Man-made mineral fiber hazardous properties assessment using transgenic rodents: example of glass fiber testing

Our plain-English summary of Man-made mineral fiber hazardous properties assessment using transgenic rodents: example of glass fiber testing, by M.C. Bottin, J.C. Vigneron, R. Rousseau, et al (Inhalation Toxicology, 2003).

The study

• Authors: M.C. Bottin, J.C. Vigneron, R. Rousseau, J.C. Micillino, C. Eypert-Blaison, E. Kauffer, P. Martin, S. Binet, B.H. Rihn
• Journal: Inhalation Toxicology
• Published: 2003;15(10):1017-27
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Transgenic BigBlue rats were exposed to CM 44 glass fibers (6.3 mg/m3) by nose only, 6 h/day for 5 days. Two endpoints were examined 1, 3, 14, 28, and 90 days following exposure: fiber biopersistence and mutations in lung DNA. The half-time of the fibers >20 microm was 12.8 days, and mutant frequencies of control and exposed rats were similar across all time points. The mutation spectra of both series were similar after 28 days of fixation time. These results showed that a glass fiber with a high clearance in the lung seems to not present any significant effect on mutagenesis on lung DNA and are in marked contrast to results for asbestos, which caused a twofold mutant frequency increase as described in a previous study.

In plain English

This animal experiment tested a man-made glass fiber, CM44, not asbestos. Genetically modified male rats (7 exposed, 5 controls per group) breathed CM44 fibers through the nose 6 hours a day for 5 days, averaging 6.3 mg/m3, while controls breathed fiber-free air. Most of the fibers were short. Rats were examined 1, 3, 14, 28 and 90 days after exposure began. Half the fibers longer than 20 µm cleared from the lungs within 12.8 days. About 20% of the total fiber mass remained at 90 days. Two lung DNA mutation tests found no statistically significant difference in mutation frequency between exposed and control rats. Of 40 mutations sequenced per group at 28 days, the broad mutation categories did not differ. C to T changes varied, but the sample was too small for statistical testing. The authors concluded that this rapidly cleared glass fiber was not mutagenic in the lung in their assays at any time point. They noted that exposure was below the European protocol's recommended level. They also noted that their clearance time was longer than an earlier study of a similar fiber found.

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 inhalation experiment in transgenic (BigBlue) rats, following the European Chemical Bureau protocol for man-made mineral fibers
• Who was studied: Transgenic male F344 BigBlue rats weighing about 240 g, three months old. Each group had 7 exposed rats and 5 control rats, killed 1, 3, 14, 28 or 90 days after the start of exposure. The work was done at the Institut National de Recherche et de Sécurité, France.
• Exposure: Nose-only inhalation of CM44 glass fibers, 6 h/day for 5 days. The mean dust concentration was 6.3 mg/m3, with 601 plus or minus 338 fibers/cm3 meeting WHO fiber criteria, 72 plus or minus 54 fibers/cm3 longer than 20 µm, and 1256 nonfibrous particles/cm3. Controls breathed ambient air.
• Main results:
  • In exposed rats, half of the fibers longer than 20 µm were cleared from the lung in 12.8 days.
  • In exposed rats, nonfibrous particles had a clearance half-time of 43 days, similar to the 38.9 days for WHO fibers.
  • Longer fibers were cleared faster than shorter ones.
  • In exposed rats, about 20% of the total fiber mass remained in the lung 90 days after exposure.
  • With both mutation tests (lacI and cII), mutant frequencies in lung DNA did not differ significantly between control and exposed rats (p greater than 0.05).
  • The mutations that were sequenced came from cII screening at the 28-day time point.
  • Among 40 sequenced mutations from each group, no differences were observed between control and exposed rats in the broad categories of transitions, transversions, and deletions/insertions. There was some variation in C to T transitions, but the sample was too small to assess it statistically.
  • Exposed rats showed a tendency toward more multinucleated alveolar macrophages in lung washings three days after exposure, but this was not statistically significant.
• The authors' conclusion: The authors concluded that this rapidly cleared glass fiber was not mutagenic in the lung in their assays at any time point.
• Limitations the authors state:
  • The exposure concentration (6.3 mg/m3) was below the European Chemical Bureau recommendation of 10 to 30 mg/m3.
  • The concentration of fibers longer than 20 µm (72 fibers/cm3) did not reach the required 100 fibers/cm3.
  • The clearance half-time for long fibers (12.8 days) was longer than the 4.1 days found in an earlier study of a closely related fiber. The authors said this calls for multicenter studies to identify the source of variation between laboratories.
  • The aerosol contained many nonfibrous particles, which the authors suggested may have slowed fiber dissolution.
  • The number of sequenced mutations was too small to test statistically the variation seen in one mutation type (C to T transitions).
  • The lung digestion method did not allow identification of where in the lung the remaining fibers were located.

Topics

Medical terms in this study, explained in our Lexicon: Mineral Fiber, biopersistence.

Related studies

• Effects of asbestos and man-made vitreous fibers on cell division in cultured human mesothelial cells in comparison to rodent cells — K. Pelin, P. Kivipensas, et al. (1995)
• Benzo[a]pyrene-enhanced mutagenesis by man-made mineral fibres in the lung of lamda-lacI transgenic rats — J. Topinka, P. Loli, et al. (2006)
• Cytotoxicity, oxidative stress and genotoxicity induced by glass fibers on human alveolar epithelial cell line A549 — V. Rapisarda, C. Loreto, et al. (2015)
• 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)
• Chronic inhalation toxicity of size-separated glass fibers in Fischer 344 rats — T.W. Hesterberg, W.C. Miiller, et al. (1993)
• Product stewardship and science: safe manufacture and use of fiber glass — T.W. Hesterberg, R. Anderson, et al. (2012)

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