Assessment of exposure to PCB 153 from breast feeding and normal food intake in individual children using a system approach model
Highlights
► Serum PCB 153 was determined serially in infants from birth to 45 months. ► So far published PCB exposure assessments did not suite our longitudinal study design. ► Original model fitted to data describes kinetics of PCB in each subject individually. ► Mean residence time of PCB molecules in the body and AUCs were evaluated. ► It is differentiated between PCB intake by breast feeding and normal food intake.
Introduction
Polychlorinated biphenyls (PCBs) are a member of the organochlorine family, and though they are no longer produced, they are still found in the environment and in numerous wildlife species, as well as human tissues. Human exposure to PCBs first occurs in utero through transplacental transfer of PCBs from mother to infant. After birth, infants are exposed to PCBs via breast feeding, and later through intake of contaminated foods. To assess the association between PCB exposure and health outcomes, investigators have typically relied on discrete time points as a measure of PCB body burden. Examples include PCB concentrations measured in maternal blood taken during pregnancy (Chevrier et al., 2008, Darnerud et al., 2010, Glynn et al., 2008, Hertz-Picciotto et al., 2008, Lopez-Espinosa et al., 2009, McGlynn et al., 2009, Roze et al., 2009, Terrell et al., 2009, Wilhelm et al., 2008), cord blood (Brucker-Davis et al., 2008, Dallaire et al., 2006, Otake et al., 2007, Sagiv et al., 2010, Tan et al., 2009), placental tissue (Laisi et al., 2008, Reichrtová et al., 1999, Wang et al., 2005), breast milk (Darnerud et al., 2010, Glynn et al., 2008, Heilmann et al., 2006), or PCB concentrations measured postnatally in the blood of infants and children (Barr et al., 2006, Darnerud et al., 2010, Grimalt et al., 2010, Sunyer et al., 2008). While these exposures are correlated across time, they may not accurately reflect PCB body burden for several reasons. First, the likelihood of PCB toxicity from a particular exposure scenario may be most strongly related to the maximum concentration (Cmax) of PCBs in the target tissue (i.e. a “peak” exposure), or a cumulative measure of PCBs over time. Second, estimating a maximum concentration or “peak” exposure is difficult in most longitudinal studies since few PCB concentrations are determined, and often, these determinations are spaced widely in time. Finally, calculating a cumulative measure of PCB exposure (a widely used metric for such an exposure scenario is the “area under the concentration curve” (AUC)) also requires serial measures of PCB concentration in the developing infant and child. Complicating the issue of assessing exposure is that for developmental effects, the chemical time course may also have to coincide with the window of susceptibility for a particular gestational or postnatal event (Young et al., 1996), leading to situations where either AUC or Cmax or the levels within a narrow time window may be the more appropriate dose metric (Verner et al., 2010).
With the aim of examining several developmental health outcomes in relation to PCB exposures occurring during pregnancy and into postnatal life, we launched a birth cohort study of mother–infant pairs (Hertz-Picciotto et al., 2003) living in an area of eastern Slovakia with significant environmental contamination (Kočan et al., 1994). The objective of this work was to use longitudinally obtained measurements to develop more useful exposure metrics which could be applied to evaluate exposure-outcome associations.
Section snippets
Study subjects
A cohort of mothers with newborns was recruited from two regions of eastern Slovakia as described elsewhere (Hertz-Picciotto et al., 2003, Sonneborn et al., 2008b). Information on breastfeeding was collected using questionnaires administered during follow up visits at 6, 16, and 45 months of age.
Analyses
Blood samples from children were collected from umbilical cord and at 6, 16 and 45 months of age by a trained nurse using venipuncture. Samples were stored in a refrigerator and within 2 h transported to
Results
Statistics on concentration of PCB 153 in cord blood serum C0 and at 6, 16 and 45 months of age (C6, C16 and C45, respectively) and duration of breast feeding tbf are shown in upper part of Table 1. The concentration data for all time intervals were positively skewed and lognormally distributed (one-sample Kolmogorov–Smirnov Test). The following weight increase in g in children of our cohort has been observed (means ± SE): birth weight 3277.87 ± 486.93, 6 months 7791.78 ± 1098.81, 16 months 11802.13 ±
Discussion
The children of our cohort have been born with widely varying concentrations of PCB 153 in serum, which is reflected by the nearly 9-fold ratio of the 95th to the 5th percentiles of PCB 153 concentration. This compares well to a report summarizing 10 earlier studies which showed a range of ratios from 3.8 to 12.3 with a median of 7.5 (Longnecker et al., 2003).
The developed model approximating PCB 153 in the body of infants belongs to the category of “system models” in distinction to the
Conclusions
The need to compare health outcomes observed in children of our cohort, characterized by relatively high and variable PCB body burdens, with time integrated individual PCB exposures, prompted us to develop an original approach: (1) customized to our time series concentration data, (2) differentiating between breast feeding and normal food PCB intake and (3) characterizing each subject’s toxicokinetic profile with a minimum model parameters enabling calculation of an area under the time curve of
Acknowledgements
This research received support from National Institutes of Health grant R01-CA096525, from the Slovak Research and Development Agency under the Contract No. LPP-0164-07 and EU Projects INTARESE (No. 018385), HEIMTSA (No. 036913-2), ENVIRISK (No. 044232) and OBELIX (No. 227391) and in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences.
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