Comparative <italic>In Vitro</italic> Cytotoxicity and Relative Pathogenicity of Mineral Dusts

Abstract

In vitro bioassays of mineral dust cytotoxicity were compared with in vivo pulmonary responses in an attempt to determine the value of bioassays as predictors of fibrogenicity. Release of alveolar macrophage enzyme and sheep red cell haemolysis were monitored as indicators of cytotoxicity for eight well characterized minerals. The pathological reaction induced by intratracheal instillation of 5 mg of three minerals (bentonite, silica and kaolin) into Fischer 344 rats were evaluated at intervals of 1, 7, 90, and 180 days. Bentonite and kaolin were found to be more haemolytic than silica. Kaolin induced greater release of macrophage cytosolic and lysosomal enzymes than silica whereas bentonite appeared to inhibit the activity of alveolar macrophage enzymes. All three minerals, silica, bentonite and kaolin, induced an acute inflammatory cellular response in vivo. However, only silica induced a progressive granulomatous and fibrotic response. The pulmonary response to bentonite and kaolin was temporary and had completely resolved six months post exposure. Although only three of the eight minerals have been assayed in vivo, these studies indicate that in vitro bioassays correlate with the acute in vivo reponses to mineral dusts but are not good predictors of fibrogenicity. It would appear that the chronic pulmonary response in animals is still the most reliable predictor of human pulmonary fibrogenic potential.