Lung tumors from PuO<sub>2</sub>‐ZrO<sub>2</sub> aerosol particles in syrian hamsters

Thomas, Robert G.; Smith, David M.

doi:10.1002/ijc.2910240512

Cited by 7 publications

(2 citation statements)

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“…Although this exposure caused a significant inflammatory response and severe pulmonary pathology with some of the fibers, it did not cause observable clinical signs or effects on body weight gain or survival. Median survival in this study (70-82 wk, includes 14 wk preexposure) compared favorably with past long-term studies in male hamsters, which typically have a median survival of 70-80 wk (NTP, 1983;Thomas & Smith, 1979;Smith et al, 1987;McConnell et al, 1995). The epizootic of enteritis depressed survival to some extent, but survival was still in line with previous lifetime studies in hamsters, and a sufficient number of hamsters survived to the end of the exposure period to evaluate the carcinogenic potential of the fibers.…”

Section: Figure 19supporting

confidence: 50%

Studies on the Inhalation Toxicology of Two Fiberglasses and Amosite Asbestos in the Syrian Golden Hamster. Part Ii. Results of Chronic Exposure

McConnell

Axten

Hesterberg³

et al. 1999

Inhalation Toxicology

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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 ...

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Section: Figure 19supporting

confidence: 50%

Studies on the Inhalation Toxicology of Two Fiberglasses and Amosite Asbestos in the Syrian Golden Hamster. Part Ii. Results of Chronic Exposure

McConnell

Axten

Hesterberg³

et al. 1999

Inhalation Toxicology

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“…In an imaginative series of studies at Los Alamos Scientific Laboratories, Syrian golden hamsters were intravenously injected with microspheres of 10 ,um diameter containing Pu and ZrO2 ceramic (51,67,68). The microspheres lodged in the pulmonary capillaries and remained immobile for the life of the hamster.…”

Section: Hamstersmentioning

confidence: 99%

Radionuclide injury to the lung.

Dagle¹,

Sanders²

1984

Environ Health Perspect

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Radionuclide injury to the lung has been studied in rats, hamsters, dogs, mice and baboons. Exposure of the lung to high dose levels of radionuclides produces a spectrum of progressively more severe functional and morphological changes, ranging from radiation pneumonitis and fibrosis to lung tumors. These changes are somewhat similar for different species. Their severity can be related to the absorbed radiation dose (measured in rads) produced by alpha, beta or gamma radiation emanating from various deposited radionuclides. The chemicophysical forms of radionuclides and spatial-temporal factors are also important variables. As with other forms of injury to the lung, repair attempts are highlighted by fibrosis and proliferation of pulmonary epithelium. Lung tumors are the principal late effect observed in experimental animals following pulmonary deposition of radionuclides at dose levels that do not result in early deaths from radiation pneumonitis or fibrosis. The predominant lung tumors described have been of epithelial origin and have been classified, in decreasing frequency of occurrence, as adenocarcinoma, bronchioloalveolar carcinoma, epidermoid carcinomas and combined epidermoid and adenocarcinoma. Mesothelioma and fibrosarcoma have been observed in rats, but less commonly in other species. Hemangiosarcomas were frequency observed in dogs exposed to beta-gamma emitters, and occasionally in rats exposed to alpha emitters. These morphologic changes in the lungs of experimental animals were reviewed and issues relevant to the prediction of human hazards discussed.

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Pulmonary Tumours in Syrian Hamsters Following Inhalation of²³⁹PuO₂

Thomas

Drake

London

et al. 1981

International Journal of Radiation Biology and Related Studies

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Syrian hamsters were exposed to various levels of aerosolized 239PuO2 particles to attain a range of initial lung burdens (medians ranged from 40 to 144 nCi). They were allowed to live without sacrifice and had gross and microscopic tissue examinations at death. Over a range of median lung doses from 4-12 000 rad there was an average 2 per cent incidence of malignant tumours (adenocarcinomas) and 9 per cent incidence of total tumours (primarily adenomas). Some of these results are consistent with those from other laboratories using plutonium oxide aerosols but they represent considerably lower lung tumour incidences than previously observed in this laboratory using aerosols of 238PuO2-ZrO2 particles.

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Lung tumors from PuO₂‐ZrO₂ aerosol particles in syrian hamsters

Cited by 7 publications

References 7 publications

Studies on the Inhalation Toxicology of Two Fiberglasses and Amosite Asbestos in the Syrian Golden Hamster. Part Ii. Results of Chronic Exposure

Studies on the Inhalation Toxicology of Two Fiberglasses and Amosite Asbestos in the Syrian Golden Hamster. Part Ii. Results of Chronic Exposure

Radionuclide injury to the lung.

Pulmonary Tumours in Syrian Hamsters Following Inhalation of²³⁹PuO₂

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Lung tumors from PuO2‐ZrO2 aerosol particles in syrian hamsters

Cited by 7 publications

References 7 publications

Studies on the Inhalation Toxicology of Two Fiberglasses and Amosite Asbestos in the Syrian Golden Hamster. Part Ii. Results of Chronic Exposure

Studies on the Inhalation Toxicology of Two Fiberglasses and Amosite Asbestos in the Syrian Golden Hamster. Part Ii. Results of Chronic Exposure

Radionuclide injury to the lung.

Pulmonary Tumours in Syrian Hamsters Following Inhalation of239PuO2

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Lung tumors from PuO₂‐ZrO₂ aerosol particles in syrian hamsters

Pulmonary Tumours in Syrian Hamsters Following Inhalation of²³⁹PuO₂