Use of Physiologically Based Kinetic Modeling-Facilitated Reverse Dosimetry to Predict In Vivo Acute Toxicity of Tetrodotoxin in Rodents.

ABSTRACT: In this study, the ability of a new in vitro/in silico quantitative in vitro-in vivo extrapolation (QIVIVE) methodology was assessed to predict the in vivo neurotoxicity of tetrodotoxin (TTX) in rodents. In vitro concentration-response data of TTX obtained in a multielectrode array assay with primary rat neonatal cortical cells and in an effect study with mouse neuro-2a cells were quantitatively extrapolated into in vivo dose-response data, using newly developed physiologically based kinetic (PBK) models for TTX in rats and mice. Incorporating a kidney compartment accounting for active renal excretion in the PBK models proved to be essential for its performance. To evaluate the predictions, QIVIVE-derived dose-response data were compared with in vivo data on neurotoxicity in rats and mice

SUBMITTER: Noorlander A 

PROVIDER: S-EPMC9041554 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature