Categorization of nano-structured titanium dioxide according to physicochemical characteristics and pulmonary...

A potentially useful means of predicting the pulmonary risk posed by new forms of nano-structured titanium dioxide (nano-TiO₂) is to use the associations between the physicochemical properties and pulmonary toxicity of characterized forms of TiO₂. In the present study, we conducted intratracheal administration studies in rats to clarify the associations between the physicochemical characteristics of seven characterized forms of TiO₂ and their acute or subacute pulmonary inflammatory toxicity. Examination of the associations between the physicochemical characteristics of the TiO₂ and the pulmonary inflammatory responses they induced revealed (1) that differences in the crystallinity or shape of the TiO₂ particles were not associated with the acute pulmonary inflammatory response; (2) that particle size was associated with the acute pulmonary inflammatory response; and (3) that TiO₂ particles coated with Al(OH)₃ induced a greater pulmonary inflammatory response than did non-coated particles. We separated the seven TiO₂ into two groups: a group containing the six TiO₂ with no surface coating and a group containing the one TiO₂ with a surface coating. Intratracheal administration to rats of TiO₂ from the first group (i.e., non-coated TiO₂) induced only acute pulmonary inflammatory responses, and within this group, the acute pulmonary inflammatory response was equivalent when the particle size was the same, regardless of crystallinity or shape. In contrast, intratracheal administration to rats of the TiO₂ from the second group (i.e., the coated TiO₂) induced a more severe, subacute pulmonary inflammatory response compared with that produced by the non-coated TiO₂. Since alteration of the pulmonary inflammatory response by surface treatment may depend on the coating material used, the pulmonary toxicities of coated TiO₂ need to be further evaluated. Overall, the present results demonstrate that physicochemical properties may be useful for predicting the pulmonary risk posed by new nano-TiO₂ materials.