STUDIES ON THE INHALATION TOXICOLOGY OF TWO FIBERGLASSES AND AMOSITE ASBESTOS IN THE SYRIAN GOLDEN HAMSTER. PART I. RESULTS OF A SUBCHRONIC STUDY AND DOSE SELECTION FOR A CHRONIC STUDY

A multidose, subchronic inhalation study was used to estimate the maximum tolerated dose (MTD) of 901 fiberglass (MMVF10.1) for a chronic inhalation study using hamsters. Subchronic study results indicated that 30 mg/m3 [250-300 WHO fibers (> 5 mum long)/ cm3 and 100-130 fibers/cm3 > 20 mum long] meets or exceeds the estimated MTD, and chronic study results confirmed this. For the subchronic study, hamsters were exposed 6 h/day, 5 days/wk, for 13 wk to MMVF10.1 at 3, 16, 30, 45, and 60 mg/m3 (36, 206, 316, 552, or 714 WHO fibers/cm3), then monitored for 10 wk. Results demonstrating MTD were: inflammatory response (all fiber exposures); elevated lung cell proliferation with 16 mg/m3; lung lavage neutrophil elevations with 16 mg/m3 and lactate dehydrogenase (LDH) and protein elevations with 30 mg/m3; and persistent abnormal macrophage/ fiber clumps in lungs exposed to 45 and 60 mg/m3, which suggest overloading of clearance mechanisms. For the chronic study, hamsters were exposed for 78 wk to MMVF10a (...