Chemical and pharmacologic skin irritation in man

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Abstract
Attention is increasingly being focused on the relationship of dissocial Ion constant (pKa) of chemicals and skin irritation presumably caused by pH effects at epidermal levels. Human skin Studies of irritation have utilized both subjective visual‐palpation scores and reflectance spectroscopy (RS) or laser Doppler velocimetry (LDV) respectively. Several studies document that erythema determined subjectively and objectively correlates with the degree of skin irritancy, but others report lack of correlation between LDV and irritancy scored subjectively. In this study, pharmacologicol and chemical in vivo, skin irritation was evaluated utilizing an improved reflectance spectrophotometer equipped with computerized data analysis. In 16 white females, a model for skin irritation was induced by a 24‐h patch application of 4 basic chemicals, imipramine, norephedrine, nicotine and 8‐aminoquinoline, with pKa's ranging from 3.8 to 9.5. Skin pigmentation (melanin) and the relative amounts of oxygenized (arterial) and deoxygenized (venous) hemoglobin present in the erythematous skin were calculated. A clear increase in the hemoglobin content was observed in chemical and vehicle exposed sites. Although skin irritation is a complex phenomenon involving chemical and solution properties, percutaneous absorption and the biological drug response, high pKa (p > 0.01) was predictive of acute skin irritation in man using computerized analysis of reflectance spectroscopy, A high correlation between visual score and RS was found (r= 0.91).