A systematic review of published physiologically-based kinetic models and an assessment of their chemical space coverage

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, i.e. 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 for which chemicals a PBK model already exists. Herein, the results of a systematic review of existing PBK models, compliant with 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 availability of model equations was captured for 7,541 PBK models. Chemical information (identifiers and physico-chemical properties) has also been recorded for 1,150 unique chemicals associated with these models. This PBK model dataset 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