Running title: Pulmonary Toxicity of Nanoscale and fine-sized TiO2 particles

D ow nloaded from 2Abstract Pulmonary toxicology studies in rats demonstrate that nanoparticles administered to the lung are more toxic than larger, fine-sized particles of similar chemistry at identical mass concentrations. The aim of this study was to evaluate the acute lung toxicity in rats of intratracheally instilled pigment-grade TiO2 particles (rutile-type- particle size = ~300 nm) vs. Nanoscale TiO2 rods (anatase – 200 nm x 35 nm) or Nanoscale TiO2 dots (anatase- ~10 nm) compared with a positive control particle-type, quartz. Groups of rats were instilled either with doses of 1 or 5 mg/kg of the various particle- types in phosphate-buffered saline (PBS). Subsequently, the lungs of PBS and particle-exposed rats were assessed using bronchoalveolar lavage (BAL) fluid biomarkers, cell proliferation methods, and by histopathological evaluation of lung tissue at 24 hrs, 1 week, 1 month and 3 months post-instillation exposure