Some alkyl hydroxy benzoate preservatives (parabens) are estrogenic
Some alkyl hydroxy benzoate preservatives (parabens) are estrogenic
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DOI：
10.1006/taap.1998.8544
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发表时间：
1998-11-01
影响因子：
3.8
通讯作者：
Sumpter, JP
中科院分区：
文献类型：
--
作者：
Routledge, EJ;Parker, J;Sumpter, JP
某些合成化学品无意中产生的雌激素性及其随后对人类和野生动物内分泌系统的影响令人关切。在本文中，我们报告的结果，在体外和体内（子宫）的研究证实，一系列的烷基羟基苯甲酸酯防腐剂（对羟基苯甲酸酯）是弱雌激素。在受体结合试验中，尼泊金丁酯能够与H-3-雌二醇竞争结合大鼠雌激素受体，其亲和力比己烯雌酚低约5个数量级，比壬基酚低1至2个数量级。在基于酵母的体外雌激素测定中，发现四种最广泛使用的对羟基苯甲酸酯（即对羟基苯甲酸甲酯、对羟基苯甲酸乙酯、对羟基苯甲酸丙酯和对羟基苯甲酸丁酯）均具有弱雌激素活性，其中最有效的对羟基苯甲酸丁酯的效力比17 β-雌二醇低10，000倍。对羟基苯甲酸酯的雌激素活性在体外被4-羟基他莫昔芬抑制，说明这些化学物质需要与雌激素受体相互作用以激活酵母。当口服给药于未成年大鼠时，对羟基苯甲酸酯无活性。然而，皮下注射尼泊金丁酯在体内产生了阳性子宫增重反应，尽管其效力比17 β-雌二醇低约100，000倍。鉴于这些化学品广泛用于市售局部制剂，建议重新评估这些化学品使用的安全性，特别注意估计人体接触这些化学品的实际全身接触水平。获得此类数据是得出对羟基苯甲酸酯可能的人体风险的可靠估计的先决条件。(C)北京：科学出版社.
The inadvertent estrogenicity of certain synthetic chemicals, and their subsequent effects on the endocrine system of humans and wildlife, is of concern. In this paper we report findings from in vitro and in vivo (uterotrophic) studies which confirm that a range of alkyl hydroxy benzoate preservatives (parabens) are weakly estrogenic. In a receptor-binding assay, butylparaben was able to compete with H-3-estradiol for binding to the rat estrogen receptor with an affinity approximately 5 orders of magnitude lower than that of diethylstilboestrol, and between 1 and 2 orders of magnitude less than nonylphenol. In an in vitro yeast-based estrogen assay, the four most widely used parabens (namely methyl-, ethyl-, propyl-, and butylparaben) were all found to be weakly estrogenic with the most potent (butylparaben) being 10,000-fold less potent than 17 beta-estradiol. The estrogenic activity of parabens was inhibited by 4-hydroxy tamoxifen in vitro, illustrating the requirement of these chemicals to interact with the estrogen receptor in order to activate the yeast, When administered orally to immature rats, the parabens were inactive. However, subcutaneous administration of butylparaben produced a positive uterotrophic response in viva, although it was approximately 100,000 times less potent than 17 beta-estradiol. Given their use in a wide range of commercially available topical preparations, it is suggested that the safety in use of these chemicals should be reassessed, with particular attention being paid to estimation of the actual levels of systemic exposure of humans exposed to these chemicals. The acquisition of such data is a prerequisite to the derivation of reliable estimates of the possible human risk of exposure to parabens. (C) 1998 Academic Press.