Garle M J, Fentem J H, Fry J R
Department of Human Morphology, University of Nottingham Medical School, Nottingham NG7 2UH, UK.
Toxicol In Vitro. 1994 Dec;8(6):1303-12. doi: 10.1016/0887-2333(94)90123-6.
Investigations of the use of in vitro cytotoxicity tests for the prediction of acute toxicity in vivo have been reviewed with particular emphasis on those studies that have been published during the past 5 years. Numerous cell types, endpoints and exposure periods have been used in cytotoxicity tests, although these appear generally to have little effect on the resulting correlation between in vitro IC(50) values and in vivo LD(50) values. The in vitro data correlate better with rodent parenteral (ip or iv) LD(50) values than with oral LD(50) values due to kinetic considerations. For certain groups of related chemicals (e.g. antitumour compounds, metal salts), and for some sets of unrelated chemicals, the in vitro data correlate very well with LD(50) values. However, while cytotoxicity tests are useful for screening chemicals for their intrinsic and relative toxicities, it is impossible to tell whether predictions based on cytotoxicity data alone would be sufficiently accurate for labelling and classifying a new chemical according to its likely acute toxicity in vivo. The in vitro endpoints need to be of greater relevance to the possible mechanisms of chemically-induced acute toxicity in vivo than most of those that are used at present.
对使用体外细胞毒性试验预测体内急性毒性的研究进行了综述，特别强调了过去5年发表的那些研究。细胞毒性试验中使用了多种细胞类型、终点指标和暴露时间，尽管这些因素总体上似乎对体外IC(50)值与体内LD(50)值之间的最终相关性影响不大。由于动力学因素，体外数据与啮齿动物经肠外途径（腹腔注射或静脉注射）的LD(50)值的相关性优于与经口LD(50)值的相关性。对于某些相关化学物组（如抗肿瘤化合物、金属盐）以及某些不相关化学物组，体外数据与LD(50)值相关性很好。然而，虽然细胞毒性试验对于筛选化学物的内在毒性和相对毒性很有用，但仅根据细胞毒性数据进行的预测对于根据新化学物在体内可能的急性毒性进行标签和分类是否足够准确则无法判断。体外终点指标需要比目前使用的大多数指标与化学诱导的体内急性毒性的可能机制有更大的相关性。
