Structure Model and Toxicity of the Product of Biodissolution of Chrysotile Asbestos in the Lungs

Our plain-English summary of Structure Model and Toxicity of the Product of Biodissolution of Chrysotile Asbestos in the Lungs, by A.F. Gualtieri, G. Lusvardi, A. Pedone, et al (Chemical Research in Toxicology, 2019).

The study

• Authors: A.F. Gualtieri, G. Lusvardi, A. Pedone, D. Di Giuseppe, A. Zoboli, A. Mucci, A. Zambon, M. Filaferro, G. Vitale, M. Benassi, R. Avallone, L. Pasquali, M. Lassinantti Gualtieri
• Journal: Chemical Research in Toxicology
• Published: 2019;32(10):2063-2077
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Asbestos is a commercial term indicating six natural silicates with asbestiform crystal habit. Of these, five are double-chain silicates (amphibole) and one is a layer silicate (serpentine asbestos or chrysotile). Although all species are classified as human carcinogens, their degree of toxicity is still a matter of debate. Amphibole asbestos species are biopersistent in the human lungs and exert their chronic toxic action for decades, whereas chrysotile is not biopersistent and transforms into an amorphous silica structure prone to chemical/physical clearance when exposed to the acidic environment created by the alveolar macrophages. There is evidence in the literature of the toxicity of chrysotile, but its limited biopersistence is thought to explain the difference in toxicity with respect to amphibole asbestos. To date, no comprehensive model describing the toxic action of chrysotile in the lungs is available, as the structure and toxic action of the product formed by the biodissolution of chrysotile are unknown. This work is aimed at fulfilling this gap and explaining the toxic action in terms of structural, chemical, and physical properties. We show that chrysotile's fibrous structure induces cellular damage, mainly through physical interactions. Based on our previous work and novel findings, we propose the following toxicity model: inhaled chrysotile fibers exert their toxicity in the alveolar space by physical and biochemical action. The fibers are soon leached by the intracellular acid environment into a product with residual toxicity, and the dissolution process liberates toxic metals in the intracellular and extracellular environment.

In plain English

This was a laboratory study, not a study of people. The authors dissolved Balangero mine (Italy) chrysotile asbestos in strong hydrochloric acid to imitate what happens to it inside lung cells. They tested the leftover product, called ASChr, on two human cell lines: THP-1 (monocytes) and Met-5A (pleural mesothelial cells). Untreated chrysotile and crocidolite were tested for comparison. ASChr kept the fibrous shape but was mainly silica and brittle, with a larger surface area (212 versus 34 square meters per gram). It produced about four times less hydroxyl radical than untreated chrysotile, but not zero. ASChr damaged cells. At its highest dose (100 micrograms per milliliter), ASChr caused 1.8-fold higher release of LDH, a cell-damage marker, from Met-5A cells than chrysotile and crocidolite; crocidolite was tested only at 50. DNA damage in Met-5A cells from ASChr did not differ significantly from chrysotile and was lower than from crocidolite. The authors concluded that the view that chrysotile is low-risk because it does not persist in the lungs is oversimplified. They noted that their lab-made product may not exactly match what forms in human lungs.

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: Laboratory experiment: acid-leaching of chrysotile, physical and chemical characterization with computer modeling of its structure, and in vitro cell toxicity and DNA-damage tests
• Who was studied: Chrysotile fibers from the Balangero mine (Torino, Italy). Two human cell lines: THP-1 (leukemia monocytic cells) and Met-5A (benign immortalized pleural mesothelial cells).
• Exposure: Acid-leached chrysotile (ASChr), made by treating 5 g of Balangero chrysotile with 500 mL of 6 M hydrochloric acid at 50 °C for 1 week. Cells were exposed to ASChr and untreated chrysotile (Chr) at 25, 50 and 100 μg/mL, and to UICC crocidolite (Croc) at 50 μg/mL only. The DNA-damage test used 50 μg/mL for 3 hours.
• Main results:
  • After leaching, the fibers kept their overall fibrous shape but were mainly composed of silica.
  • The leached fibers had fractures typical of a brittle material, unlike the flexible original chrysotile.
  • Specific surface area rose from 34(2) square meters per gram for untreated chrysotile to 212(1) square meters per gram for ASChr.
  • ASChr's hydroxyl radical signal was about 4-fold lower than that of untreated chrysotile.
  • ASChr's ability to generate free radicals was reduced but not fully suppressed.
  • In THP-1 cells, ASChr at 25, 50 and 100 μg/mL increased LDH release (a cell-damage marker) relative to unexposed control cells by 67, 88 and 91%, respectively.
  • In THP-1 cells at 50 and 100 μg/mL, ASChr caused significantly lower cellular activity than the other fiber types.
  • In Met-5A cells, the highest ASChr dose (100 μg/mL) caused 1.8-fold higher LDH release than untreated chrysotile and crocidolite. Crocidolite was tested only at 50 μg/mL. The article does not state which chrysotile dose this comparison used.
  • DNA damage in Met-5A cells (tail moment, mean plus or minus standard error) was 38.32 ± 3.5 for crocidolite, significantly higher than 21.37 ± 2.2 for chrysotile and 17.42 ± 2.1 for ASChr. Unexposed control cells measured 6.8 ± 1.0, and all fibers were significantly higher than control.
  • DNA damage in Met-5A cells did not differ significantly between untreated chrysotile and ASChr.
• The authors' conclusion: The authors concluded that the view that chrysotile has low toxicity potential compared with amphibole asbestos because it is not biopersistent is oversimplified. In their proposed model, the leached silica residue keeps the fibrous shape and continues to cause cell disturbance. The model's claim that dissolving fibers release metals rests on the authors' earlier work.
• Limitations the authors state:
  • The ASChr made in the laboratory may not exactly represent the dissolution product formed in the human body over decades.
  • The surface silanol groups could differ between fibers transformed by simulated lung fluid and fibers transformed by hydrochloric acid.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Chrysotile.

Medical terms in this study, explained in our Lexicon: Chrysotile, Silicate, Asbestiform, Habit, Double-Chain Silicate, Amphibole Group, Serpentine Group, Amphibole Asbestos.

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• Exposure to chrysotile asbestos causes carbonylation of glucose 6-phosphate dehydrogenase through a reaction with lipid peroxidation products in human lung epithelial cells — Y. Ogasawara, K. Ishii (2010)
• Effectiveness of serum megakaryocyte potentiating factor in evaluating the effects of chrysotile and its heated products on respiratory organs — A. Takata, H. Yamauchi, et al. (2011)
• Vitronectin adsorption to chrysotile asbestos increases fiber phagocytosis and toxicity for mesothelial cells — J. Wu, W. Liu, et al. (2000)
• Assessment of the physicochemical properties of chrysotile-containing brake debris pertaining to toxicity — M.S.P. Boyles, C.A. Poland, et al. (2019)

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