Toxicology Letters 168 (2007) 176–185 Acute toxicity and biodistribution of different sized titanium dioxide particles in mice after oral administration Jiangxue Wang a,b , Guoqiang Zhou a,b , Chunying Chen a,∗ , Hongwei Yu a,b , Tiancheng Wang c , Yongmei Ma d,∗,1 , Guang Jia e , Yuxi Gao a , Bai Li a , Jin Sun a , Yufeng Li a,b , Fang Jiao a,b , Yuliang Zhao a , Zhifang Chai a a Laboratory for Bio-Environmental Effects of Nanomaterials and Nanosafety and Key Laboratory of Nuclear Analytical Techniques, National Center for NanoScience and Technology (NCNST) and Institute of High Energy Physics (IHEP), Chinese Academy of Sciences, Beijing 100080, PR China b Graduate University of Chinese Academy of Sciences, Beijing 100049, China c Department of Clinical Laboratory of Medicine, 3rd Hospital of Peking University, Beijing 100083, China d Institute of Chemistry, Chinese Academy of Sciences, Beijing 100080, China e Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100083, China Received 25 July 2006; received in revised form 30 November 2006; accepted 1 December 2006 Available online 9 December 2006 Abstract In order to evaluate the toxicity of TiO 2 particles, the acute toxicity of nano-sized TiO 2 particles (25 and 80 nm) on adult mice was investigated compared with fine TiO 2 particles (155 nm). Due to the low toxicity, a fixed large dose of 5 g/kg body weight of TiO 2 suspensions was administrated by a single oral gavage according to the OECD procedure. In 2 weeks, TiO 2 particles showed no obvious acute toxicity. However, the female mice showed high coefficients of liver in the nano-sized (25 and 80nm) groups. The changes of serum biochemical parameters (ALT/AST, LDH) and pathology (hydropic degeneration around the central vein and the spotty necrosis of hepatocytes) of liver indicated that the hepatic injury was induced after exposure to mass different-sized TiO 2 particles. In addition, the nephrotoxicity like increased BUN level and pathology change of kidneys was also observed in the experimental groups. The significant change of serum LDH and alpha-HBDH in 25 and 80 nm groups showed the myocardial damage compared with the control group. However, there are no abnormal pathology changes in the heart, lung, testicle (ovary), and spleen tissues. Biodistribution experiment showed that TiO 2 mainly retained in the liver, spleen, kidneys, and lung tissues, which indicated that TiO 2 particles could be transported to other tissues and organs after uptake by gastrointestinal tract. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Acute toxicity; Fixed dose procedure; Titanium dioxide; Nanoparticles; Mice ∗ Corresponding authors. Tel.: +86 10 62652738; fax: +86 10 62650450. E-mail addresses: chenchy@nanoctr.cn, chenchy@mail.ihep.ac.cn (C. Chen), maym@iccas.ac.cn (Y. Ma). 1 Tel.: +86 10 62575431. 1. Introduction Titanium dioxide (TiO 2 ), a noncombustible and odor- less white powder, naturally exists in anatase, rutile and brookite. It is frequently used as a white pigment for a wide range of paints, paper, plastics, ceramics, and the like. TiO 2 becomes transparent at the nanoscale (par- ticle size <100 nm), is able to absorb and reflect UV 0378-4274/$ – see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.toxlet.2006.12.001