The European Chemicals Agency (ECHA)’s Risk Assessment Committee (RAC) has concluded that trifluoroacetic acid (TFA), formed in the atmosphere by the breakdown of certain f-gases, should be classified and labelled as toxic to reproduction.
In particular, RAC adopted a German proposal to classify TFA and its salts (such as sodium trifluoroacetate) as toxic to reproduction, Category 1B with the hazard statements H360Df: “May harm the unborn child. Suspected of damaging fertility.” The opinion about reproductive harm is based on studies of the effect of TFA exposure on rabbits and rats.
The Committee also agreed with the German recommendation that TFA and its salts should be classified as persistent, mobile and toxic (PMT) and very persistent and very mobile (vPvM).
RAC’s opinion cited an acute toxicity estimate (ATE) for TFA in regard to inhalation of vapors (3mg/L) and oral consumption (500mg/kg body weight), well above current concentrations in the environment.
RAC consists of independent scientific experts nominated by EU member states and appointed by ECHA’s Management Board for renewable three-year terms. RAC’s opinion on TFA was formed per the EU’s CLP (classification, labelling and packaging) law. This regulation calls for hazardous chemicals to be properly classified and labelled on behalf of workers and consumers – what’s called harmonized classification.
RAC’s opinion was included in published minutes of meetings on June 1 and 5. While a significant step in the evaluation of TFA, it still needs the approval of the European Commission before it becomes legally binding in the EU and the European Economic Area. The Commission will be advised by the CARACAL (Competent Authorities for REACH and CLP) expert group for harmonization. On average, it takes 22 months for the Commission to adopt a CLP update after ECHA’s opinion, according to the NGO CHEM Trust.
Separately, the Commission has asked the European Food Safety Authority (EFSA) to conduct risk assessments of TFA. EFSA is currently proposing an acceptable daily intake (ADI) at 0.03mg/kg bw (body weight) and an acute reference dose per day (ARfD) of 0.6mg/kg bw (both based on sodium trifluoroacetate) and is expected to announce its conclusion this year.
“For many years, TFA received less regulatory attention than well-known PFAS such as PFOA and PFOS because it was considered comparatively less toxic. The RAC opinion calls this assumption into question.”
Swiss Center for Applied Human Toxicology
According to the UN’s Globally Harmonized System (GHS) of Classification and Labelling of Chemicals, followed by the EU, reproductive toxicity refers to “adverse effects of a chemical substance/mixture on sexual function and fertility in adult males and females, as well as developmental toxicity in the offspring.” Developmental toxicity pertains to adverse toxic effects in developing embryos or fetuses. Under GHS, Category 1B refers to presumed human reproductive toxicants, largely based on animal studies. (Category 1A refers to known human reproductive toxicants based on evidence from humans.)
One of the main sources of TFA in the environment is the 100% atmospheric oxidation of fugitive HFO-1234yf (used in car air-conditioning and commercial/industrial refrigerant blends) and to a lesser extent some other f-gases, with TFA absorbed in rainfall. TFA is also formed from the breakdown of certain pesticides and pharmaceuticals, emissions from industrial plants and other anthropogenic sources. Its persistence and mobility have led to the proliferation of TFA throughout the environment in growing concentrations, including surface and groundwater, plants, drinking water, beverages and food, and human blood serum. On top of that, TFA is extremely difficult and expensive to remove from surface water.
Because it contains a fully fluorinated carbon atom, TFA falls under the EU’s definition of a PFAS (per- and polyfluoroalkyl substance) – known as forever chemicals – as an ultrashort-chain, two-carbon version. 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.
German proposal
The German proposal regarding classification of TFA, now adopted by RAC, was submitted last year to ECHA by three German government agencies – the Federal Institute for Occupational Safety and Health (BAuA), the Federal Institute for Risk Assessment (BfR) and the Federal Environment Agency (UBA).
“With our proposal, we are creating an important foundation for reducing the release of this persistent and hazardous chemical into the environment and the associated risks,” Dr. Kerstin Heesche-Wagner, Head of the German Federal Office for Chemicals (BfC), part of the BAuA, said upon the referral of the proposal to the EU. “The harmonized classification is an important tool in hazard communication and a basis for risk management.”
The German authorities based their recommendation on studies (including one by Labcorp Laboratories in 2024) showing harm done to some rabbit fetuses. In one example, for mothers who were given 750mg/kg bw/day of sodium trifluoroacetate for 23 days, 32% of their litters included offspring with multiple folded retinas and 10.7% with fused or partially fused ribs.
BfR President Andreas Hensel pointed out that this toxicological effect “was only demonstrated in animal models at TFA concentrations significantly higher than those found in the environment. Therefore, health impairments are currently not expected from consuming water or food contaminated with TFA.” However, he added, “the new classification is an important step in preparing further measures to ensure this remains the case in the future.”
But another study at the University of Milan has shed light on how even small amounts of TFA could have a human health effect. The researchers found that as little as 1mcg/L of TFA reduced antibody production in human-relevant in vitro (outside the body) tests at levels similar to those caused by perfluorooctanesulfonic acid (PFOS), which has well-documented immunotoxic effects.
Reaction to RAC opinion
Many stakeholders commented on the significance of RAC’s TFA opinion.
“For many years, TFA received less regulatory attention than well-known PFAS such as PFOA and PFOS because it was considered comparatively less toxic,” said the Swiss Center for Applied Human Toxicology, in a statement. “The RAC opinion calls this assumption into question.”
“In addition to being an important update for the regulatory hazard classification of TFA as being recognized as hazardous to human health and the environment, this is one of the first substances to have a PMT and vPvM classification from ECHA based on the new CLP regulation,” said environmental chemist Hans Peter Arp, Expert Advisor at the Norwegian Geotechnical Institute and Professor at the Norwegian University of Science and Technology, in a LinkedIn post. Arp co-authored a study calling TFA a “planetary boundary threat” and sits on the management board of ECHA.
“The European Commission must now act urgently and ensure that TFA and chemicals that turn into TFA — including relevant fluorinated gases and pesticides — are addressed under the universal PFAS restriction,” said Christine Lützkendorf, Specialist for Fluorinated Greenhouse Gases at Deutsche Umwelthilfe (DUH), an NGO focused on environmental protection, in a LinkedIn post. “Every year of delay means more irreversible contamination of our water, ecosystems and bodies. The science is clear. Now politics must catch up..”
ECHA’s assessment of TFA “is crucial as classification serves as a gateway to more comprehensive regulation,” said Dirk Nuyens, Senior Subject Matter Expert for PFAS and Senior Partner, Environmental Resources Management (ERM), a London-based consultancy, in a LinkedIn statement. “We anticipate stricter water quality thresholds, the inclusion of TFA in groundwater and surface water standards, and a strategic shift toward controlling sources rather than relying solely on treatment.”
Controlling sources of TFA precursors like f-gases includes switching to natural refrigerants in applications like supermarket refrigeration and mobile air-conditioning (MAC). For example, Hanon Systems, a major South Korean provider of automotive thermal management systems, has released a report estimating TFA generated in Europe by emissions of refrigerants HFC-134a and HFO-1234yf from car cooling and heating systems and citing the use of CO2 (R744) and propane (R290) as alternative refrigerants to avoid TFA creation.
Chemical industry position
The chemical industry in Europe has been involved in lab tests of rabbits and rats that form the basis of RAC’s opinion that TFA should be classified as reproductively toxic, Category 1B. As a stakeholder, Cefic (European Chemical Industry Council) participates in RAC meetings and contributes data. With regard to RAC’s opinion on TFA, “We acknowledge RAC’s opinion, rationale and potential regulatory implications,” said Angelica Candido, Sector Manager, Cefic. “At this stage, Cefic is making no further comment.”
The “Registry of CLH (harmonized classification and labelling) intentions until outcome” provides the status of CLH proposals received by ECHA. The Registry for TFA includes a link to comments from a range of stakeholders, including Solvay, a Belgium-based chemical manufacturer that stated last year that it would stop production of TFA and its derivatives by early 2026.
In its comments, Solvay argued that the classification of TFA as reproductively toxic, Category 1B was “unjustified.” According to the company, “the observed reproductive toxicity solely noted in fetal rabbits at elevated concentrations should be reviewed in light of the new insights on the species-differences in systemic exposure and plasma protein binding.” Solvay added that classifying TFA as toxic to reproduction, Category 2 (H361d), which designates a substance as a “suspected” human reproductive toxicant, “may be more appropriate.”
Last year the Pesticide Action Network (PAN) Europe, a Brussels-based NGO focused on the pesticide-related creation of TFA, released a report – “Manufacturing Doubt: How the Industry Downplays TFA’s Toxicity – that challenged industry interpretations of TFA animal studies.
For example, an industry group attempted to question TFA-induced eye malformations by proposing a rabbit-specific mechanism tied to lactate transport disruption, said PAN Europe in its report. But these malformations occurred at TFA levels below the proposed hypothetical threshold calculated to trigger such effects, “undermining their own argument,” said the NGO.
“We acknowledge RAC’s opinion, rationale and potential regulatory implications.”
Angelica Candido, Sector Manager, Cefic
In addition to rabbits, rats have been the focus of several TFA toxicity studies. In an extended one-generation study of rats in 2021, Solvay and Bayer claimed no adverse reproductive effects from TFA exposure, noted PAN Europe in its report. However, it added, “a closer look reveals overlooked signs of harm in offspring, including reduced thyroid hormone levels, [changed] weight of reproductive organs (testes and epididymis), liver changes, blood biochemistry alterations, and sperm abnormalities, even at lower exposures.”
Peter Boelaert, External Communication Director for Solvay, responded to the PAN Europe report by saying the company “strongly rejects the claim that the company deliberately delayed or distorted the risk assessment of TFA,” adding, “It is up to national and European regulatory authorities to proceed with an appropriate classification of TFA.”
Simone Kies, Senior Communications Manager for Leverkusen, Germany-based Bayer, responding to the PAN Europe report, said, “The toxicological data and the generic risk assessment on TFA submitted to regulators do not indicate any health risk for humans or wild mammals for the label-compliant use of our products.” Bayer manufactures pesticides that break down into TFA such as flufenacet (now banned in the EU), diflufenican and fluopyram.
