Studies on the inhalation toxicology of two fiberglasses and amosite asbestos in the Syrian golden hamster. Part II. Results of chronic exposure.
Fiberglass (FG) is the largest category of man-made mineral fibers (MMVFs). Many types of FG are manufactured for specific uses building insulation, air handling, filtration, and sound absorption. In the United States, > 95% of FG produced is for building insulation. Several inhalation studies in rodents of FG building insulation have shown no indication of pulmonary fibrosis or carcinogenic activity. However, because of increasing use and potential for widespread human exposure, a chronic toxicity/carcinogenicity inhalation study of a typical building insulation FG (MMVF 10a) was conducted in hamsters, which were shown to be highly sensitive to the induction of mesotheliomas with another MMVF. A special-application FG (MMVF 33) and amosite asbestos were used for comparative purposes. Groups of 140 weanling male Syrian golden hamsters were exposed via nose-only inhalation for 6 h/day, 5 days/wk for 78 wk to either filtered air (chamber controls) or MMVF 10a, MMVF 33, or amosite asbestos at 250-300 WHO fibers/cm(3) with two additional amosite asbestos groups at 25 and 125 WHO fibers/cm(3). They were then held unexposed for 6 wk until approximately 10-20% survival. After 13, 26, 52, and 78 wk, various pulmonary parameters and lung fiber burdens were evaluated. Groups hamsters were removed from exposure at 13 and 52 wk and were held until 78 wk (recovery groups). Initial lung deposition of long fibers (>20 microm in length) after a single 6-h exposure was similar for all 3 fibers exposed to 250-300 fibers/cm(3). MMVF 10a lungs showed inflammation (which regressed in recovery hamsters) but no pulmonary or pleural fibrosis or neoplasms. MMVF 33 induced more severe inflammation and mild interstitial and pleural fibrosis by 26 wk that progressed in severity until 52 wk, after which it plateaued. While the inflammatory lesions regressed in the recovery animals, pulmonary or pleural fibrosis did not. A single multicentric mesothelioma was observed at 32 wk. No neoplasms were found in the remainder of the study. Amosite asbestos produced dose-related inflammation and pulmonary and pleural fibrosis as early as 13 wk in all 3 exposure levels. The lesions progressed during the course of the study, and at 78 wk severe pulmonary fibrosis with large areas of consolidation was observed in the highest 2 exposure groups. Progressive pleural fibrosis with mesothelial hypertrophy and hyperplasia was present in the thoracic wall and diaphragm in most animals and increased with time in the recovery hamsters. While no pulmonary neoplasms were observed in the amosite exposed hamsters, a large number of mesotheliomas were found; 25 fibers/cm(3), 3.6%; 125 fibers/cm(3), 25.9%; and 250 fibers/cm(3), 19.5%. For the 3 fiber types, the severity of the lung and pleural lesions generally paralleled the cumulative fiber burden, especially those >20 microm length, in the lung, thoracic wall, and diaphragm. They also inversely paralleled the in vitro dissolution rates; that is, the faster the dissolution, the lower were the cumulative lung burdens and the less severe the effects.
McConnell
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ToxPath, Inc., 3028 Ethan Lane, Raleigh, NC 27613, USA. toxpathmcc@aol.com
Axten
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Hesterberg
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Chevalier
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Miiller
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Everitt
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Oberdörster
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Chase
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Thevenaz
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Kotin
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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 / Q000378:metabolism / Q000473:pathology*; D008171:Lung Diseases / Q000139:chemically induced / Q000473:pathology; D008297:Male; D008647:Mesocricetus; D019016:Mineral Fibers / Q000633:toxicity*; D023421:Models, Animal; D009929:Organ Size / Q000187:drug effects; D010994:Pleura / Q000473:pathology; D013997:Time Factors
D002273:Carcinogens; D019016:Mineral Fibers; C009753:fiberglass; D017639:Asbestos, Amosite