In vivo acute toxicity of titanium dioxide nanoparticles to mice after intraperitioneal injection

Because of its excellent optical performance and electrical properties, TiO2 has a wide range of applications in many fields. It is often considered to be physiologically inert to humans. However, some recent studies have reported that nano-sized TiO2 may generate potential harm to the environment and humans. In this paper the in vivo acute toxicity of nano-sized TiO2 particles to adult mice was investigated. Mice were injected with different dosages of nano-sized TiO2 (0, 324,648,972,1296, 1944 or 2592 mg kg(-1)). The effects of particles on serum biochemical levels were evaluated at various time points (24 h, 48 h, 7 days and 14 days). Tissues (spleen, heart, lung, kidney and liver) were collected for titanium content analysis and histopathological examination. Treated mice showed signs of acute toxicity such as passive behavior, loss of appetite, tremor and lethargy. Slightly elevated levels of the enzymes alanine aminotransferase and aspartate aminotransferase were found from the biochemical tests of serum whereas blood urea nitrogen was not significantly affected (P < 0.05). The accumulation of TiO2 was highest in spleen (P < 0.05). TiO2 was also deposited in liver, kidney and lung. Histopathological examinations showed that some TiO2 particles had entered the spleen and caused the lesion of spleen. Thrombosis was found in the pulmonary vascular system, which could be induced by the blocking of blood vessels with TiO2 particles. Moreover, hepatocellular necrosis and apoptosis, hepatic fibrosis, renal glomerulus swelling and interstitial pneumonia associated with alveolar septal thickening were also observed in high-dose groups. Copyright (C) 2009 John Wiley & Sons, Ltd.