Comparison of the Pulmonary Responses to Inhaled Pigmentary and Ultrafine Titanium Dioxide Particles in the Rat, Mouse and Hamster

Abstract

Groups of female rats, mice and hamsters were exposed to 10, 50 or 250 mg/m3 pigment grade titanium dioxide (PG-TiO 2 ) or to 0.5, 2 or 10 mg/m3 ultrafine titanium dioxide (UF-TiO 2 ) for 6 h/day, 5 days/week for 13 weeks. At the end of the exposure period, and after holding periods of 1, 3, 6 and 12 months, a range of investigations were made to assess lung burdens, indicators of pulmonary inflammation, oxidant damage, cellular proliferation and pathological responses. Findings in rats and mice exposed to 50 and 250 mg/m3 PG-TiO 2 or 10 mg/m3 UF-TiO 2 were consistent with the development of lung overload, i.e. accumulation of TiO 2 in the lungs, reduced clearance rates and pulmonary inflammation. Pulmonary lesions in rats exposed to 250 mg/m3 PG-TiO 2 continued to develop in severity throughout the post-exposure period, while those exposed to 50 mg/m3 PG-TiO 2 or 10 mg/m3 UF-TiO 2 showed diminution. Mice had similar lung burdens to rats throughout the study, but in contrast, the inflammatory and histological responses were less severe and diminished with time. Hamsters exposed to 250 mg/m3 PG-TiO 2 had similar initial lung burdens to the rat but demonstrated a high clearance rate post-exposure, with an accompanying reduction in the inflammatory and histopathological findings. Hamsters exposed to 10 mg/ml UF-TiO 2 had accumulated only ~20% of the lung burden seen in the rat and this was reflected in the limited changes observed in the measured parameters. These studies demonstrate marked species differences in the response to pulmonary overload, and will help in understanding the events and mechanisms responsible for the tumours seen in rats after lifetime exposure to dusts.