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

TiO2 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 TiO2 we investigated the inflammatory and genotoxic lung effects of two types of commercially available TiO2 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 TiO2 P25 (untreated, hydrophilic surface) or TiO2 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-a, fibronectin, and surfactant phospholipids were determined. Additionally, 8 gm frozen sections of the left lobe of the lung were cut and stored at -80degreesC. 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 TiO2 P25 or TiO2 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 TiO2 are inert at applicated doses. (C) 2003 Elsevier Science (USA). All rights reserved.