A review of the pathways of human exposure to poly- and perfluoroalkyl substances (PFASs) and present understanding of health effects

Journal of Exposure Science and Environmental Epidemiology - Tập 29 Số 2 - Trang 131-147 - 2019
Elsie M. Sunderland1, Xindi C. Hu1, Clifton Dassuncao1, Andrea K. Tokranov2, Charlotte C. Wagner2, Joseph G. Allen1
1Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
2Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA, USA

Tóm tắt

Từ khóa


Tài liệu tham khảo

OECD (The Organisation for Economic Co-operation and Development). Toward a new comprehensive global database of per- and polyfluoroalkyl substances (PFASs): summary report on updating the OECD 2007 list of per and polyfluoroalkyl substances (PFASs); 2018.

Vecitis CD, Wang Y, Cheng J, Park H, Mader BT, Hoffmann MR. Sonochemical degradation of perfluorooctane sulfonate in aqueous film-forming foams. Environ Sci Technol. 2010;44:432–8.

Wang Z, DeWitt JC, Higgins CP, Cousins ITA. Never-ending story of per- and polyfluoroalkyl substances (PFASs)? Environ Sci Technol. 2017;51:2508–18.

Hu XC, Andrews DQ, Lindstrom AB, Bruton TA, Schaider LA, Grandjean P, et al. Detection of poly- and perfluoroalkyl substances (PFASs) in U.S. drinking water linked to industrial sites, military fire training areas, and wastewater treatment plants. Environ Sci Technol Lett. 2016;3:344–50.

Banzhaf S, Filipovic M, Lewis J, Sparrenbom C, Barthel R. A review of contamination of surface-, ground, and drinking water in Sweden by perfluoroalkyl and polyfluoroalkyl substances (PFASs). Ambio. 2017;46:335–46.

Wang Z, Cousins IT, Scheringer M, Hungerbuehler K. Hazard assessment of fluorinated alternatives to long-chain perfluoroalkyl acids (PFAAs) and their precursors: status quo, ongoing challenges and possible solutions. Environ Int. 2015;75:172–9.

Armitage J, Cousins IT, Buck RC, Prevedouros K, Russell MH, MacLeod M, et al. Modeling global-scale fate and transport of perfluorooctanoate emitted from direct sources. Environ Sci Technol. 2006;40:6969–75.

Giesy J, Kannan K. Global distribution of perfluoroctane sulfonate in wildlife. Environ Sci Technol. 2001;35:1339–42.

Tomy G, Budakowski W, Halldorson T, Helm P, Stern G, Friesent K, et al. Fluorinated organic compounds in an eastern Arctic marine food web. Environ Sci Technol. 2004;38:6475–81.

Lewis RC, Johns LE, Meeker JD. Serum biomarkers of exposure to perfluoroalkyl substances in relation to serum testosterone and measures of thyroid function among adults and adolescents from NHANES 2011–2012. Int J Environ Res Public Health. 2015;12:6098–114.

CDC. Fourth national report on human exposure to environmental chemicals. Atlanta: Centers for Disease Control and Prevention; 2015.

Calafat AM, Wong L-Y, Kuklenyik Z, Reidy JA, Needham LL. 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. Environ Health Perspect. 2007;115:1696–702.

Land M, de Wit CA, Cousins IT, Herzke D, Johansson J, Martin JW. What is the effect of phasing out long-chain per- and polyfluoroalkyl substances on the concentrations of perfluoroalkyl acids and their precursors in the environment? A systematic review protocol. Environ Evid. 2015;4:3

Gomis MI, Vestergren R, MacLeod M, Mueller JF, Cousins IT. Historical human exposure to perfluoroalkyl acids in the United States and Australia reconstructed from biomonitoring data using population-based pharmacokinetic modelling. Environ Int. 2017;108:92–102.

Okada E, Kashino I, Matsuura H, Sasaki S, Miyashita C, Yamamoto J, et al. Temporal trends of perfluoroalkyl acids in plasma samples of pregnant women in Hokkaido, Japan, 2003–2011. Environ Int. 2013;60:89–96.

Nøst TH, Vestergren R, Berg V, Nieboer E, Odland JØ, Sandanger TM. Repeated measurements of per-and polyfluoroalkyl substances (PFASs) from 1979 to 2007 in males from Northern Norway: assessing time trends, compound correlations and relations to age/birth cohort. Environ Int. 2014;67:43–53.

Ritscher A, Wang Z, Scheringer M, Boucher JM, Ahrens L, Berger U et al. Zürich Statement on future actions on per- and polyfluoroalkyl substances (PFASs). Environ Heath Perspect. 2018. https://doi.org/10.1289/EHP4158 .

Gomis MI, Vestergren R, Borg D, Cousins IT. Comparing the toxic potency in vivo of long-chain perfluoroalkyl acids and fluorinated alternatives. Environ Int. 2018;113:1–9.

Buck RC, Franklin J, Berger U, Conder JM, Cousins IT, de Voogt P, et al. Perfluoroalkyl and polyfluoroalkyl substances in the environment: terminology, classification, and origins. Integr Environ Assess Manag. 2011;7:513–41.

Butt CM, Muir DCG, Mabury SA. Biotransformation pathways of fluorotelomer-based polyfluoroalkyl substances: a review. Environ Toxicol Chem. 2014;33:243–67.

Young C, Mabury S. Atmospheric perfluorinated acid precursors: chemistry, occurrence, and impacts. Rev Environ Contam Toxicol. 2010;208:1–109.

Pickard H, Criscitiello A, Spencer C, Sharp M, Muir D, De Silva A, et al. Continuous non-marine inputs of per- and polyfluoroalkyl substances to the High Arctic: a multi-decadal temporal record. Atmos Chem Phys. 2018;18:5045–58.

Haug LS, Huber S, Becher G, Thomsen C. Characterisation of human exposure pathways to perfluorinated compounds—comparing exposure estimates with biomarkers of exposure. Environ Int. 2011;37:687–93.

Vestergren R, Cousins IT, Trudel D, Wormuth M, Scheringer M. Estimating the contribution of precursor compounds in consumer exposure to PFOS and PFOA. Chemosphere. 2008;73:1617–24.

Trudel D, Horowitz L, Wormuth M, Scheringer M, Cousins IT, Hungerbühler K. Estimating consumer exposure to PFOS and PFOA. Risk Anal. 2008;28:251–69.

3M Company. Fluorochemical use, distribution and release overview. US EPA Public Docket AR226-0550. St Paul, MN: 3M Company; 1999.

Kissa, E. Fluorinated Surfactants and Repellents, 2nd ed.; Vol. 97 in Surfactant Science Series; Marcel Dekker: New York, 2001.

Dassuncao C, Hu XC, Zhang X, Bossi R, Dam M, Mikkelsen B, et al. Temporal shifts in poly-and perfluoroalkyl substances (PFASs) in North Atlantic pilot whales indicate large contribution of atmospheric precursors. Environ Sci Technol. 2017;51:4512–21.

Zhang X, Zhang Y, Dassuncao C, Lohmann R, Sunderland EM. North Atlantic deep water formation inhibits high Arctic contamination by continental perfluorooctane sulfonate discharges. Glob Biogeochem Cycles. 2017;31:1332–43.

Dassuncao C, Hu XC, Nielsen F, Weihe P, Grandjean P, Sunderland EM. Shifting global exposures to poly- and perfluoroalkyl substances (PFASs) evident in longitudinal birth cohorts from a seafood-consuming population. Environ Sci Technol. 2018. https://doi.org/10.1021/acs.est.7b06044 .

Favreau P, Poncioni-Rothlisberger C, Place BJ, Bouchex-Bellomie H, Weber A, Tremp J, et al. Multianalyte profiling of per- and polyfluoroalkyl substances (PFASs) in liquid commercial products. Chemosphere. 2017;171:491–501.

Robel AE, Marshall K, Dickinson M, Lunderberg D, Butt C, Peaslee G, et al. Closing the mass balance on fluorine on papers and textiles. Environ Sci Technol. 2017;51:9022–32.

Herzke D, Olsson E, Posner S. Perfluoroalkyl and polyfluoroalkyl substances (PFASs) in consumer products in Norway—a pilot study. Chemosphere. 2012;88:980–7.

Schaider LA, Balan SA, Blum A, Andrews DQ, Strynar MJ, Dickinson ME, et al. Fluorinated compounds in U.S. fast food packaging. Environ Sci Technol Lett. 2017;4:105–11.

Guo Z, Liu X, Krebs AK. Perfluorocarboxylic acid content in 116 articles of commerce: EPA?600/R-09/-33. Research Triangle Park, NC: Environmental Protections Agency; 2009.

Yuan G, Peng H, Huang C, Hu J. Ubiquitous occurrence of fluorotelomer alcohols in eco-friendly paper-made food-contact materials and their implication for human exposure. Environ Sci Technol. 2016;50:942–50.

Zabaleta I, Bizkarguenaga E, Bilbao D, Etxebarria N, Prieto A, Zuloaga O. Fast and simple determination of perfluorinated compounds and their potential precursors in different packaging materials. Talanta. 2016;152:353–63.

Kotthoff M, Müller J, Jürling H, Schlummer M, Fiedler D. Perfluoroalkyl and polyfluoroalkyl substances in consumer products. Environ Sci Pollut Res. 2015;22:14546–59.

Ye F, Zushi Y, Masunaga S. Survey of perfluoroalkyl acids (PFAAs) and their precursors present in Japanese consumer products. Chemosphere. 2015;127:262–8.

Bečanová J, Melymuk L, Vojta Š, Komprdová K, Klánová J. Screening for perfluoroalkyl acids in consumer products, building materials and wastes. Chemosphere. 2016;164:322–9.

Begley TH, White K, Honigfort P, Twaroski ML, Neches R, Walker RA. Perfluorochemicals: potential sources of and migration from food packaging. Food Addit Contam. 2005;22:1023–31.

Begley TH, Hsu W, Noonan G, Diachenko G. Migration of fluorochemical paper additives from food-contact paper into foods and food simulants. Food Addit Contam: Part A. 2008;25:384–90.

Harrad S, de Wit C, Abdallah M, Bergh C, Bjorklund J, Covaci A, et al. Indoor contamination with hexabromocyclododecanes, polybrominated diphenyl ethers, and perfluoroalkyl compounds: an important exposure pathway for people? Environ Sci Technol. 2010;44:3221–31.

Fromme H, Dreyer A, Dietrich S, Fembacher L, Lahrz T, Völkel W. Neutral polyfluorinated compounds in indoor air in Germany—the LUPE 4 study. Chemosphere. 2015;139:572–8.

US EPA. Lifetime health advisories and health effects support documents for perfluorooctanoic acid and perfluorooctane sulfonate. Washington, DC: Environmental Protection Agency; 2016. https://www.epa.gov/sites/production/files/2016-05/documents/pfoa_pfos_prepub_508.pdf [Accessed 31 August 2018].

ATSDR. Toxicological profile for perfluoroalkyls: draft for public comment, June 2018. Atlanta, GA: Agency for Toxic Substances and Disease Registry, U.S. Department of Health and Human Services; 2018. Available: https://www.atsdr.cdc.gov/toxprofiles/tp200.pdf [Accessed 31 August 2018].

Health Canada. Health Canada’s drinking water screening values for perfluoroalkylated substances (PFASs). Ottawa, ON; February 2016. Available: http://scottreid.ca/wp-content/uploads/2016/03/Health-Canada-PFAS-Screening-Values-Fact-Sheet-EN.pdf [Accessed 20 August 2018].

Grandjean P, Budtz-Jorgensen E. Immunotoxicity of perfluorinated alkylates: calculation of benchmark doses based on serum concentrations in children. Environ Health. 2013;12:35.

Emmett EA, Shofer FS, Zhang H, Freeman D, Desai C, Shaw LM. Community exposure to perfluorooctanoate: relationships between serum concentrations and exposure sources. J Occup Environ Med/Am Coll Occup Environ Med. 2006;48:759–70.

Post GB, Louis JB, Cooper KR, Boros-Russo BJ, Lippincott RL. Occurrence and potential significance of perfluorooctanoic acid (PFOA) detected in New Jersey public drinking water systems. Environ Sci Technol. 2009;43:4547–54.

US EPA. The Third Unregulated Contaminant Monitoring Rule (UCMR 3): Data Summary, April 2016. Office of Water, EPA 815-S-16-002; 2016.

Sun M, Arevalo E, Strynar M, Linstrom A, Richardson M, Kearns B, et al. Legacy and emerging perfluoroalkyl substances are important drinking water contaminants in the Cape Fear River watershed of North Carolina. Environ Sci Technol Lett. 2016;3:415–9.

Lindh CH, Rylander L, Toft G, Axmon A, Rignell-Hydbom A, Giwercman A, et al. Blood serum concentrations of perfluorinated compounds in men from Greenlandic Inuit and European populations. Chemosphere. 2012;88:1269–75.

Weihe P, Kato K, Calafat AM, Nielsen F, Wanigatunga A, Needham L, et al. Serum concentrations of polyfluoroalkyl compounds in Faroese whale meat consumers. Environ Sci Technol. 2008;42:6291–5.

Zhou Z, Shi Y, Vestergren R, Wang T, Liang Y, Cai Y. Highly elevated serum concentrations of perflouroalkyl substances in fishery employees from Tangxun Lake, China. Environ Sci Technol. 2014;48:3864–74.

Berger U, Glynn A, Holmstrom K, Berglund M, Ankarberg E, Tomkvist A. Fish consumption as a source of human exposure to perfluorinated alkyl substances in Sweden—analysis of edible fish from Lake Vattern and the Baltic Sea. Chemosphere. 2009;76:799–804.

European Food Safety Authority. Risk to human health related to the presence of perfluorooctane sulfonic acid and perfluorooctanoic acid in food (draft). EFSA J. 2018;16:1–293.

Stahl L, Snyder B, Olsen A, Kinkaid T, Wathen J, McCarty H. Perfluorinated compounds in fish from U.S. urban rivers and the Great Lakes. Sci Total Environ. 2014;499:185–95.

Del Gobbo L, Tittlemier S, Diamond M, Pepper K, Tague B, Yeudall F, et al. Cooking decreases observed perfluorinated compound concentrations in fish. J Agric Food Chem. 2008;56:7551–9.

Kelly B, Ikonomou M, Blair J, Surridge B, Hoover D, Grace R, et al. Perfluoroalkyl contaminants in an Arctic marine food web: trophic magnification and wildlife exposure. Environ Sci Technol. 2009;43:4037–43.

Condor J, Hoke R, de Wolf W, Russell MH, Buck RC. Are PFCAs bioaccumulative? A critical review and comparison with regulatory criteria and persistent lipophiic compounds. Environ Sci Technol. 2008;42:995–1003.

Christensen K, Raymond M, Blackowicz M, Liu Y-J, Thompson B, Anderson H, et al. Perfluoroalkyl substances and fish consumption. Environ Res. 2017;154:145–51.

Hu XC, Dassuncao C, Zhang X, Grandjean P, Weihe P, Webster G, et al. Can profiles of poly- and perfluoroalkyl substances (PFASs) in human serum provide information on major exposure sources. Environ Health. 2018;17. https://doi.org/10.1186/s12940-12018-10355-12944 .

Buser A, Morf L. Substance flow analysis of PFOS and PFOA. In: Perfluorinated surfactants perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA) in Switzerland. Bern, Switzerland: Federal Office for the Environment (FOEN); 2009.

Earnshaw MR, Paul AG, Loos R, Tavazzi S, Paracchini B, Scheringer M, et al. Comparing measured and modelled PFOS concentrations in a UK freshwater catchment and estimating emission rates. Environ Int. 2014;70:25–31.

Sepulvado JG, Blaine AC, Hundal LS, Higgins CP. Occurrence and fate of perfluorochemicals in soil following the land application of municipal biosolids. Environ Sci Technol. 2011;45:8106–12.

Washington JW, Yoo H, Ellington JJ, Jenkins TM, Libelo EL. Concentrations, distribution, and persistence of perfluoroalkylates in sludge-applied soils near Decatur, Alabama, USA. Environ Sci Technol. 2010;44:8390–6.

Venkatesan AK, Halden RU. National inventory of perfluoroalkyl substances in archived U.S. biosolids from the 2001 EPA National Sewage Sludge Survey. J Hazard Mater. 2013;252–253:413–8.

Navarro I, de la Torre A, Sanz P, Pro J, Carbonell G, de los Ángeles Martínez M. Bioaccumulation of emerging organic compounds (perfluoroalkyl substances and halogenated flame retardants) by earthworm in biosolid amended soils. Environ Res. 2016;149:32–9.

Navarro I, de la Torre A, Sanz P, Porcel MÁ, Pro J, Carbonell G, et al. Uptake of perfluoroalkyl substances and halogenated flame retardants by crop plants grown in biosolids-amended soils. Environ Res. 2017;152:199–206.

Wen B, Wu Y, Zhang H, Liu Y, Hu X, Huang H, et al. The roles of protein and lipid in the accumulation and distribution of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in plants grown in biosolids-amended soils. Environ Pollut. 2016;216:682–8.

Domingo JL, Nadal M. Per- and polyfluoroalkyl substances (PFASs) in Food and human dietary intake: a review of the recent scientific literature. J Agric Food Chem. 2017;56:533–43.

Hoffman K, Webster T, Bartell S, Weisskopf M, Fletcher T, Vieira V. Private drinking water wells as a source of exposure to perfluorooctanoic acid (PFOA) in communities surrounding a fluoropolymer production facility. Environ Health Perspect. 2010;119:92–7.

Vestergren R, Cousins IT. Tracking the pathways of human exposure to perfluorocarboxylates. Environ Sci Technol. 2009;43:5565–75.

Egeghy PP, Lorber M. An assessment of the exposure of Americans to perfluorooctane sulfonate: a comparison of estimated intake with values inferred from NHANES data. J Expo Sci Environ Epidemiol. 2011;21:150–68.

Lorber M, Egeghy PP. Simple intake and pharmacokinetic modeling to characterize exposure of Americans to perfluoroctanoic acid, PFOA. Environ Sci Technol. 2011;45:8006–14.

Johnson GW, Ehrlich R, Full W, Ramos S. Principal components analysis and receptor models in environmental forensics. San Diego: Academic Press; 2002.

Wang Z, Stout SA, Fingas M. Forensic fingerprinting of biomarkers for oil spill characterization and source identification. Environ Forensics. 2006;7:105–46.

Benskin JP, Phillips V, St Louis VL, Martin JW. Source elucidation of perfluorinated carboxylic acids in remote alpine lake sediment cores. Environ Sci Technol. 2011;45:7188–94.

D’eon JC, Mabury SA. Exploring indirect sources of human exposure to perfluoroalkyl carboxylates (PFCAs): evaluating uptake, elimination, and biotransformation of polyfluoroalkyl phosphate esters (PAPs) in the rat. Environ Health Perspect. 2011;119:344.

Zhang X, Lohmann R, Dassuncao C, Hu XC, Weber AK, Vecitis CD, et al. Source attribution of poly- and perfluoroalkyl substances (PFASs) in surface waters from Rhode Island and the New York Metropolitan Area. Environ Sci Technol Lett. 2016;3:316–21.

Tittlemier SA, Pepper K, Seymour C, Moisey J, Bronson R, Cao X-L, et al. Dietary exposure of Canadians to perfluorinated carboxylates and perfluorooctane sulfonate via consumption of meat, fish, fast foods, and food items prepared in their packaging. J Agric Food Chem. 2007;55:3203–10.

Li M, von Stackelberg K, Rheinberger CM, Hammitt JK, Krabbenhoft DP, Yin R, et al. Insights from mercury stable isotopes into factors affecting the internal body burden of methylmercury in frequent fish consumers. Elem Sci Anth. 2016;4:000103.

Thurston GD, Spengler JD. A quantitative assessment of source contributions to inhalable particulate matter pollution in metropolitan Boston. Atmos Environ. 1967;1985:9–25.

Yeung LW, Miyake Y, Taniyasu S, Wang Y, Yu H, So MK, et al. Perfluorinated compounds and total and extractable organic fluorine in human blood samples from China. Environ Sci Technol. 2008;42:8140–5.

Miyake Y, Yamashita N, So MK, Rostkowski P, Taniyasu S, Lam PK, et al. Trace analysis of total fluorine in human blood using combustion ion chromatography for fluorine: a mass balance approach for the determination of known and unknown organofluorine compounds. J Chromatogr A. 2007;1154:214–21.

Taves DR. Evidence that there are two forms of fluoride in human serum. Nature. 1968;217:1050.

Hansen KJ, Clemen LA, Ellefson ME, Johnson HO. Compound-specific, quantitative characterization of organic fluorochemicals in biological matrices. Environ Sci Technol. 2001;35:766–70.

Grandjean P. Delayed discovery, dissemination, and decisions on intervention in environmental health: a case study on immunotoxicity of perfluorinated alkylated substances. Environ Health. 2018;17. https://doi.org/10.1186/s12940-12018-10405-y .

Harris MH, Rifas-Shiman SL, Calafat AM, Ye X, Mora AM, Webster TF, et al. Predictors of per- and polyfluoroalkyl substance (PFAS) plasma concentrations in 6–10 year old American children. Environ Sci Technol. 2017;51:5193–204.

Hurley S, Goldberg D, Wang M, Park JS, Petreas M, Bernstein L, et al. Time trends in per- and polyfluoroalkyl substances (PFASs) in California women: declining serum levels, 2011–5. Environ Sci Technol. 2018;52:277–87.

Glynn A, Benskin J, Lignell S, Gyllenhammar I, Aune M, Cantillana T, et al. Temporal trends of perfluoroalkyl substances in pooled serum samples from first-time mothers in Uppsala 1997–2014. Report to the Swedish EPA; 2015.

Eriksson U, Mueller JF, Toms LL, Hobson P, Karrman A. Temporal trends of PFSAs, PFCAs and selected precursors in Australian serum from 2002 to 2013. Environ Pollut. 2017;220:168–77.

Haug LS, Thomsen C, Becher GB. Time trends and the influence of age and gender on serum concentrations of perfluorinated compounds in archived human samples. Environ Sci Technol. 2009;43:2131–6.

Yeung LW, Miyake Y, Taniyasu S, Wang Y, Yu H, So MK, et al. Perfluorinated compounds and total and extractable organic fluorine in human blood samples from China. Environ Sci Technol. 2008;42:8140–5.

Mohsin M, Sarwar N, Ahmad S, Rasheed A, Ahmad F, Afzal A, et al. Maleic acid crosslinking of C-6 fluorocarbon as oil and water repellent finish on cellulosic fabrics. J Clean Prod. 2016;112:3525–30.

Ritter SK. Fluorochemicals go short. Chem Eng News Arch. 2010;88:12–7.

Bjerregaard-Olesen C, Bach CC, Long M, Ghisari M, Bossi R, Bech BH, et al. Time trends of perfluorinated alkyl acids in serum from Danish pregnant women 2008–2013. Environ Int. 2016;91:14–21.

Kato K, Wong L-Y, Jia LT, Kuklenyik Z, Calafat AM. Trends in exposure to polyfluoroalkyl chemicals in the US population: 1999–2008. Environ Sci Technol. 2011;45:8037–45.

Paul AG, Jones KC, Sweetman AJ. A first global production, emission, and environmental inventory for perfluorooctane sulfonate. Environ Sci Technol. 2009;43:386–92.

Griffith FD, Long JE. Animal toxicity studies with ammonium perfluorooctanoate. Am Ind Hyg Assoc J. 1980;41:576–83.

Ubel FA, Sorenson SD, Roach DE. Health status of plant workers exposed to fluorochemicals–a preliminary report. Am Ind Hyg Assoc J. 1980;41:584–9.

Goldenthal EI, Jessup DC, Geil RG, Mehring JS. 90-day subacute rhesus monkey toxicity study no. 137-092. Available on USEPA Public Docket AR-226-0137. Mattawan, MI: International Research and Development Corp.; 1978.

Goldenthal EI, Jessup DC, Geil RG, Mehring JS. 90-day subacute rhesus monkey toxicity study (aborted) no. 137-087. Available on USEPA Public Docket AR-226-0138. Mattawan, MI: International Research and Development Corp.; 1978.

RIKER laboratories. Two year oral (diet) toxicity/carcinogenicity study of fluorochemical FM-3924 in rats. Available on USEPA Public Docket AR-226-0257. St. Paul, Minnesota: RIKER Laboratoreis, Inc./3M Company; 1983.

Sibinski LJ, Allen JL, Elrod SV. Two year oral (diet) toxicity—oncogenicity study of fluorocarbon FM-3924 in rats. Available on USEPA Public Docket AR-226-0262. St. Paul, MN; 1988.

Pathology Associates International. Pathology review of reported tumorigenesis in a two year study of FM-3924 in rats. Available on U.S. EPA public docket AR-226-0264. West Chester, Ohio; 1998.

McMichael AJ. Standardized mortality ratios and the “healthy worker effect”: Scratching beneath the surface. J Occup Med. 1976;18:165–8.

Gilliland FD. Fluorocarbons and human health: studies in an occupational cohort. Available on U.S. EPA Public Docket AR-226-0473. University of Minnesota; 1992.

Olsen GW, Gilliland FD, Burlew MM, Burris JM, Mandel JS, Mandel JH. An epidemiologic investigation of reproductive hormones in men with occupational exposure to perfluorooctanoic acid. J Occup Environ Med. 1998;40:614–22.

Palmer CN, Hsu M-H, Griffin KJ, Raucy JL, Johnson EF. Peroxisome proliferator activated receptor-α expression in human liver. Mol Pharmacol. 1998;53:14–22.

Barry V, Winquist A, Steenland K. Perfluorooctanoic acid (PFOA) exposures and incident cancers among adults living near a chemical plant. Environ Health Perspect. 2013;121:1313.

Lopez-Espinosa M-J, Mondal D, Armstrong B, Bloom MS, Fletcher T. Thyroid function and perfluoroalkyl acids in children living near a chemical plant. Environ Health Perspect. 2012;120:1036.

Steenland K, Zhao L, Winquist A, Parks C. Ulcerative colitis and perfluorooctanoic acid (PFOA) in a highly exposed population of community residents and workers in the mid-Ohio valley. Environ Health Perspect. 2013;121:900.

Darrow LA, Stein CR, Steenland K. Serum perfluorooctanoic acid and perfluorooctane sulfonate concentrations in relation to birth outcomes in the Mid-Ohio Valley, 2005–2010. Environ Health Perspect. 2013;121:1207.

Rappazzo K, Coffman E, Hines E. Exposure to perfluorinated alkyl substances and health outcomes in children: a systematic review of the epidemiologic literature. Int J Environ Res Public Health. 2017;14:691.

Grandjean P, Andersen E, Budtz-Jørgensen E, et al. Serum vaccine antibody concentrations in children exposed to perfluorinated compounds. JAMA. 2012;307:391–7.

Klaunig JE, Shinohara M, Iwai H, Chengelis CP, Kirkpatrick JB, Wang Z, et al. Evaluation of the chronic toxicity and carcinogenicity of perfluorohexanoic acid (PFHxA) in Sprague–Dawley rats. Toxicol Pathol. 2014;43:209–20.

Gilliland FD, Mandel JS. Mortality among employees of a perfluorooctanoic acid production plant. J Occup Med. 1993;35:950–4.

Raleigh KK, Alexander BH, Olsen GW, Ramachandran G, Morey SZ, Church TR, et al. Mortality and cancer incidence in ammonium perfluorooctanoate production workers. Occup Environ Med. 2014;71:500–6.

Vieira VM, Hoffman K, Shin HM, Weinberg JM, Webster TF, Fletcher T. Perfluorooctanoic acid exposure and cancer outcomes in a contaminated community: a geographic analysis. Environ Health Perspect. 2013;121:318–23.

Eriksen KT, Sorensen M, McLaughlin JK, Lipworth L, Tjonneland A, Overvad K, et al. Perfluorooctanoate and perfluorooctanesulfonate plasma levels and risk of cancer in the general Danish population. J Natl Cancer Inst. 2009;101:605–9.

DeWitt JC, Peden-Adams MM, Keller JM, Germolec DR. Immunotoxicity of perfluorinated compounds: recent developments. Toxicol Pathol. 2012;40:300–11.

Stein CR, McGovern KJ, Pajak AM, Maglione PJ, Wolff MS. Perfluoroalkyl and polyfluoroalkyl substances and indicators of immune function in children aged 12-19 y: National Health and Nutrition Examination Survey. Pediatr Res. 2016;79:348–57.

Granum B, Haug LS, Namork E, Stolevik SB, Thomsen C, Aaberge IS, et al. Pre-natal exposure to perfluoroalkyl substances may be associated with altered vaccine antibody levels and immune-related health outcomes in early childhood. J Immunotoxicol. 2013;10:373–9.

Stein CR, Ge YC, Wolff MS, Ye XY, Calafat AM, Kraus T, et al. Perfluoroalkyl substance serum concentrations and immune response to FluMist vaccination among healthy adults. Environ Res. 2016;149:171–8.

Looker C, Luster MI, Calafat AM, Johnson VJ, Burleson GR, Burleson FG, et al. Influenza vaccine response in adults exposed to perfluorooctanoate and perfluorooctanesulfonate. Toxicol Sci. 2014;138:76–88.

Dong G-H, Tung K-Y, Tsai C-H, Liu M-M, Wang D, Liu W, et al. Serum polyfluoroalkyl concentrations, asthma outcomes, and immunological markers in a case-control study of Taiwanese children. Environ Health Perspect. 2013;121:507–13.

Buser MC, Scinicariello F. Perfluoroalkyl substances and food allergies in adolescents. Environ Int. 2016;88:74–9.

Gilliland FD, Mandel JS. Serum perfluorooctanoic acid and hepatic enzymes, lipoproteins, and cholesterol: a study of occupationally exposed men. Am J Ind Med. 1996;29:560–8.

Liu HS, Wen LL, Chu PL, Lin CY. Association among total serum isomers of perfluorinated chemicals, glucose homeostasis, lipid profiles, serum protein and metabolic syndrome in adults: NHANES, 2013–2014. Environ Pollut. 2018;232:73–9.

Steenland K, Fletcher T, Savitz DA. Epidemiologic evidence on the health effects of perfluorooctanoic acid (PFOA). Environ Health Perspect. 2010;118:1100–8.

Cardenas A, Gold DR, Hauser R, Kleinman KP, Hivert MF, Calafat AM, et al. Plasma concentrations of per- and polyfluoroalkyl substances at baseline and associations with glycemic indicators and diabetes incidence among high-risk adults in the diabetes prevention program trial. Environ Health Perspect. 2017;125:107001.

Liu G, Dhana K, Furtado JD, Rood J, Zong G, Liang L, et al. Perfluoroalkyl substances and changes in body weight and resting metabolic rate in response to weight-loss diets: a prospective study. PLoS Med. 2018;15:e1002502.

Frisbee SJ, Shankar A, Knox SS, Steenland K, Savitz DA, Fletcher T, et al. Perfluorooctanoic acid, perfluorooctanesulfonate, and serum lipids in children and adolescents: results from the C8 Health Project. Arch Pediatr Adolesc Med. 2010;164:860–9.

Nelson JW, Hatch EE, Webster TF. Exposure to polyfluoroalkyl chemicals and cholesterol, body weight, and insulin resistance in the general U.S. population. Environ Health Perspect. 2010;118:197–202.

Maisonet M, Näyhä S, Lawlor DA, Marcus M. Prenatal exposures to perfluoroalkyl acids and serum lipids at ages 7 and 15 in females. Environ Int. 2015;82:49–60.

Lin CY, Chen PC, Lin YC, Lin LY. Association among serum perfluoroalkyl chemicals, glucose homeostasis, and metabolic syndrome in adolescents and adults. Diabetes Care. 2009;32:702–7.

Zhang C, Sundaram R, Maisog J, Calafat AM, Barr DB, Buck Louis GM. A prospective study of prepregnancy serum concentrations of perfluorochemicals and the risk of gestational diabetes. Fertil Steril. 2015;103:184–9.

Matilla-Santander N, Valvi D, Lopez-Espinosa MJ, Manzano-Salgado CB, Ballester F, Ibarluzea J, et al. Exposure to perfluoroalkyl substances and metabolic outcomes in pregnant women: evidence from the Spanish INMA Birth Cohorts. Environ Health Perspect. 2017;125:117004.

Min JY, Lee KJ, Park JB, Min KB. Perfluorooctanoic acid exposure is associated with elevated homocysteine and hypertension in US adults. Occup Environ Med. 2012;69:658–62.

Geiger SD, Xiao J, Shankar A. No association between perfluoroalkyl chemicals and hypertension in children. Integr Blood Press Control. 2014;7:1–7.

Conway B, Costacou T. Perfluoroalkyl acids and stroke risk in persons with and without diabetes: a salutatory effect of high oxygen carrying capacity environmental contaminants. Circulation. 2018;133:AP061.

Steenland K, Zhao L, Winquist A. A cohort incidence study of workers exposed to perfluorooctanoic acid (PFOA). Occup Environ Med. 2015;72:373–80.

Lin CY, Lin LY, Wen TW, Lien GW, Chien KL, Hsu SHJ, et al. Association between levels of serum perfluorooctane sulfate and carotid artery intima-media thickness in adolescents and young adults. Int J Cardiol. 2013;168:3309–16.

Koshy TT, Attina TM, Ghassabian A, Gilbert J, Burdine LK, Marmor M, et al. Serum perfluoroalkyl substances and cardiometabolic consequences in adolescents exposed to the World Trade Center disaster and a matched comparison group. Environ Int. 2017;109:128–35.

Olsen GW, Ehresman DJ, Buehrer BD, Gibson BA, Butenhoff JL, Zobel LR. Longitudinal assessment of lipid and hepatic clinical parameters in workers involved with the demolition of perfluoroalkyl manufacturing facilities. J Occup Environ Med/Am Coll Occup Environ Med. 2012;54:974–83.

Lin CY, Lin LY, Chiang CK, Wang WJ, Su YN, Hung KY, et al. Investigation of the associations between low-dose serum perfluorinated chemicals and liver enzymes in US adults. Am J Gastroenterol. 2010;105:1354–63.

Wang X, Li B, Zhao W-D, Liu Y-J, Shang D-S, Fang W-G, et al. Perfluorooctane sulfonate triggers tight junction “opening” in brain endothelial cells via phosphatidylinositol 3-kinase. Biochem Biophys Res Commun. 2011;410:258–63.

Johansson N, Fredriksson A, Eriksson P. Neonatal exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) causes neurobehavioural defects in adult mice. Neurotoxicology. 2008;29:160–9.

Liew Z, Goudarzi H, Oulhote Y. Developmental exposures to perfluoroalkyl substances (PFASs): an update of associated health outcomes. Curr Environ Health Rep. 2018;5:1–19.

Yeung LW, Mabury SA. Are humans exposed to increasing amounts of unidentified organofluorine? Environ Chem. 2016;13:102–10.

Gomis MI, Vestergren R, Nilsson H, Cousins IT. Contribution of direct and indirect exposure to human serum concentrations of perfluorooctanoic acid in an occupationally exposed group of Ski Waxers. Environ Sci Technol. 2016;50:7037–46.

Rotander A, Karrman A, Toms LM, Kay M, Mueller JF, Gomez Ramos MJ. Novel fluorinated surfactants tentatively identified in firefighters using liquid chromatography quadrupole time-of-flight tandem mass spectrometry and a case-control approach. Environ Sci Technol. 2015;49:2434–42.

Olsen GW, Chang S-C, Noker PE, Gorman GS, Ehresman DJ, Lieder PH, et al. A comparison of the pharmacokinetics of perfluorobutanesulfonate (PFBS) in rats, monkeys, and humans. Toxicology. 2009;256:65–74.

Fujii Y, Niisoe T, Harada KH, Uemoto S, Ogura Y, Takenaka K, et al. Toxicokinetics of perfluoroalkyl carboxylic acids with different carbon chain lengths in mice and humans. J Occup Health. 2015;57:1–12.

Ritter SK. Fluorochemicals go short. Chem Eng News. 2010;88:12–7.

Butt CM, Muir DC, Mabury SA. Biotransformation pathways of fluorotelomer-based polyfluoroalkyl substances: a review. Environ Toxicol Chem/SETAC. 2014;33:243–67.

Strynar M, Dagnino S, McMahen R, Liang S, Lindstrom A, Andersen E, et al. Identification of novel perfluoroalkyl ether carboxylic acids (PFECAs) and sulfonic acids (PFESAs) in natural waters using accurate mass time-of-flight mass spectrometry (TOFMS). Environ Sci Technol. 2015;49:11622–30.

Wang Z, Cousins IT, Scheringer M, Hungerbühler K. Fluorinated alternatives to long-chain perfluoroalkyl carboxylic acids (PFCAs), perfluoroalkane sulfonic acids (PFSAs) and their potential precursors. Environ Int. 2013;60:242–8.

Blum A, Balan SA, Scheringer M, Trier X, Goldenman G, Cousins IT, et al. The Madrid statement on poly-and perfluoroalkyl substances (PFASs). Environ Health Perspect. 2015;123:A107.

Boxer E, Chaves N, Niwa Y. Northestern SSEHRI PFAS contamination site tracker; 2018.

Tian Z, Kim S-K, Shoeib M, Oh J-E, Park J-E. Human exposure to per- and polyfluoroalkyl substances (PFASs) via house dust in Korea: implication to exposure pathway. Sci Total Environ. 2016;553:266–75.

Shan G, Wang Z, Zhou L, Du P, Luo X, Wu Q, et al. Impacts of daily intakes on the isomeric profiles of perfluoroalkyl substances (PFASs) in human serum. Environ Int. 2016;89-90:62–70.

Gebbink WA, Berger U, Cousins IT. Estimating human exposure to PFOS isomers and PFCA homologues: the relative importance of direct and indirect (precursor) exposure. Environ Int. 2015;74:160–9.

Wang, Z., J. M. Boucher, M. Scheringer, I. T. Cousins, and K. Hungerbühler (2017), Toward a Comprehensive Global Emission Inventory of C4–C10 Perfluoroalkanesulfonic Acids (PFSAs) and Related Precursors: Focus on the Life Cycle of C8-Based Products and Ongoing Industrial Transition, Environmental Science & Technology, 51(8), 4482-4493.