Toxicology letters最新文献

{"title":"CEC06-05 Fentanyloïds","authors":"C. Lyphout","doi":"10.1016/j.toxlet.2025.07.040","DOIUrl":"10.1016/j.toxlet.2025.07.040","url":null,"abstract":"<div><div>Fentanyl analogs – structurally related synthetic opioids within the 4-anilidopiperidine class – have become increasingly implicated in the rising incidence of opioid-related overdose deaths. These compounds, which include acetylfentanyl, butyrylfentanyl, and furanylfentanyl, are illicitly manufactured and trafficked, often sold as heroin or counterfeit prescription pills, leading to unintentional and frequently fatal exposures.</div><div>Fentanyl analogs exhibit high potency and rapid central nervous system penetration due to their lipophilicity. While they share core structural features with fentanyl, even minor chemical modifications can lead to substantial changes in receptor binding affinity, potency, and duration of action. These compounds produce classic opioid toxidromes, including respiratory depression, bradycardia, and miosis, which can be reversed with naloxone. However, due to their high potency, standard naloxone dosing may be insufficient, and higher initial doses (≥2 mg) are recommended. Law enforcement data show increasing seizure rates of various analogs, reflecting both high demand and the ease with which these compounds are synthesized and distributed. The clandestine nature of their production, coupled with a lack of clinical data, complicates diagnosis, treatment, and regulation.</div><div>Fentanyl analogs represent a relevant component of the opioid epidemic, distinguished by their high potency, rapid onset, and potential to cause fatal overdose at low doses. Their presence in the illicit drug supply steers the need for improved detection methods, targeted public health responses, and the development of effective harm-reduction and regulatory strategies.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"411 ","pages":"Page S13"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CEC05-03 EU Legislations where Regulatory Toxicology is applied: The CLP Example (Theoretical lecture)","authors":"C. Tsitsimpikou","doi":"10.1016/j.toxlet.2025.07.032","DOIUrl":"10.1016/j.toxlet.2025.07.032","url":null,"abstract":"<div><div>The Classification, Labelling and Packaging (CLP) Regulation is based on the United Nations’ Globally Harmonised System (GHS). CLP ensures that the hazards of chemicals, recognised via the classification process, are clearly communicated, once placed on the market, to workers and consumers throughout the supply chain in the European Union, regardless their quantity. Manufacturers, importers or downstream users have to (self)classify and label hazardous substances and mixtures based on the identified hazards thereof. Hazards are identified by comparing all available data on hazard information with the explicit criteria laid down in CLP. If no data are available, tests should be performed according the REACH Regulation, the OECD principles and any internationally recognised and validated methods. Any new animal tests required, should comply with the provisions for the protection of laboratory animals (Directive 2010/63/EU). Alternative methods are being developed to replace the use of animals, reduce the number of animals in a test, or refine the procedures to make them less painful or stressful to the animals under study (3Rs principle). The classification is based on the hazardous properties of a substance or mixture and not on the likelihood of exposure and risk considerations. Self-classification describes the toxicological evaluation of a chemical substance or mixture regarding physical, health and/or environmental hazards made by manufacturers, importers or downstream users. Hazard classes and categories are described in the CLP and in 2023 new hazard classes were identified on endocrine disrupting properties and persistent, bioaccumulative, toxic and mobile properties for the environment. Especially for hazards of highest concern [carcinogenicity, mutagenicity, reproductive toxicity (CMR) and respiratory sensitisers], classification and labelling should be harmonised throughout the EU to ensure adequate risk management. This is done via inclusion of a substance classification in Annex VI of the CLP Regulation and it is mandatory for all. Once the hazardous properties of a substance or mixture have been identified and classification is assigned, this information must be communicated to the other actors in the supply chain. The labeling requirements set by CLP ensure the safe use and supply of hazardous substances and mixtures. Labeling elements include among others, pictograms, signal words and standard statements for hazard, prevention, response, storage and disposal, for every hazard class and category, along with specific general packaging standards. In 2017, a new Annex VIII was added to the CLP Regulation, implementing harmonised information requirements for notifications used for emergency health response (Poison Centres). Enforcement of CLP Regulation, which is a national responsibility in EU, entails a range of actions that national authorities initiate to verify the compliance of the duty holders with the legislation.</div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"411 ","pages":"Page S11"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CEC01-03 The current biological understanding of the respiratory tract, the in vitro models available as well as their use","authors":"S. Constant","doi":"10.1016/j.toxlet.2025.07.013","DOIUrl":"10.1016/j.toxlet.2025.07.013","url":null,"abstract":"<div><div>The main function of the human airway epithelium is to generate sterile atmosphere in the alveolar region where the gas exchange occurs. As the first line of defence against airborne pathogens, the airway 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 <em>in vitro</em> 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.</div><div>Genetic and epigenetic diversity in ALIs with single donors allow stratification and patient specific profiling in toxicology and drug testing. 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.</div><div>This talk will describe the <em>in vitro</em> 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 function, local tolerance, airway inflammation, sensitization, as well as the respiratory diseases (lung fibrosis, cancers), etc.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"411 ","pages":"Pages S5-S6"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S03-04 Induction of genomic damage by natural plant constituents: development of genotoxicity testing strategies","authors":"H. Stopper ,&nbsp;S. Pfuhler ,&nbsp;S. Smith-Roe ,&nbsp;J.T. MacGregor ,&nbsp;N. Mei ,&nbsp;C.A. Mitchell ,&nbsp;M. Embry ,&nbsp;J. van Benthem ,&nbsp;E. Zeiger ,&nbsp;K.L. Witt","doi":"10.1016/j.toxlet.2025.07.053","DOIUrl":"10.1016/j.toxlet.2025.07.053","url":null,"abstract":"<div><div>Thirteen botanicals selected by the Botanical Safety Consortium as data-rich case studies were tested in four standard genotoxicity assays covering mutation and chromosome damage endpoints. The goal of this exercise was to determine whether the results from the four selected assays provided an assessment of genotoxicity consistent with the existing data for each case study, thereby supporting their use in generating genotoxicity profiles of botanicals. The four assays included the bacterial reverse mutation assay (Ames test), the <em>in vitro</em> micronucleus (MN) assay in TK6 cells and in HepaRG cells, and the ToxTrackerÒ assay. The Ames and MN tests were conducted in accord with their respective OECD Test Guidelines.</div><div>Based on existing information for the 13 botanicals tested, aristolochia, comfrey, green tea, and milk thistle were expected to be positive in the Ames test and/or were expected to induce MN. Our results were consistent with the existing literature. Four Ames-positive botanicals were identified. The MN test in TK6 cells, conducted +/– S9, identified one botanical as positive while the MN test conducted using metabolically competent HepaRG cells identified four botanicals as positive or equivocal. ToxTrackerÒ assays identified four positives, consistent with previously published data.</div><div>Our results suggest that currently available <em>in vitro</em> genotoxicity assays are suitable for testing botanicals. Currently, we are evaluating all the data to determine a recommended testing scheme. In addition, our test data will be compared with <em>in silico</em> predictions of genotoxicity that were made for each botanical based on their identified constituents to determine how to combine <em>in silico</em> data, <em>in vitro</em> test data, and human exposure data to produce a comprehensive assessment of genotoxicity.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"411 ","pages":"Page S17"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S06-01 Setting the scene: Dose level selection for development and reproductive toxicity studies","authors":"F. Sewell","doi":"10.1016/j.toxlet.2025.07.061","DOIUrl":"10.1016/j.toxlet.2025.07.061","url":null,"abstract":"<div><div>Following advice on dose selection issued by the European Chemicals Agency (ECHA) in 2022 <span><span>^[1]</span></span> for reproductive toxicity studies conducted under REACH, this presentation will cover the implications of this advice from both a 3Rs (Replacement, Reduction and Refinement of animals in research) and scientific perspective. The ECHA advice followed an evaluation of existing extended one generation reproductive toxicity (EOGRT) studies with respect to design, conduct and toxicological findings, and concerns that potential hazardous effects could be missed due to inadequate dosing. The resulting advice specified that the highest dose tested should <em>“demonstrate an aim to induce clear evidence of reproductive toxicity without excessive other toxicity and severe suffering in parental animals (e.g. prostration, severe inappetence (lack of appetite), excessive mortality as signs of severe suffering) that would compromise the interpretation of co-occurring reproductive effects.”</em> These recommendations have been evaluated by a number of expert groups, including the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) Task Force on Dose Selection <span><span>^[2]</span></span>, in relation to advice in existing Organisation for Economic Cooperation and Development (OECD) test guidelines and guidance document, including on humane endpoints and selection of the maximum tolerated dose. Other considerations relevant to dose selection include factors such as maternal clinical signs of toxicity, food consumption/nutritional intake, clinical chemistry parameters, circulatory/cardiovascular changes, target organ toxicity, maternal stress and toxicokinetics. The results of these evaluations, as well as recent discussions with ECHA and the wider scientific community (including at the EUROTOX 2024 satellite session ^[3]) which aimed to better understand the advice, will be presented, recognising a shared goal of ensuring a high level of human health protection whilst balancing scientific pragmatism and impact on animal welfare.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"411 ","pages":"Pages S19-S20"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S01-02 The Role of the Microbiome in Regulating Telomerase Activity: A New Frontier in Cellular Aging and Health","authors":"M. Biazzo","doi":"10.1016/j.toxlet.2025.07.043","DOIUrl":"10.1016/j.toxlet.2025.07.043","url":null,"abstract":"<div><div>Emerging evidence suggests a dynamic and bidirectional interplay between the gut microbiome and telomerase activity, with significant implications for systemic aging and host health. Telomerase, the enzyme responsible for maintaining telomere length, plays a central role in cellular senescence and regenerative capacity. Recent human and animal studies indicate that gut microbiota can modulate telomerase activity via multiple pathways, including oxidative stress, mitochondrial health, and the production of microbial metabolites such as shortchain fatty acids. Conversely, telomere dysfunction in the gut epithelium may disrupt mucosal integrity, trigger inflammation, and promote dysbiosis, creating a feedback loop that accelerates aging. A longitudinal human study has shown that mitochondrial energetic capacity, a factor influenced by chronic stress and potentially by the gut microbiota, predicts telomerase activity and telomere maintenance over time. Complementary experimental models in zebrafish and mice have demonstrated that gut-specific telomerase activation can restore microbial diversity, reduce systemic inflammation, and extend lifespan. Together, these findings support the novel concept that telomerase regulation is not solely intrinsic, but may be shaped by the gut microbial environment. This presentation will explore how targeting the microbiota–telomerase axis may offer new strategies to slow aging processes and improve healthspan.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"411 ","pages":"Page S14"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S01-03 The Impact of Lifestyle on Telomere Length: Exploring the Effects of smoking, vaping and alcohol consumption","authors":"A. Vlasceanu","doi":"10.1016/j.toxlet.2025.07.044","DOIUrl":"10.1016/j.toxlet.2025.07.044","url":null,"abstract":"<div><div>Healthy ageing is promoted by the adherence to beneficial habits and activities. Nonetheless, there is limited knowledge on the extent to which – age, sex, or race and ethnicity influence the correlations between lifestyle and behavioural factors such as smoking, vaping, and alcohol intake and relative telomere length (RTL), a potential biomarker of ageing.</div><div>Telomeres are protective DNA-protein complexes located at the ends of chromosomes that diminish in length with each cell division, and toxicological exposures might accelerate this reduction, causing genomic instability.</div><div>Telomere length (TL) is thus recognized as a biomarker of cellular aging and cumulative DNA damage relevant to toxicology. Recent discoveries demonstrate the impact of smoking, vaping, and alcohol intake on telomere length through pathways of oxidative stress, inflammation, and DNA damage. Cigarette smoking is consistently associated with shortened TL, as smokers have significantly shorter leukocyte telomeres than non-smokers. Tobacco smoking produces reactive oxygen species that induce telomeric DNA breakage and persistent inflammation, accelerating telomere degradation. Recent research suggests that electronic cigarette vaping may also lead to telomere erosion. E-cigarette aerosols have less hazardous byproducts than tobacco smoke; yet, can still generate oxidative stress. Cellular studies indicate that e-cigarette vapours cause DNA damage and telomere dysfunction similar to that of conventional smoking. Therefore, vapers may undergo telomere shortening similar to smokers, but the degree is still being investigated. Chronic excessive alcohol consumption is linked to a decrease in telomere length. Individuals with alcohol use disorders have significantly reduced telomere length compared to healthy controls, a phenomenon likely ascribed to oxidative stress and chronic inflammation generated by ethanol, while moderate consumption without misuse seems to exert negligible impact on telomere length.</div><div>These findings highlight the toxicological relevance of telomere dynamics as an indicator of lifestyle-related cellular ageing and emphasise the necessity of ongoing studies to determine causality and guide public health actions.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"411 ","pages":"Page S15"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S13-04 Skin sensitization potency assessment: Make full use of NAM data to conduct quantitative risk assessment","authors":"A. Natsch","doi":"10.1016/j.toxlet.2025.07.086","DOIUrl":"10.1016/j.toxlet.2025.07.086","url":null,"abstract":"<div><div>Great progress has been made over the last 15 years in the development, validation and regulatory acceptance of New Approach Methods for skin sensitization hazard assessment . However, even in the hazard-assessment driven regulatory landscape of Europe, toxicology remains a quantitative science and determining safe use levels is the cornerstone of any toxicological assessment. Thus in the past years, the focus has shifted to use NAM data in a more granular way and to harness quantitative dose-response data to derive a Point of Departure (PoD) for risk assessment. This requires on the one hand a high-quality set of <em>in vivo</em> reference data and a comprehenisve set of NAM data on the other hand. Thus, a brief summary of recent data curation efforts is given. Different approaches for data integration can then be used to predict a point of departure based on NAM data, and both a deterministic linear regression approach and a probabilistic Bayesian approach have been proposed and submitted to OECD approval. These approaches will be reviewed and compared along with other emerging approaches. Overall similar outcomes with different mathematical approaches are achieved when the same input data are used, and key differences are often in the prediction target and the treatment of missing input data. All these NAM approaches indicate a significant progress in potency assessment and it is now possible to derive a PoD without animal testing. Often the different NAM approaches are even better correlated to each other than to the <em>in vivo</em> data. This can both indicate (i) insufficient coverage of the Adverse Outcome Pathway or (ii) similar gaps in the applicability domain of different methods or (iii) significant residual uncertainty in the <em>in vivo</em> dataset, which cannot be overcome with further NAM development. These different possibilities wil be briefly discussed to give a status for NAMs for skin sensitization potency assessment and an outlook for potential improvements.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"411 ","pages":"Page S28"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CEC03-01 Introduction to PBPK modeling for exposure predictions","authors":"A. Olivares-Morales","doi":"10.1016/j.toxlet.2025.07.020","DOIUrl":"10.1016/j.toxlet.2025.07.020","url":null,"abstract":"<div><div>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 predict the anticipated therapeutic exposure/doses and the corresponding safety margins to enable decision-making before first-in-human 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.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"411 ","pages":"Page S7"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CEC03-05 Integrated PBPK/QST modeling to inform the safety assessmentpractical hands-on examples across multiple disease areas","authors":"S. Schaller,&nbsp;P. Balazki","doi":"10.1016/j.toxlet.2025.07.024","DOIUrl":"10.1016/j.toxlet.2025.07.024","url":null,"abstract":"<div><div>Building upon the foundational lectures on Physiologically Based Pharmacokinetic (PBPK) modeling and its integration with Quantitative Systems Toxicology (QST), this final session culminates in a practical demonstration of an advanced, modular approach to safety assessment. We will introduce the concept of a “Quantitative Ecosystem” designed for Next Generation Risk Assessment (NGRA). This ecosystem leverages modular PBPK-QST platforms, exemplified by the open-source Open Systems Pharmacology (OSP) Suite (www.open-systems-pharmacology.org <span><span>^[1]</span></span>), to enhance and streamline toxicological evaluations.</div><div>This presentation will feature a software demonstration focusing on how the OSP Suite facilitates this integrated and modular ecosystem. You will see how it supports the seamless development, validation, and deployment of PBPK and QST models tailored for safety applications. We will illustrate its power through practical, hands-on examples relevant to NGRA, including:\u0000\t\t\t\t<ul><li><span>•</span><span><div>A <strong>Thyroid PBPK-QST/quantitative Adverse Outcome Pathway (qAOP) platform</strong> for the risk assessment of thyroid disruptors.</div></span></li><li><span>•</span><span><div>A <strong>DILI (Drug-Induced Liver Injury) platform</strong> designed to assess and predict potential liver injury.</div></span></li></ul></div><div>The session will highlight how key features of the OSP Suite, such as its continuously evolving model libraries (PK-Sim for PBPK, MoBi for QST modules), model modularity, reusability, and pathways towards automated qualification, contribute to more robust, transparent, reproducible, and efficient safety decision-making. This demonstration will directly complement and set the stage for the hands-on exercises where participants will utilize the OSP software to explore model parameterization and predict safety risks.</div></div><div><h3>Learning Objectives for this Presentation:</h3><div>Upon completion of this session, participants will be able to:\u0000\t\t\t\t<ul><li><span>•</span><span><div>Understand the “Quantitative Ecosystem” concept and its application to modular PBPK-QST in safety and Next Generation Risk Assessment.</div></span></li><li><span>•</span><span><div>Recognize how the Open Systems Pharmacology (OSP) Suite and its components (e.g., PK-Sim, MoBi) enable this modular and integrated approach.</div></span></li><li><span>•</span><span><div>Witness practical software applications for NGRA, specifically for assessing thyroid disruption and Drug-Induced Liver Injury.</div></span></li><li><span>•</span><span><div>Appreciate how modularity, model reusability, and features supporting automated qualification can enhance the robustness, transparency, and efficiency of safety evaluations.</div></span></li></ul></div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"411 ","pages":"Page S8"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}