Lung biopersistence and in vitro dissolution rate predict the pathogenic potential of synthetic vitreous fibers

Here rye review the past decade of research on inorganic fiber toxicology, which demonstrates that fiber biopersistence and in vitro dissolution rate correlate well with fiber pathogenicity. Test fibers for these studies incl uded eight synthetic vitreous fibers (SVFs) - refractory ceramic fiber (RCF 1), four fiber glasses (FCs), rock wool, slag wool, HT stone wool-and two a sbestos types (crocidolite and amosite). Fiber toxicology and biopersistenc e were investigated using rodents exposed by inhalation. To evaluate chroni c inhalation toxicity ro dents were exposed nose-only to similar to 100 fib ers > 20 mu m in length (F > 20 mu m)/cm(3), 6 h/day, 5 days:wk, for 2 yr ( rats) or 7 1/2 yr (hamsters). To evaluate lung biopersistence, rats were ex posed nose-only for 5 days to fiber aerosol; lung burdens were then analyze d during 1 yr postexposure. In vitro dissolution rate was evaluated in a fl ow-through system using physiological solutions that mimic the inorganic co mponents of extra- and intracellular icing fluids. The 10 lest fibers encom passed a range of respiratory toxicities, from transient inflammation only to carcinogenesis. Lung clearance weighted half-times (WT1/2) for F > 20 mu m were 6-15 days for stonewool, building insulation FCs, and slag wool, 50 -80 days for rock wool, 2 special-application FCs, and RCF1; and >400 days for asbestos. WT1/2 correlated with pathogenicity: The rapidly clearing fib ers were innocuous (insulation FCs, slag wool, and stonewool), but the more biopersistent fibers were fibrogenic (rock wool) or fibrogenic and carcino genic (special-application FCs, RCF1, amosite and crocidolite asbestos). In vitro dissolution rates (k(dis) = ng/cm(2)/h) of the 10 fibers at ph 7.4 o r 4.5 ranged from < 1 to > 600. Fibers that dissolved rapidly in vitro also cleared quickly from the lung and induced only transient inflammation in t he chronic studies. In contrast fibers that dissolved slowly in vitro were biopersistent in the lung and tended to induce permanent pathogenicity. Oth er in vitro studies of fiber degradation suggest that, in addition to fiber dissolution, fiber leaching and subsequent transverse breakage may also be important mechanisms in lung biopersistence and hence pathogenicity The va lidity of using lung biopersistence for predicting the potential pathogenic ity of SVFs is confirmed by this research. The research also supports the u se of in vitro fiber degradation at pH 7.4 and/or pH 4.5 as an indicator of SVF potential pathogenicity.