Although several per- and polyfluoroalkyl substances (PFAS) have been banned or limited in their future use, they continue to have a lasting impact on the environment and human health, with detectable levels apparent in most individuals.
Per- and polyfluoroalkyl substances (PFAS) are chemicals that have many useful applications, but also pose serious threats to the environment and human health. How can we deal with this complex and urgent issue?
Update: On January 18, 2024, the U.S. Agency for Toxic Substances and Disease Registry (ATSDR) published PFAS information for clinicians to assist in decision making for patients with concerns about PFAS exposure. In deciding whether to order a PFAS blood test, they can consider a patient’s potential exposure to PFAS, assess the duration and routes of exposure, and the individual’s risk for disease. It is a topic of growing concern among the medical community and one insurers would be well served to monitor in the years ahead.
PFAS are a group of synthetic chemicals that have been widely used in the manufacture of various industrial and commercial products since the 1930s. Also referred to as “forever chemicals”, they have unique properties that make them resistant to grease, oil, water, and heat, but also pose serious environmental and health risks.
PFAS are composed of a chain of linked carbon and fluorine atoms, which form an incredibly strong bond, making them difficult to break down naturally.1 According to the Organization for Economic Co-operation and Development (OECD), as of 2021, PFAS are defined as ”fluorinated substances that contain at least one fully fluorinated methyl or methylene carbon atom.”2 Over 10,000 PFAS have been made so far, of which long-chain (> 7 carbons) PFAS, such as perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA, also known as C8), were the most widely used. They are more persistent and toxic than short-chain PFAS (< 6 carbons), which include:3
hexafluoropropylene oxide dimer acid (HFPO-DA)/Gen X
perfluorobutanesulfonic acid (PFBS)
perfluroheptanoic acid (PFHpA)
perfluorohexanoaic acid (PFHxA)
perfluorohexane sulfonic acid (PFHxS)
perfluorononanoic acid (PFNA)
perfluoroundecanoic acid (PFUA)
The effects and toxicity of PFAS vary depending on their chemical structure, making it hard to study their impact on human health. However, some PFAS have been classified as possible or probable carcinogens by agencies, such as the International Agency for Research on Cancer (IARC), which classified PFOA as possibly carcinogenic to humans (Group 2B) in 2016.4 The US National Toxicology Program (NTP) concluded that PFOA and PFOS are ”presumed to be an immune hazard to humans.”5 The NTP is currently leading several studies to further evaluate the adverse effects of PFAS, including PFNA, PFHxS, PFHxA, PFOS and PFBS.6 The U.S. Environmental Protection Agency (EPA) currently classifies PFOA, PFOS, and HFPO-DA (commonly referred to as GenX) as having suggestive evidence of carcinogenic potential.4
PFAS are used in the making of various products that are widely used in everyday life, such as school uniforms, firefighting clothing, raincoats, outdoor wear contain Gore-Tex, stain resistant upholstery and carpets, as well as nonstick cookware, cosmetics, period products, food packaging, paper straws, plastic water bottles, and more.
PFOA was originally used in the production of polytetrafluoroethylene (PTFE), more commonly known under the brand name Teflon, which was accidentally discovered in 1938. PFOA was later discontinued in the making of Teflon due to its environmental impact and toxicity on cellular life and replaced with GenX.5, 7 PFAS are also used to make fluorinated pharmaceuticals, such as fluoxetine (Prozac), sitagliptin (Januvia), atorvastatin (Lipitor), ciprofloxacin (cipro), and fluticasone propionate (Flonase).1
PFAS are released into the environment through wastewater and emissions from the manufacture and use of products containing these chemicals. They can contaminate the soil, rivers, and the air. People are exposed to these chemicals by drinking contaminated water, consuming contaminated foods, using products, or breathing in air or dust containing PFAS.
These chemicals can persist in the environment for years, but it is unknown exactly how long it takes for them to break down naturally.
Their resistance to biodegradation means that the half-life (the time taken to fall to half of the original amount) of individual PFAS such as PFOA, PFOS, and PFHxS in the human body ranges between 2.7-8 years while the half-life of PFOS and PFOA in surface water is 41 and 92 years, respectively.4,5
PFAS have been detected in the blood of most Americans, as well as in the drinking water and food. According to data from 2011-2012, PFAS were found in the blood of 97% of Americans tested.6 Tap water typically accounts for about 20% of a person’s exposure to PFAS, but the majority of PFAS intake is generally from the consumption of food.1, 4 Industrial workers involved in the creation or processing of PFAS are at increased risk of exposure, but with the elimination of the use of PFOA and PFOS in manufacturing, levels recorded in humans are slowly reducing. Biomonitoring studies show that in 1998, manufacturing workers in Decatur, Alabama had PFOA, PFOS, and PFHxS blood levels of 899, 941, and 180 micrograms per liter (µg/L), respectively. This compares to 2017-2018 data in the U.S. general population showing blood levels of 1.4, 4.3, and 1.1 µg/L, respectively. PFOS levels have fallen by more than 85% and PFOA levels by more than 70% during this period.8
PFAS can bind to proteins, such as hemoglobin and albumin, and accumulate in the blood and living organs. Exposure to PFAS may increase the risk of developing various types of cancer, as well as other health problems, such as liver and kidney damage, cardiovascular disease (CVD), high cholesterol, obesity, diabetes, and reduced immunity.9
Many PFAS are known to disrupt the normal functioning of the endocrine system, cause weakened immunity, excessive cell growth, and altered gene activity.10
A recent U.S. study showed that women who developed breast, ovarian, skin, and uterine cancers had markedly higher levels of PFAS in their bodies. The study used data from the National Health and Nutrition Examination Survey (NHANES) collected between 2005 and 2018, comprising over 16,000 individuals. It found that women exposed to elevated levels of perfluorodecanoic acid (PFDE) had twice the odds of a melanoma diagnosis (OR 2.07), while women with increased exposure to PFNA and PFUA had nearly double the risk of having a melanoma diagnosis (OR 1.72 and OR 1.76, respectively). A link was also established between PFNA and a prior diagnosis of uterine cancer (OR 1.55).11
Odds of each cancer type with interquartile range increase in each PFAS chemical, among men (A) and among women (B)11
The C8 Science Panel was set up in 2005 to conduct health studies on the mid-Ohio valley communities who had potentially been affected by the release of PFOA since the 1950s from a works plant in West Virginia. The panel collected blood samples from 69,000 individuals to look for possible links between PFOA exposure and human disease.
The panel concluded that there was a probable link between PFOA and high cholesterol, ulcerative colitis, thyroid disease, testicular and kidney cancer, and pregnancy-induced hypertension, based on PFOA levels in the blood and incidence of disease.12
In one cohort of 32,254 adults aged >20 years from the C8 Science Panel, estimated cumulative serum PFOA concentrations were positively associated with kidney cancer (HR 1.10), testicular cancer (HR 1.34), brain cancer (HR 1.13), thyroid cancer (HR 1.10), and uterine cancer (HR 1.05).13
A PFAS blood test, which can be collected either by blood draw or a finger-prick sample, measures the PFAS levels of up to 40 chemicals. Typically, a test can cost between US$400-$600. The National Health and Nutrition Examination Survey (NHANES) has been measuring blood PFAS in the U.S. population for more than 20 years.14
Some PFAS chemicals are present in blood as a mixture of related chemical structures known as isomers. Most laboratories report the total amount of linear and branched isomers, but some only report linear isomers, thereby underestimating the amount of PFAS in the blood. Detection levels are usually from 0.1 to 1 nanograms per milliliter (ng/mL). It is important to note that levels in whole blood are around half that of levels in blood serum, being more concentrated in serum. Individual test results are compared to levels found in other groups to determine if the results are elevated. In most cases, PFAS testing is not covered by insurance.14
The U.S. National Academies Press report contains clinical guidelines on the assessment of disease risk when exposed to PFAS. The report defines three risk categories based on the PFAS blood concentration: no/low risk (<2 ng/mL), moderate risk (2-20 ng/mL), and high risk (>20 ng/mL). For individuals in the moderate risk category, it is recommended that they are screened for triglyceride levels, which when high can increase the risk of heart attack or stroke. For individuals in the high-risk category, routine screening for some cancers, thyroid problems, and ulcerative colitis is recommended.15
PFAS have been regulated and restricted in different ways around the world. In the U.S., the Food and Drug Administration (FDA) regulates PFAS, while the European Chemicals Agency (ECHA) regulates PFAS in the European Union (EU). PFOS production was ceased in the U.S. in 2002 and PFOA was phased out in 2006.5 In February 2023, the ECHA proposed a significant ban on the production and use of PFAS in the EU.1 Under the EU Green Deal’s Chemical Strategy for Sustainability, it has been promised to phase out all non-essential uses of PFAS.16 In Asia, there are no regulations or restrictions on the use of PFAS, and it appears that much of the production of PFOS and PFOA has moved to this part of the world.5
In March 2023, the EPA proposed maximum contaminant levels (MCLs) for six PFAS in drinking water to help prevent thousands of deaths and serious PFAS-attributable illnesses. They include PFOA and PFOS as individual contaminants, and PFHxS, PFNA, PFBS, and HFPO-DA as a PFAS mixture. The EPA anticipates finalizing the regulation by the end of 2023.10
Proposed National Primary Drinking Water Regulation (NPDWR)10
Although several PFAS have been banned or limited in their future use, they continue to have a lasting impact on the environment and human health, with detectable levels apparent in most individuals. While more research is needed, sufficient evidence shows a probable link between PFOA and high cholesterol, ulcerative colitis, thyroid disease, testicular and kidney cancer, and pregnancy-induced hypertension. Insurers should be aware of the risks and impact of PFAS exposure and the increased risk of disease, particularly in occupational exposed individuals, and how these chemicals may affect human health in the years to come.
Tingley, K. (2023). Forever chemicals’ are everywhere. What are they doing to us? The New York Times Magazine; Aug 16, 2023. Available from: ‘Forever Chemicals’ Are Everywhere. What Are They Doing to Us? - The New York Times (nytimes.com) [accessed Oct 2023]
Hammel, E. et al (2022). Implications of PFAS definitions using fluorinated pharmaceuticals. iScience 25; 104020. Available from: Implications of PFAS definitions using fluorinated pharmaceuticals (cell.com) [accessed Oct 2023]
USDHHS (2022). Per- and polyfluoroalkyl substances (PFAS) and your health. Agency for Toxic Substances and Disease Registry; 1 Nov 2022. Available from: Learn about PFAS | ATSDR (cdc.gov) [accessed Oct 2023]
Temkin, A.M. et al (2020). Application of the key characteristics of carcinogens to per and polyfluoroalkyl substances. International Journal of Environmental Research and Public Health, 2020; 17: 1668. Available from: Application of the Key Characteristics of Carcinogens to Per and Polyfluoroalkyl Substances - PubMed (nih.gov) [accessed Oct 2023]
National Toxicology Program (2016). Immunotoxicity associated with exposure to perfluorooctanoic acid or perfluorooctane sulfonate. NTP Monograph. Available from: Monograph: Perfluorooctanoic Acid or Perfluorooctane Sulfonate; Sept. 2016 (nih.gov) [accessed Oct 2023]
NIH (2023). Perfluoroalkyl and polyfluoroalkyl substances (PFAS). Environmental Agents. Available from: Perfluoroalkyl and Polyfluoroalkyl Substances (PFAS) (nih.gov) [accessed Oct 2023]
Coyle, D. (2023). Is nonstick cookware like Teflon safe to use? Healthline May 19, 2023. Available from: Is Nonstick Cookware Like Teflon Safe to Use? (healthline.com) [accessed Oct 2023]
USDHHS (2023). PFAS in the US population. Agency for Toxic Substances and Disease Registry; 29 June 2023. Available from: PFAS in the US population | ATSDR (cdc.gov) [accessed Oct 2023]
Bailey, E. (2023). ‘Forever chemicals’ found in certain period products, researchers say. Medical News Today, Aug 21, 2023. Available from: PFAS: Some period products may contain 'forever chemicals' (medicalnewstoday.com) [accessed Oct 2023]
US EPA (2023). Per- and Polyfluoroalkyl substances (PFAS). Proposed PFAS National Primary Drinking Water Regulation. 22 Sept 2023. Available from: Per- and Polyfluoroalkyl Substances (PFAS) | US EPA [accessed Oct 2023]
Cathey, A.L. et al (2023). Exploratory profiles of phenols, parabens, and per- and poly-fluoroalkyl substances among NHANES study participants in association with previous cancer diagnosis. Journal of Exposure Science & Environmental Epidemiology; 33: 687-698. Available from: Exploratory profiles of phenols, parabens, and per- and poly-fluoroalkyl substances among NHANES study participants in association with previous cancer diagnoses | Journal of Exposure Science & Environmental Epidemiology (nature.com) [accessed Oct 2023]
C8 Science Panel (2020). C8 probable links report. Available from: C8 Science Panel Website [accessed Oct 2023]
Barry, V. et al (2013). Perfluorooctanoic acid (PFOA) exposures and incident cancer among adults living near a chemical plant. Environmental Health Perspectives; 121(11-12): 1313-1318. Available from: Perfluorooctanoic Acid (PFOA) Exposures and Incident Cancers among Adults Living Near a Chemical Plant (nih.gov) [accessed Oct 2023]
PFAS-REACH (2022). PFAS blood testing: what you need to know. National Institute of Environmental Health Sciences. Available from: PFAS-Blood-Testing-Document-May-2022.pdf (pfas-exchange.org) [accessed Oct 2023]
Newsome, M. (2022). ‘Forever chemicals’ may post a bigger risk to our health than scientists thought. Science News Nov 29, 2022. Available from: Forever chemicals, or PFAS, pose troubling health risks (sciencenews.org) [accessed Oct 2023]
ECHA (2023). Understanding REACH. Available from: Understanding REACH - ECHA (europa.eu) [accessed Oct 2023]
