Wilkinson Simon C, Williams Faith M
Skin Toxicology Unit, Department of Environmental and Occupational Medicine, The Medical School, University of Newcastle, Newcastle upon Tyne, NE2 4HH, UK.
Int Arch Occup Environ Health. 2002 Oct;75(8):519-27. doi: 10.1007/s00420-002-0367-8. Epub 2002 Aug 27.
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.
Percutaneous absorption of EE, BE and M2P, in aqueous solution (3 mg ml(-1), 200 microl) or undiluted (10.5 microl), though full thickness or dermatomed human breast skin (0.64 cm(2) 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.
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 microl 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.
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.
确定实验变量对2 - 乙氧基乙醇（EE）、2 - 丁氧基乙醇（BE）和1 - 甲氧基 - 2 - 丙醇（M2P）经人体皮肤体外真皮吸收的影响。
使用流通扩散池，测量EE、BE和M2P在水溶液（3 mg/ml，200 μl）或未稀释状态（10.5 μl）下，通过全层或经皮削切的人乳房皮肤（暴露面积0.64 cm²）24小时的经皮吸收情况。组织培养基用作接收液，部分研究中添加了2%（w/v）牛血清白蛋白（BSA）或2% - 6%（w/v）聚乙二醇20油醚（PEG 20）。挥发的测试化合物被捕集在置于细胞上方的活性炭滤器上。
在水溶液中，BE的稳态通量（544±64 nmol/cm²·h⁻¹）超过EE（143±19 nmol/cm²·h⁻¹）和M2P（48±6 nmol/cm²·h⁻¹）。将剂量体积减少至100 μl使BE的稳态通量降低约55%，而EE的通量大约翻倍。EE的剂量浓度翻倍使通量增加约八倍。使用全层皮肤增加了EE和BE的滞留时间，并降低了BE的稳态通量。有限剂量的未稀释溶剂的吸收率超过水溶液测量值，不过水溶液剂量的表观渗透系数更高。向接收液中添加BSA或PEG 20显著增加了水溶液和未稀释剂量下的吸收。
除无限未稀释剂量外，液体涂抹时M2P的真皮吸收潜力明显低于EE或BE。接收液对二醇醚真皮吸收的影响可能与体内吸收预测相关。
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