Metabolism of Butoxyethanol in excised human skin in vitro

Abstract

Glycol ethers are widely used in industrial and household applications because their chemical and physical properties make them versatile solvents, miscible with both water and organic media. Due to the ease with which the glycol ethers are absorbed through the skin and the potential for development of adverse health effects it is important to understand the extent to which local metabolism can contribute to local and systemic toxicity. Sections of previously frozen, full thickness excised human skin samples were placed on transwell supports and placed with the underside of the skin in contact with receptor fluid. The skin surface was dosed with 115.2 mg of neat butoxyethanol and the absorption and metabolism of butoxyethanol to butoxyacetic acid monitored over time. In total 64.94 ± 0.04 mg of butoxyethanol or its metabolites were removed from the surface of the skin at 24 hours, representing the equivalent of 56% of the applied dose, the equivalent of 17.5% of the applied dose was recovered from the receiver fluid, 3% from within the skin and the remaining 23.5% of the dose was lost to the atmosphere through evaporation. After 24 hours a total of 31.5 μg of butoxyacetic acid had been produced representing approximately 0.03% of the applied dose. Therefore approximately 0.16% (31.5 μg as a percentage of the total amount of butoxyethanol reaching the receiver fluid (20.17 mg) of the absorbed butoxyethanol was metabolised to butoxyacetic acid during its passage through the skin. This suggested that, although enzyme activities capable of converting butoxyethanol to butoxyacetic acid are present in skin, metabolic conversion during percutaneous absorption was small and systemic exposure to the parent compound rather than the metabolite would occur following dermal exposure to butoxyethanol. This experiment demonstrates that it is possible to maintain metabolic activity in skin samples in an in vitro set up for short, but experimentally useful, period.