Pulmonary Toxicity Induced by Intratracheal Instillation of Coarse and Fine Particles of Cerium Dioxide in Male Rats

In order to examine the short-, medium- and long-term effects of cerium dioxide par- ticles of different sizes on the lung, 10-wk-old male Wistar rats were administered a physiologi- cal saline solution with a suspension of coarse or fine particles of cerium dioxide at 34 mg/kg body weight by a single intratracheal instillation. Lungs were examined with cellular and bio- chemical analyses of the bronchoalveolar lavage (BAL) fluid and histopathology on different days after the instillation. Geometric mean and geometric standard deviation of the diameter were 3.90 ∝ m± 1.93 for the coarse (Ce-C) particles, and 0.20 ∝ m± 1.20 for the fine (Ce-F) particles. There were no lesions in the lung in the Ce-C-instilled group at any time point after the instil- lation. The instillation of Ce-F particles primarily induced inflammation, granulomas, mobi- lization and impairment of alveolar macrophages (AMs), and pulmonary alveolar proteinosis, together with very slight degrees of Type II epithelial cell hyperplasia and of collagen deposition. The pulmonary toxicity of Ce-F-instilled rats was found to be markedly enhanced in sharp con- trast to that of Ce-C-instilled rats on the basis of equal mass concentration, suggesting clear dependence of the pulmonary toxicity on numbers and sizes of particles. Causative factors for the pulmonary alveolar proteinosis are discussed with reference to the impaired AMs.