Sells P G, Laing G D, Theakston R D
Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Pembroke Place, L3 5QA, Liverpool, UK.
Toxicon. 2001 May;39(5):665-8. doi: 10.1016/s0041-0101(00)00191-4.
The preclinical evaluation of the efficacy of new antivenoms (ED(50)) in animals is required by international regulatory authorities. In vitro testing alone does not provide the end point of lethality of a living system which is essential for an antivenom to prevent. Large numbers of mice are injected with venom/antivenom mixtures and the number of surviving mice is statistically analysed to give an ED(50) value reflecting the efficacy of that antivenom. Our objective was to develop a humane alternative to the conventional rodent ED(50) test using fertile hens' eggs. The egg test combines the advantages of an in vivo system, which gives a clear end point for haemorrhage and lethality, with the certain knowledge that no distress can be experienced by the embryo which is insensate at day 6 of development. Nine different, medically-important venoms and antivenoms were tested by both the rodent and egg ED(50) assays. A good correlation between the two tests was obtained (p<0.01) suggesting that the egg ED(50) method should be considered as an alternative to the rodent ED(50) test for non-neurotoxic venoms. Use of the egg ED(50) test would substantially reduce both the numbers of experimental animals required and also the considerable costs involved in delivering improved clinical treatment of snakebite.
国际监管机构要求对新型抗蛇毒血清在动物体内的疗效进行临床前评估（半数有效剂量[ED(50)]）。仅体外试验无法提供抗蛇毒血清所必需预防的活体系统致死终点。给大量小鼠注射毒液/抗蛇毒血清混合物，并对存活小鼠数量进行统计分析，以得出反映该抗蛇毒血清疗效的ED(50)值。我们的目标是开发一种人道的替代方法，以取代使用可育鸡蛋的传统啮齿动物ED(50)试验。鸡蛋试验结合了体内系统的优点，该系统能给出出血和致死的明确终点，同时明确知道发育到第6天的胚胎没有感觉，不会遭受痛苦。通过啮齿动物和鸡蛋ED(50)试验对9种不同的、具有医学重要性的毒液和抗蛇毒血清进行了测试。两种试验之间获得了良好的相关性（p<0.01），这表明对于非神经毒性毒液，鸡蛋ED(50)方法应被视为啮齿动物ED(50)试验的替代方法。使用鸡蛋ED(50)试验将大幅减少所需实验动物的数量，以及在提供改进的蛇咬伤临床治疗方面所涉及的可观成本。
