title: Carbon nanotube dosimetry: from workplace exposure assessment to inhalation toxicology.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, USA. efi4@cdc.gov.
authors.forename: Aaron
authors.initials: A
authors.lastname: Erdely
authors.forename: Matthew
authors.initials: M
authors.lastname: Dahm
authors.forename: Bean T
authors.initials: BT
authors.lastname: Chen
authors.forename: Patti C
authors.initials: PC
authors.lastname: Zeidler-Erdely
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Fernback
authors.forename: M Eileen
authors.initials: ME
authors.lastname: Birch
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Evans
authors.forename: Michael L
authors.initials: ML
authors.lastname: Kashon
authors.forename: James A
authors.initials: JA
authors.lastname: Deddens
authors.forename: Tracy
authors.initials: T
authors.lastname: Hulderman
authors.forename: Suzan A
authors.initials: SA
authors.lastname: Bilgesu
authors.forename: Lori
authors.initials: L
authors.lastname: Battelli
authors.forename: Diane
authors.initials: D
authors.lastname: Schwegler-Berry
authors.forename: Howard D
authors.initials: HD
authors.lastname: Leonard
authors.forename: Walter
authors.initials: W
authors.lastname: McKinney
authors.forename: David G
authors.initials: DG
authors.lastname: Frazer
authors.forename: James M
authors.initials: JM
authors.lastname: Antonini
authors.forename: Dale W
authors.initials: DW
authors.lastname: Porter
authors.forename: Vincent
authors.initials: V
authors.lastname: Castranova
authors.forename: Mary K
authors.initials: MK
authors.lastname: Schubauer-Berigan
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019570:Inhalation Exposure; D051379:Mice; D008854:Microscopy, Electron; D037742:Nanotubes, Carbon; D016273:Occupational Exposure
chemical_list: D037742:Nanotubes, Carbon