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

Toxicol Appl Pharmacol. 2003 Jun 1;189(2):84-95. doi: 10.1016/s0041-008x(03)00092-9.


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-alpha, fibronectin, and surfactant phospholipids were determined. Additionally, 8 microm frozen sections of the left lobe of the lung were cut and stored at -80 degrees 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.

MeSH terms

  • Air Pollutants, Occupational / chemistry
  • Air Pollutants, Occupational / toxicity*
  • Animals
  • Bronchoalveolar Lavage
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • Cell Count
  • Cell Division / drug effects
  • DNA Damage
  • Dose-Response Relationship, Drug
  • Female
  • Guanine / analogs & derivatives*
  • Guanine / analysis
  • Instillation, Drug
  • Lung / cytology
  • Lung / drug effects*
  • Mutagens / chemistry
  • Mutagens / toxicity*
  • Particle Size
  • Pneumonia / chemically induced
  • Pulmonary Surfactants / analysis
  • Quartz / toxicity
  • Rats
  • Rats, Wistar
  • Surface Properties
  • Titanium / chemistry
  • Titanium / toxicity*


  • Air Pollutants, Occupational
  • Mutagens
  • Pulmonary Surfactants
  • Quartz
  • titanium dioxide
  • 8-hydroxyguanine
  • Guanine
  • Titanium