Dendritic cells as a tool for the predictive identification of skin sensitisation hazard - The report and recommendations of ECVAM workshop 51.
Casati-S; Aeby-P; Basketter-DA; Cavani-A; Gennari-A; Gerberick-GF; Griem-P; Hartung-T; Kimber-I; Lepoittevin-JP; Meade-BJ; Pallardy-M; Rougier-N; Rousset-F; Rubinstenn-G; Sallusto-F; Verheyen-GR; Zuang-V
Altern Lab Anim 2005 Feb; 33(1):47-62
Skin sensitisation resulting in allergic contact dermatitis is an important health issue. Many hundreds of chemicals are known to have the potential to cause skin sensitisation (albeit with widely varying potencies), and there is a need to understand the likely risks to human health. The first step in a risk assessment process requires the accurate identification of hazard. Currently, the identification of skin sensitising chemicals is most commonly achieved by using animal test methods. Included among these are guinea-pig tests, such as the occluded patch test of Buehler (1) and the guinea-pig maximisation test (GPMT; 2), and the mouse local lymph node assay (LLNA; 3). However, there is growing interest in exploring whether it might be possible to design and develop new approaches that would permit an assessment of skin sensitising activity without the need for experimental animals. To this end, attention has focused on a variety of strategies that comprise both the investigation of novel in vitro experimental systems, and the possible application of structure-activity relationships and computer based prediction methods (4-7). Among the approaches that have attracted most interest are those that make use of cultured dendritic cells (DCs) and dedicated antigen processing and presenting cells (7). The objectives of this workshop were to review the current status of, and future opportunities for, the use of cultured DCs as a basis for the development of alternative approaches to the identification of skin sensitisation hazard. In addition, several specific issues were addressed by the workshop participants, including: the most appropriate DCs for use in in vitro skin sensitisation testing; the readouts that may be available for evaluating the interaction of chemicals with DCs; and how putative in vitro test methods based on measurement of DC responses might best be integrated into a tiered testing strategy. The progress made during the workshop is summarised here, and deliberations about opportunities for in vitro test methods are preceded by a brief consideration of the basic mechanisms of skin sensitisation and of the roles played by DCs.
Contact-dermatitis; Contact-allergies; Allergic-dermatitis; Allergens; Allergic-reactions; Allergies; Skin-diseases; Skin-tests; Skin-exposure
Casati S, Commiss European Communities, Joint Res Ctr, JRC Inst Hlth & Consumer Protect, ECVAM,Inst Hlth & Consumer Protect, I-21020 Ispra, VA, Italy
Disease and Injury: Allergic and Irritant Dermatitis
Alternatives to Laboratory Animals