SHORT-TERM INHALATION AND IN-VITRO TESTS AS PREDICTORS OF FIBER PATHOGENICITY

A wide range of fiber types was tested in two in vitro assays: toxicit y to A549 epithelial cells, as detachment from substrate, and the prod uction of the proinflammatory cytokine tumor necrosis factor (TNF) by rat alveolar macrophages. Three of the fibers were also studied in viv o, using short-term inhalation followed by a) bronchoalveolar lavage t o assess the inflammatory response and b) measurement of cell prolifer ation in terminal bronchioles and alveolar ducts, using incorporation of bromodeoxyuridine (BrdU). The amount of TUF produced by macrophages in vitro depended on the fiber type, with the man-made vitreous fiber s, and refractory ceramic fibers being least stimulatory and silicon c arbide (SIG) whiskers providing the greatest stimulation. In the epith elial detachment assay there were dose-dependent differences in the to xicity of the various fibers, with long amosite being the most toxic. However, there was no clear relationship to known chronic pathogenicit y. Fibers studied by short-term inhalation produced some inflammation, bur. there was no clear discrimination between the responses to code 100/475 glass fibers and the more pathogenic amosite and SiC. Ho Never , measurements of BrdU uptake into lung cells showed that amosite and SIC produced a greater reaction than code 100/475, which itself caused no more proliferation than that seen in untreated lungs. These result s mirror the pathogenicity ranking of the fibers in long-term experime nts. In conclusion, the only test to show potential as a predictive me asure of pathogenicity was that of cell proliferation in lungs after b rief inhalation exposure (BrdU assay). We believe that this assay shou ld be validated with a wider range of fibers, doses, and time points.