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Air quality is often assessed using particulate matter (PM) mass concentration without considering its toxicity, thus possibly leading to improper control policies or inadequate health protection. Here, we studied differences in oxidative potentials (OPs) of PM samples collected using automobile air conditioning (AC) filters from 19 global cities, as well as influences from microbial contents. Dithiothreitol (DTT) assay showed remarkable differences in the PM OPs among cities (p -values ≤ 0.001, Kruskal-Wallis test). For example, the normalized index of oxidant generation (NIOG) of PM samples in San Francisco (2.20 × 10−2, annual average PM 10 = 16 μg/m3) was found to be twice that in Beijing (1.14 × 10−2, annual average PM 10 = 135 μg/m3). Limulus amebocyte lysate (LAL) assay found that PM-borne endotoxin ranged from 12.16 EU/mg (Florianopolis, Brazil) to 2518.23 EU/mg (Chennai, India) among cities. Besides, culturing method and real-time qPCR revealed significant differences of up to ∼100-fold in both bacterial and fungal levels among 19 cities. Spearman's correlation analysis implied that PM-borne microbes such as bacteria and fungi as well as metals could strongly influence the PM OP. As an example, our results in Xi'an, China further suggest that the PM 2.5 OP evolves for a particular city over the time, which is attributable to both the urbanization and air pollution control measures. This work highlights the importance in optimizing the current air quality control measures by considering the toxicity factor and its microbial constituents. Image 1 • Ambient PM toxicity per unit of mass was shown to vary greatly with different cities across the world. • PM-borne biologicals were shown to exhibit remarkable differences across major cities, contributing to the difference of PM toxicity. • PM toxicity was shown to evolve over the time as a result of ground human activities as well as air pollution control measures. • This work highlights the need of taking into account of PM toxicity for future air pollution control efforts. [ABSTRACT FROM AUTHOR]