TY - JOUR
T1 - Toxicokinetic modeling of persistent organic pollutant levels in blood from birth to 45 months of age in longitudinal birth cohort studies
AU - Verner, Marc André
AU - Sonneborn, Dean
AU - Lancz, Kinga
AU - Muckle, Gina
AU - Ayotte, Pierre
AU - Dewailly, Éric
AU - Kocan, Anton
AU - Palkovicová, Lubica
AU - Trnovec, Tomas
AU - Haddad, Sami
AU - Hertz-Picciotto, Irva
AU - Eggesbø, Merete
PY - 2013/1
Y1 - 2013/1
N2 - 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.
AB - 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.
KW - Children's health
KW - Lactational exposures
KW - Longitudinal birth studies
KW - Persistent organic pollutants
KW - Toxicokinetic modeling
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U2 - 10.1289/ehp.1205552
DO - 10.1289/ehp.1205552
M3 - Article
C2 - 23086694
AN - SCOPUS:84872070112
VL - 121
SP - 131
EP - 137
JO - Environmental Health Perspectives
JF - Environmental Health Perspectives
SN - 0091-6765
IS - 1
ER -