Characterization of Pulmonary Toxicity Following Graphene Inhalation

Details

• Personal Author:
  Barger M ; Chaudhuri IS ; Chen TB ; Erdely A ; Kodali VK ; Kyrlidis A ; McKinney W ; Orandle MS ; Roach KA ; Roberts, Jennifer R. ; Schwegler-Berry D ; Stefaniak, Aleksandr B. ; Yanamala NV
• Description:
  Graphene is a 2D nanomaterial with unique physicochemical properties making it highly marketable for applications in numerous industries. Our previous studies have shown that toxicity varies depending on size and oxidative form of graphene following a single bolus-dose aspiration in mice, with exposure to reduced graphene oxide (rGO) resulting in the greatest degree of lung injury and inflammation. The goal of this study was to characterize pulmonary toxicity following subacute inhalation of rGO. C57BL/6J mice were exposed to rGO (2.41 microm MMAD, 2.69 GSD) by whole body inhalation at 5.0 mg/m3 for 5 h/d for 19 d, 0.5 mg/m3 for 5 h/d for 19 d, or 0.5 mg/m3 for 0.5 h/d for 19 d to achieve depositions with a two order of magnitude range. Controls were exposed to filtered air. Lung burden of rGO, parameters of lung toxicity and inflammation, and histopathology was analyzed 0 d, 3 d, 1 m, and 3 m post-exposure. Lung burden at 0 d was 0.78, 6.47, and 34.4 microg per lung for the low, middle and high dose. Following high dose exposure, lactate dehydrogenase (LDH) in lung lavage fluid (LLF, lung injury) and total lavage cells (inflammation) were increased up to 1 m compared to control. The cellular increase was due primarily to macrophage influx. Neutrophils were also significantly increased; however, this cell population accounted for less than 1% of the total cells. Inflammation and injury resolved by 3 m. Inflammatory and tissue remodeling proteins in LLF followed a similar pattern. Pathologic analysis indicated increased macrophages in the lungs at 0 and 3 d scored as minimal, resolving over time. Particle burden in macrophages was also observed to decrease over time. Following middle dose exposure, total lavage cells increased at 3 d, due primarily to macrophage influx, and resolved by 1 mo. Significantly fewer inflammatory proteins were elevated in LLF following exposure to the middle dose compared to the high dose, with resolution by 1 m. There was no difference in lung cellularity following low dose exposure. No lung pathology or increased LDH in LLF were observed following middle or low dose exposures. Exposure to rGO led to an acute dose-dependent increase in lung injury and inflammation, which resolved over time, with 0.5 mg/m3 causing a minimal degree of inflammation representing the low observable effect level. [Description provided by NIOSH]
• Subjects:
  Blood Body Fluids Environmental Exposure Hazardous Substances Immune System Laboratories Lung Lung Diseases Macrophages Occupational Health Pathology Respiratory System Respiratory Tract Diseases Safety Toxicology

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• Keywords:
  Body Fluids Cellular Reactions Dose Response Exposure Assessment Exposure Levels Graphene Graphene Oxide Immune Reaction Inhalation Laboratory Animals Laboratory Testing Lung Burden Lung Cells Lung Disease Lung Tissue Nanotechnology Nanotoxicology Neutrophils Proteins Pulmonary Effects Pulmonary Function Tissue Disorders Toxic Effects Toxic Materials

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Massachusetts ; OSHA Region 1 ; OSHA Region 3 ; OSHA Region 6 ; Texas ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division ; RHD - Respiratory Health Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  162
• Issue:
  1
• NIOSHTIC Number:
  nn:20051265
• Citation:
  Toxicologist 2018 Mar; 162(1):420
• CAS Registry Number:
  Graphene (CAS RN 1034343-98-0)
• Federal Fiscal Year:
  2018
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 57th Annual Meeting and ToxExpo, March 11-15, 2018, San Antonio, Texas
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:88844ae5e1c6710b9206021e7ba11215a1bf216ae4aab6c24afe90b7d1bfaf640633538b74a63ae965ab010c8a4ddda878e0ad52afd4e68f46552412237cd9ec
• Download URL:
  https://stacks.cdc.gov/view/cdc/211322/cdc_211322_DS1.pdf
• File Type:
  [PDF - 832.65 KB ]