The results presented summarise the ones obtained in the coordinated research project TOSCA (Toxicity of Particulate Matter and Molecular Markers of Risk), which extensively analysed the impact of Milan urban PM on human health. The molecular markers of exposure and effects of seasonally and sizefractionated PMs (summer and winter PM10, PM2.5) were investigated in in vitro (human lung cell lines) and in vivo (mice) systems. The results obtained by the analyses of cytotoxic, pro-inflammatory and genotoxic parameters demonstrate that the biological responses are strongly dependent upon the PM samples seasonal and dimensional variability, which ultimately reflect their chemical composition and source. In fact, summer PM10, enriched in crustal elements and endotoxins, was the most cytotoxic and pro-inflammatory fraction, while fine winter PMs induced genotoxic effects and xenobiotic metabolizing enzymes (like CYP1B1) production, likely as a consequence of the higher content in combustion derived particles reach in PAHs and heavy toxic metals. These outcomes outline the need of a detailed knowledge of the PMs physicochemical composition on a local scale, coupled with the biological hazard directly associated to PM exposure. Apparently, this is the only way allowing scientists and policy-makers to establish the proper relationships between the respirable PM quantity/quality and the health outcomes described by clinicians and epidemiologists.

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