Center of Environmental Food and Toxicological Technology (TecnATox), Departament d'Enginyeria Química, Universitat Rovira i Virgili, Tarragona, Catalonia, Spain.
Center of Environmental Food and Toxicological Technology (TecnATox), Departament d'Enginyeria Química, Universitat Rovira i Virgili, Tarragona, Catalonia, Spain.
Environ Int. 2017 Feb;99:1-14. doi: 10.1016/j.envint.2016.09.016. Epub 2016 Sep 30.
Endocrine disruptor compounds (EDCs) are environment chemicals that cause harmful effects through multiple mechanisms, interfering with hormone system resulting in alteration of homeostasis, reproduction and developmental effect. Many of these EDCs have concurrent exposure with crosstalk and common mechanisms which may lead to dynamic interactions. To carry out risk assessment of EDCs' mixture, it is important to know the detailed toxic pathway, crosstalk of receptor and other factors like critical window of exposure. In this review, we summarize the major mechanism of actions of EDCs with the different/same target organs interfering with the same/different class of hormone by altering their synthesis, metabolism, binding and cellular action. To show the impact of EDCs on life stage development, a case study on female fertility affecting germ cell is illustrated. Based on this summarized discussion, major groups of EDCs are classified based on their target organ, mode of action and potential risk. Finally, a conceptual model of pharmacodynamic interaction is proposed to integrate the crosstalk and common mechanisms that modulate estrogen into the predictive mixture dosimetry model with dynamic interaction of mixture. This review will provide new insight for EDCs' risk assessment and can be used to develop next generation PBPK/PD models for EDCs' mixture analysis.
内分泌干扰化合物（EDCs）是通过多种机制引起有害影响的环境化学物质，干扰激素系统，导致内稳态、生殖和发育效应的改变。这些 EDC 中有许多同时存在交叉作用和共同机制，可能导致动态相互作用。为了对 EDC 混合物进行风险评估，了解详细的毒性途径、受体的交叉作用以及暴露的关键窗口等其他因素非常重要。在这篇综述中，我们总结了 EDCs 的主要作用机制，这些机制通过改变激素的合成、代谢、结合和细胞作用，干扰不同/相同靶器官的同一/不同类别的激素。为了说明 EDC 对生命阶段发育的影响，我们以影响生殖细胞的女性生育力为例进行了说明。基于这一总结性讨论，根据其靶器官、作用方式和潜在风险对主要 EDC 进行了分类。最后，提出了一个药效动力学相互作用的概念模型，将调节雌激素的交叉作用和共同机制整合到具有混合物动态相互作用的预测混合物剂量学模型中。本综述将为 EDC 的风险评估提供新的见解，并可用于开发下一代用于 EDC 混合物分析的 PBPK/PD 模型。
