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

BACKGOUND: A variety of in vivo and in vitro studies to assess the genotoxicity of titanium dioxide nanoparticles (TiO(2) NPs) have been reported, but the results are inconsistent. Recently, we reported that TiO(2) 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 TiO(2) NP accumulation in tissues. In this study, we investigated the long-term mutagenic effects of TiO(2) NPs and the localization of residual TiO(2) NPs in mouse liver after multiple intravenous injections. RESULTS: Male gpt delta C57BL/6 J mice were administered with various doses of TiO(2) 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 TiO(2) NPs in the liver using transmission electron microscopy. Although TiO(2) NPs were found in the liver cells, the gpt and Spi(−) mutation frequencies in the liver were not significantly increased by the TiO(2) NP administration. CONCLUSIONS: These results clearly show that TiO(2) NPs have no mutagenic effects on the liver, even though the particles remain in the liver long-term.