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      Thyroid Function and Perfluoroalkyl Acids in Children Living Near a Chemical Plant

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          Abstract

          Background: Animal studies suggest that some perfluoroalkyl acids (PFAAs), including perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and perfluorononanoic acid (PFNA) may impair thyroid function. Epidemiological findings, mostly related to adults, are inconsistent.

          Objectives: We investigated whether concentrations of PFAAs were associated with thyroid function among 10,725 children (1–17 years of age) living near a Teflon manufacturing facility in the Mid-Ohio Valley (USA).

          Methods: Serum levels of thyroid-stimulating hormone (TSH), total thyroxine (TT 4), and PFAAs were measured during 2005–2006, and information on diagnosed thyroid disease was collected by questionnaire. Modeled in utero PFOA concentrations were based on historical information on PFOA releases, environmental distribution, pharmacokinetic modeling, and residential histories. We performed multivariate regression analyses.

          Results: Median concentrations of modeled in utero PFOA and measured serum PFOA, PFOS, and PFNA were 12, 29, 20, and 1.5 ng/mL, respectively. The odds ratio for hypothyroidism ( n = 39) was 1.54 [95% confidence interval (CI): 1.00, 2.37] for an interquartile range (IQR) contrast of 13 to 68 ng/mL in serum PFOA measured in 2005–2006. However, an IQR shift in serum PFOA was not associated with TSH or TT 4 levels in all children combined. IQR shifts in serum PFOS (15 to 28 ng/mL) and serum PFNA (1.2 to 2.0 ng/mL) were both associated with a 1.1% increase in TT 4 in children 1–17 years old (95% CIs: 0.6, 1.5 and 0.7, 1.5 respectively).

          Conclusions: This is the first large-scale report in children suggesting associations of serum PFOS and PFNA with thyroid hormone levels and of serum PFOA and hypothyroidism.

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          Most cited references27

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          Trends in exposure to polyfluoroalkyl chemicals in the U.S. Population: 1999-2008.

          Since 2002, practices in manufacturing polyfluoroalkyl chemicals (PFCs) in the United States have changed. Previous results from the National Health and Nutrition Examination Survey (NHANES) documented a significant decrease in serum concentrations of some PFCs during 1999-2004. To further assess concentration trends of perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA), we analyzed 7876 serum samples collected from a representative sample of the general U.S. population ≥12 years of age during NHANES 1999-2008. We detected PFOS, PFOA, PFNA, and PFHxS in more than 95% of participants. Concentrations differed by sex regardless of age and we observed some differences by race/ethnicity. Since 1999-2000, PFOS concentrations showed a significant downward trend, because of discontinuing industrial production of PFOS, but PFNA concentrations showed a significant upward trend. PFOA concentrations during 1999-2000 were significantly higher than during any other time period examined, but PFOA concentrations have remained essentially unchanged during 2003-2008. PFHxS concentrations showed a downward trend from 1999 to 2006, but concentrations increased during 2007-2008. Additional research is needed to identify the environmental sources contributing to human exposure to PFCs. Nonetheless, these NHANES data suggest that sociodemographic factors may influence exposure and also provide unique information on temporal trends of exposure.
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            Thyroid hormone receptors in brain development and function.

            Thyroid hormones are important during development of the mammalian brain, acting on migration and differentiation of neural cells, synaptogenesis, and myelination. The actions of thyroid hormones are mediated through nuclear thyroid hormone receptors (TRs) and regulation of gene expression. The purpose of this article is to review the role of TRs in brain maturation. In developing humans maternal and fetal thyroid glands provide thyroid hormones to the fetal brain, but the timing of receptor ontogeny agrees with clinical data on the importance of the maternal thyroid gland before midgestation. Several TR isoforms, which are encoded by the THRA and THRB genes, are expressed in the brain, with the most common being TRalpha1. Deletion of TRalpha1 in rodents is not, however, equivalent to hormone deprivation and, paradoxically, even prevents the effects of hypothyroidism. Unliganded receptor activity is, therefore, probably an important factor in causing the harmful effects of hypothyroidism. Accordingly, expression of a mutant receptor with impaired triiodothyronine (T(3)) binding and dominant negative activity affected cerebellar development and motor performance. TRs are also involved in adult brain function. TRalpha1 deletion, or expression of a dominant negative mutant receptor, induces consistent behavioral changes in adult mice, leading to severe anxiety and morphological changes in the hippocampus.
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              Epidemiologic Evidence on the Health Effects of Perfluorooctanoic Acid (PFOA)

              Objective and sources We reviewed the epidemiologic literature for PFOA. Data synthesis Perfluorooctanoic acid (PFOA) does not occur naturally but is present in the serum of most residents of industrialized countries (U.S. median, 4 ng/mL). Drinking water is the primary route of exposure in some populations, but exposure sources are not well understood. PFOA has been used to manufacture such products as Gore-Tex and Teflon. PFOA does not break down in the environment; the human half-life is estimated at about 3 years. PFOA is not metabolized in the body; it is not lipophilic. PFOA is not directly genotoxic; animal data indicate that it can cause several types of tumors and neonatal death and may have toxic effects on the immune, liver, and endocrine systems. Data on the human health effects of PFOA are sparse. There is relatively consistent evidence of modest positive associations with cholesterol and uric acid, although the magnitude of the cholesterol effect is inconsistent across different exposure levels. There is some but much less consistent evidence of a modest positive correlation with liver enzymes. Most findings come from cross-sectional studies, limiting conclusions. Two occupational cohort studies do not provide consistent evidence for chronic disease; both are limited by sample size and reliance on mortality data. Reproductive data have increased recently but are inconsistent, and any observed adverse effects are modest. Conclusions Epidemiologic evidence remains limited, and to date data are insufficient to draw firm conclusions regarding the role of PFOA for any of the diseases of concern.
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                Author and article information

                Journal
                Environ Health Perspect
                Environ. Health Perspect
                EHP
                Environmental Health Perspectives
                National Institute of Environmental Health Sciences
                0091-6765
                1552-9924
                27 March 2012
                July 2012
                : 120
                : 7
                : 1036-1041
                Affiliations
                [1 ]Department of Social and Environmental Health Research, London School of Hygiene & Tropical Medicine, London, United Kingdom
                [2 ]Department of Environmental Health Sciences, and
                [3 ]Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, State University of New York, Rensselaer, New York, USA
                Author notes
                Address correspondence to M-J. Lopez-Espinosa. Department of Social and Environmental Health Research, London School of Hygiene & Tropical Medicine, 15–17 Tavistock Place, London WC1H 9SH, UK. Telephone: 44 20 7927 2066. Fax: 44 20 7580 4524. E-mail: maria-jose.lopez@ 123456lshtm.ac.uk
                Article
                ehp.1104370
                10.1289/ehp.1104370
                3404658
                22453676
                b08781a5-19dd-428f-bb56-73977e61abc6
                Copyright @ 2012

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 August 2011
                : 27 March 2012
                Categories
                Research

                Public health
                pfna,tsh,pfoa,thyroid disease,children,thyroid hormones,pfos,t4,pfaa
                Public health
                pfna, tsh, pfoa, thyroid disease, children, thyroid hormones, pfos, t4, pfaa

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