Monocrotaline-induced liver toxicity in rat predicted by a combined in vitro physiologically based kinetic modeling approach.

ABSTRACT: The aim of the present study was to use an in vitro-in silico approach to predict the in vivo acute liver toxicity of monocrotaline and to characterize the influence of its metabolism on its relative toxic potency compared to lasiocarpine and riddelliine. In the absence of data on acute liver toxicity of monocrotaline upon oral exposure, the predicted dose-response curve for acute liver toxicity in rats and the resulting benchmark dose lower and upper confidence limits for 10% effect (BMDL₁₀ and BMDU₁₀) were compared to data obtained in studies with intraperitoneal or subcutaneous dosing regimens. This indicated the predicted BMDL₁₀ value to be in line with the no-observed-adverse-effect levels (NOAELs) derived from availabe in vivo studies. The predicted B

SUBMITTER: Suparmi S 

PROVIDER: S-EPMC7415757 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature