Whitehead A, Curnow R N
Department of Applied Statistics, University of Reading, UK.
Food Chem Toxicol. 1992 Apr;30(4):313-24. doi: 10.1016/0278-6915(92)90009-a.
The fixed-dose procedure (FDP) was proposed by the British Toxicology Society in 1984 as an alternative to the LD50 study in the assessment of the acute oral toxicity of a substance. This paper presents a statistical evaluation of this procedure. A mathematical description of the FDP shows that the starting dose can affect the toxic classification of a substance. The toxic classification based on the FDP is compared with that based on an LD50 test. This shows that, in general, the FDP is likely to result in the same classification or a less toxic one than the LD50 procedure. However, for substances with very shallow dose-response slopes, the FDP is likely to result in the same classification or a more toxic one. The expected number of animals that will be tested and will die using the FDP will be reduced compared with the LD50 study. The results from the international validation study carried out in 1989 showed agreement with the results predicted from the mathematical model.
固定剂量法（FDP）由英国毒理学协会于1984年提出，作为评估物质急性经口毒性时替代半数致死量（LD50）研究的方法。本文对该方法进行了统计学评估。对FDP的数学描述表明，起始剂量会影响物质的毒性分类。将基于FDP的毒性分类与基于LD50试验的分类进行了比较。结果表明，一般而言，FDP与LD50法相比，可能得出相同的分类结果或毒性更低的分类结果。然而，对于剂量-反应斜率非常平缓的物质，FDP可能得出相同的分类结果或毒性更高的分类结果。与LD50研究相比，使用FDP进行测试并死亡的动物预期数量会减少。1989年进行的国际验证研究结果与数学模型预测的结果一致。
