## 3 Implications of WSOM to the Toxicity of Outdoor Air Particles
Although this association between aerosol WSOC (and therefore, SOA) and ROS activity has been reported for both urban and non-urban locations, specific local sources and/or seasons might also contribute to the oxidative activity of water-soluble OA. For example, in an urban-traffic location, in the city of Thessaloniki, a significant correlation between WSOC and DTT activity was obtained for wintertime samples, suggesting the presence of a wintertime WSOC source, other than SOA formation, which contributes to the ROS activity in winter [24]. Biomass burning emissions (a known source of water-soluble OA, particularly in cold seasons) has been highlighted as a significant contributor to the oxidative potential of aerosol WSOC in the studied location [24; 79]. In their recent review work, [PERSON] et al. [68] also highlighted that the presence of a large amount of quinones in fresh wood smoke OA could be associated with an oxidative potential response. In the metropolitan Atlanta area, [PERSON] et al. [78] also reported the important role of biomass burning to winter ROS activity of ambient water-soluble OA, whereas photochemical activity and SOA processing is likely to have a higher contribution to the summer ROS activity. [PERSON] et al. [23] also concluded that SOA was the dominant source of ROS in summer as opposed to biomass burning in winter, leading to a significant seasonal variability in the oxidative activity of aerosol WSOM. Overall, the studies published thus far on this topic have showed that the ROS activity of the water-soluble organic fraction of outdoor air particles is likely to be driven by the relative dominance of aerosol WSOC sources at different locations and/or seasons (either primary water-soluble OA, chemical aging of OA, or SOA formation). In the process of assessing which aerosol WSOM constituents contribute to the oxidative activity of this OA fraction, it has been shown that the most hydrophobic fraction of the WSOM--the so-called HULIS--is an active component generating ROS [74; 75]. According to [PERSON] and [PERSON] [74], it is assumed that HULIS contains reversible redox sites (either quinone-like or nonquinone) that serve as electron carriers to catalyze the generation of ROS. If combined with redox-active water-soluble transition metals (e.g., Cu and Fe) [81], the most hydrophobic fraction of the water-soluble OA can further enhance the production of ROS [68; 79; 82], thus suggesting the need to further clarify the interaction mechanisms between the most hydrophobic WSOM and redox-active metals and their impacts on ROS activity. Studies on the cytotoxicity and pro-inflammatory effects induced by aerosol WSOM are exceptionally limited [11; 69; 79]. Using human lung cell lines, [PERSON] et al. [69] showed that urban quasi-ultrafine PM (aerodynamic diameter \(\leq 0.2\) um), which was found to be enriched in WSOC, were capable of inducing a higher activation of antioxidant (heme oxygenase (HMOX-1) mRNA expression) and inflammatory (interleukin-8 (IL-8) mRNA expression) responses. The authors further suggested that differences in composition within different PM size-fractions (coarse (2.5-10 um), fine (0.15-2.5 um), and quasi-ultrafine) played an important role in the observed biological responses [69]. [PERSON] et al. [79] also explored the in vitro cytotoxicity of the WSOC of size-segregated PM from two urban sites (traffic and urban background) in cold and warm periods. The authors reported that the cytotoxicity of PM peaked in the 0.49-0.97 um size range, and correlated significantly with WSOC at both sites in the cold period [79]. Recently, [PERSON] et al. [11] investigated the relationship between the oxidative and pro-inflammatory potential of aerosol WSOM and their atmospheric concentrations and structural characteristics under different seasonal (autumn versus spring) and daily (day versus night) scenarios.