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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.

As part of a 2-year chronic toxicity study, the pharmacokinetics of ethylenediamine (EDA) was studied in Fischer 344 rats of both sexes at day zero (naive animals), 6 months (controls and high level animals), and 18 months (controls and high level animals). The rats, which were randomized along with the rest of the animals on the toxicity study, were taken for pharmacokinetic experiments at the specified time. A single per os (po) dose of 50 mg [14C]EDA X 2HCl/kg was given to each rat and the plasma kinetics was followed for a 24-hr period. Five pharmacokinetic parameters (absorption rate constant, terminal half-life, area under the curve, volume of distribution, and 14CO2 production rate constant) were compared with respect to age, sex, and chronic dosing. There were no apparent age-, sex-, and/or chronic dosing-related differences in absorption rate constant and terminal half-life. However, age-related changes in area under the curve (AUC) were evident. The older rats had higher values (generally two- to threefold) for AUC than the younger rats. This age-related difference in AUC is closely associated with the volumes of distribution (Vd) of the animals of varying ages. On the basis of liters per kilogram, the Vd's of the older rats are approximately one-fourth to one-half of those for the younger (zero day) rats. The 14CO2 production rate constant was derived from the rate of formation of 14CO2 as a result of [14C]EDA X 2HCl dosing. The comparison of this constant under the various experimental conditions suggests sex-related differences.(ABSTRACT TRUNCATED AT 250 WORDS)