The asbestos-carbon nanotube analogy: An update

Abstract

Nanotechnology is an emerging industry based on commercialization of materials with one or more dimensions of 100 nm or less. Engineered nanomaterials are currently incorporated into thin films, porous materials, liquid suspensions, or filler/matrix nanocomposites with future applications predicted in energy and catalysis, microelectronics, environmental sensing and remediation, and nanomedicine. Carbon nanotubes are one-dimensional fibrous nanomaterials that physically resemble asbestos fibers. Toxicologic studies in rodents demonstrated that some types of carbon nanotubes can induce mesothelioma, and the World Health Organization evaluated long, rigid multiwall carbon nanotubes as possibly carcinogenic for humans in 2014. This review summarizes key physicochemical similarities and differences between asbestos fibers and carbon nanotubes. The "fiber pathogenicity paradigm" has been extended to include carbon nanotubes as well as other high-aspect-ratio fibrous nanomaterials including metallic nanowires. This paradigm identifies width, length, and biopersistence of high-aspect-ratio fibrous nanomaterials as critical determinants of lung disease, including mesothelioma, following inhalation. Based on recent theoretical modeling studies, a fourth factor, mechanical bending stiffness, will be considered as predictive of potential carcinogenicity. Novel three-dimensional lung tissue platforms provide an opportunity for in vitro screening of a wide range of high aspect ratio fibrous nanomaterials for potential lung toxicity prior to commercialization.

Keywords: Asbestos fibers; Carbon nanotubes; Fiber pathogenicity paradigm; High aspect ratio nanomaterials.

Figure 1. Proposed mechanisms for carcinogenicity of asbestos fibres

IL-1ß, interleukin - 1ß; IL-18, interleukin-18; RNS, reactive nitrogen species; ROS, reactive oxygen species Adapted with permission from IARC Monongraphs on the Evaulation of Carcinogenic Risks to Humans: Volume 100C. Arsenic, Metals, Fibres, and Dusts. IARC, Lyon, 2012.

Figure 2. Assessment Scheme for Potential Adverse Human Health Impacts of HARNs Following Inhalation

Adapted from Arts et al., 2014 with permission from Elsevier Ltd. (pending).

Figure 3. SEM Images of Fibrous Nanomaterial Deposition in Alveoli and Penetration into Alveolar Epithelial Cells

SEM images of (A) a fiber retained in an intrapulmonary conducting airway; the fiber is completely covered by the surface lining-layer (Geiser et al., 2003a), (B) a fiber retained in the gas exchanging compartment (Geiser et al., 2003a). Figures 3A, B reproduced with permission from Environmental Health Perspectives (Geiser et al., 2003a). The fiber touched the alveolar wall with one end only and the other end projected into the airspace and was not covered by lung lining layer. Abbreviations: A, alveoli; AD, alveolar duct. (C) FESEM of MWCNT penetration of alveolar epithelial cells (Mercer et al., 2010). Micrograph shows two MWCNTs passing through an alveolar epithelial cell 1 day after pharyngeal aspiration. Figure 3C reproduced with permission (Springer Open article, Mercer et al., 2010).

Figure 4. Microscopic Anatomy of Pulmonary Lymphatics and Translocation of Fibers to the Pleural Space

A. alveoli (panel A2). Lymphatics of the interlobular septa (Ly in panel A3) drain into lymphatics beneath the visceral pleura (arrows in panels A3, 4). Immunohistochemical detection of lymphatics with toluidine blue counterstain, original magnification × 10 (Sozio et al., 2012). Reprinted with permission from John Wiley and Sons. B. Miserocchi et al. (2008) hypothesize that asbestos-induced pulmonary inflammation increases interstitial fluid pressure that allows biopersistent fibers to penetrate into pulmonary lymphatics and cross the visceral pleura. Fibers that are not cleared through lymphatic stomata are trapped at the parietal pleura leading to the development of mesothelioma as proposed in Figure 2. Reprinted with permission from an Open Access article (Miserocchi et al., 2008).

Figure 5. Pathogenicity Classification of HARNs

This pathogenicity classification is based on buckling of HARNs of different dimensions and Young’s moduli. For each material, the space above the curve is “biologically soft” and below the curve is “biologically stiff.” This classification is based on the mechanical pathway leading to lysosomal membrane damage. It is predicted the HARNs will induce lysosomal membrane permeability if their dimensions are in the region between the size range of the lysosome (in blue) and their buckling thresholds. Reproduced with permission (Zhu et al., 2016; National Academy of Sciences, USA).