Document Detail


Mechanisms of chemically induced skin irritation. I. Studies of time course, dose response, and components of inflammation in the laboratory mouse.
MedLine Citation:
PMID:  4082196     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The possibility that chemicals induce skin irritation by multiple mechanisms was studied in laboratory mice. The time course and dose response to topical application of phenol, croton oil, benzalkonium chloride, ethyl phenylpropiolate (EPP), and methyl salicylate were compared. The responses to each chemical were measured as changes in ear thickness following application to one ear. Maximal responses were as follows: methyl salicylate 20 min, phenol 1 hr, croton oil and benzalkonium chloride 6 hr, and EPP 8 hr. The response to EPP included an early, smaller response at 1 hr. Time courses of the responses were not altered by changing the vehicle in which the irritants were applied or by altering the dose. The rates of regression of the inflammatory responses also varied. Although visibly normal, thickness of ears treated with either phenol or benzalkonium chloride remained 0.05 to 1 mm thicker than solvent-treated control ears for 6 weeks. Although the incidence of prolonged thickness was dose related, it was not determined by the intensity of the acute response; doses of other irritants which produced equivalent acute increases in ear thickness did not produce similar changes. The components of the acute responses, i.e., vascular permeability, change in blood flow, and cellular infiltration, to 5 mg methyl salicylate, 2 mg EPP, and 0.05 mg croton oil were compared in studies of tissue histology, changes in vascular permeability by trypan blue and 125I-labeled bovine serum albumin, and change in local surface temperature as an index of blood flow. The histology of the reactions at the time of maximum response to the chemicals differed. Multiple periods of increased permeability and increased surface temperature were produced by the irritants. The permeability and blood flow responses produced by the irritants varied in number, time of occurrence relative to time of application and to time of maximum response, and in magnitude of the changes. Differences in time courses of the responses which were not altered by experimentally varying rate of absorption and in components of the inflammatory response to the three irritants suggest that chemicals induce skin irritation by multiple mechanisms.
Authors:
E Patrick; H I Maibach; A Burkhalter
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Toxicology and applied pharmacology     Volume:  81     ISSN:  0041-008X     ISO Abbreviation:  Toxicol. Appl. Pharmacol.     Publication Date:  1985 Dec 
Date Detail:
Created Date:  1986-01-27     Completed Date:  1986-01-27     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0416575     Medline TA:  Toxicol Appl Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  476-90     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Absorption
Alkynes / toxicity*
Animals
Croton Oil / toxicity*
Dermatitis, Contact / etiology,  pathology*
Ear / blood supply,  drug effects*
Female
Irritants / metabolism,  toxicity*
Mice
Mice, Inbred ICR
Salicylates / toxicity*
Time Factors
Grant Support
ID/Acronym/Agency:
GMO7175/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Alkynes; 0/Irritants; 0/Salicylates; 119-36-8/methyl salicylate; 2216-94-6/ethylphenylpropiolate; 8001-28-3/Croton Oil

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


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