Toxicology letters最新文献

{"title":"CEC05-06 Key endpoint considerations (Hands-on activity)","authors":"G. Kass","doi":"10.1016/j.toxlet.2025.07.035","DOIUrl":"10.1016/j.toxlet.2025.07.035","url":null,"abstract":"<div><div>No abstract has been submitted.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"411 ","pages":"Page S12"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009909","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":"S01-01 Exposomics and telomeres","authors":"E. Renieri ,&nbsp;D.A. Sarigiannis ,&nbsp;A. Tsatsakis","doi":"10.1016/j.toxlet.2025.07.042","DOIUrl":"10.1016/j.toxlet.2025.07.042","url":null,"abstract":"<div><div>Telomeres, the protective caps at the ends of chromosomes, serve as sensitive indicators of biological aging and cumulative environmental burden. The link between the exposome – the totality of environmental exposures from conception onwards – and telomere biology highlights telomere length and dynamics as biomarkers of effect and aging.</div><div>Environmental exposures such as air pollution, heavy metals, dietary patterns, and psychosocial stressors are consistently associated with telomere attrition. Mechanistic pathways include oxidative stress, inflammation, mitochondrial dysfunction, and epigenetic modifications, all of which contribute to telomere instability. Telomeres reflect the combined influence of external exposures and individual susceptibility, forming a molecular interface between environment and health outcomes.</div><div>Telomere length functions as both a genetic and metabolic biomarker for human aging. Shortened telomeres are linked to increased risk of chronic diseases including cardiovascular disease, cancer, metabolic disorders, and neurodegenerative conditions. In real-life exposure scenarios, telomere length can support the evaluation of long-term biological effects through Real-Life Risk Simulation (RLRS) models that account for low-dose, mixed exposures.</div><div>Associations between lifestyle factors and telomere length further support its relevance in population-based studies. Nutritional status, physical activity, and smoking influence telomere maintenance, with evidence pointing to protective effects of the Mediterranean diet and antioxidant intake.r</div><div>Positioning telomere dynamics within the exposome framework allows for a more integrated understanding of exposure-related health effects, aging processes, and disease risk. Telomere length provides a robust, quantifiable endpoint for advancing environmental health research and guiding preventive strategies.</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":"145009914","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":"CEC01-04 AOP and development of test methods to predict the respiratory sensitisation potential of substances","authors":"S.E. Anderson","doi":"10.1016/j.toxlet.2025.07.014","DOIUrl":"10.1016/j.toxlet.2025.07.014","url":null,"abstract":"<div><div>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 available for the identification of suspect agents. This is largely due to the different classifications for respiratory sensitizers, as well as complexity 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.</div><div>The causal linking of events at different levels of biological organization in adverse outcome pathway (AOP) concepts has evolved as important approach in chemical hazard and risk assessment. While this has been conducted for skin sensitizers, efforts to understand and assess the effect of respiratory sensitizers have been stagnant for over a decade, and no AOP has been established.</div><div>Due to the urgent need for accurate and reliable test methods for the identification of respiratory sensitizers, various testing methods are being explored. This presentation will discuss the most recent information on respiratory sensitization and key events potentially relevant in the AOP concept.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"411 ","pages":"Page S6"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010831","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":"S14-03 Comparison of Metabolism and Transport of Thiabendazole in Human and Rat In vitroModels","authors":"O. KLatt ,&nbsp;C. Gendre ,&nbsp;N. Hager ,&nbsp;U. Deppenmeier ,&nbsp;E. Dubreil ,&nbsp;J. Henri ,&nbsp;L. Hegarat ,&nbsp;S. Moco ,&nbsp;P. Jennings ,&nbsp;A. Wilmes","doi":"10.1016/j.toxlet.2025.07.089","DOIUrl":"10.1016/j.toxlet.2025.07.089","url":null,"abstract":"<div><h3>Introduction:</h3><div>Thiabendazole (TBZ) is a food preservative, anti-fungal agent and anthelmintic drug which prevents the polymerization of beta-tubulins. Its major metabolite 5-hydroxy-thiabendazole (5-OH-TBZ) has been found in the urine of over 90% of the Swedish population between 2000–2017. Traditionally human health risk assessment is conducted <em>in vivo</em>, but there are indications that TBZ is only hepatotoxic in rats while being hepato- and nephrotoxic in mice and humans. In human liver microsomes it has been shown that the major metabolite 5-OH-TBZ can undergo metabolic activation to form nephrotoxic molecules. Organic cation transporter (OCT) is believed to be involved in the uptake in the proximal tubule cells. TBZ is first metabolized by CYP1A2 in the liver and then further metabolized by UGT, SULT and GST.</div></div><div><h3>Aims:</h3><div>We aim to investigate interspecies differences in the absorption, distribution, metabolism and excretion (ADME) of TBZ in liver, kidney and gut microbiome <em>in vitro</em> systems using a tiered approach.</div></div><div><h3>Materials and Methods:</h3><div><em>In vitro</em> models including human and rat renal subcellular fractions, RPTEC/TERT1 cells, human and rat primary hepatocytes and human gut microbiome samples were exposed to TBZ or 5-OH-TBZ at different timepoints. The formation of different metabolites over time was explored using LC-MS. Additionally the renal transporter involved in the uptake of TBZ will be studied using suitable OCT inhibitors and quantified by transported TBZ.</div></div><div><h3>Results and Discussion:</h3><div>Exposure of 99 μM TBZ induced thioredoxin reductase 1 (TXNRD1) in RPTEC/TERT1 after 24 h exposure. Kinetic experiments in RPTEC/TERT1 and primary hepatocytes were performed with non-toxic maximum concentrations of 10 μM TBZ. Phase I metabolite 5-OH-TBZ was detected in rat liver microsomes. Phase II 5-OH-glucuronide formation was detected in human and rat renal microsomes. There was no 5-OH-sulfate measured in human and rat renal cytosol. Additionally, TBZ does not seem to be metabolized by the human gut microbiome.</div></div><div><h3>Conclusion:</h3><div>Phase I and II metabolites of TBZ were detected in human and rat liver and kidney <em>in vitro</em> models. The experimental data will be integrated into physiologically based kinetic (PBK) models. This will help to improve these <em>in silico</em> models and lead to more accurate xenobiotic human health risk assessment.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"411 ","pages":"Pages S28-S29"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011058","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":"S11-04 Using in vitro methods to predict respiratory sensitization potentials of industrial chemicals","authors":"A. Gutleb","doi":"10.1016/j.toxlet.2025.07.078","DOIUrl":"10.1016/j.toxlet.2025.07.078","url":null,"abstract":"<div><div>No abstract has been submitted.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"411 ","pages":"Page S25"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011068","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":"S14-02 Predicting lactation risk: an integrated modelling approach for NGRA across different species","authors":"L. Lautz","doi":"10.1016/j.toxlet.2025.07.088","DOIUrl":"10.1016/j.toxlet.2025.07.088","url":null,"abstract":"<div><div>No abstract has been submitted.</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":"145011057","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":"CEC06-01 Synthetic cannabinoids and semi-synthetic cannabinoids: understanding the acute toxicity (harms) related to these substances","authors":"D.M. Wood","doi":"10.1016/j.toxlet.2025.07.036","DOIUrl":"10.1016/j.toxlet.2025.07.036","url":null,"abstract":"<div><div>Cannabis is the mostly commonly used drug in Europe. In the European Drug Report 2024: Trends and Developments published by the European Union Drug Agency (EUDA) it was reported that last approximately 15.1 million EU residents aged 15 to 34 years had used cannabis in the last year and that 3.7 million adults aged 15 to 64 years old use cannabis on a daily or almost daily basis.</div><div>By the end of 2023, the EUDA was monitoring over 950 new psychoactive substances, and largest group of substances being monitored are the synthetic cannabinoids (previously known as the synthetic cannabinoid receptor agonists). These substances have been available in Europe since the early 2000s, although significant reports of use and acute harms did not start until the late 2000s when they started to be marketed as “Spice”. Initially these synthetic cannabinoids were structurally related to Δ9-tetrahydrocannabinol (the primary active compound in naturally occurring cannabis), but over time they structural similarity has decreased as they have evolved to evade national and international control mechanisms. The toxicity of these compounds initially appeared to be similar to that seen with cannabis, and was largely neuropsychiatric features; however, as they have evolved the toxicity has changed with increasing stimulant (agitation, tachycardia, hypertension) and neurological (seizures, coma) toxicity.</div><div>In 2022, the semi-synthetic cannabinoid, hexahydrocannabinol (HHC), was identified in Europe in May 2022, and since then there have been a number of additional semi-synthetic cannabinoids detected in Europe (for example HHC acetate, hexahydrocannabiphorol and tetrahydrocannabidiol). The majority of these compounds at this time appear to be produced from cannabidiol extracted from low-THC cannabis. Alongside the detection of these substances, there are increasing reports of acute toxicity (harms) related to their use.</div><div>This session will review the acute toxicity (harms) of the synthetic cannabinoids in detail, and provide an insight in the current information of the potential issues related to the semi-synthetic cannabinoids.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"411 ","pages":"Page S12"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009910","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":"S01-04 Oxidative stress and telomeres in aging and longevity","authors":"G. Koliakos","doi":"10.1016/j.toxlet.2025.07.045","DOIUrl":"10.1016/j.toxlet.2025.07.045","url":null,"abstract":"<div><div>No abstract has been submitted.</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":"145009917","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":"S02-01 Probabilistic Risk Assessment in Practice","authors":"A. Maertens","doi":"10.1016/j.toxlet.2025.07.046","DOIUrl":"10.1016/j.toxlet.2025.07.046","url":null,"abstract":"<div><div>Recent developments in computational methods and <em>in vitro</em> models have created opportunities to enhance traditional toxicological risk assessment through probabilistic approaches that better reflect biological reality. Modern toxicology now recognizes that biological perturbations caused by chemicals are an inherently stochastic rather than deterministic processes. From initial molecular interactions to cellular signaling disruption, loss of homeostasis, organ dysfunction, and systemic disease, each stage involves probabilistic events rather than a linear cascade. This fundamental biological understanding necessitates a shift in regulatory approaches to hazard assessment. Probabilistic exposure assessments complement this approach by characterizing the full range of potential exposure scenarios across populations, rather than relying on single point estimates or depending on worst-case assumptions to be fully protective. Moreover, it is critical for regulators to distinguish between the full spectrum of assessment outcomes: high-confidence predictions of low risk that may justify reduced testing requirements, high-confidence predictions of high risk that warrant immediate regulatory action, low-confidence predictions suggesting uncertain risk that require additional scrutiny, and knowledge gaps that require additional data. When data gathering is warranted, regulatory toxicology needs to move away from a checklist approach and develop methods to prioritize data by thinking in terms of a “value-of-information” approach to mitigate uncertainty. How can regulatory frameworks adapt a probabilistic perspective? Key aspects include: (1) transitioning from categorical classifications to dose-dependent probability distributions; (2) establishing confidence thresholds for data-poor substances; (3) developing validation protocols that explicitly model biological variability; (4) addressing expertise gaps within regulatory agencies, especially in regards to uncertainty in artificial intelligence based models; and (5) creating standardized approaches for communicating biological uncertainty in regulatory contexts.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"411 ","pages":"Pages S15-S16"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009918","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":"S02-02 Integration of Mechanistic Knowledage and Various Data within quantitative Adverse Outcome Pathways to Faciliate Risk Assessment of Human Health Concerns","authors":"S. Schaller","doi":"10.1016/j.toxlet.2025.07.047","DOIUrl":"10.1016/j.toxlet.2025.07.047","url":null,"abstract":"<div><div>No abstract has been submitted.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"411 ","pages":"Page S16"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009919","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}