In vitro approaches to the identification and characterization of skin sensitizers.
Allergic contact dermatitis (ACD) is to a considerable extent a preventable disease. Limitation of ACD can be achieved by correct detection of skin sensitizers, characterization of potency, understanding of human skin exposure, and the application of adequate risk assessment and management strategies. A range of methods now exist that have been proven to be very accurate in terms of the predictive identification of chemicals that possess skin sensitizing properties. In addition, certain methods, notably the local lymph node assay (LLNA), also deliver valuable information of the relative potency of identified sensitizers. Great use can be made of this potency information in the application of quantitative risk assessments (although of course such assessments depend also on the availability of accurate data on human skin exposure). However, the challenge now to be faced is how to obtain the same quality of information on the potency of skin sensitizing chemicals using solely in vitro and in silico methods. With the forthcoming elimination of in vivo tests, the opportunities being exploited for in vitro test development focus on key elements of the sensitization process, such as peptide binding and dendritic cell activation. What has to then be addressed is how information from such in vitro assays is integrated, together with data on epidermal bioavailability, to deliver an assessment of the allergen potency.
St John's Institute of Dermatology, St Thomas' Hospital, London, UK. david.basketter@ukonline.co.uk
David
D
Basketter
Gavin
G
Maxwell
D000485:Allergens / Q000276:immunology* / Q000633:toxicity*; D017449:Dermatitis, Allergic Contact / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D012867:Skin / Q000187:drug effects* / Q000276:immunology; D018675:Toxicity Tests / Q000379:methods*
D000485:Allergens