Modeling the Influence of Carbon Nanotube and Nanofiber Physicochemical Properties on Key Molecular Initiating Events and Functional Endpoints Using Epithelial, Macrophage, and Fibroblast Cell Models

Details

• Personal Author:
  Bauer AK ; Boots T ; Dahm, Matthew M. ; Erdely AD ; Eye T ; Hubczak J ; Kelly F ; Kodali VK ; Sargent LM ; Schubauer-Berigan, Mary K. ; Shoeb M ; Siegrist K ; Stefaniak, Aleksandr B. ; Stueckle, Todd A. ; Yanamala N
• Description:
  There is a significant interest in using in vitro systems to evaluate toxicity of ever-increasing nanomaterial variants and other toxicants. We used 7 multiwalled carbon nanotubes and 2 carbon nanofibers (CNT/F) from U.S facilities to evaluate predictability, sensitivity, and the relationship of physicochemical characteristics to key molecular initiating events and functional responses following exposure. Additionally, the predictability of in vitro model systems to in vivo outcomes from a complementary study was determined. The CNT/F represent a good model as they are known to induce cytotoxicity, inflammation, pathology, and genotoxicity. The particulates had a wide distribution in length (0.1-50 microm), diameter (6-397 nm), dustiness (0.2-4.9 %), metal contaminants (0.3-6.2 %), surface area (18-238 m2/g), and density (0.007-0.22 g/cm3). Endotoxin and PAH levels were below detection limit and zeta potential were similar for all materials. Genotoxicity was evaluated in human lung epithelial cell line, BEAS-2B, at 0-24 microg/ml. Acute toxicity, inflammation, inflammasome signaling, and phagocytic activity were evaluated in the differentiated human monocyte cell line, THP-1, at 0-60 microg/ml. Collagen production, TGFbeta levels, and alphaSMA signaling were evaluated in primary human lung fibroblast cells at 0-9.6 microg/ml. Unsupervised approaches were initially used to identify classes of materials with similar outcomes followed by supervised learning approaches to identify specific physicochemical characteristics driving toxicity responses. It was clear certain physicochemical characteristics were the primary drivers of specific outcomes. Often, a multifactorial approach, meaning a combination of physicochemical characteristics, best described a particular outcome. Analysis of complementary endpoints in a concurrent in vivo study indicated some in vitro tests shared similar predictability suggesting some utility for predictive in vitro toxicity evaluation. These included specific measures of inflammation and pathological outcomes. The general conclusions of the analysis suggest that the class of materials, carbon nanotubes and nanofibers, can be subdivided based on specific endpoints, some aspects of in vitro outcomes predict in vivo toxicity, and the methodological approach can possibly be adapted beyond the finite scope of this study. [Description provided by NIOSH]
• Subjects:
  Blood Chemistry Dust Endotoxins Hazardous Substances Immune System Lung Macrophages Metals Occupational Health Particulate Matter Pathology Respiratory System Safety Toxicology

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• Keywords:
  Acute Toxicity Analytical Processes Carbon Nanotubes Chemical Properties Dose Response Dusts Fibroblasts Genotoxicity Humans Immune Reaction In Vivo Study Lung Cells Models Molecular Signaling Nanofibers Nanomaterials Nanotoxicology Nanotubes Particle Diameter Particle Size Phagocytic Activity Physical Properties Polychlorinated Aromatic Hydrocarbons Surface Properties Toxic Effects Toxic Materials

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; Colorado ; Ohio ; OSHA Region 3 ; OSHA Region 5 ; OSHA Region 8 ; OSHA Region 9 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division ; RHD - Respiratory Health Division ; DFSE - Division of Field Studies and Engineering
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  276-277
• Volume:
  174
• Issue:
  1
• NIOSHTIC Number:
  nn:20058960
• Citation:
  Toxicologist 2020 Mar; 174(1):276-277
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2020
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 59th Annual Meeting and ToxExpo, March 15-19, 2020, Anaheim, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:2d7b2b2e1c5bf8c6a2228b0244dc4b61faf455971954d1bc2a8807dfd3c6b195963bd2e1470271db0a08e92337d786dd470813ed45310d1daa3a144e7f6fe862
• Download URL:
  https://stacks.cdc.gov/view/cdc/223308/cdc_223308_DS1.pdf
• File Type:
  [PDF - 541.39 KB ]