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A Real-time Method to Evaluate the Nasal Deposition and Clearance of Acetone in the Human Volunteer

Journal Article · · Inhalation Toxicology, 15(6):523-538
 [1];  [2]; ;  [1];  [1];  [3];  [4];  [5]
  1. BATTELLE (PACIFIC NW LAB)
  2. Otolaryngology, Head&
  3. US PA-NCEA
  4. EPA-Human Studies Division
  5. Pacific Northwest National Laboratory

Nasal dosimetry models have become increasingly quantitative as insights into tissue deposition/clearance and computational fluid dynamics have become available. Validation of these models requires sufficient experimental data. However, investigations into respiratory deposition, particularly in human volunteers, have been historically limited due to methodological limitations. To overcome this, a method for evaluating the nasal wash-in, wash-out phenomena of a highly water-soluble compound in human volunteers was developed and characterized. This methodology was assessed using controlled human inhalation exposures to uniformly labeled 13C-acetone at approximately 1 ppm concentration for 30 minutes under different breathing maneuvers (inhale nose/exhale nose; inhale nose/exhale mouth; inhale mouth/exhale nose). A small-diameter air-sampling probe inserted in the nasopharyngeal cavity of the volunteer was connected directly to an ion-trap mass spectrometer capable of sampling every 0.8 sec. A second ion-trap mass spectrometer simultaneously sampled from the volunteer?s exhaled breath stream via a breath-inlet device interface. Together, the two mass spectrometers provided real-time appraisal of the 13C-acetone concentrations in the nasopharyngeal region and in the exhaled breath stream before, during, and after the different breathing maneuvers. The breathing cycle (depth and frequency) and heart rate were concurrently monitored throughout the exposure using a heart rate monitor and a human plethysmograph to differentiate inhalation and exhalation. Graphical overlay of the plethysmography results with the mass spectrometer measurements show clear quantifiable differences in 13C-acetone levels at the nasal probe as a function of breathing maneuvers. Breath-by-breath analysis of 13C-acetone concentrations indicate that between 40-75% of the compound is absorbed upon inhalation and nearly all of that absorbed released back into the breath stream during exhalation.

Research Organization:
Pacific Northwest National Laboratory (PNNL), Richland, WA (US)
Sponsoring Organization:
USDOE
DOE Contract Number:
AC06-76RL01830
OSTI ID:
15004604
Report Number(s):
PNWD-SA-5844
Journal Information:
Inhalation Toxicology, 15(6):523-538, Journal Name: Inhalation Toxicology, 15(6):523-538 Journal Issue: 6 Vol. 15; ISSN 1091-7691; ISSN 0895-8378
Country of Publication:
United States
Language:
English

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