Coho salmon are a highly sensitive species highlighting the ecological degradation of urban watersheds caused by stormwater runoff. 6PPD-quinone is a newly discovered chemical sourced from tires that is acutely toxic to coho salmon at low, environmentally relevant concentrations, with a median lethal concentration (LC50) of 95 ng/L. To inform policy decisions on the management of this important emerging contaminant, toxicology testing is urgently needed to characterize the toxic mode of action in salmonids exposed to 6PPD-quinone and to determine lethal and sublethal effects in species of high conservation concern, such as coho salmon (Oncorhynchus kisutch), Chinook salmon (O. tshawytscha) and steelhead (O. mykiss). Building on two decades of experience investigating the toxicity and treatment of stormwater pollution, we propose to fill these knowledge gaps. We will validate our preliminary results that blood-brain barrier (BBB) disruption underlies symptom development and death in coho lethally exposed to 6PPD-quinone using fluorescent dye injection methods. We will carry out acute toxicity testing and investigate BBB disruption in Chinook and steelhead as lethal and/or sublethal effects of 6PPD-quinone exposure and explore mechanisms of BBB disruption via qPCR techniques. Our final goal is to strengthen our partnerships with Tribes by sharing our current knowledge on the toxicity of urban stormwater and 6PPD-quinone to Pacific salmon. We seek to be better informed regarding the impacts of runoff pollutants on treaty rights, tribal sovereignty, and cultural resilience, as well as create opportunities for future research collaborations to address tribal concerns.