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/m(3) [250-300 WHO fibers (>5 mu m long)/cm(3) and 700-130 fibers/cm(3) >20 mu m 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/m(3) (36, 206, 316, 552, or 714 WHO fibers/cm(3)), then monitored for 10 wk. Results demonstrating MTD were: inflammatory response tall fiber exposures); elevated lung cell proliferation with greater than or equal to 16 mg/m(3); lung lavage neutrophil elevations with greater than or equal to 16 mg/m(3) and lactate dehydrogenase (LDH) and protein elevations with greater than or equal to 30 mg/m(3); and persistent abnormal macrophage/fiber clumps in lungs exposed to 45 and 60 mg/m(3), which suggest overloading of clearance mechanisms. For the chronic study, hamsters were exposed for 78 wk to MMVF10a (901 fiber glass) or MMVF33 (special-application 475 fiberglass) at similar to 300 WHO fibers/cm(3) (similar to 100 fibers/cm(3) >20 mu m long), or to amosite asbestos at an equivalent concentration and 2 lower concentrations. All fiber-exposed animals had pulmonary inflammation, elevated lung lavage cells, and increased lung cell proliferation. Between 52 and 78 wk of exposure, lung burdens of all fibers increased at an accelerated rate, suggesting impairment of clearance mechanisms. MMVF33 and amosite induced fibrosis and pleural mesothelioma. These findings substantiate that exposures in the chronic study adequately tested the toxic potential of fiberglass.