Chronic inhalation study of fiber glass and amosite asbestos in hamsters: twelve-month preliminary results

Our plain-English summary of Chronic inhalation study of fiber glass and amosite asbestos in hamsters: twelve-month preliminary results, by T.W. Hesterberg, C. Axten, E.E. McConnell, et al (Environmental Health Perspectives, 1997).

The study

• Authors: T.W. Hesterberg, C. Axten, E.E. McConnell, G. Oberdörster, J. Everitt, W.C. Miiller, J. Chevalier, G.R. Chase, P. Thevenaz
• Journal: Environmental Health Perspectives
• Published: 1997;105 Suppl 5(Suppl 5):1223-9
• Cited by: 26 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The effects of chronic inhalation of glass fibers and amosite asbestos are currently under study in hamsters. The study includes 18 months of inhalation exposure followed by lifetime recovery. Syrian golden hamsters are exposed, nose only, for 6 hr/day, 5 day/week to size-selected test fibers: MMVF10a (Schuller 901 insulation glass); MMVF33 (Schuller 475 durable glass); amosite asbestos (three doses); or to filtered air (controls). Here we report interim results on airborne fiber characterization, lung fiber burden, and pathology (preliminary) through 12 months. Aerosolized test fibers averaged 15 to 20 microns in length and 0.5 to 1 micron in diameter. Target aerosol concentrations of World Health Organization (WHO) fibers (longer than 5 microns) were 250 fibers/cc for MMVF10a and MMVF33, and 25, 125, or 250 fibers/cc for amosite. WHO fiber lung burdens showed time-dependent and (for amosite) dose-dependent increases. After a 12-month exposure, lung burdens of fibers longer than 20 microns were greatest with amosite high and mid doses, similar for low-dose amosite and MMVF33, and smaller for MMVF10a. Biological responses of animals exposed for 12 months to MMVF10a were limited to nonspecific pulmonary inflammation. However, exposures to MMVF33 and each of three doses of amosite were associated with lung fibrosis and possible mesotheliomas (1 with MMVF33 and 2, 3, and 1 with amosite low, mid, and high doses, respectively). Pulmonary and pleural changes associated with amosite were qualitatively and quantitatively more severe than those associated with MMVF33. As of the 12-month time point, this study demonstrates that two different fiber glass compositions with similar fiber dimensions but different durabilities can have distinctly different effects on the hamster lung and pleura after inhalation exposure. (Preliminary tumor data through 18 months of exposure and 6 weeks of postexposure recovery became available as this manuscript went to press: No tumors were observed in the control or MMVF10a groups, and no additional tumors were observed in the MMVF33 group; however, a number of additional mesotheliomas were observed in the amosite groups.

In plain English

In this experiment, male Syrian golden hamsters (125 to 140 per group) breathed, nose only, 6 hours a day, 5 days a week, one of the following: filtered air, one of two glass fibers (MMVF10a, an insulation glass, or MMVF33, a durable glass), or amosite asbestos at three doses. This interim report covered 12 months of a planned 18-month exposure. Hamsters exposed to MMVF10a showed only mild lung inflammation (a macrophage response), with no treatment-related pleural changes. MMVF33 and each amosite dose were associated with lung fibrosis and pleural changes, more severe with amosite. Possible or early pleural mesotheliomas (preliminary diagnoses) were seen in 1 of 50 MMVF33 hamsters. In the low-, mid- and high-dose amosite groups they were seen in 2 of 42, 3 of 43 and 1 of 56. None were seen in 63 air controls or 63 MMVF10a hamsters. A panel of pathologists was to make the final diagnoses. Preliminary end-of-study data showed additional mesotheliomas only in the amosite groups. The authors concluded that the three fibers had strikingly different effects despite comparable aerosols, pointing to fiber biopersistence and surface reactivity.

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 nose-only inhalation study in hamsters (18 months of exposure followed by lifetime recovery), reporting interim results through 12 months
• Who was studied: Male Syrian golden hamsters, 125 to 140 per exposure group, 13 to 15 weeks old when exposure began. There were six groups: air controls and five fiber groups. Mesothelioma counts used 42 to 63 animals at risk per group. Detailed pathology scores were based on 4 to 5 animals per time point.
• Exposure: Nose-only inhalation, 6 hours a day, 5 days a week, for 18 months. Fibers were MMVF10a (from Schuller 901 insulation glass) and MMVF33 (from Schuller 475 durable glass), each at a target of 250 WHO fibers/cc, and amosite asbestos at targets of 25, 125 and 250 WHO fibers/cc. WHO fibers are fibers longer than 5 micrometers. Controls breathed filtered air.
• Main results:
  • Measured average aerosol concentrations were 323 WHO fibers/cc for MMVF10a, 283 for MMVF33 and 255 for high-dose amosite. MMVF10a was significantly higher than the other two.
  • Air controls and MMVF10a group: 0 mesotheliomas among 63 hamsters at risk in each group during 12 months of exposure.
  • MMVF33 group: 1 early-to-advanced mesothelioma among 50 hamsters at risk (incidence 2.0%).
  • Low-dose amosite group: 2 hyperplasia-borderline mesotheliomas among 42 hamsters at risk (4.8%).
  • Mid-dose amosite group: 1 hyperplasia-borderline and 2 early-to-advanced mesotheliomas among 43 hamsters at risk (7.0%).
  • High-dose amosite group: 1 hyperplasia-borderline mesothelioma among 56 hamsters at risk (1.8%).
  • MMVF10a: lung changes in most hamsters were consistent with Wagner grade 2 (minimal cellular change, a macrophage response). There were no treatment-related pleural changes through 12 months.
  • MMVF33: by 12 months most alveolar ducts and terminal bronchioles showed mild interstitial fibrosis (Wagner grade 4).
  • Lung and pleural lesions in amosite-exposed hamsters were more severe than, and qualitatively different from, those with MMVF33.
  • Mid-dose amosite: at 12 months, interstitial fibrosis had progressed to interlobular linking (Wagner grade 5).
  • High-dose amosite: areas of consolidation were prominent in most lung lobes (Wagner grade 6).
  • Lung weights in the mid- and high-dose amosite groups were significantly higher than in air controls after 13 and 52 weeks.
  • At 52 weeks, the WHO fiber lung burden in the high-dose amosite group was 8-fold greater than in the MMVF10a group.
  • Increased deaths in all groups during weeks 17 to 26 were due to an infectious disease (wet tail). Because deaths were also high in air controls and unexposed sentinel hamsters, this mortality was judged unrelated to fiber exposure.
  • Preliminary data through the end of exposure (18 months plus 6 weeks of recovery) showed no additional tumors in air controls or fiber glass-exposed hamsters. A number of additional mesotheliomas were observed in the amosite groups.
• The authors' conclusion: The authors concluded that the three fiber compositions produced strikingly different effects even though the aerosols had comparable fiber dimensions and concentrations. In their view, this points to the importance of fiber biopersistence and surface reactivity.
• Limitations the authors state:
  • Pathology findings were the study pathologist's preliminary results. A panel of pathologists was to review the lesions independently at the end of the study.
  • Because of increased mortality, the planned 6-month sacrifice was not carried out.
  • The Wagner grading system could not distinguish some clearly more severe lesions (mid-dose amosite still scored grade 4 at one stage).
  • Without data on initial lung deposition, long-fiber deposition could have been greater for amosite because its fibers were thinner than the glass fibers.

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, Fiber Burden, Pathology, Inflammation, Fibrosis, Mesothelioma, Fiber Dimensions, Pleura.

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)
• 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 toxicity of size-separated glass fibers in Fischer 344 rats — T.W. Hesterberg, W.C. Miiller, et al. (1993)
• Pathogenicity of a special-purpose glass microfiber (E glass) relative to another glass microfiber and amosite asbestos — R.T. Cullen, A. Searl, et al. (2000)
• Relationship between lung biopersistence and biological effects of man-made vitreous fibers after chronic inhalation in rats — T.W. Hesterberg, W.C. Miiller, et al. (1994)
• Pulmonary response of hamsters to fibrous glass: chronic effects of repeated intratracheal instillation with or without benzo[a]pyrene — V.J. Feron, P.M. Scherrenberg, et al. (1985)

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