Prediction of dose-dependent in vivo acetylcholinesterase inhibition by profenofos in rats and humans using physiologically based kinetic (PBK) modeling-facilitated reverse dosimetry.

ABSTRACT: Organophosphate pesticides (OPs) are known to inhibit acetylcholine esterase (AChE), a critical effect used to establish health-based guidance values. This study developed a combined in vitro-in silico approach to predict AChE inhibition by the OP profenofos in rats and humans. A physiologically based kinetic (PBK) model was developed for both species. Parameter values for profenofos conversion to 4-bromo-2-chlorophenol (BCP) were derived from in vitro incubations with liver microsomes, liver cytosol, and plasma from rats (catalytic efficiencies of 1.1, 2.8, and 0.19 ml/min/mg protein, respectively) and humans (catalytic efficiencies of 0.17, 0.79, and 0.063 ml/min/mg protein, respectively), whereas other chemical-related parameter values were derived using in silico calculations. The rat

SUBMITTER: Omwenga I 

PROVIDER: S-EPMC8032624 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature