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48种化学物质的体内急性致死效力与体外细胞毒性比较

Comparison of in vivo acute lethal potency and in vitro cytotoxicity of 48 chemicals.

作者信息

Shrivastava R, Delomenie C, Chevalier A, John G, Ekwall B, Walum E, Massingham R

机构信息

RL-CERM, Riom, France.

出版信息

Cell Biol Toxicol. 1992 Apr-Jun;8(2):157-70. doi: 10.1007/BF00260565.

Abstract

The cytotoxicity of 48 compounds included in the MEIC (Multicenter Evaluation of In Vitro Cytotoxicity) list was determined in cultures of rat hepatocytes, McCoy, and MDBK cells. The average minimum concentration of each compound inducing cytotoxicity was measured in each cell type. The cytotoxicity values were then compared with published oral LD50 values for rats and mice. The logarithmic transformation of in vivo toxic doses and the corresponding in vitro cytotoxic concentrations showed a statistically significant correlation between the in vitro and in vivo values. The results show that an accurate in vivo LD50 dose could be predicted from in vitro data for at least 75% of the selected compounds. It is hoped that this finding will not only stimulate others to pursue in vitro technique but will eventually lead to elimination of the in vivo LD50 test.

摘要

测定了MEIC(体外细胞毒性多中心评估)清单中包含的48种化合物在大鼠肝细胞、 McCoy细胞和MDBK细胞培养物中的细胞毒性。在每种细胞类型中测量了诱导细胞毒性的每种化合物的平均最低浓度。然后将细胞毒性值与已发表的大鼠和小鼠口服LD50值进行比较。体内毒性剂量和相应的体外细胞毒性浓度的对数转换显示体外和体内值之间存在统计学上的显著相关性。结果表明,至少75%的所选化合物的体内LD50剂量可以根据体外数据准确预测。希望这一发现不仅能刺激其他人采用体外技术,最终还能导致体内LD50试验的淘汰。

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