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      A critical review of perfluorooctanoate and perfluorooctanesulfonate exposure and immunological health conditions in humans

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          Abstract

          Whether perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS), two widely used and biopersistent synthetic chemicals, are immunotoxic in humans is unclear. Accordingly, this article systematically and critically reviews the epidemiologic evidence on the association between exposure to PFOA and PFOS and various immune-related health conditions in humans. Twenty-four epidemiologic studies have reported associations of PFOA and/or PFOS with immune-related health conditions, including ten studies of immune biomarker levels or gene expression patterns, ten studies of atopic or allergic disorders, five studies of infectious diseases, four studies of vaccine responses, and five studies of chronic inflammatory or autoimmune conditions (with several studies evaluating multiple endpoints). Asthma, the most commonly studied condition, was evaluated in seven studies. With few, often methodologically limited studies of any particular health condition, generally inconsistent results, and an inability to exclude confounding, bias, or chance as an explanation for observed associations, the available epidemiologic evidence is insufficient to reach a conclusion about a causal relationship between exposure to PFOA and PFOS and any immune-related health condition in humans. When interpreting such studies, an immunodeficiency should not be presumed to exist when there is no evidence of a clinical abnormality. Large, prospective studies with repeated exposure assessment in independent populations are needed to confirm some suggestive associations with certain endpoints.

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          Perfluoroalkyl and Polyfluoroalkyl Substances in the Environment: Terminology, Classification, and Origins

          The primary aim of this article is to provide an overview of perfluoroalkyl and polyfluoroalkyl substances (PFASs) detected in the environment, wildlife, and humans, and recommend clear, specific, and descriptive terminology, names, and acronyms for PFASs. The overarching objective is to unify and harmonize communication on PFASs by offering terminology for use by the global scientific, regulatory, and industrial communities. A particular emphasis is placed on long-chain perfluoroalkyl acids, substances related to the long-chain perfluoroalkyl acids, and substances intended as alternatives to the use of the long-chain perfluoroalkyl acids or their precursors. First, we define PFASs, classify them into various families, and recommend a pragmatic set of common names and acronyms for both the families and their individual members. Terminology related to fluorinated polymers is an important aspect of our classification. Second, we provide a brief description of the 2 main production processes, electrochemical fluorination and telomerization, used for introducing perfluoroalkyl moieties into organic compounds, and we specify the types of byproducts (isomers and homologues) likely to arise in these processes. Third, we show how the principal families of PFASs are interrelated as industrial, environmental, or metabolic precursors or transformation products of one another. We pay particular attention to those PFASs that have the potential to be converted, by abiotic or biotic environmental processes or by human metabolism, into long-chain perfluoroalkyl carboxylic or sulfonic acids, which are currently the focus of regulatory action. The Supplemental Data lists 42 families and subfamilies of PFASs and 268 selected individual compounds, providing recommended names and acronyms, and structural formulas, as well as Chemical Abstracts Service registry numbers. Integr Environ Assess Manag 2011;7:513–541. © 2011 SETAC
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            Polyfluoroalkyl Chemicals in the U.S. Population: Data from the National Health and Nutrition Examination Survey (NHANES) 2003–2004 and Comparisons with NHANES 1999–2000

            Background Polyfluoroalkyl chemicals (PFCs) have been used since the 1950s in numerous commercial applications. Exposure of the general U.S. population to PFCs is widespread. Since 2002, the manufacturing practices for PFCs in the United States have changed considerably. Objectives We aimed to assess exposure to perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and eight other PFCs in a representative 2003–2004 sample of the general U.S. population ≥ 12 years of age and to determine whether serum concentrations have changed since the 1999–2000 National Health and Nutrition Examination Survey (NHANES). Methods By using automated solid-phase extraction coupled to isotope dilution–high-performance liquid chromatography–tandem mass spectrometry, we analyzed 2,094 serum samples collected from NHANES 2003–2004 participants. Results We detected PFOS, PFOA, PFHxS, and PFNA in > 98% of the samples. Concentrations differed by race/ethnicity and sex. Geometric mean concentrations were significantly lower (approximately 32% for PFOS, 25% for PFOA, 10% for PFHxS) and higher (100%, PFNA) than the concentrations reported in NHANES 1999–2000 (p < 0.001). Conclusions In the general U.S. population in 2003–2004, PFOS, PFOA, PFHxS, and PFNA serum concentrations were measurable in each demographic population group studied. Geometric mean concentrations of PFOS, PFOA, and PFHxS in 2003–2004 were lower than in 1999–2000. The apparent reductions in concentrations of PFOS, PFOA, and PFHxS most likely are related to discontinuation in 2002 of industrial production by electrochemical fluorination of PFOS and related perfluorooctanesulfonyl fluoride compounds.
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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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                Author and article information

                Journal
                Crit Rev Toxicol
                Crit. Rev. Toxicol
                ITXC
                itxc20
                Critical Reviews in Toxicology
                Taylor & Francis
                1040-8444
                1547-6898
                20 April 2016
                13 January 2016
                : 46
                : 4
                : 279-331
                Affiliations
                [ a ]Health Sciences Practice, Exponent, Inc , Menlo Park, CA, USA
                [ b ]Division of Epidemiology, Department of Health Research and Policy, Stanford University School of Medicine , Stanford, CA, USA
                [ c ]Department of Epidemiology, Harvard T. H. Chan School of Public Health , Boston, MA, USA
                [ d ]Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute , New York, NY, USA
                [ e ]Division of Allergy and Immunology, Washington University School of Medicine , St. Louis, MO, USA
                Author notes
                CONTACT Ellen T. Chang echang@ 123456exponent.com Exponent, Inc., Health Sciences Practice , 149 Commonwealth Drive, Menlo Park, CA 94025, USA

                Supplemental data for this article can be accessed at http://dx.doi.org/10.3109/10408444.2015.1122573.

                Article
                1122573
                10.3109/10408444.2015.1122573
                4819831
                26761418
                1314bb56-6bd4-4d5f-b414-d6e126d71baf
                © 2016 Exponent, Inc. Published by Taylor & Francis.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.

                History
                : 7 September 2015
                : 13 November 2015
                : 17 November 2015
                Page count
                Pages: 53
                Categories
                Review
                Review Articles

                Toxicology
                asthma,autoimmune diseases,cas no. 335-67-1,cas no. 1763-23-1,epidemiology,hypersensitivity,immune system, immunization,immunological factors,infection,perfluoroalkyl substances,polyfluoroalkyl substances

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