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全身局部应用邻苯二甲酸二乙酯、邻苯二甲酸二丁酯和对羟基苯甲酸丁酯后的全身吸收及人体生殖和甲状腺激素水平

Systemic uptake of diethyl phthalate, dibutyl phthalate, and butyl paraben following whole-body topical application and reproductive and thyroid hormone levels in humans.

作者信息

Janjua Nadeem Rezaq, Mortensen Gerda Krogh, Andersson Anna-Maria, Kongshoj Brian, Skakkebaek Niels E, Wulf Hans Christian

机构信息

Department of Dermatology, Bispebjerg Hospital, Denmark.

出版信息

Environ Sci Technol. 2007 Aug 1;41(15):5564-70. doi: 10.1021/es0628755.

Abstract

In vitro and animal studies have reported endocrine-disrupting activity of chemicals used commonly as additives in cosmetics and skin care products. We investigated whether diethyl phthalate (DEP), dibutyl phthalate (DBP), and butyl paraben (BP) were systemically absorbed and influenced endogenous reproductive and thyroid hormone levels in humans after topical application. In a two-week single-blinded study, 26 healthy young male volunteers were assigned to daily whole-body topical application of 2 mg/cm2 basic cream formulation each without (week one) and with (week two) the three 2% (w/w) compounds. The concentrations of BP and the main phthalate metabolites monoethyl (MEP) and monobutyl phthalate (MBP) were measured in serum together with the following reproductive hormones: follicle stimulating hormone (FSH), lutenising hormone (LH), testosterone, estradiol, and inhibin B and thyroid hormones (thyroid stimulating hormone (TSH), free thyroxine (FT4), total triiodothyroxine (T3), and total thyroxine (T4)). MEP, MBP, and BP peaked in serum a few hours after application, reaching mean +/- SEM levels of 1001 +/- 81 microg/L, 51 +/- 6 microg/ L, and 135 +/- 11 microg/L, respectively. Only MEP was detectable in serum before treatment. Minor differences in inhibin B, LH, estradiol, T4, FT4, and TSH were observed between the two weeks, but these were not related to exposure. We demonstrated for the first time that DEP, DBP, and BP could be systemically absorbed in man after topical application. The systemic absorption of these compounds did not seem to have any short-term influence on the levels of reproductive and thyroid hormones in the examined young men.

摘要

体外研究和动物研究报告称,常用于化妆品和护肤品中的添加剂具有内分泌干扰活性。我们调查了邻苯二甲酸二乙酯(DEP)、邻苯二甲酸二丁酯(DBP)和对羟基苯甲酸丁酯(BP)在局部应用后是否会被人体全身吸收并影响内源性生殖激素和甲状腺激素水平。在一项为期两周的单盲研究中,26名健康年轻男性志愿者被分配每天全身局部应用2mg/cm²的基础乳膏配方,第一周不添加三种2%(w/w)的化合物,第二周添加。同时测定血清中BP以及主要邻苯二甲酸酯代谢物单乙基邻苯二甲酸酯(MEP)和单丁基邻苯二甲酸酯(MBP)的浓度,以及以下生殖激素:促卵泡激素(FSH)、促黄体生成素(LH)、睾酮、雌二醇、抑制素B和甲状腺激素(促甲状腺激素(TSH)、游离甲状腺素(FT4)、总三碘甲状腺原氨酸(T3)和总甲状腺素(T4))。应用后数小时,MEP、MBP和BP在血清中达到峰值,平均±标准误水平分别为1001±81μg/L、51±6μg/L和135±11μg/L。治疗前血清中仅可检测到MEP。两周之间观察到抑制素B、LH、雌二醇、T4、FT4和TSH有微小差异,但这些差异与暴露无关。我们首次证明,DEP、DBP和BP在局部应用后可被人体全身吸收。这些化合物的全身吸收似乎对所检测的年轻男性的生殖激素和甲状腺激素水平没有任何短期影响。

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