Lower toxicity of HFPO-DA compared to its predecessor PFOA to the earthworm Eisenia fetida: Evidence from oxidative stress and transcriptomic analysis.

Hexafluoropropylene oxide dimer acid (HFPO-DA), an emerging perfluoroalkyl substance (PFAS) that is replacing traditional PFASs, has a wide range of industrial applications and has been detected globally in the environment. However, it remains unclear whether HFPO-DA, is genuinely less toxic than perfluorooctanoic acid (PFOA) in terms of soil environmental hazards. Therefore, this study aimed to compare differences in toxicity between PFOA and its substitute, HFPO-DA, in a common species of earthworm, Eisenia fetida. Our findings revealed that both HFPO-DA and PFOA caused oxidative damage, apoptosis, reproductive disorders, and neurotoxicity in E. fetida at a concentration of 0.2 mg/kg following exposure for 28 d. Specifically, at the molecular level, PFOA resulted in a significant decline in total antioxidant capacity and lipid peroxidation, whereas HFPO-DA did not have the same effect. The Integrated Biomarker Response (IBR) index, based on the indicators studied, showed that HFPO-DA exhibited lower toxicity than PFOA. The transcriptomic results suggest that HFPO-DA can induce neurotoxicity, similar to PFOA; however, the specific mechanisms differ. Although HFPO-DA appears to be less toxic than PFOA to E. fetida, its potential hazards at the transcriptional level, affecting different pathways, require further investigation. This study provided new insights into the safety of HFPO-DA as a novel substitute for PFOA.