Abstract
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.
Highlights
Nanoscale titanium dioxide is widely used in the food industry
The results revealed that titanium was accumulated in the organs of mice treated with different doses of nano-TiO2 (Fig. 1)
The results suggest that nano-TiO2 can be absorbed through GI track and distributed to tissues through the circulatory system and deposited in the organs liver, kidney, spleen, lung, brain, and heart
Summary
Nanoscale titanium dioxide (nano-TiO2) is widely used in the food industry. It has been used for the production of coated candy, preserved fruits, chewing gum, carbonated drinks, powdered drinks (in unsweetened dosage form or concentrated), milk and dairy products, and other food categories [1, 2]. Nano-TiO2 has been widely used in biomedicine, organic pollutant treatment, materials engineering, and cosmetics [4,5,6]. Studies have shown that nano-TiO2 can become enriched and toxic in multiple organs after entering the Studies have revealed several mechanisms by which these nanoparticles cause toxicity. Reactive oxygen species (ROS), such as hydroxyl radicals, are generated and cause DNA oxidation, generating 8-OHG, leading to errors and mutations in DNA replication [16, 17]
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