The Global Burden of Disease estimated that approximately 7.1 million deaths worldwide were related to air pollution in 2016. However, only a limited number of small-and middle-sized cities have air quality monitoring networks.To date, air quality in terms of particulate matter is still mainly focused on mass concentration, with limited compositional monitoring even in mega cities, despite evidence indicating differential toxicity of particulate matter. As this evidence is far from conclusive, we conducted PM2.5 bioaccessibility studies of potentially harmful elements (PHE) in a medium-sized city, Londrina-Brazil. The data was interpreted in terms of source apportionment, the health risk evaluation, and the bioaccessibility of inorganic contents in an artificial lysosomal fluid. The daily average concentration of PM2.5 was below the WHO guideline, however, the chemical health assessment indicated a considerable health risk. The in vitro evaluation showed different potential mobility when compared to previous studies in large-sized cities, those with 1 million inhabitants or more (Curitiba and Manaus). The new WHO guideline for PM2.5 mass concentration puts additional pressure on cities where air pollution monitoring is limited and/or neglected, because decision making is mainly revenue-and not socioeconomical-driven. Given the further emerging evidence that PM chemical composition is as, or even more, important than mass concentration levels, the research reported in the paper could pave the way for the necessary inter-and intra-city collaborations that are needed to address this global health challenge.