Comparison of in vivo acute lethal potency and in vitro cytotoxicity of 48 chemicals.
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.
Shrivastava
R
R
RL-CERM, Riom, France.
Delomenie
C
C
Chevalier
A
A
John
G
G
Ekwall
B
B
Walum
E
E
Massingham
R
R
D000826:Animal Testing Alternatives; D000818:Animals; D002417:Cattle; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007928:Lethal Dose 50; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D051381:Rats; D014116:Toxicology / Q000379:methods*; D015262:Xenobiotics / Q000633:toxicity
D015262:Xenobiotics; D007770:L-Lactate Dehydrogenase