ABSTRACT

Theoretically, both synthetic endocrine-disrupting chemicals (S-EDCs) and natural (exogenous and endogenous) endocrine-disrupting chemicals (N-EDCs) can interact with endocrine receptors and disturb hormonal balance. However, compared to endogenous hormones, S-EDCs are only weak partial agonists with receptor affinities several orders of magnitude lower than S-EDCs. Thus, to elicit observable effects, S-EDCs require considerably higher concentrations to attain sufficient receptor occupancy or to displace natural hormones and other endogenous ligands.

Significant exposures to exogenous N-EDCs may result from ingestion of foods such as soy-based diets, green tea, and sweet mustard. While their potencies are lower as compared to natural endogenous hormones, they usually are considerably more potent than S-EDCs.

Effects of exogenous N-EDCs on the endocrine system were observed at high dietary intakes. A causal relation between their mechanism of action and these effects is established and biologically plausible. In contrast, the assumption that the much lower human exposures to S-EDCs may induce observable endocrine effects is not plausible. Hence, it is not surprising that epidemiological studies searching for an association between S-EDC exposure and health effects have failed.

Regarding testing for potential endocrine effects, a scientifically justified screen should use in vitro tests to compare potencies of S-EDCs with those of reference N-EDCs. When the potency of the S-EDC is similar or smaller than that of the N-EDC, further testing in laboratory animals and regulatory consequences are not warranted.

摘要

从理论上讲，破坏合成内分泌的化学药品（S-EDC）和天然（外源和内源）破坏内分泌的化学药品（N-EDC）都可以与内分泌受体相互作用，破坏荷尔蒙平衡。但是，与内源激素相比，S-EDCs只是弱的部分激动剂，其受体亲和力比S-EDCs低几个数量级。因此，为了引起可观察到的效果，S-EDC需要相当高的浓度才能获得足够的受体占有率或取代天然激素和其他内源性配体。

摄入诸如大豆饮食，绿茶和甜芥末等食物可能会导致大量暴露于外源N-EDC。尽管它们的功效比天然内源激素低，但它们通常比S-EDC更有效。

在高饮食摄入下，观察到外源性N-EDC对内分泌系统的影响。它们的作用机理与这些作用之间存在因果关系，并且在生物学上是合理的。相比之下，假设人类的S-EDC暴露量低得多可能会引起可观察到的内分泌作用，这一假设是不合理的。因此，在流行病学研究中寻找S-EDC暴露与健康影响之间的联系并不令人感到意外。

关于潜在内分泌作用的测试，科学合理的筛查应使用体外测试，以比较S-EDC与参考N-EDC的效能。如果S-EDC的效力与N-EDC相似或比N-EDC的效力小，则不保证对实验动物进行进一步测试和监管后果。