Toxicology最新文献

{"title":"Corrigendum to “Chronic exposure of bisphenol-A impairs cognitive function and disrupts hippocampal insulin signaling pathway in male mice” [Toxicology 472 (2022) 153192]","authors":"Huimin Wang , Xuepei Lei , Zhuo Zhang , Mohammad Mehdi Ommati , Zhongwei Tang , Jianqin Yuan","doi":"10.1016/j.tox.2025.154238","DOIUrl":"10.1016/j.tox.2025.154238","url":null,"abstract":"","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"517 ","pages":"Article 154238"},"PeriodicalIF":4.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708879","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":"Utilization of the CometChip assay for detecting PAH-induced DNA bulky adducts in a 3D primary human bronchial epithelial cell model","authors":"Victoria C. Colvin ,&nbsp;Norah A. Owiti ,&nbsp;Bevin P. Engelward ,&nbsp;Susan C. Tilton","doi":"10.1016/j.tox.2025.154241","DOIUrl":"10.1016/j.tox.2025.154241","url":null,"abstract":"<div><div>Polycyclic aromatic hydrocarbons (PAHs), which are formed during incomplete combustion of organic materials, may cause cancer through DNA damage mediated by formation of bulky DNA adducts from PAH reactive metabolites. The airway epithelium is a primary route of exposure for inhaled PAHs, and primary human bronchial epithelial cells (HBECs) in monolayer or organotypic cultures offer a more realistic testing scenario compared to traditional cell lines. However, lack of knowledge about their capacity to mediate DNA damage through generation of reactive chemical intermediates limits their use in quantitative studies for toxicity assessment or predictive modeling compared to <em>in vivo</em> studies. In this study, we explored the capacity of monolayer HBECs to generate DNA damage from metabolic activation of benzo[<em>a</em>]pyrene (BAP, 0.001 – 1 µg/mL, 24 h) using the high-throughput CometChip assay in comparison to HepG2 and MEF cells, as positive and negative metabolic controls, respectively. The CometChip assay was further adapted to evaluate DNA damage in HBECs cultured at the air-liquid interface (ALI) exposed to BAP (0.04–1.14 µg/cm², 24 h). Monolayer and ALI-HBECs displayed a statistically significant increase in DNA damage from BAP exposure with repair trapping agents in a dose-dependent manner similar to the response from HepG2 cells. Monolayer HBECs also showed a greater sensitivity to DNA damage compared to ALI-HBECs, which correlated with induction of CYP1A1 activity at similar exposure conditions. Results from the CometChip assay were also observed at lower BAP concentrations compared to CYP1A1 activity, cytotoxicity, or barrier integrity disruption demonstrating the sensitivity of the CometChip assay.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"517 ","pages":"Article 154241"},"PeriodicalIF":4.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144704589","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":"Polyethylene microplastics disrupt focal adhesion kinase (FAK) signaling and sertoli cell metabolism, compromising blood-testis barrier function and spermatogenesis","authors":"G. Vigneshwaran ,&nbsp;Itishree Dubey ,&nbsp;Anand Kumar ,&nbsp;Lalruatmawii ,&nbsp;Aditya Hylalij ,&nbsp;Sree Vaishnavi Nalla ,&nbsp;Rohit Kumar Gautam ,&nbsp;Shivani Bhardwaj ,&nbsp;Gurvinder Singh ,&nbsp;Dinesh Kumar ,&nbsp;Sapana Kushwaha","doi":"10.1016/j.tox.2025.154240","DOIUrl":"10.1016/j.tox.2025.154240","url":null,"abstract":"<div><div>Polyethylene microplastics (PE-MPs), used extensively in personal care applications, are non-biodegradable pollutants with demonstrated bioaccumulation potential and toxicological relevance. Recent studies have detected microplastics in human semen and testicular tissues, raising concerns about their effect on male reproductive health. This study investigates the toxicological effects of orally administered polyethylene microplastics (PE-MPs) at 20 µg/mL, 200 µg/mL, and 2000 µg/mL doses in rats for 56 days, with a focus on disruption of the blood-testis barrier (BTB) and destabilization of ectoplasmic specialization (ES), both essential for normal spermatogenesis. Western blot analysis showed a marked reduction in BTB-associated tight junction proteins occludin, claudin-11, N-cadherin, E-cadherin, and adaptor protein ZO-1, as well as the steroidogenic marker StAR in PE-MPs-treated rats, indicating disruption of barrier integrity and steroidogenic function. PE-MPs exposure significantly reduced p-FAK (Tyr407), could impair the F-actin organization, and lead to an open BTB. At the same time, increased p-FAK (Tyr397) expression resulted in decreased spermatid adhesion, disrupting apical ES dynamics and contributing to a leaky BTB with increased permeability. These alterations led to spermiation failure, premature germ cell exfoliation, and impaired spermatogenesis. Additionally, the Akt and mammalian rapamycin (mTOR) expression targets were explored to understand their potential role in PE-MPs-induced testicular toxicity. The exposure to PE-MPs significantly altered 17 serum metabolites, indicating metabolic disturbances identified through ¹H NMR metabolomics. High doses of PE-MPs significantly elevated serum pyruvate and lactate levels in rats, possibly infiltrating the testis due to disruption of the BTB. Also, PE-MPs exposure significantly elevated the serum histidine-to-tyrosine ratio, indicating disrupted amino acid metabolism. These findings demonstrate that PE-MPs compromise BTB integrity, disrupt ES dynamics, impair spermatogenesis, and induce systemic metabolic alterations, highlighting their potential risk to male reproductive health.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"517 ","pages":"Article 154240"},"PeriodicalIF":4.8,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699627","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":"Toxicological profiling of polystyrene microplastics in raw 264.7 macrophages: Linking microplastic exposure to immune cell impairment","authors":"Shramana Koner,&nbsp;Seenivasan Ramasubbu,&nbsp;Natarajan Chandrasekaran","doi":"10.1016/j.tox.2025.154239","DOIUrl":"10.1016/j.tox.2025.154239","url":null,"abstract":"<div><div>The pervasive presence of microplastics (MPs), particularly polystyrene microplastics (PSMPs), has raised urgent concerns regarding their effects on human health. This study investigates the toxicological effects of spherical PSMPs (&lt;0.50 µm) on Raw 264.7 murine macrophages, critical immune cells that actively internalize foreign materials. At exposure concentrations ranging from 50 to 500 µg/mL, PSMPs were rapidly internalized within 2 h, with accumulation increasing over time. Notably, high-dose exposure (500 µg/mL) resulted in significant mitochondrial membrane damage, lysosomal dysfunction, elevated reactive oxygen species (ROS) levels, and lipid peroxidation. These cellular stress responses were accompanied by increased levels of LDH and SOD, as well as the induction of apoptosis and cellular senescence. The findings show that PSMPs disrupt mitochondrial function and contribute to senescence responses, ultimately compromising immune cell viability and function. This study provides new insight into the intracellular fate and toxicity of environmentally relevant PSMPs and emphasizes the need for urgent evaluation of plastic pollution's impact on human health.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"517 ","pages":"Article 154239"},"PeriodicalIF":4.6,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708880","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":"EGFR and CYP signaling disruption underlies 6PPD-quinone hepatotoxicity: Insights from a network and machine learning approach","authors":"Wenjie Zhang ,&nbsp;Banghua Wu ,&nbsp;Chengbin Hu ,&nbsp;Weifeng Rong ,&nbsp;Yongshun Huang ,&nbsp;Shijie Hu ,&nbsp;Yiru Qin","doi":"10.1016/j.tox.2025.154235","DOIUrl":"10.1016/j.tox.2025.154235","url":null,"abstract":"<div><div>N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine quinone (6PPD-quinone), an emerging environmental contaminant derived from the common tire additive 6PPD, has been alarmingly detected in human biology samples and is associated with liver injury. However, the underlying molecular mechanisms driving its hepatotoxicity remain largely unexplored. We employed an integrated <em>in silico</em> strategy encompassing ADMET profiling, network toxicology analysis, molecular docking, molecular dynamics (MD) simulations, and machine learning (ML) to uncover the hepatotoxic mechanisms of 6PPD-quinone. Our analysis identified 62 critical intersection genes between 6PPD-quinone targets and hepatotoxicity-related genes. Protein-protein interaction analysis revealed two distinct functional modules: Epidermal Growth Factor Receptor (EGFR)-mediated signaling pathways and Cytochrome P450 (CYP) enzyme-driven metabolic processes. Molecular docking and MD simulations confirmed remarkably strong and stable binding interactions between 6PPD-quinone and EGFR. An advanced ML model further classified 6PPD-quinone as a potent EGFR inhibitor, achieving a validation accuracy of 0.90 and an F1-score of 0.90. Comprehensive ADMET and docking analyses additionally indicated multi-CYP enzyme inhibition capabilities. In conclusion, our findings suggest that 6PPD-quinone induces liver injury through a dual mechanism involving EGFR signaling suppression and CYP-mediated metabolic disruption. This work provides a critical mechanistic framework for assessing the hepatotoxic risks of tire-derived environmental pollutants and highlights potential intervention targets for mitigating their adverse health effects.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"517 ","pages":"Article 154235"},"PeriodicalIF":4.8,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144680490","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":"Machine learning classification of steatogenic compounds using toxicogenomics profiles","authors":"Brian Bwanya ,&nbsp;Saad Lodhi ,&nbsp;Theo M. de Kok ,&nbsp;Luiz Ladeira ,&nbsp;Marcha CT Verheijen ,&nbsp;Danyel GJ Jennen ,&nbsp;Florian Caiment","doi":"10.1016/j.tox.2025.154237","DOIUrl":"10.1016/j.tox.2025.154237","url":null,"abstract":"<div><div>The transition toward new approach methodologies for toxicity testing has accelerated the development of computational models that utilize transcriptomic data to predict chemical-induced adverse effects. Here, we applied supervised machine learning to gene expression data derived from primary human hepatocytes and rat liver models (<em>in vitro</em> and <em>in vivo</em>) to predict drug-induced hepatic steatosis. We evaluated five machine learning classifiers using microarray data from the Open TG-GATEs database. Among these, support vector machine (SVM) consistently achieved the highest performance, with area under the receiver operating characteristic curve (ROC-AUC) of 0.820 in primary human hepatocytes, 0.975 in the rat <em>in vitro</em> model, and 0.966 in the rat <em>in vivo</em> model. To gain mechanistic insights, we functionally profiled the top-ranked predictive genes. Enrichment analyses revealed strong associations with lipid metabolism, mitochondrial function, insulin signalling, oxidative stress, all biological processes central to steatosis pathogenesis. Key predictive genes such as <em>CYP1A1</em>, <em>PLIN2</em>, and <em>GCK</em> mapped to lipid metabolism networks and liver disease annotations, while others highlighted novel transcriptomics signals. Integration with differentially expressed genes and known steatosis markers highlighted both overlapping and distinct molecular features, suggesting that machine learning models capture biologically relevant signals. These findings demonstrate the potential of machine learning models guided by transcriptomic data to identify early molecular signatures of drug-induced hepatic steatosis. The support vector machine model’s strong predictive accuracy across species highlights its promise as a scalable and interpretable tool for chemical risk assessment. As data limitations in human toxicology persist, expanding high-quality transcriptomic resources will be critical to further advance non-animal approaches in regulatory toxicology.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"517 ","pages":"Article 154237"},"PeriodicalIF":4.8,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675649","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":"Bisphenol S exacerbates CRC progression through dual mechanisms of immune microenvironment reprogramming and SLC4A2-mediated EMT activation","authors":"Abudushalamu Yalikun ,&nbsp;Jinfeng Cai ,&nbsp;Runkai Zhou ,&nbsp;Haonan Chen ,&nbsp;Jiawei Pan ,&nbsp;Paheredini Yusufu ,&nbsp;Jikun Li","doi":"10.1016/j.tox.2025.154236","DOIUrl":"10.1016/j.tox.2025.154236","url":null,"abstract":"<div><div>Bisphenol S (BPS) is frequently utilized in the domain of food packaging materials as well as in the sphere of industrial plastic manufacturing. Although existing studies suggest potential associations between BPS exposure and the development of various malignancies, the exact biological function of BPS in colorectal cancer (CRC) advancement is still not fully understood. This research intends to thoroughly explore how BPS influences the malignant characteristics of CRC at the molecular level, particularly its impact on the epithelial-mesenchymal transition (EMT) in tumor cells. This study employed a LASSO regression model to screen key genes associated with BPS exposure in CRC progression and constructed a prognostic prediction model. The ESTIMATE algorithm was employed to evaluate the stromal and immune scores within the tumor microenvironment, while the CIBERSORT technique was applied to examine the infiltration profiles of 22 distinct immune cell subsets. The impact of BPS on HCT8 cell proliferation, migratory ability, and EMT progression were systematically evaluated through Western blot, CCK-8 proliferation assays, scratch wound healing experiments, and Transwell assays for migration and invasion. BPS exposure within the concentration range of 10⁻¹ ⁰ to 10⁻⁶ M did not significantly inhibit HCT8 cell viability but markedly enhanced migration and invasion capabilities, accompanied by EMT progression. A prognostic model constructed from nine key genes linked to BPS and determined via LASSO regression exhibited robust predictive efficacy. Tumor microenvironment analysis indicated a substantial association between SLC4A2 gene expression and activated memory CD4 + T lymphocyte infiltration. Notably, BPS exposure specifically induced SLC4A2 upregulation, while siRNA-mediated SLC4A2 knockdown significantly suppressed BPS-induced cell migrationand reversed EMT phenotypes. This study first demonstrates that BPS promotes CRC cell migration by activating the EMT signaling pathway via SLC4A2 upregulation. SLC4A2, being a key player in BPS-induced tumorigenesis, could function as a promising biomarker and therapeutic target for CRC. These findings not only elucidate the molecular mechanisms underlying environmental pollutant-induced carcinogenesis but also provide experimental evidence for developing prevention strategies targeting BPS-associated CRC risks.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"517 ","pages":"Article 154236"},"PeriodicalIF":4.8,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144634135","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":"AI-based toxicity prediction models using ToxCast data: Current status and future directions for explainable models","authors":"Donghyeon Kim ,&nbsp;Jinhee Choi","doi":"10.1016/j.tox.2025.154230","DOIUrl":"10.1016/j.tox.2025.154230","url":null,"abstract":"<div><div>Artificial intelligence (AI) offers new opportunities for developing toxicity prediction models to screen environmental chemicals. U.S. EPA’s ToxCast program provides one of the largest toxicological databases and has consequently become the most widely used data source for developing AI-driven models. ToxCast In this review, we analyzed 93 peer-reviewed papers published since 2015 to provide an overview of ToxCast data-based AI models. We overviewed the current landscape in terms of database structure, target endpoints, molecular representations, and learning algorithms. Most models focus on data-rich endpoints and organ-specific toxicity mechanisms, particularly endocrine disruption and hepatotoxicity. While conventional molecular fingerprints and descriptors are still common, recent studies employ alternative representations—graphs, images, and text—leveraging advances in deep learning. Likewise, traditional supervised machine-learning algorithms remain prevalent, but newer work increasingly adopts semi- and unsupervised approaches to tackle data-sparsity challenges. Beyond classical structure-based QSAR, ToxCast data are also being used as biological features to predict in vivo toxicity. We conclude by discussing current limitations and future directions for applying ToxCast-based AI models to accelerate next-generation risk assessment (NGRA).</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"517 ","pages":"Article 154230"},"PeriodicalIF":4.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620698","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":"Screening industrial chemicals for human developmental toxicity in the DevTox Germ Layer Reporter platform","authors":"John T. Gamble ,&nbsp;Jesse Rogers ,&nbsp;Kristen Breaux ,&nbsp;Madison Feshuk ,&nbsp;Carter Thunes ,&nbsp;Katie Paul Friedman ,&nbsp;Chad Deisenroth","doi":"10.1016/j.tox.2025.154232","DOIUrl":"10.1016/j.tox.2025.154232","url":null,"abstract":"<div><div>The EPA New Chemicals Collaborative Research Program (NCCRP) seeks to maximize the efficiency and robustness of the new chemical review process under the Toxic Substances Control Act (TSCA) using new approach methods (NAMs) that represent the best available science. Consideration of the possible health hazards to pregnant women, and their developing offspring, for new chemical submissions is challenged by an insufficient number of acceptable screening modalities to quickly identify potential hazards to humans. The DevTox Germ Layer Reporter (GLR) assay platform evaluates chemical effects on early germ layer development and has been demonstrated to be a viable option for rapid chemical screening. The objective of this study was to screen a structurally diverse set of 171 representative chemicals selected from the TSCA non-confidential active inventory, and 54 <em>in vitro</em> assay reference chemicals, for potential developmental toxicity in the DevTox GLR-Endo assay. Assay performance metrics, as well as predictivity across a set of 16 reference developmental toxicants, were consistent with prior reporting and within acceptable parameters. Of the 38 reference chemicals not previously evaluated in the assay, 25 were identified as active, with 13 demonstrating selectivity for the SOX17 assay endpoint. For the test chemical set, 60 of the 165 chemicals analyzed were active, with 29 exhibiting a degree of selective activity. The results provide coverage of a critical toxicological domain for a set of chemicals relevant to the development of NAM-based methods for the NCCRP and may inform the development of tools in a NAMs-based hazard assessment strategy.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"517 ","pages":"Article 154232"},"PeriodicalIF":4.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144620699","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":"Two roads to fibrosis: Contrasting initiating mechanisms of Bleomycin and TGFβ-1 in lung fibroblasts","authors":"Nicoletta D’Alessandro ,&nbsp;Lena Möbus ,&nbsp;Giusy del Giudice ,&nbsp;Noora Perho ,&nbsp;Angela Serra ,&nbsp;Dario Greco","doi":"10.1016/j.tox.2025.154233","DOIUrl":"10.1016/j.tox.2025.154233","url":null,"abstract":"<div><div>Pulmonary fibrosis, a progressive and debilitating disease, presents a significant global health challenge. Even though often idiopathic, drug-induced fibrosis is increasing its incidence. Traditional chemical safety assessments, relying on apical endpoints from <em>in-vivo</em> models, are limited in capturing the early molecular events initiating fibrosis, consequently limiting the potential for early diagnosis and mechanism-driven treatment. This study employed a toxicogenomic approach on <em>in-vitro</em> MRC-5 fibroblasts, a crucial cell type involved in fibrosis, to dissect the initiating profibrotic mechanisms of Bleomycin (1, 1.5, 2 μg/mL), a profibrotic triggering stimulus, comparing it with TGFβ-1(5, 10, 15 ng/mL), a known sustaining mediator of fibrosis over 24, 48, and 72 h. Our analysis reveals that while both agents alter matrix-related processes, their initiation mechanisms diverge. Specifically, TGFβ-1 directly induces myofibroblast transition, whereas Bleomycin potentially induces an indirect transition through the establishment of a senescence-associated secretory phenotype (SASP). By capturing the early SASP signature, we identified a critical driver of Bleomycin-induced fibroblast fibrosis, relevant to drug-induced fibrosis where antineoplastic agents are a major concern. This study underscores the critical importance of integrating mechanistic understanding into chemical safety assessment, thereby facilitating the development and implementation of safer, more sustainable chemical development.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"517 ","pages":"Article 154233"},"PeriodicalIF":4.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144614328","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}