Chronic inhalation toxicity of size-separated glass fibers in Fischer 344 rats

Our plain-English summary of Chronic inhalation toxicity of size-separated glass fibers in Fischer 344 rats, by T.W. Hesterberg, W.C. Miiller, E.E. McConnell, et al (Fundamental and Applied Toxicology, 1993).

The study

• Authors: T.W. Hesterberg, W.C. Miiller, E.E. McConnell, J. Chevalier, J.G. Hadley, D.M. Bernstein, P. Thevenaz, R. Anderson
• Journal: Fundamental and Applied Toxicology
• Published: 1993;20(4):464-76
• Cited by: 137 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

This study was initiated to determine the chronic biological effects in Fisher 344 rats of inhaled size-separated respirable fractions of fibrous glass (FG) having compositions representative of common building insulation wools. Rats were exposed using nose-only inhalation chambers, 6 hr/day, 5 days/week, for 24 months to three concentrations (3, 16, and 30 mg/m3) of two different compositions of FG (designated MMVF 10 and MMVF 11), or to filtered air (negative control). Fibrous glass findings were compared to those from a concurrent inhalation study of chrysotile asbestos and refractory ceramic fiber (RCF). The FGs used in this study were size selected to be largely respirable in the rat and the aerosol generation technique did not alter the dimensions of the fibers. Interim euthanizations took place at 3- to 6-month intervals to monitor progression of pulmonary changes. Fibers were recovered from digested lung tissue for determination of changes in fiber number and morphology. In animals exposed to 30 mg/m3 of MMVF 10 or MMVF 11, 4.2 +/- 0.9 x 10(5) and 6.4 +/- 3.1 x 10(5) fibers/mg dry lung tissue, respectively, were recovered after 24 months of exposure. Exposure to chrysotile asbestos (10 mg/m3) and to a lesser extent RCF (30 mg/m3) resulted in pulmonary fibrosis as well as mesothelioma and significant increases in lung tumors. FG exposure was associated with a nonspecific inflammatory response (macrophage response) in the lungs that did not appear to progress after 6-12 months of exposure. These cellular changes are reversible and are similar to the effects observed after inhalation of an inert dust. No lung fibrosis was observed in the FG-exposed animals. Further, FG exposure resulted in no mesotheliomas and no statistically significant increase in lung tumor incidence when compared to that of the negative control group. These findings, along with previous inhalation studies, suggest that respirable fibrous glass does not represent a significant hazard for fibrotic or neoplastic lung disease in humans.

In plain English

This was an animal experiment. Male Fischer 344 rats breathed fine, size-separated fractions of two glass wool insulation fibers, MMVF 10 and MMVF 11, through nose-only chambers at 3, 16 or 30 mg/m³, 6 hours a day, 5 days a week, for 24 months. A control group breathed filtered air; each group had 140 rats. After 24 months at 30 mg/m³, lungs held 4.2 ± 0.9 × 10⁵ (MMVF 10) and 6.4 ± 3.1 × 10⁵ (MMVF 11) fibers per milligram of dry lung. Glass fibers caused a mild, dose-related increase in lung cells, which the authors described as reversible. There was no lung or pleural fibrosis, no mesothelioma, and no statistically significant increase in lung tumors versus controls. In the filtered-air control group, 4 of the 123 rats counted as at risk (3.3%) had lung tumors. In a concurrent comparison study reported elsewhere, 13 of 69 chrysotile asbestos-exposed rats counted as at risk (18.9%) had lung tumors, and one had a mesothelioma. The authors concluded the results suggest respirable fibrous glass represents no significant hazard for fibrotic or neoplastic disease in humans. Two pages of article text were missing.

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: Chronic (24-month) nose-only inhalation experiment in rats, with an air-exposed control group and comparison to a concurrent chrysotile asbestos and refractory ceramic fiber (RCF) study
• Who was studied: Male Fischer 344/N rats, six weeks old, 140 per glass fiber group and 140 unexposed controls; study done at Research and Consulting Company, Geneva, Switzerland. For tumor counts, only fiber-exposed rats exposed for at least 1 year were counted as at risk. The tumor table gives a separate at-risk number for each group, including 123 controls.
• Exposure: Size-separated respirable fractions of two glass wool insulation fibers (MMVF 10 from Manville 901 glasswool and MMVF 11 from CertainTeed B glasswool) at 3, 16 and 30 mg/m³, 6 hours a day, 5 days a week, for 24 months. Comparison groups from a concurrent study breathed chrysotile asbestos (10 mg/m³) or RCF 1 (30 mg/m³).
• Main results:
  • After 24 months at 30 mg/m³, lung burdens were 4.2 ± 0.9 × 10⁵ fibers/mg dry lung (MMVF 10) and 6.4 ± 3.1 × 10⁵ fibers/mg dry lung (MMVF 11)
  • In rats removed from exposure, lung fiber levels fell with increasing recovery time after exposure stopped
  • Glass fibers caused no abnormal clinical signs, and there were no statistically significant body weight changes or excess mortality during the 2 years of exposure
  • No treatment-related lung or pleural fibrosis was seen in the glass fiber-exposed rats
  • The only exposure-related finding in glass fiber-exposed rats was a dose-dependent increase in mild cellularity in the lungs that did not appear to progress after 6 months of exposure
  • Glass fiber-exposed groups had no mesotheliomas, and no biological or statistically significant increase in lung tumor incidence compared with the air control group
  • Among fiber-exposed rats, only those exposed for at least 1 year were counted as at risk for tumors
  • In the filtered-air control group, 4 of 123 rats counted as at risk (3.3%) had lung tumors
  • In the concurrent comparison study (Mast et al., 1993), 13 of 69 at-risk chrysotile-exposed rats (18.9%) had lung tumors, and 1 (1.4%) had a mesothelioma
  • In the concurrent comparison study, RCF exposure (30 mg/m³) resulted in a statistically significant increase in lung tumors (13%) and two mesotheliomas
• The authors' conclusion: The authors concluded that their results suggest respirable fibrous glass represents no significant hazard for fibrotic or neoplastic disease in humans. They also concluded that the chemical composition of man-made vitreous fibers is a critical determinant of their potential for adverse biological effects.
• Limitations the authors state:
  • Because the first lung burden was measured at 13 weeks, the study could not assess the relative roles of deposition, dissolution or clearance in the shorter, thinner fibers found in the lung
  • Despite size separation, the glass fibers did not exactly match the RCF 1 dimensions: MMVF 10 was thicker on average, and both glass fibers were on average shorter than RCF 1
  • Chrysotile fiber lengths and diameters were very different from the man-made fibers, making fiber-to-fiber comparisons difficult

Topics

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

Medical terms in this study, explained in our Lexicon: Respirable Fraction, Chrysotile, Pulmonary Fibrosis, Mesothelioma, Macrophage, Fibrosis.

Related studies

• Chronic inhalation study of fiber glass and amosite asbestos in hamsters: twelve-month preliminary results — T.W. Hesterberg, C. Axten, et al. (1997)
• 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)
• Studies on the chronic toxicity (inhalation) of four types of refractory ceramic fiber in male Fischer 344 rats — R.W. Mast, E.E. McConnell, et al. (1995)
• 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)
• 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)
• The chronic effects of exposure of rats to sized glass fibres — R.T. Drew, M. Kuschner, et al. (1987)

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