Environmental toxicity of tire wear and latex particle leachates in zebrafish embryos: Oxidative stress and ferroptosis as key mechanisms.

Microrubber, a subset of microplastics, has raised global concerns due to its persistence and ecological risks in aquatic systems. This study systematically compared the toxicity of leachates (0, 0.5, 2.5, 5, 7.5, and 10 g/L) from tire wear particles (TWP) and latex particles (LAP) in zebrafish embryos for 5 days, integrating physiological endpoints, oxidative stress biomarkers, and transcriptomic profiling. LAP leachate exhibited significantly higher toxicity than TWP, causing increased mortality (100 % vs. 56.3 %), delayed hatching (0 % vs. 35.4 %), and severe malformations (e.g., tail and spine curvature). Chemical analyses identified elevated levels of heavy metals and biologically active organic compounds in LAP leachate, including higher zinc concentrations and benzothiazole derivatives, likely contributing to its greater toxicity. Oxidative stress markers revealed that LAP exposure induced a 1.46-fold increase in malondialdehyde (MDA) and suppressed glutathione S-transferase (GST) activity (31.6 % reduction), indicating impaired detoxification. Transcriptomics identified ferroptosis as a central putative toxicity pathway: LAP exposure was associated with dysregulated iron metabolism genes (mt2↑, fthl31↑, slc40a1↓), and an exacerbation of lipid peroxidation, whereas TWP exposure was linked to adaptive responses via cyp1a and gstt1b upregulation. Functional rescue experiments using ferrostatin-1 further supported the involvement of ferroptosis, showing consistent but non-significant trends of physiological mitigation. These findings highlight distinct mechanistic pathways: LAP exposure correlated with pathways consistent with iron dyshomeostasis-driven ferroptosis, while TWP exposure appeared to induce phase I/II detoxification, providing molecular insights into microrubber toxicity. The study underscores the urgent need for source-specific risk assessments and regulatory measures to mitigate microrubber pollution in aquatic ecosystems.