Jean Lou Dorne has been working at EFSA as Senior Scientific Officer in Toxicology for18 years and currently as the lead expert in NAMs within the Scientific committee team of the Methodological and Scientific Support Unit and the Chief Scientist Office. Previously, he spent 9 years at the University of Southampton for his PhD/5 years Postdoctoral research UK on “human variability in kinetics and metabolism and refinement of uncertainty factors for chemical risk assessment”. At EFSA, his work focuses on supporting other units in chemical risk assessment and guidance development, open-source toxicological databases such as EFSA's OpenFoodTox as well as physiologically-based kinetic models including the TKPlate platform published in November 2023, NAMs in toxicology and ecotoxicology including QSARs and training in chemical risk assessment at EFSA and internationally. Active member of Eurotox and the international consortium "Accelerating the pace of chemical risk assessment (APCRA) with over 250 members across the world. Over 180 peer reviewed publications, 120 EFSA outputs, 10 book chapters (H-index:49).
QIVIVE and reverse dosimetry using TKPlate
EFSA’s‘TKPlate 1.0’ is an open access platform which integrates a number of generic physiologically-based kinetic (PBK) models and toxicokinetic-toxicodynamic models for human health, animal health and ecological risk assessment. These models allow the derivation of quantitative metrics related to toxicokinetic processes and toxicodynamic (TD) processes for hazard characterisation and risk characterisation. These in silico tools as new approach methodologies (NAMs) support the integration of mechanism-based understanding of chemical toxicity and the reduction of animal testing in risk assessment. TKPlate includes suite of generic PBK models for humans, test species (rat, mouse, rabbit, dog), farm animals (cattle, sheep, pig, chicken) and species of ecological relevance. The workflow is structured in seven modules: 1) an input module to select the model, the chemical-specific data, exposure patterns and related time scales, 2) a forward dosimetry module allowing prediction of kinetic parameters and concentrations in blood plasma and a range of organs, 3) a reverse dosimetry module to reconstruct exposure distributions from internal dose profiles using blood and urine biomonitoring data, 4) a toxicodynamic module for benchmark dose modelling on an internal dose basis, 5) a dynamic energy budget module to investigate chemical toxicity on the life cycle of individuals and populations of species of ecological relevance, 6) a MIXTOX module for risk characterisation of chemical mixtures, 7) an automated report summarising inputs provided by the user and outputs, graphs and datasets. Here, we describe practical examples to perform quantitative in vitro in vivo extrapolations/PBK modelling using in vitro metabolism data and reverse dosimtery using human biomonitoring data. Future perspectives on the future development of TKPlate will conclude the presentation.
