Kinetics and bioavailability of N-nitrosodiethanolamine after intravenous and cutaneous administration to rats

Male CD-COBS rats were given N-nitrosodiethanolamine (NDELA) by intravenous or cutaneous administration at a dose of 5 mg/kg. Blood and liver were analysed for NDELA at various times after administration. The excretion of unchanged NDELA and its acidic metabolite N-(2-hydroxyethyl)-N-carboxymethylnitrosamine (ECMN) was determined in urine for 24 hr after treatment. The semilogarithmic blood concentration-time plot after iv injection showed a triphasic profile indicating that a three-compartment model may adequately describe the kinetics of this compound. After cutaneous application NDELA was rapidly absorbed through the skin, and the absolute bioavailability was calculated to be 27% from blood data, and to be 32% (NDELA + ECMN) from urine data. Hepatic NDELA levels reflected blood levels after both treatments, indicating that this organ does not accumulate NDELA to a significant extent. Urinary excretion of unchanged NDELA after iv and cutaneous administration was 83 and 25% of the administered dose, respectively. ECMN excretion was 4.9 and 2.5% of the administered dose after iv and cutaneous administration, respectively.