ASSURING SAFETY WITHOUT ANIMAL TESTING: DEVELOPMENT OF MECHANISTIC UNDERSTANDING OF DENDRITIC CELL ACTIVATION RESPONSE TO CHEMICAL SENSITISERS.

• TR Number: 675
• Keywords: Antigen presentation, Antigen processing, CCR2, CCR7, Chemokine receptors, Coagulation cascades, Complement cascade, Cytokine-cytokine receptor interactions, DC maturation, DC migration, Gene expression, MatTek DC-100 cells, Mechanistic understanding, Metacore analysis, Non sensitizers, NRF2 pathway, Principle component analysis (PCA), Sensitizers, Toll-like receptor signaling, Transcription factor network

Assuring consumer safety without the generation of new animal data is currently a considerable challenge but one that we believe is ultimately achievable. Skin allergy (sensitisation) is an important consumer safety endpoint for home and personal care products and an endpoint where animal data (e.g. mouse local lymph node assay data) are often needed to inform risk assessments. We are investigating a number of in vitro approaches to model key events in the biology of skin sensitisation including dendritic cell activation. In this study, transcriptomic analysis was used to examine the ability of a dendritic cell (DC) activation model using cultured DCs (Mattek DC-100), derived from CD34+ progenitor cells, to differentiate between sensitisers and non-sensitisers.