Physiologically based kinetic modelling based prediction of in vivo rat and human acetylcholinesterase (AChE) inhibition upon exposure to diazinon.

ABSTRACT: The present study predicts in vivo human and rat red blood cell (RBC) acetylcholinesterase (AChE) inhibition upon diazinon (DZN) exposure using physiological based kinetic (PBK) modelling-facilitated reverse dosimetry. Due to the fact that both DZN and its oxon metabolite diazoxon (DZO) can inhibit AChE, a toxic equivalency factor (TEF) was included in the PBK model to combine the effect of DZN and DZO when predicting in vivo AChE inhibition. The PBK models were defined based on kinetic constants derived from in vitro incubations with liver fractions or plasma of rat and human, and were used to translate in vitro concentration-response curves for AChE inhibition obtained in the current study to predicted in vivo dose-response curves. The predicted dose-response curves for rat matched avail

SUBMITTER: Zhao S 

PROVIDER: S-EPMC8113213 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature