TOXLET VOL 411 SUPPL

Volume 411S, September 2025 ISSN 0378-4274 411S S1-S507 (2025) Abstracts of the 59th Congress of the European Societies of Toxicology (EUROTOX 2025) TOXICOLOGY ADDRESSES SOCIETY’S REAL LIFE RISKS FOR SUSTAINABLE HEALTH AND WELL BEING Athens, Greece, 14–17 September 2025

Aims and Scope An international journal for the rapid publication of novel reports on a range of aspects of toxicology, especially mechanisms of toxicity. Toxicology Letters serves as a multidisciplinary forum for research in toxicology. The prime aim is the rapid publication of research studies that are both novel and advance our understanding of a particular area. In addition to hypothesis-driven studies on mechanisms of mammalian toxicity, Toxicology Letters welcomes seminal work in the following areas: • In silico toxicology • Toxicokinetics • Physiologically-based pharmacokinetic (PBPK) modeling • Systems toxicology • Predictive toxicology • 3R research in toxicology • New approach methodology (NAMs) • Adverse outcome pathways (AOPs) • Integrated testing strategies Systematic and narrative reviews and mini-reviews in various areas of toxicology will be published. Clinical, occupational and safety evaluation, hazard and risk assessment, regulatory toxicology, impact on man, animal and environment studies of suffi cient novelty to warrant rapid publication will be considered. Toxicology Letters also publishes editorials, commentaries and contemporary issues in toxicology. The following types of work are not within the scopes of Toxicology Letters: • Ecotoxicology studies • Case studies • Chemoprevention studies • Pharmacological investigations Authors are advised to follow the ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments; https://arriveguidelines.org/) and the OECD guidance document on Good In Vitro Method Practices (GIVIMP; https://www.oecd.org/env/guidance-document-on-good-in-vitro-methodpractices-givimp-9789264304796-en.htm). In vitro or in vivo investigations conducted at concentrations or doses of no relevance to human or animal exposure will not be considered. 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Amsterdam—Boston—London—New York—Oxford—Paris—Philadelphia—San Diego—St. Louis Abstracts of the 59th Congress of the European Societies of Toxicology (EUROTOX 2025) TOXICOLOGY ADDRESSES SOCIETY’S REAL LIFE RISKS FOR SUSTAINABLE HEALTH AND WELL BEING Athens, Greece, 14 –17 September 2025 Publication of this supplement is supported by EUROTOX. An International Journal for the Rapid Publication of Short Reports on all Aspects of Toxicology Especially Mechanisms of Toxicity Editor-in-Chief Angela Mally Associate editors Timothy W. Grant, Scott Garrett, Emanuela Testai, and Alicia Paini

Editor-in-Chief A. Mally, Julius-Maximilians-University Würzburg, Department of Toxicology, Versbacher Straße 9, 97078 Würzburg, Fax. +49 931 31 811940 Co-Editors T. W. Gant, Imperial College London Faculty of Medicine, SW7 2AZ, London, United Kingdom S. Garrett, University of North Dakota School of Medicine and Health Sciences, 501 N. Columbia Road Stop 9037, ND 58202, Grand Forks, North Dakota, United States of America A. Paini, European Food Safety Authority, Parma, 43100, Italy E. Testai, National Institute of Health Laboratory of Comparative Toxicology and Ecotoxicology, Roma, Italy Emeritus Editors W. Dekant, Julius-Maximilians-University Würzburg, Department of Toxicology, Versbacher Straße 9, 97078 Würzburg, Germany J. P. Kehrer, University of Alberta Faculty of Pharmacy and Pharmaceutical Sciences, 8613 – 114th St., Edmonton, T6G 2N8, Alberta, Canada Editorial Board J. T. Ahokas, Victoria, Australia B. Akingbemi, Alabama, United States of America L. Aleksunes, New Jersey, United States of America M. van den Berg, Utrecht, Netherlands W. M Caudle, Georgia, United States of America V. Cuomo, Roma, Italy M. Lucia Zaidan Dagli, Sao Paulo, Brazil / 'HOODˡRUD 3DUPD ,WDO\ M. P. Dent, Bedford, United Kingdom P. Diel, Koln, Germany D. R. Dietrich, Konstanz, Germany J. A. Doorn, Iowa, United States of America Z. Dvorak, Olomouc, Czechia A. O. S. El-Kadi, Alberta, Canada N. Filipov, Georgia, United States of America A.-M. Florea, Berlin, Germany R. Ge, Wenzhou, China K. O. Goyak, Texas, United States of America J. A. Harrill, North Carolina, United States of America P. Hewitt, Darmstadt, Germany H. Jaeschke, Kansas, United States of America N. Kramer, Wageningen, Netherlands C. Yanfei Li, California, United States of America B. Liu, Florida, United States of America D. Marko, Vienna, Austria P. Marx-Stoelting, Berlin, Germany N. Mei, Arkansas, United States of America B. van Ravenzwaay, Ludwigshafen, Germany Q. Shi, Arkansas, United States of America S. Somji, North Dakota, United States of America M. Adrian Williams, Maryland, United States of America F. Worek, Munich, Germany Processed at Thomson Digital, Gangtok (India) IV

Abstracts of the 59th Congress of the European Societies of Toxicology (EUROTOX 2025) TOXICOLOGY ADDRESSES SOCIETY’S REAL LIFE RISKS FOR SUSTAINABLE HEALTH AND WELL BEING Athens, Greece, 14 –17 September 2025 Preface Keynote Lectures KL01 | Opening Ceremony & Keynote Lecture KL02 | EUROTOX Lecture Award KL03 | EUROTOX - SOT Debate KL04 | SOT Merit Award Lecture KL05 | HESI CITE Lecture KL06 | Keynote Lecture Continuing Education Courses (CECs) &(& _ &KDOOHQJHV LQ WKH LGHQWLˡFDWLRQ RI FKHPLFDO respiratory allergens CEC02 | Developmental Neurotoxicity (DNT): bridging from mammal to cellular behavior CEC03 | Using quantitative modeling to predict exposures and support safety assessment CEC04 | How to assess the internal validity of toxicokinetic studies CEC05 | Regulatory Toxicology in the context of the EU Legislations CEC06 | Toxicities from the emerging new psychotropic drugs Sessions S01 | Exposomics and telomeres S02 | Assessing and Communicating Uncertainty in Next Generation Risk Assessment S03 | Botanical safety: toxicological methods for evaluating complex mixtures S04 | Carcinogenicity testing after the ICH S1B revision – where are we now? S05 | Mechanical-driven carcinogenesis and implications for organ-on-chip development S06 | Dose level selection for Developmental and Reproductive Toxicology (DART) studies under REACH S07 | Potential developmental neurotoxicity of glyphosate. &DQ WKH DYDLODEOH HYLGHQFH ˡOO WKLV GDWD JDS LGHQWLˡHG during the peer review process in the EU? S08 | Cardiotoxicity: A roadmap to regulatory acceptance Where we are and future steps. S09 | Advances in Regulatory Science with NAMs and Animal Models S10 | Crossing Boundaries: Non-Animal Methods Linking Human and Environmental Health S11 | Current update and future perspectives on in vitro inhalation toxicity testing S12 | New approaches of epigenetic mechanisms in toxicology S13 | New Approaches Methodology (NAM) in Immunotoxicology: from in vitro to risk-assessment 6 _ 7KH ,PSDFW RI ,QWHUVSHFLHV 'L˫HUHQFHV RQ $'0( 3URFHVVHV S15 | The Virtual Human in Toxicology S16 | Biopesticides: how to evaluate the safety S17 | Fundamentals and Evolving Uses of Cell Painting in Toxicology Studies S18 | Global Coalitions are Essential to Advancing New Approach Methods for Chemical Risk Assessment S19 | The mitochondria in toxicology S20 | ECF session; Towards Inclusive Toxicology: Bridging Diversity in Research and Practice S21 | How safe is cannabidiol (CBD)? S22 | Advanced human liver test systems for drug and chemical safety assessment S23 | HOT TOPIC: Safety and Toxicology Issues Related to microRNA and mRNA Applications in Medical Practice S24 | Accounting for the role of time in the development of toxicity in the context of next generation risk assessment 6 _ %H\RQG WKH ˡUVW K\SH UHDO OLIH DSSOLFDWLRQV RI DUWLˡFLDO intelligence in contemporary toxicology and risk assessment S26 | Thyroid-hormone related neurodevelopmental toxicity S27 | The gut microbiome and its implementation in the risk assessment of xenobiotics: where are we now and where are we going? S28 | New approaches to assessing and predicting CNS injury S29 | Toxic talk: cellular communication as a revisited target of toxicity S30 | Toxicology regulatory angle and Gen AI (by Elsevier) V

Abstracts of the 59th Congress of the European Societies of Toxicology (EUROTOX 2025) TOXICOLOGY ADDRESSES SOCIETY’S REAL LIFE RISKS FOR SUSTAINABLE HEALTH AND WELL BEING Athens, Greece, 14 –17 September 2025 6FLHQWLˡF 3URJUDPPH &RPPLWWHH • Emanuela Corsini Chair, EUROTOX Executive Committee • Felix Carvalho EUROTOX Executive Committee • Manon Beekhuijzen EUROTOX Executive Committee • Aristidis Tsatsakis EUROTOX 2025 Congress President • Constantine Vardavas (85272; /RFDO 6FLHQWLˡF 6XEFRPPLWWHH • Giorgia Del Favero EUROTOX 2026 Congress Delegate Chairs of the EUROTOX Specialty Sections • Jan Vondracek Carcinogenesis • Corrado Galli EUROTOX Risk Assessment (ERASS) • Saadia Kerdine-Römer Immunotoxicology & Chemical Allergy (ITCASS) • Nynke Kramer In Vitro and In Silico Toxicology Speciality Section (In2TOX) • Sibel Özden Molecular Toxicology /RFDO 6FLHQWLˡF 6XEFRPPLWWHH • Aristidis Tsatsakis (Chair) University of Crete • Dimosthenis Sarigiannis (Chair) National Hellenic Research Foundation • Vassiliki A. Boumba University of Ioannina • Nikolaos Georgiadis European Chemicals Agency • Marina Goumenou University of Crete • Dimitris Kouretas • Kiriaki Machaira Benaki Phytopathological Institute • Andreas Tsakalof Hellenic Society of Toxicology • Manolis Tzatzarakis University of Crete • Constantine Vardavas National and Kapodistrian University of Athens VII

Abstracts of the 59th Congress of the European Societies of Toxicology (EUROTOX 2025) TOXICOLOGY ADDRESSES SOCIETY’S REAL LIFE RISKS FOR SUSTAINABLE HEALTH AND WELL BEING Athens, Greece, 14 –17 September 2025 Reviewers The abstracts of the poster presentations and short oral communications were peer-reviewed by the following reviewers (in alphabetical order): • Saadia Kerdine-Römer EUROTOX Immunotoxicology & Chemical Allergy Speciality Section (ITCASS) • Karolina Kopánska EUROTOX Corporate Programme Subcommittee, Early Career Forum • Nynke Kramer EUROTOX In Vitro and In Silico Toxicology Speciality Section (In2TOX), EUROTOX Communication Subcommittee • Eliska Kuchovska Early Career Forum Chair • Jyrki Liesivuori EUROTOX Individual Member Delegate • Marina Marinovich (85272; 5HJLVWUDWLRQੇ ੇ (57 6XEFRPPLWWHH • Doris Marko EUROTOX Executive Committee, (85272; 5HJLVWUDWLRQੇ ੇ (57 6XEFRPPLWWHH • Joana Miranda EUROTOX Communication Subcommittee • Fabrice Nesslany EUROTOX Nomination Subcommittee • Mattias Öberg EUROTOX Executive Committee, EUROTOX Education Subcommittee • Hilmi Orhan EUROTOX Nomination Subcommittee • Sibel Özden EUROTOX Molecular Toxicology Speciality Section • Marc Pallardy EUROTOX Executive Committee, EUROTOX Education Subcommittee • /XFLMD 3HUKDULǩ EUROTOX Risk Assessment Speciality Section (ERASS) • Semra Sardas (85272; 5HJLVWUDWLRQ (57 6XEFRPPLWWHH • João Pedro Silva EUROTOX Molecular Toxicology Speciality Section • João Paulo Teixeira EUROTOX Executive Committee, (85272; 5HJLVWUDWLRQ (57 6XEFRPPLWWHH • Andreas Tsakalof (85272; /RFDO 6FLHQWLˡF 6XEFRPPLWWHH • Yanis Tsakiris EUROTOX 2025 Local Public Relations & Social Events Subcommittee • Aristidis Tsatsakis EUROTOX 2025 Congress President, (85272; 6FLHQWLˡF 3URJUDPPH &RPPLWWHH • Christina Tsitsimpikou EUROTOX 2025 Local Public Relations & Social Events Subcommittee • Manolis Tzatzarakis (85272; /RFDO 6FLHQWLˡF 6XEFRPPLWWHH • Alexander Vardavas EUROTOX 2025 Local Public Relations & Social Events Subcommittee • Mathieu Vinken EUROTOX Executive Committee, EUROTOX Communication Subcommittee • Jan Vondracek EUROTOX Carcinogenesis Speciality Section • Carola Voss EUROTOX Education Subcommittee • Greta Waissi EUROTOX Communication Subcommittee • Thomas Weiser EUROTOX President, EUROTOX Corporate Programme Subcommittee • Martin Wilks EUROTOX Executive Committee • Johanna Zilliacus EUROTOX Education Subcommittee • Danilo Basili EUROTOX Education Subcommittee, Early Career Forum • 9DVVLOLNL $ ੇ %RXPED (85272; /RFDO 6FLHQWLˡF 6XEFRPPLWWHH • Alessandro Brigo EUROTOX Education Subcommittee • Matthew Burbank (85272; 5HJLVWUDWLRQੇ ERT Subcommittee, Early Career Forum • Félix Carvalho EUROTOX Executive Committee, EUROTOX Nomination Subcommittee, (85272; 6FLHQWLˡF 3URJUDPPH &RPPLWWHH • Emanuela Corsini EUROTOX Executive Committee, Chair of the EUROTOX 2025 6FLHQWLˡF 3URJUDPPH &RPPLWWHH • Giorgia Del Favero (85272; 6FLHQWLˡF 3URJUDPPH &RPPLWWHH EUROTOX Carcinogenesis Speciality Section • Corrado Galli EUROTOX Risk Assessment Speciality Section (ERASS) • Nikolaos Georgiadis (85272; /RFDO 6FLHQWLˡF 6XEFRPPLWWHH • Tzveta Georgieva EUROTOX Education Subcommittee • Sarah Gould (85272; 5HJLVWUDWLRQੇ ੇ (57 6XEFRPPLWWHH • Marina Goumenou (85272; /RFDO 6FLHQWLˡF 6XEFRPPLWWHH • Hande Gürer Orhan EUROTOX Education Subcommittee • Maximilian Jobst EUROTOX Communication Subcommittee, Early Career Forum • Georges Kass EUROTOX Honorary Member VIII Organising Societies

journal homepage: www.elsevier.com/locate/toxlet Toxicology Letters Contents lists available at ScienceDirect 0378-4274 / © 2025 Published by Elsevier B.V. Toxicology Letters 411S (2025) S1 Preface Dear colleagues, esteemed guests, and friends, It is with great pleasure that we welcome you to the 59th Congress of the European Toxicologists and European Societies of Toxicology (EUROTOX 2025), taking place from September 14 to 17, 2025, in the historic and vibrant city of Athens, Greece. In an era marked by rapid technological innovation and unprecedented global challenges, our societies face a multitude of risks – from environmental pollution to the evolving impact of new and emerging technologies. These realities underscore the urgent need for a proactive, science-based approach to safeguarding public health and promoting sustainable development. Toxicology plays a pivotal role in this enGHDYRXU R˫HULQJ WKH VFLHQWLˡF WRROV QHFHVVDU\ WR DVVHVV UHDO ZRUOG ULVNV and support the development of evidence-based strategies that protect human, animal, and environmental health. The central theme of EUROTOX 2025, “Toxicology Addresses Society’s Real-Life Risks for Sustainable Health and Well-Being”, UHˣHFWV RXU FRPPLWPHQW WR H[SORULQJ DQG FRPPXQLFDWLQJ WKH LPSDFW of toxicological science in addressing the complex challenges of our time. We express our deepest gratitude to all contributors for their high- quality submissions, as well as to the 6FLHQWLˡF 3URJUDP &RPPLWWHH (SPC), session chairs, and invited speakers, who have curated a dynamLF DQG FRPSUHKHQVLYH VFLHQWLˡF SURJUDP 7KH FRQJUHVV ZLOO DGGUHVV FXWWLQJ HGJH WRSLFV LQFOXGLQJ DUWLˡFLDO LQWHOOLJHQFH DQG GDWD VFLHQFH DSSOLcations in toxicology, validation of novel methodologies, and advances in preclinical safety assessment. EUROTOX 2025 will serve as a vital forum for scientists, regulators, industry professionals, and policymakers to exchange ideas, share discoveries, and forge collaborative solutions to safeguard health and DGYDQFH VXVWDLQDELOLW\ 2XU SURJUDP UHˣHFWV WKH EUHDGWK DQG GHSWK RI modern toxicology, covering areas such as public health protection, chemical safety, environmental justice, and the responsible use of innovative materials. Highlights of this year’s congress include: • Six Continuing Education Courses • 7KLUW\ 6FLHQWLˡF 6HVVLRQV, including two sessions dedicated to Early Career Toxicologists • Two Keynote Lectures • A broad array of award lectures, including the EUROTOX Lecture Award, the SOT Merit Award, the HESI Lecture, and the highly anticipated EUROTOX/SOT Debate • Over 900 poster presentations and three short oral communication sessions, showcasing cutting-edge research • Eight industry-hosted events and a vibrant trade exhibition, fostering interdisciplinary dialogue and partnerships We are proud to announce that EUROTOX 2025 has already surpassed all previous attendance records, both in terms of registered participants and exhibition booths, making it the largest EUROTOX Congress to date. We extend our heartfelt thanks to all those who contributed to the organization and success of this event. In particular, we are grateful to the Local Organizing Committee for their outstanding work, and to the members of the Executive, Nomination, Education, Communication, Registration, and Corporate Committees for their expertise and unwavering commitment. Special thanks also go to our Specialty Sections – Carcinogenesis, Immunotoxicology, ERASS, In2TOX, and Molecular Toxicology – as well as to the K.I.T. Group, our professional congress organizer, and the dedicated team at the (85272; 6HFUHWDULDW 2˥FH. To our national societies and all EUROTOX members: your support, engagement, and collaboration form the cornerstone of our shared mission. $V ZH FRPH WRJHWKHU IRU WKLV VLJQLˡFDQW FRQJUHVV ZH DUH FRQˡGHQW that the exchange of ideas, knowledge, and diverse perspectives will spark innovation and progress. Together, we will continue to advance toxico- logical science, inform policy, and protect health for future generations. We warmly welcome you to EUROTOX 2025 and wish you a productive, inspiring, and memorable experience in Athens. With sincere appreciation and kind regards, Professor Emanuela Corsini EUROTOX 2025 Chair of the 6FLHQWLˡF 3URJUDP &RPPLWWHH 63& Professor Aristidis Tsatsakis EUROTOX 2025 Congress President Volume 411S, September 2025 ISSN 0378-4274 411S S1-S507 (2025) Abstracts of the 59th Congress of the European Societies of Toxicology (EUROTOX 2025) TOXICOLOGY ADDRESSES SOCIETY’S REAL LIFE RISKS FOR SUSTAINABLE HEALTH AND WELL BEING Athens, Greece, 14–17 September 2025

journal homepage: www.elsevier.com/locate/toxlet Toxicology Letters Contents lists available at ScienceDirect Toxicology Letters 411S (2025) Volume 411S, September 2025 ISSN 0378-4274 411S S1-S507 (2025) Abstracts of the 59th Congress of the European Societies of Toxicology (EUROTOX 2025) TOXICOLOGY ADDRESSES SOCIETY’S REAL LIFE RISKS FOR SUSTAINABLE HEALTH AND WELL BEING Athens, Greece, 14–17 September 2025 0378-4274 / © 2025 Published by Elsevier B.V. /LYHU ˡEURVLV LQYROYHV D VHULHV RI NH\ HYHQWV GHVFULEHG LQ WKH DGYHUVH outcome pathway (AOP) #38, based on the interaction of at least three FHOOXODU SOD\HUV KHSDWRF\WHV .XS˫HU FHOOV DQG KHSDWLF VWHOODWH FHOOV +HQFH FRPSOH[ LQ YLWUR V\VWHPV DUH UHTXLUHG WR DVVHVV WKHVH H˫HFWV )RU H[DPSOH ' FR FXOWXUH VSKHURLG PRGHOV FDQ UHSURGXFH D ˡEURWLF SKHQRW\SH DQG PLPLF WKH NH\ HYHQWV FKDUDFWHULVWLF RI WKH OLYHU ˡEURVLV $23 KHSDWRFHOOXODU GDPDJH DFWLYDWLRQ RI .XS˫HU FHOOV DFWLYDWLRQ RI stellate cells and deposition of extracellular matrix). However, in these FRPSOH[ V\VWHPV LW LV GL˥FXOW WR XQGHUVWDQG WKH FRQWULEXWLRQ RI HDFK cell type to the observed response. Studies implementing co-cultures, PRQRFXOWXUHV DQG FHOO W\SH VSHFLˡF HQGSRLQWV VXFK DV FHOOXODU UHVSLUDWLRQ DQG UHOHDVH RI PL51$V FDQ KHOS EHWWHU GLVFHUQ WKH VSHFLˡF LQYROYHPHQW RI WDUJHW FHOOV $V VSHFLˡF H[DPSOHV ZH HYDOXDWHG WKH H˫HFWV of methotrexate and the response to adeno-associated viruses (AAVs) of several liver cell types. KWWSV GRL RUJ M WR[OHW KL03 | EUROTOX – SOT Debate Are electric vehicles actually bad for the environment? EUROTOX Debater: U. Olofsson, Royal Institute of Technology, Stockholm, Sweden SOT Debater: M. Aschner, Albert Einstein College of Medicine, New York, USA 7KH DQQXDO 627 (85272; GHEDWH IHDWXUHV OHDGLQJ WR[LFRORJLVWV SUHsenting contrasting perspectives on a controversial or pressing issue in toxicology. The debate began in the early 1990s and has been a highly anticipated event ever since. This year, the debaters will address the proposition, “Are Electric Vehicles Actually Bad for the Environment? ”The debaters will introduce the issues that should be considered in weighing the costs and EHQHˡWV RI HOHFWULF YHKLFOHV WR WKH HQYLURQPHQW &ULWLFDO WR WKLV GHEDWH are considerations of emissions, natural resources, energy consumption, cost, and lifecycle. Relevant questions include: 1. What are the most important factors for evaluating the environmental impact of gas versus electric vehicles? 2. What is the environmental impact of electric vehicle batteries? 3. What populations are most impacted in the switch to electric vehicles? 4. How can risk be compared across the entire lifecycle of the materials? KL01 | Opening Ceremony & Keynote Lecture 6WUHVV DQG +HDOWK\ /RQJHYLW\ YV ੇ $JLQJ G. P. Chrousos National and Kapodistrian University of Athens, Medical School, Aghia Sophia Children’s Hospital, Athens, Greece 6WUHVV LV GHˡQHG DV D GLVWXUEDQFH LQ WKH dynamic equilibrium or homeostasis of a complex system, such as the human organism. A stressor is the force that causes this disturbance, while the adaptive response is the internal force that restores its homeostasis to the normal level. In humans, the adaptive response is mediated by a specialized system in the brain and body, known as the stress system, which is activated in a time-limited fashion to help us cope with stress when a stressor of any type exceeds a certain threshold. Chronic activation of the stress system unfortunately causes the FKURQLF VWUHVV DQG LQˣDPPDWLRQ V\QGURPH, which represents the background of all the chronic noncommunicable diseases, renders the organism vulnerable to certain infections and DFFHOHUDWHV DJLQJ $JLQJ LV D FRPSOH[ ELRORJLFDO SURFHVV LQˣXHQFHG E\ genetic, epigenetic, and environmental factors, ultimately leading to a JUDGXDO GHFOLQH LQ FHOOXODU DQG RUJDQ IXQFWLRQ DQG ˡQDOO\ GHDWK 7KHUH is evidence of genetically programmed aging, including a theoretical OLIHVSDQ RI XS WR \HDUV GHˡQHG E\ WKH UHJHQHUDWLYH OLPLWV RI DGXOW VWHP FHOOV 7KHUH DUH WZR SHULRGV GXULQJ WKH ˡIWK DQG VHYHQWK GHFDGHV of life, when aging appears to accelerate, likely due to genetically timed epigenetic shifts. We know of over 10 discrete molecular mechanisms of aging and all of them are worsened by the presence of chronic stress. KWWSV GRL RUJ M WR[OHW KL02 | EUROTOX Lecture Award Multicellular liver systems and how to deconvolute toxicity in a complex system? L. Suter-Dick School of Life Sciences (FHNW), Muttenz, Switzerland The liver is a major site for xenobiotic-induced toxicity and in vitro systems often focus on the hepatocyte. However, multicellular 3D-sysWHPV DUH EHWWHU VXLWHG WR UHˣHFW VRPH W\SHV RI WR[LFLWLHV VXFK DV LPPXQH PHGLDWHG UHVSRQVHV DQG OLYHU ˡEURVLV ,PPXQH PHGLDWHG OLYHU WR[LFLW\ PD\ LQYROYH .XS˫HU FHOOV RU +HSDWLF VLQXVRLGDO FHOOV /6(&V Keynote Lectures

S3 Toxicology Letters 411S (2025) S02–S04 KL05 | HESI CITE Lecture From data silos to virtual humans: guardrails for a new era in safety prediction 6 0 ੇ /HYLQH Dassault Systèmes, USA No abstract has been submitted. KWWSV GRL RUJ M WR[OHW KL06 | Keynote Lecture Operationalising the exposome across environmental, consumer and industrial chemicals for public-health protection ' $ ੇ 6DULJLDQLV - National Hellenic Research Foundation, Athens, Greece - Aristotle University of Thessaloniki, HERACLES Health and Exposome research center, Center for Interdisciplinary Research and Innovation, Thessaloniki, Greece - University Institute of Advanced Study IUSS, Pavia, Italy Purpose: To demonstrate how the exposome can deliver decision-grade, life-course evidence across a broad chemical universe – encompassing environmental contaminants, consumer-product ingredients and industrial chemicals – and to show how this evidence translates into prevention targets and policy. Methods: Building on developments and results of past and running exposome and chemical risk assessment projects (HEALS, ICARUS, URBANOME, PARC, ENVESOME), we propose a comprehensive methRGRORJLFDO SLSHOLQH WKDW LQWHJUDWHV L JHQHULF OLIHORQJ 3%3. 3%%. models to translate multi-route, multi-chemical exposures (inhalation, ingestion, dermal) into internal dosimetry across developmental stagHV SDUDPHWHULVDWLRQ OHYHUDJHV 46$5 UHDG DFURVV %D\HVLDQ FDOLEUDWLRQ to human biomonitoring, and mixture kinetics. (ii) Human-centred H[SRVXUH PRGHOOLQJ WKDW IXVHV ZHDUDEOHV DQG LQGRRU RXWGRRU PXOWLPHGLD IDWH ZLWK DJHQW EDVHG DFWLYLW\ DQG SURGXFW XVH SURˡOHV FDSWXULQJ microenvironments (home, work, transport) and socio-spatial heterogeneity. (iii) High-resolution mass spectrometry (suspect screening and QRQ WDUJHW DQDO\VLV H˫HFW GLUHFWHG DVVD\V DGGXFWRPLFV DQG PXOWL omics readouts mapped to AOP networks to connect external dose with HDUO\ ELRORJLFDO H˫HFWV LY &DXVDO PL[WXUH DQDO\WLFV H J J PHWKRGV %.05 :46 DQG WDUJHW WULDO HPXODWLRQ XQGHU FRPSXWH WR GDWD IHGHUated learning to respect governance of sensitive health and product data. (v) Decision engines that run intervention scenarios (safe and sustainable chemical innovation, substitution, reformulation, procurePHQW YHQWLODWLRQ ˡOWUDWLRQ GLHWDU\ VKLIWV DQG UDQN RSWLRQV E\ DWWULEXWDEOH ULVN EHQHˡW FRVW DQG HTXLW\ Results: Across European cohorts and cities, the pipeline resolves contributions from persistent and semi-volatile organics (PFAS, phthalates, ELVSKHQROV ˣDPH UHWDUGDQWV SHVWLFLGHV VROYHQWV PHWDOV LQGRRU HPLVsions and air pollutants, alongside chemical mixtures arising from IRRG GULQNLQJ ZDWHU GXVW DQG SHUVRQDO FDUH SURGXFWV ,W TXDQWLˡHV ZLQGRZ VSHFLˡF YXOQHUDELOLWLHV SUHFRQFHSWLRQ SUHJQDQF\ LQIDQF\ DGROHVFHQFH VH[ VSHFLˡF GL˫HUHQFHV DQG KLJK LPSDFW PLFURHQYLURQments. Federated analyses enable cross-site generalisation and full ELDV FDOLEUDWLRQ DXGLWV ZLWKRXW FHQWUDOLVLQJ SHUVRQDO RU SURSULHWDU\ data. Scenario tests show that targeted chemical substitution and in5. How do extraction processes for fossil fuels versus HOHFWULF YHKLFOH EDWWHU\ PDWHULDOV GL˫HU" In addition to inclusion as a Keynote Lecture at this meeting, this debate took place already (with the debaters having taken the reverse positions) in Orlando, US, during the 2025 SOT Annual Meeting, March 16–20. KWWSV GRL RUJ M WR[OHW KL04 | SOT Merit Award Lecture 0HFKDQLVP )RFXVHG 5HVHDUFK 7KH )RXQGDWLRQ RI 6FLHQWLˡFDOO\ Based Carcinogen Risk Assessment J. Klaunig ,QGLDQD 8QLYHUVLW\ 6FKRRO RI 3XEOLF +HDOWK࡭%ORRPLQJWRQ Zionsville, USA This year, 2025, marks the 5th decade of my initiation into carcinogenesis research. Work in my laboratory has focused on understanding the mechanisms by which environmental and pharmaceutical chemical agents induce cancer. We have focused on the liver as the target organ, given that it is the predominate site of neoplasms induced by chemical in chronic rodent bioassays. Our work has utilized a multistage, multistep liver tumor model as the foundation for dissecting the key events of the carcinogenesis process in the liver. Historically, it was assumed WKDW DOO FKHPLFDO FDUFLQRJHQV ZHUH JHQRWR[LF PXWDJHQLF LQ DFWLRQ SURducing DNA damage and mutation of key growth regulatory genes resulting in neoplasia. However, subsequent studies revealed that this simplest approach was not apparent seen with many agents that produced cancer in rodents and humans. While a mutational event is needed for neoplasia, the induction of cell proliferation by the carcinogen in the target tissue has been shown to be of utmost importance in the neoplastic process. In the case of liver carcinogenesis, the induction of cell growth either through increased cell proliferation or decreased apoptosis. In the liver this can occur through a mitogenic stimulus (nuclear receptor mediated) or through compensatory hyperplasia subsequent to cytotoxicity. My lab has combined these mechanistic concepts with the pathology of the multistep liver carcinogenesis process to further develop a mode of action approach. The importance of the multistep concept is WKDW HDFK VWHS LV GHˡQHG E\ PROHFXODU DQG SKDUPDFRORJLFDO DWWULEXWHV of the carcinogen and mechanisms. Therefore, each step has dose response and threshold characteristics that need to be considered for the entire neoplastic process to occur. We are faced to with an increasing number of new and untested chemicals that require proper risk evaluation for cancer. This coupled with the approach to reduce the animal usage in testing and the development of more molecular and cellular knowledge of the biological processes has put additional stress on developing modalities to properly perform cancer risk assessment. Although there is a tendency to streamline the process, it is important to note that proper risk evaluation is not easy and requires the input of multiple discipline and expertise. Understanding the mechanism(s) of chemical carcinogenesis in the context of the multistage model is important in GHYHORSLQJ VFLHQWLˡFDOO\ EDVHG KXPDQ ULVN HYDOXDWLRQ RI SRWHQWLDO FKHPical carcinogens. In considering carcinogen risk evaluations several concepts need to be addressed based on Bradford Hills criteria. The development of a mode of action framework 20 years ago was an important step in utilizing the Bradford hill approach to chemical risk assessment. It is important that we as scientists don’t default to poor science in an attempt to perform simpler and faster cancer risk assessment. The pubOLF DQG UHJXODWRUV LQ SDUWLFXODU QHHG WR KDYH FRQˡGHQFH WKDW WKH HYDOXation of cancer risk is founded in proper science. KWWSV GRL RUJ M WR[OHW

S4 Toxicology Letters 411S (2025) S02–S04 door-environment controls often deliver larger near-term health gains than uniform ambient measures, while combined strategies maximise equity by reducing exposures in disadvantaged groups. Outputs include GHFLVLRQ JUDGH LQWHUQDO GRVH DQG H˫HFW ELRPDUNHU PHWULFV PL[WXUH aware hazard indices and auditable uncertainty bounds suitable for regulatory uptake. Conclusions: The exposome becomes operational for regulators and public-health agencies when mechanistic dosimetry, discovery-oriented analytics and data-proximate causal inference are implemented under Good Exposome Practices and EHDS-aligned governance. Priorities LQFOXGH PL[WXUH UHDG\ 3%3. OLEUDULHV VWDQGDUGLVHG UHSRUWLQJ YDOLGDWLRQ URXWLQH FRPSXWH WR GDWD IRU FRQˡGHQWLDO GDWDVHWV DQG HPEHGGLQJ H[SRVRPH PHWULFV LQWR SUHYHQWLRQ WDUJHWV IRU YXOQHUDEOH SRSXODWLRQVੇ ² turning complex chemical realities into tractable, actionable and equitable protection. KWWSV GRL RUJ M WR[OHW

journal homepage: www.elsevier.com/locate/toxlet Toxicology Letters Contents lists available at ScienceDirect Toxicology Letters 411S (2025) Volume 411S, September 2025 ISSN 0378-4274 411S S1-S507 (2025) Abstracts of the 59th Congress of the European Societies of Toxicology (EUROTOX 2025) TOXICOLOGY ADDRESSES SOCIETY’S REAL LIFE RISKS FOR SUSTAINABLE HEALTH AND WELL BEING Athens, Greece, 14–17 September 2025 0378-4274 / © 2025 Published by Elsevier B.V. &XUUHQW UHJXODWRU\ SDUDGLJPV IRU WKH PDQDJHPHQW RI 2$ DUH QRW ˡW IRU SXUSRVH )RU ERWK H˫HFWLYH KXPDQ KHDOWK SURWHFWLRQ DQG DSSURSULate and proportionate regulation there is an important, yet unmet need, WKDW VXE W\SHV RI ZRUN UHODWHG DVWKPD FDQ EH DFFXUDWHO\ LGHQWLˡHG DQG FODVVLˡHG DQG WKDW FKHPLFDO UHVSLUDWRU\ DOOHUJHQV WKDW GULYH DOOHUJLF DVWKPD FDQ EH GL˫HUHQWLDWHG DFFRUGLQJ WR SRWHQF\ In my presentation I will address presently available strategies for the diagnosis and characterisation of asthma in the workplace, such as human health studies, clinical investigations and experimental approaches (structure-activity relationships, assessments of chemical reactivity, experimental animal studies and in vitro methods). Each of these approaches has limitations with respect to providing a clear discrimination between WEA and OA, and between AOA and IIOA. Against this background the need for improved characterisation of work-related asthma, in the context of more appropriate regulation is discussed. References [1] 3HPEHUWRQ 0$ $UWV -+( .LPEHU , ,GHQWLˡFDWLRQ RI WUXH FKHPLFDO respiratory allergens: current status, limitations and recommendations. Regul. Toxicol. Pharmacol. 147, 105568 KWWSV GRL RUJ M WR[OHW CEC01-03 The current biological understanding of the respiratory tract, the in vitro models available as well as their use 6 ੇ &RQVWDQW EpiThelix, Switzerland The main function of the human airway epithelium is to generate sterile atmosphere in the alveolar region where the gas exchange ocFXUV $V WKH ˡUVW OLQH RI GHIHQFH DJDLQVW DLUERUQH SDWKRJHQV WKH DLUZD\ epithelium acts as key barrier through mucociliary clearance and innate immune defence mechanisms. Airway epithelium is also an important immuno-regulator through production of key messengers and physical interactions with immune cells. Upon activation, respiratory epithelial cells react by producing pro-inflammatory cytokines, chemokines and metalloproteinases to recruit and activate immune cells such as neutrophils, basophils, or to initiate the adaptive immunity via dendritic cells. Interest in the use of 3D reconstituted human in vitro tissues (ALI cultures) is increasing in recent years for the study of respiratory diseases such as Asthma, Chronic Obstructive Pulmonary Disease (COPD), Bacterial and viral infections, etc. Genetic and epigenetic diversity in ALIs with single donors allow VWUDWLˡFDWLRQ DQG SDWLHQW VSHFLˡF SURˡOLQJ LQ WR[LFRORJ\ DQG GUXJ WHVW- &(& _ &KDOOHQJHV LQ WKH LGHQWLˡFDWLRQ of chemical respiratory allergens CEC01-01 The regulatory needs 6 ੇ&DVDWL EURL-ECVAM, Italy Respiratory sensitization poses a considerable threat to human health, especially in workplaces and during the use of consumer products. Consequently, the detection and evaluation of respiratory sensitizers are mandated by numerous chemical regulations designed to safeguard public health, encompassing pesticides, biocides, cosmetics, pharmaceuticals, medical devices, and industrial chemicals. Notably, within the European Union’s REACH framework, potent respiratory sensitizers are FODVVLˡHG DORQJVLGH RWKHU 6XEVWDQFHV RI 9HU\ +LJK &RQFHUQ 69+&V such as carcinogenic, mutagenic, or reproductive toxicants (CMRs), reˣHFWLQJ WKHLU HTXLYDOHQW OHYHO RI FRQFHUQ +RZHYHU SLQSRLQWLQJ JHQXLQH respiratory sensitizers, particularly low molecular weight (LMW) chemLFDOV SUHVHQWV D VLJQLˡFDQW KXUGOH DV QR R˥FLDOO\ UHFRJQL]HG DQG YDOLdated animal or in vitro tests exist to produce standardized data. Thus, assessments typically rely on a tailored, case-by-case approach that involves a thorough examination of available human and non-human data, XOWLPDWHO\ DLPLQJ WR GHˡQH VDIH H[SRVXUH OLPLWV 7KLV SUHVHQWDWLRQ ZLOO R˫HU D FRPSUHKHQVLYH RYHUYLHZ RI WKH VWLSXODWLRQV ZLWKLQ NH\ FKHPLFDO legislation and delve into the complexities associated with evaluating the diverse evidence used in respiratory sensitizer assessment. KWWSV GRL RUJ M WR[OHW CEC01-02 Chemical Respiratory Allergy: ,GHQWLˡFDWLRQ RI WUXH FKHPLFDO UHVSLUDWRU\ DOOHUJHQV - ੇ$UWV Nouryon, PSRA, Deventer, Netherlands See Pemberton et al. (2024): Asthma in the workplace (work-related asthma) is an important occupational health issue. It comprises two main subtypes: viz. pre-existing asthma which is exacerbated by work (work-exacerbated asthma or WEA) or asthma caused by work (occupational asthma or OA). The latter can be subdivided in non-allergic irritant-induced occupational asthma (IIOA) and in allergic occupational asthma (AOA). AOA may be fatal. Continuing Education Courses (CECs)

S6 Toxicology Letters 411S (2025) S05–S13 EXW DOVR 7K 7UHJV LPEDODQFH IRUP DQ H[WUHPH FRPSOH[ LQWHUDFWLYH network. Recent evidences reported alterations in miRNA expression in a variety of lung diseases, including allergic asthma. Several miR1$V KDYH EHHQ DVVRFLDWHG ZLWK DVWKPD DQG DLUZD\V LQˣDPPDWLRQ EXW WDUJHW LGHQWLˡFDWLRQ UHPDLQ QRW \HW GHWHUPLQHG IRU WKH PDMRULW\ RI WKH studies. Despite research for more than three decades, there are still no validated methods for the assessment of respiratory sensitizing potential of LMW compounds. The main idea of this project is based on the assessment of a new in vitro approach to better study and investigate the allergic asthma pathology. The central hypothesis of this project is that miRNAs play a key role in the activation and maintenance of the allergic asthma through the active involvement of the immune V\VWHP 7KH VSHFLˡF DLP RI WKLV SURMHFW WKDW LV HQWLUHO\ EDVHG RQ KXPDQ FHOOV LV WR LGHQWLI\ PL51$ SDWWHUQV DQG FRQVHTXHQWO\ ZKLFK VSHFLˡF targets are involved in the interaction between the respiratory system and the immune system in the allergic asthma disease. The project could be ideally divided in two parts: the in vitro part (Part I) and the human part (Part II). Part I – For the in vitro approach the human lung epithelial cells, namely Calu-3, will be exposed to 5 respiratory sensitizers (hexamethylen, methylene diphenyl, and toluene diisocyanate; ammonium hexachloroplatinate; trimellitic anhydride), 1 skin sensitizer (2,4-dinitrochlorobenzene) and 1 irritant (sodium dodecyl sulphate) through a liquid aerosols system (Cloud Alpha System – VITROCELL® Systems). A microRNA panels will be performed in control conditions and exposed conditions. A bibliographic research will be PDGH WR LQYHVWLJDWH PL51$V SRVVLEO\ LQYROYHG LQ DOOHUJLF DVWKPD DQG RU LPPXQH V\VWHP DFWLYDWLRQ GH UHJXODWLRQ 3DUW ,, ² LQ FROODERUDWLRQ with Dott. Liviero (Occupational Unit of Padova University) a broad miRNA evaluation in asthmatic patients will be conducted, through the analysis of miRNA expression in blood microvesicles and in exhaled breath condensate obtained from healthy and asthmatic patients. The translational potential of the project is due to the use of a primary cell culture model as well as human samples. Furthermore, implementation of miRNA patterns could be useful as prevention tool (biomarkers for diagnosis) of allergic asthma. CEC02 | Developmental Neurotoxicity (DNT): Bridging from Mammal to Cellular Behavior CEC02-01 Brief Session Introduction on DNT ( ੇ )ULWVFKH SCAHT, Switzerland No abstract has been submitted. KWWSV GRL RUJ M WR[OHW CEC02-02 Current regulatory (in vivo) neurotoxicity testing 3 ੇ *ROGVWHHQ Charles River Laboratories, Netherlands An overview will be given on the applicable guidelines and the implementation thereof in general toxicity and reproductive and developmental toxicity studies. The DNT endpoints and their methodology as well as the results they provide will be discussed, together with the FKDOOHQJHV OLPLWDWLRQV WKDW DUH IDFHG KWWSV GRL RUJ M WR[OHW ing. On the other hand, ALIs generated with a mixture of cells from several individuals give a snapshot of global reaction of a small population when exposed to a chemical compound. This talk will describe the in vitro upper and lower respiratory tract models currently available to simulate the structure and function of human lung epithelial tissues, such as organoids, lung-on-a-chip, transwell inserts ALI cultures. The use of these models for diverse applications will also be discussed, including the evaluation of the barrier IXQFWLRQ ORFDO WROHUDQFH DLUZD\ LQˣDPPDWLRQ VHQVLWL]DWLRQ DV ZHOO DV WKH UHVSLUDWRU\ GLVHDVHV OXQJ ˡEURVLV FDQFHUV HWF KWWSV GRL RUJ M WR[OHW CEC01-04 AOP and development of test methods to predict the respiratory sensitisation potential of substances 6 ( ੇ $QGHUVRQ &'& 1,26+ 86$ Asthma is one of the most prevalent lung diseases in developed countries and is induced by exposure to sensitizing agents. Respiratory sensitization is a complex immunological process that is a result of continued or long-term expose to agents which can eventually lead to hypersensitivity. Although respiratory hypersensitivity has been known for decades, there are currently no validated approaches availDEOH IRU WKH LGHQWLˡFDWLRQ RI VXVSHFW DJHQWV 7KLV LV ODUJHO\ GXH WR WKH GL˫HUHQW FODVVLˡFDWLRQV IRU UHVSLUDWRU\ VHQVLWL]HUV DV ZHOO DV FRPSOH[- ity of the response and the late manifestation of symptoms. Additionally, it has been challenging to make a clear distinction between respiratory reactions triggered by sensitization of the respiratory tract and those triggered by other factors, including type and duration of exposure and concurrent exposure to other agents that may amplify the symptoms. 7KH FDXVDO OLQNLQJ RI HYHQWV DW GL˫HUHQW OHYHOV RI ELRORJLFDO RUJDQization in adverse outcome pathway (AOP) concepts has evolved as important approach in chemical hazard and risk assessment. While WKLV KDV EHHQ FRQGXFWHG IRU VNLQ VHQVLWL]HUV H˫RUWV WR XQGHUVWDQG DQG DVVHVV WKH H˫HFW RI UHVSLUDWRU\ VHQVLWL]HUV KDYH EHHQ VWDJQDQW IRU RYHU a decade, and no AOP has been established. Due to the urgent need for accurate and reliable test methods for WKH LGHQWLˡFDWLRQ RI UHVSLUDWRU\ VHQVLWL]HUV YDULRXV WHVWLQJ PHWKRGV are being explored. This presentation will discuss the most recent information on respiratory sensitization and key events potentially relevant in the AOP concept. KWWSV GRL RUJ M WR[OHW CEC01-05 An integrated human-in vitro approach to explore the role of miRNAs in occupational asthma 9 ੇ *DOELDWL Università degli Studi di Milano, Pharmacological and Biomolecular Sciences, Milan, Italy Asthma resulting from sensitization of the respiratory tract to chemiFDOV DQG GHˡQHG DOOHUJLF DVWKPD LV DVVRFLDWHG ZLWK VLJQLˡFDQW PRUELGity, and is clearly an important health concern with serious clinical consequences. Occupational allergic asthma resulting from sensitization of the respiratory tract to chemicals is clearly an important health concern with serious clinical consequences. The main pathological feature of allergic asthma is due to the complex interactions between LPPXQH FHOOV DQG LPPXQRORJLFDO PHGLDWRUV %DVLFDOO\ 7K 7K UDWLR imbalance is one of the essential immunological mechanisms of asthma

S7 Toxicology Letters 411S (2025) S05–S13 cokinetics. A strategy whereby PBPK models integrating in vitro data DUH YHULˡHG DJDLQVW SUHFOLQLFDO LQ YLYR SKDUPDFRNLQHWLF GDWD SULRU WR prediction for humans will be described and compared to empirical methods. This will be supported by data collected in Roche projects LOOXVWUDWLQJ WKH EHQHˡWV DQG KLJKOLJKWLQJ JDSV DQG DUHDV ZKHUH WKH strategy can fail. Several illustrative case studies will be shared. The linking of PK predictions to pharmacodynamic models for a model based estimation of safe starting doses will also be compared to empirical Maximum Recommended Starting Dose (MRSD) calculations. PBPK to aid the design of preclinical toxicology studies for clinical GHYHORSPHQW FRPSRXQGV ZLOO EULHˣ\ EH FRYHUHG DV ZHOO DV DSSOLFDWLRQV associated with clinical safety such as : prediction of pharmacokinetic YDULDELOLW\ HYDOXDWLRQ RI GUXJ GUXJ LQWHUDFWLRQ ULVN DQG ˡUVW LQ SHGLatric studies. References [1] Jones HM, Parrott N, Jorga K, Lavé T. A novel strategy for physiologically based predictions of human pharmacokinetics. Clin Pharmacokinet. 2006;45(5):511-42. PMID: 16640456. KWWSV GRL RUJ [2] Miller, N.A., Reddy, M.B., Heikkinen, A.T. et al. Physiologically Based Pharmacokinetic Modelling for First-In-Human Predictions: An Updated Model Building Strategy Illustrated with Challenging Industry Case Studies. Clin Pharmacokinet 58, 727–746 (2019). KWWSV GRL RUJ V [3] Parrott N, Delporte M, Lave T, Peck R, Ricci B. Physiologically based pharmacokinetic (PBPK) predictions for entry into human. An analysis of small PROHFXOH GHYHORSPHQW FDQGLGDWHV DW +R˫PDQQ /D5RFKH ² &OLQ Pharmacol Ther. 2017;101(Suppl 1):S82. [4] Weber, Cornelia & Delporte, Marie-Laure & Peck, Richard & NJ, Parrot & Lavé, Thierry & B, Ricci. (2017). Dose selection in Entry into Human (EIH) studies: Learnings from a retrospective survey on EiH studies with small molecules FRQGXFWHG EHWZHHQ DQG DW +R˫PDQ /D 5RFKH KWWSV GRL RUJ M WR[OHW CEC03-03 Case studies of PBPK enabled safety assessments - ੇ3OHW] ) +R˫PDQQ /D 5RFKH 6ZLW]HUODQG Accurate exposure assessment is fundamental to ensuring safety in drug development. Physiologically based (pharmaco-)kinetic (PB(P)K) and organ-level mechanistic models have emerged as pivotal tools in predicting exposure over time for a target organ or tissue, in particular IRU VPDOO PROHFXOHV 7KHVH PRGHOV HQDEOH VLPXODWLRQV DFURVV GL˫HUHQW dosing scenarios, facilitate interspecies extrapolation, help assess interindividual variability, and support in vitro to in vivo extrapolation (IVIVE). Overall, these approaches greatly promote the integration and contextualisation of in vitro data and, as a result, enhance the relevance and applicability of in vitro ˡQGLQJV WR UHDO ZRUOG ELRORJLFDO V\VWHPV Incorporating toxicologically relevant mechanistic in vitro data enables WKH TXDQWLWDWLYH HYDOXDWLRQ RI H[SRVXUH H˫HFW UHODWLRQVKLSV ZLWKLQ WR[- icological pathways, which are otherwise challenging to assess, thereby improving the accuracy of safety assessments. In addition to evaluating the toxicokinetics of a compound, toxicodynamic components may be added to a PB(P)K or organ-level mechDQLVWLF PRGHO WR LQYHVWLJDWH KRZ H[SRVXUH DQG D WR[LF H˫HFW DUH UHODWHG DQG KRZ DQ DGYHUVH H˫HFW ZRXOG HYROYH ZLWK YDU\LQJ H[SRVXUH RYHU time. If data and knowledge of the mechanism of action allow for this, such approaches have the potential to greatly enhance the interpretation of in vivo toxicity testing outcomes, in particular in the context of GHOD\HG DGYHUVH H˫HFWV ,Q FRPSOH[ RUJDQ V\VWHPV LQ ZKLFK VHYHUDO PHFKDQLVPV W\SLFDOO\ FRQWULEXWH WR DQ RUJDQ OHYHO H˫HFW WKHVH PRGHOV can help to dissect individually contributing factors. For instance, in the kidneys, damage or impairment of the vascular system may induce D VHFRQGDU\ DGYHUVH H˫HFW RQ UHQDO IXQFWLRQ WKURXJK D SULPDU\ GDPDJH of the renal vasculature. CEC02-03 EFSA perspective on DNT testing for pesticides , ੇ0DQJDV EFSA, Italy No abstract has been submitted. KWWSV GRL RUJ M WR[OHW CEC02-04 Science and use of the current DNT in vitro battery ( ੇ )ULWVFKH SCAHT, Switzerland KWWSV GRL RUJ M WR[OHW CEC02-05 Bridging across cell-based assays/simple model organisms, rodent behavioral studies and human disease 3 - ੇ/HLQ UC-Davis, USA No abstract has been submitted. KWWSV GRL RUJ M WR[OHW CEC03 | Using quantitative modeling to predict exposures and support safety assessment CEC03-01 Introduction to PBPK modeling for exposure predictions $ ੇ 2OLYDUHV 0RUDOHV Eli Lilly and Company, Indianapolis, USA This lecture will provide an introduction to the use of physiologically-based pharmacokinetic (PBPK) modeling as a tool to predict the pharmacokinetics of novel small molecule therapeutics in both humans and non-clinical safety species, such as animals. This modeling helps SUHGLFW WKH DQWLFLSDWHG WKHUDSHXWLF H[SRVXUH GRVHV DQG WKH FRUUHVSRQGLQJ VDIHW\ PDUJLQV WR HQDEOH GHFLVLRQ PDNLQJ EHIRUH ˡUVW LQ KXPDQ trials. The lecture will cover an introductory component to the concept of PBPK, its usefulness in safety prediction, and provide examples of a step-by-step estimation of safety margins, which is common practice in the pharmaceutical industry. KWWSV GRL RUJ M WR[OHW CEC03-02 How PBPK modeling can be used to enable safety assessments for FIM studies 1 ੇ3DUURWW ) +R˫PDQQ /D 5RFKH /WG 6ZLW]HUODQG This presentation will build on the previous introductory lecture to extend to the application of PBPK for prediction of clinical pharma-

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