EC Cardiology

Due to their distinctive properties, per- and poly-fluoroalkyl substances (PFAS) are widely used in various products. The discovery of PFAS dates back to the middle of the twentieth century. The initial research focused on their commercial applications and non-stick properties. Concerns about the environmental and health effects of PFAS arose in the 1970s when their presence in human and animal blood samples sparked alarm. Significant studies have found PFAS in residents' blood near manufacturing facilities, highlighting the potential health risks. Industrial sites, fire-fighting foam, landfills, and wastewater treatment plants have been linked to PFAS contamination, and their chemical stability and resistance to degradation are responsible for their environmental persistence. Studies have linked PFAS exposure to adverse health effects in humans, including dysfunction of the immune system, liver and kidney damage, and an increased risk of certain cancers and developmental disorders. PFAS can cross the placenta and harm fetuses. PFAS exposure during pregnancy has been linked to miscarriages, lower birth weight, pre-eclampsia, and fecundity. Early PFAS exposure delays mammary gland development, while adult exposure causes liver toxicity, endocrine disruption, immune system dysfunction, cardiovascular, neurodevelopmental, and metabolic effects. Increased cholesterol levels, thyroid issues, gastrointestinal issues, liver damage, kidney cancer, testicular cancer, reproductive issues, breast cancer, decreased vaccine response, impaired immune function, and neurological problems are just a few of the metabolic effects of PFAS exposure. More research is required to understand the mechanisms and long-term health effects of PFAS exposure and develop preventive measures.

Keywords: Adverse Effects of Prenatal Life; Causes of Miscarriages; Environmental Toxins; Epigenetic Changes; Polyfluoroalkyl Substances

1. Agency for Toxic Substances and Disease Registry. Perfluoroalkyls: Background. Atlanta: Centers for Disease Control and Prevention (2020). https://www.atsdr.cdc.gov/pfas/background.html
2. American Chemical Society. National Historic Chemical Landmarks: Perfluoropolyether Fluids and High-Temperature Superconductors. https://www.acs.org/content/acs/en/education/whatischemistry/landmarks/polymerchem.html
3. Frisbee SJ., et al. “Perfluorooctanoic acid, perfluorooctanesulfonate, and serum lipids in children and adolescents: results from the C8 Health Project”. Archives of Pediatrics and Adolescent Medicine9 (2010): 860-869. https://pubmed.ncbi.nlm.nih.gov/20819969/
4. Bartell SM., et al. “Rate of decline in serum PFOA concentrations after granular activated carbon filtration at two public water systems in Ohio and West Virginia”. Environmental Health Perspectives2 (2010): 222-228. https://pubmed.ncbi.nlm.nih.gov/20123620/
5. Giesy JP andKannan K. “Global distribution of perfluorooctane sulfonic acid in wildlife”. Environmental Science and Technology7 (2001): 1339-1342. https://pubs.acs.org/doi/10.1021/es001834k
6. Drinking Water Health Advisories for PFOA and PFOS | US EPA. US EPA (2016). https://www.epa.gov/sdwa/drinking-water-health-advisories-pfoa-and-pfos
7. Grandjean P and Budtz-Jørgensen E. “Immunotoxicity of perfluorinated alkylates: Calculation of benchmark doses based on serum concentrations in children”. Environmental Health1 (2013): 35. https://ehjournal.biomedcentral.com/articles/10.1186/1476-069X-12-35
8. Steenland K., et al. “Perfluorooctane sulfonate and perfluorooctanoic acid and early kidney cancer: a nested case-control study”. Cancer Epidemiology, Biomarkers and Prevention7 (2018): 747-754. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10351502/
9. Hu XC., 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”. Environmental Science and Technology Letters10 (2016): 344-350. https://pubs.acs.org/doi/full/10.1021/acs.estlett.6b00260
10. Braun JM., et al. “What can epidemiological studies tell us about the impact of chemical mixtures on human health?” Environmental Health Perspectives1 (2016): A6-A9. https://pubmed.ncbi.nlm.nih.gov/26720830/
11. United States Environmental Protection Agency. Per- and Polyfluoroalkyl Substances (PFAS). https://www.epa.gov/pfas
12. National Fire Protection Association. Foam Systems. https://www.nfpa.org/~/media/files/foamtech/foamtechguide_05242018.pdf
13. US Government Accountability Office. Per- and Polyfluoroalkyl Substances: EPA Needs to Take Action to Reduce Risks from Existing PFAS Use (2019): GAO-20-440.
14. Wang Z., et al. “A never-ending story of per- and polyfluoroalkyl substances (PFASs)?” Environmental Science and Technology5 (2017): 2508-2518. https://pubs.acs.org/doi/10.1021/acs.est.6b04806
15. Buck RC., et al. “Perfluoroalkyl and polyfluoroalkyl substances in the environment: Terminology, classification, and origins”. Integrated Environmental Assessment and Management4 (2011): 513-541. https://setac.onlinelibrary.wiley.com/doi/10.1002/ieam.258
16. Cousins IT., et al. “The precautionary principle and chemicals management: The example of perfluoroalkyl acids in groundwater”. Environment International 124 (2019): 336-346. https://www.sciencedirect.com/science/article/abs/pii/S0160412016301775
17. Post GB., et al. “Key scientific issues in developing drinking water guidelines for perfluoroalkyl acids: Contaminants of emerging concern”. PLOS Biology12 (2017): e2002855. https://pubmed.ncbi.nlm.nih.gov/29261653/
18. Liu J., et al. “Reverse osmosis performance in removal of perfluoroalkyl substances (PFASs) and their precursors and by-products from drinking water”. Environmental Science and Technology8 (2017): 4636-4644. https://www.sciencedirect.com/science/article/abs/pii/S0043135419311558
19. Gomis MI., et al. “Comparing the in vitro estrogenic potency of per- and polyfluoroalkyl substances (PFASs) with other organic pollutants”. Environmental Science and Technology18 (2017): 10754-10761. https://pubs.acs.org/doi/10.1021/acs.est.0c03468
20. Wang Z., et al. “Fluorinated alternatives to long-chain perfluoroalkyl acids (PFAAs): Status, practical considerations and challenges ahead”. Environmental Science and Technology19 (2015): 11549-11559. https://pubmed.ncbi.nlm.nih.gov/24660230/
21. Lau C., et al. “Effects of perfluorooctanoic acid exposure during pregnancy in the mouse”. Toxicological Sciences2 (2006): 510-518. https://pubmed.ncbi.nlm.nih.gov/29862542/
22. D'Eon JC., et al. “Observations on the isomer-specific bioaccumulation of perfluorinated carboxylates in rainbow trout (Oncorhynchus mykiss)”. Environmental Science and Technology6 (2009): 1875-1881. https://pubs.acs.org/doi/10.1021/es404867w
23. Barry V., et al. “Perfluorooctanoic acid (PFOA) exposures and incident cancers among adults living near a chemical plant”. Environmental Health Perspectives11-12 (2013): 1313-1318. https://pubmed.ncbi.nlm.nih.gov/24007715/
24. Apelberg BJ., et al. “Determinants of fetal exposure to polyfluoroalkyl compounds in Baltimore, Maryland”. Environmental Science and Technology11 (2007): 3891-3897. https://pubs.acs.org/doi/10.1021/es0700911
25. Mamsen LS., et al. “Association between perfluoroalkyl substance exposure and reproductive outcomes in an infertility cohort”. Reproductive Toxicology 79 (2018): 41-48. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9692248/
26. Louis GM., et al. “Perfluorochemicals and human semen quality: the LIFE study”. Environmental Health Perspectives1 (2015): 57-63. https://pubmed.ncbi.nlm.nih.gov/25127343/
27. Fei C., et al. “Prenatal exposure to PFOA and PFOS and risk of hospitalization for infectious diseases in early childhood”. Environmental Research8 (2010): 773-777. https://pubmed.ncbi.nlm.nih.gov/20800832/
28. Verner MA., et al. “Measured prenatal and estimated postnatal levels of polychlorinated biphenyls (PCBs) and ADHD-related behaviors in 8-year-old children”. Environmental Health Perspectives10 (2015): 888-894. https://pubmed.ncbi.nlm.nih.gov/25769180/
29. Liu J., et al. “Association between prenatal exposure to perfluoroalkyl substances and asthma-related outcomes in children”. Science of the Total Environment 669 (2019): 128-136. https://pubmed.ncbi.nlm.nih.gov/31399834/
30. Andersen CS., et al. “Prenatal exposures to perfluorinated chemicals and anthropometry at 7 years of age”. American Journal of Epidemiology6 (2013): 921-927. https://academic.oup.com/aje/article/178/6/921/108073
31. Zhang Y., et al. “Biomonitoring of perfluoroalkyl acids in human urine and estimates of biological half-life”. Environmental Science and Technology18 (2013): 10619-10627. https://pubmed.ncbi.nlm.nih.gov/23980546/
32. Darrow LA., et al. “Serum perfluorooctanoic acid and perfluorooctane sulfonate concentrations in relation to birth outcomes in the Mid-Ohio Valley, 2005-2010”. Environmental Health Perspectives10 (2013): 1207-1213. https://pubmed.ncbi.nlm.nih.gov/23838280/
33. Maisonet M., et al. “Maternal concentrations of polyfluoroalkyl compounds during pregnancy and fetal and postnatal growth in British girls”. Environmental Health Perspectives10 (2012): 1432-1437. https://pubmed.ncbi.nlm.nih.gov/22935244/
34. Starling AP., et al. “Perfluoroalkyl substances during pregnancy and offspring weight and adiposity at birth: Examining mediation by maternal fasting glucose in the Healthy Start study”. Environmental Health Perspectives6 (2017): 067016. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5743451/
35. Braun JM., et al. “Prenatal perfluoroalkyl substance exposure and child adiposity at 8 years of age: The HOME study”. Obesity1 (2016): 231-237. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688224/
36. White SS., et al. “Gestational and chronic low-dose PFOA exposures and mammary gland growth and differentiation in three generations of CD-1 mice”. Environmental Health Perspectives7 (2011): 1070-1076. https://pubmed.ncbi.nlm.nih.gov/21501981/
37. Lv L., et al. “Perfluorooctanoic acid exposure disrupts mammary gland development in pregnant and lactating mice”. Journal of Applied Toxicology8 (2019): 1203-1211. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477546/
38. Genuis SJ and Birkholz D. “Human excretion of polyfluoroalkyl compounds: A systematic review of PFAS elimination rates in urine, sweat, and feces and effects of biomonitoring time frame”. Journal of Environmental and Public Health (2019): 363804. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8959433/
39. Fromme H., et al. “Perfluorinated compounds-exposure assessment for the general population in Western countries”. International Journal of Hygiene and Environmental Health3 (2009): 239-270. https://www.sciencedirect.com/science/article/abs/pii/S1438463908000308
40. D'Hollander W., et al. “Perfluorinated substances in human food and other sources of human exposure”. Reviews of Environmental Contamination and Toxicology 208 (2010): 179-215. https://link.springer.com/chapter/10.1007/978-1-4419-6880-7_4
41. Liu C., et al. “Human liver sinusoidal endothelial cells (LSECs) show high capacity for degradation of PFOA”. Environmental Science and Technology9 (2011): 3844-3850. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703927/
42. Kortenkamp A., et al. “State of the art assessment of endocrine disrupters”. Final Report European Commission (2011). https://www.higieneambiental.com/sites/default/files/images/pdf/disruptores-endocrinos-kortenkamp.pdf
43. Taylor KW., et al. “Polyfluoroalkyl chemicals and pregnancy”. Current Environmental Health Reports3 (2014): 167-177.
44. Granum B., et al. “Prenatal exposure to perfluoroalkyl substances may be associated with altered vaccine antibody levels and immune-related health outcomes in early childhood”. Journal of Immunotoxicology4 (2013): 373-379. https://www.tandfonline.com/doi/full/10.3109/1547691X.2012.755580
45. Loveless SE., et al. “Comparative responses of rats and mice exposed to linear/branched, linear, or branched ammonium perfluorooctanoate (APFO)”. Toxicology2-3 (2006): 203-217. https://pubmed.ncbi.nlm.nih.gov/16448737/
46. Barry V., et al. “Early-life perfluorooctanoic acid (PFOA) exposure and ulterior outcomes in adulthood”. Journal of Epidemiology and Community Health8 (2014): 724-731. https://pubmed.ncbi.nlm.nih.gov/36037606/
47. Dallaire R., et al. “Prenatal exposure to environmentally persistent organic pollutants and male anogenital distance: the INUENDO cohort study”. Environmental Health Perspectives7 (2013): 881-887. https://pubmed.ncbi.nlm.nih.gov/30212819/
48. Steenland K., et al. “Epidemiologic evidence on the health effects of perfluorooctanoic acid (PFO?A)”. Environmental Health Perspectives8 (2010): 1100-1108. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2920088/
49. Grandjean P., et al. “Serum vaccine antibody concentrations in children exposed to perfluorinated compounds”. The Journal of the American Medical Association4 (2012): 391-397. https://pubmed.ncbi.nlm.nih.gov/22274686/
50. DeWitt JC., et al. “Immunotoxicity of perfluorinated compounds: recent developments”. Toxicologic Pathology2 (2012): 300-311. https://pubmed.ncbi.nlm.nih.gov/22109712/
51. López-Espinosa MJ., et al. “Thyroid function and perfluoroalkyl acids in children living near a chemical plant”. Environmental Health Perspectives7 (2012): 1036-1041. https://pubmed.ncbi.nlm.nih.gov/22453676/
52. Nelson JW., et al. “Exposure to polyfluoroalkyl chemicals and cholesterol, body weight, and insulin resistance in the general U.S. population”. Environmental Health Perspectives2 (2010): 197-202. https://ehp.niehs.nih.gov/doi/10.1289/ehp.0901165
53. Steenland K., et al. “Predictors of PFOA levels in a community surrounding a chemical plant”. Environmental Health Perspectives7 (2009): 1083-1088. https://pubmed.ncbi.nlm.nih.gov/19654917/
54. Boas M., et al. “Thyroid effects of endocrine disrupting chemicals”. Molecular and Cellular Endocrinology2 (2012): 240-248. https://pubmed.ncbi.nlm.nih.gov/21939731/
55. Taylor KW., et al. “Polyfluoroalkyl chemicals and thyroid hormone concentrations in pregnant women”. Epidemiology3 (2014): 459-468. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690128/
56. Liu X., et al. “Endocrine disruption potentials of PFOS and PFOA”. Toxicology Letters3 (2012): 215-222. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926449/
57. Vieira VM., et al. “Perfluorooctanoic acid exposure and cancer outcomes in a contaminated community: a geographic analysis”. Environmental Health Perspectives3 (2013): 318-323. https://pubmed.ncbi.nlm.nih.gov/23308854/
58. Liu C., et al. “Occurrence, sources, and health effects of poly- and perfluoroalkyl substances (PFASs) in drinking water: a review”. Water Research 195 (2021): 117012. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7433796/
59. Gao Y., et al. “Perfluorooctane sulfonate (PFOS)-induced Sertoli cell injury through a disruption of F-actin cytoskeleton and microtubule network in rats”. Environmental Science and Pollution Research International1 (2017): 560-568. https://www.nature.com/articles/s41598-017-01016-8
60. Shankar A., et al. “Perfluoroalkyl chemicals and chronic kidney disease in US adults”. American Journal of Epidemiology8 (2011): 893-900. https://pubmed.ncbi.nlm.nih.gov/21873601/
61. Costa G., et al. “Thirty years of medical surveillance in perfluooctanoic acid production workers”. Journal of Occupational and Environmental Medicine3 (2009): 364-372. https://www.semanticscholar.org/paper/Thirty-Years-of-Medical-Surveillance-in-Acid-Costa-Sartori/190f11eb38c52e69063a5c34dd6331cea0e88180
62. Weiss JM., et al. “Competitive binding of poly- and perfluorinated compounds to the thyroid hormone transport protein transthyretin”. Toxicological Sciences2 (2009): 206-216. https://pubmed.ncbi.nlm.nih.gov/19293372/
63. Lau C., et al. “Perfluoroalkyl acids: a review of monitoring and toxicological findings”. Toxicological Sciences2 (2007): 366-394. https://pubmed.ncbi.nlm.nih.gov/17519394/
64. Joensen UN., et al. “Do perfluoroalkyl compounds impair human semen quality?” Environmental Health Perspectives6 (2009): 923-927. https://pubmed.ncbi.nlm.nih.gov/19590684/
65. Fei C., et al. “Perfluorinated chemicals and fetal growth: a study within the Danish National Birth Cohort”. Environmental Health Perspectives2 (2008): 165-170. https://pubmed.ncbi.nlm.nih.gov/18008003/
66. Darrow LA., et al. “Serum perfluorooctanoic acid and perfluorooctane sulfonate concentrations in relation to birth outcomes in the Mid-Ohio Valley, 2005-2010”. Environmental Health Perspectives10 (2013): 1207-1213. https://pubmed.ncbi.nlm.nih.gov/23838280/
67. Huang R., et al. “Perfluorooctane sulfonate and perfluorooctanoic acid in human serum: new method and levels in Tianjin, China”. Chemosphere6 (2009): 755-760.
68. Grandjean P and Landrigan PJ. “Developmental neurotoxicity of industrial chemicals”. Lancet9553 (2006): 2167-2178. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(06)69665-7/fulltext
69. Gutzkow KB., et al. “Placental transfer of perfluorinated compounds is selective - a Norwegian Mother and Child sub-cohort study”. International Journal of Hygiene and Environmental Health2 (2012): 216-219. https://pubmed.ncbi.nlm.nih.gov/21937271/
70. Granum B., et al. “Prenatal exposure to perfluoroalkyl substances may be associated with altered vaccine antibody levels and immune-related health outcomes in early childhood”. Journal of Immunotoxicology4 (2013): 373-379. https://www.tandfonline.com/doi/full/10.3109/1547691X.2012.755580
71. Dong GH., et al. “Serum polyfluoroalkyl concentrations, asthma outcomes, and immunological markers in a case-control study of Taiwanese children”. Environmental Health Perspectives4 (2013): 507-513. https://pubmed.ncbi.nlm.nih.gov/23309686/
72. Grandjean P and Herz KT. “Perfluorinated compounds and human fetal development: an epidemiologic review with clinical and toxicological perspectives”. Reproductive Toxicology3 (2011): 349-357. https://pubmed.ncbi.nlm.nih.gov/19429401/
73. Vieira VM., et al. “Perfluorooctanoic acid exposure and cancer outcomes in a contaminated community: a geographic analysis”. Environmental Health Perspectives3 (2013): 318-323. https://pubmed.ncbi.nlm.nih.gov/23308854/
74. Zhang X., et al. “Effects of perfluoroalkyl acids on DNA methylation, hydroxymethylation, and gene expression in human umbilical cord blood”. Environmental Science and Technology15 (2013): 8759-8767. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10037903/
75. Winquist A., et al. “Perfluoroalkyl substances in placental tissue and associations with DNA methylation”. Environment International 132 (2019): 105118. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473499/
76. Grandjean P and Clapp R. “Perfluorinated alkyl substances: Emerging insights into health risks”. NEW Solutions2 (2015): 147-163. https://pubmed.ncbi.nlm.nih.gov/26084549/
77. Balan SA., et al. “Per- and polyfluoroalkyl substances (PFASs) in products and indoor environments in Norway: Implications for human exposure from household use”. Environment International 69 (2014): 35-43. https://link.springer.com/article/10.1007/s11356-021-13343-5
78. UNEP/AMAP. Chemicals of emerging Arctic concern”. United Nations Environment Programme and Arctic Monitoring and Assessment Programme (2017). https://www.amap.no/documents/download/3003/inline
79. Miller MF., et al. “Evaluation of adverse effects of maternal exposure to perfluorinated compounds on fetal development”. International Journal of Environmental Research and Public Health3 (2016): 273.
80. Lindstrom AB., et al. “Polyfluorinated compounds: Past, present, and future”. Environmental Science and Technology20 (2011): 7954-7961. https://pubs.acs.org/doi/10.1021/es2011622
81. Gomis MI., et al. “Toxicity of poly- and perfluorinated compounds in human embryonic stem cell-derived hepatocytes”. Archives of Toxicology1 (2017): 311-320.
82. Per- and Polyfluoroalkyl Substances (PFAS) | US EPA. US EPA (2016). https://www.epa.gov/pfas
83. Drinking Water Health Advisories for PFOA and PFOS | US EPA. US EPA (2016). https://www.epa.gov/sdwa/drinking-water-health-advisories-pfoa-and-pfos
84. Shahsavari E., et al. “Challenges and Current Status of the Biological Treatment of PFAS-Contaminated Soils”. Frontiers in Bioengineering and Biotechnology (2021): 8. https://www.frontiersin.org/articles/10.3389/fbioe.2020.602040/full
85. Brennan NM., et al. “Trends in the Regulation of Per- and Polyfluoroalkyl Substances (PFAS): A Scoping Review”. International Journal of Environmental Research and Public Health20 (2021): 10900. https://www.mdpi.com/1660-4601/18/20/10900
86. Stoiber T., et al. “Disposal of products and materials containing per- and polyfluoroalkyl substances (PFAS): A cyclical problem”. Chemosphere 260 (2020): 127659. https://www.sciencedirect.com/science/article/pii/S0045653520318543
87. Arctic region. UNEP - UN Environment Programme. http://www.unep.org/explore-topics/oceans-seas/what-we-do/working-regional-seas/regional-seas-programmes/arctic-region
88. Shahsavari E., et al. “Challenges and Current Status of the Biological Treatment of PFAS-Contaminated Soils”. Frontiers in Bioengineering and Biotechnology (2021): 8. https://www.frontiersin.org/articles/10.3389/fbioe.2020.602040/full
89. Brennan NM., et al. “Trends in the Regulation of Per- and Polyfluoroalkyl Substances (PFAS): A Scoping Review”. International Journal of Environmental Research and Public Health20 (2021): 10900. https://www.mdpi.com/1660-4601/18/20/10900
90. Stoiber T., et al. “Disposal of products and materials containing per- and polyfluoroalkyl substances (PFAS): A cyclical problem”. Chemosphere 260 (2020): 127659. https://www.sciencedirect.com/science/article/abs/pii/S0045653520318543
91. Liu F., et al. “Recent Advances in the Analytical Techniques for PFASs and Corresponding Intermediates During Their Chemical Decomposition”. Chemical Research in Chinese Universities3 (2023): 361-369. https://link.springer.com/article/10.1007/s40242-023-3047-8
92. Fenton SE., et al. “Per‐ and Polyfluoroalkyl Substance Toxicity and Human Health Review: Current State of Knowledge and Strategies for Informing Future Research”. Environmental Toxicology and Chemistry3 (2020): 606-630. https://pubmed.ncbi.nlm.nih.gov/33017053/
93. OECD, PFASs and Alternatives in Food Packaging (Paper and Paperboard) Report on the Commercial Availability and Current Uses, OECD Series on Risk Management, No. 58, Environment, Health and Safety, Environment Directorate, OECD (2020).
94. Harclerode M., et al. “Preparing for effective, adaptive risk communication about per‐ and polyfluoroalkyl substances in drinking water”. AWWA Water Science5 (2021). https://awwa.onlinelibrary.wiley.com/doi/full/10.1002/aws2.1236