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An overview of the InhalT-90 project - a 90-day inhalation toxicity study with CeO2 nanoparticles

: Schwotzer, Daniela; Hansen, Tanja; Niehof, Monika; Creutzenberg, Otto

Naunyn-Schmiedebergs archives of pharmacology 388 (2015), Supplement 1, S.S71, Abstract 283
ISSN: 0028-1298
ISSN: 1432-1912
Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie (Annual Meeting) <81, 2015, Kiel>
Fraunhofer ITEM ()

The application of nanomaterial and the use of its advantageous characteristics for many different products is strongly expanding during the last decades. Cerium dioxide nanoparticles are commonly used as additive in diesel fuel, due to its catalytic activity. As a consequence they are released into the environment via fuel combustion, and organisms might be exposed via inhalation. This example shows that the investigation of nanoparticle toxicity is important for adequate regulation and risk assessment. However, little is known about the adverse effects of CeO2 nanoparticles after inhalation especially regarding the long term exposure of humans and the environment. The BMBF-funded project InhalT-90 (contract number: 03X0149) was initiated to investigate the effects of CeO2 nanoparticles following a 90-day nose-only inhalation in the rat according to OECD 413. In order to compare the results to a combined chronic inhalation toxicity and carcinogenicity study (BASF, Ludwigshafen, Germany), early indicators of genotoxic and carcinogenic effects should be determined. This will particularly be facilitated by gene expression analyses. Groups of rats will be exposed to the test substance CeO2 in concentrations of 0, 0.1, 0.3, 1 and 3 mg/cm³ or to one high concentration of barium sulfate (50 mg/m³) for a time period of 90 days (6 h/day, 5 days/week) in a nose-only exposure system. After one and 28 days of exposure, as well as after one, 28 and 90 days recovery period, animals will be sacrificed for different investigations including hematology, histopathology, immunohistochemistry, retention analytics, bronchoalveolar lavage and gene expression analyses. The latter will be performed in isolated pneumocytes type II using pathway arrays for genotoxicity, oxidative stress, inflammation, apoptosis and lung cancer related genes. Subsequently, genes will be selected as marker, whose mRNA expression is markedly modified by nanoparticle exposure. Based on this an in vitro screening system for nanomaterials should be developed: a lung cell line will be exposed to the nanoparticles in an air-liquid exposure system. The in vivo selected marker genes will be evaluated in this in vitro system, checking if the gene expression is consistent and if it is comparable to the in vivo situation. All in all, these investigations should contribute to the improvement of nanomaterial risk assessment by the development of screening methods and the supply of toxicity data.