Lung Toxicity and Gene Expression Changes in Response to Multiwalled Carbon Nanotubes Exposure in Rats

Details

• Personal Author:
  Boots T ; Joseph P ; Kashon M ; McKinney W ; Mustafa G ; Sager T ; Umbright C
• Description:
  Carbon-based nanomaterials have many applications and, therefore, human exposure to them potentially resulting in adverse health effects should be anticipated. Determination of the molecular mechanisms underlying the toxicity induced by carbon nanotubes has merit in the prevention of the adverse health effects potentially resulting from their exposures. Currently, a rat toxicity model was employed to investigate the molecular mechanisms underlying the lung toxicity induced by exposure to multi-walled carbon nanotubes (MWCNT). Rats were exposed, by whole-body inhalation, to air or an aerosol containing MWCNT particles to result in cumulative doses (concentration x time) ranging from 22.5 to 180 (mg/m3).h over a three-day period. Toxicity and global gene expression profiles were determined in the rat lungs, 16-hours following the last exposure. MWCNT particles, associated with alveolar macrophages (AMs), were detected in the lungs of the exposed rats. Mild to moderate histological changes consisting of increased cellularity, thickening of the alveolar wall, alveolitis, fibrosis, and granuloma formation were detected in the rat lungs. Bronchoalveolar lavage (BAL) toxicity parameters such as lactate dehydrogenase activity, number of AMs and PMNs, oxidant production by phagocytes, and levels of multiple cytokines (IL-1B, IL-10, IL-13, IL-16, IL-18, MCP-1, MIP-2, and TNF-a) were significantly altered in response to inhalation exposure to MWCNT in the rats. Global gene expression profiling identified several significantly differentially expressed genes (fold change >1.5 and FDR p value <0.05) in the lungs of the MWCNT exposed rats, compared with the controls. Bioinformatics analysis of the gene expression data identified significant enrichment of several diseases/biological functions (for example, cancer, leukocyte migration, inflammatory response, mitosis, and cell movement of phagocytes) and canonical pathways (for example, kinetochore metaphase signaling pathway, granulocyte and agranulocyte adhesion and diapedesis, acute phase response, and LXR/RXR activation). The alterations in the lung toxicity parameters and gene expression changes exhibited a dose-response to the MWCNT exposure. Taken together, the data provided insights into the molecular mechanisms underlying the pulmonary toxicity induced by inhalation exposure of rats to MWCNT. [Description provided by NIOSH]
• Subjects:
  Aerosols Animals Environmental Exposure Hazardous Substances Laboratories Lung Lung Diseases Neoplasms Occupational Health Particulate Matter Respiratory System Respiratory Tract Diseases Risk Assessment Risk Factors Safety

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• Keywords:
  Lung; Toxins; Gene expression; Multi-walled carbon nanotubes; MWCNT; Exposure levels; Risk factors; Animals; Laboratory animals; Health effects; Molecular biology; Models; Aerosols; Particulates; Bioinformatics; Biological function; Cancer; Dose response; Pulmonary system disorders; Respiratory system disorders
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; 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:
  186
• NIOSHTIC Number:
  nn:20064945
• Citation:
  Toxicologist 2022 Mar; 186(S1):217
• CAS Registry Number:
  Carbon (CAS RN 7440-44-0) ; Carbon nanotubes (CAS RN 308068-56-6)
• Federal Fiscal Year:
  2022
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 61st Annual Meeting & ToxExpo, March 27-31, 2022, San Diego, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:aa5abd62a7cfe697495fe12e12f9dde31ccbd42c9c71203d26a7ca6eda34d5357b91a301447da4cf23ad3de22ce2269d83b1d40654be31d13e18d4460477d8f4
• Download URL:
  https://stacks.cdc.gov/view/cdc/248912/cdc_248912_DS1.pdf
• File Type:
  [PDF - 207.58 KB ]