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 particles of different sizes on the lung, 10-wk-old male Wistar rats were administered a physiological 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 biochemical 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 microm +/- 1.93 for the coarse (Ce-C) particles, and 0.20 microm +/- 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 instillation. The instillation of Ce-F particles primarily induced inflammation, granulomas, mobilization 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 contrast 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.

Dissolution of functional materials and rare earth oxides into pseudo alveolar fluid.

The dissolution rates of rare earth oxides and two types of rare earth containing functional materials into water, saline solution, and Gamble's fluid were measured in order to evaluate the biological effects of rare earth-containing functional materials. The tested materials were yttrium, lanthanum, cerium and neodymium oxides, and neodymium-boron-iron magnet alloy (NdBFe) and lanthanum-mish-metal-nickel-cobalt (LmNiCo) hydrogen-containing alloy. The dissolution rates of the rare earth oxides were very low, resulting in concentrations of rare earth elements in the test solutions of the order of ppb. In the most extreme case, Gamble's fluid dissolved 1,400 times more of the rare earth oxides than pure water. Fairly high concentration of neodymium were found in the dissolving fluids, which means that trace neodymium present as an impurity in each rare earth oxide dissolved preferentially. For yttrium oxide, the ratio of neodymium to yttrium that dissolved in the saline solution was greater than 78,000 to 1, taking into account the amount of each that was originally present in the yttrium oxide.

Effects of surface characteristics of potassium titanate whisker samples on acute lung injury induced by a single intratracheal administration in rats.

We compared in vivo biological effects, focusing on lung inflammatory responses after a single intratracheal administration of two types of well-characterized whiskers: potassium octatitanate and potassium hexatitanate, which have similar fiber sizes and chemical compositions, except their surface morphology. The geometrical mean of length (microm), width (microm), and geometric standard deviation (GSD) are: K(2)Ti(8)O(17) (PT1), 6.0[2.0], 0.35[1.51], having rough surface; K(2)Ti(6)O(13) (PT2), 5.0[2.18], 0.31[1.63], having smooth surface. Sixty male Wistar rats (8 wk old) under anesthesia were injected intratracheally with 2 doses of fibers (0.2 mg/0.5 ml/rat, 1.0 mg/0.5 ml/rat) or the same amount of saline solution (group C). Animals were sacrificed on days 1, 3, and 7 after fiber administration, and then the lung tissue and bronchoalveolar lavage (BAL) were collected. There were no obvious differences among the three groups in the yield of BAL fluid. Total protein concentration in BAL increased significantly from day 1; BAL fucose level increased significantly from day 3 in a dose-dependent manner, which gradually recovered by day 7 in groups PT1 and PT2. BAL total protein and fucose in group PT1 increased significantly compared with those in group PT2 at a dose level of 1.0 mg. A dose-independent increase of beta-glucuronidase activity and decrease of superoxide dismutase activity were observed in both fibers. BAL tumor necrosis factor-alpha (TNF-alpha) increased significantly in animals treated with 1.0 mg dosage of PT1 and PT2 on day 1. However, BAL IL-1beta did not show any marked change during the experimental period in animals treated with both fibers. On day 1, BAL cytokine-induced neutrophil attractants (CINC)/growth-related gene product (GRO) increased significantly in the PT1 group treated with 0.2 and 1.0 mg dosage. On day 3, the group treated with 1.0 mg PT1 showed significant increase of CINC/GRO compared with the group treated with 1.0 mg PT2, which recovered to the control level on day 7. Expression of various chemokine mRNAs (MCP-3, MIP-1alpha, RANTES, and eotaxin) increased in rats treated with PT1 or PT2 on day 1 and/or day 3. Increase of gene expression in the PT1 group was greater than that of the PT2 group at 0.2 mg dosage level. These results suggest that differences in the surface morphology of the whisker fibers of similar length and diameter, density, and chemical composition appear to be related to the facilitation of macrophage phagocytes in the macrophage-derived biological effects in acute lung injury induced by inhaled fibers.