In vitro studies on biological effects of fibrous minerals

Our plain-English summary of In vitro studies on biological effects of fibrous minerals, by Y. Ishihara (Industrial Health, 2001).

The study

• Author: Y. Ishihara
• Journal: Industrial Health
• Published: 2001;39(2):94-105
• Type of article: Review
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Asbestos substitutes have been used recently in industrial various applications. Since certain asbestos substitutes have similar characteristics of asbestos, they require urgent in vitro and in vivo evaluation of these asbestos substitutes prior to occupational applications. Though in vitro studies do not offer precise assessment of toxicity of the fibers, it is possible to provide useful information as to the biological effects of asbestos and its substitutes. This review articles described the findings of in vitro experiments in investigation of biological effects of asbestos and man made mineral fibers (MMMF) and their correlation with in vivo assays; 1. Cytotoxicity, geometry and dimension of fibers. 2. In vitro biological effects of fibers on a mass basis and a numerical basis. 3. Mechanism of cytotoxicity, carcinogenecity and cell proliferation including in vitro cytokines production. The relationships between the in vitro and the in vivo biological effects of fibers do not always coincide. Therefore, safety of the fibers must be assessed in both in vivo and in vitro using an inert fiber as negative control. Additionally, evaluation of safety of these fibers in vitro must be conducted in comparable concentrations, sizes and numbers of fibers for used in in vivo experiments.

In plain English

This was a review of laboratory (in vitro) studies on how asbestos and man-made mineral fibers (MMMF) affect cells, and how those results compare with animal (in vivo) studies. It covered fiber size, dosing by fiber weight versus fiber number, and mechanisms such as reactive oxygen species, genetic damage, cell growth and cytokine release. Reviewed studies reported that longer, thinner fibers were more biologically active. One cited study found two erionite samples far more toxic than crocidolite when equal fiber numbers were compared. Another found that chromosome missegregation in rat pleural mesothelial cells, but not cytotoxicity, corresponded with mesothelioma induction in animals. The author also presented the author's own earlier experiments. Three whisker fibers gave very similar TNF-α responses per fiber number in a murine macrophage cell line. Cytokine levels also changed in human alveolar macrophages treated with asbestos and in a macrophage-like cell line treated with MMMF. The author noted that in vitro tests cannot show how fibers are breathed in, deposited, retained and cleared. The author concluded that in vitro and in vivo results do not always coincide, so fiber safety should be tested in both, using an inert fiber as a negative control.

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: Narrative review of published in vitro studies, including some of the author's own earlier experiments, and their correlation with in vivo assays
• Who was studied: Published in vitro studies using red blood cells, cell lines, primary cells, organ cultures and bacterial systems. Cells included macrophages, fibroblasts and mesothelial cells. The number of studies reviewed is not stated.
• Exposure: Asbestos (chrysotile, crocidolite, amosite), erionite, and man-made mineral fibers (MMMF), including glass fibers, ceramic fibers, and titanium oxide (TiO2), potassium titanate (K2Ti8O17) and silicon carbide (SiC) whiskers
• Main results:
  • Studies cited in the review reported that longer, thinner fibers (lengths over 8 to 10 µm, diameters under 0.25 µm) were more efficient in exerting biological effects in vitro.
  • In the author's earlier work in RAW264.7 murine macrophage cells, the titanium oxide whisker (TO1) induced about double the TNF-α of the other whiskers.
  • When compared on the basis of fiber number per unit mass, the three whiskers showed very similar TNF-α profiles. The author attributed the whisker effects to fiber shape and size rather than chemical composition.
  • In the author's earlier rat experiments, the differences among the three whiskers in size and fiber number per unit mass did not reflect the degree of inflammation and fibrosis in the lungs of whisker-treated rats.
  • In a cited study by Palekar et al. using V79 fibroblasts, there was no difference in cytotoxicity on a mass basis. On an equal-fiber-number basis, both erionite samples were several orders of magnitude more potent in causing cell death than crocidolite.
  • In a cited study of rat pleural mesothelial cells, cytotoxicity did not correlate with mesothelioma induction in animals, but the ability to produce chromosome missegregation in vitro did.
  • In cited work by Barrett's group on Syrian hamster embryo cells, chrysotile treatment at 2.0 µg per square cm for 48 hours produced chromosome abnormalities in up to 50% of cells.
  • In a cited bacterial mutation study, no mutagenic activity was found for any of the asbestos and glass fibers tested.
  • In the author's earlier experiments, cytokine levels changed in human alveolar macrophages treated with asbestos in vitro, and in a macrophage-like cell line treated with MMMF in vitro.
• The authors' conclusion: The author concluded that in vitro and in vivo biological effects of fibers do not always coincide, so fiber safety should be evaluated in both in vivo and in vitro studies, using inert fibers as negative controls.
• Limitations the authors state:
  • In vitro studies cannot show factors that determine respirability, deposition, retention and clearance of fibers in the respiratory tract.
  • Crude dosimetry and poorly defined fiber characteristics in the reviewed studies did not allow precise comparison of fiber types.
  • In vitro findings on MMMF to date are not sufficient to confirm their toxicity and safety.

Topics

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

Related studies

• In vitro studies on the biologic effects of fibers: correlation with in vivo bioassays — B.T. Mossman (1990)
• An in vitro/in vivo study into the short term effects of exposure to mineral fibres — A. Clouter, C.E. Houghton, et al. (1996)
• Biological mechanisms of non-linear dose-response for respirable mineral fibers — L.A.T. Cox (2018)
• Biological effects of naturally occurring and man-made fibres: in vitro cytotoxicity and mutagenesis in mammalian cells — R. Okayasu, L. Wu, et al. (1999)
• Biological response of an in vitro human 3D lung cell model exposed to brake wear debris varies based on brake pad formulation — H. Barosova, S. Chortarea, et al. (2018)
• 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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