Technical report 122

Ultrafine TiO2 particles

In a study with ultrafine TiO2 (80% anatase: 20% rutile; average primary particle size = 21 nm), female rats, mice or hamsters were exposed to aerosol concentrations of 0.5, 2.0 or 10 mg/m3 TiO2 for 6 hours/day, 5 days/week for 13 weeks followed by 4, 13, 26 or 52 weeks of post exposure (49 weeks for hamsters)(Bermudez et al, 2004). Retained lung burdens increased in a concentration-related manner in all three species. Mice and rats had similar lung burdens at the end of exposures but hamsters were significantly lower. Retardation of particle clearance in rats and mice at the highest exposure concentration (10 mg/m3) was a strong signal that pulmonary particle overload had been achieved. Pulmonary lesions of the lungs in rats included foci of alveolar epithelial proliferation of metaplastic epithelial cells (alveolar bronchiolisation) concomitant with focal areas of heavy, particle-laden macrophages. In rats, these alterations were manifested by increased alveolar epithelial cell labelling indices, as evidenced by increases in cell proliferation indices. Associated with these overload-related developments were areas of interstitial particle accumulation and alveolar septal fibrosis. These pulmonary lesions measured and observed in rat lungs were progressive, i.e., became more pronounced with time. Mice developed a less severe inflammatory response without the progressive epithelial and fibroproliferativefibro proliferative changes.

These data are consistent with the results of a companion study using inhaled pigmentary (fine mode) TiO2 (Bermudez et al, 2002) and demonstrate that the pulmonary responses of rats exposed to ultrafine particulate concentrations likely to induce pulmonary overload are different from the effects measured in similarly exposed mice and hamsters. These differences can be explained both by pulmonary responses and by particle dosimetry differences between these rodent species.