Review : The 'Particle Overload' Phenomenon and Human Risk Assessment

Abstract

The last decade has seen the publication of an increasing number of scientific papers in which lung tumours have been induced in rats following chronic exposure by inhalation to a range of insoluble, respiratory-sized particulate dusts which hitherto have been considered to be biologically inert. Such sub stances include talc, titanium dioxide, volcanic ash and carbon black. Such particles have generally been considered 'nuisance dusts', possibly capable of eliciting fibrogenic changes, but not cancer. The one feature that all these stud ies in rats have in common is that the experimental exposures induced 'over loading' of the lung as evidenced by an increase in lung weight, retention of particles and chronic and marked inflammatory changes. All of this was pre ceded by an underlying 'overloading' of the alveolar macrophages to the point where they stopped removing particles from the lung. This can happen in a number of experimental species, but it is only the rat that appears to respond with lung tumours as an additional pathological response. This points to the lung tumours being a rat-specific response and thus not a very useful end-point for human risk evaluation for such biologically inert particles. In support of this view is the remarkable observation that in the one well-studied occupa tional group that routinely has 'particle overload' in the lungs, namely coal miners, there is no evidence that they experience an excess risk of lung cancer.