Structure-activity relationships in allergic contact dermatitis

Abstract

Skin sensitization by simple chemicals involves reaction with nucleophilic groups on skin proteins or possibly on proteins in cell membranes to form haptenic groups, which act as allergenic determinants. A quantitative model for sensitization by ‘alkylating agents’, the RAI (Relative Alkylation Index) theory, has been devised and applied to the sensitization observed with three model series of compounds— p-nitrobenzyl halides and saturated and unsaturated sultones. Examination of chemical structures, and predictions of the types of chemical reaction that substances may undergo, can be used to assess the likely reactivity of unknown materials towards skin proteins. In addition such examinations of structure may be used to assess the likely cross-reactivity of materials. The pro-hapten concept of Dupuis & Benezra ( Allergic Contact Dermatitis to Simple Chemicals. A Molecular Approach. Marcel Dekker, New York) offers an explanation for the sensitization potential of substances that do not contain chemically reactive groups prior to in vivo conversion and for cross-reactions between apparently unrelated chemicals.