Inhalation of poorly soluble particles. II. Influence of particle surface area on inflammation and clearance

In this article the volumetric overload hypothesis, which predicts the impa irment of clearance of particles deposited in the lung in terms of particle volume, is reevaluated. The degree to which simple expressions of retained lung burden explain pulmonary responses to overload was investigated using data from a series of chronic inhalation experiments on rats with two poor ly soluble dusts, titanium dioxide and barium sulfate. The results indicate d that the difference between the dusts in the level of inflammation and tr anslocation to the lymph nodes could be explained most simply when the lung burden was expressed as total particle surface area. The shape of the stat istical relationship for both lung responses indicated the presence of a th reshold at approximately 200-300 cm(2) of lung burden. On the basis of this and other similar results, a hypothesis regarding a generic mechanism for the impairment of clearance and associated lung responses is proposed for s uch "low-toxicity" dusts.