P74 Categorisation of human sensitisation potency using local lymph node assay EC3 values

Abstract

Effective evaluation of skin sensitisation demands that potential contact allergens are identified and the risk of sensitisation amongst exposed populations assessed. Sensitisation hazard is not an all or nothing phenomenon; dose response relationships can be discerned and thresholds identified for induction and elicitation of contact allergy. These parameters, under the heading of potency, are vital for the risk assessment process. The murine local lymph node assay (LLNA) is an accepted method for the identification of sensitisation hazards (a sensitiser is a chemical that induces a stimulation index 3 or more times that of the concurrent vehicle control). The LLNA has also been used to determine the potency of sensitisers, by derivation of an EC3 value, the estimated concentration of chemical required to induce a stimulation index of 3. At present, various agencies, including in EU and OECD, together with industry bodies, are considering whether and how to adapt these data into regulations which would place sensitisers into one of several potency categories. It is our view, based on an evaluation of over 300 chemicals, that five categories: extreme, strong, moderate, weak and negative represent the optimal approach and is consistent with what is understood regarding the potency of these skin sensitisers in humans. To illustrate this approach, an example dataset of 100 selected organic chemicals is shown, where the accuracy of prediction of human potency is in the region of 90%. This categorisation has utility as a simple guide for risk management strategies as well as representing an important first step in risk assessment.