Inter-continental variability in the relationship of oxidative potential and cytotoxicity with PM_2.5 mass

Most fine ambient particulate matter (PM_2.5)-based epidemiological models use globalized concentration-response (CR) functions assuming that the toxicity of PM_2.5 is solely mass-dependent without considering its chemical composition. Although oxidative potential (OP) has emerged as an alternate metric of PM_2.5 toxicity, the association between PM_2.5 mass and OP on a large spatial extent has not been investigated. In this study, we evaluate this relationship using 385 PM_2.5 samples collected from 14 different sites across 4 different continents and using 5 different OP (and cytotoxicity) endpoints. Our results show that the relationship between PM_2.5 mass vs. OP (and cytotoxicity) is largely non-linear due to significant differences in the intrinsic toxicity, resulting from a spatially heterogeneous chemical composition of PM_2.5. These results emphasize the need to develop localized CR functions incorporating other measures of PM_2.5 properties (e.g., OP) to better predict the PM_2.5-attributed health burdens.