Tissue-specific bioaccumulation and hepatotoxicity of 6PPD and 6PPD-Quinone in zebrafish

Tire additive 6PPD and its transformation product 6PPD-Quinone have garnered substantial attention due to their association with mass salmon mortality events. This study investigated the bioaccumulation and sublethal toxicological effects of 6PPD and 6PPD-Q using zebrafish ( Danio rerio ) as a model fish. Both 6PPD and 6PPD-Q exhibited distinct distribution and bioaccumulation potential in the fish. Specifically, 6PPD was enriched in the guts and liver, whereas 6PPD-Q was enriched in the brain, liver, and gills. Zebrafish liver exhibited strong absorption capacity for both compounds, while the eyes and gills showed selective absorption for 6PPD and 6PPD-Q, respectively. At elevated exposure concentrations, 6PPD demonstrated lower bioaccumulation potential but higher adsorption capacity. In contrast, 6PPD-Q displayed the opposite pattern. This suggested that depuration processes predominantly regulated the accumulation dynamics of these compounds. Exposure to both chemicals at concentrations ranging from environmentally relevant to high concentrations induced multi-levels of toxic responses in zebrafish. These included behavioral impairments with reduced swimming activity and histopathological damages of inflammation, fat droplets, vacuoles, and cell gap enlargement in liver tissue. Transcriptomic analysis revealed that both compounds induced pathological liver damage in zebrafish through disruption of glycolysis and gluconeogenesis pathways. Additionally, effects on P450 metabolic systems led to differential bioaccumulation patterns between the two compounds. This study provides important toxicological evidence for assessing the ecological risks of tire-derived pollutants and emphasizes the necessity of monitoring both parent compounds and their transformation products in environmental surveillance. Both 6PPD and 6PPD-Q showed distinct distribution and bioaccumulation potentials and induced multi-levels of toxic responses in zebrafish. • 6PPD and 6PPD-Q exhibited distinct distribution and bioaccumulation potentials in zebrafish. • 6PPD was enriched in guts and liver whereas 6PPD-Q was enriched in brain, liver, and gills. • Depuration predominantly regulated the accumulation dynamics of these compounds. • Exposure to both chemicals induced behavioral impairments with reduced swimming activity. • Pathological damage included inflammation, fat droplets, vacuoles, and cell gap enlargement.