Causes of Death in Rodent Toxicity and Carcinogenicity Studies
Causes of Death in Rodent Toxicity and Carcinogenicity Studies
复制标题
啮齿动物毒性和致癌性研究中的死亡原因
DOI：
10.1177/019262339402200210
复制
发表时间：
1994
影响因子：
1.5
通讯作者：
D. Prentice
中科院分区：
文献类型：
--
作者：
R. Ettlin;P. Stirnimann;D. Prentice
对致癌性研究进行统计评估的Peto试验程序要求，在死亡期间（或在极端情况下牺牲）死亡的动物体内的每个肿瘤被分类为致命的、可能致命的、偶然的或可能偶然的。关于在啮齿动物研究中是否可以准确地确定死亡原因，存在相当大的争议。在本文中，对10个连续的致癌性研究中发现的死亡或疾病原因进行了重新检查，其中5个研究对象是2400只OFA （sprague - dawley衍生）和Wistar大鼠，5个研究对象是2400只OF1和NMRI小鼠。超过80%的大鼠病例和超过70%的小鼠病例已确定死亡或垂死状态的原因。在大鼠中，这些原因主要是垂体肿瘤、慢性进行性肾病（雄性）、乳腺肿瘤（雌性）和皮下肿瘤（雄性）；在小鼠中，主要是淋巴网状瘤、肺肿瘤、肝肿瘤（雄性）和肾小球肾病。用于确定肿瘤或非肿瘤病变作为死亡原因的标准是基于生活和病理结果。讨论了这些程序的有效性，未来改进标准的可能性，以及在安全评估中确定死亡原因的实用性。
Peto test procedures for the statistical evaluation of carcinogenicity studies require that each tumor in an animal that died intercurrently (or was sacrificed in extremis) be classified as either fatal, probably fatal, incidental, or probably incidental. There is considerable controversy as to whether or not the cause of death can be established with accuracy in rodent studies. In the present article, the causes of death or ill-being as found in 10 consecutive carcinogenicity studies—5 studies with 2400 OFA (Sprague-Dawley-derived) and Wistar rats and 5 studies with 2400 OF1 and NMRI mice—were re-examined. A cause of death or moribund state had been established in more than 80% of the cases in rats and in more than 70% in mice. These causes were, in rats, mainly pituitary tumors, chronic progressive nephropathy (males), mammary gland tumors (females), and subcutaneous tumors (males); in mice, mainly hemolymphoreticular tumors, lung tumors, liver tumors (males), and glomerulonephropathy. The criteria used for determining the tumorous or non-tumorous lesions as the cause of death were based on in-life and pathological findings. The validity of such procedures, the possibility of improving criteria in the future, and the usefulness of establishing causes of death in safety assessment are discussed.