In vitro studies on the biologic effects of fibers: correlation with in vivo bioassays

Our plain-English summary of In vitro studies on the biologic effects of fibers: correlation with in vivo bioassays, by B.T. Mossman (Environmental Health Perspectives, 1990).

The study

• Author: B.T. Mossman
• Journal: Environmental Health Perspectives
• Published: 1990;88:319-22
• Type of article: Review
• Cited by: 27 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

In vitro studies employing organ cultures, primary cell cultures, cell lines, and bacterial systems have been used to assess the toxicity, mutagenicity, and carcinogenic potential of asbestos and nonasbestos fibers. These experiments have been useful in defining mechanisms contributing to the causation of fiber-associated lung diseases. Long (greater than 8 microns), thin asbestos fibers are more active in vitro than short (less than or equal to 2 microns) fibers or nonfibrous particles, an observation supporting the importance of fiber dimension in disease. Although in vitro bioassays cannot evaluate characteristics such as clearance and/or durability of fibers which may be critical determinants of fiber toxicity in lung, they can be used both to address dosimetry at the cellular level (i.e., number of fibers per cell that elicit a measurable biologic end point) and to evaluate preventive approaches to fiber-induced cell injury. Development of in vitro models employing target cells of the lung, i.e., mesothelial cells, tracheobronchial epithelial cells, and lung fibroblasts, as well as carefully characterized preparations of fibers and particles, will be necessary to evaluate whether in vitro bioassays are amenable to predicting the pathogenic potential of synthetic and naturally occurring fibers comparatively.

In plain English

In this review, the author summarized laboratory (in vitro) studies in which asbestos and non-asbestos fibers were added to organ cultures, cell cultures, cell lines and bacteria, and compared them with whole-animal studies. In the studies reviewed, longer, thinner fibers of asbestos and glass were more toxic to cells than short, blunt fibers or nonfibrous particles. In one cited study, erionite did not differ from chrysotile or crocidolite when doses were measured by weight. When equal numbers of fibers were compared, it was several orders of magnitude more potent at killing cells. Asbestos tested negative in bacterial mutation assays but caused morphologic transformation in hamster embryo cells. A cited rat inhalation study found that long chrysotile and amosite fibers caused asbestosis and lung tumors, while short amosite produced no lung disease. The author concluded that in vitro models had been valuable for defining mechanisms and the fiber dimensions involved. The author also noted that crude dosing and poorly defined fiber samples limited comparisons, and that whether these tests can predict cancer-causing potential was questionable.

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: Review of published in vitro (laboratory) studies on fibers, compared with whole-animal studies
• Who was studied: No people or animals were studied directly. The review covered in vitro systems (organ cultures, primary cell cultures, cell lines, bacterial systems) and also discussed rodent studies from other authors.
• Exposure: Various types of asbestos (chrysotile, crocidolite, amosite) and non-asbestos fibers and particles, including glass fibers, rockwool, attapulgite, sepiolite, erionite, potassium octatitanate (Fybex), nonfibrous silica and titanium dioxide
• Main results:
  • In the cell studies reviewed, longer, thinner fibers of both asbestos and glass were more toxic to cells than short, blunt fibers or nonfibrous particles. The fiber dimensions given (lengths of about 8-10 micrometers, diameters of about 0.25 micrometer) have comparison symbols lost in scanning.
  • In a cited study in V79 fibroblasts, chrysotile, crocidolite and two erionite samples showed no differences in toxicity when dosed by mass. When equal numbers of fibers were used, both erionite samples were several orders of magnitude more potent in causing cell death than crocidolite (intermediate) or chrysotile (least toxic). The author noted this matched erionite's higher tumor-causing potential in rodent inhalation experiments.
  • In the studies reviewed, asbestos tested negative in bacterial mutation assays, unlike most chemical carcinogens.
  • In the studies reviewed, crocidolite, chrysotile, glass fibers and nonfibrous silica caused morphologic transformation in Syrian hamster embryo (SHE) cells. Transformation frequencies varied appreciably from laboratory to laboratory.
  • In hamster trachea organ cultures, long fibers (asbestos and non-asbestos) increased markers of cell growth, squamous metaplasia and keratinization. Nonfibrous particles did not cause these changes, and short fibers had to be added at several-fold higher amounts to produce them.
  • In a cited rat inhalation study, long chrysotile and amosite fibers caused asbestosis and pulmonary tumors, and short amosite fibers produced no lung disease. Short chrysotile caused a small proportion of asbestosis and malignancies, which that study's author attributed to contamination by some longer chrysotile fibers.
  • A cited study found that human mesothelial cells in vitro were 100- and 1000-fold more sensitive to the toxic effects of asbestos than human tracheobronchial epithelial cells or lung fibroblasts. Lung fibroblasts were the most insensitive cell type.
• The authors' conclusion: The author concluded that in vitro models had been valuable in defining how fibers interact with cells and which fiber dimensions matter. The author also stated that whether in vitro models can predict the cancer-causing potential of fibers is questionable, because results with asbestos in bacterial and cell transformation systems are inconsistent.
• Limitations the authors state:
  • In vitro tests cannot evaluate fiber clearance or durability, which may be critical to fiber toxicity in the lung.
  • Crude dosimetry and poorly defined fiber characteristics in the studies reviewed did not allow precise comparison of individual fiber types over a range of concentrations.
  • Fibers were usually added to cultures by mass rather than by number of fibers, which makes results difficult to interpret.
  • Most experiments used rodent fibroblast lines, which may be less sensitive than mesothelial or tracheobronchial cells, the target cells of asbestos-induced tumors.

Topics

Medical terms in this study, explained in our Lexicon: Carcinogenic, Causation, Fiber Dimensions, Mesothelial Cells, Fibroblast.

Related studies

• Correlation of in vitro and in vivo methods by means of mass dose and fiber distribution for amosite and fibrous ferroactinolite — D.L. Coffin, L.D. Palekar, et al. (1983)
• Assessment of the pathogenic potential of asbestiform vs. nonasbestiform particulates (cleavage fragments) in in vitro (cell or organ culture) models and bioassays — B.T. Mossman (2008)
• Solubility of asbestos and man-made mineral fibers in vitro and in vivo: its significance in lung disease — A. Morgan, A. Holmes (1986)
• In vitro studies on biological effects of fibrous minerals — Y. Ishihara (2001)
• Role of fibre characteristics on cytotoxicity and induction of anaphase/telophase aberrations in rat pleural mesothelial cells in vitro: correlations with in vivo animal findings — M. Yegles, X. Janson, et al. (1995)
• The pulmonary toxicity of talc and granite dust as estimated from an in vivo hamster bioassay — B.D. Beck, H.A. Feldman, et al. (1987)

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