Document Detail


A new method for estimating dermal absorption from chemical exposure. 3. Compared with steady-state methods for prediction and data analysis.
MedLine Citation:
PMID:  7494817     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: This paper compares unsteady-state and steady-state methods for estimating dermal absorption or analyzing dermal absorption data. The unsteady-state method accounts for the larger absorption rates during short exposure times as well as the hydrophilic barrier which the viable epidermis presents to lipophilic chemicals. METHODS: Example calculations for dermal absorption from aqueous solutions are presented for five environmentally relevant chemicals with molecular weights between 50 and 410 and log10Kow between 0.91 and 6.8: chloromethane, chloroform, chlordane, 2,3,7,8-TCDD, and dibenz(a,h)anthracene. Also, the new method is used to evaluate experimental procedures and data analyses of in vivo and in vitro permeation measurements. RESULTS: In the five example cases, we show that the steady-state approach significantly underestimated the dermal absorption. Also, calculating permeability values from cumulative absorption data measured for exposure periods less than 18 times the stratum corneum lag time will overestimate the actual permeability. CONCLUSIONS: In general, steady-state predictions of dermal absorption will underestimate dermal absorption predictions which consider unsteady-state conditions. Permeability values calculated from data sets which include unsteady-state data will be incorrect. Strategies for analyzing in vitro diffusion cell experiments and confirming steady state are described.
Authors:
A L Bunge; R L Cleek; B E Vecchia
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Pharmaceutical research     Volume:  12     ISSN:  0724-8741     ISO Abbreviation:  Pharm. Res.     Publication Date:  1995 Jul 
Date Detail:
Created Date:  1996-01-11     Completed Date:  1996-01-11     Revised Date:  2010-03-24    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  972-82     Citation Subset:  IM    
Affiliation:
Chemical Engineering and Petroleum Refining Department, Colorado School of Mines, Golden 80401, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Membrane Permeability
Environmental Exposure
Environmental Pollutants / pharmacokinetics*
Humans
Mathematical Computing
Models, Biological*
Predictive Value of Tests
Skin Absorption*
Chemical
Reg. No./Substance:
0/Environmental Pollutants

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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