Supersite Project: Toxicological profiles of atmospheric aerosol

In recent years, a shift from in vivo costly and time-consuming animal studies to short term in vitro assays, supported by omics technologies, has been proposed as a model to provide reliable toxicity prediction for single chemical and relevant information to assess the hazard and risk of complex mixtures. Among omics techniques, transcriptomics is a powerful tool to assess the impact of exposure to complex mixtures. It allows the identification of the metabolic signaling and regulatory networks in cells exposed to the mixture, providing at the same time information for the mechanism of action and for predicting the final adverse outcome. The global gene modulation caused by complex mixtures, such as cigarette smoking, diesel exhaust and urban dust, have been intensively investigated, giving more insight into their effects on toxicological relevant endpoints. This approach would be useful to investigate the exposure at low concentrations of multiple chemicals in environmental media and to support the identification of key events through the pathway leading to adverse outcomes. Airborne particulate matter could be regarded as the prototypical example of the environmental complex mixtures. Within the Supersite project, we applied an integrated approach, including in vitro tests and toxicogenomics, to highlight the effects of air particulate matter on toxicological relevant endpoints and to identify the key events at molecular and cellular level. Several cell lines were used in this study. Each cell model was chosen for its ability to highlight specific key events or endpoints related to adverse outcomes. Cells were exposed to extracts of PM2.5 and PM1 samples, which had been collected in an urban background site. Results gave evidence for the modulation of genes playing a key role mainly in immune diseases and reproduction toxicity, suggesting that the pathway-based toxicity approach we used could support the prediction of risk from environmental exposures.