Urban stormwater runoff frequently contains the car tire transformation product 6PPD-quinone, which is highly toxic to juvenile and adult coho salmon (Onchorychus kisutch). However, it is currently unclear if embryonic stages are impacted. We addressed this by exposing developing coho salmon embryos starting at the eyed stage to three concentrations of 6PPD-quinone twice weekly until hatch. Impacts on survival and growth were assessed. Further, whole-transcriptome sequencing was performed on recently hatched alevin to address the potential mechanism of 6PPD-quinone-induced toxicity. Acute mortality was not elicited in developing coho salmon embryos at environmentally measured concentrations lethal to juveniles and adults, however, growth was inhibited. Immediately after hatching, coho salmon were sensitive to 6PPD-quinone mortality, implicating a large window of juvenile vulnerability prior to smoltification. Molecularly, 6PPD-quinone induced dose-dependent effects that implicated broad dysregulation of genomic pathways governing cell–cell contacts and endothelial permeability. These pathways are consistent with previous observations of macromolecule accumulation in the brains of coho salmon exposed to 6PPD-quinone, implicating blood–brain barrier disruption as a potential pathway for toxicity. Overall, our data suggests that developing coho salmon exposed to 6PPD-quinone are at risk for adverse health events upon hatching while indicating potential mechanism(s) of action for this highly toxic chemical.
The tire wear transformation product 6PPD-quinone (6PPDQ) has been implicated as the causative factor for broad scale mortality events for coho salmon in the Pacific Northwest. Highly variable sensitivity to 6PPDQ in closely related salmonids complicates efforts to evaluate the broader toxicological impacts to aquatic ecosystems. Our goals were to (1) validate the large range of in vivo species sensitivities reported for coho, Chinook, and sockeye salmon and (2) develop an in vitro platform for assessing 6PPDQ toxicity. In vivo studies confirmed the acute sensitivity of juvenile coho (12 h LC50 = 80.4 ng/L) and demonstrated that sockeye salmon were not vulnerable to mortality. Chinook salmon were sensitive to 6PPDQ mortality at initial concentrations >25 μg/L, ∼10-fold greater than reported environmental measurements. In vitro, the coho salmon cell line CSE-119 was acutely sensitive to 6PPDQ (metabolic EC50 = 7.9 μg/L, cytotoxicity EC50 = 6.1 μg/L). Analogous Chinook (CHSE-214) and sockeye salmon (SSE-5) cell lines were nonresponsive in both assays, and rainbow trout RTG-2 cells began showing metabolic effects at 68 μg/L (EC5). Recreation of species-specific 6PPDQ sensitivity in vitro implicates conserved modes of action in CSE-119 that could be utilized for mechanistic studies of 6PPDQ toxicity and screening of other PPD transformation products.
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