HTTPS://doi.org/10.1021/acs.estlett.2c00431

Mahoney, H., da Silva Junior, F. C., Roberts, C., Schultz, M., Ji, X., Alcaraz, A. J., Montgomery, D., Selinger, S., Challis, J. K., Giesy, J. P., Weber, L., Janz, D., Wiseman, S., Hecker, M., Brinkmann, M. (2022) Exposure to the Tire Rubber-Derived Contaminant 6PPD-Quinone Causes Mitochondrial Dysfunction In Vitro. Envir. Sci. Technol. Lett. 9:1265-1271. HTTPS://doi.org/10.1021/acs.estlett.2c00431

N-(1,3-Dimethylbutyl)-N?-phenyl-p-phenylenediamine-quinone (6PPD-quinone), a rubber tire oxidation product found in road runoff, is highly and acutely toxic to selected salmonids including coho salmon, brook trout, and rainbow trout but not other fish species and invertebrates studied to date. Sensitive species displayed increased ventilation and gasping, suggesting a possible impact on respiration. Here, adherent cell lines RTL-W1 and RTgill-W1 were exposed to 5–80 ?g/L 6PPD-quinone, and cytotoxicity, oxygen consumption rate (OCR), and biotransformation of 6PPD-quinone were measured to assess the ability of 6PPD-quinone to uncouple mitochondrial respiration in vitro. RTL-W1 cells were not sensitive to 6PPD-quinone, and exposure did not result in significant impacts on cytotoxicity or OCR. In contrast, RTgill-W1 cells demonstrated decreased cell viability at 80 ?g/L and a 2-fold increase in OCR at 20 ?g/L. Effects appear to be partly driven by toxicokinetic differences where incubation of RTL-W1 cells with 6PPD-quinone led to almost quantitative conversion of 6PPD-quinone into a suspected hydroxy-metabolite, which was not observed in RTgill-W1 cells. Exposure studies with primary cultures of rainbow trout gill cells indicated that 6PPD-quinone increased OCR by uncoupling the mitochondrial electron transport chain. Together, these findings suggest that 6PPD-quinone toxicity might be driven by a tissue-specific disruption of mitochondrial respiration

HTTPS://doi.org/10.1021/acs.estlett.2c00431