Investigations on the inflammatory and genotoxic lung effects of two types of titanium dioxide: untreated and surface treated

Abstract

TiO 2 is considered to be toxicologically inert, at least under nonoverload conditions. To study if there are differences in lung effects of surface treated or untreated TiO 2 we investigated the inflammatory and genotoxic lung effects of two types of commercially available TiO 2 at low doses relevant to the working environment. Rats were exposed by instillation to a single dose of 0.15, 0.3, 0.6, and 1.2 mg of TiO 2 P25 (untreated, hydrophilic surface) or TiO 2 T805 (silanized, hydrophobic surface) particles, suspended in 0.2 ml of physiological saline supplemented with 0.25% lecithin. As control, animals were instilled with the vehicle medium only or with a single dose of 0.6 mg quartz DQ12. At days 3, 21, and 90 after instillation bronchoalveolar lavage was performed and inflammatory signs such as cells, protein, tumor necrosis factor-α, fibronectin, and surfactant phospholipids were determined. Additionally, 8 μm frozen sections of the left lobe of the lung were cut and stored at −80°C. The sections were used for immunohistochemical detection of 8-oxoguanine (8-oxoGua) by a polyclonal antibody in the DNA of individual lung cells. In the quartz-exposed animals a strong progression in the lung inflammatory response was observed. Ninety days after exposure a significant increase in the amount of 8-oxoGua in DNA of lung cells was detected. In contrast, animals exposed to TiO 2 P25 or TiO 2 T805 showed no signs of inflammation. The amount of 8-oxoGua as a marker of DNA damage was at the level of control. The results indicate that both types of TiO 2 are inert at applicated doses.