Pulmonary impact of titanium dioxide nanorods: examination of nanorod-exposed rat lungs and human alveolar cells

Background: Titanium dioxide nanoparticles have numerous applications, resulting in human exposure. Nonetheless, available toxicological and safety data are insufficient regarding aspherical particles, such as rod-shaped nanoparticles. Methods: In a combined in vitro in vivo approach, cultured A549 lung alveolar adenocarcinoma cells were treated with approximately 15x65 nm TiO2 nanorod-containing medium, while young adult rats received the same substance by intratracheal instillation for 28 days in 5 and 18 mg/kg body-weight doses. Nanoparticle accumulation in the lungs and consequent oxidative stress, cell damage, and inflammation were assessed by biochemical and histopathological methods. Results: Titanium was detected in tissue samples by single-particle inductively coupled plasma mass spectrometry. Nanoparticles were visualized inside cultured A549 cells, within pulmonary macrophages, and in hilar lymph nodes of the rats. A549 cells showed dose-dependent oxidative stress and lethality, and the observed nanoparticle-laden endosomes suggested deranged lysosomal function and possible autophagy. Strongly elevated Ti levels were measured in the lungs of nanorod-treated rats and moderately elevated levels in the blood of the animals. Numerous cytokines, indicating acute and also chronic inflammation, were identified in the lung samples of TiO2-exposed rodents. Conclusion: Several signs of cell and tissue damage were detected in both the cultured alveolar cells and in treated rats' lungs. Rod-shaped nanoparticulate TiO2 may consequently be more harmful than has generally been supposed. The occupational health risk suggested by the results calls for improved safety measures.