A new study by a team of 16 Chinese researchers has determined that trifluoroacetic acid (TFA), a byproduct of certain f-gases and other substances, interferes with the energy production needed to maintain and grow human blood vessels.
The researchers are affiliated with the Shenzhen Center for Disease Control & Prevention, Sun Yat-sen University, Guangzhou Medical University and Shanghai Jiao Tong University. The team was led by Yanhong Wei of Sun Yat-sen University and Xifei Yang at the Shenzhen Center for Disease Control and Prevention.
Their study – “Trifluoroacetic Acid Competitively Inhibits Lactate Dehydrogenase to Disrupt Endothelial Glycolysis and Impair Vascular Development” – appears in the September 29, 2026, issue of Environmental Science & Technology.
This is one of the few studies that have linked TFA to adverse human health outcomes. A number of animal studies have also shown harmful effects of TFA, albeit at concentrations generally above what is found in the environment. The chemical industry, backed by reports issued under the Montreal Protocol, contends that TFA is not harmful to people at current or projected concentrations.
But TFA concentrations in the global environment – water, soil, air and leaves – have been steadily growing in recent years. A 2022 study, for example, found a median TFA of 1.5mcg/L in German drinking water. The chemical is turning up in food, beverages and human blood serum and raising concerns about potential harm to human health.
Most recently, medium concentrations of TFA has been measured in human blood serum in a Duke University study of firefighters (20.1mcg/kg), by researchers at North Carolina State University (17mcg/L) and in a European study initiated by the Greens/EFA group in the EU Parliament (21.2mcg/L)
TFA is a two-carbon molecule, with one of the carbons attached to three fluorine atoms, thus making it an ultrashort-chain PFAS (per- and polyfluoroalkyl substance), or “forever chemical,” according to the most widely used definition of PFAS (though not employed by the U.S. government). TFA is considered the most abundant PFAS in the environment.
One of the chief sources of TFA is the complete and rapid atmospheric breakdown of HFO-1234yf that leaks from car AC systems and other HVAC&R applications, supporting the argument for using non-TFA-producing natural refrigerants. Other sources of TFA include certain pesticides, pharmaceuticals and other industrial sources.
Opening the door to TFA
It is TFA’s small structure and extreme solubility in water that gives it “high accessibility to the innermost layer of vasculature [blood vessels],” the Chinese study said. Moreover, it added, “the vasculature relies on metabolic processes to sustain function and is particularly highly responsive to environmental chemical insults.”
The study did, in fact, discover “TFA-induced vascular toxicity” that “reinforces the need to reassess the health risks of TFA.” The European Chemical Industry Council (Cefic) declined to comment on the TFA study.
This is not the first study to show that TFA can bind to proteins and cause a disruption in a cellular process, noted Hans Peter Arp, an environmental chemist at the Norwegian Geotechnical Institute, in a LinkedIn comment.
Arp pointed to a 2025 study demonstrating cognitive impairments in mice following TFA treatment. He has previously referenced a 1998 study showing that aquatic organisms incorporated TFA into their biomolecule fractions such that the TFA was “metabolically transformed,” and a 1999 study that found a low level of TFA incorporation by natural microbial communities.
“We still have so little data about the TFA in our bodies, yet the world is being exposed to increasing amounts each day.”
Hans Peter Arp, the Norwegian Geotechnical Institute
One drawback of the Chinese study is that it is based on in vitro (laboratory) analysis. In an article in Chemical & Engineering News (C&EN), one of the primary researchers, Wei, was quoted as saying at the American Chemical Society 2026 meeting in Chicago in August that, to date, no one has measured the levels of TFA in real human blood vessel tissues. “Researchers may need to investigate how quickly TFA diffuses from blood into endothelial cells, which line the inside of blood vessels,” the article said.
The study shows “why we need to not only track the rising blood concentrations of TFA in the human population, but also in the blood vessel tissues,” Arp said in his LinkedIn comments. “We still have so little data about the TFA in our bodies, yet the world is being exposed to increasing amounts each day, and this will continue for the foreseeable future.”
It’s another warning, Arp added, “to start reducing exposure by phasing out processes and substances that emit TFA.” He led a 2024 study that said TFA meets the criteria of a “planetary boundary threat” because of increasing planetary-scale exposure.
Hampering energy production
The Chinese study investigated the toxicity of TFA in blood vessels using human umbilical vein endothelial cells. The study employed TFA at environmentally relevant concentrations of 0.8–2,000mcg/L.
The researchers found that TFA hampers glycolysis, which is the primary energy-producing mechanism in endothelial cells. In glycolysis, glucose is converted to pyruvate, which is then turned into lactate; the energy released allows cells to generate ATP (adenosine triphosphate), the primary energy currency of cells. But TFA exposure reduced the production of lactate and ATP and thus stymied the overall glycolytic flux (the breakdown of glucose).
Notably, the amount of pyruvate, the initial byproduct of glucose breakdown, increased. This happened, the researchers said, because the TFA, rather than similarly structured pyruvate, interfaced with the enzyme lactate dehydrogenase (LDH), which would normally turn pyruvate into lactate. “TFA competitively inhibits LDH, thereby blocking pyruvate-to-lactate conversion and sequentially diminishing ATP generation,” said the study.
ATP and lactate concentrations fell in a dose-dependent manner upon TFA exposure. For example, ATP levels dropped by 7% at 0.8mcg/L of TFA, 26% at 2mcg/L and 45% at 200mcg/L; however, at 2,000mcg/L of TFA, ADP decreased by 43%.
“Environmentally realistic concentrations of TFA probably cause health risk through metabolic perturbation of the vasculature.”
Study: Trifluoroacetic Acid Competitively Inhibits Lactate Dehydrogenase to Disrupt Endothelial Glycolysis and Impair Vascular Development
The study determined that the benchmark dose lower confidence limit (BMDL5) values for TFA – the lowest amount likely to cause an adverse change of 5% – ranged from 0.44mcg/L (lactate) to 2.65 mcg/L(ATP), falling within the range of environmental levels. This suggests that “environmentally realistic concentrations of TFA probably cause health risk through metabolic perturbation of the vasculature,” said the study.
Along with the study of TFA’s human vascular effects, the researchers looked at the impact of exposure in zebrafish larvae, finding TFA inhibited endothelial migration (movement of blood-vessel cells), induced cellular F-actin disruption (damaged cell function) and impaired vascular development.
“Collectively, our research demonstrates that environmentally relevant concentrations of TFA exposure competitively inhibit LDH, suppress glycolytic flux, and impair endothelial migration, leading to a defective vascular development,” the study said, adding that the results highlight “the urgent need for strengthened monitoring.”
Other in vitro study
The Chinese TFA study is not the first in vitro analysis of the effects of TFA on human health. A 2025 study by Italian researchers found that TFA reduced antibody production in human-relevant tests at levels similar to those caused by perfluorooctanesulfonic acid (PFOS), which has well-documented immunotoxic effects.
The Italian study was supported by the European Food Safety Authority (EFSA), which has significantly lowered health-based guidance values for TFA, indicators of what is considered a safe level in daily food, beverage and drinking-water consumption.
The European Chemicals Agency (ECHA) concluded in June that TFA, based on animal studies, should be classified and labelled as toxic to reproduction, persistent, mobile and toxic (PMT) and very persistent and very mobile (vPvM); ECHA’s opinion still needs the approval of the European Commission before it becomes legally binding in the EU.
Under another regulation called REACH (Registration, Evaluation, Authorisation and Restriction of Chemicals), ECHA is currently considering a sweeping restriction of PFAS that would ultimately ban certain f-gas refrigerants and TFA, with a possible enactment of regulations in 2028.
In defending the use of TFA-producing refrigerants, the fluorochemical Industry has pointed to the UN Environment Programme (UNEP) and its 2022 Environmental Effects Assessment Panel (EEAP) report. The report said 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.”
