A Critical Review of Perfluorooctanoate and Perfluorooctanesulfonate Exposure and Immunological Health Conditions in Humans

Overview

Journal Crit Rev Toxicol

Publisher Informa Healthcare

Specialty Toxicology

Date 2016 Jan 14

PMID 26761418

Citations 52

Authors

Ellen T Chang

Hans-Olov Adami

Paolo Boffetta

H James Wedner

Jack S Mandel

Affiliations

Soon will be listed here.

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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References

Peden-Adams M, Keller J, EuDaly J, Berger J, Gilkeson G, Keil D . Suppression of humoral immunity in mice following exposure to perfluorooctane sulfonate. Toxicol Sci. 2008; 104(1):144-54. DOI: 10.1093/toxsci/kfn059. View

Loveless S, Hoban D, Sykes G, Frame S, Everds N . Evaluation of the immune system in rats and mice administered linear ammonium perfluorooctanoate. Toxicol Sci. 2008; 105(1):86-96. DOI: 10.1093/toxsci/kfn113. View

Lefebvre D, Curran I, Armstrong C, Coady L, Parenteau M, Liston V . Immunomodulatory effects of dietary potassium perfluorooctane sulfonate (PFOS) exposure in adult Sprague-Dawley rats. J Toxicol Environ Health A. 2008; 71(23):1516-25. DOI: 10.1080/15287390802391943. View

Kato K, Wong L, Jia L, Kuklenyik Z, Calafat A . Trends in exposure to polyfluoroalkyl chemicals in the U.S. Population: 1999-2008. Environ Sci Technol. 2011; 45(19):8037-45. DOI: 10.1021/es1043613. View

Shin H, Vieira V, Ryan P, Steenland K, Bartell S . Retrospective exposure estimation and predicted versus observed serum perfluorooctanoic acid concentrations for participants in the C8 Health Project. Environ Health Perspect. 2011; 119(12):1760-5. PMC: 3261988. DOI: 10.1289/ehp.1103729. View

Lin C, Wen L, Lin L, Wen T, Lien G, Chen C . Associations between levels of serum perfluorinated chemicals and adiponectin in a young hypertension cohort in Taiwan. Environ Sci Technol. 2011; 45(24):10691-8. DOI: 10.1021/es201964x. View

Han X, Nabb D, Russell M, Kennedy G, Rickard R . Renal elimination of perfluorocarboxylates (PFCAs). Chem Res Toxicol. 2011; 25(1):35-46. DOI: 10.1021/tx200363w. View

Grandjean P, Andersen E, Budtz-Jorgensen E, Nielsen F, Molbak K, Weihe P . Serum vaccine antibody concentrations in children exposed to perfluorinated compounds. JAMA. 2012; 307(4):391-7. PMC: 4402650. DOI: 10.1001/jama.2011.2034. View

Woskie S, Gore R, Steenland K . Retrospective exposure assessment of perfluorooctanoic acid serum concentrations at a fluoropolymer manufacturing plant. Ann Occup Hyg. 2012; 56(9):1025-37. DOI: 10.1093/annhyg/mes023. View

10.

Xie S, Wang T, Liu S, Jones K, Sweetman A, Lu Y . Industrial source identification and emission estimation of perfluorooctane sulfonate in China. Environ Int. 2012; 52:1-8. DOI: 10.1016/j.envint.2012.11.004. View

11.

Dong G, Tung K, Tsai C, Liu M, Wang D, Liu W . Serum polyfluoroalkyl concentrations, asthma outcomes, and immunological markers in a case-control study of Taiwanese children. Environ Health Perspect. 2013; 121(4):507-13. PMC: 3620752. DOI: 10.1289/ehp.1205351. View

12.

Smit L, Lenters V, Hoyer B, Lindh C, Pedersen H, Liermontova I . Prenatal exposure to environmental chemical contaminants and asthma and eczema in school-age children. Allergy. 2015; 70(6):653-60. DOI: 10.1111/all.12605. View

13.

Ashley-Martin J, Dodds L, Levy A, Platt R, Marshall J, Arbuckle T . Prenatal exposure to phthalates, bisphenol A and perfluoroalkyl substances and cord blood levels of IgE, TSLP and IL-33. Environ Res. 2015; 140:360-8. DOI: 10.1016/j.envres.2015.04.010. View

14.

Pennings J, Jennen D, Nygaard U, Namork E, Haug L, Van Loveren H . Cord blood gene expression supports that prenatal exposure to perfluoroalkyl substances causes depressed immune functionality in early childhood. J Immunotoxicol. 2015; 13(2):173-80. DOI: 10.3109/1547691X.2015.1029147. View

15.

Kielsen K, Shamim Z, Ryder L, Nielsen F, Grandjean P, Budtz-Jorgensen E . Antibody response to booster vaccination with tetanus and diphtheria in adults exposed to perfluorinated alkylates. J Immunotoxicol. 2015; 13(2):270-3. PMC: 4739630. DOI: 10.3109/1547691X.2015.1067259. View

16.

Olsen G, Burris J, Burlew M, Mandel J . Plasma cholecystokinin and hepatic enzymes, cholesterol and lipoproteins in ammonium perfluorooctanoate production workers. Drug Chem Toxicol. 2000; 23(4):603-20. DOI: 10.1081/dct-100101973. View

17.

Yang Q, Xie Y, Depierre J . Effects of peroxisome proliferators on the thymus and spleen of mice. Clin Exp Immunol. 2000; 122(2):219-26. PMC: 1905771. DOI: 10.1046/j.1365-2249.2000.01367.x. View

18.

Giesy J, Kannan K . Global distribution of perfluorooctane sulfonate in wildlife. Environ Sci Technol. 2001; 35(7):1339-42. DOI: 10.1021/es001834k. View

19.

Yang Q, Xie Y, Eriksson A, Nelson B, Depierre J . Further evidence for the involvement of inhibition of cell proliferation and development in thymic and splenic atrophy induced by the peroxisome proliferator perfluoroctanoic acid in mice. Biochem Pharmacol. 2001; 62(8):1133-40. DOI: 10.1016/s0006-2952(01)00752-3. View

20.

Yang Q, Abedi-Valugerdi M, Xie Y, Zhao X, Moller G, Nelson B . Potent suppression of the adaptive immune response in mice upon dietary exposure to the potent peroxisome proliferator, perfluorooctanoic acid. Int Immunopharmacol. 2002; 2(2-3):389-97. DOI: 10.1016/s1567-5769(01)00164-3. View