Effect of PBPK Model Structure on Interpretation of In Vivo Human Aqueous Dermal Exposure Trials

Details

• Personal Author:
  Bunge AL ; Kissel JC ; Norman AM ; Shirai JH ; Smith JA ; Stumbaugh KL
• Description:
  Multiple research teams have reported data from in vivo human trials in which breath was monitored during and after whole-body or partial immersion in aqueous solutions of volatile organic compounds. Estimation of total dermal absorption from exhaled breath measurements requires modeling, a task to which physiologically based pharmacokinetic (PBPK) models have often been applied. In the context of PBPK models, the exposed skin compartment can be modeled in many different ways. To demonstrate potential effects of alternative skin models on overall PBPK model performance, alternative models of skin have been incorporated in a PBPK model used to predict chloroform in breath during and after immersion in aqueous solution. The models investigated include treatment of skin as both a homogeneous phase and as a membrane in which concentration varies with depth. Model predictions are compared with in vivo human experimental results reported in the prior literature. In the example chosen, the common practice of modeling skin as a homogenous phase leads to prediction of more rapid initial uptake and lower cumulative uptake than does modeling skin as a membrane. Numerical estimates of the permeability coefficient are shown to be dependent upon skin model form and temperature of the aqueous solution. [Description provided by NIOSH]
• Subjects:
  Occupational Exposure Occupational Health Safety Skin Skin Absorption Workplace
• Keywords:
  Aqueous-solutions Mathematical-models Models Occupational-hazards Occupational-health Skin-absorption Skin-exposure Skin-irritants Skin-sensitivity Work-environment Work-performance Work-practices Worker-health Workplace-studies

  More +
• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Colorado ; OSHA Region 10 ; OSHA Region 8 ; Washington
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  210-217
• Volume:
  104
• Issue:
  1
• NIOSHTIC Number:
  nn:20034630
• Citation:
  Toxicol Sci 2008 Jul; 104(1):210-217
• Contact Point Address:
  John C. Kissel, Environmental & Occupational Health Sciences, University of Washington, 4225 Roosevelt Way NE, Suite 100, Seattle, WA 98105-6099
• Email:
  jkissel@u.washington.edu
• Federal Fiscal Year:
  2008
• Performing Organization:
  University of Washington
• Peer Reviewed:
  True
• Start Date:
  19940701
• Source Full Name:
  Toxicological Sciences
• End Date:
  20060630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ea2ff42342520c59d5a8220efee2b12e6b3bc2c683d717106a74bc51c3c79655c521bb3c9a7eaefc84ef71bec9c3f7df28628370987b7aec9a9bf742f73370dc
• Download URL:
  https://stacks.cdc.gov/view/cdc/186769/cdc_186769_DS1.pdf
• File Type:
  [PDF - 194.82 KB ]