Pulmonary toxicity in response to inhalation exposure to nanocrystalline cellulose in the rat

Details

• Personal Author:
  Chen BT ; Joseph P ; McKinney W ; Orandle M ; Roberts, Jennifer R. ; Sager T ; Umbright C
• Description:
  The physical and/or chemical properties of nanocrystalline cellulose (NCC) offer multiple commercial and industrial applications. Human exposure to NCC is possible during the production and/or use of products containing NCC, and such exposures may result in adverse health effect(s). However, neither the toxicity potential nor the mechanisms underlying any toxicity are characterized for NCC. Currently, the pulmonary toxicity potential of NCC and the possible molecular mechanisms underlying the toxicity, if any, were studied by employing a rat inhalation toxicity model. Male Fischer rats were exposed by whole body inhalation to air or NCC (20 mg/m3, 6 hours/day, 14 days), and pulmonary toxicity determined at 16-hours following the last exposure. Compared with the controls, increases in lactate dehydrogenase activity, pro-inflammatory cytokine levels, phagocyte oxidant production, and macrophage and neutrophil counts were detected in the bronchoalveolar lavage cells or fluid of the NCC exposed rats. Mild lung histological changes, such as the accumulation of macrophages and neutrophils, were observed in the NCC exposed rats. Together, these findings suggested that NCC exposure resulted in pulmonary toxicity in rats. Global gene expression profiling by next generation sequencing identified approximately 1000 genes whose expressions were significantly different (FDR p <0.01) in the lungs of the NCC exposed rats compared with the controls. Bioinformatic analysis of the gene expression data identified significant enrichment of several biological functions (for example, cellular movement, immune cell trafficking, inflammatory diseases and response, respiratory disease, and free radical scavenging) and canonical pathways (for example, complement system, acute phase response, leukocyte extravasion signaling, granulocyte and agranulocyte adhesion and diapedesis, IL-10 signaling, phagosome formation and maturation, NRF2-mediated oxidative stress response, and production of nitric oxide and reactive oxygen species in macrophages) in the lungs in association with NCC-induced pulmonary toxicity. In summary, our data demonstrated that NCC exposure can induce pulmonary toxicity in rats. Furthermore, we have identified the induction of inflammation and oxidative stress as two of the major mechanisms underlying the pulmonary toxicity induced by NCC in rats. [Description provided by NIOSH]
• Subjects:
  Blood Body Fluids Cellulose Environmental Exposure Enzymes 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:
  Analytical Models Bioinformatics Biological Function Body Fluids Cell Signaling Cellular Effects Cellular Reactions Cellulose Fibers Cytokines Enzyme Activity Exposure Assessment Exposure Levels Free Radicals Gene Expression Genes Immune Reaction Immune System Inhalation Laboratory Animals Laboratory Testing Leukocytes Lung Cells Lung Disorders Lung Function Nanocellulose Nanocrystals Nanomaterials Nanotechnology Nanotoxicology Neutrophils Nitric Oxide Oxidative Stress Phagocytes Phagocytic Activity Pulmonary System Disorders Reactive Oxygen Species Respiratory System Disorders 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
• Volume:
  156
• Issue:
  1
• NIOSHTIC Number:
  nn:20049464
• Citation:
  Toxicologist 2017 Mar; 156(1):329
• CAS Registry Number:
  Cellulose (CAS RN 9004-34-6) ; Nitric oxide (CAS RN 10102-43-9)
• Federal Fiscal Year:
  2017
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 56th Annual Meeting and ToxExpo, March 12-16, 2017, Baltimore, Maryland
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:1a112ef0eef15bd13ec6baf760b2751ea2423b1a5d09b7320024a76ca38829c60c22b28e9ab9c293dffda102ce5f2131d3c6d4d9dfdb99e5cb8a7b0a8c6ad9e8
• Download URL:
  https://stacks.cdc.gov/view/cdc/203908/cdc_203908_DS1.pdf
• File Type:
  [PDF - 944.94 KB ]