval, Université Laval, Québec, Québec, Canada; ³Institut National de la Recherche Scientifique – Institut Armand-Frappier, Université du Québec, Laval, Québec, Canada

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 postnatally for exposure assessment, an approach that might not capture some key events in the toxicokinetics of POPs.

Objectives: 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) , β-hexachlorocyclohexane (β-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 β-HCH for which levels were near the limits of detection.

Conclusion: 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.

Key words: epidemiology, exposure assessment, infants, persistent organic pollutants, physiologically based pharmacokinetic modeling. Environ Health Perspect 117:481–487 (2009) . doi:10.1289/ehp.0800047 available via http://dx.doi.org/ [Online 10 November 2008]

Address correspondence to S. Haddad, Université du Québec à Montréal, C.P. 8888 Succ. Centreville, Montréal, Québec, Canada H3C 3P8. Telephone: (514) 987-3000. Fax: (514) 987-4647. E-mail: haddad.sami@uqam.ca

Supplemental Material is available online at http://www.ehponline.org/members/2008/0800047/suppl.pdf

We thank R. McDougall from Aegis Technologies for his valuable input in the PBPK model development.

M.A.V. is the recipient of a Natural Sciences and Engineering Research Council of Canada (NSERC) doctoral scholarship.

The authors declare they have no competing financial interests.

Received 28 July 2008 ; accepted 10 November 2008.