posted on 2023-12-04, 20:03authored byDavid Montgomery, Xiaowen Ji, Jenna Cantin, Danielle Philibert, Garrett Foster, Summer Selinger, Niteesh Jain, Justin Miller, Jenifer McIntyre, Benjamin de Jourdan, Steve Wiseman, Markus Hecker, Markus Brinkmann
N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine-quinone (6PPD-Q)
is a recently identified
contaminant that originates from the oxidation of the tire antidegradant
6PPD. 6PPD-Q is acutely toxic to select salmonids at environmentally
relevant concentrations, while other fish species display tolerance
to concentrations that surpass those measured in the environment.
The reasons for these marked differences in sensitivity are presently
unknown. The objective of this research was to explore potential toxicokinetic
drivers of species sensitivity by characterizing biliary metabolites
of 6PPD-Q in sensitive and tolerant fishes. For the first time, we
identified an O-glucuronide metabolite of 6PPD-Q
using high-resolution mass spectrometry. The semiquantified levels
of this metabolite in tolerant species or life stages, including white
sturgeon (Acipenser transmontanus), chinook salmon
(Oncorhynchus tshawytscha), westslope cutthroat trout
(Oncorhynchus clarkii lewisi), and nonfry life stages
of Atlantic salmon (Salmo salar), were greater than
those in sensitive species, including coho salmon (Oncorhynchus
kisutch), brook trout (Salvelinus fontinalis), and rainbow trout (Oncorhynchus mykiss), suggesting
that tolerant species might detoxify 6PPD-Q more effectively. Thus,
we hypothesize that differences in species sensitivity are a result
of differences in basal expression of biotransformation enzyme across
various fish species. Moreover, the semiquantification of 6PPD-Q metabolites
in bile extracted from wild-caught fish might be a useful biomarker
of exposure to 6PPD-Q, thereby being valuable to environmental monitoring
and risk assessment.