DATASET

A Systematic Review of Published Physiologically-based Kinetic Models and an Assessment of their Chemical Space Coverage

Collection: EURL-ECVAM : European Union Reference Laboratory for Alternatives to Animal Testing 

Description

Across multiple sectors, including food, cosmetics and pharmaceutical industries, there is a need to predict the potential effects of xenobiotics. These effects are determined by the intrinsic ability of the substance, or its derivatives, to interact with the biological system, and its concentration–time profile at the target site. Physiologically-based kinetic (PBK) models can predict organ-level concentration–time profiles, however, the models are time and resource intensive to generate de novo. Read-across is an approach used to reduce or replace animal testing, wherein information from a data-rich chemical is used to make predictions for a data-poor chemical. The recent increase in published PBK models presents the opportunity to use a read-across approach for PBK modelling, that is, to use PBK model information from one chemical to inform the development or evaluation of a PBK model for a similar chemical. Essential to this process, is identifying the chemicals for which a PBK model already exists. Herein, the results of a systematic review of existing PBK models, compliant with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) format, are presented. Model information, including species, sex, life-stage, route of administration, software platform used and the availability of model equations, was captured for 7541 PBK models. Chemical information (identifiers and physico-chemical properties) has also been recorded for 1150 unique chemicals associated with these models. This PBK model data set has been made readily accessible, as a Microsoft Excel® spreadsheet, providing a valuable resource for those developing, using or evaluating PBK models in industry, academia and the regulatory sectors.

The funding support and scientific advice provided by the European Partnership for Alternative Approaches to animal testing (EPAA) for the development of this tool (excel spreadsheet) is gratefully acknowledged.

Contact

Email
andrew.worth (at) ec.europa.eu

Contributors

How to cite

European Commission, Joint Research Centre (JRC) (2021): A Systematic Review of Published Physiologically-based Kinetic Models and an Assessment of their Chemical Space Coverage. European Commission, Joint Research Centre (JRC) [Dataset] PID: http://data.europa.eu/89h/f98e9abf-8435-4578-acd6-3c35b5d1e50c

Keywords

PBK PBPK, PBTK, systematic review, pharmacokinetic modelling, read-across pharmacokinetic modelling, read-across read-across systematic review, pharmacokinetic modelling, read-across PBTK, systematic review, pharmacokinetic modelling, read-across

Data access

Data catalogue of available PBK models
Download 
  • The tab "Controlled Vocab" explains which are free text and which are controlled vocabulary cells, used to make searching easier and content more consistent. Explanations/interpretation of the selected vocabulary is given under the lists

    The tab "Key Extraction Sheet" contains the captured PBK model data. For the initial phase of an EPAA-funded project we have used a Systematic Review to identify the chemicals for which PBK models are available. Each model has been subdivided as appropriate so that it can be searched for individually (e.g. if there are models for males and females for iv and oral - this will appear as 4 models). The structure means that the spreadsheet can be filtered, for example, to find out how many human, male, oral studies there are as well as searching for chemicals by name or identifiers.

    The tab "Phys-Chem Properties" is information obtained for identifiable chemicals with existing PBK models; canonicalised SMILES were obtained using OpenBabel and properties generated using the freely available RDKit tools.

    The tab "ToxPrint analysis" shows the results of the ToxPrints analysis using the Chemotyper software to identify frequency of occurrence of key functional groups and other structural feature of interest in the chemicals of the PBK model dataset.

    5% of entries in the spreadsheet were checked by a second researcher as well as 5% of the papers that were considered unsuitable for data extraction.

    Further curation of the database and addition of other models from

    the literature is an on-going process.

    Authors acknowledge the funding and scientific advice of the European Partnership for Alternative Approaches to animal testing (EPAA) with respect to the funding that allowed the creation of this database.

    The funding support and scientific advice provided by the European Partnership for Alternative Approaches to animal testing (EPAA) for the development of this tool (excel spreadsheet) is gratefully acknowledged.

Publications

Publication
A Systematic Review of Published Physiologically-based Kinetic Models and an Assessment of their Chemical Space Coverage
Courtney V. Thompson, James W. Firman, Michael R. Goldsmith, Christopher M. Grulke, Yu-Mei Tan, Alicia Paini, Peter E. Penson, Risa R Sayre, Steven Webb, Judith C. Madden. First A Systematic Review of Published Physiologically based Kinetic Models and an Assessment of their Chemical Space Coverage (2021) ATLA Journal Published November 26, 2021 Review Article

Additional information

Published by
European Commission, Joint Research Centre
Created date
2022-01-12
Modified date
2022-01-13
Issued date
2021-11-26
Data theme(s)
Health, Science and technology
Update frequency
unknown
Identifier
http://data.europa.eu/89h/f98e9abf-8435-4578-acd6-3c35b5d1e50c
Popularity