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      Phlebotomy Treatment for Elimination of Perfluoroalkyl Acids in a Highly Exposed Family: A Retrospective Case-Series

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          Abstract

          Background

          Perfluoroalkyl acids (PFAAs) are a family of commonly used synthetic chemicals that have become widespread environmental contaminants. In human serum, perfluorohexane sulfonate (PFHxS), perflurooctane sulfonate (PFOS), and perfluorooctanoate (PFOA) are most frequently detected, in part owing to their long elimination half-lives of between 3.8 yrs (PFOA) and 8.5 yrs (PFHxS). These PFAAs also cross the placenta and have been associated with developmental toxicity, and some are considered likely human carcinogens. Interventions to eliminate PFAAs in highly contaminated individuals would reduce future health risks, but minimal research has been conducted on methods to facilitate accelerated human clearance of these persistent substances.

          Methods

          Six patients with elevated serum concentrations from a single family were treated by intermittent phlebotomy over a 4–5 year period at intervals similar to, or less frequent than what is done for routine blood donation at Canadian Blood Services. The apparent elimination half-life (HL app) for PFHxS, PFOS, and PFOA in this treated population was calculated in each patient and compared to the intrinsic elimination half-lives (HL in) from a literature reference population of untreated fluorochemical manufacturing plant retirees (n = 26, age >55 yrs).

          Results

          For all three PFAAs monitored during phlebotomy, HL app in each of the family members (except the mother, who had a low rate of venesection) was significantly shorter than the geometric mean HL measured in the reference population, and in some cases were even shorter compared to the fastest eliminator in the reference population.

          Conclusion

          This study suggests significantly accelerated PFAA clearance with regular phlebotomy treatment, but the small sample size and the lack of controls in this clinical intervention precludes drawing firm conclusions. Given the minimal risks of intermittent phlebotomy, this may be an effective and safe clinical intervention to diminish the body burden of PFAAs in highly exposed people.

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          Most cited references34

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          Perfluorinated compounds--exposure assessment for the general population in Western countries.

          Perfluorinated compounds (PFCs) can currently be detected in many environmental media and biota, as well as in humans. Because of their persistence and their potential to accumulate they are of toxicological concern. The present review presents the current knowledge of PFC monitoring data in environmental media relevant for human exposure. In this context, PFC concentrations in indoor and ambient air, house dust, drinking water and food are outlined. Furthermore, we summarize human biomonitoring data of PFC levels in blood, breast milk, and human tissues. An estimate of the overall exposure of the general adult population is provided and compared with tolerable intake values. Using a simplified model, the average (and upper) level of daily exposure including all potential routes amounts to 1.6 ng/kg(body weight) (8.8 ng/kg(body weight)) for PFOS and 2.9 ng/kg(body weight) (12.6 ng/kg(body weight)) for PFOA in adults in the general population. The majority of exposure can be attributed to the oral route, mainly to diet. Overall, the contribution of PFOS and PFOA precursors to total exposure seems to be limited. Besides this background exposure of the general population, a specific additional exposure may occur which causes an increased PFC body burden. This has been observed in populations living near PFC production facilities or in areas with environmental contamination of PFCs. The consumption of highly contaminated fish products may also cause an increase in PFC body burdens.
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            Biomonitoring of perfluoroalkyl acids in human urine and estimates of biological half-life.

            Perfluoroalkyl acids (PFAAs) are persistent and bioaccumulative compounds that have been associated with adverse health outcomes. In human blood, PFAAs exist as both linear and branched isomers, yet for most linear homologues, and for all branched isomers, elimination rates are unknown. Paired blood and urine samples (n = 86) were collected from adults in China. They were analyzed by a sensitive isomer-specific method that permitted the detection of many PFAAs in human urine for the first time. For all PFAAs except perfluoroundecanoate (PFUnA), levels in urine correlated positively with levels in blood. Perfluoroalkyl carboxylates (PFCAs) were excreted more efficiently than perfluoroalkane sulfonates (PFSAs) of the same carbon chain-length. In general, shorter PFCAs were excreted more efficiently than longer ones, but for PFSAs, perfluorooctanesulfonate (PFOS, a C8 compound) was excreted more efficiently than perfluorohexanesulfonate (PFHxS, a C6 compound). Among PFOS and perfluorooctanoate (PFOA) isomers, major branched isomers were more efficiently excreted than the corresponding linear isomer. A one-compartment model was used to estimate the biological elimination half-lives of PFAAs. Among all PFAAs, the estimated arithmetic mean elimination half-lives ranged from 0.5 ± 0.1 years (for one branched PFOA isomer, 5m-PFOA) to 90 ± 11 years (for one branched PFOS isomer, 1m-PFOS). Urinary excretion was the major elimination route for short PFCAs (C ≤ 8), but for longer PFCAs, PFOS and PFHxS, other routes of excretion likely contribute to overall elimination. Urinary concentrations are good biomarkers of the internal dose, and this less invasive strategy can therefore be used in future epidemiological and biomonitoring studies. The very long half-lives of long-chain PFCAs, PFHxS, and PFOS isomers in humans stress the importance of global and domestic exposure mitigation strategies.
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              The C8 Health Project: Design, Methods, and Participants

              Background The C8 Health Project was created, authorized, and funded as part of the settlement agreement reached in the case of Jack W. Leach, et al. v. E.I. du Pont de Nemours & Company (no. 01-C-608 W.Va., Wood County Circuit Court, filed 10 April 2002). The settlement stemmed from the perfluorooctanoic acid (PFOA, or C8) contamination of drinking water in six water districts in two states near the DuPont Washington Works facility near Parkersburg, West Virginia. Objectives This study reports on the methods and results from the C8 Health Project, a population study created to gather data that would allow class members to know their own PFOA levels and permit subsequent epidemiologic investigations. Methods Final study participation was 69,030, enrolled over a 13-month period in 2005–2006. Extensive data were collected, including demographic data, medical diagnoses (both self-report and medical records review), clinical laboratory testing, and determination of serum concentrations of 10 perfluorocarbons (PFCs). Here we describe the processes used to collect, validate, and store these health data. We also describe survey participants and their serum PFC levels. Results The population geometric mean for serum PFOA was 32.91 ng/mL, 500% higher than previously reported for a representative American population. Serum concentrations for perfluorohexane sulfonate and perfluorononanoic acid were elevated 39% and 73% respectively, whereas perfluorooctanesulfonate was present at levels similar to those in the U.S. population. Conclusions This largest known population study of community PFC exposure permits new evaluations of associations between PFOA, in particular, and a range of health parameters. These will contribute to understanding of the biology of PFC exposure. The C8 Health Project also represents an unprecedented effort to gather basic data on an exposed population; its achievements and limitations can inform future legal settlements for populations exposed to environmental contaminants.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                12 December 2014
                : 9
                : 12
                : e114295
                Affiliations
                [1 ]Faculty of Medicine and Dentistry. University of Alberta, Edmonton, Alberta, Canada
                [2 ]Division of Analytical & Environmental Toxicology, Department of Laboratory Medicine & Pathology, University of Alberta, Edmonton, Alberta, Canada
                [3 ]MD Program, Faculty of Medicine and Dentistry. University of Alberta, Edmonton, Alberta, Canada
                Chiba University, Graduate School of Medicine, Japan
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: SG. Performed the experiments: SG. Analyzed the data: SG YL JM QG. Contributed reagents/materials/analysis tools: QG YL. Contributed to the writing of the manuscript: SG YL JM QG.

                Article
                PONE-D-14-39711
                10.1371/journal.pone.0114295
                4264749
                25504057
                f18c182e-72ae-4ef4-aa9c-8b24f05e1ff9
                Copyright @ 2014

                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 author and source are credited.

                History
                : 4 September 2014
                : 7 November 2014
                Page count
                Pages: 18
                Funding
                The authors have no support or funding to report.
                Categories
                Research Article
                Biology and Life Sciences
                Toxicology
                Ecology and Environmental Sciences
                Environmental Chemistry
                Medicine and Health Sciences
                Clinical Medicine
                Public and Occupational Health
                Custom metadata
                The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper and its Supporting Information files.

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