SENS-IT-IV - Novel testing strategies for in vitro assessment of allergens
Allergies to sensitising agents are steadily increasing. Risk assessment for potential skin- or lung-sensitisers, completely depends on animal testing. The overall objective of Sens-it-iv is to produce in vitro alternatives for these assays, and develop them upto the level of pre-validation. Besides reducing animal experimentation, an increase the accuracy of predicting sensitising potencies is expected. In vitro mechanisms, relevant for in vivo sensitisation, will be identified at the level of human lung or skin epithelial cells (EC), dendritic cells (DC) and T-cells.These efforts imply specific scientific (S) and technologic (T) objectives:a. Existing data on sensitising, irritating and toxic compounds are collected (S).b. In vivo changes induced by selected compounds in the specified cell types are described using functional genomics (S).c. Similarly, the impact of compounds on individual cells, and the interaction between these cells is assessed in vitro (S).d. The physico-chemical properties of chemicals responsible for metabolic activation and hapten-formation are determined (S).e. The data are collected in an Inductive Database allowing queries for data patterns and predictive models (T).f. Mechanisms specifically involved in skin and respiratory sensitisation are identified using bio-informatics (S).g. The information is used to adapt/improve existing techniques, and to develop organotypic models derived from human cells assays (T).h. A proof of principle is established on a set of selected skin and respiratory sensitisers, irritants and toxic compounds (T).Sens-it-iv is innovative primarily by the coordinated and extensive characterisation of the impact of compounds on cell-cell interactions for identification of the key mechanisms of sensitisation. Consistency with existing and ongoing projects, and optimal exploitation of these achievements is ensured by the involvement of ECVAM, COLIPA, ECOPA, IVTIP and OECD in various levels of the project.