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Imprint
Establishment of an in vitro test platform for nanoparticle toxicity testing under physiologically relevant exposure conditions
Project
Project code: BfR-CPS-08-1322-594
Contract period: 01.03.2014
- 31.12.2017
Purpose of research: Applied research
The aim of this project is to establish an in vitro test platform for inhalation toxicity of nanoparticles. To work as close as possible to real conditions, it is planned to use materials and conditions for exposure according to the subacute and chronic in vivo studies carried out within the EU-project NANoREG. Cerium dioxide, barium sulphate and zinc oxide in nanoform will be tested first. For the establishment of the test platform, the alveolar epithelial cell line A549, derived from the lung carcinoma cells of a 58-year old caucasian male (Giard et al. 1973) will we used. This model was already employed in numerous other studies on inhalation toxicity. In the following, the MucilAir 3D bronchiolar epithelium system, a fully differentiated three dimensional model, will be included in the investigations. The MucilAir system possesses all functional features of the airway epithelium, e.g. mucus secretion, beating cilia responsible for clearance of airways and tight junctions, membrane proteins functioning as intercellular links. As a further system, Precision Cut Lung Slices (PCLS) should be used in comparison. PCLS represent slices of rat lung that can be kept alive and exposed against particles under laboratory conditions. This system is of particular importance since it can mimic the interaction between different cell types that occurs in vivo. To perform the exposure as realistic as possible, all investigated cell models will be cultivated on microporous membranes at the Air-Liquid-Interface (ALI) in an exposure chamber. The cell cultures will be supplemented with medium from the basal side, and nanoparticles will be applied as part of a dried aerosol. It is foreseen to quantify both the applied as well as the internal dose by mass spectrometric methods and to compare the results with data from subacute and chronic studies performed at NANoREG. Cytotoxicity, genotoxicity and oxidative stress are the first toxicological endpoints to be focused on.
Section overview
Subjects
- Biotechnology
- Process engineering
- Toxicology
