Identification of Contact Allergens by In Vitro Cell Culture-Based Methods
If an in vitro model is to replace an animal model, it should perform to at least the same degree of accuracy as current animal models. Most importantly it should correlate to the human experience.
Currently it is thought that no single assay will meet these requirements and that a battery of assays that mimic sensitization in vitro should be developed.
It is thought that such a battery of human cell-based assays will mimic the human situation more than animal cell-based assays.
Assays reflecting epidermal penetration and activation, dendritic cell maturation and migration, and T cell priming assays are being developed.
The irritant property of a sensitizer may be related to sensitizer potency and may enable sensitizer potency to be determined with the aid of an epidermal equivalent assay.
A proteomic approach to investigate the effect of chemical sensitizers on keratinocyte metabolism may identify novel biomarkers.
Genomic and proteomic studies are identifying dendritic cell signatures which identify sensitizers from non-sensitizers.
In vitro T cell priming assays can be used to distinguish sensitizers from non-sensitizers. The nature of these assays, however, makes it currently unlikely that they will be suitable for high-throughput screening.
Progress toward validation is slow but steadily moving forward. A number of assays are being identified which may be suitable for pre-validation studies and then validation studies.
KeywordsIn vitro skin sensitisation Epidermal equivalent (EE) potency assay Epidermal penetration Keratinocytes IL-18 biomarker assay Human T cell priming assay (hTCPA) Dendritic Cell-Based Assays DC maturation DC migration MUTZ-3 Proteomics approach Genomics approach GARD Nrf2-Keap1-Antioxidant Response Element (ARE) h-CLAT U-SENS AOP Cytokines Human monocytic leukaemia cell line THP1 Human histiocytic lymphoma cell line U937
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