Pulmonary toxicity of well-dispersed titanium dioxide nanoparticles following intratracheal instillation

In order to investigate the pulmonary toxicity of titanium dioxide (TiO(2)) nanoparticles, we performed an intratracheal instillation study with rats of well-dispersed TiO(2) nanoparticles and examined the pulmonary inflammation and histopathological changes in the lung. Wistar Hannover rats were intratracheally administered 0.2 mg (0.66 mg/kg) and 1.0 mg (3.3 mg/kg) of well-dispersed TiO(2) nanoparticles (P90; diameter of agglomerates: 25 nm), then the pulmonary inflammation responses were examined from 3 days to 6 months after the instillation, and the pathological features were examined up to 24 months. Transient inflammation and the upregulation of chemokines in the broncho-alveolar lavage fluid were observed for 1 month. No respiratory tumors or severe fibrosis were observed during the recovery time. These data suggest that transient inflammation induced by TiO(2) may not lead to chronic, irreversible legions in the lung, and that TiO(2) nanoparticles may not have a high potential for lung disorder.