Approaches for the development of cell-based in vitro methods for contact sensitization

Allergic contact dermatitis (ACD) is a cell-mediated immune response to sma ll molecular weight chemicals that contact and penetrate the skin. There ar e a variety of characteristics that determine whether a chemical can functi on as a contact sensitizer (or allergen) including the ability to penetrate into the skin, react with protein and be recognized as antigenic by immune cells. The ultimate challenge for developing non-animal test methods for s kin sensitization testing will be applying our mechanistic understanding of ACD to the design of predictive in vitro alternative test methods. Specifi cally, the in vitro approach should be designed so that a chemical's potent ial to penetrate the skin, react with protein/peptide (biotransformation ma y be required) and initiate an antigen-specific immune response is incorpor ated in the test methods developed. In this review, we have focused on cell ular-based assays that have been developed or proposed far assessing a chem ical's skin sensitization potential in vitro. All of the promising leads to date are based on observations made from in vivo studies conducted in anim als and humans, and therefore have a strong mechanistic foundation. However , it remains to be demonstrated whether a single in vitro test, or several in vitro tests in combination, which model the critical steps in sensitizat ion, can replace animal experiments for predicting contact allergic reactio ns in humans. Regardless, the future looks promising with continued develop ment of our understanding of the chemical and biological aspects of allergi c contact dermatitis, and most importantly, with the application of genomic s/proteomics to this field on the immediate horizon. (C) 2001 Elsevier Scie nce Ltd. All rights reserved.