Toxicity differences between HFPO-TA and PFOA, and combination with PP-MPs: evidence against HFPO-TA as a safe PFOA alternative.

Perfluorooctanoic acid (PFOA) has been banned worldwide due to its high environmental persistence and biological toxicity, and hexafluoropropylene oxide trimer acid (HFPO-TA) has become the most widely used alternative. However, the safety of HFPO-TA and its combined toxic effects with polypropylene microplastics (PP-MPs) remain unclear, posing challenges for soil pollution risk management. This study for the first time compared the toxicity of HFPO-TA and PFOA to Eisenia fetida under the same experimental conditions, and investigated the effects of environmentally relevant concentrations of PP-MPs on their toxicity, and the underlying mechanisms. Results demonstrated that HFPO-TA suppressed superoxide dismutase and glutathione S-transferase to trigger severe lipid peroxidation and DNA damage, while PFOA activated superoxide dismutase and glutathione S-transferase yet still caused DNA injury. HFPO-TA/PFOA alone and with PP-MPs exert adverse effects on genes related to reproduction, growth, and immunity. The integrated biomarker response analysis revealed that HFPO-TA exhibited higher comprehensive toxicity than PFOA. Notably, PFOA + PP-MPs exhibit synergistic toxicity, while HFPO-TA + PP-MPs exhibit antagonistic toxicity, possibly due to differing binding affinities. Both HFPO-TA and PFOA altered the shape of intestinal cell nuclei, PP-MPs exacerbated physical damage. Transcriptome analysis revealed that HFPO-TA targeted immune and growth pathways, PFOA affected transport/metabolism, and the PP-MPs complex induced inflammatory responses by regulating immune pathways. The results indicate that HFPO-TA may not be a safe alternative to PFOA, and provides scientific evidence for the soil environmental control policies of PFAS alternatives and the risk prevention of combined pollution by microplastics and organic pollutants.