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对羟基苯甲酸酯类:近期内分泌毒性、吸收、酯酶及人体暴露研究综述以及潜在人体健康风险探讨

Paraben esters: review of recent studies of endocrine toxicity, absorption, esterase and human exposure, and discussion of potential human health risks.

作者信息

Darbre Philippa D, Harvey Philip W

机构信息

School of Biological Sciences, The University of Reading, Reading RG6 6AJ, UK.

出版信息

J Appl Toxicol. 2008 Jul;28(5):561-78. doi: 10.1002/jat.1358.

Abstract

This toxicology update reviews research over the past four years since publication in 2004 of the first measurement of intact esters of p-hydroxybenzoic acid (parabens) in human breast cancer tissues, and the suggestion that their presence in the human body might originate from topical application of bodycare cosmetics. The presence of intact paraben esters in human body tissues has now been confirmed by independent measurements in human urine, and the ability of parabens to penetrate human skin intact without breakdown by esterases and to be absorbed systemically has been demonstrated through studies not only in vitro but also in vivo using healthy human subjects. Using a wide variety of assay systems in vitro and in vivo, the oestrogen agonist properties of parabens together with their common metabolite (p-hydroxybenzoic acid) have been extensively documented, and, in addition, the parabens have now also been shown to possess androgen antagonist activity, to act as inhibitors of sulfotransferase enzymes and to possess genotoxic activity. With the continued use of parabens in the majority of bodycare cosmetics, there is a need to carry out detailed evaluation of the potential for parabens, together with other oestrogenic and genotoxic co-formulants of bodycare cosmetics, to increase female breast cancer incidence, to interfere with male reproductive functions and to influence development of malignant melanoma which has also recently been shown to be influenced by oestrogenic stimulation.

摘要

本毒理学综述回顾了自2004年首次测量人乳腺癌组织中对羟基苯甲酸(对羟基苯甲酸酯)完整酯类以来过去四年的研究,以及关于它们在人体中的存在可能源于身体护理化妆品局部应用的观点。人体组织中完整对羟基苯甲酸酯的存在现已通过对人尿液的独立测量得到证实,并且不仅通过体外研究,还通过使用健康人体受试者的体内研究,证明了对羟基苯甲酸酯能够完整穿透人体皮肤而不被酯酶分解并被全身吸收。使用多种体外和体内检测系统,对羟基苯甲酸酯及其常见代谢物(对羟基苯甲酸)的雌激素激动剂特性已得到广泛记录,此外,对羟基苯甲酸酯现在还被证明具有雄激素拮抗活性,可作为磺基转移酶的抑制剂,并具有遗传毒性活性。鉴于大多数身体护理化妆品中仍持续使用对羟基苯甲酸酯,有必要详细评估对羟基苯甲酸酯以及身体护理化妆品的其他雌激素和遗传毒性共配方成分增加女性乳腺癌发病率、干扰男性生殖功能以及影响恶性黑色素瘤发展的可能性,最近研究表明恶性黑色素瘤也受雌激素刺激影响。

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