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Toxicity of CeO2 nanoparticles estimated in a 90-day nose-only inhalation study

: Schwotzer, Daniela; Niehof, Monika; Hansen, Tanja; Schuchardt, Sven; Tillmann, Thomas; Ernst, Heinrich; Creutzenberg, Otto H.

Naunyn-Schmiedebergs archives of pharmacology 389 (2016), Supplement 1, S.S51, Abstract 210
ISSN: 0028-1298
ISSN: 1432-1912
Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie (Annual Meeting) <82, 2016, Berlin>
Network Clinical Pharmacology Germany (Annual Meeting) <18, 2016, Berlin>
Fraunhofer ITEM ()

Since the use of cerium dioxide nanoparticles is known to be beneficial e.g. in terms of reducing fuel consumption when added to diesel fuel it has become a frequently used nanomaterial. To compensate the concurrent lack of information on its toxicology a 90-day nose-only inhalation study was initiated. By comparing the results to a combined chronic inhalation toxicity and carcinogenicity study using the same test items and experimental conditions (BASF, Ludwigshafen, Germany) early indicators for genotoxic and carcinogenic effects should be determined. Rats were exposed to 0, 0.1, 0.3, 1 and 3 mg/cm³ CeO2 as well as 50 mg/m³ BaSO4 nanoparticles (6 h/day, 5 days/week, 13 weeks). Animal dissections were conducted at five time points (exposure day 1 and 28; recovery day 1, 28 and 90) aiming for endpoints mandatory according to OECD guideline 413. Additionally, gene expression analyses in isolated pneumocytes type II were performed using Pathway Arrays for inflammation, oxidative stress, genotoxicity, apoptosis and lung cancer. The given results intend the identification of marker genes displaying modulated expression in response to nanoparticle exposure. Investigations on CeO2 and BaSO4 retention in the lung are also included in this project. In bronchoalveolar lavage fluid (BALF) a time and dose-dependent increase of inflammatory cells has been detected up to the end of exposure. The amount of inflammatory cells decreased during post-exposure; however, in the high dose group a persistent inflammation up to 90 days was detected by BALF and histopathology examination. Based on our current results effects of CeO2 nanoparticles on the respiratory system are suggested. Its relevance in the context of long term effects such as tumor development needs to be estimated considering all investigations included in this study. The InhalT-90 project is funded by the German Federal Ministry of Education and Research (BMBF) – 03X0149A.