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 test which made it possible to quickly and reliably differentiate between irritative and allergic skin 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 swelling after topical application of the test substance on three consecutive days. In contrast to the 'classic' skin sensitisation test in guinea-pigs the 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 underlying immunological mechanisms, but also considers the behaviour of immune competent cells following non-specific activation by irritants. In addition, the 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 systemic 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 examined each type of reaction in reference to one single standard; the next logical step was therefore a broad-based intra-laboratory validation. An important factor in the validation was the use of standards that had been thoroughly 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 show that the IMDS is a simple and reliable tool for obtaining fast and reproducible assessments of potential (photo)allergic and (photo)irritant skin reactions to substances.
Vohr
H W
HW
Institute of Toxicology, Bayer AG, 42096 Wuppertal, Germany.
Blümel
J
J
Blotz
A
A
Homey
B
B
Ahr
H J
HJ
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000485:Allergens / Q000633:toxicity; D000818:Animals; D002454:Cell Differentiation; D017453:Dermatitis, Irritant / Q000175:diagnosis* / Q000209:etiology; D017454:Dermatitis, Photoallergic / Q000175:diagnosis* / Q000209:etiology; D004195:Disease Models, Animal; D004431:Ear, External / Q000187:drug effects; D005260:Female; D007509:Irritants / Q000633:toxicity; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology*; D051379:Mice; D015203:Reproducibility of Results; D012867:Skin / Q000473:pathology; D012882:Skin Tests / Q000592:standards; D018675:Toxicity Tests / Q000592:standards; D014466:Ultraviolet Rays
D000485:Allergens; D007509:Irritants