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

The glycol ethers methoxyethanol (ME), ethoxyethanol (EE), andbutoxyethanol (BE) are widely used in industrial and householdproducts. Rodent studies indicate the ME and EE are potentiallytoxic compounds causing teratogenic, fetotoxic, hematotoxic,and testicular effects. Exposure of rodents to high concentrationsof BE resulted in anemia due to hemolysis of blood cells, leukopenia,hemoglobinuria, and liver and kidney damage. The purpose ofthis study was to determine the uptake, metabolism, and excretionof dermally administered glycol ethers as a function of theexternally applied dose. Three different amounts of the ¹⁴C-labeledglycol ethers (450-4000 µmole/kg) were applied to same-sizedareas on the clipped backs of F344/ N rats, and nonoccludedpercutaneous absorption was measured. The rates of excretionof the ^l4C-labeled parent compound and metabolites by differentroutes were measured, as well as the amount of ¹⁴C remainingin the carcass. Within the dose range studied, the absorptionand metabolism of these three glycol ethers by F344/N rats waslinearly related to the dermally applied dose. The absorptionof all three glycol ethers was approximately 20–25%, regardlessof 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 CO₂ represented minor routes of excretion.The alkoxyacetic acid was a major metabolite for all three glycolethers. The formation of small amounts of ethylene glycol indicatedcleavage of the ether bond. Dermally administered glycol etherswere metabolized differently than glycol ethers administeredin 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, administrationin drinking water enhanced the production of ethylene glycoland glycol ether-derived CO₂.