The importance of exposure estimation in the assessment of skin sensitization risk

The development of new ingredients and products for the consumer market req uires a thorough assessment of their potential for skin sensitization and t he possible clinical manifestation of allergic contact dermatitis. The proc ess by which low molecular weight chemicals induce and elicit skin sensitiz ation reactions is complex and dependent on many factors relevant to the ab ility of the chemical to penetrate the skin, react with protein, and trigge r the cell-mediated immune response. These major factors include inherent p otency, chemical dose, duration and frequency of exposure, vehicle or produ ct matrix, and occlusion. The fact that a chemical is a contact allergen do es not mean that it cannot be formulated into a consumer product at levels well tolerated by most individuals. Many common ingredients (e.g., fragranc es, preservatives) are known skin allergens. However, all allergens show do se-response and threshold characteristics. Therefore, one should be able to incorporate these chemicals into products at levels that produce acceptabl y low incidences of skin sensitization under foreseeable conditions of expo sure. The critical exposure determinant for evaluating skin sensitization r isk is dose per unit area of skin exposed. Use of this parameter allows for comparative assessments from different types of skin sensitization tests ( including cross-species comparisons), and, at least for known potent allerg ens, there is remarkable similarity in threshold dose/unit area determinati ons across species. The dose/unit area calculation enables a judgment of th e sensitization risk for different product types. This is illustrated using the chemical preservative methylchloroisothiazoline/methylisothiazolinone (MCI/MI) as a case study.