Barton H A, Andersen M E
ICF Kaiser, Research Triangle Park, NC 27709, USA.
Crit Rev Toxicol. 1998 Jul;28(4):363-423. doi: 10.1080/10408449891344227.
Endocrine active compounds (EACs) alter signaling processes responsible for regulation and coordination of physiological functions during development and adulthood. The potential that adverse effects of these compounds have gone unrecognized has focused attention on their toxicology. The primary response to this concern has been development of additional hazard identification methods. This review discusses issues for dose response (DR) analyses for EACs, including definitions of adversity, implications of alternative modes of action, the roles homeostatic and developmental regulatory feedback processes play in creating DR behaviors, uses of in vitro data in DR analyses, and induction of effects by natural and synthetic compounds in the context of endogenous hormone background. Current risk assessment guidance applicable to endocrine-mediated effects provide limited default methods for evaluating DR behaviors and making interspecies comparisons. Improved DR methods for EACs will be achieved through the use of mode of action and dosimetry data to better characterize potential human risks.
内分泌活性化合物（EACs）会改变在发育和成年期负责生理功能调节与协调的信号传导过程。这些化合物的不良影响未被认识到的可能性已将人们的注意力集中在它们的毒理学上。针对这一担忧的主要应对措施是开发更多的危害识别方法。本综述讨论了EACs剂量反应（DR）分析的相关问题，包括逆境的定义、替代作用模式的影响、稳态和发育调节反馈过程在产生DR行为中所起的作用、DR分析中体外数据的使用，以及在内源激素背景下天然和合成化合物的效应诱导。当前适用于内分泌介导效应的风险评估指南提供的用于评估DR行为和进行种间比较的默认方法有限。通过使用作用模式和剂量学数据来更好地表征潜在的人类风险，将实现改进的EACs DR方法。
