Inhalation Exposure to Cellulose Nanocrystals: Study of Pulmonary and Reproductive Outcomes in Male Mice

Details

• Personal Author:
  Farcas M ; Guppi S ; Gutkin D ; Kagan VE ; Kisin ER ; McKinney W ; Shurin MR ; Shvedova AA ; Yanamala N
• Description:
  Cellulose(s) are bio-based lightweight natural materials with high aspect ratios, excellent physical strength, transparency and chemical resistance. Crystalline nanocelluloses (CNC) have better electrical, optical, and mechanical properties compared to non-nanosized original forms. These features are very desirable for a number of novel applications. Eco-friendly technology and sustainability along with biodegradable nature made CNCs very attractive for manufacturing and high demand in industrial world market. We investigated adverse pulmonary and reproductive outcome caused by inhalation exposure to CNC aerosol generated from a bulk supply of wood pulp derived cellulose nanocrystals (freeze dried powder, FPL, USFS). C57BL6/J male mice were exposed to precise concentration of dispersed airborne CNC (5 mg/m3, 5 h/day, 5 days/week for 3 weeks). Measurements of pulmonary functions in mice were conducted prior to bronchoalveolar lavage (BAL), lungs and testes collection for histopathology, and measurements of oxidative stress, inflammation, and effects on male reproductive functions at 24 h, 2-, 6- and 12-months post exposure. Exposure to CNC significantly increased airway responsiveness to methacholine and decreased tidal volume at 12 months of recovery as compared to air-control group. Hierarchical clustering analysis of the inflammatory cytokine responses revealed a shift in inflammatory responses from a Th1 type at early recovery time points to a Th2 response at the later stages. Similarly, BAL cytology indicated the preferential accumulation of polymorphonuclear neutrophils (PMNs) or eosinophils, respectively, at 24h and 12 months post exposure. Moreover, CNC inhalation resulted in the prominent perivascular lymphoid aggregates along with stronger peribronchial and perivascular fibrosis in the lungs (6-12 months of recovery). Histological analysis of testes showed pathological manifestations suggestive of abnormal sperm functions and production at the later time points of recovery. Inhalation exposure was associated with sperm DNA damage, changes in sperm motility and morphology. Accumulation of oxidative damage was observed as evidenced by elevated contents of oxidatively modified protein carbonyls in the testes. In conclusion: Exposure of C57BL6 mice to respirable CNC caused pulmonary and male reproductive toxicity observed up to 12 months post inhalation. [Description provided by NIOSH]
• Subjects:
  Aerosols Cellulose Cytotoxins Environmental Exposure Hazardous Substances Immune System Laboratories Lung Lung Diseases Methacholine Compounds Occupational Health Respiratory System Respiratory Tract Diseases Safety Toxicology Urogenital System Wood

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• Keywords:
  Airway Resistance Carbonyls Cellular Reactions Cytokines Cytotoxicity DNA Damage Exposure Assessment Exposure Levels Histopathology Immune Reaction Inhalation Laboratory Animals Laboratory Testing Lung Fibrosis Methacholines Morphology Nanocellulose Nanocrystals Nanotoxicology Neutrophils Oxidative Stress Proteins Pulmonary Effects Pulmonary Function Reproductive Effects Spermatozoa Testes Toxic Effects Toxic Materials

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; OSHA Region 3 ; OSHA Region 9 ; Pennsylvania ; 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:
  174
• Issue:
  1
• NIOSHTIC Number:
  nn:20058922
• Citation:
  Toxicologist 2020 Mar; 174(1):261
• CAS Registry Number:
  Cellulose (CAS RN 9004-34-6)
• Federal Fiscal Year:
  2020
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 59th Annual Meeting and ToxExpo, March 15-19, 2020, Anaheim, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:bfe8d9217c9038858e18e61e1e3a546f5b1f41b54c19d5a6096d2fb7750c7330ef2b785ad4992c2dc55ea9f61d444dd33cabbcab8370e7034b35b246a69fd946
• Download URL:
  https://stacks.cdc.gov/view/cdc/223280/cdc_223280_DS1.pdf
• File Type:
  [PDF - 522.58 KB ]