Bayesian population analysis of a harmonized Physiologically Based Pharmacokinetic Model for Inorganic Mercury Salts
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Background: Inorganic mercury salts (iHg) are a family of mercury compounds that do not contain carbon-hydrogen bonds. iHg exposure is linked with a range of adverse toxic effects.
Objective: To develop and validate the very first physiologically based pharmacokinetic (PBPK) model for iHg by incorporating a hierarchical Bayesian approach to help estimate model parameters and evaluating kinetic uncertainty and variability in mice, rats, and humans.
Methods: Model parameters were obtained from the scientific literature and estimated through fitting published data. A comprehensive species-specific iHg database, primarily focusing on mercuric chloride (HgCl2), was developed for model calibration and validation. Results: The proposed model demonstrates a good alignment with the validation datasets, as the model predictions closely match the empirical data equally well. Except for human absorption and elimination characteristics, posterior distribution values are largely similar to prior distributions but with reduced uncertainty (95% CI).
Discussion: The complex toxicokinetics of iHg require the use of PBPK model for interspecies extrapolation of animal data to inform human hazards.Additional empirical data on critical parameters, such as mercury renal excretion kinetics under high dose settings, might improve its predictive powers.