Adverse outcome pathways (AOPs) define a series of sequential steps which describe the main biological processes involved in an adverse event. The AOP for skin sensitisation is well understood, and a panel of in vitro assays have been identified as being suitable surrogates for three of the Key Events in the AOP for skin sensitisation. These are described below:
Key Event 1: The Direct Peptide Reactivity Assay (DPRA) mimics the molecular initiating event where the test chemical reacts with the proteins in the skin.
Key Event 2: The ARE-Nrf2 Luciferase method (or KeratinoSens™ method) monitors the keratinocyte inflammatory response by assessing induction of expression of genes regulated by the antioxidant response element (ARE).
Key Event 3: The human Cell Line Activation Test (h-CLAT) quantifies changes in expression of cell surface markers associated with dendritic cell activation.
According to current OECD recommendations, a combination of these in vitro assays alongside in silico predictions of skin sensitisation can be used to discriminate between skin sensitisers and non-sensitisers within an IATA (integrated Approaches to Testing and Assessment). This non-animal approach for determining skin sensitisation risk is important in the cosmetic, personal care and chemical industries where animal studies are banned, or can only be used as a last resort.
Cyprotex is one of the few companies who can offer a package of all three in vitro assays for assessing the Key Events within the skin sensitisation AOP.