Toxicity of cerium dioxide nanoparticles - effects from a 90-day inhalation study

Frequent use of cerium dioxide nanoparticles e.g. as diesel fuel additive requires assessment of possible health effects. Although exposure via the respiratory tract is likely, little is known about impacts after inhalation. To address this issue, a 90-day nose-only inhalation study was initiated. Early indicators of genotoxic and carcinogenic effects were determined. Results will be compared to a combined chronic inhalation toxicity and carcinogenicity study with similar test items and conditions (BASF, Ludwigshafen, Germany). Rats were exposed to 0, 0.1, 0.3, 1 and 3 mg/m3 CeO2 nanoparticles (6 h/day, 5 days/week, 13 weeks). Exposure to a high concentration of nanoscaled barium sulfate (50 mg/m3) was included as well. Investigations were performed after one and 28 exposure days, as well as after one, 28 and 90 days post-exposure. Obligatory endpoints (OECD guideline 413) were extended by gene expression analysis in pneumocytes type II and immunohistochemistry to identify biomarkers for effects including genotoxicity, oxidative stress and apoptosis. Histopathological findings indicated the presence of inflammatory cells in lung tissue after treatment to 3 mg/m3 CeO2. Severity of effects was increasing over time and remained persistent during post-exposure. Bronchoalveolar lavage fluid analysis displayed a similar trend. Expression of over 30 genes was significantly influenced by nanoparticle exposure. The present findings suggest that CeO2 nanoparticles affect the rats' respiratory system. Importance of those observations, especially regarding long term effects will be assessed including all upcoming investigations of this study. This project is funded by the German Federal Ministry of Education and Research (BMBF) - 03X0149A.