Endocrine disruptors and childhood social impairment.

Department of Preventive Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
NeuroToxicology (Impact Factor: 3.05). 12/2010; 32(2):261-7. DOI: 10.1016/j.neuro.2010.12.009
Source: PubMed

ABSTRACT Prenatal exposure to endocrine disruptors has the potential to impact early brain development. Neurodevelopmental toxicity in utero may manifest as psychosocial deficits later in childhood. This study investigates prenatal exposure to two ubiquitous endocrine disruptors, the phthalate esters and bisphenol A (BPA), and social behavior in a sample of adolescent inner-city children. Third trimester urines of women enrolled in the Mount Sinai Children's Environmental Health Study between 1998 and 2002 (n=404) were analyzed for phthalate metabolites and BPA. Mother-child pairs were asked to return for a follow-up assessment when the child was between the ages of 7 and 9 years. At this visit, mothers completed the Social Responsiveness Scale (SRS) (n=137), a quantitative scale for measuring the severity of social impairment related to Autistic Spectrum Disorders (ASD) in the general population. In adjusted general linear models increasing log-transformed low molecular weight (LMW) phthalate metabolite concentrations were associated with greater social deficits (β=1.53, 95% CI 0.25-2.8). Among the subscales, LMWP were also associated with poorer Social Cognition (β=1.40, 95% CI 0.1-2.7); Social Communication (β=1.86, 95% CI 0.5-3.2); and Social Awareness (β=1.25, 95% CI 0.1-2.4), but not for Autistic Mannerisms or Social Motivation. No significant association with BPA was found (β=1.18, 95% CI -0.75, 3.11). Prenatal phthalate exposure was associated with childhood social impairment in a multiethnic urban population. Even mild degrees of impaired social functioning in otherwise healthy individuals can have very important adverse effects over a child's lifetime. These results extend our previous finding of atypical neonatal and early childhood behaviors in relation to prenatal phthalate exposure.


Available from: Latha Soorya, Apr 16, 2015
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    ABSTRACT: Perinatal exposure to endocrine disrupting chemicals (EDCs) can induce promiscuous neurobehavioral disturbances. Bisphenol A and phthalates are two widely prevalent and persistent EDCs reported to lead to such effects. Parental and social behaviors are especially vulnerable to endocrine disruption, as these traits are programmed by the organizational-activational effects of testosterone and estrogen. Exposure to BPA and other EDCs disrupts normal maternal care provided by rodents and non-human primates, such as nursing, time she spends hunched over and in the nest, and grooming her pups. Paternal care may also be affected by BPA. No long-term study has linked perinatal exposure to BPA or other EDC and later parental behavioral deficits in humans. The fact that the same brain regions and neural hormone substrates govern parental behaviors in animal models and humans suggests that this suite of behaviors may also be vulnerable in the latter. Social behaviors, such as communication, mate choice, pair bonding, social inquisitiveness and recognition, play behavior, social grooming, copulation, and aggression, are compromised in animal models exposed to BPA, phthalates, and other EDCs. Early contact to these chemicals is also correlated with maladaptive social behaviors in children. These behavioral disturbances may originate by altering the fetal or adult gonadal production of testosterone or estrogen, expression of ESR1, ESR2, and AR in the brain regions governing these behaviors, neuropeptide/protein hormone (oxytocin, vasopressin, and prolactin) and their cognate neural receptors, and/or through epimutations. Robust evidence exists for all of these EDC-induced changes. Concern also exists for transgenerational persistence of such neurobehavioral disruptions. In sum, evidence for social and parental deficits induced by BPA, phthalates, and related chemicals is strongly mounting, and such effects may ultimately compromise the overall social fitness of populations to come.
    Frontiers in Neuroscience 03/2015; 9:57. DOI:10.3389/fnins.2015.00057
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    ABSTRACT: Context: Epidemiological studies and animal models demonstrate that endocrine disrupting chemicals (EDCs) contribute to cognitive deficits and neurodevelopmental disabilities. Objective: To estimate neurodevelopmental disability and associated costs that can be reasonably attributed to EDC exposure in the European Union. Design: An expert panel applied a weight-of-evidence characterization adapted from the Intergovernmental Panel on Climate Change. Exposure-response relationships and reference levels were evaluated for relevant EDCs, and biomarker data were organized from peer-reviewed studies to represent European exposure and approximate burden of disease. Cost estimation as of 2010 utilized lifetime economic productivity estimates, lifetime cost estimates for autism spectrum disorder (ASD) and annual costs for attention deficit hyperactivity disorder (ADHD). Setting, Patients and Participants and Intervention: Cost estimation was carried out from a societal perspective, i.e. including direct costs (e.g. treatment costs) and indirect costs such as productivity loss. Results: The panel identified 70-100% probability that polybrominated diphenyl ether (PBDE) and organophosphate (OP) exposures contribute to IQ loss in the European population. PBDE exposures were associated with 873,000 (sensitivity analysis: 148,000-2.02 million) lost IQ points and 3,290 (sensitivity analysis: 3,290-8,080) cases of intellectual disability, at costs of €9.59 billion (sensitivity analysis: €1.58-22.4 billion). OP exposures were associated with 13.0 billion (sensitivity analysis: 4.24-17.1 billion) lost IQ points and 59,300 (sensitivity analysis: 16,500-84,400) cases of intellectual disability, at costs of €146 billion (sensitivity analysis: €46.8-194 billion). ASD causation by multiple EDCs was assigned a 20-39% probability, with 316 (sensitivity analysis: 126-631) attributable cases at a cost of €199 million (sensitivity analysis: €79.7-399 million). ADHD causation by multiple EDCs was assigned a 20-69% probability, with 19,300-31,200 attributable cases at a cost of €1.21-2.86 billion. Conclusions: EDC exposures in Europe contribute substantially to neurobehavioral deficits and disease, with a high probability of >€150 billion costs/year. These results emphasize the advantages of controlling EDC exposure.
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    ABSTRACT: Bisphenol A (BPA), a ubiquitous endocrine disruptor that is present in many household products, has been linked to obesity, cancer, and, most relevant here, childhood neurological disorders such as anxiety and hyperactivity. However, how BPA exposure translates into these neurodevelopmental disorders remains poorly understood. Here, we used zebrafish to link BPA mechanistically to disease etiology. Strikingly, treatment of embryonic zebrafish with very low-dose BPA (0.0068 μM, 1,000-fold lower than the accepted human daily exposure) and bisphenol S (BPS), a common analog used in BPA-free products, resulted in 180% and 240% increases, respectively, in neuronal birth (neurogenesis) within the hypothalamus, a highly conserved brain region involved in hyperactivity. Furthermore, restricted BPA/BPS exposure specifically during the neurogenic window caused later hyperactive behaviors in zebrafish larvae. Unexpectedly, we show that BPA-mediated precocious neurogenesis and the concomitant behavioral phenotype were not dependent on predicted estrogen receptors but relied on androgen receptor-mediated up-regulation of aromatase. Although human epidemiological results are still emerging, an association between high maternal urinary BPA during gestation and hyperactivity and other behavioral disturbances in the child has been suggested. Our studies here provide mechanistic support that the neurogenic period indeed may be a window of vulnerability and uncovers previously unexplored avenues of research into how endocrine disruptors might perturb early brain development. Furthermore, our results show that BPA-free products are not necessarily safer and support the removal of all bisphenols from consumer merchandise.
    Proceedings of the National Academy of Sciences 01/2015; 112(5). DOI:10.1073/pnas.1417731112 · 9.81 Impact Factor