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

In order to investigate the pulmonary toxicity of titanium dioxide (TiO₂) nanoparticles, we performed an intratracheal instillation study with rats of well-dispersed TiO₂ 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 TiO₂ 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 TiO₂ may not lead to chronic, irreversible legions in the lung, and that TiO₂ nanoparticles may not have a high potential for lung disorder