The Importance of Surface Area and Specific Reactivity in the Acute Pulmonary Inflammatory Response to Particles

Abstract

A range of different particle types cause excessive lung inflammation that is thought to play a role in the various types of pathology they produce. Recently attention has been focused on ultrafine particles and the phenomenon of rat lung overload. The authors and their collaborators have shown previously that the surface area metric drives the overload response. Acute inflammatory response following instillation of particles has also been used to evaluate hazard but has been criticized because of the non-physiological delivery and the problems of local overload. We have instilled a number of low-toxicity dusts of various particle sizes and assessed neutrophil influx into the lung at 18–24 h. The extent of inflammation has been shown to be a function of the surface area instilled. Since ultrafine particles present a ‘special’ case of high surface area, they are relatively inflammogenic. There is no evidence that ultrafine particles of carbon black, titanium dioxide or latex have any special reactivity in addition to their large surface area. We tested whether we could use this approach to model the reactivity of highly toxic dusts. Rats were instilled with either DQ12 quartz or aluminium lactate-treated DQ12 and, as anticipated, the high specific surface toxicity of DQ12 meant that it was much more inflammogenic than was predicted using the relationship described for low-toxicity dusts. By contrast, aluminium lactate-treated DQ12 fell on to the line of ‘low-toxicity’ dusts. This approach presents the possibility of modelling potential toxicity for nuisance dusts based on the inflammatory response of a given instilled surface area dose.