Empirical model of mesothelioma potency factors for different mineral fibers based on their chemical composition and dimensionality

Abstract

Context: The potency of various mineral fiber types to produce mesothelioma was previously evaluated for numerous cohorts, but the differences in potencies for distinct fiber types have yet to be explained. Objective: To develop an empirical model that would reconstruct mesothelioma potency factors for various types of fiber based on their chemical composition and dimensionality. Methods: Typical chemical composition and dimensionality metrics (aspect ratios) were obtained and combined with mesothelioma potency factors estimated by Hodgson and Darnton method for Quebec chrysotile, South Africa amosite, South Africa and Australian crocidolite, Russian anthophyllite, Libby amphiboles, and Turkey erionite. The forward stepwise log-log regression method was utilized to determine the best combination of input parameters. Results: Mesothelioma potency factors (R M) for selected cohorts were effectively reconstructed utilizing the median aspect ratio of fibers and equivalent fractions of SiO 2 , total Fe oxides or total equivalent Fe 3þ as Fe 2 O 3 , and MgO. Modeled potency factors increase as the aspect ratio, SiO 2 , and total Fe oxide (or Fe 2 O 3) content grow, and as the MgO content diminishes. Correlation coefficients up to 0.999, p < 0.01, were achieved. The models also yield reasonable estimates of mesothelioma potencies for other fiber types, including Bolivian crocidolite, Russian chrysotile, fluoro-edenite, and others. Conclusion: In spite of the empirical approach, the proposed models provide a starting point for targeted studies of mesothelioma mechanisms by elucidating significant contributing physicochemical factors. The models have an exploratory and preliminary character but can potentially be useful to introduce quantitative structure-activity relationship approaches for the toxicology of fibrous minerals.

Modeling mesothelioma risk factors from amphibole fiber dimensionality: mineralogical and epidemiological perspective

“…All amphiboles are durable in the body and have the same general atomic structure. In general, the coefficient k (i) would be expected to vary among categories of mineral fibers, e.g., serpentine, zeolite and clay mineral, and perhaps with composition within each mineral species, including the amphiboles (Korchevskiy et al, ).…”

“…However, examples of the modeling of fiber toxicity characteristics based on their physical and chemical properties are remarkably rare (Berman & Crump, 2008). Such models must be consistent with the facts that (a) mesothelioma mortality rate per unit of cumulative exposure (that is often called "mesothelioma potency factor" or "mesothelioma potency") among those occupationally exposed to similar doses of asbestos containing amphibole varies by more than an order of magnitude (Korchevskiy, Rasmuson, & Rasmuson, 2019;Garabrant & Pastula, 2018;Hodgson & Darnton, 2000), and (b) amphibole dimensional characteristics vary significantly among occurrences (Wylie, 2016). Identifying and quantifying the potency factors that influence the observed variation in cancer mortality is our goal.…”

Laser ablation inductively coupled plasma mass spectrometry as a novel clinical imaging tool to detect asbestos fibres in malignant mesothelioma

“…erionite), despite all of these being previously reported to cause ARD. 9,12,13 More established methods of asbestos identification and quantification, such as scanning electron microscopy (SEM) and transmission electron microscopy (TEM), generally employ chemical digestion of the tissues in order to eliminate the organic matrix, thus losing all the spatial information offered by imaging methods such as optical and polarised light microscopy. 14 However, these imaging methods cannot differentiate between asbestiform and nonasbestiform fibres and fail to detect low concentrations of MF or fibres that are less than 0.20 μm in diameter.…”

Metabolic rewiring and redox alterations in malignant pleural mesothelioma

“…16,17 Consistent with this notion, the carcinogenicity of asbestos fibres is, at least in part, linked to their iron content and iron oxidation status (Fe 2+ versus Fe 3+ ). 20 Due to their increased iron content 20 and rigidity, amphiboles are more carcinogenic than chrysotile fibres. Nevertheless, the content of iron alone is not sufficient to predict the grade of carcinogenicity of asbestos fibres.…”