Toxicokinetic Modeling of Persistent Organic Pollutant Levels in Blood from Birth to 45 Months of Age in Longitudinal Birth Cohort Studies

Marc-André Verner,^1,2 Dean Sonneborn,³ Kinga Lancz,⁴ Gina Muckle,⁵ Pierre Ayotte,⁵ Éric Dewailly,⁵ Anton Kocan,⁶ Lubica Palkovicová,⁴ Tomas Trnovec,⁴ Sami Haddad,⁷ Irva Hertz-Picciotto,³ and Merete Eggesbø⁸

¹Institute of Environmental Medicine, Karolinska Institutet, Solna, Sweden; ²Channing Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA; ³Department of Public Health Sciences, University of California, Davis, Davis, California, USA; ⁴Department of Environmental Medicine, Slovak Medical University, Bratislava, Slovakia; ⁵Centre de recherche du CHUQ-CHUL, Université Laval, Quebec City, Quebec, Canada; ⁶Research Centre for Toxic Compounds in the Environment, Faculty of Science, Masaryk University, Brno, Czech Republic; ⁷Department of Environmental Health and Occupational Health, IRSPUM (Université de Montréal Public Health Research Institute), Université de Montréal, Montreal, Quebec, Canada; ⁸Department of Genes and Environment, Norwegian Institute of Public Health, Oslo, Norway


Abstract

Background: Despite experimental evidence that lactational exposure to persistent organic pollutants (POPs) can impact health, results from epidemiologic studies are inconclusive. Inconsistency across studies may reflect the inability of current methods to estimate children’s blood levels during specific periods of susceptibility.


Objectives: We developed a toxicokinetic model to simulate blood POP levels in children from two longitudinal birth cohorts and aimed to validate it against blood levels measured at 6, 16, and 45 months of age.


Methods: The model consisted of a maternal and a child lipid compartment connected through placental diffusion and breastfeeding. Simulations were carried out based on individual physiologic parameters; duration of breastfeeding; and levels of POPs measured in maternal blood at delivery, cord blood, or breast milk. Model validity was assessed through regression analyses of simulated against measured blood levels.


Results: Simulated levels explained between 10% and 83% of measured blood levels depending on the cohort, the compound, the sample used to simulate children’s blood levels, and child’s age when blood levels were measured. Model accuracy was highest for estimated blood POP levels at 6 months based on maternal or cord blood levels. However, loss in model precision between the 6th and the 45th month was small for most compounds.


Conclusions: Our validated toxicokinetic model can be used to estimate children’s blood POP levels in early to mid-childhood. Estimates can be used in epidemiologic studies to evaluate the impact of exposure during hypothesized postnatal periods of susceptibility on health.


Key words: children’s health, lactational exposures, longitudinal birth studies, persistent organic pollutants, toxicokinetic modeling. 


Environ Health Perspect 121:131–137 (2013). http://dx.doi.org/10.1289/ehp.1205552 [Online 17 October 2012]


Address correspondence to M.-A. Verner, Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Harvard School of Medicine, 181 Longwood Ave., Boston, MA 02115 USA. Telephone: (617) 525-4210. E-mail: marcandre.verner@channing.harvard.edu


Supplemental Material is available online (http://dx.doi.org/10.1289/ehp.1205552).


We thank R. McDougall from Aegis Technologies Group, Inc. for his help in coding the global sensitivity analyses. 


This study was funded by the European Community’s Seventh Framework Programme FP7/2007-2013 under grant agreement OBELIX 227391; the National Institutes of Health grants R01-CA096525, R01-ES015359, P01-ES011269, R01-ES020392, and R01-ES007902; U.S. Environmental Protection Agency STAR R833292; Indian and Northern Affairs Canada; Health Canada; Fonds de Recherche Québec-Santé–Hydro-Québec; Joseph Young Sr. Fund from the State of Michigan; the Nunavik Regional Board of Health and Social Services; and the Natural Sciences and Engineering Council of Canada (NSERC). M.-A.V. is recipient of a postdoctoral scholarship from the Fonds de Rercherche du Québec–Santé. 


The authors declare they have no actual or potential competing financial interests.


Received 1 June 2012; Accepted 17 October 2012; Online 17 October 2012.