Tire-Derived Transformation Product 6PPD-Quinone Induces Mortality and Transcriptionally Disrupts Vascular Permeability Pathways in Developing Coho Salmon

Large-scale mortality of coho salmonin urbanized streamshas been linked to the stormwater pollutant 6PPD-quinone. This studyreports dysregulation of endothelial permeability pathways as a possibleprominent mechanism of toxicity. Urban stormwater runoff frequently contains the car tiretransformationproduct 6PPD-quinone, which is highly toxic to juvenile and adultcoho salmon (Onchorychus kisutch).However, it is currently unclear if embryonic stages are impacted.We addressed this by exposing developing coho salmon embryos startingat the eyed stage to three concentrations of 6PPD-quinone twice weeklyuntil hatch. Impacts on survival and growth were assessed. Further,whole-transcriptome sequencing was performed on recently hatched alevinto address the potential mechanism of 6PPD-quinone-induced toxicity.Acute mortality was not elicited in developing coho salmon embryosat environmentally measured concentrations lethal to juveniles andadults, however, growth was inhibited. Immediately after hatching,coho salmon were sensitive to 6PPD-quinone mortality, implicatinga large window of juvenile vulnerability prior to smoltification.Molecularly, 6PPD-quinone induced dose-dependent effects that implicatedbroad dysregulation of genomic pathways governing cell-cellcontacts and endothelial permeability. These pathways are consistentwith previous observations of macromolecule accumulation in the brainsof coho salmon exposed to 6PPD-quinone, implicating blood-brainbarrier disruption as a potential pathway for toxicity. Overall, ourdata suggests that developing coho salmon exposed to 6PPD-quinoneare at risk for adverse health events upon hatching while indicatingpotential mechanism(s) of action for this highly toxic chemical.