Allergic Contact Dermatitis––Formation, Structural Requirements, and Reactivity of Skin Sensitizers

作者：Ann‐Therése Karlberg, Moa Andresen Bergström, Anna Börje, Kristina Luthman, Jonas Nilsson · 发表于：Chemical Research in Toxicology · 年份：2007 · DOI：10.1021/tx7002239 · 被引用次数：282 · 研究领域：Contact Dermatitis and Allergies、Skin Protection and Aging、Dermatology and Skin Diseases

Contact allergy is caused by a wide range of chemicals after skin contact. Its clinical manifestation, allergic contact dermatitis (ACD), is developed upon repeated contact with the allergen. This perspective focuses on two areas that have yielded new useful information during the last 20 years: (i) structure-activity relationship (SAR) studies of contact allergy based on the concept of hapten-protein binding and (ii) mechanistic investigations regarding activation of nonsensitizing compounds to contact allergens by air oxidation or skin metabolism. The second area is more thoroughly reviewed since the full picture has previously not been published. Prediction of the sensitizing capacity of a chemical is important to avoid outbreaks of ACD in the population. Much research has been devoted to the development of in vitro and in silico predictive testing methods. Today, no method exists that is sensitive enough to detect weak allergens and that is robust enough to be used for routine screening. To cause sensitization, a chemical must bind to macromolecules (proteins) in the skin. Expert systems containing information about the relationship between the chemical structure and the ability of chemicals to haptenate proteins are available. However, few designed SAR studies based on mechanistic investigations of prohaptens have been published. Many compounds are not allergenic themselves but are activated in the skin (e.g., metabolically) or before skin contact (e.g., via air oxidatio...