Health Effects of Per- and Polyfluoroalkyl Substances

K.H. is a 46-year-old man who presents to my clinic for evaluation of a painless testicular mass he first noticed a few weeks ago while showering. He is otherwise asymptomatic, including no fevers or penile discharge. He has a history of hyperlipidemia but no history of cancer. On physical examination, there is a 3-cm, nontender, firm mass on the right testicle. The left testicle appears normal, and there is no lymphadenopathy or abdominal mass. While discussing your concerns regarding malignancy and the need for further diagnostics, K.H. asks whether his occupation as a firefighter could be somehow related. He is currently employed as a civilian firefighter; during his previous military service as a firefighter, he reports extensive use of aqueous film-forming foams that contained per- and polyfluoroalkyl substances (PFAS) when extinguishing airport and military installation fires. In addition to treating my patient, how can I best answer his question about the relevance of PFAS in causing his condition?

PFAS are a class of chemicals that are widely used in industry and commonly found in the environment. There are thousands of different PFAS, but some have been studied more comprehensively than others (eg, perfluorooctanoic acid, perfluorooctanesulfonic acid, perfluorohexanesulfonic acid, perfluorodecanoic acid, perfluorononanoic acid). Of these, perfluorooctanoic acid and perfluorooctanesulfonic acid are more common in industrial use, although less often now because of industrial phaseout or regulation against their use worldwide.¹

PFAS are primarily used as fluorosurfactants; they are included in several consumer products such as nonstick cookware and stain-, wrinkle-, and water-resistant fabrics.² The unique property of PFAS to resist oil and water makes them a key component in aqueous film-forming foams and, thus, an excellent firefighting tool when addressing petroleum-based fires.³ These foams have been in use since the 1970s but are currently planned for phaseout by the US Department of Defense.

PFAS are highly concerning to environmental regulators because of their prevalence in water due to their water solubility. They are also extremely long lasting, receiving the nickname forever chemicals. Within the United States alone, PFAS have been detected in nearly 50% of all tap water, and they are widely used outside of the United States, making them a significant cause for global concern.⁴

Health Effects

The Agency for Toxic Substances and Disease Registry has a toxicologic profile for PFAS.⁵ The Centers for Disease Control and Prevention also has included data on PFAS since 1999 in the National Health and Nutrition Examination Survey.⁶ Based on these and other observational data, sufficient evidence supports association between PFAS and decreased antibody response after vaccination or infection, elevated risk for dyslipidemia, decreased infant and fetal growth, and heightened risk of kidney cancers in adults.³ Evidence suggests associations between PFAS and increased risk of liver and thyroid dysfunction.⁵ Other cancers, including breast and testicular, may be linked to PFAS.⁷ Suggestive evidence also supports an elevated risk of ulcerative colitis in adults.³

Some literature has described other adverse health effects, although according to current Agency for Toxic Substances and Disease Registry recommendations, there is insufficient evidence to suggest that this is the case.⁵ These effects include infertility, metabolic syndrome, obesity, and reproductive effects. Associations also include cancers other than kidney, breast, and testicular; however, considerable gaps are found in current research.³ Most research focused on PFAS has concentrated on a limited number of compounds (eg, perfluorooctanoic acid, perfluorooctanesulfonic acid), leaving more than a thousand others unstudied or understudied to determine their toxicity and possible adverse health effects.