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Differential mouse pulmonary dose and time course responses to titanium dioxide nanospheres and nanobelts.
Porter-DW; Wu-N; Hubbs-A; Mercer-R; Funk-K; Meng-F; Li-J; Wolfarth-M; Battelli-L; Friend-S; Andrew-M; Hamilton-R; Sriram-K; Yang-F; Castranova-V; Holian-A
Toxicol Sci 2013 Jan; 131(1):179-193
Three anatase titanium dioxide (TiO(2)) nanoparticles were prepared; nanospheres (NS), short nanobelts (NB1) and long nanobelts (NB2). These nanoparticles were used to investigate the effect of nanoparticle shape and length on lung toxicity. Mice were exposed (0-30 microg per mouse) by pharyngeal aspiration and pulmonary toxicity was assessed over a 112 day time course. Whole lung lavage data indicated that NB1- and NB2-exposed mice, but not NS-exposed mice, had significant dose- and time-dependent pulmonary inflammation and damage. Histopathological analyses at 112 days post-exposure determined no interstitial fibrosis in any NS-exposed mice, an increased incidence in 30 microg NB1-exposed mice, and significant interstitial fibrosis in 30 microg NB2-exposed mice. At 112 days post-exposure, lung burden of NS was decreased by 96.4% and NB2 by 80.5% from initial deposition levels. At 112 days post-exposure, enhanced dark field microscopy determined that alveolar macrophages were the dominant deposition site, but a fraction of NB1 and NB2 was observed in the alveolar interstitial spaces. For the 30 microg exposure groups at 112 days post-exposure, confocal microscopy and immunofluorescent staining demonstrated that retained NB2 but not NS were present in the interstitium subjacent to the terminal bronchiole near the normal location of the smallest lymphatic capillaries in the lung. These lymphatic capillaries play a critical role in particle clearance, and the accumulation of NB2, but not NS, suggests possible impaired lymphatic clearance by the high aspect ratio particles. In summary, our data indicate that TiO(2) nanoparticle shape alters pulmonary responses, with severity of responses being ranked as NS<NB1<NB2.
Nanotechnology; Laboratory-animals; Dose-response; Toxic-dose; Toxic-effects; Particulates; Respiratory-system-disorders; Pulmonary-function; Pulmonary-system; Pulmonary-system-disorders; Lung-cells; Lung-disorders; Lung-function; Lung-irritants; Laboratory-testing; Exposure-assessment; Exposure-methods; Histopathology; Author Keywords: nanoparticles; Agents; lung; pulmonary or respiratory system; Respiratory Toxicology; nanoparticles; Respiratory Toxicology
Dale W. Porter, Ph.D., Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, M/S 2015, Morgantown, WV, 26505, USA
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