Fisher Jane S
The School of Pharmacy, The University of London, 29-39 Brunswick Square, London, WC1N 1AX, UK.
Toxicology. 2004 Dec 1;205(1-2):33-41. doi: 10.1016/j.tox.2004.06.035.
Despite the surge of interest in the endocrine disruption field, there is still no globally accepted definition of the term. There is a great political will to test chemicals to determine whether they have endocrine disrupting potential. This is a huge task and the US Environmental Protection Agency has taken the lead by setting up an Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC), which with international co-operation, will ultimately deliver a validated testing strategy to detect endocrine disrupting chemicals (EDCs) in humans and wildlife. One of the major developments will be the use of high throughput pre-screening (HTPS) methods that will detect binding to steroid receptor hormones, although many other testing methods will be employed. This paper describes two mechanisms of EDC action that are not mediated via steroid receptors; firstly, the suppression of fetal testosterone synthesis in rodents by in utero exposure to phthalates; and secondly, the ability of several chemicals to interfere with steroid metabolism by inhibiting estrogen sulfotransferases. These examples will be discussed with reference to pertinent human disorders, which have been associated with exposure to EDCs. Issues and questions about how scientists and regulators can deal with these types of chemicals or potential mechanisms in a risk assessment paradigm are raised.
尽管内分泌干扰领域受到了极大关注,但该术语仍未得到全球公认的定义。人们有着强烈的政治意愿对化学物质进行测试,以确定它们是否具有内分泌干扰潜力。这是一项艰巨的任务,美国环境保护局已率先成立了内分泌干扰物筛选和测试咨询委员会(EDSTAC),该委员会将通过国际合作,最终提供一个经过验证的测试策略,以检测人类和野生动物体内的内分泌干扰化学物质(EDC)。其中一个主要进展将是使用高通量预筛选(HTPS)方法,该方法将检测与类固醇受体激素的结合,不过也会采用许多其他测试方法。本文描述了两种并非通过类固醇受体介导的EDC作用机制;其一,子宫内接触邻苯二甲酸盐会抑制啮齿动物胎儿睾酮的合成;其二,几种化学物质通过抑制雌激素磺基转移酶来干扰类固醇代谢的能力。将结合与接触EDC相关的人类相关疾病来讨论这些例子。还提出了关于科学家和监管机构如何在风险评估范式中处理这类化学物质或潜在机制的问题。