Yamanaka S, Hashimoto M, Tobe M, Kobayashi K, Sekizawa J, Nishimura M
Department of Hygiene, Tokyo Dental College, Chiba, Japan.
Arch Toxicol. 1990;64(4):262-8. doi: 10.1007/BF01972985.
We proposed a simple method for screening assessment of acute oral and dermal toxicity using only three rats and mice of each sex at each dose level. Animals were first treated with chemicals at a dose of 2000 mg/kg and were carefully observed for compound-related morbidity and mortality. If none of the animals died, the following toxicity tests were suspended. If some of the animals died, toxicity tests at doses of 200 and 20 mg/kg were performed. The approximate LD50 values calculated by this method showed little difference between two separate laboratories and were in good agreement with LD50 values reported in the literature. Our toxicological data also showed that LD50 values were about 2-2.5 times the MNLD (maximum non lethal dose) in acute oral and dermal toxicity. This meant that a chemical could be regarded as having an LD50 of about 4000 mg/kg or higher when there was no mortality at the dose of 2000 mg/kg. A chemical with such low toxicity would not require further testing for lethal effects. Therefore, this simple method combining the fixed-dose procedure with the limit test is suitable for determination of approximate LD50 values of chemicals and for screening for necessity for classical full LD50 test using many animals.
我们提出了一种简单的方法,用于急性经口和经皮毒性的筛选评估,每个剂量水平每种性别仅使用三只大鼠和小鼠。首先以2000 mg/kg的剂量用化学物质处理动物,并仔细观察与化合物相关的发病情况和死亡率。如果没有动物死亡,则暂停后续毒性试验。如果有一些动物死亡,则进行200和20 mg/kg剂量的毒性试验。通过该方法计算的近似半数致死剂量(LD50)值在两个独立实验室之间差异很小,并且与文献报道的LD50值高度一致。我们的毒理学数据还表明,在急性经口和经皮毒性中,LD50值约为最大非致死剂量(MNLD)的2 - 2.5倍。这意味着当在2000 mg/kg剂量下没有死亡时,一种化学物质可被视为LD50约为4000 mg/kg或更高。具有如此低毒性的化学物质不需要进一步进行致死效应测试。因此,这种将固定剂量程序与限量试验相结合的简单方法适用于确定化学物质的近似LD50值,并筛选是否有必要使用许多动物进行经典的完整LD50试验。