Percutaneous penetration and dermal metabolism of triclosan (2,4,4′-trichloro-2′-hydroxydiphenyl ether)
Percutaneous penetration and dermal metabolism of triclosan (2,4,4′-trichloro-2′-hydroxydiphenyl ether)
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DOI：
10.1016/s0278-6915(99)00164-7
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发表时间：
2000-04-01
影响因子：
4.3
通讯作者：
Williams, FM
中科院分区：
文献类型：
--
作者：
Moss, T;Howes, D;Williams, FM
三氯生广泛用于许多接触消费者皮肤的产品中。本研究比较了三氯生的体内和体外皮肤吸收，并确定了皮肤在三氯生进入血流之前代谢三氯生的潜力。将64.5 mM [H-3]三氯生酒精溶液体内局部应用于大鼠皮肤后，在应用后24小时，在粪便中回收了12%的放射性，在尸体中回收了8%，在尿液中回收了1%，在角质层中回收了30%，并且从皮肤表面冲洗了26%。在尿液和粪便中仅发现游离三氯生和三氯生的葡糖苷酸和硫酸盐结合物，三氯生在体外渗透大鼠皮肤比人皮肤更快和更广泛。到24小时时，23%的剂量已完全透过大鼠皮肤进入受体液体，而透过人皮肤的渗透率仅为6.3%。受体溶液的色谱分析表明，三氯生代谢为葡糖苷酸，在较小程度上代谢为硫酸盐，在通过皮肤的过程中，三氯生葡糖苷酸迅速出现在受体液体中，而三氯生硫酸盐保留在皮肤中，尽管代谢的主要部位是皮肤，但在体外和体内也证明了三氯生在皮肤中的结合，特别是更容易从皮肤上除去的葡糖苷酸缀合物。体外系统提供了大鼠经皮吸收的合理估计值（以rho计）。因此，通过对人体和大鼠皮肤的体外比较数据进行外推，可以合理推断，相同剂量下三氯生在人体中的皮肤吸收约为大鼠体内吸收的三分之一。(C)2000爱思唯尔科技有限公司版权所有。
triclosan is widely used in many products that contact the skin of consumers. This study compares in vivo and in vitro skin absorption of triclosan and determines the potential of skin to metobolize it prior to entering the blood stream. After in vivo topical application of a 64.5 mM alcoholic solution of [H-3]triclosan to rat skin, 12% radioactivity was recovered in the faeces, 8% in the carcass 1% in the urine, 30% in the stratum corneum and 26% was rinsed from the skin surface at 24 hours after application. Free triclosan and the glucuronide and sulfate conjugates of triclosan mere found in urine and faeces, triclosan penetrated rat skin more rapidly and extensively than human skin in vitro. 23% of the dose had penetrated completely through rat skin into the receptor fluid by 24 hours, whereas penetration through human skin tvas only 6.3% of the dose. Chromatographic analysis of the receptor solutions showed that triclosan was metabolized to the glucuronide, and to a lesser extent to the sulfate, during passage through the skin, triclosan glucuronide appeared rapidly in the receptor fluid whereas triclosan sulfate remained in the skin, Although the major site of metabolism was the li,er, conjugation of triclosan in skin was also demonstrated in vitro and in vivo, particularly to the glucuronide conjugate which was more readily removed from the skin. The in vitro system provides a reasonable estimate of dermal absorption in rho for the rat. Therefore by extrapolation of the comparative in vitro data for human and rat skin it is reasonable to deduct that dermal absorption in human of triclosan applied at the same dose is about one-third of that in the rat in vivo. (C) 2000 Elsevier Science Ltd. All rights reserved.