Effects of experimental conditions on absorption of glycol ethers through human skin in vitro

Abstract

Objectives. To determine effects of experimental variables on the dermal absorption of 2-ethoxyethanol (EE), 2-butoxyethanol (BE) and 1-methoxy-2-propanol (M2P) through human skin in vitro.

Methods. Percutaneous absorption of EE, BE and M2P, in aqueous solution (3 mg ml^–1, 200 µl) or undiluted (10.5 µl), though full thickness or dermatomed human breast skin (0.64 cm² exposed area) was measured for 24 h using flow-through diffusion cells. Tissue culture medium was used as receptor fluid, with 2% (w/v) bovine serum albumin (BSA) or 2%–6% (w/v) polyethylene glycol 20 oleyl ether (PEG 20) added for some studies. Volatilised test compounds were trapped on charcoal filters placed above cells.

Results. In aqueous solution, steady-state flux of BE (544±64 nmol cm^–2 h^–1) exceeded that of EE (143±19 nmol cm^–2 h^–1) and M2P (48±6 nmol cm^–2 h^–1). Reducing the dose volume to 100 µl decreased the steady-state flux of BE by about 55%, though the flux of EE was approximately doubled. Doubling the dose concentration of EE increased the flux by about eight-fold. Using full thickness skin increased tau of both EE and BE and reduced the steady-state flux of BE. Absorption rates of undiluted solvents in finite doses exceeded those measured with aqueous solutions, though the apparent permeability coefficient was higher with aqueous doses. Addition of BSA or PEG 20 to receptor fluid markedly increased absorption in both aqueous and undiluted doses.

Conclusions. The dermal absorption potential of M2P from a liquid application was markedly lower than from EE or BE in all but infinite undiluted doses. The influence of receptor fluid on dermal absorption of glycol ethers could be relevant to prediction of absorption in vivo.