The chronic effects of exposure of rats to sized glass fibres

Our plain-English summary of The chronic effects of exposure of rats to sized glass fibres, by R.T. Drew, M. Kuschner, D.M. Bernstein (The Annals of Occupational Hygiene, 1987).

The study

• Authors: R.T. Drew, M. Kuschner, D.M. Bernstein
• Journal: The Annals of Occupational Hygiene
• Published: 1987;31(4B):711-29
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The long-term effects of exposure to sized (1.5 x 5 µm or 1.5 x 60 µm) man-made glass fibres have been investigated. After instillation of a single bolus of fibres, short fibres were observed inside macrophages. In contrast, macrophages could not engulf the long fibres and the macrophages were often seen arrayed along the long fibres. Intratracheal instillation caused formation of large granulomata which often blocked major airways. These granulomata are thought to be artefacts caused by the method of administration. The limited amount of fibres available for the studies (about 10 g of each size range) precluded the use of standard inhalation techniques. Therefore, a transoral inhalation technique was developed that allowed airborne fibres to bypass the turbinates and be inhaled directly into the lung. The resulting fibre deposition pattern of these inhaled fibres was found to be similar to that resulting from the multiple intratracheal instillation of aqueous suspensions of low concentrations of fibres. Having validated the intratracheal instillation technique, the long-term effects of long and short fibres were evaluated. These results were compared with those resulting from repeated instillation of crocidolite asbestos. The principal lesion resulting from exposure to either the long or the short glass fibres was one in which macrophages were found associated with the glass fibres. In contrast, the asbestos caused a marked granulomatous lesion with fibrosis. Neither glass nor crocidolite asbestos caused marked shortening of the lifespan. Neither instilled nor inhaled fibre glass produced tumours in any animals.

PubMed has no abstract for this study. This is the authors' abstract, copied from the article.

In plain English

This paper summarized five experiments in male Fischer-344 rats. The Thermal Insulation Manufacturers' Association funded the work. Rats received uncoated glass fibres about 1.5 by 5 micrometres (short) or 1.5 by 60 micrometres (long). Most doses were fibre suspensions placed directly into the windpipe. One study compared this with inhaling fibres through a windpipe tube; another gave UICC crocidolite asbestos for comparison. A single 20 mg dose produced large granulomata (clusters of inflammatory cells around fibres), which the authors attributed to the dosing method. No fibrosis was detected in these single-dose glass-fibre groups. Macrophages could not engulf long fibres but took up short ones. With repeated doses totalling 5 mg, glass fibres caused mainly a macrophage response. At 24 months this response was minimal for long fibres and mild for short fibres. Crocidolite, also 5 mg in total, caused a more intense response with fibrosis. Exposures generally did not affect growth or mortality. Among rats surviving past 500 days, 11 to 55% had monocytic leukemia, with similar tumour rates in exposed and control groups. The authors stated that none of the exposures appeared to have caused cancer.

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: Series of five laboratory animal experiments (rats), mainly repeated or single intratracheal instillation, plus one comparison with trachea-only inhalation; lifetime follow-up in several studies
• Who was studied: Male SPF Fischer-344 rats from Charles River, usually about 15 weeks old at the start. Table 1 lists 30 to 50 animals per group (8 per inhalation group and 14 per instillation group in Study 3). The text gives 41 per group for Study 4 and 50 per group for the crocidolite study. The work was done at Brookhaven National Laboratory and the State University of New York at Stony Brook. Study dates are not stated.
• Exposure: Uncoated research glass fibres (63% SiO2, plus Na2O, CaO, Al2O3, B2O3, MgO and K2O), nominally 1.5 by 5 micrometres (short; geometric mean length 5.1 micrometres) or 1.5 by 60 micrometres (long; geometric mean length 54 micrometres). Doses were a single 20 mg (long or short) or 2 mg (short) instillation, 10 weekly 0.1 mg instillations, or 10 weekly 0.5 mg instillations (5 mg total). The inhalation groups were exposed 1 hour weekly for 10 weeks at average concentrations of 0.26 (long) and 1.3 (short) mg per litre. UICC crocidolite asbestos was given as 1 mg weekly for 5 weeks (5 mg total).
• Main results:
  • Apart from a transient weight loss, no exposure affected growth rate or mortality, regardless of route or dose.
  • After a single 20 mg dose of long glass fibres, giant-cell granulomata with clumped fibres were seen up to 24 months, but no fibrosis was detected.
  • After a single dose of short glass fibres, fibres in the thoracic lymph nodes and lymphoid tissue at 2 years elicited only a macrophage response.
  • Macrophages could not ingest long glass fibres; short fibres were almost always inside macrophages.
  • In Study 3, the lung distribution of long fibres after trachea-only inhalation was similar to that after repeated instillation. Few short fibres remained by either route.
  • After repeated instillation of long glass fibres (5 mg total), only a minimal macrophage response was seen at the final 24-month sacrifice.
  • After repeated instillation of short glass fibres (5 mg total), a mild macrophage response was the major reaction seen at 12, 18 and 24 months.
  • Crocidolite asbestos caused a more intense response than glass fibres, with thickening of the alveolar walls from macrophage infiltration and fibrosis.
  • In the crocidolite study, mortality in exposed and control rats was very similar from 600 to 800 days. After 800 days, mortality in the exposed group exceeded that of controls. Median lifespan was greater than 800 days in both groups.
  • Tumour incidence was tabulated for rats surviving beyond 500 days. Among these survivors, monocytic leukemia incidence ranged from 11 to 55% across experiments, but within each experiment it was similar in exposed and control groups.
  • Within each experiment, monocytic leukemia incidence was similar in exposed and control groups.
  • Other tumours showed no differences between exposed and control groups and were within published rates for this rat strain. The authors stated that none of the exposures appeared to have caused cancer.
• The authors' conclusion: The authors concluded that a single 20 mg bolus of long or short glass fibres produces a granulomatous foreign-body response. Low-concentration multiple doses produce a simple macrophage response. Similar weights of crocidolite asbestos produce a strikingly more severe response accompanied by fibrosis.
• Limitations the authors state:
  • Only about 10 g of each fibre size was available, which ruled out standard inhalation methods.
  • The granulomata seen after single large doses appeared to be caused by giving the fibres as a bolus.
  • The uniformity of fibre deposition after multiple instillations could not be measured.
  • The asbestos was given at twice the concentration of the glass fibres, which may explain where the asbestos fibres were located in the lung.
  • The inhaled dose estimate relied on an assumed 10% deep-lung deposition.

Topics

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

Medical terms in this study, explained in our Lexicon: Macrophage, Deposition, Crocidolite, Fibrosis.

Related studies

• 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)
• 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)
• Long-term health effects in hamsters and rats exposed chronically to man-made vitreous fibres — D.M. Smith, L.W. Ortiz, et al. (1987)
• Chronic inhalation study of fiber glass and amosite asbestos in hamsters: twelve-month preliminary results — T.W. Hesterberg, C. Axten, et al. (1997)
• Response of perifused alveolar macrophages to glass fibers: effect of exposure duration and fiber length — G. Forget, M.J. Lacroix, et al. (1986)

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