COMPARISON OF THE CHEMICAL EVOLUTION OF MMVF FOLLOWING INHALATION EXPOSURE IN RATS AND ACELLULAR IN-VITRO DISSOLUTION

In the process of developing new fibers or evaluating existing fibers, the dissolution coefficient is often determined using an acellular in vitro assay. This coefficient has been found useful in selecting fibe rs based on solubility and has been shown to be related to the clearan ce half-time of long fibers (>20 mu m) following inhalation in rats. T he chemical evolution of fibers following in vitro dissolution and inh alation was examined to evaluate the comparability of these two method s. The fibers studied ranged from compositions similar to commercial i nsulation materials to new glasses and stone wools that have been deve loped for enhanced solubility. The inhalation studies were performed u sing Fischer 344 male rats exposed to a well-defined rat respirable ae rosol (mean diameter of similar to 1 mu m) at a concentration of 30 mg /m(3), 6 h/day for 5 days, with postexposure sacrifices at I h, I day, 5 days, 4 wk, 13 wk, and 26 wk. The in vivo results reported have bee n from fibers recovered from the lung that were primarily less than 20 mu m length. The in vitro dissolution measurements were performed usi ng a continuous-flow model with simulated lung fluid based upon a modi fied Gamble's media using either 1- or 10-mu m-diameter fibers without discrimination of length. The inhalation studies show that the compos ition of many of the fibers recovered from the lung changes with time in the lungs, with a depletion in Na2O, CaO, and MgO and a relative en richment in SiO2 and Al2O3, with this evolution strongly depending upo n glass composition. B2O3 has been found (on 10 mu m-diameter fibers i n vitro as analyzed by secondary ion mass spectrometry) to also be dep leted. The chemical evolution of these shorter fibers (L < 20 mu m) is consistent with that obtained from the in vitro experiments at pH 7.4 , although the rate of variation observed with the two methods varied. These results clearly demonstrate that those fibers whose composition changes quickly during in vivo studies are the same as those whose co mposition changes quickly during in vitro assays. These studies demons trate that the chemical evolution of the shorter fibers recovered foll owing in vivo inhalation studies mirrors closely the changes found fro m the in vitro assays. These results complement those already reported for fibers longer than 20 mu m, which have been shown to be removed f rom the lung primarily by dissolution.