PCS.04 Establishment of safe exposure limits for the induction of allergy. Theory

Abstract

For new chemicals introduced into the workplace or marketplace, and which come into contact with the skin, it is necessary, to conduct a thorough skin safety testing and risk assessment program to be certain that the exposures will be well tolerated. One vital risk assessment process involves the determination of allergic skin reactions, referred to as skin sensitization, the clinical manifestation of which is allergic contact dermatitis. The process by which low molecular weight chemicals induce and elicit skin sensitization is dependent on many factors including the ability of the chemical to penetrate the skin, react with protein, and trigger a cell‐mediated immune response. Based on our chemical, cellular and molecular understanding of allergic contact dermatitis, it is possible to carry out a quantitative risk assessment. It has been well known for years that chemical allergens display dose‐response characteristics regardless of whether the sensitization is induced in an experimental system or in humans. Moreover, it is well known that the critical exposure determinant for evaluating skin sensitization risk is dose per unit area of skin exposed. The skin sensitization testing and risk assessment process for new ingredients and consumer products generally follows a step‐wise approach that may involve structure‐activity evaluations, analytical assessments, preclinical skin sensitization testing (e.g., the mouse local lymph node assay), confirmatory clinical testing (e.g., the human repeat insult patch test), and benchmarking of resulting data against similar ingredients and product types. Essential elements for conducting a sound risk assessment involve the development of an understanding of the sensitization potential of the contact allergen and the likely dose, nature, extent and duration of exposure. With an understanding of the exposure and potency of the chemical one can assess whether the chemical, under the specific conditions of exposure, ould pose an acceptable or unacceptable risk of induction of skin sensitization. As with any test method or risk assessment approach, it is critical to understand the strengths and limitations so that one can conduct the best assessment possible and assure the skin safety of the chemical under evaluation.