salicylates and ethylphenylpropiolate

The time course, dose response, components of inflammation, and involvement of putative mediators of inflammation in irritation induced by different chemicals was compared using a mouse ear swelling technique. Differences in time courses of inflammation produced by the irritants were not solely due to differences in rates of penetration. Changes in blood flow and permeability of vessels were phasic with different numbers of phases induced by different irritants. Effects of antagonist, synthesis, inhibitors, and depleting agents of putative inflammatory mediators on intensity of inflammation varied for different irritants. These studies demonstrate that all chemicals do not produce skin irritation by a common inflammatory pathway.

Topics: Alkynes; Animals; Animals, Laboratory; Capillary Permeability; Croton Oil; Dermatitis; Dose-Response Relationship, Drug; Female; Mice; Mice, Inbred ICR; Regional Blood Flow; Salicylates; Skin; Skin Absorption

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.

Topics: Absorption; Alkynes; Animals; Croton Oil; Dermatitis, Contact; Ear; Female; Irritants; Mice; Mice, Inbred ICR; Salicylates; Time Factors