Enhancing PFAS Risk Characterisation Through a Cloud-based PBK Model Repository

Enhancing PFAS Risk Characterisation Through a Cloud-based PBK Model Repository Periklis Tsiros 1Vasileios Minadakis 1Paraskevi Papakyriakopoulou 1 Haralambos Sarimveis* 1 1National Technical University of Athens, School of Chemical engineering, 9 Heroon Polytechniou St, 15780, Athens, Greece PFAS: The Forever Chemicals Definition: Human-made chemicals containing at least one fully fluorinated carbon atom, known for their persistence in the environment and resistance to heat, water, and oil. Applications: Used in products like non-stick cookware, waterproof clothing, firefighting foams, and food packaging due to their resistance to heat, water, and grease. Concerns: High persistence to degradation and excretion lead to high half-lives in humans and have been linked to various adverse health effects. Physiologically Based Kinetic (PBK) Models Physiologically Based Kinetic (PBK) models are computational tools used to simulate how chemicals behave inside living organisms. Simulate absorption, distribution, metabolism, and elimination (ADME) of chemicals using systems of differential equations based on mass balance principles. Represent the body as interconnected compartments (e.g., liver, kidney, blood), parameterized using physiological and chemical-specific data. Serve as key tools in chemical risk assessment, enabling forward dosimetry (predicting internal concentrations from exposure) and inverse dosimetry (estimating exposure needed to reach a target internal dose). PFAS PBK Models of SCENARIOS on Jaqpot The SCENARIOS project is a European initiative focused on improving the understanding and risk assessment of PFAS. As part of this effort, it provides a curated library of PBK models, either newly developed or adapted from existing ones, which are hosted as fully documented online services on the Jaqpot platform. The list already consists of 14 PBK models. A sublist of these models is presented in Figure 1. Jaqpot is an open-source platform that enables the deployment, sharing, and execution of computational models through a user-friendly web interface or through API. Figure 1. List of available PBK models for PFAS on SCENARIOS organisation on Jaqpot. Figure 2. Structural representation of the PFOA PBK developed for male rats by Tsiros et al. (2024) [1]. Jaqpot Interface & SDK: The gateway to PBK Modeling Interaction with PBK models on Jaqpot is possible via an intuitive Graphical User Interface (GUI) or through the Python SDK in a programming environment. Users of the model can: Simulate custom exposure scenarios and generate predictions with a single click, View outputs as interactive plots and downloadable tables (as CSV files), Automate predictions using the Jaqpot Python SDK, Integrate models into custom risk assessement pipelines and with in silico tools like QSAR models. Figure 2 showcases the PFOA PBK by Tsiros et al. (2024) [1]. This model is an extended version of the one presented by Worley and Fisher (2015) [2]. The model was developed using available data from the literature. The GUI of this model is presented in Figure 3. An example of calling this model through the Python SDK is presented in Figure 4. Figure 3. Jaqpot user interface for PBK models. Figure 4. Making predictions with the PBK models on Jaqpot through a programming environment using the Jaqpot Python SDK. Acknowledgements This work has been financially supported by the SCENARIOS project (Grant Agreement 101037509) which has been funded by the European Commission under the Horizon 2020 Programme. References [1] Periklis Tsiros, Vasileios Minadakis, Dingsheng Li, and Haralambos Sarimveis. Parameter grouping and co-estimation in physiologically based kinetic models using genetic algorithms. Toxicological Sciences, 200(1):31–46, 04 2024. ISSN 1096-6080. doi: 10.1093/toxsci/kfae051. URL https://doi. org/10.1093/toxsci/kfae051. [2] Rachel Rogers Worley and Jeffrey Fisher. Application of physiologically-based pharmacokinetic modeling to explore the role of kidney transporters in renal reabsorption of perfluorooctanoic acid in the rat. Toxicology and Applied Pharmacology, 289(3):428–441, 2015. ISSN 0041-008X. doi: https://doi.org/10.1016/j.taap.2015.10.017. URL https://www.sciencedirect.com/science/article/pii/S0041008X15301204. https://cemepe12.civil.auth.gr CEMEPE & SECOTOX 2025, Mykonos