Chronic Inhalation Toxicity of Size-Separated Glass Fibers in Fischer 344 Rats

This study was initiated to determine the chronic biologicaleffects in Fisher 344 rats of inhaled size-separated respirablefractions of fibrous glass (FG) having compositions representativeof common building insulation wools. Rats were exposed usingnose-only inhalation chambers, 6 hr/day, 5 days/week, for 24months to three concentrations (3, 16, and 30 mg/m³) of twodifferent compositions of FG (designated MMVF 10 and MMVF 11),or to filtered air (negative control). Fibrous glass findingswere compared to those from a concurrent inhalation study ofchrysotile asbestos and refractory ceramic fiber (RCF). TheFGs used in this study were size selected to be largely respirablein the rat and the aerosol generation technique did not alterthe dimensions of the fibers. Interim euthanizations took placeat 3- to 6-month intervals to monitor progression of pulmonarychanges. Fibers were recovered from digested lung tissue fordetermination of changes in fiber number and morphology. Inanimals exposed to 30 mg/m³ of MMVF 10 or MMVF 11, 4.2±0.9x10⁵and 6.4±3.1x10⁵ fibers/mg dry lung tissue, respectively,were recovered after 24 months of exposure. Exposure to chrysotileasbestos (10 mg/m³) and to a lesser extent RCF (30 mg/m³) resultedin pulmonary fibrosis as well as mesothelioma and significantincreases in lung tumors. FG exposure was associated with anonspecific inflammatory response (macrophage response) in thelungs that did not appear to progress after 6–12 monthsof exposure. These cellular changes are reversible and are similarto the effects observed after inhalation of an inert dust. Nolung fibrosis was observed in the FG-exposed animals. Further,FG exposure resulted in no mesotheliomas and no statisticallysignificant increase in lung tumor incidence when compared tothat of the negative control group. These findings, along withprevious inhalation studies, suggest that respirable fibrousglass does not represent a significant hazard for fibrotic orneoplastic lung disease in humans.