School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK.
School of Pharmacy, University of Wolverhampton, Wolverhampton, UK.
Altern Lab Anim. 2021 Jan-Mar;49(1-2):10-21. doi: 10.1177/0261192921994754. Epub 2021 Feb 24.
The prediction of human toxicities from animal toxicity tests is often poor, and is now discouraged and in some cases banned, especially those involving the LD test. However, there is a vast number of historical LD data in both public and in-house repositories that are being put to little use. This study examined the correlations between human lethality (doses and concentrations) of 36 MEIC chemicals and the median values of a large number of mouse and rat LD values obtained for four different routes of administration. The best correlations were found with mouse and rat intraperitoneal LD values (r = 0.838 and 0.810 for human lethal dose, and r = 0.753 and 0.785 for human lethal concentration). The results show that excellent prediction of human lethal dose and concentration can be made, for this series of chemicals at least, by using uncurated rodent LD values, thus offering some reparation for the millions of rodent lives sacrificed in LD testing.
从动物毒性试验预测人类毒性往往效果不佳,现在这种方法不仅不被鼓励,甚至在某些情况下被禁止,尤其是涉及 LD 测试的情况。然而,现在有大量的动物毒性试验 LD 数据,无论是公共的还是内部的,都没有得到充分利用。本研究考察了 36 种 MEIC 化学物质的人类致死剂量(剂量和浓度)与大量经不同给药途径获得的小鼠和大鼠 LD 值中位数之间的相关性。研究发现,与小鼠和大鼠腹腔内 LD 值相关性最好(人类致死剂量的 r 值分别为 0.838 和 0.810,人类致死浓度的 r 值分别为 0.753 和 0.785)。结果表明,至少对于这一系列化学物质,可以通过使用未经整理的啮齿动物 LD 值来进行人类致死剂量和浓度的准确预测,从而为在 LD 测试中牺牲的数百万只啮齿动物的生命提供一些补偿。