Testing of fibrous particles: short-term assays and strategies

Our plain-English summary of Testing of fibrous particles: short-term assays and strategies, by D. Bernstein, V. Castranova, K. Donaldson, et al (Inhalation Toxicology, 2005).

The study

• Authors: D. Bernstein, V. Castranova, K. Donaldson, B. Fubini, J. Hadley, T. Hesterberg, A. Kane, D. Lai, E.E. McConnell, H. Muhle, G. Oberdorster, S. Olin, D.B. Warheit, ILSI Risk Science Institute Working Group
• Journal: Inhalation Toxicology
• Published: 2005;17(10):497-537
• Cited by: 70 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

In plain English

This article is a working group report, not an original study. Experts convened by the ILSI Risk Science Institute in spring 2003 reviewed short-term tests, meaning 3 months or less of exposure, for screening fibers for possible toxicity and cancer. They also proposed a testing strategy. The group found that no single physical or chemical property predicts cancer for all fiber types. It found that test-tube cell assays are not well standardized and may give false positive results for fibers that do not persist in the lung. It also reported that subchronic animal studies of lung injury are considered more predictive. The proposed strategy had three parts: preparing a well-characterized sample of long, respirable fibers; measuring how long fibers persist in rodent lungs; and a subchronic rodent study of endpoints such as inflammation, cell proliferation and fibrosis, with an unexposed recovery period of at least 3 months. The authors concluded that this subchronic study is the major criterion for hazard evaluation. They noted that its validity for fiber classes other than synthetic vitreous fibers and asbestos is less defined.

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: Expert working group consensus report reviewing short-term assays and proposing a testing strategy (no new data)
• Who was studied: No human or animal subjects. An expert working group convened by the ILSI Risk Science Institute in spring 2003 reviewed published short-term assay methods for fibers.
• Exposure: Natural and synthetic fibers in general, including asbestos, silica-based synthetic vitreous fibers and organic fibers, as tested in short-term assays of 3 months or less
• Main results:
  • The group found no single physicochemical property that predicts carcinogenicity for all fiber classes.
  • In vitro cellular assays are not well standardized, and fibers that do not persist in the lung may give false positive results.
  • Subchronic studies of lung injury biomarkers are considered more predictive of carcinogenic potential.
  • The proposed strategy has three components: sample preparation and characterization, in vivo biopersistence testing, and a subchronic rodent study of toxicologic endpoints.
  • In a subchronic inhalation study, one exposure concentration should contain at least 150 fibers per cubic centimeter of fibers longer than 20 micrometers.
  • A recovery group should be held unexposed for at least 3 months after exposure ends, to see whether effects persist.
  • Current in vitro test systems have limited usefulness for hazard identification.
• The authors' conclusion: The authors concluded that the subchronic inhalation study, covering both biopersistence and biological activity in the lung, is the major criterion for hazard evaluation. In their view, the existing data point to biopersistence and persistent lung inflammation as particularly important.
• Limitations the authors state:
  • The key parameters have been validated in 90-day studies for synthetic vitreous fibers and asbestos, but their validity for other fiber classes is less defined.
  • Many of the available tests are unvalidated and have been used with only a few fiber types.
  • Few studies have been done on organic fibers.

Related studies

• Quantification of the pathological response and fate in the lung and pleura of chrysotile in combination with fine particles compared to amosite-asbestos following short-term inhalation exposure — D.M. Bernstein, R.A. Rogers, et al. (2011)
• The pathological response and fate in the lung and pleura of chrysotile in combination with fine particles compared to amosite asbestos following short-term inhalation exposure: interim results — D.M. Bernstein, R.A. Rogers, et al. (2010)
• Biopersistence of rock wool in lungs after short-term inhalation in rats — Y. Kudo, Y. Aizawa (2008)
• Detection of mineral fibre carcinogenicity with the intraperitoneal test--recent results and their validity — F. Pott (1995)
• An introduction to the short-term toxicology of respirable industrial fibres — K. Donaldson, C.L. Tran (2004)
• Short-term inhalation and in vitro tests as predictors of fiber pathogenicity — R.T. Cullen, B.G. Miller, et al. (1997)

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