Are you into computational toxicology? Then these resources may be worth bookmarking.

What are PBK models?

Physiologically based kinetic (PBK) models were originally developed to assess pharmaceuticals, where they are called PBPK models. They are increasingly used in toxicology, where the term PBTK is common. By predicting how a chemical is absorbed, distributed, metabolised, and excreted, these models can support the 3Rs: reducing, refining, and replacing animal use.

Model predictions are only as good as their input data

Additional data are sometimes needed, but before running new experiments it is worth checking whether the parameters already exist in curated sources or can be estimated in silico. The resources below can help you avoid unnecessary experiments.

Estimating and retrieving physicochemical properties

EPI Suite (US EPA). Estimation software for properties such as log P, water solubility, vapour pressure, and Henry’s law constant (link).

OPERA. An open-source and open-data suite of QSAR models, developed in collaboration between NICEATM and the US EPA, with predictions for physicochemical properties, environmental fate, toxicity endpoints, and ADME properties. The code is available for download on GitHub (link).

PubChem. A searchable database with physicochemical properties including log P, TPSA, water solubility, pKa, and vapour pressure (link).

Integrated tools and partition coefficients

OECD QSAR Toolbox. Provides multiple physicochemical properties and brings together databases with data on plasma protein binding, absorption, and rat and human metabolism (skin and liver) (link).

UFZ-LSER database. Stores experimentally determined solute descriptors from the literature and uses them to calculate partition coefficients for a range of systems. These descriptors can be combined with LSER equations to calculate partition coefficients for various systems. It also offers calculators for applications such as Caco-2 monolayer permeability and the freely dissolved concentration of a neutral analyte (link).

Drug data

US FDA drug databases. The Orange Book lists approved drug products (link). Drugs@FDA review documents can contain clinical pharmacology and ADME data for approved drugs.

A platform to put it all together

TKPlate (EFSA). An open-access web application from the European Food Safety Authority for toxicokinetic and toxicodynamic modelling, supporting PBPK modelling and the use of NAMs. Its modules cover input, forward dosimetry, reverse dosimetry, toxicodynamics, dynamic energy budget, mixture toxicity, and an automated report. (link).