Taylor J M, Morgenroth V H
J Assoc Off Anal Chem. 1979 Jul;62(4):883-8.
A review of long term animal studies of saccharin and sodium nitrite was undertaken to assess the effect of variability of selected protocol elements on the results obtained. These elements were divided into 4 general categories: design, including selection of test animals, basal diet, dosage form and doses of test substance, route of administration, and duration of exposure; observations, including gross observations during life and at necropsy, clinical tests, and histopathology; performance, including conduct of the test and animal husbandry; and analytical procedures, including chemical and statistical analyses. Because many of the protocol elements are not fully discussed in study reports, it was often impossible to determine what actually had been done. The review of various saccharin studies suggests that bladder tumors resulted following in utero exposure. In utero exposure with sodium nitrite did not appear to cause reticuloendothelial changes. The numerous variations in protocol elements in the nitrite studies precluded identification of a prime element responsible for the variation in reticuloendothelial changes observed. It can be concluded from this review that achievement of reproducibility in long term studies requires minimal variation of protocol elements for the new study.
对糖精和亚硝酸钠的长期动物研究进行了综述，以评估所选实验方案要素的变异性对所得结果的影响。这些要素分为4大类：设计，包括实验动物的选择、基础饮食、受试物质的剂型和剂量、给药途径以及暴露持续时间；观察，包括动物存活期间和尸检时的大体观察、临床检测以及组织病理学检查；实施，包括实验操作和动物饲养管理；以及分析程序，包括化学分析和统计分析。由于研究报告中对许多实验方案要素未进行充分讨论，因此常常无法确定实际所做的工作。对各种糖精研究的综述表明，子宫内暴露会导致膀胱肿瘤。子宫内暴露于亚硝酸钠似乎不会引起网状内皮系统变化。亚硝酸钠研究中实验方案要素的众多变化使得无法确定导致所观察到的网状内皮系统变化差异的主要因素。从该综述可以得出结论，在长期研究中实现可重复性需要新研究的实验方案要素变化最小。
