Nordmann H
Arch Toxicol Suppl. 1985;8:435-41. doi: 10.1007/978-3-642-69928-3_99.
Acute toxicity testing in-vivo seeks a new approach minimising the number of animals used and increasing the number of quantitative and qualitative observations. The measurement of grip strength of mice (forelimbs), a classical tool for the evaluation of muscular force and the emitted heat measurement, as a tool for evaluation of basic metabolism, have been used. The aim of acute toxicity was, up to now, to determine LD50 level or eventually a minimal lethal dose. These non-invasive tests give an idea of general health condition and allow the determination of the minimal toxic dose while in the search for the minimal lethal dose. A computer-assisted grip strength test and an infrared thermometry test have been developed and calibrated with Na+ pentobarbital, theophylline and diazepam given once orally or intraperitoneally to 10 male NMRI (MAI) mice/dose. The tests were performed within one hour after administration and daily until the values of the surviving animals went back to normal. Dose-response curves were obtained and plotted against control animals (n = 10). Oral and intraperitoneal administration in ascending doses of Na+-pentobarbital, theophylline and diazepam (i.p. only) up to the lethal level have a parallel influence on grip strength and heat emission; the correlation with mortality is clear for Na+-pentobarbital and diazepam but not for theophylline.
体内急性毒性试验正在寻找一种新方法,以减少所用动物的数量,并增加定量和定性观察的数量。已采用测量小鼠(前肢)握力(评估肌肉力量的经典工具)和测量散发的热量(评估基础代谢的工具)。到目前为止,急性毒性试验的目的是确定半数致死剂量(LD50)水平或最终确定最小致死剂量。这些非侵入性试验能让人了解总体健康状况,并在寻找最小致死剂量的同时确定最小中毒剂量。已开发出一种计算机辅助握力试验和一种红外体温测定试验,并用戊巴比妥钠、茶碱和地西泮进行了校准,将这些药物以口服或腹腔注射的方式一次性给予每组10只雄性NMRI(MAI)小鼠。给药后1小时内进行试验,并每天进行,直到存活动物的值恢复正常。获得了剂量反应曲线,并与对照动物(n = 10)进行了对比绘制。以递增剂量口服和腹腔注射戊巴比妥钠、茶碱和地西泮(仅腹腔注射)直至致死水平,对握力和热量散发有平行影响;戊巴比妥钠和地西泮与死亡率的相关性明显,但茶碱则不然。