Lung toxicity of industrial particles
Résumé
The frame of the Nanoreg2 European project, which aimed at helping industrials partners to safely design nanomaterials, we studied in vivo toxicity of different nanomaterials produced by industry. Three industrial partners provided five nanomaterials. Two silicium nanomaterials were studied, one without and one with a carbon coating (named Si and Si-WC). Two carbon nanofibers with different degrees of purity and graphitization). And finally, one graphene. To study the lung toxicity of these products, we exposed rats to 0.1, 1 and 2 mg/kg of nanomaterials with one endo-tracheal instillation. Animals were then killed 24h, 3 and 28 days after exposure. Broncho-Alveolar Lavages (BAL) were performed in order to count and identify BAL cells but also to dose inflammatory cytokines secreted in BAL supernatant. Lungs were also fixed and analyzed by an histo-pathologist. The coated Si (Si-WC) induced a greater lung inflammatory response which was also more persistent in time compared to the response observed with Si without coating. Si-WC treated group developed within the lung parenchyma, interstitial thickening which were slightly more intense than Si particle treated group. Bronchial alterations were presents only in the highest exposed groups, but slightly more frequently observed in Si-WC40 exposed groups, but a minimal dose related effects tend to be observed for both particles. A dose related effect was observed for the presence of particle rich macrophages density suggesting a high clearance activity, only for Si-WC40 treated groups. The less pure carbon nanofiber induced a higher lung inflammatory response just after exposure which did not last in time. A very similar histologic lung profile was observed for both carbon nanofibers exposed groups with higher lesionnal score at early stages than late stages, suggesting an efficient clearance of the particles. No dose related effect has been observed. Bronchial alterations were observed only at the highest dose for both particles. However, a slightly more important number of bronchiolitis obliterans was observed after less pure carbon nanofiber exposure but tend to decrease in time. A dose related effect was observed for the presence of particle rich macrophages density suggesting a high clearance activity. The graphene induced the most important inflammatory response, but it did not last in time. Alveolar and bronchi alterations were quite high after graphene powder exposure. The lesions were slightly less intense with time suggesting an ongoing recovery. No dose-related effect could be observed. Within the bronchi, hyperplasia associated with inflammation leading to bronchial obstruction (bronchiolitis obliterans) was observed for all doses and all times after graphene powder exposure. Particles rich macrophages were not as high as expected, suggesting a less efficient clearance process, thus consistent with more alveolar and bronchi lesions.