You have probably heard of PFAS, the so-called “forever chemicals.”  What you might not know is that there are more than 15,000 PFAS compounds categorized by the EPA. PFAS refers to perfluoroalkyl and polyfluoroalkyl substances, and what gives them the moniker “forever chemicals” is the strong bond between the carbon and fluorine molecules that make them almost indestructible and persistent in the environment. This commentary will address PFAS generally and also several of the most worrisome ones: PFOA (perfluorooctanoic acid) and PFOS (perfluorooctanesulfonate acid). Because of their ability to repel things, like oil water, or heat, they became ubiquitous throughout our society – think food packaging, nonstick coatings for cookware, firefighting foams, clothing, and countless more consumer products. Even much of the rainproof outdoor gear that supports our recreational lifestyle in Colorado gains its water resistance from PFAS. It has only been recently that the outdoor industry has been moving to alternatives.

PFAS are a public health concern because exposure has been widespread, primarily through consumption of contaminated food and water. They accumulate in the body and are excreted very slowly. According to the National Health and Nutrition Examination Survey, measurements of PFAS levels in blood samples show their almost ubiquitous presence in all of us. Fortunately, this survey shows blood levels of two notorious PFAS compounds are declining across the 21^st century. However, we still have significant uncertainty about the specific mechanisms by which PFAS harms health. 

THE BIRTH OF PFAS

The first PFAS were invented in the late 1930s with the synthesis of polytetrafluorethylene (PTFE), a saturated fluorocarbon polymer later marketed as Teflon. Many new compounds and applications followed but concerns about the health and environmental risks of PFAS did not emerge until the 1990s. From legal proceedings and discovery, we now know both 3M and DuPont carried out toxicological (animal) research indicating that PFAS could pose risks to health decades earlier than was made public. 3M’s researchers also documented the presence of PFAS, not only in workers but in blood samples from the population at-large. In a recent ProPublica/New Yorker article, Sharon Lerner tells the story of Kris Hansen, a 3M chemist, who documented the presence of PFOS in Red Cross blood samples, a finding of great public health significance that was buried by the company. Woodruff and colleagues analyzed industry documents describing research findings that provided evidence of health risk by 1970, long before there was any documentation in the general scientific literature.

One key milestone in the PFAS story is the litigation against DuPont brought by Robert Bilott, a now famous lawyer whose long battle against DuPont is chronicled in the movie Dark Waters, his book Exposure. Poisoned Water, Corporate Greed, and One Lawyer’s Twenty-Year Battle Against Dupont, and the documentary The Devil We Know. Bilott represented one case on behalf of Wilbur Tennant whose cattle were killed by drinking from a PFAS-contaminated creek downstream from a site where DuPont dumped PFOA sludge from its Washington Works plant in Parkersburg, West Virginia, and another class action lawsuit on behalf of residents of six water districts with PFOA contaminated water from the plant. The class action lawsuit sought medical monitoring of those exposed to PFOA to identify any PFOA-caused diseases as early as possible. 

Under the initial settlement reached with DuPont in 2004, a science panel of three epidemiologists was created to carry out a collaborative community study to identify links between PFOA and adverse health effects. Based on the study findings from 70,000 participants and other relevant scientific literature, the science panel concluded that the evidence was sufficient (i.e., more probable than not) to link PFOA to six diseases and conditions: kidney cancer, testicular cancer, ulcerative colitis, thyroid disease, hypercholesterolemia, and pregnancy-induced hypertension. Under the terms of the settlement, medical monitoring was to be implemented for these conditions. Further litigation has followed, which is well detailed in Billot’s book.

I offer the personal disclosure that from 2001-2007, I was a member of Dupont’s Epidemiology Review Board, which provided guidance on the company’s studies of its workforce, many of whom were PFAS-exposed. While the Board’s members were not involved in the PFOA litigation, the worker studies, involving a highly exposed group, were relevant. In 2006, the Board wrote to Dupont, admonishing the company for making a “…public expression asserting, with what appears to be great confidence, that PFOA does not pose a risk to health.” In the letter, we also urged DuPont to develop a comprehensive plan for epidemiological studies of PFOA risk in the Dupont workforce and to give highest priority to its implementation. That advice was not heeded.

Billot’s tenacious search for what Dupont knew and when the company knew it is reminiscent of the revelations in industry documents obtained in the “Big Tobacco” lawsuits. In Exposure, Billot describes sifting through thousands of documents to find those describing Dupont’s knowledge of the risks posed by PFOA. His document discoveries are another example of how litigation can benefit public health.

HUMAN HEALTH EFFECTS

Since the findings of the science panel in the early 2000s, there have been other significant advances in understanding the human health consequences of PFAS exposure. In 2021, the CDC’s Agency for Toxic Substances and Disease Registry (ATSDR) linked these forever chemicals with pregnancy-induced hypertension/pre-eclampsia, abnormalities of liver function, elevated serum lipid levels, decreased antibody responses to vaccines, and a small decrease in birth weight. In 2023, the WHO’s International Agency for Research on Cancer (IARC) classified PFOA as a Group 1 carcinogen (carcinogenic to humans) and PFOS as possibly carcinogenic to humans (Group 2B). The findings of ATSDR and IARC were echoed by a recent report from a committee of the National Academies of Sciences, Engineering, and Medicine. With much research in progress, I anticipate further conclusions on the risks posed to human and ecosystem health by PFAS. 

Billot faults the Environmental Protection Agency (EPA) for a slow response to the situation with the Washington Works Plant. Unfortunately, there are thousands of chemicals in use that have not been tested for toxicity, because prospective evidence of safety is not required under current regulations. More recently, the agency has taken regulatory steps around PFAS, following its strategic plans for these chemicals. In April, the EPA designated PFOA and PFOS as hazardous substances under the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA), known as Superfund. Also in April, the agency announced regulation of six PFAS, setting Maximum Contaminant Levels to be met within five years. Funding is available for implementing testing and providing solutions to reduce concentrations if the standards are not met. In Colorado, Senate Bill 81, passed during the just completed session of the 2024 General Assembly, accelerates the pace of phaseout of certain PFAS-containing products. Undoubtedly, there will be further regulation as scientific evidence on PFAS grows.

COLORADO RESEARCHERS AT THE FOREFRONT

While there is now greater awareness of the risks posed by PFAS, many questions need to be answered to control these risks. My colleagues at the Colorado School of Public Health are addressing key gaps related to exposure and child health. Professor John Adgate and his team have shown that run-off from Peterson Air Force Base, which used aqueous film forming foam (AFFF) in firefighter training exercises, has reached municipal drinking in El Paso County. The Colorado School of Public Health team assessed PFAS concentrations in the water in the affected communities before steps were taken in 2015 to remove PFAS, finding PFAS typical of those in AFFF. Blood concentrations were compared  between 2018-2019 and 2021-2023. In the initial survey, perfluorohexanesulphonic acid (PFHxS), commonly used in AFFF, was detectable in all blood samples but the follow-up data was encouraging, showing declining levels from the initial sample (Figure). Research by Professor Dana Dabelea and her team have addressed PFAS exposure and child health, a topic of concern because exposure starts during gestation and continues across the lifecourse. Recent papers show that the maternal level of PFAS during gestation is associated with the child’s risk for obesity and higher body-mass index (BMI) on follow-up at ages 2 and 5 and that higher mid-gestation levels for some PFAS are associated with lower antibody titers in response to childhood vaccinations.

Translating what we have learned from research into clinical care is challenging. Professor Ned Calonge, Associate Dean for Public Health Practice and Chief Medical Officer for the Colorado Department of Public Health and Environment, chaired the committee of the National Academies of Sciences, Engineering and Medicine that developed needed guidance on testing and clinical follow-up. The committee’s community-based work led to revision of the ATSDR guidance around testing.

Back to my title for this commentary; these forever chemicals will be a never-ending story.  Remembering the lessons learned from DDT and chlorofluorocarbons, PFAS are yet another reminder that we should not be making environmental contaminants that are persistent and that are of unknown risk. 

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This article is part of a monthly column, The Jon Samet Report, on the biggest issues facing us today in public health, written by the former dean of the Colorado School of Public Health, Jon Samet, a pulmonary physician and epidemiologist, and Professor of Epidemiology and Occupational and Environmental Health. Dr. Samet is a global health leader, shaping the science and conversation on issues ranging from tobacco control to air pollution to chronic disease prevention and more. Each month he shares expert insights on public health issues from local to global.