Submitted Abstract
The VitralizeMe project brings at further develop and bring to the market an innovative alveolar in vitro model that is able to predict respiratory sensitization. Respiratory sensitization is one of the biggest emerging problems in toxicology with tremendous economical and safety implications. Sensitization is an immunological response that leads to the development of allergies and to the development of clinical symptoms like asthma, rhinitis, conjunctivitis or alveolitis. Identification of a chemicals as a respiratory sensitizers can lead to its classification as a SVHC (substance of very high concern), which could lead to the ban or restriction of the chemical. At present, the only reliable way to assess respiratory sensitization is by using in vivo models based on experimental animals, since there are no in vitro assay able to reliably detect and predict respiratory sensitization. The technology proposed by the VitralizeMe project aims at overcoming the current limitation by further improving and optimizing the in vitro alveolar model developed by LIST. This model is based on a combination of multiple cell lines (epithelial cells, endothelial cells, macrophages and dendritic cells) cultivated at the air-liquid-interface. The model can be exposed in a realistic way to naïve aerosol generated starting from materials in different physical form (gas, liquid or powder). Through the measurement of different biological endpoints (e.g. surface markers on dendritic cells or the amount of released cytokines) is able to predict is the tested chemical is able to induce respiratory sensitization and/or respiratory irritation. At present, the model has been tested on a limited number of positive controls showing good sensitivity and specificity. However, it is necessary to increase the number of positive and negative controls prior of the submission of the model to formal validation (by EURL ECVAM). Also, improvements are needed for the shipment of the model to final users. A significant part of the VitralizeMe will be dedicated to the determination of the intra- and inter-laboratory variability, as this aspect will determine what kind of products we have and in which way it can be commercialized (e.g. as an “in-house” service or as a “ready-to-use” assay).