Assessment of human health risks due to environmental exposures to TFA
A recently published hazard and risk assessment reviews the mammalian toxicity of trifluoroacetic acid (TFA) and human exposure to assess the margin of exposures (MoE) (see note 1). The publication is particularly timely, due to its relevance to the public consultation for the PFAS restriction proposal. TFA administered to rats did not induce adverse effects in an extended one-generation study and a developmental toxicity study or induce genotoxic responses.
The review summarises the available mammalian toxicity data on trifluoroacetate and integrates this information with potential human exposures to trifluoroacetate based on the measured concentrations of TFA in water and food using the margin of exposure methodology. The paper also explains that the potential of TFA to induce acute toxicity is very low and that the liver can be considered as the target organ, with mild hypertrophy, after repeated oral administration of TFA. However, the effects of TFA on the liver are generally mild as judged by the small changes in “liver enzymes” and the minimal to slight liver hypertrophy seen even at daily doses > 1000 mg/kg body weight in the 90-day oral study. Effects of TFA on the liver seem to be mediated by peroxisome proliferation, which is a mode of action not considered relevant to humans, as human liver, in contrast to rodents, does not respond to the proliferative effects of peroxisome proliferator-activated receptor α-agonists.
The paper considers that a highly conservative approach is applied by UBA regarding the presence of contaminants in drinking water in Germany. The MoEs regarding potential exposures of the general population to TFA from drinking water are very large and orders of magnitude above the required MoE > 100 even when using the highest measured concentrations of TFA in surface water as a surrogate for drinking water levels. Therefore, it does not indicate health risks. Drinking water, based on the highest concentration (4.8 μg TFA/L) detected in environmental water samples taken from 2014 to 2022, as reported in the review paper, results in a 62,500 margin of exposure compared to the No Observed Adverse Effect Level (NOAEL) of 10 mg/kg bw/day in rats, identified in the review paper as the applicable NOAEL.
The forecast generation of TFA from the use of HFO-1234yf in Europe as been published and can be compared to the reported TFA concentrations in environmental water samples, see note 2.
Explanatory Notes:
- Margin of exposure (MOE) is the ratio of no-observed-adverse-effect level (NOAEL) obtained from animal toxicology studies to the predicted or estimated human exposure level or dose. It is commonly used in human health risk assessment (e.g. assessing the safety of a a food impurity).
- A simulation study from 2012 by Henne et al. for the complete conversion of mobile air conditioning in cars in Europe from HFC-134a to HFO-1234yf, which yields 100% of TFA on degradation in the atmosphere, calculated, based on a high emissions scenario, concentrations of TFA in precipitation averaging 0.6 μg/L to 0.8 μg/L with peaks of 2 μg/L in Southern Germany.
References
Dekant, W., Dekant, R. Mammalian toxicity of trifluoroacetate and assessment of human health risks due to environmental exposures. Arch Toxicol 97, 1069–1077 (2023). https://doi.org/10.1007/s00204-023-03454-y
Henne, S.; Shallcross, D. E.; Reimann, S.; Xiao, P.; Brunner, D.;O’Doherty, S.; Buchmann, B., Future emissions and atmospheric fate of HFC-1234yf from mobile air conditioners in Europe, Environmental Science and Technology, 2012, 46, 1650−1658, https://doi.org/10.1021/es2034608