Useful method for evaluation of local irritation using auricular subcutis of rabbits

For the local irritation caused by Doxorubicin hydrochloride (DXR) which have leaked to the subcutis from the vein, the usefulness of the model using the auricular subcutis of rabbits was examined. DXR was administered to the subcutis in the ear auricle, abdominal region and dorsal region, and the local irritation reactions induced were evaluated according to the Draize criteria, by comparison of the damaged area and by the histopathological method. Macroscopic formations of erythema, edema and eschar were observed in the auricular subcutis, but there were no changes in the abdominal or dorsal subcutis. Histopathological examination showed changes such as edema, hemorrhage and necrosis at all administration sites and the changes were most severe in the auricular subcutis among the 3 regions. The reactions in the ear auricle observed were closest to the skin damage noted in humans by administration of DXR. In order to find out why the degree of local damage is different in these 3 regions, Evans blue was administered to these regions to compare its diffusibility in these regions. The diffusibility of Evans blue was lowest in the ear auricle. It is estimated that the difference in the local damage induced by DXR in these regions might be due to the difference in the retention time of DXR in the subcutis. Therefore, the evaluation for local irritation using the auricular subcutis model in rabbits is considered to be useful for estimation of skin damage caused by leakage of DXR to the subcutis.