Toxicology letters最新文献

{"title":"CEC02-04 Science and use of the current DNT in vitro battery","authors":"E. Fritsche","doi":"10.1016/j.toxlet.2025.07.018","DOIUrl":"10.1016/j.toxlet.2025.07.018","url":null,"abstract":"","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":"145010911","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":"S12-01 Epigenetic induced changes and mechanisms of celluoar toxicity- an update on fusariotoxins (Fumonisin B1 and Fusaric acid) and Patulin","authors":"A. Chuturgoon,&nbsp;T. Ghazi","doi":"10.1016/j.toxlet.2025.07.079","DOIUrl":"10.1016/j.toxlet.2025.07.079","url":null,"abstract":"<div><div>Fusariotoxins (Fumonisin B1 and Fusaric acid) and Patulin are foodborne mycotoxins known for their mutagenic, carcinogenic and genotoxic effects. Recent studies have highlighted their ability to induce epigenetic modifications that contribute to organ toxicity.</div><div><em>Fusarium</em> mycotoxins are the most economically important toxins with fumonisin B1 (FB1) being the most toxic and fusaric acid (FA), a neglected toxin, regarded as mildly toxic. FB1 inhibits sphingolipid biosynthesis and modifies cell survival and cell death processes, whilst FA was shown to be a hypotensive agent, altered brain neurochemistry and a putative putative mitochondrial toxin. Both these toxins alter the host epigenome that can lead to adverse health outcomes. FB1 alters the epigenetic landscape by modulating DNA methylation and histone modifications which can lead to chromatin instability and carcinogenesis. FB1 increases H3K4Me3 at the PTEN promoter, enhancing its transcription but inhibiting its translation via miR-30c, thereby activating the PI3K/AKT pathway and impairing DNA damage checkpoint regulation.</div><div>FA triggers global DNA hypomethylation, upregulates miR-29b and increases expression of MBD2. FA affects histone modifications by reducing levels of H3K9me3, which disrupts genome instability and induces apoptosis Patulin (Pat), produced by <em>Penicllium</em> species, induces epigenetic changes that can lead to kidney injury. Pat disrupts α-1 and α-2 adrenergic receptor signalling pathways and alters DNA methylation patterns; it upregulates DNMT1 and MBD2 (demethylase) that results in DNA hypomethylation. These epigenetic modifications influence gene expression and contributes to adverse health effects.</div><div>Epigenetic modifications have been implicated in various human diseases, including carcinogenesis. FB1, FA and Pat induced epigenetic changes in <em>in vitro,</em> animal models and humans. Our data showed that FA was genotoxic and post-translationally modified p53 and m6A RNA methylation. FB1 induced global DNA hypomethylation, modulated miR27b expression and apoptosis; and contributed to an additional mode of neoplastic transformation. Further, FB1 was immunolocalised in human brain tumour tissue samples (49/76), with many patients having matched high serum FB1 levels.</div><div>In conclusion, the results show that that these three mycotoxins alter the epigenetic landscape and contribute to disease.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"411 ","pages":"Pages S25-S26"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011011","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":"S10-02 Integrated approaches for chemical safety assessment: towards one health models for SSbD","authors":"D. Greco","doi":"10.1016/j.toxlet.2025.07.072","DOIUrl":"10.1016/j.toxlet.2025.07.072","url":null,"abstract":"<div><div>Toxicology is going through profound changes as the focus of investigation is shifting from the observation of apical phenomena to mechanistic aspects of the exposure. Toxicogenomics aims at clarifying the mechanism of action (MOA) of chemicals by using omics assays. The Adverse Outcome Pathways (AOP) concept is also emerging to contextualise toxicogenomics-derived MOA.</div><div>At the Finnish Hub for Development and Validation of Integrated Approaches (FHAIVE) of Tampere University, we use advanced modelling of large amounts of data to anchor molecular assays to AOPs. We also combine big data science, artificial intelligence (AI), network science, toxicogenomics, molecular assays and cell technology to analyse a comprehensive knowledge graph comprising tens of millions of data points with the aim to develop AOP-derived New Methodology Approaches (NAMs). The goal is to build multi-scale models to clarify the mechanism of action of exposures from molecular to planetary scales.</div><div>In this talk, I will discuss how integrated data-driven approaches can be used to unify the currently fragmented comprehension of the chemical-biological interactions, while guiding the development of safe and sustainable by design (SSbD) and effective by design (EbD) chemicals, drugs, and materials.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"411 ","pages":"Page S23"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011127","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":"S03-03 Tools and approaches for the risk assessment of plant-derived substances of concern in food – the EFSA's perspective","authors":"E. Kouloura,&nbsp;A. Nathanail,&nbsp;B. Bottex,&nbsp;P. Manini,&nbsp;C. Eskes,&nbsp;M.B. Gilsenan,&nbsp;D. Maurici,&nbsp;C. Roncancio-Pena","doi":"10.1016/j.toxlet.2025.07.052","DOIUrl":"10.1016/j.toxlet.2025.07.052","url":null,"abstract":"<div><div>Botanicals and botanical preparations are widely present in the European market as food, or ingredients of food supplements, or food/feed additives. Plants contain substances that are beneficial for human nutrition, however, a number of plant-derived substances can exert toxicological effects and thus pose potential health risks to consumers. The risk assessment of these substances is a complex procedure that requires a comprehensive approach to evaluate their inherent toxicity, exposure and potential adverse effects for human health.</div><div>EFSA is assessing hazards and risks of botanicals and plant-derived substances under different regulatory frameworks. By characterising the potential risks associated with substances of concern in plants, the risk assessments inform regulatory decisions (e.g. in the area of contaminants, maximum levels in food/feed) and are used for the evaluation of the safety of regulated products (e.g. novel food, food and feed additives).</div><div>As an overarching activity, EFSA has developed a toolkit to help assess the safety of botanicals and derived preparations intended for use as food, food supplements, or food/feed additives. Specifically, the development of the EFSA Compendium of Botanicals, an open-source hazard database, which is used to facilitate the hazard identification of plant-derived substances of potential concern.</div><div>This presentation will provide an overview with examples of the tools and approaches used by EFSA for the hazard identification and risk assessment of plant-derived substances of concern.</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":"145011128","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":"S04-03 Sponsor Perspectives on Implementing WOE Approaches","authors":"J. Vahle","doi":"10.1016/j.toxlet.2025.07.056","DOIUrl":"10.1016/j.toxlet.2025.07.056","url":null,"abstract":"<div><div>The revision of ICH S1B to allow for a WoE option for carcinogenicity assessments in certain cases is a landmark change in carcinogenicity testing of small molecule pharmaceuticals. This presentation will review the benefits of a WOE approach from a sponsor's perspective. A key is moving from a “check the box” approach of conducting 2-year rat carcinogenicity studies to a more scientifically based approach that considers key pharmacologic and toxicologic properties for the compound. The WoE approach can provide for a substantial reduction in animal use will be realized, as the standard 2-year rat carcinogenicity studies require between 500-700 rats. The current status of implementation will be discussed and include highlights from an industry survey on implementation issues. Drawing on the work on the industry members of the ICH S1B Expert Working Group, best practices for adopting a weight of evidence approach will be included along with case examples to illustrate key points.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"411 ","pages":"Page S18"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011196","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":"S07-01 Integration of different streams of evidence supporting possible developmental neurotoxicity (DNT) of glyphosate","authors":"A.F. Hernández","doi":"10.1016/j.toxlet.2025.07.064","DOIUrl":"10.1016/j.toxlet.2025.07.064","url":null,"abstract":"<div><div>Glyphosate, the active ingredient in glyphosate-based herbicides (GBHs), is extensively used for weed control, with recent concerns emerging over its potential developmental neurotoxicity (DNT). Regulatory assessments in the EU have identified a critical data gap regarding DNT studies on glyphosate acid. This presentation synthesises evidence from epidemiological, <em>in vivo</em>, and new approach methodologies (NAMs) to assess its neurodevelopmental effects. Epidemiological studies yielded inconsistent findings. Some reported associations between prenatal glyphosate exposure and autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and developmental delays, while others find no significant links. These inconsistencies can be attributed to variations in exposure assessment and study design. Animal studies provide more consistent evidence supporting neurodevelopmental effects. Rodent models indicate that glyphosate exposure disrupts neurotransmitter systems, induces oxidative stress, alters endocrine signalling, and promotes neuroinflammation, leading to cognitive impairments, anxiety-like behaviours, and deficits in social interaction. However, these effects are primarily observed with GBHs rather than glyphosate alone. Regulatory guideline studies remain limited, with a single DNT study on glyphosate trimesium reporting positive effects, though this form is not representative of glyphosate acid's toxicological profile. Zebrafish studies further corroborate glyphosate's neurotoxic potential. <em>In vitro</em> research shows that glyphosate induces apoptosis, disrupts neuronal differentiation, and activates glial cells, while <em>in silico</em> modelling predicts interactions with neurotransmitter receptors and endocrine pathways. Remarkably, GBHs appear more neurotoxic than glyphosate alone, likely due to surfactant components enhancing toxicity. A weight-of-evidence approach suggests that while GBHs may pose neurodevelopmental risks, no definitive DNT liabilities for glyphosate acid have been established. Addressing the identified data gap through further research is essential to refine its neurotoxicological profile.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"411 ","pages":"Page S20"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011204","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":"Stress and Healthy Longevity vs. Aging","authors":"G.P. Chrousos","doi":"10.1016/j.toxlet.2025.07.005","DOIUrl":"10.1016/j.toxlet.2025.07.005","url":null,"abstract":"<div><div>Stress is defined as a disturbance in the <em>dynamic equilibrium</em> or <em>homeostasis</em> of a complex system, such as the human organism. A stressor is the force that causes this disturbance, while the <em>adaptive response</em> 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 <em>stress system</em>, 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 <em>chronic stress and inflammation syndrome</em>, which represents the background of all the <em>chronic noncommunicable diseases</em>, renders the organism vulnerable to certain infections and accelerates aging. Aging is a complex biological process influenced by genetic, epigenetic, and environmental factors, ultimately leading to a gradual decline in cellular and organ function and finally death. There is evidence of genetically programmed aging, including a theoretical lifespan of up to 130 years, defined by the regenerative limits of adult stem cells. There are two periods, during the fifth and seventh decades 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.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"411 ","pages":"Page S2"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010836","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":"CEC06-04 Gamma-hydroxybutyrate and analogues","authors":"E. Salgado","doi":"10.1016/j.toxlet.2025.07.039","DOIUrl":"10.1016/j.toxlet.2025.07.039","url":null,"abstract":"<div><div>No abstract has been submitted.</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":"145010756","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":"CEC02-02 Current regulatory (in vivo) neurotoxicity testing","authors":"P. Goldsteen","doi":"10.1016/j.toxlet.2025.07.016","DOIUrl":"10.1016/j.toxlet.2025.07.016","url":null,"abstract":"<div><div>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 challenges/limitations that are faced.</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":"145010909","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":"S12-02 Promises and Challenges of Toxico-Epigenomics: Environmental Chemicals and Their Impacts on the Epigenome and Cancer Risk","authors":"Z. Herceg","doi":"10.1016/j.toxlet.2025.07.080","DOIUrl":"10.1016/j.toxlet.2025.07.080","url":null,"abstract":"<div><div>Recent years have witnessed a remarkable pace of discoveries in epigenetics which have revolutionized our understanding of complex human diseases. The spectacular advances in epigenomics that allow the analysis of the epigenome with unprecedented resolution in high throughput and genome-wide settings have further accelerated investigations in this area. The challenge posed by major international sequencing efforts is to identify changes in the (epi)genome that precede and promote tumour development, and to differentiate functionally important (“drivers”) from non-functional <em>“</em>passenger<em>”</em> events. In addition, there is little understanding about whether epigenetic changes can be used as biomarkers for exposure assessment, risk stratification, and early detection. The epigenome has been proposed to function as an interface between environmental factors and the genome, therefore, the identification and functional characterization of epigenetic events deregulated by specific environmental and lifestyle stressors should enhance our understanding of mechanisms of carcinogenesis linked to risk-factor exposures. The intrinsic reversibility of epigenetic changes represents a tremendous opportunity for the development of novel strategies for cancer treatment and prevention. I will discuss recent conceptual and technological advances in epigenetics and ongoing efforts aiming to identify epigenetic targets that could be exploited in cancer prevention and therapy as well as molecular epidemiology. I will also discuss the issues related to opportunities and challenges in the application of epigenetic testing in carcinogen identification and evaluation.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"411 ","pages":"Pages S26-S27"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011012","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}