Development of a Web-Based Toolbox to Support Quantitative In-Vitro-to-In-Vivo Extrapolations (QIVIVE) within...

Area of Science:

• Toxicology and Pharmacology
• Computational Chemistry
• Risk Assessment

Background:

• Quantitative in-vitro-to-in-vivo extrapolation (QIVIVE) is crucial for chemical safety assessment.
• Physiologically based kinetic (PBK) models offer a robust framework for predicting internal chemical exposure.
• Accessible tools are needed to facilitate QIVIVE and risk assessment for various chemicals.

Purpose of the Study:

• To develop a web-based toolbox with generic PBK models for rats and humans.
• To enable prediction of plasma protein binding and tissue distribution for chemicals.
• To facilitate QIVIVE for assessing chemical safety and prioritizing further evaluation.

Main Methods:

• Development of generic PBK models for rats and humans.
• Integration of tools for predicting plasma protein binding and tissue distribution.
• Application of the toolbox for QIVIVE using in vitro bioactivity data and human exposure estimates.

Main Results:

• The toolbox successfully estimated internal plasma and tissue concentrations based on chemical properties (logP, pKa) and clearance values.
• Propyl gallate intake showed potential for internal plasma concentrations near in vitro effect levels, specifically for thyroid peroxidase inhibition.
• Estrogenic effects were unlikely at typical exposure levels, remaining significantly below in vitro effect thresholds.

Conclusions:

• The developed toolbox provides a valuable resource for initial chemical dose estimations and QIVIVE.
• It enables effective prioritization of chemicals for further safety assessment by comparing oral equivalent doses with human exposure.
• The freely accessible toolbox (www.qivivetools.wur.nl) supports informed decision-making in chemical risk assessment.