| High dissociation constants (pKa) of basic permeants are associated with in vivo skin irritation in man. | |
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MedLine Citation:
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PMID: 8730159 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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A Nangia; P H Andersen; B Berner; H I Maibach |
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Publication Detail:
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Type: Clinical Trial; Journal Article; Randomized Controlled Trial |
Journal Detail:
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Title: Contact dermatitis Volume: 34 ISSN: 0105-1873 ISO Abbreviation: Contact Derm. Publication Date: 1996 Apr |
Date Detail:
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Created Date: 1996-09-17 Completed Date: 1996-09-17 Revised Date: 2006-09-18 |
Medline Journal Info:
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Nlm Unique ID: 7604950 Medline TA: Contact Dermatitis Country: DENMARK |
Other Details:
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Languages: eng Pagination: 237-42 Citation Subset: IM |
Affiliation:
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Glaxo Canada, Toronto, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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0/Hemoglobins; 0/Irritants |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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