Dang ZhiChao, van der Ven Leo T M, Kienhuis Anne S
National Institute for Public Health and the Environment (RIVM), A. van Leeuwenhoeklaan 9, Bilthoven, The Netherlands.
National Institute for Public Health and the Environment (RIVM), A. van Leeuwenhoeklaan 9, Bilthoven, The Netherlands.
Chemosphere. 2017 Nov;186:677-685. doi: 10.1016/j.chemosphere.2017.08.047. Epub 2017 Aug 11.
The acute fish toxicity test (AFT) is requested by EU legal frameworks for hazard classification and risk assessment. AFT is one of the few regulatory required tests using death as an endpoint. This paper reviews efforts made to reduce, refine and replace (3Rs) AFT. We make an inventory of information requirements for AFT, summarize studies on 3Rs of AFT and give recommendations. The fish embryo toxicity test (FET) is proposed as a replacement of AFT and analyses have focused on two aspects: assessing the capacity of FET in predicting AFT and defining the applicability domain of FET. Six comparison studies have consistently shown a strong correlation of FET and AFT. In contrast, the applicability domain of FET has not yet been fully defined. FET has not yet been accepted as a replacement of AFT by any EU legal frameworks to fulfill information requirements because FET is insensitive to some chemicals. It is recommended that the outlier chemicals that do not correlate between FET and AFT should be further investigated. When necessary, additional FET data should be generated. Another effort to reduce and refine AFT is incorporation of FET into the threshold approach. Furthermore, moribund as an endpoint of fish death has been introduced in revising AFT guideline to reduce the duration of suffering for refinement. This endpoint, however, needs further work on the link of moribund and death. Global regulatory acceptance of the moribund endpoint would be critical for this development.
欧盟法律框架要求进行急性鱼类毒性试验（AFT）以进行危害分类和风险评估。AFT是少数几个以死亡为终点的法规要求试验之一。本文回顾了为减少、优化和替代（3R）AFT所做的努力。我们列出了AFT的信息要求清单，总结了AFT的3R研究并给出了建议。鱼类胚胎毒性试验（FET）被提议作为AFT的替代方法，分析主要集中在两个方面：评估FET预测AFT的能力以及确定FET的适用范围。六项比较研究一致表明FET和AFT之间有很强的相关性。相比之下，FET的适用范围尚未完全确定。由于FET对某些化学物质不敏感，任何欧盟法律框架都尚未接受FET作为满足信息要求的AFT替代方法。建议对FET和AFT之间不相关的异常化学物质进行进一步研究。必要时，应生成额外的FET数据。减少和优化AFT的另一项努力是将FET纳入阈值方法。此外，在修订AFT指南时引入了濒死作为鱼类死亡的终点，以减少痛苦持续时间从而实现优化。然而，这个终点在濒死与死亡的联系方面还需要进一步研究。全球监管机构对濒死终点的认可对这一发展至关重要。
