6PPD-quinone (6PPDQ), a transformation product of the tire rubber antioxidant 6PPD, is an emerging contaminant of growing concern in coastal waters, yet its immune-hepatic and behavioral effects on marine fish remain poorly understood. In this study, adult marine medaka (Oryzias melastigma) were exposed for 14 days to 0.3, 3, and 6 μg/L of 6PPDQ, concentrations reflecting levels reported in contaminated coastal environments. Survival declined in a concentration-dependent manner, reaching statistical significance at the highest concentration, while body weight and length remained unaffected. Histopathological examination revealed a concentration-dependent progression of hepatic damage, from mild cytoplasmic vacuolization at 0.3 μg/L to extensive necrosis at 6 μg/L, accompanied by significant elevations in hepatic triglyceride, total cholesterol, and ALT activity at the highest concentration. Liver transcriptomic analysis identified consistent enrichment of the PPAR signaling pathway across exposure concentrations, and qPCR validation revealed dose-dependent upregulation of apoptosis-related genes (casp3, casp8) alongside a biphasic immune response, with early pro-inflammatory cytokine induction (tnfα, il1β, cox2) at lower concentrations giving way to immune gene collapse and strong nfkb activation at 6 μg/L. Behaviorally, fish exposed to 6 μg/L showed increased light zone preference and increased social interaction zone entry frequency, alongside significantly elevated cortisol and reduced thyroid hormone (T3) levels, suggesting a link between endocrine disruption and the observed behavioral changes. Preliminary findings in unexposed F1 offspring of exposed parents revealed reduced embryo diameter and altered embryonic and larval heartbeat rates, indicating that some effects of parental 6PPDQ exposure may extend to subsequent generations. Together, these findings demonstrate that 6PPDQ produces combined hepatotoxic, immune, and behavioral-endocrine effects in marine medaka at environmentally relevant concentrations, with preliminary evidence of transgenerational consequences, underscoring an underappreciated ecological risk posed by this tire-derived contaminant in coastal ecosystems.
 

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