Assessment of the pathogenic potential of asbestiform vs. nonasbestiform particulates (cleavage fragments) in in vitro (cell or organ culture) models and bioassays

Our plain-English summary of Assessment of the pathogenic potential of asbestiform vs. nonasbestiform particulates (cleavage fragments) in in vitro (cell or organ culture) models and bioassays, by B.T. Mossman (Regulatory Toxicology and Pharmacology, 2008).

The study

• Author: B.T. Mossman
• Journal: Regulatory Toxicology and Pharmacology
• Published: 2008;52(1 Suppl):S200-3
• Cited by: 50 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Asbestos fibers are highly fibrous silicate fibers that are distinguished by having a large aspect (length to diameter) ratio and are crystallized in an asbestiform habit that causes them to separate into very thin fibers or fibrils. These fibers are distinct from nonasbestiform cleavage fragments and may appear as thick, short fibers which break along cleavage planes without the high strength and flexibility of asbestiform fibers. Since cleavage fragments of respirable dimensions have generally proven nonpathogenic in animal studies, little data exists on assessing well-characterized preparations of cleavage fragments in in vitro models. The available studies show that cleavage fragments are less bioreactive and cytotoxic than asbestiform fibers.

In plain English

This article was a single-author review, not a new study. It summarized laboratory studies, mostly from the author's own laboratory, comparing asbestos with nonasbestiform cleavage fragments. Cleavage fragments resemble asbestos chemically but break into thicker, shorter pieces. The asbestos was mainly crocidolite and chrysotile; the cleavage fragments, mainly riebeckite and antigorite. The test systems included hamster windpipe tissue and rodent airway, lung, pleural and immune cells. The cleavage fragments did not cause the windpipe tissue changes, enzyme activity or gene activation seen with asbestos, and were less toxic than asbestos to hamster airway cells. In rat lung immune cells, the nonasbestiform particles riebeckite and mordenite triggered release of superoxide, a reactive oxygen compound, only at concentrations 5 to 10 times higher than crocidolite; hamster immune cells never showed a significant increase. One reviewed study found asbestos, but not fibrous talc, toxic to rat mesothelial cells. The author concluded that cleavage fragments were less potent than asbestos and virtually inactive in most assays. The author noted that laboratory tests do not mimic lung clearance of fibers, and that results can vary by cell type and species.

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 the author's own laboratory's and others' in vitro (cell and organ culture) studies comparing asbestiform fibers with nonasbestiform cleavage fragments
• Who was studied: No human subjects. The reviewed studies used hamster tracheal organ cultures, hamster tracheal epithelial cells, rat lung epithelial cells, normal rat pleural mesothelial cells, rodent alveolar macrophages, sheep red blood cells and Chinese hamster ovary cells
• Exposure: Crocidolite and chrysotile asbestos compared with their nonasbestiform analogs: riebeckite (similar in chemistry to crocidolite) and antigorite (similar in chemistry to chrysotile). Also nonasbestiform mordenite, fibrous talc samples, and amosite compared with other crystallization habits of cummingtonite-grunerite
• Main results:
  • In hamster tracheal organ cultures, crocidolite and chrysotile fibers (and long glass fibers) caused squamous metaplasia and increased DNA synthesis. Riebeckite and antigorite did not cause these changes at the concentrations and exposure times tested
  • In hamster tracheal epithelial cells, crocidolite and chrysotile stimulated the enzyme ornithine decarboxylase, but neither cleavage-fragment preparation did
  • In hamster tracheal epithelial cells, antigorite and riebeckite were less potent than crocidolite in stimulating cell survival or proliferation. They were also less cytotoxic than crocidolite or chrysotile, measured by release of radioactive chromium
  • Rodent alveolar macrophages took up the nonasbestiform particles (riebeckite and mordenite). Rat macrophages released superoxide in response to these particles only at concentrations 5- to 10-fold higher than crocidolite asbestos. Hamster macrophages never showed significantly increased release
  • In studies of cancer-related genes (fos/jun) and signaling pathways in hamster tracheal, rat lung epithelial and rat pleural mesothelial cells, riebeckite and antigorite were inactive regardless of endpoint
  • Crocidolite and chrysotile, but not fibrous talcs, were cytotoxic to rat pleural mesothelial cells. Hamster tracheal cells proliferated in response to asbestos at lower nontoxic concentrations, but not to fibrous talcs. Mineral type appeared to matter more than fiber length
  • In a study by another group (Palekar and colleagues), four cummingtonite-grunerite samples were tested at the same surface-area doses. The samples were hemolytic and cytotoxic in this order: amosite asbestos, predominantly asbestiform cummingtonite, acicular cummingtonite, acicular grunerite
• The authors' conclusion: The author concluded that nonasbestiform minerals were less potent than asbestos fibers in a number of in vitro bioassays and that in most assays the cleavage fragments or non-fibrous minerals were virtually inactive
• Limitations the authors state:
  • Responses can be specific to cell type and species, so results from different laboratories testing the same mineral might be inconsistent
  • Concentrations used in short-term in vitro assays do not mimic normal clearance and long-term dissolution after inhalation into the human lung
  • Comparing minerals on an equal-weight basis might be misleading, because equal weights may contain very different numbers of fibers and surface areas
  • Few in vitro studies have tested cleavage fragments, which have mostly been used only as negative controls

Topics

Medical terms in this study, explained in our Lexicon: Asbestiform, Non-Asbestiform, Cleavage Fragment, Silicate, Fibril, Flexibility.

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