Studies on the inhalation toxicology of two fiberglasses and amosite asbestos in the Syrian golden hamster. Part II. Results of chronic exposure

Our plain-English summary of Studies on the inhalation toxicology of two fiberglasses and amosite asbestos in the Syrian golden hamster. Part II. Results of chronic exposure, by E.E. McConnell, C. Axten, T.W. Hesterberg, et al (Inhalation Toxicology, 1999).

The study

• Authors: E.E. McConnell, C. Axten, T.W. Hesterberg, J. Chevalier, W.C. Miiller, J. Everitt, G. Oberdörster, G.R. Chase, P. Thevenaz, P. Kotin
• Journal: Inhalation Toxicology
• Published: 1999;11(9):785-835
• Cited by: 56 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

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.

In plain English

In this animal experiment, male Syrian golden hamsters breathed fibers nose-only, 6 hours a day, 5 days a week, for up to 78 weeks. Groups of 125 received one of two fiberglasses or amosite asbestos; 140 controls breathed filtered air. The fiberglasses were MMVF 10a, a typical insulation glass, and the more durable special-application MMVF 33. Amosite targets were 25, 125 or 250 WHO fibers/cm3 (measured averages 36, 165 and 263). Controls and MMVF 10a hamsters had no lung or mesothelial tumors; MMVF 10a inflammation regressed after exposure stopped. MMVF 33 produced lung and pleural fibrosis. One MMVF 33 hamster developed a mesothelioma at about 32 weeks. The authors called it possibly spurious and not statistically significant but treated it as exposure-related. Amosite produced dose-related fibrosis. Mesotheliomas occurred in 3 of 83 low-dose (not statistically significant), 22 of 85 mid-dose and 17 of 87 high-dose hamsters. No hamster had a primary lung tumor; the authors suggested hamsters resist particle-induced lung tumors. Enteritis reduced survival. The authors concluded that MMVF 33 caused irreversible disease and amosite was the most pathogenic.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment: chronic inhalation toxicity and carcinogenicity study, with nose-only exposure for up to 78 weeks and some groups followed during unexposed recovery periods
• Who was studied: Weanling male Syrian golden hamsters (from Charles River Canada): 140 in the filtered-air control group and 125 in each of five fiber-exposed groups
• Exposure: Size-separated fibers of MMVF 10a (insulation fiberglass) and MMVF 33 (special-application fiberglass), each at a target of about 250 WHO fibers/cm3, and amosite asbestos at targets of about 250, 125 and 25 WHO fibers/cm3 (measured averages are given under results)
• Main results:
  • Measured average amosite concentrations were 36 ± 23 (low), 165 ± 61 (mid) and 263 ± 90 (high) WHO fibers/cm3, against targets of 25, 125 and 250
  • Achieved average concentrations of WHO fibers were 24–44% above the 250 fibers/cm3 target for the two fiberglasses and 5% above it for high-dose amosite
  • No lung or mesothelial tumors occurred in the control or MMVF 10a hamsters
  • MMVF 10a caused lung inflammation that regressed in recovery hamsters, without pulmonary or pleural fibrosis
  • MMVF 10a hamsters showed a mild but statistically significant increase in pleural collagen over controls at 52 weeks only
  • MMVF 33 produced inflammation and mild interstitial and pleural fibrosis by 26 weeks; these progressed until 52 weeks and then plateaued
  • One MMVF 33 hamster developed a mesothelioma at about 32 weeks (1 of 83, 1.2%, in Table 8)
  • Amosite lung and pleural lesions were dose related and progressed throughout the study
  • At the end of the study, the lungs of mid- and high-dose amosite hamsters weighed more than twice those of controls
  • Amosite mesotheliomas, among hamsters surviving at least 32 weeks: low dose 3 of 83 (4%; 3.6% in Table 8), mid dose 22 of 85 (26%; 25.9%), high dose 17 of 87 (20%; 19.5%). The mid-dose incidence was higher than the high-dose incidence
  • The low-dose amosite mesothelioma incidence was not statistically significant compared to controls
  • The mid- and high-dose amosite mesothelioma incidences were statistically significant (p less than 0.001)
  • No hamster in any group developed a primary lung tumor
  • Amosite was poorly cleared from the lungs: 7–39% clearance during 65 weeks of recovery after 13 weeks of exposure
  • Over the same recovery period, lung clearance was 98% or more for MMVF 10a and 87% or more for MMVF 33
• The authors' conclusion: The authors concluded that MMVF 33, a more biopersistent fiber, caused irreversible disease, and that amosite asbestos, practically indestructible in the body, was the most pathogenic
• Limitations the authors state:
  • An outbreak of enteritis (enterotoxemia associated with Clostridium difficile) reduced survival to some extent
  • The single MMVF 33 mesothelioma may be spurious and was not statistically significant, although the authors chose to treat it as exposure-related
  • Hamsters appear resistant to lung tumors from particles, so the absence of lung tumors in hamsters may be misleading
  • It was not known whether the hamsters carried SV40 virus, which has been linked to mesothelioma in hamsters

Topics

The National Library of Medicine indexes this study under subjects our site covers: Amosite.

Medical terms in this study, explained in our Lexicon: Amosite, Mineral Fiber, Pulmonary Fibrosis, Carcinogenic, Mesothelioma, Fiber Burden, Deposition, Inflammation.

Related studies

• 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 — T.W. Hesterberg, C. Axten, et al. (1999)
• Chronic inhalation study of fiber glass and amosite asbestos in hamsters: twelve-month preliminary results — T.W. Hesterberg, C. Axten, et al. (1997)
• Chronic effects of dietary exposure to amosite and chrysotile asbestos in Syrian golden hamsters — E.E. McConnell, A.M. Shefner, et al. (1983)
• Investigations on the effects of chronic cigarette-smoke inhalation in Syrian golden hamsters — W. Dontenwill, H.J. Chevalier, et al. (1973)
• Evaluation of the exposure, dose-response and fate in the lung and pleura of chrysotile-containing brake dust compared to TiO2, chrysotile, crocidolite or amosite asbestos in a 90-day quantitative inhalation toxicology study - Interim results Part 1: Experimental design, aerosol exposure, lung burdens and BAL — D.M. Bernstein, B. Toth, et al. (2020)
• Evaluation of the dose-response and fate in the lung and pleura of chrysotile-containing brake dust compared to TiO2, chrysotile, crocidolite or amosite asbestos in a 90-day quantitative inhalation toxicology study - Interim results Part 2: Histopathological examination, Confocal microscopy and collagen quantification of the lung and pleural cavity — D.M. Bernstein, B. Toth, et al. (2020)

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