Document Detail


High dissociation constants (pKa) of basic permeants are associated with in vivo skin irritation in man.
MedLine Citation:
PMID:  8730159     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Previously, we have investigated the relationship between dissociation constant (pKa) and skin irritation potential. In the present experiment, 12 basic compounds, with varying pKa values ranging from 1.4 to 11.2, were applied on the backs of 12 healthy adult panellists. Cutaneous reactions were measured objectively, using reflectance spectroscopy and transepidermal water loss (TEWL), and evaluated subjectively with a modified Draize scale. A positive correlation between increasing pKa and skin irritation capacity, measured either visually or by reflectance spectroscopy, was found, but only mecamylamine (pKa = 11.2) induced a significant increase in transepidermal water loss. Compounds with low pKa also induced a paradoxical vasoconstriction measured by reflectance spectroscopy. Only high pKa appeared predictive of in vivo skin irritation, and these chemicals apparently induce skin irritation with only minimal disruption of the skin barrier. A simple 1-variable model is predictive of skin irritation for this series of organic permeants with increasing pKa.
Authors:
A Nangia; P H Andersen; B Berner; H I Maibach
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial    
Journal Detail:
Title:  Contact dermatitis     Volume:  34     ISSN:  0105-1873     ISO Abbreviation:  Contact Derm.     Publication Date:  1996 Apr 
Date Detail:
Created Date:  1996-09-17     Completed Date:  1996-09-17     Revised Date:  2006-09-18    
Medline Journal Info:
Nlm Unique ID:  7604950     Medline TA:  Contact Dermatitis     Country:  DENMARK    
Other Details:
Languages:  eng     Pagination:  237-42     Citation Subset:  IM    
Affiliation:
Glaxo Canada, Toronto, Canada.
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MeSH Terms
Descriptor/Qualifier:
Adult
Cell Membrane Permeability / drug effects
Dermatitis, Irritant / etiology*,  metabolism
Female
Hemoglobins / metabolism
Humans
Hydrogen-Ion Concentration
Irritants / adverse effects*,  chemistry*
Middle Aged
Patch Tests
Skin / drug effects,  metabolism
Skin Absorption / drug effects
Water Loss, Insensible / drug effects,  physiology
Chemical
Reg. No./Substance:
0/Hemoglobins; 0/Irritants

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


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