In an ongoing study of North Carolina firefighters, Duke University researchers are examining a potential link between PFAS exposure and biomarkers of thyroid dysfunction and disease. This study includes trifluoroacetic acid (TFA), a degradation product of some fluorine-containing gases and other substances, and it is one of the first studies to investigate human health outcomes related to TFA exposure.
While the researchers found that levels of one thyroid antibody was correlated in a small number of firefighters who had TFA in their blood serum, the results to date are inconclusive.
The lead researcher in the study is environmental chemist and exposure scientist Heather Stapleton, a Professor of Environmental Health at Duke University and Director of Duke’s Superfund Research Center. She described the firefighter study at the 46th Annual Meeting of the Society of Environmental Toxicology and Chemistry (SETAC) in Portland, Oregon, held November 16–20, 2025.
The study is looking broadly at PFAS and its potential association with thyroid disease, Stapleton said. “TFA happens to be one of the PFAS we are including, but this study did not set out to focus on TFA.”
TFA is regarded by scientists as an ultrashort-chain PFAS (per- and polyfluoroalkyl substance), or “forever chemical”; it has two carbon atoms, one attached to three fluorine atoms. Longer-chain PFAS such as PFOA (perfluorooctanoic acid) and PFOS (perfluorooctanesulfonic acid) are linked to thyroid disease and to kidney and testicular cancer in the case of PFOA, among other adverse health outcomes.
TFA also falls under the category of haloacetic acids such as DCA (dichloroacetic acid) and TCA (trichloroacetic acid), which are considered potential human carcinogens and disruptive to thyroid function. As a haloacetic acid, TFA is a substance that “we should look at,” said Stapleton at the SETAC conference.
The TFA found in the study is not correlated with any of the longer-chain and legacy PFAS, making it easier to assess independently in statistical models. But it is highly correlated with the ultrashort-chain (three-carbon) perfluoropropionic acid (PFPrA), suggesting that TFA and PFPrA may have “unique exposure sources” compared to other PFAS commonly studied in firefighters, it said.
As a haloacetic acid, TFA is a substance that “we should look at.”
Heather Stapleton, Professor of Environmental Health at Duke University
Stapleton acknowledged that there could be a “mixture effect” where TFA would work in concert with other PFAS in impacting thyroid function. “We’re hoping to explore that but we’re trying to get more data before we run those models.”
TFA itself has been found harmful in low concentrations to lab animals, sounding alarms about its potential effect on humans, especially over long-term exposure as TFA builds up in the environment. The European Chemicals Agency (ECHA) is evaluating a German proposal to classify TFA as reproductively toxic under the EU’s classification, labelling and packaging (CLP) regulation.
In defending the use of TFA-producing refrigerants, (notably HFO-1234yf), the fluorochemical Industry points to the UN Environment Programme (UNEP) and its 2022 Environmental Effects Assessment Panel (EEAP) report. The report says that TFA is not bioaccumulative, is “not expected to pose significant risk to humans or the environment at the present time” and “is unlikely to cause adverse effects out to 2100.” The report does not comment on the contribution of pesticides and other precursors to TFA since they don’t fall under the purview of the Montreal Protocol, under which UNEP is an implementing agency.
Chemours, which operates in North Carolina, told state regulators last year that “based on risk assessment modelling and available toxicological data for similar compounds, [TFA] is not believed to be harmful to human health or the environment.”
Part of a national study
Since July 2024, the Duke researchers have been analyzing concentrations of 54 PFAS in the blood serum of more than 700 firefighters (94% male) in North Carolina, part of the National Firefighter Cancer Cohort Study (FFCCS) that was launched in 2018. The researchers are particularly interested in “examining associations between exposure to PFAS such as TFA and the risk for thyroid disease among firefighters,” said Stapleton
In North Carolina, environmental TFA in the Cape Fear River and drinking water has been linked to emissions from a Chemours facility in Fayetteville as a byproduct of chemicals producer there. But TFA is also generated by the complete atmospheric breakdown in under two weeks of fugitive emissions of the refrigerant HFO-1234yf and the partial breakdown of other fluorinated refrigerants, as well as the decomposition of certain agricultural pesticides and pharmaceuticals, among other sources. HFO-1234yf is widely used in car air-conditioning and in blends with HFC refrigerants used in supermarket and cold-storage refrigeration.
Among the PFAS analyzed in the Duke study, TFA was the most abundant compound in blood serum of the first 516 firefighters with a 100% detection frequency, a median concentration of 20.1 ng/g and a maximum concentration of 570 ng/g, according to the abstract. The next most abundant PFAS was PFOS, with a median serum concentration of 3.62 ng/g.
TFA levels were not associated with participant age, sex or years of firefighting service, in contrast to other legacy PFAS measured, the abstract said.
Stapleton noted that TFA levels are “significantly higher” – about 15% – in spring, summer and fall, compared to measurements from participants who were recruited in the winter; she did not offer an explanation for the difference. The Duke team plans to look at the ambient temperature on the days they collected blood samples. Their findings correlate with a 2025 study by Canadian researchers, which found that the amount of TFA in the atmosphere, formed by the oxidation of HFO-1234yf and other f-gases, is greatest in the summer and near urban areas, consistent with the leakage of HFO-1234yf from mobile air conditioners (MAC).
The TFA levels found in the firefighters exceeds that in blood serum in other studies, including a recent one done at North Carolina State University that reported 17ng/mL and a 2023 study of Indiana households where it was found to be 6ng/mL.
The researchers at Duke have compared their overall PFAS data with that of the study at North Carolina State University, where researchers have been analyzing blood samples from the general population in Wilmington, North Carolina. “When we make that comparison, our levels are actually pretty similar, with the exception of PFHxS [perfluorohexane sulfonic acid], which is clearly elevated in the firefighters,” said Stapleton in her SETAC presentation.
Higher cancer rates in firefighters
The Duke researchers explored potential associations between TFA and thyroid hormones in the study’s firefighter group. Stapleton noted that firefighters reportedly have higher rates of thyroid cancer and higher levels of thyroid autoantibodies than the general population.
Preliminary findings, the abstract said, “highlight the prominence of TFA as a novel PFAS of concern in firefighters and point to potential associations with thyroid-related biomarkers.” However, Stapleton cautioned at her SETAC presentation that more data is required to come to any conclusions about the effect of TFA on the thyroid.
“It’s important to remember that most of those measurements are still at a thyroid antibody level that’s considered normal or background,” she said. “it’s not above the threshold for what a medical doctor would refer to as positive or high.”
The researchers conducted a pilot analysis for the presence of two thyroid autoantibodies – thyroglobulin antibody (TGab) and thyroid peroxidase antibody (TPOab) – in 20 firefighters; these antibodies can attack the thyroid and cause autoimmune dysfunction such as hypothyroidism and Graves’ disease (hyperthyroidism).
As of November she reported seeing “a number of firefighters testing positive for thyroid antibodies right now – four for TGab and seven for TPOab, which does seem higher than normal for males,” said Stapleton. Most of the samples are restricted to male firefighters, who make up 94% of the study participants.
In the initial batch of TGab results, the Duke researchers “observed a significant and positive correlation between serum TFA and continuous TGab levels [correlation coefficient r = 0.54], raising questions about a possible immunomodulatory role for TFA,” the abstract said. However, Stapleton said at the SETAC conference, “as more data has come in from other batches, [the TFA–TGab link] has been muted a bit.” Overall, the correlation is 0.18, which is “almost barely statistically significant. So we’ll see if this changes as we collect more data.”
Stapleton also reported at SETAC having data on levels of free thyroxine (T4) and thyroid stimulating hormone (TSH) – two key hormones involved in metabolic regulation – as well as TFA measurements in 249 firefighters. Her team found “somewhat positive but not statistically significant associations” between TFA and TSH: the higher the TFA, the higher the TSH, but no correlation with T4. These findings were separate from the antibody results, she said; the firefighters that were positive for thyroid antibodies did not have abnormal thyroid hormone levels.
The Duke team plans to start investigating how much TFA levels in drinking water in North Carolina predict TFA levels in blood serum for the firefighters in the study.
