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 (TiO ₂-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 TiO ₂ 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.