EURL ECVAM Recommendation on the human Cell Line Activation Test (h-CLAT) for skin sensitisation testing

Identification of the skin sensitisation hazard of chemicals has traditionally relied on the use of animals. Progress in the development of alternative methods has been prompted by the increasing knowledge of the key biological mechanisms underlying this human health effect, as summarised in the OECD report on: "The Adverse Outcome Pathway (AOP) for Skin Sensitisation Initiated by Covalent Binding to Proteins". Within this AOP the activation of dendritic cells (DC), typically assessed by expression of cell surface markers, chemokines and cytokines, is considered to be a key event. Therefore, test methods able to provide information on the ability of a chemical to up-regulate markers of DC activation may contribute to skin sensitisation hazard assessment. The human Cell Line Activation Test (h-CLAT) measures the upregulation of the CD86 and CD54 markers of DC activation in THP-1 cells, a human monocytic leukemia cell line. The test method has undergone a validation study addressing the test method's transferability and withinand between-laboratory reproducibility. Following independent peer-review by the EURL ECVAM's Scientific Advisory Committee (ESAC) and having considered input from regulators, stakeholders, international partners and the general public, EURL ECVAM concluded that the h-CLAT test method should prove valuable within Integrated Approaches to Testing and Assessment (IATA) for hazard assessment. The h-CLAT may also be able to contribute to the assessment of sensitising potency, however it is recognised that further efforts are required to explore how h-CLAT data may contribute to potency assessment.