Pulmonary Tissue Access of Ultrafine Particles

Rats were exposed to different sizes of Ti02 or AI2O3 particles by intratracheal instillation or by aerosol inhalation. The lungs were analyzed at days 1, 29 and 59 or 60 after exposure for TiO2 and Al2O3 content and for the lung's free cell responses. An extensive lung lavage was used in an attempt to distinguish between the particles retained in the alveoli and airways and particles translocated into the pulmonary tissue itself. After intratracheal instillation of 500 μg, particles of TiO2 and A12O3 with a primary particle diameter of ∼20 nm were translocated into the pulmonary tissue from the alveoli to a greater extent than particles with 250-500 nm diameter. The enhanced translocation resulted in an increase of particle content in the hilar lymph nodes. This was accompanied by an acute inflammatory response as indexed by the abnormal abundance of polymorphonuclear leukocytes. After 10 similar inhalation exposures, no difference in translocation of ultrafine (∼20 nm) and larger (∼250 nm) TiO2 particles could be observed, indicating the importance of particle delivery rates. Phagocytosis of particles by alveolar macrophages in the alveoli appears to be the mechanism which prevents the rapid translocation of particles from the alveoli into the pulmonary tissue.