Existing physiologically-based kinetic (PBK) models, identified via PubMed searches (with associated EndNote library)
For the safety assessment of chemicals, it is important to consider both the intrinsic toxicity and the internal exposure of the chemical. PBK models (also referred to as physiologically-based pharmacokinetic/toxicokinetic (PBPK/TK) models) can provide detailed information on the time-course of chemicals in different organs of the body. This information can be incorporated as part of the safety assessment process and/or used to support read-across predictions during product development. Model parameters and chemical information taken from existing PBK models for “source” chemicals (i.e. those with the relevant data) can be used to inform PBK model development for “target” chemicals (i.e. those lacking the relevant data). This approach was demonstrated successfully by Lu et al (2016; PLOS Computational Biology; DOI:10.1371/journal.pcbi.1004495) who developed a “Knowledgebase” of existing PBK models for 307 unique chemicals. This Knowledgebase included chemical identities, species, life-stage, organs and basic physico-chemical properties of the chemicals (along with the list of published articles and abstracts). Appropriate analogues to use as source chemicals were selected using physico-chemical property information, demonstrating the utility of the approach to assist development of new PBK models. The first step in this process is to identify the existing PBK models. Whilst the original “Knowledgebase” comprised publications from 1977 – 2013, many more models have been published since.
More recent research at the United States Environment Protection Agency (US EPA), has involved identification of additional published PBK models, obtained through a search of the PubMed database. The resulting Excel spreadsheet lists existing PBK models (identified via PubMed) for 1,290 individual chemical entities, as recorded in 972 separate publications (up to 2016). The data available in the Excel spreadsheet include chemical name, additional information on the chemical (e.g. isomer, metabolite of another chemical, administration as a mixture etc), species, gender, life-stage, administration route, compartments/organs considered and the PubMed ID number.
The associated Endnote library gives the full details of all the references obtained via PubMed (including abstracts); PBK models of interest can be searched via their PubMed ID number.
This information is provided as an indication of models available, it does not represent an exhaustive search of all existing models.
