Detection of 6-PPD and 6-PPDQ in airborne particulates and assessment of their toxicity in lung cells

Chemosphere, Journal Year: 2024, Volume and Issue: 364, P. 143205 - 143205

Published: Aug. 28, 2024

Language: Английский

Structure and Toxicity Characterization of Alkyl Hydroxylated Metabolites of 6PPD-Q

Environmental Science & Technology, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

Distinct from other nontoxic phenyl-p-phenylenediamine (PPD) quinones, N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q) was recently discovered to be regioselectively metabolized alkyl hydroxylated metabolites (alkyl-OH-6PPD-Q) in rainbow trout. It remains unknown whether the unique alkyl-OH-6PPD-Q contributes toxicity of 6PPD-Q. To test this, we herein synthesized chemical standards isomers and investigated their metabolic formation mechanism toxicity. The predominant confirmed on C4 tertiary carbon (C4-OH-6PPD-Q). C4-OH-6PPD-Q only observed microsomal but not cytosolic fractions trout (O. mykiss) liver S9. A general cytochrome P450 (CYP450) inhibitor fluoxetine inhibited 6PPD-Q, supporting that CYP450 catalyzed hydroxylation. This well-explained compound- regio-selective C4-OH-6PPD-Q, due weak C-H bond carbon. Surprisingly, while cytotoxicity for 6PPD-Q C3-OH-6PPD-Q a coho salmon kisutch) embryo (CSE-119) cell line, no C4-OH-6PPD-Q. further confirm this under physiologically relevant conditions, fractionated formed microsome Cytotoxicity fraction In summary, study highlighted as key moiety both metabolism hydroxylation is detoxification pathway

Language: Английский

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

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 14, 2024

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

Language: Английский