Nangia A, Andersen P H, Berner B, Maibach H I
Glaxo Canada, Toronto, Canada.
Contact Dermatitis. 1996 Apr;34(4):237-42. doi: 10.1111/j.1600-0536.1996.tb02192.x.
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.
此前，我们研究了解离常数（pKa）与皮肤刺激潜力之间的关系。在本实验中，将12种pKa值在1.4至11.2之间变化的碱性化合物涂抹于12名健康成年受试者的背部。使用反射光谱法和经表皮水分流失（TEWL）客观测量皮肤反应，并使用改良的Draize量表进行主观评估。发现pKa升高与通过视觉或反射光谱法测量的皮肤刺激能力之间呈正相关，但只有美加明（pKa = 11.2）会导致经表皮水分流失显著增加。低pKa的化合物通过反射光谱法测量也会引起反常的血管收缩。只有高pKa似乎可预测体内皮肤刺激，并且这些化学物质显然仅在对皮肤屏障造成最小破坏的情况下诱导皮肤刺激。一个简单的单变量模型可预测这一系列有机渗透剂随着pKa增加的皮肤刺激情况。
