Shen Ouxi, Du Guizhen, Sun Hong, Wu Wei, Jiang Yi, Song Ling, Wang Xinru
Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Hanzhong Road 140, Nanjing 210029, China.
Toxicol Lett. 2009 Dec 1;191(1):9-14. doi: 10.1016/j.toxlet.2009.07.019. Epub 2009 Jul 28.
Phthalates are widely used in the plastic industry and food packaging, imparting softness and flexibility to normally rigid plastic medical devices and children's toys. Even though phthalates display low general toxicity, there is increasing concern on the effects of endocrine system induced by some of phthalate compounds. The hormone activity of dibutyl phthalate (DBP), mono-n-butyl phthalate (MBP) and di-2-ethylhexyl phthalate (DEHP) were assessed using the luciferase reporter gene assays. The results showed that DBP, MBP and DEHP, not only exhibited potent antiandrogenic activity, with IC(50) value of 1.05x10(-6), 1.22x10(-7)M and exceeding 1x10(-4)M respectively, but also showed the androgenic activity with EC(50) value of 6.17x10(-6), 1.13x10(-5)M and exceeding 1x10(-4)M. We also found that all the three related chemicals possessed thyroid receptor (TR) antagonist activity with IC(50) of 1.31x10(-5), 2.77x10(-6)M and exceeding 1x10(-4)M respectively, and none showed TR agonist activity. These results indicate that TR might be the targets of industrial chemicals. In the ER mediate reporter gene assay, three chemicals showed no agonistic activity except for DBP, which appeared weakly estrogenic at the concentration of 1.0x10(-4)M. Together, the findings demonstrate that the three phthalates could simultaneously disrupt the function of two or more hormonal receptors. Therefore, these phthalates should be considered in risk assessments for human health.
邻苯二甲酸盐广泛应用于塑料工业和食品包装中，能使通常坚硬的塑料医疗设备和儿童玩具变得柔软且具有柔韧性。尽管邻苯二甲酸盐总体毒性较低，但人们对某些邻苯二甲酸酯化合物对内分泌系统的影响越来越关注。使用荧光素酶报告基因检测法评估了邻苯二甲酸二丁酯（DBP）、邻苯二甲酸单丁酯（MBP）和邻苯二甲酸二（2-乙基己基）酯（DEHP）的激素活性。结果表明，DBP、MBP和DEHP不仅表现出强大的抗雄激素活性，其半数抑制浓度（IC50）值分别为1.05×10⁻⁶、1.22×10⁻⁷M和超过1×10⁻⁴M，而且还表现出雄激素活性，其半数有效浓度（EC50）值分别为6.17×10⁻⁶、1.13×10⁻⁵M和超过1×10⁻⁴M。我们还发现，这三种相关化学物质均具有甲状腺受体（TR）拮抗活性，IC50分别为1.31×10⁻⁵、2.77×10⁻⁶M和超过1×10⁻⁴M，且均未表现出TR激动剂活性。这些结果表明TR可能是工业化学品的作用靶点。在内质网介导的报告基因检测中，除DBP在浓度为1.0×10⁻⁴M时表现出微弱的雌激素活性外，其他三种化学物质均未表现出激动活性。总之，研究结果表明这三种邻苯二甲酸盐可同时干扰两种或更多激素受体的功能。因此，在对人类健康进行风险评估时应考虑这些邻苯二甲酸盐。
