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 microm long)/cm(3) and 100-130 fibers/cm(3) >20 microm 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 (all fiber exposures); elevated lung cell proliferation with @ges;16 mg/m(3); lung lavage neutrophil elevations with @ges;16 mg/m(3) and lactate dehydrogenase (LDH) and protein elevations with > or = 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 approximately 300 WHO fibers/cm(3) ( approximately 100 fibers/cm(3) @gt;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.
Hesterberg
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Johns Manville Technical Center, PO Box 625005, Littleton, CO 80162-5005, USA. hesterbe@jm.com
Axten
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McConnell
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Hart
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Miiller
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Chevalier
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Everitt
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Thevenaz
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Oberdörster
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D000336:Aerosols; D000818:Animals; D017639:Asbestos, Amosite / Q000008:administration & dosage / Q000633:toxicity*; D001822:Body Burden; D001835:Body Weight / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D005898:Glass; D019570:Inhalation Exposure / Q000009:adverse effects*; D008168:Lung / Q000473:pathology*; D008171:Lung Diseases / Q000139:chemically induced / Q000473:pathology; D008297:Male; D008647:Mesocricetus; D008863:Microspheres; D019016:Mineral Fibers / Q000633:toxicity*; D023421:Models, Animal; D009929:Organ Size / Q000187:drug effects; D013997:Time Factors
D000336:Aerosols; D002273:Carcinogens; D019016:Mineral Fibers; C009753:fiberglass; D017639:Asbestos, Amosite