Mass spectrometry-based metabolomics investigation of a ubiquitous tire rubber-derived quinone

N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6-PPD) is a globally ubiquitous tire rubber antioxidant. Its quinone product, 6PPD-quinone, has been found to be highly toxic and can cause acute mortality of coho salmon in Pacific Northwest before they spawn in freshwater streams, a phenomenon called “Urban runoff mortality syndrome”. Recent scientific reports indicates that this emerging pollutant is pervasive in different environmental media, including urban road runoff and watersheds, dust, and fine particulate matters, which are closely related to human activities. However, there is the paucity of research on its biotoxicity to human health. In this proposed study, we aim to investigate possible toxicological effects of human exposure to 6PPD-quinone. Firstly, in vivo cell and in vivo mouse models will be established. Cell cytotoxicity and mouse mortality induced by 6PPD-quinone exposure will be determined, which are expected to provide initial evidence to indicate toxicity of 6PPD-quinone. Secondly, mass spectrometric methods will be developed and applied for analysis of biotransformation products of 6PPD-quinone in the samples of cells, tissues, and body fluids. The results will clarify whether 6PPD-quinone and its downstream metabolites can enter the circulatory system and accumulate in various organs (e.g., liver, kidney, spleen, and lung). Thirdly, nontargeted and targeted metabolomics approaches will be utilized for the investigation of perturbed metabolites induced by 6PPD-quinone exposure. Dysregulated metabolic pathways between control and exposed groups will be examined. Collectively, the results of this proposal may provide new insights into 6PPD-quinone induced toxicity at the cellular and molecular levels.