Applications of TKPlate 1.0 for toxicokinetic and toxicodynamic modelling of chemicals: Case Studies

This technical report is associated with the external scientific report and user guide of TKPlate 1.0 and provides case studies for each of the modules performing either toxicokinetic and/or toxicodynamic modelling. For each case study, input data are provided and the procedure to run them is described and can be uploaded from the TKPlate info page and input module. The case studies presented here include forward dosimetry, reverse dosimetry, toxicodynamic modelling, dynamic energy budget modelling and risk characterisation of combined exposure to multiple chemicals from the MIXTOX module. For forward dosimetry, four case studies are presented for fipronil (human one‐compartment kinetic model), caffeine and amiodarone (generic human physiologically‐based kinetic (PBK) model), chlorpyrifos (QIVIVE and generic human PBK model) and a generic case study using the multi‐route 6 compartment generic human PBK model. For reverse dosimetry, two case studies are available namely melatonin using the one‐compartment kinetic model and deltamethrin using the generic PBK chicken model for laying hens. Both case studies allow reconstruction of plausible exposure distributions using internal dose such as biomonitoring data. For TD modelling, a generic case study from a 90‐day toxicological study in male rats is illustrated and the procedure to perform internal benchmark dose modelling is presented. For dynamic energy budget modelling, two case studies are illustrated as individual and population effects of fenvalerate on Daphnia magna survival and effects of lead on Eisenia fetida growth. Finally, mixture risk characterisation is illustrated for three contaminants using a deterministic hazard index methodology.

This publication is linked to the following EFSA Journal article: http://onlinelibrary.wiley.com/doi/10.2903/j.efsa.2023.e211101/full

This publication is linked to the following EFSA Supporting Publications articles: http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2023.EN-8441/full, http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2023.EN-8437/full