Early warning of aquatic ecological risks for trifluoromethanesulfonimide: Oxidative stress-driven adverse outcome...

The latent ecotoxicological effects of emerging contaminants (ECs) necessitate the development of early warning systems. Trifluoromethanesulfonimide (TFSI), a lithium battery electrolyte additive, has been recognized as a contaminant of emerging concern. This study established a "mechanism prediction - biological validation - threshold derivation - risk assessment" framework to enable ecological risks early warning for TFSI, with extensibility to ECs. Network toxicology predicted NFKB1 and PTGS2 as key targets of TFSI, with psoriatic arthritis (PsA) identified as a TFSI-associated disease. By reverse translation of PsA pathogenesis, we predicted adverse outcome pathways (AOPs) of TFSI based on the AOP-Wiki network and screened biomarkers for validation. Cross-species validation in zebrafish models demonstrated dysregulated expression of GCH1/NFKB1/IL34 concomitantly driving dose-dependent oxidative damage and biphasic behavioral alterations, biochemical analysis identified the brain as the target organ. A novel Hormesis model was constructed, which revealed that after correction, EC¯₁₀ and EC¯₅₀ resulted in reductions of 90.59 % and 91.37 %, respectively, compared to the traditional model. The combined threshold EC¯_10,overall was derived as 1154.48 ng/L. Risk assessments revealed potential aquatic ecological risks in multiple regions worldwide, a conclusion further supported by risk probabilities quantified through the quantitative adverse outcome pathway (qAOP) model. This work comprehensively uncovered the latent ecotoxicological effects of TFSI, offering theoretical substantiation for addressing regulatory gaps spanning from its initial environmental release to risk manifestation.