Titanium dioxide (TiO2) nanoparticles are in wide commercial use worldwide.To evaluate if acute pulmonary toxicity can be induced by nano-TiO2 particles,rats were intra-tracheally instilled with 0.5,5,or 50 mg/kg of 5,21,and 50 nm TiO2 primary particles.Toxic effects were determined with the coefficients of lung tissues to body weight,histopathology,biochemical parameters of blood,activity of lactate dehydrogenase (LDH),alkaline phosphatase (ALP) and acid phosphatase (ACP) in tissues,and the phagocytotic ability of alveolar macrophages (AMs).All the indicators were observed in sacrificed rats one week post-exposure.There was a significant difference of coefficients of pulmonary tissues between the high-dose group and the low- or moderate-dose groups with an exposure of 5 nm TiO2.At the same time,5 nm TiO2 primary particles increased the activity of LDH and ALP when exposure dose was ＞5 mg/kg.A significant difference in LDH and ALP activity was observed between the 50 mg/kg group and 0.5 or 5 mg/kg group with exposure of 5 nm TiO2.Lung tissues showed increased ALP activity only if treated with 5 and 50 mg/kg of 21 nm TiO2 particles.There was no significant difference in LDH and ALP activity in the 50 nm TiO2 group and control group.Histopathologic examination of lung tissues indicated that the pulmonary response to exposure to TiO2 particles in rats manifested as dosedependent inflammatory lesions,which mainly consisted of infiltration of inflammatory cells and interstitial thickening.Analysis of uptake of neutral red dye showed that 50 nm TiO2 particles significantly increased phagocytotic ability of AMs compared with controls (P ＜ 0.05),whereas exposure with 5 nm TiO2 reduced the phagocytotic ability of AMs when the exposure dose was 50 mg/kg.These results suggest that particle size and exposure dose may have important roles in pulmonary toxicity.The toxic effect of TiO2 nanoparticles in lung tissue exhibited a dose-response relationship.After exposure with TiO2 particles of ＞5.0 mg/kg,5 and 21 nm TiO2 particles induced standing pulmonary lesions;and 5 nm TiO2 particles may suppress the phagocytotic ability of AMs if exposure dose was ≥ 50 mg/kg.Pulmonary toxicity caused by 5 nm TiO2 particles was more severe than that caused by 21 and 50 nm TiO2 particles.(C) 2008 National Natural Science Foundation of China and Chinese Academy of Sciences.Published by Elsevier Limited and Science in China Press.All rights reserved.