Beekhuijzen Manon, Barentsen Helma, Marsden Edward, Zmarowski Amy, Aujoulat Michel, Picut Catherine, Sloter Eddie
a WIL Research Europe , Den Bosch , the Netherlands ;
b WIL Research Europe , Lyon , France ;
Crit Rev Toxicol. 2016;46(4):332-47. doi: 10.3109/10408444.2015.1137863. Epub 2016 Mar 3.
The hallmark of the extended one-generation reproductive toxicity study (EOGRTS) is that, based on certain criteria or triggers, selected offspring are assigned at weaning to different cohorts for further investigation of sexual maturation, reproductive organ integrity and function, neuropathological and behavioral endpoints, and/or immune function. The triggers allow for a more customizable design based directly on the data, while minimizing animal usage. Compared to the two-generation reproductive toxicity study, the EOGRTS design increases the number, extent, and duration of F1-offspring assessments resulting in more thorough and efficient utilization of the first generation while excluding the second generation of offspring unless triggered. Therefore, the EOGRTS has the potential to reduce the number of rats required by nearly 1200 animals per study. When performing the EOGRTS, the complexity of this study should not be underestimated and experienced flexible testing laboratories with sufficient resources and historical control data for all parameters are essential. The aim of this review is to discuss the important aspects of this challenging study design and to share our knowledge on the implementation of this study in our laboratories. In addition, we elaborate on the type of criteria for expansion of the study and logistical considerations. Altogether, this review can be used as guidance by other labs, study monitors, and registration officers.
扩展一代生殖毒性研究（EOGRTS）的标志是，根据某些标准或触发因素，在断奶时将选定的后代分配到不同的队列中，以进一步研究性成熟、生殖器官完整性和功能、神经病理学和行为终点以及/或免疫功能。这些触发因素允许直接基于数据进行更可定制的设计，同时最大限度地减少动物使用。与两代生殖毒性研究相比，EOGRTS设计增加了对F1代后代评估的数量、范围和持续时间，从而更彻底、高效地利用第一代，同时除非触发，否则排除第二代后代。因此，EOGRTS有可能将每项研究所需的大鼠数量减少近1200只。进行EOGRTS时，不应低估这项研究的复杂性，拥有足够资源和所有参数历史对照数据的经验丰富、灵活的测试实验室至关重要。本综述的目的是讨论这一具有挑战性的研究设计的重要方面，并分享我们在实验室中开展这项研究的知识。此外，我们详细阐述了研究扩展的标准类型和后勤考虑因素。总之，本综述可供其他实验室、研究监测人员和注册官员参考。
