Crystalline Nanocellulose-Induced Lung Toxicity and Global Gene Expression Changes in the Rat

Details

• Personal Author:
  Chen T ; Joseph P ; McKinney W ; Orandle M ; Roberts J ; Sager T ; Umbright C
• Description:
  Crystalline nanocellulose (CNC) is an emerging nanomaterial with multiple commercial and industrial applications. Occupational exposure to CNC during the production and/or use of products containing the nanomaterial potentially resulting in adverse health effects among workers is possible. Therefore, there is an immediate need to determine the toxicity potential and mechanisms underlying CNC toxicity. Male Fischer rats were exposed by whole body inhalation exposure to air or CNC (20 mg/m3, 6 hours/day, 14 days), and pulmonary toxicity and lung gene expression changes were determined one day following the last exposure. CNC particles were detected in the lung alveoli of the exposed rats. Compared with the air-only exposed controls, significant increases (p<0.05) in the incidence of bi-nucleated alveolar macrophages (AM), lactate dehydrogenase activity, pro-inflammatory cytokine levels, phagocyte oxidant production, and AM and neutrophil counts were detected in the bronchoalveolar lavage of the CNC exposed rats. Mild lung histological changes, such as the accumulation of AM and neutrophils, were observed in the CNC exposed rats. Global gene expression profiling by next generation sequencing identified 573 genes whose expressions were significantly different (fold change >1.5 and FDR p <0.05) in the lungs of the CNC exposed rats, compared with the controls. Bioinformatic analysis of the lung gene expression data identified significant enrichment of several biological functions and canonical pathways related to inflammation (cellular movement, immune cell trafficking, inflammatory diseases and response, respiratory disease, and free radical scavenging, complement system, acute phase response, leukocyte extravasation signaling, granulocyte and agranulocyte adhesion and diapedesis, IL-10 signaling, phagosome formation and maturation, etc) and oxidative stress (NRF2-mediated oxidative stress response, production of nitric oxide and reactive oxygen species in macrophages, etc). In summary, the data demonstrated the induction of pulmonary toxicity and global gene expression changes in the lungs of the rats in response to inhalation exposure to CNC. [Description provided by NIOSH]
• Subjects:
  Blood Environmental Exposure Free Radicals Genetics Hazardous Substances Histology Immune System Laboratories Lung Lung Diseases Macrophages Nitric Oxide Occupational Health Respiratory System Respiratory Tract Diseases Safety Toxicology

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• Keywords:
  Alveolar Cells Bioinformatics Biological Function Cellular Effects Cellular Reactions Cytokines Dose Response Emerging Technology Exposure Assessment Exposure Levels Free Radicals Gene Expression Genes Immune Reaction Inhalation Laboratory Animals Laboratory Testing Lung Cells Lung Disorders Nanocellulose Nanomaterials Neutrophils Nitric Oxide Oxidative Stress Phagocytes Phagocytic Activity Pulmonary Effects Pulmonary System Disorders Reactive Oxygen Species ROS Toxic Effects Toxic Materials

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Maryland ; 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
• Pages in Document:
  291-292
• Volume:
  168
• Issue:
  1
• NIOSHTIC Number:
  nn:20055014
• Citation:
  Toxicologist 2019 Mar; 168(1):291-292
• CAS Registry Number:
  Cellulose (CAS RN 9004-34-6) ; Nitric oxide (CAS RN 10102-43-9)
• Federal Fiscal Year:
  2019
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 58th Annual Meeting and ToxExpo, March 10-14, 2019, Baltimore, Maryland
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:c8bbd73ebe1d0ccc1e2f208aa87bdd7144ac0a3689f7b9edd8cf05b8ebbfe606711188fd0e856ead4c267bb1831164acd68ba29923a6aeed879f2d68f988f9fd
• Download URL:
  https://stacks.cdc.gov/view/cdc/217418/cdc_217418_DS1.pdf
• File Type:
  [PDF - 909.42 KB ]