Surface modified titanium dioxide nanoparticles induce fibrosis-like changes in lungs at high doses [set 4]

Previous studies have shown that TiO2NPs induce lung inflammation in mice and have suggested that the degree of inflammation varies with their size and other physical and chemical properties, e.g., shapes, surface modifications and surface charge. It is currently unknown if the observed inflammation in mouse lungs following exposure to TiO2NPs will cause any disease in the long term. This study examined mouse lung responses to six individual TiO2NPs of varying sizes (10, 20 and 300 nm), surface modifications and shapes. C57BL/6 mice were exposed to 18 µg, 54 µg, 162 µg or 486 µg of TiO2NPs/mouse via direct deposition of particles in lungs. Lung fluid and lung tissue were sampled on day 1, day 28 and day 90. Changes in inflammation and gene expression in lung were profiled. Histopathological changes in lungs indicative of diseases were examined by microscopic techniques. The results confirmed that all TiO2NPs induce lung inflammation immediately after exposure. At the highest dose tested, this particular TiO2NPs with surface modification induced signs of lung fibrosis (a disease of regulatory importance for NMs. Although lung response induced by TiO2NPs is influenced by many of their properties, the results of the study indicated that certain surface modification may play role in causing a disease. This experiment examined the the lung transcriptomic responses to single intratracheal instillation of mix rutile/anatase TiO2NPs of 20 nm diameter. Four diferent doses were selected:18, 54, 162, or 486 µg/animal. Samples were collected at day 1, day 28, and day 90 post-exposure