中文摘要：

目的分析不同实验设计组合对基准剂量的影响，以实验数据验证SLOB的计算机模拟结果（即计算基准剂量的最优实验方案是：在总样本量确定的情况下，通过减少每组的实验动物量、适当增加实验组数），以利于该实验设计方法的应用和推广。方法80只清洁级成年雌性SD大鼠，每天灌胃染毒给予0．5、1、2、4、8、16和32mg／kg，连续21天。然后处死大鼠，测定大鼠海马、皮质和血清乙酰胆碱酯酶（AChE）活性，采用PROAST28．1软件包计算基准剂量。从8X10设计方案的结果中选择数据构成8×10和8×5设计方案，分析实验设计对基准剂量的影响。结果与正常对照组比较，乐果2、4、8、16和32mg／kg使海马AChE活性明显降低（P〈0．05）；乐果0．5、1、2、4、8、16和32mg／kg使皮质和血清AChE活性明显降低（P〈0．05）。以8X10实验设计的结果作为标准，4×10和8×5两种实验设计方案得出的BMD置信区间均包括了8×10实验设计的BMD；4×10实验设计中的方案1、2、3、4和6得出的BMD置信区间宽于8X5的结果，方案5得出的BMD置信区间窄于8×5的结果。结论常规毒性实验设计（即设置对照组、低剂量组、中剂量组和高剂量组四个剂量组）用于计算基准剂量不是最优的选择，最优的实验设计方案是在总样本量确定的情况下，应适当增加实验组数。

英文摘要：

Objective To obtain the impacts of experimental design on benchmark dose （BMD）, and the resuh was applied to test the computer simulation by software Slob （optimal method to calculate the BMD： for a cer：ain sample capacity, to add the experimental groups by reducing the amount of animals in each group） , consequently, this method can be widely used in the future. Methods Eighty adult female SD rats were ig given dimethoate 0. 5,1,2,4,8,16 and 32 mg/kg for 21 d, respectively. Rats were sacrificed, and acetylcholinesterase （ACHE） activity in the hippocampus, cerebral cortex and serum of rats was determined after dimethoate was ig given to rats for 21 d. And then, the software package PROAST28.1 was applied to calculate the BMD. The four doesgroups of 10 animals （4 × 10 design） and 8 ×5 design were selected from 8× 10 design to study the impacts of experimental design on BMD. Results Comparing with the normal control, the significant decline of AChE in hippocampus was observed in 2, 4, 8, 16 and 32 mg/kggroups （P〈0.05）, whereas the significant decrease was obtained in 0.5, 1, 2, 4, 8, 16 and 32 mg/kggroups （P 〈0.05）. Taking the 8 × 10 design as the standard, the confidence interval of BMD calculated by both of 4 × 10 design and 8× 5 design covered the BMD by 8 × 10 design. And also, confidence interval of BMD, calculated by design scheme 1 , 2, 3, 4 and 6 of 4 × 10 design, wider than that of 8 × 5 design, but its scheme 5 narrower than 8 × 5 design. Conclusion To add experimental groups in a certain sample capacity was the optimal method to calculate BMD, but was not the common toxicity experimental design （e. g. set four groups including control, low-dose, moderate-dose, high-dose group）.