CORRELATION BETWEEN PARTICLE-SIZE, IN-VIVO PARTICLE PERSISTENCE, AND LUNG INJURY

Dosimetry parameters such as deposition, clearance, retention, and tra nslocation and dissolution of inhaled particles in and to different lu ng compartments may be important for the persistence of particles in t he lung and may correlate with adverse pulmonary effects. We investiga ted such correlations using a model involving TiO2 particles of two pa rticle sizes (20 nm diameter, ultrafine; 250 nm diameter, fine) of the same crystalline structure (anatase). A 12-week inhalation experiment in rats resulted in a similar mass deposition of the two particle typ es in the lower respiratory tract. The ultrafine particles elicited a persistently high inflammatory reaction in the lungs of the animals co mpared to the larger-sized particles. In the postexposure period (up t o 1 year) retention in the alveolar space per se was not different bet ween fine and ultrafine TiO2. However, the following differences betwe en the particle types were noted: a significantly different total pulm onary retention, both quantitatively (significantly prolonged retentio n of the ultrafine TiO2) and qualitatively (increased translocation to the pulmonary interstitium and persistence there of the ultrafine TiO 2); greater epithelial effects (Type II cell proliferation; occlusion of pores of Kohn) and the beginning of interstitial fibrotic foci with ultrafine TiO2; significant sustained impairment of alveolar macropha ge function after ultrafine TiO2 exposure as measured by the clearance of test particles. A correlation between particle surface area and ef fects was observed. A comparison of the adverse reactions with dosimet ric parameters of TiO2 in different lung compartments in the postexpos ure period showed a correlation of the persistence of effects in both the alveolar and interstitial space with the persistence of particles in the respective compartment.