Relationship between lung biopersistence and biological effects of man-made vitreous fibers after chronic inhalation in rats

Our plain-English summary of Relationship between lung biopersistence and biological effects of man-made vitreous fibers after chronic inhalation in rats, by T.W. Hesterberg, W.C. Miiller, R. Mast, et al (Environmental Health Perspectives, 1994).

The study

• Authors: T.W. Hesterberg, W.C. Miiller, R. Mast, E.E. McConnell, D.M. Bernstein, R. Anderson
• Journal: Environmental Health Perspectives
• Published: 1994;102 Suppl 5(Suppl 5):133-7
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

This article describes the relationship between fiber biopersistence and the chronic toxicity of different chemical compositions of man-made vitreous fibers (MMVF) in the lung. Rats were exposed in "nose-only" inhalation chambers, 6 hr/day, 5 days/week, for 24 months to aerosol concentrations of 30 mg/m3 containing comparable fiber numbers and similar dimensions of fibrous glass (FG) or refractory ceramic fiber (RCF). Interim sacrifices were performed periodically to monitor fiber number and dimensions in the lung and the progression of pulmonary alterations. At each interim sacrifice, three to six recovery animals were removed from each exposure group and held until two years to determine the biopersistence of fibers after different exposure times. Fibers were recovered from the ashed lungs, counted, and measured using optical and scanning electron microscopy (SEM). Fiber chemistry was assessed in 91-week recovery lungs using energy dispersive spectroscopy (EDS) analysis. RCF induced lung fibrosis and an elevation in lung tumors and pleural mesotheliomas. FG exposure resulted in no lung fibrosis, no statistically significant increase in the lung tumor incidence, and no mesotheliomas. After two years of continuous exposure, the number of World Health Organization fibers per milligram dry lung recovered from RCF and FG exposed lungs was comparable. EDS analysis of recovery lungs showed that most of the alkalis and alkaline earths had leached from the FG fibers over time. A slight change in RCF chemistry was observed. These findings indicate that the change in the chemical composition of fibers may be an important determinant of the chronic toxicity of MMVFs.

In plain English

This animal experiment compared two kinds of man-made vitreous fibers in the lungs of male Fischer 344 rats. Groups of 140 rats breathed, nose-only, a kaolin-based refractory ceramic fiber (RCF1) or one of two fibrous glass insulation fibers (MMVF 10 or MMVF 11) at 30 mg/m3, 6 hours a day, 5 days a week, for 24 months. Control rats breathed filtered air, and 80 positive-control rats breathed chrysotile asbestos at 10 mg/m3. RCF1 caused lung fibrosis by 6 months, and 13% of these rats developed lung tumors and 1.6% pleural mesotheliomas. In the chrysotile group, 18.9% had lung tumors and one rat (1.4%) had a mesothelioma. The glass fibers caused no fibrosis, no mesotheliomas and no statistically significant increase in lung tumors. Lung fiber counts rose comparably for all three test fibers. In rats exposed for 13 weeks and then held unexposed for 91 weeks, counts fell by similar amounts. MMVF 11 glass fibers lost nearly all their calcium and sodium oxides in the lung, while RCF1 changed only slightly. The authors concluded that an MMVF's toxic potential may depend on its chemical composition.

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 (24-month) nose-only inhalation study in rats, with interim sacrifices and recovery groups
• Who was studied: Weanling male Fischer 344 rats, groups of 140 per test fiber and 80 chrysotile positive controls, plus filtered-air negative controls; study performed at Research and Consulting Company, Geneva, Switzerland, and Mountain Technical Center, Littleton, Colorado
• Exposure: Kaolin-based refractory ceramic fiber (RCF1) and two fibrous glass building-insulation compositions (MMVF 10 and MMVF 11), each at 30 mg/m3; positive controls given intermediate-length NIEHS chrysotile asbestos at 10 mg/m3; negative controls given filtered air
• Main results:
  • RCF1-exposed rats had progressed to minimal lung fibrosis (Wagner grade 4) by the 6-month sacrifice
  • RCF1-exposed rats had a significant increase in lung tumors (13%; Table 2 lists 16, 13.0%) and two pleural mesotheliomas (1.6%)
  • Chrysotile positive controls had lung fibrosis from 3 months, a lung tumor incidence of 18.9%, and one mesothelioma (1.4%)
  • Fibrous glass (MMVF 10 and 11) exposed rats showed no treatment-related interstitial lung fibrosis at any time
  • Fibrous glass exposed rats had no mesotheliomas and no statistically significant rise in lung tumor incidence compared with negative controls (Table 2: MMVF 10, 7 (5.9%); MMVF 11, 3 (2.7%); their air controls, 4 (3.3%))
  • Lung fiber levels during continuous exposure increased comparably in the fibrous glass and RCF exposed rats
  • In RCF1-exposed rats, lung burden rose to 3.6 ± 1.0 x 10^5 WHO fibers/mg dry lung at 78 weeks, then leveled off at 2.8 ± 0.6 x 10^5
  • In MMVF 11-exposed rats, lung burden was 2.5 ± 0.3 x 10^5 WHO fibers/mg at 13 weeks and 5.0 ± 2.9 x 10^5 at 24 months
  • In MMVF 10-exposed rats, lung burden rose from 6.6 ± 1.8 x 10^4 WHO fibers/mg at 13 weeks to 2.9 ± 0.6 x 10^5 at 24 months
  • In rats exposed for 13 weeks and then held without exposure for 91 weeks, WHO fibers/mg fell 87% for RCF1
  • In rats exposed for 13 weeks and then held for 91 weeks, WHO fibers/mg fell 95% for MMVF 11 and 88% for MMVF 10
  • The authors reported that, over the 91-week recovery period after 13 weeks of exposure, the disappearance of fibrous glass from the lung was similar to that of RCF
  • RCF1 fibers recovered after 91 weeks in the lung showed a small but significant change in aluminum oxide content
  • MMVF 11 fibers recovered after 91 weeks in the lung had lost nearly all their calcium oxide and sodium oxide
• The authors' conclusion: The authors concluded that the toxic potential of an MMVF may depend on its chemical composition, and suggested that fibers more readily altered chemically in the lung may be less biologically active
• Limitations the authors state:
  • The authors stated that further analysis is needed before the role of changes in chemistry, fiber number, or shape can be linked to the differences in biological effects
  • The chemistry of fibers recovered from MMVF 10-exposed lungs had not yet been analyzed in this study

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Jeffrey mine, Asbestos, Quebec

All asbestos mines

Topics

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

Medical terms in this study, explained in our Lexicon: biopersistence, Vitreous, Scanning Electron Microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), Fibrosis, Pleural Mesothelioma, Mesothelioma.

Related studies

• Chronic inhalation toxicity of size-separated glass fibers in Fischer 344 rats — T.W. Hesterberg, W.C. Miiller, et al. (1993)
• Biopersistences of man-made vitreous fibers and crocidolite fibers in rat lungs following short-term exposures — R.P. Musselman, W.C. Miiller, et al. (1994)
• The importance of fiber biopersistence and lung dose in determining the chronic inhalation effects of X607, RCF1, and chrysotile asbestos in rats — T.W. Hesterberg, G.A. Hart, et al. (1998)
• Fiber localization and its relationship to lung reaction in rats after chronic inhalation of chrysotile asbestos — K.E. Pinkerton, P.C. Pratt, et al. (1984)
• Chronic inhalation study of fiber glass and amosite asbestos in hamsters: twelve-month preliminary results — T.W. Hesterberg, C. Axten, et al. (1997)
• Chronic inhalation studies of man-made vitreous fibres: characterization of fibres in the exposure aerosol and lungs — T.W. Hesterberg, W.C. Miiller, et al. (1995)

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