Comparison of Selected Pulmonary Responses of Rats, Mice, and Syrian Golden Hamsters to Inhaled Pigmentary Titanium Dioxide.

We present a preliminary report of a bioassay designed to compare and contrast selected pulmonary responses of female B6C3F1 mice, Fischer 344 rats, and Syrian golden hamsters to inhaled pigmentary titanium dioxide (TiO2). Animals were administered 10, 50, or 250 mg/m(3) TiO2 for 6 h/day and 5 days/wk, for 13 wk. Recovery groups were held for an additional 4-, 13-, or 26-wk period. Following exposure and at each recovery time, TiO2 burdens in the lung and lung-associated lymph nodes were determined. A separate group of animals was used at each time point to assess the inflammatory response of the lung by assaying total protein in bronchoalveolar lavage fluid (BALF) and cytologic examination of cells recovered in BALF. Burdens (mg/mg dry weight) of TiO2 in the lung following exposure to 10, 50, or 250 mg/m(3) TiO2 were 5.2, 53.5, and 170.2 for the mouse; 7.1, 45.1, and 120.4 for the rat; and 2.6, 14.9, and 120.3 for the hamster. With time after exposure, lung burdens of TiO2 particles were decreased and lymph-node burdens increased. Changes in the hamsters' burdens were more rapid than those in mice and rats. Increases in BALF cell numbers (macrophages and neutrophils) and in total protein were observed in all 3 species following exposure to 50 and 250 mg/m(3) TiO2, with the magnitude of response being the grea test in the rat. These responses remained elevated relative to control levels at 26 wk postexposure. Histopathologic examination of lungs showed a concentration-dependent retention pattern of particles that varied by species. Hypertrophy and hyperplasia of alveolar epithelium along with alveolar metaplastic and fibrotic changes were observed in rats exposed to 250 mg/m(3) TiO2. Alveolar epithelial proliferative changes were associated with inflammation in mice and hamsters, but the metaplastic and fibrotic changes noted in rats were not present in similarly exposed mice or hamsters. These data suggest that rats exposed subchronically to extremely high concentrations of pigmentary TiO2 differ from mice and hamsters in their cellular responses in the lung as well as in the way they clear and sequester particles. These differences may partly explain the differential outcome of pulmonary responses in various rodent species following chronic inhalation exposure to poorly soluble particles.