Genotoxicity assessment of titanium dioxide nanoparticle accumulation of 90 days in the liver of gpt delta transgenic mice.

ABSTRACT

BACKGOUND A variety of in vivo and in vitro studies to assess the genotoxicity of titanium dioxide nanoparticles (TiO2 NPs) have been reported, but the results are inconsistent. Recently, we reported that TiO2 NPs exhibit no genotoxic effects in the liver and erythrocytes during a relatively brief period following intravenous injection into mice. However, there is no information about long-term genotoxicity due to TiO2 NP accumulation in tissues. In this study, we investigated the long-term mutagenic effects of TiO2 NPs and the localization of residual TiO2 NPs in mouse liver after multiple intravenous injections. RESULTS: Male gpt delta C57BL/6 J mice were administered with various doses of TiO2 NPs weekly for 4 consecutive weeks. The long-term mutagenic effects on the liver were analyzed using gpt and Spi- mutation assays 90 days after the final injection. We also quantified the amount of titanium in the liver using inductively coupled plasma mass spectrometry and observed the localization of TiO2 NPs in the liver using transmission electron microscopy. Although TiO2 NPs were found in the liver cells, the gpt and Spi- mutation frequencies in the liver were not significantly increased by the TiO2 NP administration. CONCLUSIONS: These results clearly show that TiO2 NPs have no mutagenic effects on the liver, even though the particles remain in the liver long-term.