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

Our plain-English summary of 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, by T.W. Hesterberg, C. Axten, E.E. McConnell, et al (Inhalation Toxicology, 1999).

The study

• Authors: T.W. Hesterberg, C. Axten, E.E. McConnell, G.A. Hart, W. Miiller, J. Chevalier, J. Everitt, P. Thevenaz, G. Oberdörster
• Journal: Inhalation Toxicology
• Published: 1999;11(9):747-84
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

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.

In plain English

This was an animal inhalation experiment in male Syrian golden hamsters. Its main part was a 13-week study of nose-only inhalation of MMVF10.1, a glass fiber representing Johns Manville 901 building insulation. Doses were 0, 3, 16, 30, 45 or 60 mg/m3, followed by 10 weeks without exposure. The aim was to pick the maximum tolerated dose for a longer study. From 16 mg/m3 upward, lung-wash neutrophils and lung cell division were significantly raised after 13 weeks. Clumps of fiber-filled macrophages appeared at 45 and 60 mg/m3, and no interstitial fibrosis was seen. The article also reported selected results of an 18-month study of essentially the same insulation glass (MMVF10a), a special-application glass (MMVF33) and amosite asbestos at three concentrations. No lung or pleural tumors were observed with MMVF10a. MMVF33-exposed hamsters developed interstitial and pleural fibrosis, and one had a mesothelioma. Pleural mesotheliomas were seen in all three amosite groups, but no lung tumors. The authors concluded that, for 901 insulation fiberglass such as MMVF10a, 30 mg/m3 achieved or exceeded the maximum tolerated lung dose in a hamster chronic study.

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 inhalation experiment: a multidose 13-week (subchronic) study used to choose the maximum tolerated dose, plus selected results from a 78-week (chronic) hamster study reported in full elsewhere
• Who was studied: Male Syrian golden hamsters. Subchronic study: at least 31 per exposure group, from Charles River Laboratories, Sulzfeld, Germany. Chronic study: 125-140 males per exposure group, from Charles River Laboratories, Quebec, Canada.
• Exposure: Nose-only inhalation, 6 h/day, 5 days/wk. Subchronic study: MMVF10.1 (901 building insulation fiberglass) at target concentrations of 0, 3, 16, 30, 45 or 60 mg/m3 for 13 weeks, then 10 weeks of recovery. Chronic study: for 78 weeks, MMVF10a (901 fiberglass, about 30 mg/m3, 339 WHO fibers/cc), MMVF33 (475 special-application fiberglass, 36.8 mg/m3, 310 WHO fibers/cc), or amosite asbestos at low, mid and high concentrations (0.8, 3.7 and 7.3 mg/m3; 36, 165 and 263 WHO fibers/cc).
• Main results:
  • Subchronic study, after 13 weeks: lung-wash (bronchoalveolar lavage) neutrophils were significantly elevated at 16 mg/m3 and above, and were sevenfold greater than in air controls at 30 and 60 mg/m3.
  • Subchronic study: lung-wash LDH, NAG and total protein in the fiber-exposed groups did not differ significantly from controls, either after 13 weeks of exposure or after 10 weeks of recovery.
  • Subchronic study: lung epithelial cell proliferation was significantly elevated after 13 weeks of exposure at 16 mg/m3 and above, but not after the 10-week recovery period.
  • Subchronic study: lung changes did not exceed Wagner grade 2 at any time point, and there was no evidence of interstitial fibrosis.
  • Subchronic study: abnormal clumps of fiber-containing macrophages were seen in hamsters exposed to 45 and 60 mg/m3 and persisted through at least 6 weeks of recovery.
  • Chronic study: after 52 weeks, lung fiber burdens in all five fiber-exposure groups rose faster than before.
  • Chronic study, after 78 weeks: all five fiber groups had significantly elevated fiber numbers in the mediastinal tissue (lymph nodes) and the thoracic wall. The MMVF33 group and all three amosite groups also had elevated fiber numbers in the diaphragm.
  • Chronic study, after 13 weeks: the average time to clear 50% of test microspheres from the lower lung was 28 days in air controls, 19 days for MMVF10a, 22 days for MMVF33, and 37, 62 and 87 days for low-, mid- and high-dose amosite.
  • Chronic study: lung-wash neutrophils were elevated 10-fold or more in all fiber groups after 13 weeks of exposure.
  • Chronic study: no pulmonary or pleural tumors were observed in MMVF10a-exposed hamsters, and their lung lesions completely regressed in the recovery animals.
  • Chronic study: MMVF33-exposed hamsters had interstitial and pleural fibrosis at 26 weeks, which progressed until 52 weeks.
  • Chronic study: a single mesothelioma was observed in the MMVF33 group, at 32 weeks.
  • Chronic study: amosite-exposed hamsters in the mid- and high-dose groups had massive inflammation and interstitial and pleural fibrosis. No lung tumors were found, but pleural mesotheliomas were observed in all three amosite groups. The numbers of animals affected are not given in this article.
  • Chronic study: mortality and body weights were not affected by the fiber exposures.
• The authors' conclusion: The authors concluded that a set of short-term lung and chest changes can be used to estimate the maximum tolerated dose for a chronic inhalation study of fiberglass. They also concluded that for a fiber they described as innocuous, such as MMVF10a, this dose for a hamster chronic study is achieved or exceeded at 30 mg/m3, roughly 300 WHO fibers/cm3 (100-130 fibers/cm3 longer than 20 micrometers).
• Limitations the authors state:
  • In the subchronic study, lung fiber burdens did not correlate well with aerosol concentration.
  • The authors stated that proof the maximum tolerated dose was reached can only come from the chronic study.
  • In the fiberglass groups, the faster rise in lung fiber burdens (suggesting impaired fiber clearance) conflicted with the finding that microsphere clearance was not impaired.
  • For very rapidly dissolving fibers, it may be impossible to reach the maximum tolerated lung dose by inhalation.

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, Lactate Dehydrogenase (LDH), Macrophage, Inflammation, Fibrosis, Pleural Mesothelioma.

Related studies

• Studies on the inhalation toxicology of two fiberglasses and amosite asbestos in the Syrian golden hamster. Part II. Results of chronic exposure — E.E. McConnell, 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)
• 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)
• Investigations on the effects of chronic cigarette-smoke inhalation in Syrian golden hamsters — W. Dontenwill, H.J. Chevalier, et al. (1973)
• 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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