The environmental research community widely accepts trifluoroacetic acid (TFA) as the most abundant per- and polyfluoroalkyl substance (PFAS) in the environment, although the US Environmental Protection Agency does not recognize it as a PFAS. Precursors such as pesticides, pharmaceuticals, and refrigerants break down into TFA, and the molecule is also sometimes used directly as a chemical reagent. While a large-scale research effort in the 1990s established that TFA exerts minimal acute toxic effects, little is known about TFA’s long-term effects on more-sensitive biological functions.
Now new research in human endothelial cells indicates that TFA can impair blood vessel development (Environ. Sci. Technol. 2026, DOI: 10.1021/acs.est.6c06569). It can interfere with how endothelial cells produce energy, which they need to maintain and grow new blood vessels.
A team of researchers led by Yanhong Wei of Sun Yat-sen University and Xifei Yang at the Shenzhen Center for Disease Control and Prevention exposed cultures of endothelial cells to TFA at concentrations spanning 0.8–2,000 µg/L. The lowest dose of TFA—0.8 µg/L—reduced the concentrations of adenosine triphosphate (ATP) within cells by 7% compared with those in cells that were not exposed to TFA. For the most part, ATP concentrations dropped even further with higher doses of TFA: for instance, by 26% in cells exposed to 2 µg/L TFA and 45% with 200 µg/L TFA. But at 2,000 µg/L, ATP concentrations dropped only 43%.
In the human body, trifluoroacetic acid dissociates to its salt, trifluoroacetate, which can bind to a key enzyme for energy production in blood vessel cells. This binding may happen because trifluoroacetate’s molecular structure resembles that of the enzyme’s substrate, pyruvate.
Subsequent analysis led the researchers to pinpoint glycolysis as the cellular pathway that TFA disturbs. In glycolysis, glucose is converted to pyruvate, which is then reduced to lactate; the energy released in this process allows cells to create ATP. The researchers found that TFA interferes with the second step: molecular modeling showed that TFA can bind to the lactate dehydrogenase enzyme, preventing the enzyme from binding pyruvate and converting it to lactate.
Currently, no one has measured the levels of TFA in real human blood vessel tissues, Wei explained at the American Chemical Society Fall 2026 meeting in Chicago in August, where she presented this research before publication. Researchers may need to investigate how quickly TFA diffuses from blood into endothelial cells, which line the inside of blood vessels. For reference, studies that measured TFA levels in blood serum from participants in Indiana and China have found median levels around 6–8 µg/L, and one study reported exceptionally high levels of 17 µg/L in blood samples from people in a North Carolina community historically exposed to PFAS.
These new findings add to the growing number of health effects that TFA has been found to exert. In animal studies, TFA has caused eye deformations in rabbit fetuses and a lowered level of the thyroxine (T4) hormone in rats. Those findings and TFA’s growing concentrations in the environment prompted European agencies this summer to label TFA as a reproductive toxin and to lower the acceptable daily intake limit for TFA from 50 µg/kg of body weight per day down to 14 µg/kg (EFSA J., DOI: 10.2903/j.efsa.2026.10227).
