The Xenometabolome of Early-Life Stage Salmonids Exposed to 6PPD-Quinone

N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine-quinone (6PPD-Q) is a
ubiquitous transformation product (TP) derived from the rubber tire
antioxidant N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) and is acutely
toxic to certain species of Salmonidae. Not all salmonids
are sensitive to acute lethality caused by 6PPD-Q, with 6PPD-Q potency
varying by several orders of magnitude among teleosts. The main driver(s)
of species sensitivity differences is (are) a pressing question, with
one area of interest examining whether differences in teleosts’
ability to biotransform and detoxify 6PPD-Q could be a key factor.
This study utilized liquid-chromatography high-resolution mass spectrometry
(LC-HRMS) to assess biotransformation and metabolome-wide effects
of 6PPD-Q on early life stage salmonids, including two sensitive species,
rainbow trout (Oncorhynchus mykiss)
and lake trout (Salvelinus namaycush), and one tolerant species, brown trout (Salmo trutta). Three phase I TPs and seven phase II TPs were detected, with differences
in peak area ratios revealing that brown trout had the greatest ability
to conjugate phase I TPs. Monohydroxylated TPs were verified using
codeveloped analytical standards that will be of use for future biomonitoring
and exposure assessment. Several endogenous metabolites were found
to be dysregulated in rainbow and lake trout, indicative of mitochondrial
dysfunction, altered metabolism, and disrupted membrane permeability.
Results of this study indicate a potential difference in the biotransformation
capability of 6PPD-Q among Salmonidae fish species,
detection of a unique phase I TP in sensitive Salmonidae species, and subsequent unique metabolome responses.