Experimental approaches for exposure to sized glass fibers

Our plain-English summary of Experimental approaches for exposure to sized glass fibers, by D.M. Bernstein, R.T. Drew, M. Kuschner (Environmental Health Perspectives, 1980).

The study

• Authors: D.M. Bernstein, R.T. Drew, M. Kuschner
• Journal: Environmental Health Perspectives
• Published: 1980;34:47-57
• Cited by: 28 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

A number of studies have shown that glass fibers induce both malignant mesothelioma and fibrosis in rats and that these reactions may be primarily a function of the physical properties of the fiber. However, these studies were carried out with fibers having broad size distributions and used methods of administration which bear little resemblance to the way man is exposed. To better characterize the health effects of glass fibers, techniques have been developed to expose rats to glass fibers of defined sizes by intratracheal instillation of aqueous suspensions and by "nose only" inhalation exposure, and to determine the deposition, translocation, and ultimate fate of these fibers in the rat. The fibers have known size distributions with geometric mean diameters of 1.5 micrometers (sigma g = 1.1) and lengths of either 5 micrometers (sigma g = 1.49) or 60 micrometers (sigma g = 3.76). The fibers have been activated with neutron irradiation. Of the several resulting radionuclides, 65Zn appeared to be the most suitable for long-term clearance studies by use of in vivo whole body radioassay techniques. A fluidized bed aerosol generator has been developed to expose rats by "nose only" inhalation to approximately 500 fibers/cm3. The generator and exposure system permits reuse of fibers which pass through the exposure chamber and produces no significant alteration of the fiber size distribution. Rats were exposed by intratracheal instillations to 20 mg of the longer fibers and to equal numbers (2 mg) and equal mass (20 mg) of the shorter fibers. Through approximately 19 weeks little difference was observed in the whole rat clearance rate of long versus short fibers in the initial exposure group. Histopathology, however, showed differences at this time with the short fibers apparently successfully phagocytized by alveolar macrophages and cleared to the lymph nodes, while the long fibers were not.

In plain English

This animal experiment developed ways to expose rats to sized glass fibers and reported early results. The Johns Manville fibers were nominally 1.5 by 5 (short) or 1.5 by 60 micrometers (long); lengths varied, with measured geometric means of 5.1 and 54 micrometers. Neutron irradiation made them radioactive for tracking. The authors built a nose-only inhalation system delivering about 500 fibers per cubic centimeter. Results were reported only for male Fisher 344 rats given fibers into the windpipe. Groups of four rats received 20 mg of long fibers, or 2 mg or 20 mg of short fibers, and were examined at 17 to 19 weeks. Estimated clearance half-times were 35.0, 22.5 and 38.5 days, respectively. Long fibers produced foreign body granulomas with giant cells; none were seen in lymph nodes. Short fibers were taken up by macrophages and reached lymph nodes. The authors found no fibrosis in the long-fiber or 20 mg short-fiber groups. The authors concluded that clearance differed little by fiber length, but tissue responses differed. They cautioned that a single time point allowed no statement about progression.

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: development of exposure methods (intratracheal instillation and nose-only inhalation), with clearance and histology results reported only for intratracheal instillation
• Who was studied: Male Fisher 344 rats, about 10 weeks old at exposure. Four groups of 4 rats each (three fiber groups and a saline-only group) were examined at 17 to 19 weeks. Further rats were instilled for later serial sacrifices not reported here.
• Exposure: Neutron-activated glass fibers (Johns-Manville Batch JM-753 glass) in two nominal size groups, 1.5 by 5 micrometers or 1.5 by 60 micrometers. The actual lengths varied within each group, but the two groups did not overlap significantly. Doses were 20 mg of long fibers, 2 mg of short fibers (about the same number of fibers as the long-fiber group) or 20 mg of short fibers (the same weight), each in 0.5 cm3 saline instilled into the trachea. A nose-only inhalation system at about 500 fibers per cubic centimeter was also developed.
• Main results:
  • Measured fiber lengths in this study: geometric mean 5.1 micrometers (geometric SD 1.49, 250 fibers) for the short group and 54 micrometers (geometric SD 3.76, 500 fibers) for the long group
  • Clearance curves of the 20 mg long-fiber group and the 20 mg short-fiber group were not significantly different. The 2 mg short-fiber group showed a small but significant difference (p less than 0.05) from both.
  • Long fibers, 20 mg group: clearance half-time 35.0 days, 16.3 plus or minus 1.2 percent of the dose remaining at about 114 days
  • Short fibers, 2 mg group: clearance half-time 22.5 days, 14.3 plus or minus 7.8 percent remaining at about 114 days
  • Short fibers, 20 mg group: clearance half-time 38.5 days, 14.8 plus or minus 1.6 percent remaining at about 114 days
  • Long fibers (20 mg) caused numerous large foreign body granulomas with giant cells. One of the four rats showed a much milder process. There was no fibrosis.
  • No 60 micrometer fibers were seen in the lymph nodes of the long-fiber group, and none were seen fully engulfed by macrophages.
  • Short fibers at 2 mg produced little change in three rats and a mild macrophage response in the fourth.
  • Short fibers at 20 mg produced large numbers of fiber-laden macrophages and no fibrosis. The fibers reached the lymph nodes in large numbers.
  • Few, if any, fibers were found by light microscopy outside the respiratory tissues.
• The authors' conclusion: The authors concluded that through 17 to 19 weeks, whole-rat clearance of long and short fibers differed little. Tissue responses differed: short fibers were engulfed by macrophages and cleared to lymph nodes, while long fibers were not and produced a granulomatous foreign body response.
• Limitations the authors state:
  • Histology came from a single time point with four rats per group, so nothing can be said about how the changes progress.
  • The fiber detection system may not have been able to detect fiber movement between lung and lymph nodes.
  • Intratracheal instillation bears little resemblance to how people are exposed.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Fibrosis, Deposition, Translocation, Histopathology, Alveolar Macrophage.

Related studies

• The chronic effects of exposure of rats to sized glass fibres — R.T. Drew, M. Kuschner, et al. (1987)
• Chronic inhalation toxicity of size-separated glass fibers in Fischer 344 rats — T.W. Hesterberg, W.C. Miiller, et al. (1993)
• Formation of pseudo-asbestos bodies on sized glass fibres in the hamster lung — A. Holmes, A. Morgan, et al. (1983)
• Response of perifused alveolar macrophages to glass fibers: effect of exposure duration and fiber length — G. Forget, M.J. Lacroix, et al. (1986)
• Chronic inhalation study of fiber glass and amosite asbestos in hamsters: twelve-month preliminary results — T.W. Hesterberg, C. Axten, et al. (1997)
• Man-made mineral fiber hazardous properties assessment using transgenic rodents: example of glass fiber testing — M.C. Bottin, J.C. Vigneron, et al. (2003)

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