A large and growing number of studies have reported the rapid proliferation in the environment of trifluoroacetic acid (TFA), a by-product of certain f-gases in the atmosphere (notably HFO-1234yf) as well as the breakdown of certain pharmaceuticals, pesticides and other chemicals.

This begs the question: how harmful is TFA to human beings?

TFA is an ultrashort-chain (two-carbon) example of PFAS (per- and polyfluoroalkyl substances), a category of chemical pollutants, according to the scientifically accepted definition of PFAS. Similarly structured, longer-chain PFAS, like eight-carbon PFOA (perfluorooctanoic acid), are bioaccumulative in organs like the liver and cancer-causing. However, TFA is not considered toxic by the chemical industry, which cites certain studies to back its claims.

But some researchers believe that TFA, which continues to accumulate in water supplies and food, could pose a threat to human health over time. That is particularly because TFA has been found in human blood, usually at levels higher than that of longer-chain PFAS. In a 2024 study that reviewed research done between 1990 and 2024 on TFA and other ultrashort-chain PFAS, 17 detections of TFA in blood were cited, with a median concentration of 9ng/mL.

In the US, Emory University researchers in 2023 reported TFA as the predominant perfluoroalkyl acid (PFAA) in blood serum samples, with a detection frequency of 74% and a median concentration of 6.0 ng/mL. An earlier study in China found TFA in human serum samples with median concentrations of 8.46 ng/mL Older persons showed a higher concentration of TFA than younger persons.

The Emory University study noted that protein binding affinity – TFA was reported to bind to proteinaceous fractions and lipids in biota – “could be a driving force behind the bioaccumulation mechanism of the ultrashort- and short-chain PFAAs in human blood.”

Germany’s environmental authorities have suggested toxic effects from TFA. For example, the German Federal Office for Chemicals (Bundesstelle für Chemikalien or BfC) last year submitted to the European Chemical Agency (ECHA), a proposal linking reproductive toxicity to TFA and its inorganic salts. Based on TFA studies showing liver dysfunction in rats, the German Environment Agency (Umweltbundesamt or UBA) has set a human health-based guideline value of 60mcg/L for TFA in drinking water and a “precautionary measure” of 10mcg/L.  The Netherlands and Denmark also have precautionary thresholds for TFA in drinking water – 2.2mcg/L and 9mcg/L, respectively.

In 2014, Iranian researchers reviewed earlier studies showing that oxidation of the anaesthetic halothane leads to production of TFA, which acts on liver proteins to produce liver-harming trifluoroacetylated components. Halothane is no longer used as an anaesthetic in developed countries.

Meanwhile a recent European study makes the case that TFA meets the criteria of a “planetary boundary threat” because of increasing planetary-scale exposure, where “potential irreversible disruptive impacts on vital earth system processes could occur.”

To gain further insight into the potential toxicity of TFA, NaturalRefrigerants.com spoke to Shira Joudan, Assistant Professor of Analytical Environmental Chemistry at the University of Alberta in Edmonton, Canada. Her research group studies the environmental fate of PFAS, halogenated contaminants, and other organic chemicals in the environment, including TFA. She was part of a study debunking the claim that TFA is found naturally in the environment, recently published a paper exploring the degradation of the drug fluoxetine (Prozac) into TFA, and another looking at the presence of TFA in the atmosphere. She is currently studying how the breakdown of pesticides contributes to environmental TFA and how certain fluoropolymers can leach TFA into aqueous systems.

The following interview was edited for brevity and clarity.

NaturalRefrigerants.com: We know that TFA is persistent, accumulating and ubiquitous in the environment, it’s absorbed by people through drinking water, food and air, and turns up in blood serum. Do you agree that it’s a planetary boundary threat?

Shira Joudan: If we are emitting a chemical into the environment – whether that’s directly or via many other chemicals that are useful but then form it – and it has no way to break down and it keeps increasing, that’s concerning. Because the idea is that we may reach a concentration that has major harmful effect, and then we can’t deal with it.

The chemical industry and some studies contend that TFA is not bioaccumulative and therefore does not harm humans at current environmental levels and is not a threat in the future. What is your view on the degree of toxicity represented by TFA, given that it’s present in the blood?

It’s one thing to say a chemical accumulates in the body. That’s concerning because it can provide a higher exposure concentration compared to what’s in the environment. TFA is not really like that, but it has a high concentration in the body because it’s also high in the environment. Ultimately, the concern is we don’t want potentially harmful chemicals in high concentrations in our body. To me, if you make a measurement, you have the answer. So the question about whether TFA bioaccumulates or builds up in your organs is sort of irrelevant if you’ve made a measurement of TFA and you know its concentration.

You mean the concentration of TFA in the blood?

 Yes.  Let’s say that the TFA concentration in blood is exactly the same as what’s in the drinking water. But what’s in the drinking water is 100 times higher than some other contaminant or PFAS, then that’s bad.

Of course, if TFA is in the blood, then it travels throughout the body and through all of the organs, even crossing the placenta in pregnant women. But critics would argue that it is not getting into, say, the liver like PFOA or PFOS.

I don’t think that’s true. It’s not going to be 100 times higher, let’s say, in your liver, like the longer PFAS building up there. It’s more like TFA is in a balance with drinking water or your blood or your liver, whereas the longer chain PFAS like PFOS will be highest in the liver, but lower in the drinking water and in the blood.

So you’re saying there still might be some TFA that gets into the organs because it’s in the  bloodstream and has every opportunity to infiltrate the liver and every other organ.

 Exactly. What people usually are trying to say about TFA is that it doesn’t build up [in biota], it doesn’t accumulate [in organs]. That means they’re saying the ratio is not higher. For example, in [the Emory University study of TFA in Indiana households] they measured it in urine and they measured it in blood. So the urine means it’s leaving the body, but if it’s a high concentration in the blood, it’s still there. And that’s not a question of whether it’s accumulating [in organs]. It’s just there. If that’s the blood concentration every day of this person’s life, does it matter if it’s accumulating or not [in organs]?

And given the fact that TFA continues to be building up in the environment, the level in the blood could build up as well.

Exactly

So, ultimately, even if TFA is not bioaccumulative in the sense that PFOA is, it’s still concerning from a health impact.

We’re still being exposed to it, and it’s still in our bodies. As context, people are used to contaminants that do bioaccumulate and build up in our bodies, such as those described in the Stockholm Convention on Persistent Organic Pollutants. And so the idea of being exposed to something every day – and maybe it’s building up in the environment, so we’re exposed more – that’s not what people think about all the time. And that sort of paradigm is hard for people to change, I think, even in my field.

 TFA is not at this point widely considered to be harmful to human health the way PFOA and PFOS are, but the German Federal Office for Chemicals has proposed to the EU linking TFA to reproductive toxicity. That link was found in rabbit studies.

I’m not a toxicologist, but I do follow the literature, and it seems that historically people thought TFA doesn’t behave like a traditional contaminant that accumulates in the body, so it was not prioritized for toxicological studies. But now we know it is in the body, so it doesn’t matter if it accumulates or not. I think that’s why there’s more of a push for research now.  We know that it’s not going to be an acute, short term exposure. It’s going to be one of these long term exposures at the lower concentrations that need to be studied in toxicity studies.

Over the past 30 years, toxicologists have learned more about how to do those studies of chronic low dose exposure, and so that needs to be done for TFA. Way back, they did some TFA tests, but they were not like what we would do now, based on everything that’s been learned about related chemicals.

I would prefer that TFA is harmless, given how much of it is out there.

For me, anything that doesn’t degrade and we keep putting more and more of that into the environment – it’s not a positive feeling if we don’t have all the information. It’s unsettling.

Some European countries – Germany, Denmark and The Netherlands – have started to establish drinking water limits for TFA, so there is already a sense that it is hazardous. And then there’s the precautionary principle – if you don’t look at it and it truly is harmful, then it’s a much worse problem.

Yes, that’s what I think, because that’s the reality of our exposure [that we should consider the precautionary principle].

And the chemical industry does not exactly have a good track record when it comes to PFAS and other chemical pollutants.

Another thing about TFA that’s different than most of the other chemicals we think of as PFAS, is that it doesn’t come from just one product; it forms in the environment from other things. There are a lot of different industries that are involved and not one is entirely responsible. It seems that a lot of the environmental TFA comes from refrigerants, but that’s not all of it. Some of it’s from burning fluoropolymers. Some of my work is trying to figure out how much TFA comes from pharmaceuticals and pesticides, but right now we don’t know.

 I think when it’s not one group’s responsibility, that makes it easy to push it off.  The refrigerant people were saying, “It’s naturally occurring, and we’re polluting just a small percentage.” And then when we tried to debunk them on that claim – that there is no evidence for it – they said, ‘Well, maybe it’s coming from all the pesticides.” Being able to blame other people for TFA is very different than, say, PFOA, where someone made that and now it’s in the environment.

Ultimately, the concern is we don’t want potentially harmful chemicals in high concentrations in our body.

Shira Joudan, Assistant Professor of Analytical Environmental Chemistry, the University of Alberta