Functional and molecular responses to inhalation of MWCNT from the perspective of occupationally-relevant depositions

Details

• Personal Author:
  Aragon M ; Battelli L ; Bilgesu S ; Bishop L ; Campen M ; Castranova, Vincent ; Chen T-hB ; Cumpston A ; Cumpston JL ; Erdely A ; Eye T ; Frazer D ; Gu JK ; Kashon ML ; Kodali VK ; McKinney W ; Mercer R ; Shah S ; Tugendreich S ; Zeidler-Erdely PC
• Description:
  In order to assess the toxic response to occupationally-relevant depositions of multi-walled carbon nanotubes (MWCNTs), a dose- and time-dependent 4-week inhalation exposure (0.5-5 mg/m3) to MWNCTs (Mitsui-7) was conducted to model a worker exposed to 76 (40 microg alveolar deposition), 7.6 (4 microg) and 0.76 (0.4 microg) years at average inhalable workplace concentrations of 10.6 microg/m3. Mice were sacrificed at 0, 28, and 84 d post-exposure with lung, liver, and aorta collected for microarray-based gene expression profiling analyzed in conjunction with alterations in lavage proteins, alveolar macrophage function, histopathology, extrathoracic translocation, and systemic effects. Differentially expressed genes, upstream transcriptional regulators, and responses corresponding to inflammation/immune function and pathological changes (e.g. fibrosis) were persistent in the high dose but transient in the middle dose. The responses reflected the 58 lavage proteins measured and morphometric analysis of alveolar fibrosis which was increased in the high dose only. Similarly, isolated alveolar macrophages challenged with LPS (1 ug/ml) ex vivo had enhanced cytokine production that was sustained only in the high dose. At all doses, MWCNT translocated to extrathoracic organs indicating a dependence on physicochemical properties instead of a specific molecular mechanism. Analysis of systemic effects showed minimal to no changes in liver or aorta transcriptomics, 58 analyzed plasma proteins, or liver and renal histopathology. Endothelial cells challenged with plasma collected from the high dose group showed enhanced expression of adhesion molecules. In summary, altered molecular pathways, histopathology changes, and systemic effects occur primarily at depositions (or dose rates) predicted to be significantly higher than what was measured in 8 MWCNT workplaces. [Description provided by NIOSH]
• Subjects:
  Blood Cells, Cultured Chemistry Environmental Exposure Fibrosis Immune System Laboratories Lung Macrophages Occupational Health Pathology Respiratory System Safety Toxicology

  More +
• Keywords:
  Alveolar Cells Analytical Processes Cell Alteration Cell Cultures Cell Culture Techniques Cell Signaling Chemical Deposition Chemical Properties Cytokines Dose Response Endothelial Cells Exposure Assessment Exposure Levels Gene Expression Gene Regulation Heart Histopathology Immune Reaction Inhalation Laboratory Animals Laboratory Testing Liver Lung Cells Multi-walled Carbon Nanotubes MWCNT Physical Properties Proteins Thorax

  More +
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; Louisiana ; New Mexico ; OSHA Region 3 ; OSHA Region 6 ; OSHA Region 9 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  150
• Issue:
  1
• NIOSHTIC Number:
  nn:20047817
• Citation:
  Toxicologist 2016 Mar; 150(1):583
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2016
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 55th Annual Meeting and ToxExpo, March 13-17, 2016, New Orleans, Louisiana
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:1ba68fb5aa25195a943f0ebf858e6bcc58df465a6e22a47f6140181e18dd4c4843faf69535fb35bbc779d294dbb7a6db451f3eabe729dd7d63f46a304f99d3c1
• Download URL:
  https://stacks.cdc.gov/view/cdc/202786/cdc_202786_DS1.pdf
• File Type:
  [PDF - 441.75 KB ]