Theunissen P T, Beken S, Cappon G D, Chen C, Hoberman A M, van der Laan J W, Stewart J, Piersma A H
Reprod Toxicol. 2014 Aug;47:27-32. doi: 10.1016/j.reprotox.2014.04.004.
Based on a proposal made at the ICH Workshop in Tallinn, Estonia (2010), the value of the rabbit embryo-fetal development (EFD) versus the rodent EFD was examined by the HESI DART group. A cross-industry data survey provided anonymised EFD and toxicokinetic data from EFD studies on over 400 marketed and unmarketed drugs (over 800 studies) that were entered by experts at RIVM into US EPA’s ToxRefDB style database. The nature and severity of findings at the lowest observed adverse effect level (LOAEL) are being reviewed to quantitate the frequency with which lesser signs of embryo-fetal effects (e.g., delays in ossification, minor changes in frequency of variants) are driving the LOAELs. Interpretation was based on exposure rather than administered dose. This paper provides an update of this ongoing project as discussed during a workshop of the European Teratology Society in Ispra, Italy (2013). This was the first presentation of the initial data set, allowing debate on future directions, to provide a better understanding of the implications of either delaying a rabbit EFD or waiving the need in particular circumstances.
根据在爱沙尼亚塔林举行的人用药品注册技术国际协调会研讨会（2010年）上提出的一项提议，HESI DART小组对兔胚胎-胎儿发育（EFD）相对于啮齿动物EFD的价值进行了研究。一项跨行业数据调查提供了来自400多种已上市和未上市药物的EFD研究的匿名EFD和毒代动力学数据（超过800项研究），荷兰国家公共卫生与环境研究所的专家将这些数据录入了美国环境保护局的ToxRefDB样式数据库。正在对最低观察到有害作用水平（LOAEL）下的发现的性质和严重程度进行审查，以量化胚胎-胎儿效应的较轻迹象（例如骨化延迟、变异频率的微小变化）导致LOAEL的频率。解释基于暴露而非给药剂量。本文提供了该正在进行项目的最新情况，该情况在意大利伊斯普拉举行的欧洲致畸学学会研讨会（2013年）上进行了讨论。这是初始数据集的首次展示，允许就未来方向展开辩论，以便更好地理解推迟兔EFD或在特定情况下放弃该需求的影响。
