An in vivo but insensate model for the evaluation of antivenoms (ED50) using fertile hens' eggs

The preclinical evaluation of the efficacy of new antivenoms (ED50) in anim als is required by international regulatory authorities. In vitro testing a lone does not provide the end point of lethality of a living system which i s essential for an antivenom to prevent. Large numbers of mice are injected with venom/antivenom mixtures and the number of surviving mice is statisti cally analysed to give an ED50 value reflecting the efficacy of that antive nom. Our objective was to develop a humane alternative to the conventional rodent ED50 test using fertile hens' eggs. The egg test combines the advant ages of an in vivo system, which gives a clear end point fur haemorrhage an d 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 an d egg ED50 assays. A good correlation between the two tests was obtained (p < 0.01) suggesting that the egg ED50 method should be considered as an alt ernative to the rodent ED50 test for non-neurotoxic venoms. Use of the egg ED50 test would substantially reduce both the numbers of experimental anima ls required and also the considerable costs involved in delivering improved clinical treatment of snakebite. (C) 2000 Elsevier Science Ltd. All rights reserved.