An intra-laboratory validation of the Integrated Model for the Differentiation of Skin Reactions (IMDS): discrimination between (photo)allergic and (photo)irritant skin reactions in mice

We recently presented a modified local lymph node rest which made it possib le to quickly and reliably differentiate between irritative and allergic sk in reactions with extremely simple parameters. The Integrated Model for the Differentiation of Skin Reactions (IMDS) test combines measurement of cell proliferation in draining lymph nodes with measurement of primary ear swel ling after topical application of the test substance on three consecutive d ays. In contrast to the 'classic' skill sensitisation test in guinea-pigs t he IMDS test is considerably faster and is based on objective measured data , not subjective skin evaluations. Like the Local Lymph Node Assay (LLNA), measurement of allergic potential in the IMDS test is based on the underlyi ng immunological mechanisms, but also considers the behaviour of immune com petent cells following non-specific activation by irritants. In addition, t he IMDS test can employ UV radiation after application of the substance and , therefore, make differentiation possible between different types of skin photoreaction (photoallergy and photoirritation) after both topical and sys temic administration. Attempts to achieve this kind of discrimination with the LLNA necessitate considerably greater expenditure, as proliferation in the draining lymph nodes can also be induced by moderate to extreme (photo) irritants. In a previous paper in which we presented the IMDS test, we exam ined each type of reaction in reference to one single standard; the next lo gical step was therefore a broad-based intra-laboratory validation. An impo rtant factor in the validation was the use of standards that had been thoro ughly examined in both guinea pig and mouse systems and were also relevant with regard to estimation of the risk for humans. The data presented here s how that the IMDS is a simple and reliable tool for obtaining fast and repr oducible assessments of potential (photo)allergic and (photo)irritant skin reactions to substances.