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

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.

Characterization and assessment of the potential toxicity/pathogenicity of Russian commercial chrysotile

“…A non-biodurable fiber like chrysotile appears less prone to induce long term chronic effects in vivo and for this reason is assumed to be less potent in inducing malignant mesothelioma. On the other hand, silica relicts produced by the dissolution of chrysotile may be eventually responsible for mid/long term chronic effects in vivo due to reiterated frustrated phagocytosis and eventually production of ROS at the reacting surface (Gualtieri et al 2019a).…”

Crystal structure determination of a lifelong biopersistent asbestos fibre using single-crystal synchrotron X-ray micro-diffraction

“…Because in vitro (biodurability) and in vivo (biopersistence) animal and human studies have shown that chrysotile is much less biodurable/biopersistent (Bernstein et al, 2005;IARC, 2012;Utembe et al, 2015) than amphibole asbestos in the body, the toxic potential of chrysotile is assumed to be low with respect to that of amphibole asbestos (Mossman, 1993). It was demonstrated that during the process of phagocytosis by alveolar macrophages (AMs) in vivo the acid environment produced intracellularly attacks chrysotile fibres that rapidly undergo a process of dissolution, with leaching of Mg and production of amorphous silica relicts (Gualtieri et al, 2019) easily eliminated by macrophages (Bernstein et al, 2013). Oppositely, amphibole asbestos fibres are biodurable (Bernstein et al, 2013) and are prone to induce chronic inflammation responsible for adverse effects in vivo.…”

In vitro toxicity of fibrous glaucophane

“…CRL-9444) cell lines. The THP-1 cell line consists of human leukemia monocytic cells extensively used to study monocyte/macrophage functions (Auwerx, 1991;Gualtieri et al, 2019c). The Met-5A cell line are constituted by human pleural mesothelial cells transformed with SV40 large T antigen from the SV40 virus.…”

“…The Met-5A cell line are constituted by human pleural mesothelial cells transformed with SV40 large T antigen from the SV40 virus. This cell line is ideal for detection of potential asbestos and asbestos-like genotoxic effects (Ke et al, 1989;Cardile et al, 2004;Gualtieri et al, 2019c). Cells lines were maintained in controlled atmosphere (37 • C, 5 % CO 2 ) using RPMI-1640 for THP-1 cells and M-199 for Met-5A cells, supplemented with 10 % fetal bovine serum (Gibco, USA), 100 U/mL penicillin and 100 U/mL streptomycin (Sigma-Aldrich, Milan, Italy).…”

“…Treatments were performed in triplicate. This experimental configuration was chosen because it allows a good interaction fibre/cell in culture systems and produces well-defined cellular responses as reported in previous studies (Hamilton et al, 1996;Cardile et al, 2004Cardile et al, , 2007aCardile et al, , 2007bPugnaloni et al, 2010Pugnaloni et al, , 2015Gualtieri et al, 2019c).…”