Accumulation of inhaled mineral dust in the lung and associated lymph nodes: implications for exposure and dose in occupational lung disease

Experiments have been carried out using laboratory rats exposed to non-fibrous, toxic and non-toxic, and relatively insoluble mineral dusts under chronic exposure conditions for airborne respirable concentrations from 0.1 to 90 mg m −3 . The aim was to investigate the accumulation of dust in the lung and associated lymph nodes. The results have shown consistently that, after an initial non-linear phase during the early part of the exposure history, lung burden becomes a linearly-increasing function of exposure time. Furthermore, lung burden increases directly with respect to the respirable concentration over the full range of conditions examined. The corresponding results for the lung-associated lymph nodes suggest that substantial accumulation of dust in them does not begin until lung burden itself has reached a certain threshold. That threshold is lower for toxic than for non-toxic dust. However, once accumulation has begun, the actual rate of transport is not markedly dependent on toxicity. The experimental results form the basis of an improved mathematical model for the kinetics of accumulation of dust in the lung and associated lymph nodes. The central feature of the model is the sequestration of particles at locations from which they cannot be cleared (possibly by focal aggregation in macrophages in alveolar spaces, entrapment within epithelial cells and in the alveolar interstitium and/or entrapment within areas of fibrotic pathological change). This model is now being used to explore the relationship between exposure and dose for humans chronically exposed to mineral dusts in the occupational environment. It provides results which are markedly different from those obtained using previous models.