Biochemical and morphological studies on the percutaneous uptake of [14C]ethylenediamine in the rat

Abstract

Male Wistar rats were exposed to aqueous [14C]ethylenediamine (EDA) solutions (10, 25, or 50%) percutaneously over a 7 x 7 cm area on the back with occlusion for 24 h. For each rat dosed, three types of studies were conducted: (1) plasma kinetics, (2) material balance, and (3) histological evaluation, including autoradiography of the skin sample from the dosing area. Adequate kinetic measurements were obtained only from animals treated with 25 and 50% EDA, but not from the 10% treatment group, due to analytical limitations. The uptake of [14C]EDA percutaneously by the rat was relatively slow in comparison with uptake following peroral or endotracheal administration. The absorption of EDA by the animals was estimated to be greater than 61, 55, and 12%, respectively, for the 50, 25, and 10% treatment groups. A large portion (11-32%) of the dose was left on/in the dosing area. Urinary excretion was the predominant route for the disposition of EDA. The recovery of the administered dose was low (70-83%), possibly due to volatilization of EDA from the skin during dosing and holding. Histologic examination of skin sections (dosing areas) revealed a normal, intact epidermis in rats dosed with 10% EDA, but full-thickness epidermal necrosis in rats dosed with 25% or 50% EDA solutions. The damage of the epidermis apparently enhanced the penetration of EDA. Autoradiographic preparations revealed a concentration of the [14C]EDA radiolabel over the keratin layer and hair shafts.