Mechanisms of toxicity of the tire-wear compound N-(1,3-dimethylbutyl)-N’-phenyl-p-phenylenediamine-quinone (6PPD-quinone) in fathead minnows (Pimephales promelas)
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Date
2025
Authors
Anderson-Bain, Katherine Arianne
University of Lethbridge. Faculty of Arts and Science
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Lethbridge, Alta. : University of Lethbridge, Dept. of Biological Sciences
Abstract
N-(1,3-dimethylbutyl)-N’-phenyl-p-phenylenediamine-quinone (6PPD-quinone), is an emerging contaminant of concern (ECC) that has been recently identified as the primary cause of an acute lethality event observed in coho salmon (Oncorhynchus kisutch), termed Urban Runoff Mortality Syndrome (URMS). Given the widespread occurrence of 6PPD-quinone, there is a need to identify other species of fishes that experience acute lethality and sublethal toxicity following exposure, and to characterize mechanisms of toxicity. It is not known if fathead minnows (Pimephales promelas), a native species in North America, and a model species in ecotoxicology, are sensitive to 6PPD-quinone. Aqueous exposure to 6PPD-quinone did not cause mortality or embryo malformations in fathead minnows. Fathead minnow adults showed biochemical signatures of oxidative stress in both the livers and gills, including altered glutathione metabolism and an increase in methionine sulfoxide. This result suggested that fathead minnows could be used as a model species to investigate sublethal effects of 6PPD-quinone. However, fathead minnow embryos microinjected with 6PPD-quinone experienced a suit of cardiovascular abnormalities, including abnormal heart morphology, lack of common cardinal vein development, and hemorrhaging. Fathead minnow embryos that were microinjected with 6PPD-quinone showed a strong transcriptomic response, with alterations in pathways such as vascular endothelial growth factor signalling, endothelial cell-cell adhesion, and inflammation, providing a molecular basis for the cardiotoxicities. This supports the hypothesis that toxicokinetics is a critical determinant of 6PPD-quinone toxicity. This is the first study to demonstrate that sensitivity to 6PPD-quinone can be induced under laboratory conditions in insensitive species of fishes. Overall, this study fills critical knowledge gaps underlying mechanisms of toxicity of 6PPD-quinone to fishes.
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Keywords
fathead minnows , toxicology , tires