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Fate of ultrafine (UFTiO2) or fine titanium dioxide (FTiO2) following intratracheal instillation in rats.

Sager-TM; Castranova-V
Toxicologist 2009 Mar; 108(1):51
Nanotechnology is expanding due to the unique properties of nanoparticles. Studies report that pulmonary exposure to nano-sized particles may produce greater pulmonary effects than their larger fine-sized particle counterparts. However, differences in fate and clearance of inhaled nano-sized and fine-sized particles are unclear. This study explores differences in lung burden as well as translocation to the interstitium and the bronchial-associated lymphatic tissue (BALT) between rats exposed to UFTiO2 vs. FTiO2. Rats were exposed to an equal surface area dose of UFTiO2 or FTiO2 (0.52 mg/rat or 10.7 mg/rat, respectively). Metal analysis indicates that the amount of UFTiO2 remaining in the lung decreased by 51% from 7 to 42 days post-exposure, while the lung burden of FTiO2 decreased by only 12% . The amount of TiO2 present in the tracheo-bronchial (TBL) and thymic lymph nodes (TLN) was also assessed. Lymph node burden for UFTiO2 from 7 to 42 days post-exposure increased by 246%, while a 134% increase was observed for FTiO2. Although relative migration of UFTiO2 to the lymph nodes exceeded that for FTiO2, this difference could not account fully for the much lower lung clearance of FTiO2 relative to UFTiO2, suggesting particle overload in rats exposed to FTiO2. Lung burden of TiO2 was measured in both lavaged and unlavaged lungs at 7 and 42 days post-exposure. The amount of TiO2 present in the lavagable fraction represents particles phagocytosed by lavagable alveolar macrophages or present as free particles in the airspaces. The non-lavagable UFTiO2 or FTiO2 fraction in the lung increased from 7 to 42 days post-exposure. With UFTiO2, the majority of the particles were non-lavagable, suggesting migration to the interstitium. In contrast, the majority of FTiO2 was found in lavagable alveolar macrophages. In summary, the results indicate that UFTiO2 migrates more rapidly to the interstitium than FTiO2 which is phagocytosed more avidly by alveolar macrophages.
Biological-distribution; Biological-effects; Biological-function; Biological-systems; Biological-transport; Breathing; Exposure-assessment; Exposure-levels; Exposure-methods; Laboratory-animals; Lung-disorders; Lung-irritants; Lung-fibrosis; Lung-function; Particle-aerodynamics; Particulate-dust; Pulmonary-disorders; Pulmonary-function; Particulates; Pulmonary-clearance; Pulmonary-system; Pulmonary-system-disorders; Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-system-disorders; Statistical-analysis; Nanotechnology
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The Toxicologist. Society of Toxicology 48th Annual Meeting and ToxExpo, March 15-19, 2009, Baltimore, Maryland