Effect of engineered titanium dioxide nanoparticle shape on toxicity in vivo.
Porter-DW; Wolfarth-MG; Wu-N; Holian-A; Hubbs-A; Funk-KA; Castranova-V
Toxicologist 2011 Mar; 120(Suppl 2):312
The hypothesis of this study is that nanoparticle (NP) shape will affect pulmonary inflammation and fibrosis. To test this hypothesis, three types of anatase TiO2 NPs were used: nanospheres (NS), short nanobelts (NB-1) and long nanobelts (NB-2). For in vivo studies, we exposed C57Bl/6 mice by pharyngeal aspiration to TiO2 nanoparticles (0-30 mu g/mouse). Whole lung lavage (WLL) and histopathology studies were conducted. WLL demonstrated that TiO2 NPs induced dose- and time-dependent pulmonary inflammation (WLL PMNs) and damage (WLL fluid albumin concentration and lactate dehydrogenase activity). Cytokine and chemokine inflammatory mediators also showed dose- and time-dependent changes in WLL fluid. The pattern of responses was NS/_NB-1/_NB-2. Pulmonary clearance of NS and NB-2 indicated that relative to initial deposition, at 28 days post-exposure 69% of NS were cleared verusus 54% for NB-2, and at 112 days post-exposure 96% of NS were cleared versus 80% for NB-2. Histopathology studies showed that at 28 days post-exposure, TiO2 NPs were observed in alveolar macrophages within the lung, and to a lesser degree within the tracheal-bronchiolar lymph nodes (TBLN). There was an increase in the incidence of the latter finding at 112 days post-exposure, suggesting NP clearance from the lung to the lymph nodes. Persistent alveolitis was observed in mice exposed to NB-1 and NB-2. Interstitial fibrosis was only observed in the NB-1 and NB-2 groups at 28 days post-exposure, and this change persisted at an increased incidence at 112 days postexposure. Taken together, the data suggest that NP shape does affect lung toxicity and exposure to TiO2 nanobelts may result in adverse health outcomes.
Airborne-particles; Biohazards; Biological-effects; Dose-response; Exposure-levels; Fibrogenicity; Fibrosis; Fibrous-bodies; Health-hazards; Inhalation-studies; Laboratory-animals; Lung-disorders; Lung-fibrosis; Lung-irritants; Nanotechnology; Physiological-effects; Pulmonary-disorders; Pulmonary-system; Pulmonary-system-disorders; Quantitative-analysis; Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-system-disorders; Statistical-analysis; Time-weighted-average-exposure
The Toxicologist. Society of Toxicology 50th Annual Meeting and ToxExpo, March 6-10, 2011, Washington, DC