A risk assessment process for allergic contact sensitization

Abstract

This review describes an approach that has been used to assess the skin sensitization risk of new chemicals and product formulations prior to launching the new chemical or product on the market. The risk assessment process utilizes a comparative toxicological approach, in which data on the inherent toxicity of a material, and the exposure to it through manufacturing or consumer use or foreseeable misuse, are integrated and compared with data generated by ‘benchmark’ materials of similar chemistry or product application, or both. This approach has been valuable in providing an accurate assessment of the skin sensitization potential for a wide range of consumer products and pharmaceuticals, ranging from products with a very transient skin exposure (e.g. some paper products), to cosmetics, to products whose ingredients may be deposited on fabrics and thus result in chronic skin exposure. The risk assessment process described includes both guinea-pig (Buehler) and human skin sensitization test methodologies to evaluate inherent toxicity under relevant epicutaneous exposure conditions. Alternative guinea-pig test methods have been reported to be more sensitive than the Buehler method, particularly those employing intradermal injection of the test material in Freund's complete adjuvant (e.g. maximization test). However, by bypassing the skin barrier at induction, these methods can overstate the sensitization risk of epicutaneous exposure to weak sensitizers (Andersen and Hamann, 1983 and 1984; Matsushita et al., 1975a,b), and can understate the risk to very strong sensitizers possibly through tolerance induction (Buehler, 1985). In addition, materials are tested and classified at concentrations that may not be relevant to anticipated human exposure. The Buehler guinea-pig test data are important in assessing skin sensitization risk in the early phases of product development, where human exposure can be limited, controlled and monitored (e.g. manufacturing employees). The Buehler test can often define consumer skin sensitization risk; however, the ultimate consumer skin safety assessment should in general be developed through a series of controlled human tests; the human repeat insult patch test and, when necessary, the provocative or extended product use tests. Post-market monitoring of skin-related consumer comments is the final phase of the data gathering process. These results can be used to assess further each product and to provide valuable feedback to confirm the validity of the overall risk assessment process. Risk assessment for skin sensitization potential is seldom a simple process. Unexpected results, for example clinical patch test reactions that resemble allergic contact dermatitis, but are poorly reproducible, can lead to the expenditure of considerable effort. Fortunately, the various assessment tools, such as the provocative use test, can greatly aid in the resolution of such cases. Thus the knowledge that people reacting under exaggerated patch test exposure conditions (regardless of the nature of the reaction) can safely use the product, increases the assurance that consumers will suffer no adverse reactions from long-term product use. The risk assessment approach outlined is of value from two perspectives. First, it provides manufacturing and product development employees with safer working conditions, and it provides the consumer with safer products from a skin sensitization standpoint. Secondly, it provides an extensive database on skin sensitization potential from predictive animal testing, predictive human testing, clinical use testing and long-term worker and consumer exposure. It thus strengthens the confidence we have in extrapolating data obtained from each phase of skin sensitization testing for a new chemical or product in order to protect the well-being of the skin.