The Application of a Physiologically Based Toxicokinetic Model in Health Risk Assessment

Abstract

Toxicokinetics plays a crucial role in the health risk assessments of xenobiotics. Classical compartmental models are limited in their ability to determine chemical concentrations in specific organs or tissues, particularly target organs or tissues, and their limited interspecific and exposure route extrapolation hinders satisfactory health risk assessment. In contrast, physiologically based toxicokinetic (PBTK) models quantitatively describe the absorption, distribution, metabolism, and excretion of chemicals across various exposure routes and doses in organisms, establishing correlations with toxic effects. Consequently, PBTK models serve as potent tools for extrapolation and provide a theoretical foundation for health risk assessment and management. This review outlines the construction and application of PBTK models in health risk assessment while analyzing their limitations and future perspectives.

Advances in Physiologically Based Pharmacokinetic (PBPK) Modeling of Nanomaterials

“…4 Protein binding Binds to plasma proteins after the absorption into systemic circulation Protein-corona formation on their surface 50 Extrapolation Traditional route-to-route extrapolation approaches of PBPK models 65 Route-specific approach of PBPK models 65 models provide a more comprehensive approach in identifying the chemical concentrations in specific organs or tissues compared to the classical compartmental models. 70 PBTK models serve as valuable tools for extrapolating data and providing a theoretical foundation for health risk assessment and management. 70 The internal kinetics of nine chemicals (three endocrine disrupters, three liver steatosis inducers, and three developmental toxicants) were anticipated by using PBTK modeling in data-rich and data-poor conditions, and higher degrees of parametrization complexity were applied.…”

“…70 PBTK models serve as valuable tools for extrapolating data and providing a theoretical foundation for health risk assessment and management. 70 The internal kinetics of nine chemicals (three endocrine disrupters, three liver steatosis inducers, and three developmental toxicants) were anticipated by using PBTK modeling in data-rich and data-poor conditions, and higher degrees of parametrization complexity were applied. 71 The results revealed that the parametrization significantly influences the outputs of the model since it can alter the prioritization of chemicals based on internal concentration factors.…”

“…Toxicokinetics is essential in evaluating the health risks associated with xenobiotics by integrating the principles and approaches in pharmacokinetics and toxicology. 70 Physiologically Based Toxicokinetic (PBTK) Absorption and uptake by cells Diffusion and/or active transport by transporters 12 Paracellular transport, 12 transcytosis, 12 M cell uptake, 12 macrophage uptake and diffusion, 12 lymphatic uptake, 12 internalization by phagocytic cells (PCs) by endocytosis/phagocytosis 67…”

A Predictive Toxicokinetic Model for Nickel Leaching from Vascular Stents

“…The FDA suggests that a relatively easy and promising approach to obtain such quantitative relationships is the use of modeling and simulation tools. ,, Physiologically based toxicokinetic (PBTK) models bear the capability to connect in vivo ion release with clinically measurable parameters such as ion concentrations in blood or urine. This allows for a direct comparison between the inferred in vivo exposure from these measurements and the outcomes of in vitro testing . Establishing such correlations necessitates a combination of computational modeling and in vitro , ex vivo , and in vivo testing and eventually clinical studies to parameterize and validate the model predictions.…”

“…This allows for a direct comparison between the inferred in vivo exposure from these measurements and the outcomes of in vitro testing. 34 Establishing such correlations necessitates a combination of computational modeling and in vitro , ex vivo , and in vivo testing and eventually clinical studies to parameterize and validate the model predictions. Although a number of studies have reported data regarding the concentration of different metal ions in serum and urine for healthy adults, 35 − 38 there is still limited information about the levels of released ions, especially their accumulation in tissues/organs following the in situ implantation of medical devices.…”