Stewart Ian, McLeod Catherine
J AOAC Int. 2014 Mar-Apr;97(2):356-72. doi: 10.5740/jaoacint.sgestewart.
Mouse bioassays have been a mainstay for detecting harmful concentrations of marine algal toxins in shellfish for over 70 years. Routine monitoring involves intraperitoneal injection of shellfish extracts into mice; shellfish contaminated with algal toxins are thus identified by mortality in exposed mice. With the advent of alternative test methods to detect and quantify specific algal toxins has come increasing criticism of enduring use of mouse bioassays for shellfish safety testing. However, the complete replacement of shellfish safety mouse bioassays by chemical, antibody-based, and functional assays has been and will continue to be a gradual process for various reasons, including skills availability and instrument costs for chromatography-based toxin monitoring. Mouse bioassays for shellfish safety testing do not comply with modern standards for laboratory animal welfare, specifically the requirement in published official methods for death as a test outcome. Mouse bioassays for algal biotoxins in shellfish, as well as fundamental algal toxin research endeavors using in vivo models, are amenable to revision and refinement from a humane endpoints perspective. Regulated hypothermia may be a useful and easily acquired nonlethal toxicological endpoint; objective determination of neuromuscular blockade may allow algal neurotoxin testing and research to enter the domain of humane endpoints evaluation. Relinquishing reliance on subjective test endpoints, including death, will likely also deliver collateral improvements in assay variability and sensitivity.
70多年来,小鼠生物测定法一直是检测贝类中有害浓度海洋藻毒素的主要方法。常规监测包括将贝类提取物腹腔注射到小鼠体内;因此,通过暴露小鼠的死亡率来识别受藻毒素污染的贝类。随着检测和量化特定藻毒素的替代测试方法的出现,人们越来越批评长期使用小鼠生物测定法进行贝类安全性测试。然而,由于各种原因,包括基于色谱的毒素监测所需的技能和仪器成本,用化学、基于抗体和功能测定法完全取代贝类安全性小鼠生物测定法一直是且将继续是一个渐进的过程。用于贝类安全性测试的小鼠生物测定法不符合现代实验动物福利标准,特别是已公布的官方方法中以死亡作为测试结果的要求。用于检测贝类中藻生物毒素的小鼠生物测定法,以及使用体内模型的基础藻毒素研究工作,都适合从人道终点的角度进行修订和完善。调节体温过低可能是一个有用且易于实现的非致死性毒理学终点;对神经肌肉阻滞的客观测定可能使藻神经毒素测试和研究进入人道终点评估领域。放弃对包括死亡在内的主观测试终点的依赖,也可能会附带改善测定的变异性和灵敏度。