Greim Helmut A
Institute of Toxicology and Environmental Hygiene, Technical University of Munich, Munich, Germany.
Pediatrics. 2004 Apr;113(4 Suppl):1070-5.
Chemicals that have the intrinsic property to modulate or even disrupt the endocrine system are present in the human environment. Because it is the potency of such chemicals that determines the toxicologic relevance, assessment of the risk to human health must consider both the endocrine disrupting potential and the potency. Usually in vitro assays are applied to detect the potential of a hormone-like effect, and such data are considered useful to set priorities for additional testing and for mechanistic studies. However, such data allow only determination of relative potency of a chemical as compared with other xenobiotics, natural compounds, or endogenous hormones. Relevant information on the endocrine-disrupting potency can be taken only from in vivo assays, eg, the Hershberger (male reproductive organs) and uterotrophic (female reproductive organs) assays, the updated versions of the 28- and 90-day toxicity studies in rodents, and the 2-generation studies in rodents. With the use of this information and the concentration of these chemicals in humans, the potency of the effect as compared with endogenous hormone activity can be estimated. So far, the relative potencies of chemicals tested in in vitro systems as compared with estradiol are several orders of magnitude smaller, whereas potency of the phytoestrogen, eg, isoflavones such as genistein or daidzein, can even exceed that of estradiol, especially in infants who are fed soy-based formula as a sole source of nutrition. Although there are still open questions regarding in utero or early postnatal exposure, the low potencies and concentrations of manmade chemicals as compared with the endogenous hormones in humans make it unlikely that adverse effects occur at common exposure.
具有调节甚至破坏内分泌系统内在特性的化学物质存在于人类环境中。由于此类化学物质的效力决定了其毒理学相关性，因此对人类健康风险的评估必须同时考虑内分泌干扰潜力和效力。通常采用体外试验来检测激素样效应的潜力，此类数据被认为有助于确定进一步检测和进行机理研究的优先次序。然而，此类数据仅能确定一种化学物质与其他外源性物质、天然化合物或内源性激素相比的相对效力。关于内分泌干扰效力的相关信息只能从体内试验中获取，例如赫什伯格试验（雄性生殖器官）和子宫增重试验（雌性生殖器官）、啮齿动物28天和90天毒性研究的更新版本以及啮齿动物的两代研究。利用这些信息以及这些化学物质在人体内的浓度，可以估算出与内源性激素活性相比的效应效力。到目前为止，与雌二醇相比，在体外系统中测试的化学物质的相对效力要小几个数量级，而植物雌激素（如染料木黄酮或大豆苷元等异黄酮）的效力甚至可能超过雌二醇，尤其是对于以大豆配方奶粉作为唯一营养来源的婴儿。尽管关于子宫内或出生后早期暴露仍存在一些未解决的问题，但与人体内的内源性激素相比，人造化学物质的效力和浓度较低，因此在常见暴露情况下不太可能产生不良影响。
