There is a new acid in our rain - should we be worried?

Scientists and regulators are divided on the threat posed by the increase in the level of a chemical substance called TFA.

Whenever rain or snow falls from the sky, a man-made chemical called trifluoroacetic acid (TFA) falls with it. All over the world, this chemical appeared in lakes and rivers; bottled water and beer; cereals and animal liver; and even in human blood and urine. And wherever researchers measure changes in TFA levels, they find that concentrations are increasing.

Over the past four decades, TFA levels have increased five to ten times in the leaves and needles of tree species in Germany. The researchers also documented an increase in the level of TFA in Canadian Arctic ice cores and in groundwater in Denmark.

TFA accumulates partly because natural processes cannot destroy its strong carbon-fluorine bonds. According to some definitions, TFA is the smallest example of per- and polyfluoroalkyl substances (PFAS), which persist for so long that scientists call them eternal chemicals (see "TFA: controversial molecule" and "Rising levels of TFA").

Some PFAS are already associated with a higher risk of harm to health and are banned internationally. Many countries are limiting the levels of certain PFAS in drinking water and are embarking on expensive purification operations.

But the health consequences of TFA are less obvious. Several existing animal studies show that current levels are thousands of times lower than those that have been shown to have biological effects. The United Nations Environment Programme (UNEP), which has been assessing the risks of TFA since 1998, says that it believes that the chemical represents the minimum risk at the moment and at least until 2100, although UN Member States last year asked it to review its assessment.

Nevertheless, some countries have already begun to suppress the TFA. And in June 2024, two federal agencies in Germany appealed to the European Chemicals Agency (ECHA) to label TFA as a reproductive toxin and a very persistent and very mobile substance. ECHA opened this petition for public comments, which closes on July 25.

In October 2024, concerned European environmental scientists said that an increase in the level of TFA could cause irreversible harm, calling the chemical a threat to "planetary boundaries". They support a large-scale ban on all PFAS considered by ECHA, which covers TFA.

But other scientists say that TFA should not be taken into account in the definition of PFAS, partly because it does not accumulate in humans and animals, as other PFAS do. The U.S. Environmental Protection Agency, for example, does not currently consider TFA PFAS.

The stakes are high because TFA regulation can have a far-reaching impact on powerful industries such as the refrigeration, agrochemical and pharmaceutical industries.

Here Nature explains the struggle that is brewing because of this small but contradictory molecule.

Simple molecule, complex origin

TFA enters the environment in different ways. It is used in academic research, for example, to prepare peptides for biological research, says Reza Gadiri, a chemist at the Scripps Research Institute in La Jolla, California. However, in a broader sense, the agrochemical, pharmaceutical and fine chemical industries use TFA as an ingredient to produce larger fluorine-containing molecules, and it can escape from industrial facilities.

In Germany, for example, interest in TFA was aroused in 2016 after researchers from the German Water Center (TZW) in Karlsruhe discovered a high level of chemical in the river and traced it to the chemical plant.

Industry users have made a large-scale effort called the Alternative Fluorocarbon Environmental Acceptability Study (AFEAS) to assess the environmental impact of F-gases that have been proposed as substitutes. It was soon discovered that some of them, including the widely used HFC-134a, were decaying into TFAs in the lower layer of the Earth's atmosphere.

Concerned that the replacement of F-gas would lead to the introduction of a foreign substance on the planet, the researchers began to intensively study TFA. Suddenly, they discovered that TFA already exists in rains, springs and rivers at noticeable levels, which suggests that there are other sources. Indeed, a later analysis of ice cores from the Arctic shows that TFA was deposited there with snow back in 19694.

Absent TFA

This marked the beginning of the search for other predecessors of TFA in the 1990s. Surprisingly, they included anesthetics that have been used since the 1950s and that are exhaled or exhaled into the atmosphere.

A turn in history appeared in 2002, when researchers funded by AFEAS measured significant TFA in the Atlantic and Southern Oceans. In 2005, an international team of researchers discovered similar levels of TFA in 22 locations in the Atlantic, North and Pacific Oceans. They extrapolated that the oceans contained a huge amount of TFA - from 60 to 200 million tons.

It was too much TFA to explain by known artificial sources. Thus, the authors of both studies suggested that TFA could be a natural salt in the oceans.

Some industrial companies use this theory to argue that any anthropogenic TFA is washed into the oceans and increases a large amount of natural TFA there by inconspicuous fractions. Groups of scientists convened by UNEP have repeatedly relied on this argument when they have concluded that TFA poses minimal risks at current environmental levels.

But many scientists do not agree that an inexplicable large amount of TFA in the oceans must mean that it is natural. Measurements from several places should not extrapolate to entire oceans, says Cora Young, an environmental chemist at York University in Toronto, Canada, whose team documented an increase in TFA levels in Arctic ice cores (see "TFA in ice cores").

And no one reported on the plausible mechanism of TFA formation naturally, says Scott Mabery, an environmental chemist from the University of Toronto, who identified the predecessors of TFA.

David O'Hagan, a fluorine chemist at the University of St. Andrews, UK, who studies natural fluorinated compounds, says he is still "still not sure" whether TFA can occur naturally. Several microorganisms do create fluorinated molecules, but since they have only one fluorine atom, not three, O'Hagan does not think that microbial processes will create TFA. He adds that scientists have not yet identified possible geological mechanisms.

New data confirm long-standing conclusions that oceans may contain a large amount of TFA. Last year, the German Environment Agency published measurements of TFA levels from 31 locations in the Atlantic Ocean, which are higher than those reported in 2005 (however, it is still too early to say whether TFA is growing in the ocean).

But in the end, it doesn't matter if there is a natural TFA in the oceans, says Finnian Freeling, an analytical chemist at TZW, who conducted both the Atlantic Ocean and German tree research. A sharp increase in the level of TFA on land is important. "These sharp increases must come from anthropogenic activities," he says.

Even if some TFAs turn out to be natural, it doesn't make it safe and doesn't make it safe to add more, says Mark Hanson, an ecotoxicologist at the University of Manitoba in Winnipeg, Canada, who works for the current UNEP group.

Researchers, including Shira Judan, an environmental chemist at the University of Alberta in Edmonton, Canada, suggest that TFA emissions from sources other than F-gases were underestimated.

These researchers are investigating how much and how quickly precursors such as pesticides and pharmaceuticals are broken down into TFA. "If we are going to make any decisions to limit emissions, we need to know where it comes from," says Judan.

Is TFA harmful?

In the 1990s, AFEAS researchers concluded that TFA was not acutely toxic, referring to earlier studies that fed or injected TFA to mice and rats. It took a huge amount to kill animals, and according to this metric, TFA turned out to be "about as toxic as table salt," says Thomas Cahill, an environmental toxicologist at Arizona State University in Tempe.

The molecular structure of TFA differs from the molecular structure of well-pollutants of PFAS. The typical structure of molecules associated with harm to health has a hydrophilic head and a long hydrophobic tail wrapped in fluorine atoms. TFA has only a tail plug, with one carbon atom carrying fluorine.

For this reason, some scientists believe that TFA should not even be considered PFAS. Because it is so small, TFA is highly soluble in water, which allows mammals to easily excrete it. In 1976, to test whether TFA is a harmful metabolite of halotan, researchers injected TFA to two volunteers and restored all this in the urine within three days. Many scientists believe that TFA does not accumulate in organs and tissues, but instead behaves like salt. "I see it as a chloride," Mabery says.

However, TFA levels can still rise in humans because the molecule is constantly consumed through food and water, and the levels in these sources are rising, says Freeling. After measuring TFA in human urine samples, he believes that dietary exposure is higher than many scientists assume. Cahill, who found TFA in dozens of food products, agrees.

And there is more and more evidence that TFA can have biological effects. In March, the Gadiri team reported in a preprint about the accidental discovery that TFA is a bioactive component that reduces lipid and cholesterol levels in mice. In a 1999 study, the researchers noticed that as a laboratory pollutant, TFA inhibits the proliferation of certain bone cells in Petri dishes. Gadiri emphasizes that there is no human data about the TFA; his conclusion is simply that it should not be considered harmless.

The most important are the animal data currently relied on by German agencies to convince ECHA to label TFA as a reproductive toxin.

In 2017, ECHA informed some companies that register TFA as a "high-volume" chemical (in accordance with updated European chemicals legislation) to provide more data on safety risks. This included reproductive toxicity data that AFEAS did not evaluate. Industry groups commissioned safety studies in a contract laboratory that fed rats and TFA rabbits and evaluated their offspring; animals that were given more chemical had fruits with less weight and more deformation, especially in the eyes, compared to those that gave lower doses. (The studies were not published, but the data were published together with the German petition.)

Nevertheless, these animals were given TFA at levels that are hundreds of thousands of times higher than the researchers measured in drinking water.

Although these results may not be observed in humans, studies show that a high level of TFA can be harmful to human health, says Jamie DeWitt, a toxicologist at Oregon State University in Corvallis. DeWitt plans to start a 30-day study that exposes mice to TFA through their skin, in search of effects on the immune system.

Some researchers are more concerned about the impact of TFA on plants and ecosystems. Plants absorb TFA along with water through their roots, but TFA does not leave the plant with water vapor. "He can't evaporate," Cahill says. "He's stuck."

AFEAS researchers tried to solve these problems in the 1990s by growing crops, including sunflower, wheat, corn (corn), rice and soybeans, in soil and water contaminated with TFA. Apart from inhibiting growth at high levels (svysra 1 milligram per liter), the researchers mostly found nothing.

Mabery and Hanson, as well as their employees, also studied the impact of TFA on pond ecosystems. Concentrations of up to 10 milligrams per liter for one year do not seem to have influenced organisms in these ecosystems.

But this does not mean that TFA will not harm other species of plants and animals, says David Boehringer, an environmental scientist who studies F-gases at Öko-Recherche, an environmental consulting firm in Frankfurt, Germany.

Cahill began to study the impact of TFA on specific desert plants that cannot shed TFA due to biomass loss, such as their leaves. In his unpublished experiments, the same exposure to TFA killed ten times more seedlings when it lasted 36 weeks, compared to one or two weeks.

For long-term, chronic exposure to TFA, standard ecotoxicity studies that simply check whether organisms survive are probably inadequate, says Ge Se, an ecotoxicologist from the Free University of Amsterdam. New ecotoxicity studies are needed to study processes sensitive to disorders, such as gene expression, she says.

One study showed that a high level of TFA can reduce the pH of the soil and slow down the decomposition of leaf litter, a process that replenishes nutrients in forest soils.

"We don't know what we don't know," Cahill emphasizes. He points out that CFCs were considered harmless before researchers eventually discovered that gases damage the ozone layer.

What should we do about it?

Researchers agree that there are many gaps in knowledge. Filling them out will entail the collection of more toxicological data on long-term, chronic exposures, as well as the identification and quantification of all TFA sources.

However, such studies take time, and a new and large source of TFA in the atmosphere is already flowing from vehicles on our roads. After the Kigali amendment to the 2016 Montreal Protocol on the phase-out of refrigerants, which are strong greenhouse gases, the industry began to move to a new class of F-gases called hydrofluoroolefins (HFO).

Modeling by Behringer and others shows that one of these gases, HFO-1234yf, will make the greatest contribution in the coming years, because all this can break down and form TFA within a few days.

Behringer advocates a "quick transition" from HFO-1234yf to vehicle air conditioning systems for which other refrigerants exist to give other users without good alternatives more time to phase out TFA-forming chemicals.

Currently, regulations on F-gases, such as the Montreal Protocol, do not consider the formation of TFA or other persistent products as a criterion for preventing certain gases.

To close this gap, European regulators from five countries have included both TFA and its atmospheric precursors in the proposed wholesale ban on PFAS, which is currently being evaluated by ECHA scientific committees. Regulators advocate excluding the use of HFCs and HFCs as much as possible.

Several places have taken measures against pesticides. In July, the Danish authorities announced a ban on TFA-creating pesticides, while starting in 2032, Minnesota will require users of TFA-producing pesticides to prove that their use cannot be avoided.

The Netherlands and Germany have issued recommendations on the concentration of TFA in drinking water, 2.2 micrograms per liter and 60 micrograms per liter, respectively. At the moment, the measured TFA levels in drinking water are usually an order of magnitude lower. But a separate European Union directive requires that the total concentration of PFAS in drinking water should not exceed 0.5 micrograms per liter; if the TFA is considered PFAS under these regulations, which has not yet been decided, it will lead to exceeding this limit in many places.

With such uncertainty about the impact of TFA on health and the environment, some researchers believe that broad prohibitions are premature. Mabery, for example, says that the emphasis on TFA distracts from more disturbing molecules in the PFAS group, especially those that can generate harmful reactive compounds in the human body after their intake. "I'm puzzled that the toxicological community has not moved on to a real problem," he says.

While researchers and regulators argue about what to do, TFA and its predecessors continue to penetrate rivers, lakes and the atmosphere. If there is nothing to remove it, TFA levels - and any potential problems that a chemical can cause - will simply rise; we can't wait for this, says Friling. "Time is not on your side."