J Hazard Mater. 2026 Jun 25;514:142781. doi: 10.1016/j.jhazmat.2026.142781. Online ahead of print.
ABSTRACT
N-(1,3-dimethylbutyl)-N’-phenyl-p-phenylenediamine quinone (6PPD-Q), a redox-active transformation product of the tire antioxidant 6PPD, has emerged as a pervasive urban contaminant. Although acute lethality (LC50 ≥ 100 μg/L) occurs above most environmental concentrations, growing evidence indicates that environmentally relevant levels (0.1-10 μg/L), which overlap with measured biological effect thresholds and can reach up to 19 μg/L in urban storm runoff, induce substantial sublethal toxicity across taxa. Using Caenorhabditis elegans as an in vivo model, this review synthesizes mechanistic evidence across multiple biological systems. At 0.1-10 μg/L, 6PPD-Q reduces neurotransmitter levels, including dopamine, glutamate, serotonin, and GABA, and promotes degeneration of dopaminergic and D-type motor neurons, resulting in behavioral impairment. Similar exposures decrease fecundity, trigger germline apoptosis, and activate ferroptosis through Fe2+ accumulation and lipid peroxidation. Additional effects include intestinal barrier dysfunction, nutrient malabsorption, oxidative stress, immune suppression, and increased pathogen susceptibility. Systemically, 6PPD-Q disrupts mitochondrial electron transport, suppresses ATP production and mitophagy, dysregulates glucose and lipid metabolism, and alters amino acid homeostasis. Importantly, exposure to 1-10 μg/L induces transgenerational effects mediated by histone methylation, with unexposed F3-F5 progeny exhibiting neurodegeneration, metabolic dysfunction, and immune suppression. By integrating these findings within a systems-level framework of molecular initiating events and adverse outcome pathways, this review identifies critical knowledge gaps and priorities for toxicity testing and environmental risk assessment of tire-derived quinones.
PMID:42391944 | DOI:10.1016/j.jhazmat.2026.142781