USE OF LUNG TOXICITY AND LUNG PARTICLE CLEARANCE TO ESTIMATE THE MAXIMUM TOLERATED DOSE (MTD) FOR A FIBER GLASS CHRONIC INHALATION STUDY INTHE RAT

Short-term toxicity and lung clearance were assessed in rats exposed b y inhalation to size-selected fibrous glass (FG) for 13 weeks. Results from this study and from a recent FG chronic inhalation study are pre sented here as guidelines for the selection of a maximum tolerated dos e (MTD) for chronic inhalation studies of fibers. Fischer 344 rats wer e exposed using nose-only inhalation chambers, 6 hr/day, 5 days/week, for 13 weeks to one of five concentrations of FG (36, 206, 316, 552, o r 714 fibers/cc; expressed gravimetrically, 3, 16, 30, 45, or 60 mg/m( 3)) or to filtered air. Rats were then held for an additional 10 weeks of postexposure recovery. Test fiber was size-selected from glass woo l having a chemical composition representative of building insulation. Rats were terminated at 7, 13, 19, and 23 weeks after the onset of ex posure to evaluate pulmonary pathology, lung epithelium cell prolifera tion, lung fiber burden, and lung lavage cells and chemistry. The effe ct of fiber inhalation on lung clearance of innocuous microspheres was also evaluated: following fiber exposure, six rats/group were exposed to Sr-85-labeled 3.0-mu m polystyrene microspheres by intratracheal i nhalation and then monitored for whole body radioactivity during the 1 0-week recovery period. Data from the short-term study support the cho ice of 30 mg/m(3) as the MTD for the previous chronic FG study and als o provide indicators of long-term lung toxicity and functional impairm ent that can be used to estimate the MTD for future chronic fiber inha lation studies. (C) 1996 Society of Toxicology