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Relationship between permeation of ethanol and leaching of hemoglobin from capillary blood, as a possible index of skin irritancy, was examined in hairless rats. Ethanol solutions were applied in vivo on the abdominal skin for 5h and then content of Fe, instead of hemoglobin, in the application site was measured. Permeation of ethanol through the skin was examined in vitro in the corresponding condition. The index, i. e. Fe content in the skin, shows correlation with cumulative amount of ethanol permeated or maximum flux of ethanol through the skin, while that wasn't correlated with concentration and content of ethanol in the applied solution. Since a slow and continuous permeation of ethanol for 8h didn't damage the skin, the maximum flux is more important parameter for the effect of ethanol on the skin irritation than the cumulative amount of ethanol permeated. Relationship between permeation of ethanol and morphine hydrochloride (MPH) was also examined. The cumulative amount of MPH was correlated with the maximum flux of ethanol. A formulation containing ethanol should be designed carefully so as to attain effective skin permeation of drug while avoiding the occurrence of skin irritation

Relationship among permeation of ethanol, leaching of hemoglobin from capillary blood, and permeation of morphine hydrochloride in hairless rat skin.