Modeling acetylcholine esterase inhibition resulting from exposure to a mixture of atrazine and chlorpyrifos using a physiologically-based kinetic model in fish

Aquatic organisms are exposed to mixtures of chemicals that may interact. Mixtures atrazine (ATR) and chlorpyrifos (CPF) elicit synergic effects on the permanent inhibition acetylcholinesterase (AChE) in certain aquatic organisms, causing severe damage. Mechanistic mathematical models toxicokinetics toxicodynamics (TD) be used better characterize understand interactions these two chemicals. In this study, a previously published generic physiologically-based toxicokinetic (PBTK) model for fish was adapted ATR CPF. A sub-model kinetics one main metabolites CPF, chlorpyrifos-oxon (CPF-oxon), included, as well TD model. Inhibition esterases, AChE carboxylesterase, by ATR, CPF CPF-oxon, modeled using modeling quantities total inactive esterases. Specific attention given parameterization calibration accurately predict concentration observed Bayesian inference data from fathead minnow (Pimephales promelas), zebrafish (Danio rerio) common carp (Cyprinus carpio L.). PBTK-TD dose-response relationships comparison with available adult data. Synergistic joint exposure could not demonstrated fish.