Patrick E, Maibach H I, Burkhalter A
Toxicol Appl Pharmacol. 1985 Dec;81(3 Pt 1):476-90. doi: 10.1016/0041-008x(85)90419-3.
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.
在实验室小鼠中研究了化学物质通过多种机制诱发皮肤刺激的可能性。比较了苯酚、巴豆油、苯扎氯铵、苯丙炔酸乙酯（EPP）和水杨酸甲酯局部应用后的时间进程和剂量反应。每种化学物质的反应通过应用于一只耳朵后耳朵厚度的变化来测量。最大反应时间如下：水杨酸甲酯20分钟，苯酚1小时，巴豆油和苯扎氯铵6小时，EPP 8小时。对EPP的反应包括1小时时早期较小的反应。通过改变刺激物的赋形剂或改变剂量，反应的时间进程没有改变。炎症反应的消退率也有所不同。虽然外观正常，但用苯酚或苯扎氯铵处理的耳朵厚度在6周内比用溶剂处理的对照耳朵厚0.05至1毫米。虽然厚度延长的发生率与剂量有关，但它不是由急性反应的强度决定的；其他刺激物产生相同急性耳朵厚度增加的剂量并没有产生类似的变化。在组织学研究、台盼蓝和125I标记牛血清白蛋白测定血管通透性变化以及局部表面温度变化作为血流指标的研究中，比较了5毫克水杨酸甲酯、2毫克EPP和0.05毫克巴豆油引起的急性反应成分，即血管通透性、血流变化和细胞浸润。对化学物质最大反应时的反应组织学不同。刺激物产生了多个通透性增加和表面温度升高的时期。刺激物产生的通透性和血流反应在数量、相对于应用时间和最大反应时间的发生时间以及变化幅度方面各不相同。反应时间进程的差异不受实验性改变吸收速率的影响，以及对三种刺激物炎症反应成分的差异表明化学物质通过多种机制诱发皮肤刺激。
