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Histopathological findings after 12 months inhalation to nano Ceria

: Ernst, Heinrich; Ma-Hock, Lan; Keller, J.; Groeters, Sibylle; Ravenzwaay, Bennard van; Gebel, Thomas; Schaudien, Dirk; Rittinghausen, Susanne; Landsiedel, Robert

Naunyn-Schmiedebergs archives of pharmacology 389 (2016), Supplement 1, pp.S53, Abstract 219
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 ()

Lung carcinogenicity and putative systemic effects of low-dose life-time inhalation exposure to biopersistent nanoparticles were examined in a chronic inhalation study performed according to OECD test guideline no. 453 with several protocol extensions. Female rats (100/group) were exposed to cerium dioxide (NM-212, 0.1; 0.3; 1; 3 mg/m³) for two years; a control group was exposed to clean air. After one year exposure, 42µg/lung was found in animals exposed to 0.1 mg/m³ and 2.6 mg/lung in animals exposed to 3 mg/m³. Histological examination of lungs revealed several adverse and non-adverse effects in the lung. The non-adverse effects comprised accumulation of particle-laden macrophages in alveolar/interstitial areas and in the BALT, particle-laden syncytial giant cells in the BALT and bronchiolo-alveolar hyperplasia (alveolar bronchiolization). The adverse effects included (mixed) alveolar/interstitial inflammatory cell infiltration, alveolar/interstitial granulomatous inflammation, interstitial fibrosis and alveolar lipoproteinosis. The incidence and severity of the effects were concentration-related. Alveolar lipoproteinosis was not observed at low concentrations of 0.1 and 0.3 mg/m³CeO2. Neither pre-neoplastic nor neoplastic changes were observed after 12-monthsexposure. A no observed adverse effect concentration could not be established in this study. The comprehensive histopathological examinations of lungs and other tissues will be finalized in 2017.This project is part of the EU Project NanoReg. Moreover, German Federal Ministry for the Environment, Nature Conservation, Building and Nuclear Safety, German Federal Institute for Occupational Safety and Health, German Federal Environment Agency funded this project.