The Potential Liver, Brain, and Embryo Toxicity of Titanium Dioxide Nanoparticles on Mice

Nanoscale titanium dioxide (nano-TiO₂) has been widely used in industry and medicine. However, the safety of nano-TiO₂ exposure remains unclear. In this study, we evaluated the liver, brain, and embryo toxicity and the underlying mechanism of nano-TiO₂ using mice models. The results showed that titanium was distributed to and accumulated in the heart, brain, spleen, lung, and kidney of mice after intraperitoneal (i.p.) nano-TiO₂ exposure, in a dose-dependent manner. The organ/body weight ratios of the heart, spleen, and kidney were significantly increased, and those of the brain and lung were decreased. High doses of nano-TiO₂ significantly damaged the functions of liver and kidney and glucose and lipid metabolism, as showed in the blood biochemistry tests. Nano-TiO₂ caused damages in mitochondria and apoptosis of hepatocytes, generation of reactive oxygen species, and expression disorders of protective genes in the liver of mice. We found ruptured and cracked nerve cells and inflammatory cell infiltration in the brain. We also found that the activities of constitutive nitric oxide synthases (cNOS), inducible NOS (iNOS), and acetylcholinesterase, and the levels of nitrous oxide and glutamic acid were changed in the brain after nano-TiO₂ exposure. Ex vivo mouse embryo models exhibited developmental and genetic toxicity after high doses of nano-TiO₂. The size of nano-TiO₂ particles may affect toxicity, larger particles producing higher toxicity. In summary, nano-TiO₂ exhibited toxicity in multiple organs in mice after exposure through i.p. injection and gavage. Our study may provide data for the assessment of the risk of nano-TiO₂ exposure on human health.