Selection of chemicals for the development and evaluation of in vitro methods for skin sensitisation testing

There is a general, indeed pressing, need to develop, validate and bring into common use alternative methods to obviate the use of animals in toxicity testing. Specifically in the field of skin sensitisation, considerable investments are being made, at both the industry and university levels, in the development of alternative approaches to incorporate novel biomarkers or to enhance the functioning of existing models. In the development and/or optimisation phases of a method, the testing of reference chemicals with well characterised responses in predictive in vivo tests, would allow for an early appreciation of the utility of a method. More specifically, challenging a method with the same set of chemicals would facifitate the assessment of its possible contribution to an integrated testing approach. With such a small number of substances, the limited feasibility of fully representing the chemical and biological diversity of known chemical (skin) allergens is acknowledged. However, an attempt was made to cover, as much as possible, the range of known potencies for skin allergens, and to reflect the variety of physicochemical and reaction mechanisms involved in the sensitisation process. Furthermore, chemicals known to require biotransformation or other types of activation were included in the list, in order to evaluate the potential of the test system to detect them correctly. It is acknowledged that other chemical sets also might be appropriate for test development purposes. However, it was deemed important both to make public this recommendation and to encourage the use of a core set. It is therefore proposed that these selected substances are used as reference compounds for the primary development of new tests, or for the improvement of existing tests. In our view, a test that is able to correctly identify these chemicals should be considered very promising and worthy of further evaluation.