Suspect screening and effect evaluation for small-molecule agonists of the antioxidant response element pathway in fine particulate matter

Oxidative stress is an important mechanism by which fine particulate matter (PM2.5) generates toxicity. However, few inducers have been identified, and the combined effects of the contributing chemicals have rarely been examined. In this study, the occurrence of small-molecule agonists of the antioxidant response element (ARE) pathway was explored in 59 PM2.5 samples from urban Beijing over a one-year period via target and suspect screening analysis. In total, 31 chemicals with diverse structures and use categories were identified and quantified, among which polycyclic aromatic hydrocarbons (PAHs), pesticides, and phytochemicals were the most abundant chemical groups in terms of cumulative concentrations. PAHs and organonitrogen pesticides were also prioritized as the predominant contributors to the cumulative effect of ARE pathway activation, accounting for 55 % and 37 %, respectively. A combination of the prioritized chemicals (i.e., benzo[b]fluoranthene, benzo[k] fluoranthene, pyridaben, and acetochlor) was mixed at a fixed dosing ratio according to the measured average concentrations in samples, and synergism was revealed as the mode of mixture interaction. These findings highlight the importance of high-throughput chemical screening for identifying hazardous components in complex environmental samples, and also expand the knowledge regarding the components contributing to PM2.5-induced oxidative stress.