Pulmonary toxicity studies in rats with triethoxyoctylsilane (OTES)-coated, pigment-grade titanium dioxide particles: Bridging studies to predict inhalation hazard

The aim of this study was to assess and compare the acute lung toxicities of intratracheally instilled hydrophobic relative to hydrophilic surface-coated titanium dioxide (TiO2 ) particles using a pulmonary bridging methodology. In addition, the results of these instillation studies were bridged with data previously generated from inhalation studies with hydrophilic, pigment-grade (base) TiO2 particles, using the base, pigment-grade TiO2 particles as the inhalation/instillation bridgematerial. To conduct toxicity comparisons, the surface coatings of base pigment-grade TiO2 particles were made hydrophobic by application of triethoxyoctylsilane (OTES), a commercial product used in plastics applications. For the bioassay experimental design, rats were intratracheally instilled with 2 or 10 mg/kg of the following TiO2 particle-types: (1) base (hydrophilic) TiO2 particles; (2) TiO2 with OTES surface coating; (3) base TiO2 with Tween 80; or (4) OTES TiO2 with Tween 80. Saline instilled rats served as controls. Following exposures, the lungs of sham- and TiO2 -exposed rats were assessed both using bronchoalveolar lavage (BAL) biomarkers and by histopathology of lung tissue at 24 hours, 1 week, 1 month, and 3 months post exposure. The results demonstrated that only the base, high-dose (10 mg/kg) pigment-grade TiO2 particles and those with particle-types containing Tween 80 produced a transient pulmonary inflammatory response, and this was reversible within 1 week postexposure. The authors conclude that the OTES hydrophobic coating on the pigment-grade TiO2 particle does not cause significant pulmonary toxicity.