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Health
14 November 2023

TKPlate 1.0: An Open-access platform for toxicokinetic and toxicodynamic modelling of chemicals to implement new approach methodologies in chemical risk assessment

EFSA along with several national agencies and academic partners have developed an open-access platform: ‘TKPlate 1.0’ that integrates a number of physiologically-based kinetic models and toxicokinetic-toxicodynamic models used in human health, animal health and ecological risk assessment. These models allow the derivation of quantitative metrics related to toxicokinetic (TK) processes (what the body does to the chemical) and toxicodynamic (TD) processes (what the chemical does to the body) for hazard and risk characterisation. Such in silico new approach methodologies (NAMs) support the integration of mechanism-based understanding of chemical toxicity and the reduction of animal testing in risk assessment. Among NAM-based approaches, biologically-based models are increasingly applied in chemical risk assessment.This editorial describes EFSA's TKPlate platform and its suite of models for humans, test species (rat, mouse, rabbit, dog), farm animals (cattle, sheep, pig, chicken) and species of ecological relevance. TKPlate 1.0 consists of a workflow with seven modules: (1) input module to set the model, the chemical-specific data, exposure patterns and related time scales, (2) forward dosimetry module to predict kinetic parameters and concentrations in blood plasma and organs of interests, (3) reverse dosimetry module to back-calculate exposure from an internal dose profile using, for example, blood and urine biomonitoring data, (4) toxicodynamic module for benchmark dose modelling on an internal dose basis, (5) dynamic energy budget module to assess the impact of chemicals on the life cycle of individuals and populations of species of ecological relevance, (6) MIXTOX module for deterministic risk characterisation from exposure to multiple chemicals, (7) an automated report summarising inputs provided by the user and outputs, graphs and datasets. We conclude with perspectives on current and future development of TKPlate.