Comparative pulmonary toxicity inhalation and instillation studies with different TiO2 particle formulations:: Impact of surface treatments on particle toxicity

Most pigment-grade titanium dioxide (TiO2) samples that have been tested in pulmonary toxicity tests have been of a generic variety-i.e., generally either uncoated particles or TiO2 particles containing slightly hydrophilic surface treatments/coatings (i.e., base TiO2). The objectives of these studies were to assess in rats, the pulmonary toxicity of inhaled or intratracheally instilled TiO2 particle formulations with various surface treatments, ranging from 0-6% alumina (Al2O3) or alumina and 0-11% amorphous silica (SiO2). The pulmonary effects induced by TiO2 particles with different surface treatments were compared to reference base TiO2 particles and controls. In the first study, groups of rats were exposed to high exposure (dose) concentrations of TiO2 particle formulations for 4 weeks at aerosol concentrations ranging from 1130-1300 mg/m(3) and lung tissues were evaluated by histopathology immediately after exposure, as well as at 2 weeks and 3, 6, and 12 months postexposure. In the second study, groups of rats were intratracheally instilled with nearly identical TiO2 particle formulations (when compared to the inhalation study) at doses of 2 and 10 mg/kg. Subsequently, the lungs of saline-instilled and TiO2-exposed rats were assessed using both bronchoalveolar (BAL) biomarkers and by histopathology/cell proliferation assessment of lung tissues at 24 h, 1 week, 1 and 3 months postexposure. The results from these studies demonstrated that for both inhalation and instillation, only the TiO2 particle formulations with the largest components of both alumina and amorphous silica surface treatments produced mildly adverse pulmonary effects when compared to the base reference control particles. In summary, two major conclusions can be drawn from these studies: (1) surface treatments can influence the toxicity of TiO2 particles in the lung; and (2) the intratracheal instillation-derived, pulmonary bioassay studies represent an effective preliminary screening tool for inhalation studies with the identical particle-types used in this study.