Stable isotope-assisted mass spectrometry reveals in vivo distribution, metabolism, and excretion of tire rubber-derived 6PPD-quinone in mice

Jing Zhang, Guodong Cao, Wei Wang, Han Qiao, Yi Chen, Xiaoxiao Wang, Fuyue Wang, Wenlan Liu, Zongwei Cai*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

Abstract

6PPD-quinone (6PPD-Q) has been identified as a ubiquitous contaminant in the surrounding locality, including air particles, roadside soils, dust, and water. Recently, the prevalence of 6PPD-Q in human urine has accentuated the urgency for investigating its biological fate. To address this, we conducted a stable isotope-assisted high-resolution mass spectrometry (HRMS) assay to unveil the distribution, metabolism, excretion, and toxicokinetic properties of this contaminant in a mouse model. Mice were fed with a single dose of deuterated 6PPD-Q-d5 at human-relevant exposure levels. Results indicated that 6PPD-Q was quickly assimilated and distributed into bloodstream and main organs of mice, with the concentrations reaching peaks under 1 h following administration. Notably, 6PPD-Q was primarily distributed in the adipose tissue, marked by a significant Cmax (p < 0.05), followed by the kidney, lung, testis, liver, spleen, heart, and muscle. In addition, our measurement demonstrated that 6PPD-Q can penetrate the blood-brain barrier of mice within 0.5 h after exposure. The half-lives (t1/2) of 6PPD-Q in serum, lung, kidney, and spleen of mice were measured at 12.7 ± 0.3 h, 20.7 ± 1.4 h, 21.6 ± 5.3 h, and 20.6 ± 2.8 h, respectively. Using HRMS combined with isotope tracing techniques, two novel hydroxylated metabolites of 6PPD-Q in the mice liver were identified for the first time, which provides new insights into its rapid elimination in-vivo. Meanwhile, fecal excretion was identified as the main excretory pathway for 6PPD-Q and its hydroxylated metabolites. Collectively, our findings extend the current knowledge on the biological fate and exposure status of 6PPD-Q in a mouse model, which has the potential to be extrapolated to humans.

Original languageEnglish
Article number169291
Number of pages8
JournalScience of the Total Environment
Volume912
Early online date15 Dec 2023
DOIs
Publication statusPublished - 20 Feb 2024

Scopus Subject Areas

  • Environmental Engineering
  • Environmental Chemistry
  • Waste Management and Disposal
  • Pollution

User-Defined Keywords

  • 6PPD-quinone
  • Emerging contaminant
  • High-resolution mass spectrometry
  • Isotope labeling
  • Toxicokinetics

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