Particle Overload in the Lung: Approaches to Improving Our Knowledge

Abstract

Lung overload is a condition characterized by (1) an overwhelming of normal clearance processes under certain exposure conditions, (2) resulting in lung burdens greater than predicted from disposition kinetics observed at low exposure concentrations, (3) with associated pathophysiological changes including altered macrophage function, inflammation and pulmonary fibrosis and (4) an uncertain association with an increased incidence of lung tumors in studies conducted in rats. Our present knowledge is not sufficient to distinguish between the role of compound specific mechanisms and non-compound specific mechanisms in the development of the lung overload condition. This is of particular concern when assessing the potential human health risks of exposure to particles using information from inhalation studies conducted in rats. An improved knowledge base on this issue can be developed through appropriately designed and interpreted studies. This paper (a) reviews the role of studies with an exposure-dose-response orientation conducted at multiple levels of biological organization in understanding and assessing human health risks for airborne particles, (b) discusses the overload condition with particular reference to understanding compound specific versus non-specific effects of inhaled materials, and (c) recommends approaches to the conduct and interpretation of inhalation studies with particulate materials conducted in rats.