Carbon nanotube dosimetry: from workplace exposure assessment to inhalation toxicology

Details

• Alternative Title:
  Part Fibre Toxicol
• Personal Author:
  Erdely, Aaron ; Dahm, Matthew ; Chen, Bean T. ; Zeidler-Erdely, Patti C. ; Fernback, Joseph E. ; Birch, M. Eileen ; Evans, Douglas E. ; Kashon, Michael L. ; Deddens, James A. ; Hulderman, Tracy ; Bilgesu, Suzan A. ; Battelli, Lori ; Schwegler-Berry, Diane ; Leonard, Howard D. ; McKinney, Walter ; Frazer, David G. ; Antonini, James M. ; Porter, Dale W. ; Castranova, Vincent ; Schubauer-Berigan, Mary K.
• Description:
  Background
  
  Dosimetry for toxicology studies involving carbon nanotubes (CNT) is challenging because of a lack of detailed occupational exposure assessments. Therefore, exposure assessment findings, measuring the mass concentration of elemental carbon from personal breathing zone (PBZ) samples, from 8 U.S.-based multi-walled CNT (MWCNT) manufacturers and users were extrapolated to results of an inhalation study in mice.
  
  Results
  
  Upon analysis, an inhalable elemental carbon mass concentration arithmetic mean of 10.6 μg/m3 (geometric mean 4.21 μg/m3) was found among workers exposed to MWCNT. The concentration equates to a deposited dose of approximately 4.07 μg/d in a human, equivalent to 2 ng/d in the mouse. For MWCNT inhalation, mice were exposed for 19 d with daily depositions of 1970 ng (equivalent to 1000 d of a human exposure; cumulative 76 yr), 197 ng (100 d; 7.6 yr), and 19.7 ng (10 d; 0.76 yr) and harvested at 0, 3, 28, and 84 d post-exposure to assess pulmonary toxicity. The high dose showed cytotoxicity and inflammation that persisted through 84 d after exposure. The middle dose had no polymorphonuclear cell influx with transient cytotoxicity. The low dose was associated with a low grade inflammatory response measured by changes in mRNA expression. Increased inflammatory proteins were present in the lavage fluid at the high and middle dose through 28 d post-exposure. Pathology, including epithelial hyperplasia and peribronchiolar inflammation, was only noted at the high dose.
  
  Conclusion
  
  These findings showed a limited pulmonary inflammatory potential of MWCNT at levels corresponding to the average inhalable elemental carbon concentrations observed in U.S.-based CNT facilities and estimates suggest considerable years of exposure are necessary for significant pathology to occur at that level.
  
  
• Subjects:
  Animals Dose-Response Relationship, Drug Gene Expression Humans Inhalation Exposure Mice Microscopy, Electron Mouse Model MWCNT Dose Response And Time Dependence Nanotubes, Carbon Occupational Exposure Protein Research Workplace Exposure Assessment

  More +
• Source:
  Part Fibre Toxicol. 2013; 10:53.
• Document Type:
  Journal Article
• Volume:
  10
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:1be2cf97e50318018e6f67ceae844c7af52a237621cc0c6a4a3476d6f60efd9f
• Download URL:
  https://stacks.cdc.gov/view/cdc/28324/cdc_28324_DS1.pdf
• File Type:
  [PDF - 2.59 MB ]