Pulmonary retention of ultrafine and fine particles in rats.

In aerosol research, particle size has been mainly considered in the context of the role it plays in particle deposition along the respiratory tract. The possibility that the primary particle size may affect the fate of particles after they are deposited was explored in this study. Rats were exposed for 12 wk to aerosolized ultrafine (integral of 21 nm diameter) or fine (integral of 250 nm diameter) titanium dioxide (TiO2) particles. Other rats were exposed to TiO2 particles of various sizes (12, 21, 230, and 250 nm) by intratracheal instillation. After the rat lungs were extensively lavaged, analysis of particle content in the lavaged lungs, lavage fluid, and of lymphatic nodes was performed. Electron and light microscopy was also performed using unlavaged lungs. Both acute instillation and subchronic inhalation studies showed that ultrafine particles (integral of 20 nm) at equivalent masses access the pulmonary interstitium to a larger extent than fine particles (integral of 250 nm). An increasing dose in terms of particle numbers and a decreasing particle size promoted particle access into the interstitium. The translocation of particles into the interstitium appeared to be a function of the number of particles, and the process appeared to be related to the particle size, the delivered dose, and the delivered dose rate. A net effect of the preferential translocation of the smaller particles into the interstitium was a prolongation in their lung retention. After the 12-wk inhalation exposure, pulmonary clearance of ultrafine particles was slower (t1/2 = 501 days) than of larger particles (t1/2 = 174 days).(ABSTRACT TRUNCATED AT 250 WORDS)