The aim of this work package is to evaluate biological models for standardised aerosol toxicity assessment. Currently, many different models are used for assessing toxicity following aerosol exposures however, there is no consensus as to what constitutes an optimal system, nor the most informative end-points.

The overall goal will be to mimic and quantify the exposure of aerosol inhalation in vivo using novel methods for exposing cells to aerosols, in order to find suitable model systems. Cellular responses to chemically defined aerosols will be obtained in relevant cell and tissue-based biological models of different complexities and reflecting different regions of the lungs (larger airways versus more peripheral airways and lung parenchyma) and will be compared. Their response will be characterised in terms of broad categories of toxicologically important mechanisms: oxidative stress, inflammation, and genotoxicity (objective 2: Task 2.1).

This information will then be used as a basis for the investigation of the suitability of the models for evaluating the causal pathways related to health effects reported in epidemiological literature. The obtained results should enable identification of key particulate parameters which affect human health and provide new insights into the mechanisms by which such particles disrupt normal cellular function. In addition, cellular response to the defined aerosols will be investigated using untargeted transcriptomic and proteomic techniques, allowing the identification of novel, component specified pathways (objective 3; Task 2.2).

Task 2.1: Aerosol particles exposure in cell and tissue cultures of different complexity

The aim of this task is to mimic and quantify the exposure of aerosol inhalation in vivo using novel methods for exposing cells to aerosols at the ALI, in order to find suitable model systems. This will be done by establishing and use relevant biological models (of different complexity ranging from more basic systems composed of monolayers to more complex novel in vitro lung model systems) following exposure to well characterised aerosols.

Task 2.2: Screening of cellular response using established toxicity panels and transcriptomic/proteomic approaches

The aim of this task is to evaluate at the cellular and subcellular level the response of the biological models in Task 2.1 to defined aerosols. The task will measure the response of large cell populations using fluorescent reporters for response biomarkers (including cytotoxicity, ROS and inflammation) as well as using proteomic and transcriptomic analyses.