Perchlorate is a stable and readily transportable thyroid hormone disruptor, and prevalent exposure to perchlorate through food and drinking water has raised public concern about its health effects. The physiologically based toxicokinetic (PBTK) model as a dose prediction method is effective to predict the toxicant exposure dose of an organism and helps quantitatively assess the dose-dependent relationship with toxic effects. The current study aimed to establish a multi-compartment PBTK model based on updated time-course datasets of single oral exposure to perchlorate in rats. With adjustment of the kinetic parameters, the model fitted well the toxicokinetic characteristics of perchlorate in urine, blood, and thyroid from our experiments and the literature, and the coefficient of determination (R2) between the fitting values and the experimental data in regression analysis was greater than 0.91, indicating the robustness of the current model. The results of sensitivity analysis and daily repeated exposure simulations together confirmed its effective renal clearance. According to the distribution characteristic of perchlorate, a correlation study of internal and external exposure was conducted using urinary perchlorate as a bioassay indicator. The developed multi-compartment model for perchlorate updates important toxicokinetic data and kinetic parameters, providing analytical and modeling tools for deriving total exposure levels in the short term.
Scopus Subject Areas
- Health, Toxicology and Mutagenesis
- Exposure correlation analysis
- Physiologically-based toxicokinetic model
- Quantitative analysis