INFLUENCE OF PARTICLE DOSE ON THE CYTOTOXICITY OF HAMSTER AND RAT PULMONARY ALVEOLAR MACROPHAGE IN-VITRO

Silica and ferric oxide are common industrial exposures. Studies have indicated that all commonly occurring forms of crystalline silica can cause fibrotic lung disease. There is evidence to indicate that crysta lline silica is carcinogenic in humans who have not developed silicosi s, while amorphous silica is not carcinogenic in humans. An important biological response to particles deposited deep in the lung is their e ngulfment by pulmonary alveolar macrophages (AM). To assess the role o f AM in silica-induced lung disease, particle size distribution and su rface area of crystalline, gelled, precipitated, and fumed silica, Fer ric oxide, and aluminum oxide were characterized; the cytotoxicity of the particles to hamster and rat AM in vitro was measured at 0.0-0.5 m g/1 x 10(6) cells at 24 and 48 h using dye exclusion procedures. The c ount medium diameter for aluminum oxide, ferric oxide, and amorphous s ilica was equal to or less than 0.38 mu m, while for crystalline silic a the value was 0.83 mu m. The surface areas for the amorphous silicas and the aluminum oxide ranged from 253 to 125 m(2)/g with gelled sili ca having the highest value; the values for crystalline silica and fer ric oxide were 4.3 and 10.8 m(2)/g, respectively. Crystalline silica ( 1.6%) was detected in the fumed silica, while none was detected in pre cipitated or gelled silica. With gelled silica, based on the dose of t he particle, the viability of the hamster AM decreased to 27% at 0.05 mg and to zero at 0.1 mg at 24 h. At doses of 0.05 and 0.1 mg of cryst alline, precipitated, or fumed silica, the percent viability decreased significantly to 76-67% and 51-42%, respectively, and to zero at 0.5 mg. Macrophages viable at 24 h decreased further at 48 h compared with the control culture. The ferric oxide and the aluminum oxide showed m inimal to no changes in viability. Similar results for the particles w ere obtained with rat AM. The results indicate that precipitated and f umed amorphous silica tested at equivalent doses are equally as toxic to AM lavaged from two species of rodents as crystalline silica; gelle d silica is more toxic than crystalline. Ferric oxide and aluminum oxi de are noncytotoxic in this system. The results of this study indicate that the dose as well as the surface area and surface characterizatio n are important determinants in the cytotoxicity of hamster and rat AM to these particles.