The growing threat of atmospheric environmental issues, specifically the rise of particulate matter (PM) pollution, poses a significant risk to human health. Atmospheric fine particulate matter, commonly called PM2.5, has been identified as an important contributor to the global burden of disease (Butt et al., 2017; Southerland et al., 2022). Numerous epidemiological studies have confirmed the association of PM2.5 with morbidity and mortality from cardiovascular and respiratory diseases (Alexeeff et al., 2021; Vodonos et al., 2018). Likewise, diabetes (Bowe et al., 2018; Li et al., 2023) and preterm neonatal birth (Malley et al., 2017; Ren et al., 2023) have also been linked to PM2.5 pollution.

The health risks of PM2.5 have been shown to arise from its complex and diverse chemical composition (Rönkkö et al., 2018; Zhou et al., 2022). The sources, regions, and seasons of sample collection may influence the composition of PM2.5 (Park et al., 2018; Rönkkö et al., 2021; Song et al., 2020), and thus toxic effects attributed to PM2.5 may vary significantly (Chen et al., 2020; Longhin et al., 2020). Different components of PM2.5 may induce diverse toxicological responses. For instances, transition metals have a strong inhibitory effect on cell viability (Jin et al., 2019; Zhang et al., 2016). Water-soluble ions (WSIs, SO42− and NH4+) are significantly associated with intracellular reactive oxygen species (ROS) production (Zhang et al., 2015). Generally, the PM comprises two components: water-soluble (WS) and water-insoluble (WIS) fractions. The WS species mainly contains water-soluble ions and organic acids, while the WIS component mainly contains calcium carbonate, kaolinite and some organic carbon (Liu et al., 2020a). When PM2.5 enters the human lungs and reaches the alveoli, dissolution separates WS-PM2.5 and WIS-PM2.5. Each chemical species has the potential to interact with human cells. WS-PM2.5 is more likely to enter cells and cause early adverse responses rapidly (Huang et al., 2003), inducing oxidative stress and inflammatory injury (Cachon et al., 2014; Gualtieri et al., 2010; Lin et al., 2022). WIS-PM2.5 causes physical damage to cell membranes when absorbed by cells through active processes and plays an important role in inflammatory response as a carrier of the WS component (Jalava et al., 2008; Qi et al., 2019; Zou et al., 2016). These mechanisms lead to reduced cell viability and may cause impairment of lung function (Deng et al., 2013; Zhang et al., 2021). Therefore, related to these components, detailed knowledge about the variability in cytotoxicity of PM2.5 from different places and seasons is critical in understanding its toxicological effects and mechanisms.

To clarify the toxicological effects of the chemical compositions relating to solubility, this study collected and analyzed PM2.5 from different functional areas (urban and industrial sites) of a megacity covering different seasons. Besides various Total-PM2.5, the toxicity of WS-PM2.5 and WIS-PM2.5 were also compared by in vitro human lung cell exposure tests. These results will help recognizing and controlling the toxicity and health risks of PM2.5 pollution.