Urinary excretion of phthalates and paraben after repeated whole-body topical application in humans
Urinary excretion of phthalates and paraben after repeated whole-body topical application in humans
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DOI：
10.1111/j.1365-2605.2007.00841.x
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发表时间：
2008-04-01
影响因子：
--
通讯作者：
Andersson, Anna-Maria
中科院分区：
文献类型：
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作者：
Janjua, Nadeem Rezaq;Frederiksen, Hanne;Andersson, Anna-Maria
邻苯二甲酸二乙酯 (DEP)、邻苯二甲酸二丁酯 (DBP) 和对羟基苯甲酸丁酯 (BP) 是用于个人护理产品（例如乳液和面霜）的人造化学品。在动物研究中，接触这些化学物质会导致各种不良的生殖结果。人类可以通过皮肤吸收接触到这些化学物质，但目前还没有关于皮肤应用后吸收、代谢和排泄的数据公布。本研究调查了局部应用后尿液中 BP 浓度以及 DEP 和 DBP 代谢物的浓度。在一项为期 2 周的单盲研究中，26 名健康白人男性受试者每日全身局部涂抹 2 mg/cm(2) 基础霜（对照周），然后每日涂抹含有 2%（w/w）DEP、DBP 和 BP 的霜（治疗周）。收集二十四小时的尿液样本。通过液相色谱-串联质谱 (LC-MS/MS) 分析尿总血压和非结合血压、邻苯二甲酸单乙酯 (MEP) 和邻苯二甲酸单丁酯 (MBP) 代谢物。所有 26 名受试者在局部应用后均表现出 MEP、MBP 和 BP 排泄增加。治疗周中尿液中排出的总 MEP、MBP 和 BP（平均值+/-SEM）分别为 41 +/- 1.9、11.8 +/- 0.6 和 2.6 +/- 0.1 mg/24 小时。平均分别有 5.79%、1.82% 和 0.32% 的 DEP、DBP 和 BP 可以在尿液中以 MEP、MBP 和 BP 的形式回收。施用后8-12小时尿液中化合物的浓度达到峰值。未结合的 MEP、MBP 和 BP 的分数分别为 78%、8.0% 和 2.1%。通过皮肤吸收 DEP、DBP 和 BP 可能会对健康产生不利影响。这三种化学物质以乳霜制剂的形式涂在皮肤上后，会被全身吸收、代谢并通过尿液排出。吸收的 DEP 多于 DBP，可能是因为 DEP 的吸收速率更快。
Diethyl phthalate (DEP), dibutyl phthalate (DBP) and butyl paraben (BP) are man-made chemicals used in personal care products, such as lotions and creams. Exposure to these chemicals causes a variety of adverse reproductive outcomes in animal studies. Humans can be exposed to these chemicals through dermal absorption, but there are no published data on absorption, metabolism, and excretion after dermal application. This study investigates urinary concentrations of BP and metabolites of DEP and DBP after topical application. In a 2-week single-blinded study, 26 healthy Caucasian male subjects were given a whole body topical application of basic cream 2 mg/cm(2) (control week) and then a cream containing 2% (w/w) of DEP, DBP and BP each (treatment week) daily. Twenty-four-hour urine samples were collected. Urinary total, and unconjugated BP, monoethyl phthalate (MEP) and monobutyl phthalate (MBP) metabolites were analysed by Liquid Chromatography-Tandem Mass Spectroscopy (LC-MS/MS). All 26 subjects showed increased excretion of MEP, MBP and BP following topical application. Total MEP, MBP and BP (mean +/- SEM) excreted in urine in the treatment week were, respectively, 41 +/- 1.9, 11.8 +/- 0.6 and 2.6 +/- 0.1 mg/24 h. On average 5.79, 1.82 and 0.32%, respectively, of the applied DEP, DBP and BP could be recovered in urine as MEP, MBP and BP. The concentration of the compounds peaked in urine 8-12 h after application. The fractions of unconjugated MEP, MBP, and BP were 78, 8.0 and 2.1%, respectively. Absorption of DEP, DBP and BP through skin could potentially contribute to adverse health effects. The three chemicals are systemically absorbed, metabolized and excreted in urine following application on the skin in a cream preparation. More DEP than DBP was absorbed, presumably because of a faster absorption rate for DEP.