PULMONARY RESPONSES TO INHALED POORLY SOLUBLE PARTICULATE IN THE HUMAN

Abstract

This review focuses on the human pulmonary effects of talc, carbon black, coal dust, diesel exhaust, and titanium dioxide as examples of poorly soluble, nonfibrous particles (PSPs). Other particulates with similar characteristics (e.g., iron oxide) are included when considering the question of whether there is a characteristic human response to this class of compounds. The overall objective is to characterize the responses to these compounds using information from epidemiology, pathology, and cell biology so that comparisons with animal responses can be made. Exposure to PSPs is associated with two broad classes of disease in the human: pneumoconiosis and chronic obstructive lung disease. The basic pathologic features and pathogenesis of the different lesions associated with exposure to PSPs are described. This is followed by a review of the evidence linking exposure to coal, carbon black, diesel exhaust, talc, and titanium dioxide with these diseases. With the exception of diesel exhaust, which contains genotoxic constituents, PSPs have not been definitely linked to human lung cancer. Some questions relevant to this review are: 1. How does the human lung respond to PSPs? Specifically, (a) what are the morphologic features, and (b) what is their pathogenesis? 2. Is there evidence for clearance overload in the human, and if so, what are the characteristics of the associated tissue response? 3. Are PSPs associated with lung cancer in the human? 4. What are the major similarities and differences between human and rodent lung cancers? 5. Do inflammation, epithelial hyperplasia, and fibrosis play a role in the development of human lung cancer?