Metabolism and excretion of 2-ethoxyethanol in the adult male rat

The routes of 14C excretion following the administration of a single oral 230 mg/kg body weight dose of 2-ethoxyethanol [ethanol-1,2-14C] or 2-ethoxyethanol [ethoxy-1-14C] to male Sprague-Dawley rats were investigated. Elimination of the 14C by the urinary route accounted for 76 to 80% of the dose within 96 hr. The main pathway of biotransformation is oxidation to the corresponding acid, with some subsequent conjugation of the acid metabolite with glycine. The major metabolites, ethoxyacetic acid and N-ethoxy-acetyl glycine, representing 73 to 76% of the administered dose, were eliminated in the urine. The major difference in the metabolic profiles of the two radiochemicals was in the rate and amount of 14CO2 expired via the lung. Of the administered 14C, 11.7% of the ethoxy-labeled and 4.6% of the ethanol-labeled compounds were eliminated as CO2. The biological half-time was 9.9 +/- 1.5 hr for the ethoxy-labeled compound and 12.5 +/- 1.9 hr for the ethanol label. After administration of the ethanol-labeled compound, the only radiolabeled component found in the rat testes was identified as ethoxyacetic acid. Results of this study suggest that the reported testicular effects in the rat may be a result of tissue levels of ethoxyacetic acid.