Oxidative potential (OP) has been proposed as a useful descriptor for the ability of particulate matter (PM) to generate reactive oxygen species (ROS) and consequently induce oxidative stress in biological systems, which has been recognized as one of the most important mechanisms responsible for PM toxicity. The dithiothreitol (DTT) assay is one of the most frequently used techniques to quantify OP because it is low-cost, easy-to-operate, and has high repeatability. With two thiol groups, DTT has been used as a surrogate of biological sulfurs that can be oxidized when exposed to ROS. Within the DTT measurement matrix, OP is defined as the DTT consumption rate. Often, the DTT consumption can be attributed to the presence of transition metals and quinones in PM as they can catalyze the oxidation of DTT through catalytic redox reactions. However, the DTT consumption by non-catalytic PM components has not been fully investigated. In addition, weak correlations between DTT consumption, ROS generation, and cellular responses have been observed in several studies, which also reveal the knowledge gaps between DTT-based OP measurements and their implication on health effects. In this review, we critically assessed the current challenges and limitations of DTT measurement, highlighted the understudied DTT consumption mechanisms, elaborated the necessity to understand both PM-bound and PM-induced ROS, and concluded with research needs to bridge the existing knowledge gaps.
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