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      Prenatal and postnatal bisphenol A exposure and social impairment in 4-year-old children

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          Abstract

          Background

          Prenatal and postnatal exposure to bisphenol A (BPA) may affect early brain development. Rodent studies suggest that prenatal and postnatal neurodevelopmental toxicity from BPA exposure may manifest as social deficits in offspring. We investigated the association between prenatal and postnatal exposure to BPA and social impairments in a sample of 4-year-old children.

          Methods

          We recruited second-trimester pregnant women between 2008 and 2011, and measured their creatinine-adjusted prenatal urine BPA levels. In 2014-2015, a subset of 4-year-old children born to these women underwent neurobehavioral assessment and physical examination. We collected urine and blood from the children and assessed social impairments, including deficits in social interaction, social communication, and other behavior patterns using the Korean version of the Social Communication Questionnaire (K-SCQ) ( n = 304). We examined social impairments associated with prenatal exposure at mid-term pregnancy and postnatal exposure to BPA at 4 years of age, using linear and piecewise linear regression models.

          Results

          The relationship between prenatal BPA exposure and social communication was non-linear and statistically significant at or above the flexion point for BPA levels of 3.0 μg/g creatinine in girls (58.4%, 95% confidence interval [CI], 6.5% to 135.8%). Each 2-fold increase in postnatal BPA exposure was significantly associated with an 11.8% (95% CI, 0.6% to 24.3%) increase in impairment in social communication in 4-year old girls, as indicated by the linear regression model.

          Conclusion

          Prenatal and postnatal BPA exposure is associated with social impairment at 4 years of age, particularly in girls.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12940-017-0289-2) contains supplementary material, which is available to authorized users.

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          Most cited references45

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          Environmental Chemicals in Pregnant Women in the United States: NHANES 2003–2004

          Background Exposure to chemicals during fetal development can increase the risk of adverse health effects, and while biomonitoring studies suggest pregnant women are exposed to chemicals, little is known about the extent of multiple chemicals exposures among pregnant women in the United States. Objective We analyzed biomonitoring data from the National Health and Nutritional Examination Survey (NHANES) to characterize both individual and multiple chemical exposures in U.S. pregnant women. Methods We analyzed data for 163 chemical analytes in 12 chemical classes for subsamples of 268 pregnant women from NHANES 2003–2004, a nationally representative sample of the U.S. population. For each chemical analyte, we calculated descriptive statistics. We calculated the number of chemicals detected within the following chemical classes: polybrominated diphenyl ethers (PBDEs), perfluorinated compounds (PFCs), organochlorine pesticides, and phthalates and across multiple chemical classes. We compared chemical analyte concentrations for pregnant and nonpregnant women using least-squares geometric means, adjusting for demographic and physiological covariates. Results The percentage of pregnant women with detectable levels of an individual chemical ranged from 0 to 100%. Certain polychlorinated biphenyls, organochlorine pesticides, PFCs, phenols, PBDEs, phthalates, polycyclic aromatic hydrocarbons, and perchlorate were detected in 99–100% of pregnant women. The median number of detected chemicals by chemical class ranged from 4 of 12 PFCs to 9 of 13 phthalates. Across chemical classes, median number ranged from 8 of 17 chemical analytes to 50 of 71 chemical analytes. We found, generally, that levels in pregnant women were similar to or lower than levels in nonpregnant women; adjustment for covariates tended to increase levels in pregnant women compared with nonpregnant women. Conclusions Pregnant women in the U.S. are exposed to multiple chemicals. Further efforts are warranted to understand sources of exposure and implications for policy making.
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            Urinary Concentrations of Bisphenol A and 4-Nonylphenol in a Human Reference Population

            Bisphenol A (BPA) is used to manufacture polycarbonate plastic and epoxy resins, which are used in baby bottles, as protective coatings on food containers, and for composites and sealants in dentistry. 4-Nonylphenol (NP) is used to make nonylphenol ethoxylates, nonionic surfactants applied as emulsifying, wetting, dispersing, or stabilizing agents in industrial, agricultural, and domestic consumer products. The potential for human exposure to BPA and NP is high because of their widespread use. We measured BPA and NP in archived urine samples from a reference population of 394 adults in the United States using isotope-dilution gas chromatography/mass spectrometry. The concentration ranges of BPA and NP were similar to those observed in other human populations. BPA was detected in 95% of the samples examined at concentrations ≥0.1 μg/L urine; the geometric mean and median concentrations were 1.33 μg/L (1.36 μg/g creatinine) and 1.28 μg/L (1.32 μg/g creatinine), respectively; the 95th percentile concentration was 5.18 μg/L (7.95 μg/g creatinine). NP was detected in 51% of the samples examined ≥0.1 μg/L. The median and 95th percentile concentrations were < 0.1 μg/L and 1.57 μg/L (1.39 μg/g creatinine), respectively. The frequent detection of BPA suggests widespread exposure to this compound in residents of the United States. The lower frequency of detection of NP than of BPA could be explained by a lower exposure of humans to NP, by different pharmacokinetic factors (i.e., absorption, distribution, metabolism, elimination), by the fact that 4-n-nonylphenol—the measured NP isomer—represents a small percentage of the NP used in commercial mixtures, or a combination of all of the above. Additional research is needed to determine the best urinary biomarker(s) to assess exposure to NP. Despite the sample population’s nonrepresentativeness of the U.S. population (although sample weights were used to improve the extent to which the results represent the U.S. population) and relatively small size, this study provides the first reference range of human internal dose levels of BPA and NP in a demographically diverse human population.
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              A review of dietary and non-dietary exposure to bisphenol-A.

              Due to the large number of applications of bisphenol-A (BPA), the human exposure routes are multiple. We aimed to review shortly the food and non-food sources of BPA, and to evaluate their contribution to the human exposure. Food sources discussed here include epoxy resins, polycarbonate and other applications, such as paperboard and polyvinylchloride materials. Among the non-food sources, exposures through dust, thermal paper, dental materials, and medical devices were summarized. Based on the available data for these exposure sources, it was concluded that the exposure to BPA from non-food sources is generally lower than that from exposure from food by at least one order of magnitude for most studied subgroups. The use of urinary concentrations from biomonitoring studies was evaluated and the back-calculation of BPA intake seems reliable for the overall exposure assessment. In general, the total exposure to BPA is several orders of magnitude lower than the current tolerable daily intake of 50 μg/kg bw/day. Finally, the paper concludes with some critical remarks and recommendations on future human exposure studies to BPA. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                limyounhee@gmail.com
                sanghyukb@dankook.ac.kr
                kbn1@snu.ac.kr
                chshinpd@snu.ac.kr
                nina337@hanmail.net
                iambabyvox@hanmail.net
                +82-2-740-8394 , ychong1@snu.ac.kr
                Journal
                Environ Health
                Environ Health
                Environmental Health
                BioMed Central (London )
                1476-069X
                26 July 2017
                26 July 2017
                2017
                : 16
                : 79
                Affiliations
                [1 ]ISNI 0000 0001 0302 820X, GRID grid.412484.f, Institute of Environmental Medicine, , Seoul National University Medical Research Center, ; Seoul, Republic of Korea
                [2 ]ISNI 0000 0004 0470 5905, GRID grid.31501.36, Environmental Health Center, , Seoul National University College of Medicine, ; Seoul, Republic of Korea
                [3 ]ISNI 0000 0001 0705 4288, GRID grid.411982.7, Department of Preventive Medicine, , Dankook University, ; Cheonan, Republic of Korea
                [4 ]ISNI 0000 0001 0302 820X, GRID grid.412484.f, Division of Children and Adolescent Psychiatry, Department of Psychiatry, , Seoul National University Hospital, ; Seoul, Republic of Korea
                [5 ]ISNI 0000 0004 0484 7305, GRID grid.412482.9, Department of Pediatrics, , Seoul National University Children’s Hospital, ; Seoul, Republic of Korea
                [6 ]ISNI 0000 0004 0470 5905, GRID grid.31501.36, Department of Preventive Medicine, , Seoul National University College of Medicine, ; Seoul, Republic of Korea
                Article
                289
                10.1186/s12940-017-0289-2
                5530578
                28747197
                d8f4a196-8eac-457b-8af5-3c59e3949388
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 16 January 2017
                : 18 July 2017
                Funding
                Funded by: Korea Ministry of Environment
                Funded by: FundRef http://dx.doi.org/10.13039/501100003569, Ministry of Food and Drug Safety;
                Funded by: the Ministry of Science, ICT, and Future Planning
                Award ID: 2015R1A1A3A04001325
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2017

                Public health
                bisphenol a,childhood exposure,children’s environmental health,prenatal exposure,social impairment

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