Effect of Dose on the Disposition of Methoxyethanol, Ethoxyethanol, and Butoxyethanol Administered Dermally to Male F344/N Rats

Abstract The glycol ethers methoxyethanol (ME), ethoxyethanol (EE), and butoxyethanol (BE) are widely used in industrial and house-hold products. Rodent studies indicate the ME and EE are potentially toxic compounds causing teratogenic, fetotoxic, hematotoxic, and testicular effects. Exposure of rodents to high concentrations of BE resulted in anemia due to hemolysis of blood cells, leukopenia, hemoglobinuria, and liver and kidney damage. The purpose of this study was to determine the uptake, metabolism, and excretion of dermally administered glycol ethers as a function of the externally applied dose. Three different amounts of the 14 C-labeled glycol ethers (450–4000 μmole/kg) were applied to same-sized areas on the clipped backs of F344 N rats, and nonoccluded percutaneous absorption was measured. The rates of excretion of the 14 C-labeled parent compound and metabolites by different routes were measured, as well as the amount of 14 C remaining in the carcass. Within the dose range studied, the absorption and metabolism of these three glycol ethers by F344 N rats was linearly related to the dermally applied dose. The absorption of all three glycol ethers was approximately 20–25%, regardless of the chain length of the alkyl group or the dose administered. The majority of the absorbed dose was excreted in the urine. Feces and exhaled CO 2 represented minor routes of excretion. The alkoxyacetic acid was a major metabolite for all three glycol ethers. The formation of small amounts of ethylene glycol indicated cleavage of the ether bond. Dermally administered glycol ethers were metabolized differently than glycol ethers administered in drinking water ( M. A. Medinsky, G. Singh, W. E. Bechtold, J. A. Bond, P. J. Sabourin, L. S. Birnbaum, and R. F. Henderson, 1990 , Toxicol. Appl. Pharmacol. 102, 443–455). In general, administration in drinking water enhanced the production of ethylene glycol and glycol ether-derived CO 2 .