Relationship of PKA and Acute Skin Irritation in Humans

The relationship between pKa and skin irritation in humans was studied for a homologous series of benzoic acid derivatives with predicted permeation through human skin at comparable rates (15-90 μg/cm2/hr). Skin irritation and pKa are strongly correlated, and, for pKa ≤4, skin irritation rapidly increases. Laser Doppler velocimetric assessment of skin blood flow, color meter readings, erythema, edema, and the primary irritation index are all linearly correlated and related to pKa; erythema at 24 hr appears to be the most sensitive variable.