Recognition, distribution, and toxicities of novel per- and polyfluoropolyether carboxylic acids

Per- and polyfluoroalkyl substances (PFAS) possess distinct properties, such as hydrophobicity, oleophobicity, and thermal and chemical stability, resulting in their wide application in various industrial processes, including electroplating, fire protection, and textile, paper, and leather production. However, due to their propensity for high bioaccumulation, long-distance transport, resistance to degradation, and potential adverse effects on animal and human health, certain PFAS, including "legacy" perfluorooctanoic acid (PFOA), were listed in Annex A of the Stockholm Convention in 2019, leading to a global ban on their production and usage. Consequently, per- and poly-fluoropolyether carboxylic acids (PFECA), containing ether oxygen bonds in their structure, have emerged as processing-additive substitutes for PFOA in different industries. Recently, with the increasing concern, more and more PFECA have been identified and detected in various environmental matrix and human samples. Epidemiological research and toxicity experiments have also found that some PFECA have health hazards comparable to or even stronger than PFOA. In the present study, we focus on the classification, environmental impacts, and toxic hazards associated with PFECA and summarize recent research regarding non-targeted identification, environmental behavior and fate, biological/human exposure levels, toxic effects, and related molecular mechanisms. The overall aim of this review is to provide a valuable reference for environmental pollution research and biological risk assessment of PFAS alternatives, thereby supporting the regulation and reduction of PFAS alternatives in China. In terms of PFECA recognition, with the rapid development of non-targeted and targeted screening techniques, researchers have identified a series of PFECA with feature structure in various environmental matrix, such as unsaturated PFECA, chlorinated PFECA and homologues of hexafluoropropylene oxide trimer acid (HFPO-TA). However, non-targeted and targeted screening research is still in its infancy, with only 11 reports identifying dozens of PFECA, more and more novel PFECA will definitely be recognized in the future. In terms of quantitative detection, PFECA has been detected in various environmental matrix (including surface water, soil, atmosphere), organisms (including plants, fish and frogs) and even human samples (serum, urine and milk). Among them, there are many reports on water bodies and population samples. Among the existing reports, the PFECA levels in water and human samples accounts for a relatively large proportion. It is worth noting that the detection rate of HFPO-TA homologues in the serum of residents living around fluoride factories exceeds 90%, and the concentration of HFPO-TA ranking the fourth among all the detected PFAS. In terms of the toxic effects, it has been confirmed through several animal exposure experiments that PFECA, such as HFPO-TA, hexafluoropropylene oxide tetramer acids (HFPO-TeA) and perfluoro (3,5,7,9-tetraoxadecanoic) acid (PFO4DA), can cause liver damage, decreased sex hormone levels, metabolic disorders, and developmental abnormalities by interfering with PPAR pathways and metabolic pathways. In addition to in vivo experiments, we also noticed that researchers have carried out in-depth in vitro and in sillico studies on the interaction between PFECA and nuclear receptors or transporters in order to provide a possible explanation for the bioaccumulation and toxic effects of PFECA. Our paper also discusses the challenges, potential risks, and future research directions concerning the application of PFECA. For example, in the development and application of green alternatives, several problems, including unclear information on their structure, physical and chemical properties, and immature quantitative analysis methods, should be addressed to reduce the potential environmental and health hazards caused by the new PFECA at the source. At the same time, developing efficient degradation methods in contaminant treatment is also one of the future research directions. It is also worth paying more attention to combine regulatory, scientific research, and market aspects to provide guarantees for the rational use of novel PFECA.