A Generic, Cross-Chemical Predictive PBTK Model with Multiple Entry Routes Running as Application in MS Excel; Design of the Model and Comparison of Predictions with Experimental Results

Abstract

Aim: Physiologically based toxicokinetic (PBTK) models are computational tools, which simulate the absorption, distribution, metabolism, and excretion of chemicals. The purpose of this studywas to develop a physiologically based pharmacokinetic (PBPK) model with a high level of transpar-ency. The model should be able to predict blood and urine concentrations of environmental chem-icals and metabolites, given a certain environmental or occupational exposure scenario. Model: The model refers to a reference human of 70 kg. The partition coefficients of the parent compound and its metabolites (blood:air and tissue:blood partition coefficients of 11 organs) are estimated by means of quantitative structure–property relationship, in which five easily available physicochemical properties of the compound are the independent parameters. The model gives a prediction of the fate of the compound, based on easily available chemical properties; therefore, it can be applied as a generic model applicable to multiple compounds. Three routes of uptake are considered (inhalation, dermal, and/or oral) as well as two built-in exercise levels (at rest and at light work). Dermal uptake is estimated by the use of a dermal diffusion-based module that con-siders dermal deposition rate and duration of deposition. Moreover, evaporation during skin con-tact is fully accounted for and related to the volatility of the substance. Saturable metabolis