Biological response to nano-scale titanium dioxide (TiO2): role of particle dose, shape, and retention

Titanium dioxide (TiO2) is one of the most widely used nanomaterials, valued for its highly refractive, photocatalytic, and pigmenting properties. TiO2 is also classified by the International Agency for Research on Cancer (IARC) as a possible human carcinogen. The objectives of this study were to (1) establish a lowest-observed-effect level (LOEL) for nano-scale TiO2, (2) determine TiO2 uptake in the lungs, and (3) estimate toxicity based on physicochemical properties and retention in the lungs. In vivo lung toxicity of nano-scale TiO2 using varying forms of well-characterized, highly dispersed TiO2 was assessed. Anatase/rutile P25 spheres (TiO2-P25), pure anatase spheres (TiO2-A), and anatase nanobelts (TiO2-NB) were tested. To determine the effects of dose and particle characteristics, male Sprague-Dawley rats were administered TiO2 (0, 20, 70, or 200 μg) via intratracheal instillation. Bronchoalveolar lavage fluid (BALF) and lung tissue were obtained for analysis 1 and 7 d post exposure. Despite abundant TiO2 inclusions in all exposed animals, only TiO2-NB displayed any significant degree of inflammation seen in BALF at the 1-d time point. This inflammation resolved by 7 d, although TiO2 particles had not cleared from alveolar macrophages recovered from the lung. Histological examination showed TiO2-NB produced cellular changes at d 1 that were still evident at d 7. Data indicate TiO2-NB is the most inflammatory with a LOEL of 200 μg at 1 d post instillation.