Environmental Toxicology and Pharmacology ( IF 4.2 ) Pub Date : 2020-04-29 , DOI: 10.1016/j.etap.2020.103396 Herman Autrup 1 , Frank A Barile 2 , Sir Colin Berry 3 , Bas J Blaauboer 4 , Alan Boobis 5 , Herrmann Bolt 6 , Christopher J Borgert 7 , Wolfgang Dekant 8 , Daniel Dietrich 9 , Jose L Domingo 10 , Gio Batta Gori 11 , Helmut Greim 1 , Jan Hengstler 6 , Sam Kacew 12 , Hans Marquardt 13 , Olavi Pelkonen 14 , Kai Savolainen 15 , Pat Heslop-Harrison 16 , Nico P Vermeulen 17
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. 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.
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.
中文翻译:
与具有更高或相当内分泌活性的天然化合物相比,人类对合成内分泌干扰化学物质(S-EDC)的暴露通常可以忽略不计。如何评估S-EDC的风险?
从理论上讲,合成内分泌干扰化学物质(S-EDC)和天然(外源和内源)内分泌干扰化学物质(N-EDC)都可以与内分泌受体相互作用并扰乱激素平衡。但是,与内源激素相比,S-EDCs只是弱的部分激动剂,其受体亲和力要低几个数量级。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,假设人类对S-EDCs的暴露量低得多可能会引起可观察到的内分泌作用,这是不合理的。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惊讶。
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。当S-EDC的效价与N-EDC的效价相近或小于N-EDC的效价时,不保证在实验动物中进行进一步的测试和监管后果。