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Effect of PBPK model structure on interpretation of in vivo human aqueous dermal exposure trials.

Authors
Norman-AM; Kissel-JC; Shirai-JH; Smith-JA; Stumbaugh-KL; Bunge-AL
Source
Toxicol Sci 2008 Jul; 104(1):210-217
NIOSHTIC No.
20034630
Abstract
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.
Keywords
Work-environment; Work-performance; Work-practices; Worker-health; Workplace-studies; Occupational-hazards; Occupational-health; Skin-absorption; Skin-exposure; Skin-irritants; Skin-sensitivity; Models; Aqueous-solutions; Mathematical-models
Contact
John C. Kissel, Environmental & Occupational Health Sciences, University of Washington, 4225 Roosevelt Way NE, Suite 100, Seattle, WA 98105-6099
CODEN
TOSCF2
Publication Date
20080701
Document Type
Journal Article
Email Address
jkissel@u.washington.edu
Funding Type
Grant
Fiscal Year
2008
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-T42-CCT-010418; Grant-Number-T42-OH-008433
Issue of Publication
1
ISSN
1096-6080
Source Name
Toxicological Sciences
State
WA; CO
Performing Organization
University of Washington
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