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Clarification of early end-points for refinement of animal experiments, with specific reference to fish
Laboratory Animals ( IF 2.4 ) Pub Date : 2020-12-01 , DOI: 10.1177/0023677220971002
Tim Ellis 1 , Ioanna Katsiadaki 1
Affiliation  

Appropriate end-points are integral to the refinement of laboratory animal experiments. Our recent experience has highlighted that ambiguity around end-points is hampering their adoption in experiments that cause severe suffering to fish. In toxicology, the term endpoint (single word) refers to the response variable to the treatment that is measured and analysed. This differs to usage within laboratory animal experimentation, where end-point (hyphenated) refers to the time-point when exposure of the animal(s) to the treatment (and suffering) ends. Within laboratory animal experimentation, standardised terminology is needed for different types of early end-point which are based on the condition of the animal(s) or progress of the experiment. We propose that those involved in regulating and conducting animal experiments consider seven distinct types of early end-point (aim, technical error, biological error, mortality, moribundity, prognostic humane, non-prognostic humane) in addition to the planned experimental end-point (i.e. maximum duration). Moribundity (not morbidity) refers to an animal in a severely debilitated state close to death. Moribundity in fish is not yet defined, so we propose identification via a lack of response to external stimuli, loss of equilibrium (i.e. loss of righting reflex), and a slow opercular ventilation rate. As these clinical signs equate to those of deep/surgical anaesthesia, this moribundity end-point cannot be considered a humane end-point as the fish is likely to be unconscious and have passed the point of maximum suffering. We believe that identification of earlier humane end-points based on clinical signs and wider recognition of other types of early end-point can reduce suffering in experiments.



中文翻译:

澄清动物实验的早期终点,具体参考鱼类

适当的终点是实验室动物实验改进的组成部分。我们最近的经验表明,端点周围的模糊性阻碍了它们在对鱼类造成严重痛苦的实验中的采用。在毒理学中,术语终点(单个词)是指测量和分析的治疗反应变量。这与实验室动物实验中的用法不同,其中终点(连字符)是指动物暴露于治疗(和痛苦)结束的时间点。在实验室动物实验中,根据动物的状况或实验的进展,不同类型的早期终点需要标准化的术语。我们建议那些参与管理和进行动物实验的人除了计划的实验终点之外,还要考虑七种不同类型的早期终点(目标、技术错误、生物学错误、死亡率、垂死性、预后人道、非预后人道) (即最长持续时间)。濒死(不是病态)是指动物处于接近死亡的严重虚弱状态。鱼类的濒死状态尚未确定,因此我们建议通过对外部刺激缺乏反应、失去平衡(即失去翻正反射)和缓慢的鳃盖通气率来进行识别。由于这些临床症状等同于深度/手术麻醉的症状,因此该垂死终点不能被视为人道终点,因为鱼很可能失去知觉并已超过最大痛苦点。

更新日期:2020-12-02
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