"Comparative Pulmonary Toxicity Study of 3 Different Dispersions of Nano- TiO2 Particles in Rats." 

Masato Naya, Norihiro Kobayashi, Shigehisa Endoh, Kazuhiro Yamamoto, Junko Nakanishi  

National Institute of Advanced Industrial Science and Technology

Society of Toxicology (Seattle, 2008/3/18)

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Abstract

In order to evaluate the effects of size of poorly soluble, low-toxicity (PSLT) particles on pulmonary toxicity, not only the effects of the primary sizes of these particles but also the effects of their dispersion need to be examined.
The aim of this study was to assess the lung toxicity of 3 different, well-characterized dispersions of anatase nano-TiO2 particles in rats. The average secondary particle size of these TiO2 particles, which were prepared from the same primary-sized nanoparticles, was approximately 18, 65, and 300 nm. Groups of male Crl:CD (SD) rats were intratracheally instilled with 5 mg/kg of these nano-TiO2 particles dispersed in 0.2–1.3% of disodium phosphate (DSP) solution. DSP solution- and Min-U-Sil quartz-instilled rats served as vehicle and positive controls, respectively. Following the instillations, the bronchoalveolar lavage fluid of the rats was examined for inflammatory markers such as the number of white blood cells, LDH and protein. The histopathology of the lung, liver, kidney, spleen, and cerebrum at post-instillation timepoints of 24 hours, 3 days, 1 week, 4 weeks, and 3 months was also examined.
Mild inflammatory responses in the lung were observed in the 18 nm- and 300 nm-sized TiO2 particle-instilled groups at 24 hours, 3 days, and 1 week after the instillations. In contrast, in the 65 nm-sized TiO2 particle-instilled group, only minimal inflammatory responses were observed in the lung at all the timepoints. At 4 weeks after the instillation, the lung inflammatory responses were comparable among these 3 TiO2 groups and the vehicle control group. Thus, it was concluded that these TiO2 particle types produced only transient pulmonary inflammatory effects. In all the groups, no histopathological changes were observed in the liver, kidney, spleen, or cerebrum.

Keywords

nanoparticle, toxicology, intratracheal instillation, rats