Neurodevelopmental toxicity of prenatal polychlorinated biphenyls (PCBs) by chemical structure and activity: A birth cohort study

Divisions of Epidemiology, and of Environmental and Occupational Health, Department of Public Health Sciences, School of Medicine, University of California, Davis 95616, USA.
Environmental Health (Impact Factor: 3.37). 08/2010; 9(1):51. DOI: 10.1186/1476-069X-9-51
Source: PubMed


Polychlorinated biphenyls (PCBs) are ubiquitous environmental toxins. Although there is growing evidence to support an association between PCBs and deficits of neurodevelopment, the specific mechanisms are not well understood. The potentially different roles of specific PCB groups defined by chemical structures or hormonal activities e.g., dioxin-like, non-dioxin like, or anti-estrogenic PCBs, remain unclear. Our objective was to examine the association between prenatal exposure to defined subsets of PCBs and neurodevelopment in a cohort of infants in eastern Slovakia enrolled at birth in 2002-2004.
Maternal and cord serum samples were collected at delivery, and analyzed for PCBs using high-resolution gas chromatography. The Bayley Scales of Infant Development -II (BSID) were administered at 16 months of age to over 750 children who also had prenatal PCB measurements.
Based on final multivariate-adjusted linear regression model, maternal mono-ortho-substituted PCBs were significantly associated with lower scores on both the psychomotor (PDI) and mental development indices (MDI). Also a significant association between cord mono-ortho-substituted PCBs and reduced PDI was observed, but the association with MDI was marginal (p = 0.05). Anti-estrogenic and di-ortho-substituted PCBs did not show any statistically significant association with cognitive scores, but a suggestive association between di-ortho-substituted PCBs measured in cord serum and poorer PDI was observed.
Children with higher prenatal mono-ortho-substituted PCB exposures performed more poorly on the Bayley Scales. Evidence from this and other studies suggests that prenatal dioxin-like PCB exposure, including mono-ortho congeners, may interfere with brain development in utero. Non-dioxin-like di-ortho-substituted PCBs require further investigation.

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    • "During pregnancy , PCBs and PCDD/F may cross the placenta, leading to fetal exposure (Langer, 2008). Fetal exposure to PCBs and PCDD/F has been reported to be associated with impaired neurological development in infancy and early childhood (Boersma and Lanting, 2000; Park et al., 2010), decreased birth weight and impaired growth in newborns (Patandin et al., 1998), and impaired growth in childhood (Lamb et al., 2006). There is also evidence suggesting that thyroid hormone concentrations are altered in newborns and in children exposed in utero to PCDD/F and PCBs (Alvarez-Pedrerol et al., 2008; Baccarelli et al., 2008; Otake et al., 2007; Su et al., 2010; Wang et al., 2005). "
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    ABSTRACT: The objective of this study was to examine the effects of in utero exposure to polychlorinated biphenyls (PCBs) and dioxins (polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/F) on thyroid and growth hormone concentrations and growth in 8-year-old children. A total of 56 children (23 boys, 33 girls) were included in the study. All were stratified into high and low PCDD/F + PCB exposure groups based on maternal median indicator PCB and PCDD/F + PCB concentrations during pregnancy. Height, weight, body mass index, and thyroid and growth hormone concentrations were assessed and compared among the different exposure groups. There were no significant effects of indicator PCB or PCDD/F + PCB exposure levels on growth (height, weight, and bone age) among 8-year-old boys or girls. Boys exposed to high PCDD/F + PCB levels had significantly higher thyroxine-binding globulin (TBG) concentrations than boys exposed to low levels (P = 0.027). Girls exposed to high PCB levels had significantly lower IGF-binding protein-3 (IGFBP-3) concentrations than girls exposed to low levels (P = 0.038). Low levels of in utero exposure to PCDD/F+PCB and high indicator PCB levels were significantly associated with reduced serum concentrations of IGFBP-3. High levels of in utero exposure to PCDD/F+PCB plus either high or low indicator PCB levels were significantly associated with increased serum concentrations of growth hormone, T3, T4, and TBG. These findings suggest that the level of in utero exposure to PCBs and dioxins may affect serum concentrations of growth hormone, thyroid hormones, TBG, and IGFBP-3 in 8-year-old children.
    The Journal of Toxicological Sciences 05/2015; 40(3):309-19. DOI:10.2131/jts.40.309 · 1.29 Impact Factor
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    • "(Kubo et al., 2003; Wang et al., 2002). A number of epidemiological studies have found negative associations between prenatal exposure to several xenoestrogens including dichlorodiphenyldichloroethylene (DDE), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), or phthalates on neuropsychological development in children in the first two years of life (Forns et al., 2012; Gascon et al., 2012; Herbstman et al., 2010; Koopman-Esseboom et al., 1996; Park et al., 2010; Ribas-Fito et al., 2003; Torres-Sanchez et al., 2007), and later in childhood on mental and psychomotor development, fine motor abilities, cognition and full scale and verbal IQ (Eskenazi et al., 2013; Herbstman et al., 2010; Puertas et al., 2010). Although synergistic effects of co-exposure to mixtures of EDCs on neurodevelopment have been demonstrated both in vivo and in vitro (He et al., 2009; Pellacani et al., 2012), the short-and longterm risks from early exposure to environmentally relevant doses of complex mixtures in humans are unclear and represent an area of increasing concern. "
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    ABSTRACT: Background: To date, no epidemiological studies have explored the impact and persistence of in utero exposure to mixtures of xenoestrogens on the developing brain. We aimed to assess whether the cumulative effect of xenoestrogens in the placenta is associated with altered infant neuropsychological functioning at two and at four years of age, and if associations differ among boys and girls. Methods: Cumulative prenatal exposure to xenoestrogens was quantified in the placenta using the biomarker Total Effective Xenoestrogen Burden (TEXB-alpha) in 489 participants from the INMA (Childhood and the Environment) Project. TEXB-alpha was split in tertiles to test its association with the mental and psychomotor scores of the Bayley Scales of Infant Development (BSID) at 1-2 years of age, and with the McCarthy Scales of Children׳s Abilities (MSCA) general cognitive index and motor scale assessed at 4-5 years of age. Interactions with sex were investigated. Results: After adjustment for potential confounders, no association was observed between TEXB-alpha and mental scores at 1-2 years of age. We found a significant interactions with sex for the association between TEXB-alpha and infant psychomotor development (interaction p-value=0.029). Boys in the third tertile of exposure scored on average 5.2 points less than those in the first tertile on tests of motor development at 1-2 years of age (p-value=0.052), while no associations were observed in girls. However, this association disappeared in children at 4-5 years of age and no association between TEXB-alpha and children׳s cognition was found. Conclusions: Our results suggest that boys' early motor development might be more vulnerable to prenatal exposure to mixtures of xenoestrogens, but associations do not persist in preschool children.
    Environmental Research 07/2014; 134C:98-104. DOI:10.1016/j.envres.2014.07.002 · 4.37 Impact Factor
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    • "A more recent study also found the same relationship (Korrick & Sagiv, 2008). Prenatal exposure to PCBs also appears to have deleterious effects (Jacobson & Jacobson, 2002; Park et al., 2010). One of these studies, however, also found that in children prenatally exposed to PCBs who were also breast-fed, no negative effects were evident, suggesting a possible role of the beneficial nutrients in breast milk offsetting the effects of PCBs (Jacobson & Jacobson, 2002). "
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    ABSTRACT: Extensive literature has already documented the deleterious effects of heavy metal toxins on the human brain and nervous system. These toxins, however, represent only a fraction of the environmental hazards that may pose harm to cognitive ability in humans. Lead and mercury exposure, air pollution, and organic compounds all have the potential to damage brain functioning yet remain understudied. In order to provide comprehensive and effective public health and health care initiatives for prevention and treatment, we must first fully understand the potential risks, mechanisms of action, and outcomes surrounding exposure to these elements in the context of neurocognitive ability. This article provides a review of the negative effects on cognitive ability of these lesser-studied environmental toxins, with an emphasis on delineating effects observed in child versus adult populations. Possible differential effects across sociodemographic populations (e.g., urban versus rural residents; ethnic minorities) are discussed as important contributors to risk assessment and the development of prevention measures. The public health and clinical implications are significant and offer ample opportunities for clinicians and researchers to help combat this growing problem.
    Journal of environmental health 03/2014; 76(6):130-8. DOI:10.11648/j.cmr.20140305.13 · 0.96 Impact Factor
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