"Comparative Pulmonary Toxicity Study of 3 Different Primary-sized TiO2 Particles in Rats" 

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

National Institute of Advanced Industrial Science and Technology

SOT2008 Annual Meeting (Seattle, 2008/3/16)

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Abstract

Lung toxicity of 3 different-sized, well-characterized, anatase TiO2 particles was assessed in rats. The average primary size of these particles was approximately 7, 20, and 200 nm, respectively. Groups of male Crl:CD (SD) rats were intratracheally instilled with 5 mg/kg of the TiO2 particles dispersed in disodium phosphate solution. Following the instillations, the bronchoalveolar lavage fluid (BALF) of the rats was examined for inflammatory markers, and the histopathology of the lung, liver, spleen, and cerebrum at post-instillation timepoints of 24 hours, 3 days, 1 week, and 4 weeks was also examined.
In all the groups, toxicological effects were observed only in the lung and not in the liver, spleen, or cerebrum. The pulmonary inflammatory responses were different among the groups. In the 7 nm-TiO2-instilled group, the BALF measurements indicated significant increase in total cell and neutrophil numbers and in LDH and IL-6 concentrations. Further, macrophage infiltration in the alveoli and interstitium, inflammatory-cell infiltration, and hypertrophy of the alveolar epithelium cells were observed in the histopathological evaluations. In the 20 nm-TiO2-instilled group, the inflammatory responses were almost the same as in the 7 nm-TiO2-instilled group. However, no significant increases in the IL-6 concentrations in the BALF, or macrophage infiltration in the interstitium were observed. In the 200 nm-TiO2-instilled group, no significant differences were observed for any of the inflammatory biomarkers in the BALF. Further, in the 200 nm-TiO2-instilled group, the levels of the macrophage infiltration in the alveoli and inflammatory-cell infiltration were much lower than those observed in the 7 nm- TiO2 or 20 nm-TiO2-instilled groups.
All the above-mentioned TiO2 particle types produced only transient pulmonary inflammatory effects, and these changes were recovered at 1 month after the instillations.

Keywords

nanoparticle, intratracheal instillation, titanium dioxide