Vitosens™

Abstract

VITOSENS™ is an in vitro assay based on dendritic cell (DC) activation that is a key event in the adverse outcome pathway (AOP) on skin sensitization. Exposure induced expression changes of gene transcripts are quantified in DC derived from CD34+ progenitor cells in human cord blood. The assay was initially designed as a classifier and it is able to discriminate chemical skin sensitizers from non-sensitizers. By combining different VITOSENS™ variables in vitro potency values are modelled that closely fit in vivo-derived data, and this over the entire range from weak to extremely sensitizing chemicals. As such the assay can provide valuable information in the context of chemical risk assessment. Furthermore, the biomarkers in the assay display a concentration-dependent response relation that shifts when non-sensitizing compounds (e.g. irritants, endotoxin, anti-oxidants) are added to the chemical sensitizer. This indicates that our assay can be applied for mixture assessment and efficacy testing. Finally, a reliable test system should be based on key events of the in vivo disease process it is screening for. The functional relevance of the VITOSENS™ gene markers in the skin sensitization pathways are demonstrated. In a first step their differential protein expression was shown, and in a second phase changes in DC surface molecules were altered by counteracting the sensitizer-induced activity of VITOSENS™ markers. In conclusion, these results point to the feasibility of applying VITOSENS™ in an integrated approach for in vitro assessment of the sensitizing risk of chemical ingredients and mixtures. The assay represents the key event of DC maturation in the AOP of chemical-induced skin sensitization.