Rowan A
Acta Pharmacol Toxicol (Copenh). 1983;52 Suppl 2:52-64. doi: 10.1111/j.1600-0773.1983.tb02683.x.
The author argues that the standard practice of determining an LD50 with 95% confidence limits is a waste of animals since the extra statistical precision is undermined by numerous other factors. For example, the LD50 of a given chemical often varies by at least 10-fold between different animal species and strains. Also, environmental factors can result in substantial differences in the LD50 of a given chemical in a given animal strain. Therefore, the use of this measure as a general index of toxicity, as a guide to further pharmacological or toxicological studies, or as a guide to human toxicity involves unnecessary and needless taking of animal life. These points will be amplified and substantiated by actual examples. Finally, the author will make some suggestions as to what could constitute a satisfactory acute animal test given current scientific and regulatory needs.
作者认为,采用95%置信区间来确定半数致死剂量(LD50)的标准做法是对动物的浪费,因为额外的统计精度会受到许多其他因素的影响。例如,给定化学物质的LD50在不同动物物种和品系之间通常至少相差10倍。此外,环境因素会导致给定化学物质在给定动物品系中的LD50存在显著差异。因此,将该指标用作毒性的通用指标、进一步药理或毒理学研究的指南或人类毒性的指南,涉及不必要且毫无必要地夺取动物生命。这些观点将通过实际例子加以详述和证实。最后,作者将根据当前的科学和监管需求,就什么可以构成令人满意的急性动物试验提出一些建议。