52 research outputs found

    Perfluorooctanoic Acid–Induced Immunomodulation in Adult C57BL/6J or C57BL/6N Female Mice

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    BackgroundPerfluorooctanoic acid (PFOA), an environmentally persistent compound of regulatory concern, has been reported to reduce antibody responses in mice at a single dose.ObjectiveThe aim of this study was to evaluate PFOA effects on humoral and cellular immunity using standard assays for assessing immune function, and to derive dose–response data.MethodsC57BL/6J mice received 0 or 30 mg PFOA/kg/day for 10 days; half of the exposed groups were switched to vehicle and half continued on PFOA for five days. C57BL/6N mice received 0–30 mg/kg/day of PFOA in drinking water for 15 days. Mice were immunized with sheep red blood cells or sensitized to bovine serum albumin in Freund’s complete adjuvant on day 10 of exposure; immune responses were determined 1 day post-exposure.ResultsWe found that 30 mg PFOA/kg/day given for 10 or 15 days reduced IgM synthesis; serum collected 1 day postexposure contained 8.4 × 104 or 2.7 × 105 ng PFOA/mL, respectively. IgM synthesis was suppressed at exposures ≥ 3.75 mg PFOA/kg/day in a dose-dependent manner, and IgG titers were elevated at 3.75 and 7.5 mg PFOA/kg/day. Serum PFOA at 3.75 mg/kg/day was 7.4 × 104 ng/mL 1 day postexposure, or 150-fold greater than the levels reported in individuals living near a PFOA production site. Using a second-degree polynomial model, we calculated a benchmark dose of 3 mg/kg/day, with a lower bound (95% confidence limit) of 1.75 mg/kg/day. Cell-mediated function was not affected.ConclusionsIgM antibodies were suppressed after PFOA exposure. The margin of exposure for reduced IgM antibody synthesis was approximately 150 for highly exposed human populations

    Breaking Patterns of Environmentally Influenced Disease for Health Risk Reduction: Immune Perspectives

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    Diseases rarely, if ever, occur in isolation. Instead, most represent part of a more complex web or “pattern� of conditions that are connected via underlying biological mechanisms and processes, emerge across a lifetime, and have been identified with the aid of large medical databases. Objective We have described how an understanding of patterns of disease may be used to develop new strategies for reducing the prevalence and risk of major immune-based illnesses and diseases influenced by environmental stimuli. Findings Examples of recently defined patterns of diseases that begin in childhood include not only metabolic syndrome, with its characteristics of inflammatory dysregulation, but also allergic, autoimmune, recurrent infection, and other inflammatory patterns of disease. The recent identification of major immune-based disease patterns beginning in childhood suggests that the immune system may play an even more important role in determining health status and health care needs across a lifetime than was previously understood. Conclusions Focusing on patterns of disease, as opposed to individual conditions, offers two important venues for environmental health risk reduction. First, prevention of developmental immunotoxicity and pediatric immune dysfunction can be used to act against multiple diseases. Second, pattern-based treatment of entryway diseases can be tailored with the aim of disrupting the entire disease pattern and reducing the risk of later-life illnesses connected to underlying immune dysfunction. Disease-pattern–based evaluation, prevention, and treatment will require a change from the current approach for both immune safety testing and pediatric disease management

    Association of Perfluoroalkyl Substances, Bone Mineral Density, and Osteoporosis in the U.S. Population in NHANES 2009-2010

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    Background Perfluoroalkyl substances (PFASs), including perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA), are detectable in the serum of 95% of the U.S. population. Objective Considering the role of PFASs as endocrine disruptors, we examined their relationships with bone health. Methods The association between serum PFAS concentration and bone mineral density at total femur (TFBMD), femoral neck (FNBMD), lumbar spine (LSBMD), and physician-diagnosed osteoporosis was assessed in 1,914 participants using data from the National Health and Nutritional Examination Survey 2009–2010. Results The mean age of the participants was 43 years. Men had higher serum PFAS concentrations than women (p < 0.001) except for PFNA. In both sexes, serum PFOS concentrations were inversely associated with FNBMD (p < 0.05). In women, significant negative associations were observed for natural log (ln)–transformed PFOS exposure with TFBMD and FNBMD, and for ln-transformed PFOA exposure with TFBMD (p < 0.05). In postmenopausal women, serum PFOS was negatively associated with TFBMD and FNBMD, and PFNA was negatively associated with TFBMD, FNBMD, and LSBMD (all p < 0.05). With one log unit increase in serum PFOA, PFHxS, and PFNA, osteoporosis prevalence in women increased as follows: [adjusted odds ratios (aORs)] 1.84 (95% CI: 1.17, 2.905), 1.64 (95% CI: 1.14, 2.38), and 1.45 (95% CI: 1.02, 2.05), respectively. In women, the prevalence of osteoporosis was significantly higher in the highest versus the lowest quartiles of PFOA, PFHxS, and PFNA, with aORs of 2.59 (95% CI: 1.01, 6.67), 13.20 (95% CI: 2.72, 64.15), and 3.23 (95% CI: 1.44, 7.21), respectively, based on 77 cases in the study sample. Conclusion In a representative sample of the U.S. adult population, serum PFAS concentrations were associated with lower bone mineral density, which varied according to the specific PFAS and bone site assessed. Most associations were limited to women. Osteoporosis in women was also associated with PFAS exposure, based on a small number of cases

    An Overview of the Uses of Per- and Polyfluoroalkyl Substances (PFAS)

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    Per- and polyfluoroalkyl substances (PFAS) are of concern because of their high persistence (or that of their degradation products) and their impacts on human and environmental health that are known or can be deduced from some well-studied PFAS. Currently, many different PFAS (on the order of several thousands) are used in a wide range of applications, and there is no comprehensive source of information on the many individual substances and their functions in different applications. Here we provide a broad overview of many use categories where PFAS have been employed and for which function; we also specify which PFAS have been used and discuss the magnitude of the uses. Despite being non-exhaustive, our study clearly demonstrates that PFAS are used in almost all industry branches and many consumer products. In total, more than 200 use categories and subcategories are identified for more than 1400 individual PFAS. In addition to well-known categories such as textile impregnation, fire-fighting foam, and electroplating, the identified use categories also include many categories not described in the scientific literature, including PFAS in ammunition, climbing ropes, guitar strings, artificial turf, and soil remediation. We further discuss several use categories that may be prioritised for finding PFAS-free alternatives. Besides the detailed description of use categories, the present study also provides a list of the identified PFAS per use category, including their exact masses for future analytical studies aiming to identify additional PFAS

    Addressing Urgent Questions for PFAS in the 21st Century

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    Despite decades of research on per- and polyfluoroalkyl substances (PFAS), fundamental obstacles remain to addressing worldwide contamination by these chemicals and their associated impacts on environmental quality and health. Here, we propose six urgent questions relevant to science, technology, and policy that must be tackled to address the “PFAS problem”: (1) What are the global production volumes of PFAS, and where are PFAS used? (2) Where are the unknown PFAS hotspots in the environment? (3) How can we make measuring PFAS globally accessible? (4) How can we safely manage PFAS-containing waste? (5) How do we understand and describe the health effects of PFAS exposure? (6) Who pays the costs of PFAS contamination? The importance of each question and barriers to progress are briefly described, and several potential paths forward are proposed. Given the diversity of PFAS and their uses, the extreme persistence of most PFAS, the striking ongoing lack of fundamental information, and the inequity of the health and environmental impacts from PFAS contamination, there is a need for scientific and regulatory communities to work together, with cooperation from PFAS-related industries, to fill in critical data gaps and protect human health and the environment

    Information Requirements under the Essential-Use Concept: PFAS Case Studies

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    Per- and polyfluoroalkyl substances (PFAS) are a class of substances for which there are widespread concerns about their extreme persistence in combination with toxic effects. It has been argued that PFAS should only be employed in those uses that are necessary for health or safety or are critical for the functioning of society and where no alternatives are available (“essential-use concept”). Implementing the essential-use concept requires a sufficient understanding of the current uses of PFAS and of the availability, suitability, and hazardous properties of alternatives. To illustrate the information requirements under the essential-use concept, we investigate seven different PFAS uses, three in consumer products and four industrial applications. We investigate how much information is available on the types and functions of PFAS in these uses, how much information is available on alternatives, their performance and hazardous properties and, finally, whether this information is sufficient as a basis for deciding on the essentiality of a PFAS use. The results show (i) the uses of PFAS are highly diverse and information on alternatives is often limited or lacking; (ii) PFAS in consumer products often are relatively easy to replace; (iii) PFAS uses in industrial processes can be highly complex and a thorough evaluation of the technical function of each PFAS and of the suitability of alternatives is needed; (iv) more coordination among PFAS manufacturers, manufacturers of alternatives to PFAS, users of these materials, government authorities, and other stakeholders is needed to make the process of phasing out PFAS more transparent and coherent
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