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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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