Toxicological Research最新文献

{"title":"Exploring the molecular association between Di(2-ethylhexyl)phthalate and dilated cardiomyopathy based on interpretable machine learning and molecular docking.","authors":"Xiao Xia, Lanshuo Hu, Shiyi Tao, Jun Li, Xuanchun Huang","doi":"10.1007/s43188-025-00334-8","DOIUrl":"10.1007/s43188-025-00334-8","url":null,"abstract":"<p><p>This study aims to explore the molecular association between di(2-ethylhexyl)phthalate (DEHP) and dilated cardiomyopathy (DCM) through interpretable machine learning and molecular docking techniques. DCM transcriptome datasets (GSE120895, GSE9800, GSE29819) are integrated. Disease-related genes are screened through differential expression analysis and weighted gene co-expression network analysis (WGCNA). Potential targets of DEHP are predicted using CHEMBL, SwissTargetPrediction, and PharmMapper databases. The associated targets of DEHP and DCM are identified via intersection analysis, and a multi-algorithm machine learning framework is used to further screen core genes. Finally, molecular docking is performed to verify the binding affinity between DEHP and core targets. A total of 1364 potential targets of DEHP are identified. Intersection with 61 DCM-related genes yields 11 key targets. Functional enrichment analysis shows that these genes are involved in ion homeostasis, metabolic reprogramming, and regulation of inflammatory pathways. Machine learning further screens eight core genes: ABAT, ACE2, BLM, C3, IGFBP2, KCNIP2, NPPA, and TYMS. Molecular docking confirms that DEHP has strong binding specificity with all eight core proteins.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"42 4","pages":"443-459"},"PeriodicalIF":3.3,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13332083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148391680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The bioaccumulation and carcinogenic potential of micro- and nanoplastics in humans.","authors":"Ghulam Nabi, Tariq Aziz, Lin Lin","doi":"10.1007/s43188-025-00332-w","DOIUrl":"10.1007/s43188-025-00332-w","url":null,"abstract":"<p><p>The rising concentrations of anthropogenic microplastics (MPs; 1 µm to 5 mm) and nanoplastics (NPs; < 1 µm) pollution pose a global crisis, presenting a grave threat to the ecosystem and the health of living creatures within. Studies between 2024 and 2025 reported the bioaccumulation of MPs and NPs (MNPs) in several human organs. However, unlike animal and cell line studies, the relationship between MNPs exposure and carcinogenesis in humans remains unclear. To our knowledge, this is the first comprehensive review article to summarize the bioaccumulation of different types of MNPs in human multi-system organs reported to date. In this article, we investigated the link between various types of MNPs and cancer in multi-system organs. Furthermore, we explored potential carcinogenic pathways and identified research gaps and populations at-risk. This article will provide a comprehensive understanding of the carcinogenic potential of MNPs and their implications for global public health. It highlights important directions for future research and emphasizes the necessity for interdisciplinary collaboration to tackle this significant global health challenge.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"42 3","pages":"273-287"},"PeriodicalIF":3.3,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13096292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transferability and reproducibility of IMMUNOTOX-T assay, an <i>in vitro</i> method for evaluation of chemical-mediated immunotoxicity.","authors":"SoYeon Kim, Anju Maharjan, DaHee Son, HeeEon Kim, GiYong Lee, ChangYul Kim, Yong Heo, HyoungAh Kim","doi":"10.1007/s43188-025-00333-9","DOIUrl":"10.1007/s43188-025-00333-9","url":null,"abstract":"<p><p><i>In vivo</i> evaluation of the immunotoxicity of xenobiotics is mainly carried out in rodents. Recent trends following the 3R (reduction, refinement, replacement) principle have driven development of <i>in vitro</i> methods for screening immunotoxic chemicals. The recently reported IMMUNOTOX-T immunotoxicity assay uses the human monocytic leukemia cell line THP-1, and evaluates potential immunotoxicity by profiling production of various cytokines by cells treated with test chemicals. Development of the assay involved small-scale evaluation of transferability, within-laboratory repeatability (WLR), and between-laboratory reproducibility (BLR). The IMMUNOTOX-T assay was transferred to, and tested by, a Participating laboratory in compliance with Good Laboratory Practice. All test substances were tested under blinded conditions. Selected vehicles, 75% cell viability (CV75), and relative cytokine production levels (RCPL, %) of IL-6, IL-8, and TNF-α at three concentrations (0.01x, 0.1x, and 0.5 × CV75) of each test compound were compared with levels induced by respective vehicle controls. The following chemicals were tested by the Lead and Participating laboratory: dexamethasone, chlorambucil, and glycerol. There was no statistically significant difference in the data generated by the two laboratories. Regarding WLR, eight chemical substances (two immunosuppressants, three non-immunotoxicants and three immune-modulatory chemicals) were tested twice (independently), and RCPLs for 24 cytokines calculated, by the Participating laboratory. The duplicate experiments showed 93.8% similarity in mean RCPLs (i.e., no significant differences between the duplicate values for 180/192 cytokine tests for all eight substances). The BLR for the eight test substances was evaluated by comparing the mean RCPLs of 24 cytokines calculated by the two laboratories. Combining all of the results for the eight tests revealed that the magnitude of similarity between the data from the Lead and Participating laboratory was 88.5% (there were no significant differences in mean RCPLs for 170/192 cytokine tests). Thus, the IMMUNOTOX-T assay is transferable, with good WLR and BLR.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-025-00333-9.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"42 3","pages":"371-382"},"PeriodicalIF":3.3,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13096424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polymer- and size-dependent toxicological behavior of environmentally relevant secondary microplastics: a comprehensive review.","authors":"Sijoon Lee","doi":"10.1007/s43188-025-00331-x","DOIUrl":"10.1007/s43188-025-00331-x","url":null,"abstract":"<p><p>Microplastics (MPs) generated from commonly used consumer polymers are increasingly recognized as emerging contaminants of toxicological concern. Despite growing evidence, a consolidated understanding of how polymer identity and particle size influence the biological behavior and systemic effects of environmentally relevant secondary MPs remains limited. This review summarizes recent in-vivo evidence using fragmented MPs derived from five major polymers-polyethylene (PE), polytetrafluoroethylene (PTFE), polypropylene (PP), polystyrene (PS), and polyethylene terephthalate (PET). Across studies, smaller particles exhibit greater tendencies for systemic distribution, epithelial barrier disruption, and immune activation compared with larger fragments. Comparative evaluation of biodistribution, histopathology, and physicochemical characteristics highlights consistent polymer- and size-dependent patterns, with PE, PS, and PET showing higher translocation potential, while PTFE and PP often display limited retention. By integrating findings from these in-vivo evaluations, this review provides a clearer understanding of the mechanistic factors governing MP toxicity and identifies key gaps related to exposure duration, environmentally aged particles, and analytical limitations. These insights contribute to establishing polymer-specific and size-resolved perspectives necessary for future microplastic risk assessment.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-025-00331-x.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"42 3","pages":"261-271"},"PeriodicalIF":3.3,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13096367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PK/PD interactions of antiarrhythmic drugs and oral anticoagulants in atrial fibrillation patients: clinical implications for stroke and dementia prevention.","authors":"Min Gyeong Oh, Byoungduck Park, Yu Chul Kim","doi":"10.1007/s43188-025-00328-6","DOIUrl":"10.1007/s43188-025-00328-6","url":null,"abstract":"<p><p>Atrial fibrillation (AF), the most prevalent arrhythmia affecting over 33 million individuals worldwide, markedly increases the risk of stroke and dementia. AF confers a nearly fivefold higher risk of stroke, accounting for up to one-third of cases, and independently elevates dementia risk even in the absence of overt cerebrovascular events. Oral anticoagulants (OACs) are the cornerstone of stroke prevention in AF and may also reduce AF-associated cognitive decline. However, their concomitant use with antiarrhythmic drugs (AADs), widely prescribed for rhythm or rate control, introduces toxicological and safety concerns due to clinically significant pharmacokinetic and pharmacodynamic interactions. Both drug classes commonly share cytochrome P450 enzyme and P-glycoprotein pathways, leading to altered systemic exposure, therapeutic efficacy, and safety. These interactions can enhance bleeding risk or reduce anticoagulant protection, highlighting the need for mechanistic insight and careful monitoring. This review emphasizes the toxicological dimensions of AAD-OAC co-therapy, focusing on exposure-toxicity relationships, bleeding thresholds, and variability in high-risk populations. It first outlines the mechanistic basis linking AF, stroke, and dementia, establishing the rationale for anticoagulation. It then examines AAD-anticoagulant interactions involving warfarin and direct oral anticoagulants (dabigatran, rivaroxaban, apixaban, and edoxaban), emphasizing enzyme inhibition, induction, and transporter modulation. Clinical, experimental, and case-based evidence is integrated to identify combinations associated with increased hemorrhagic risk and toxicological implications. Finally, practical recommendations are provided to optimize therapy, minimize adverse outcomes, and guide safer management of patients with AF. By integrating pharmacological mechanisms with toxicological perspectives, this review aims to advance risk assessment and safety evaluation in AAD-OAC co-therapy, ultimately improving prevention of stroke and dementia in AF.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"42 3","pages":"307-323"},"PeriodicalIF":3.3,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13096381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methylmercury causes pain disorders by disrupting the neuronal function of spinal dorsal horn neurons in mice.","authors":"Ryota Yamagata, Miyu Fujishima, Yuna Shoji, Naoya Yamashita, Wataru Nemoto, Gi-Wook Hwang","doi":"10.1007/s43188-025-00330-y","DOIUrl":"10.1007/s43188-025-00330-y","url":null,"abstract":"<p><p>Methylmercury is a neurotoxic substance that is ubiquitously present in the environment and is known to cause a variety of neurological symptoms, including sensory impairment. Although methylmercury exposure causes conflicting symptoms of hyperalgesia and hypoalgesia, the relationship between methylmercury toxicity and these symptoms has not been clarified. In this study, C57BL/6 male mice exposed to methylmercury chloride (final concentration 30 ppm) in drinking water ad libitum were temporally evaluated for changes in pain sensitivity. The results show that hyperalgesia (increased mechanosensitivity and thermosensitivity) was induced from 3 to 7 weeks after methylmercury exposure, followed by hypoalgesia (decreased mechanosensitivity and thermosensitivity) from 13 to 15 weeks after exposure. Furthermore, immunohistochemical staining of neuronal activity in spinal cord dorsal horn neurons reveals a dramatic increase in c-Fos-positive neurons (activated neurons) after 4 weeks of methylmercury exposure and a decrease in the number of activated neurons after 14 weeks of exposure. In addition, the amount of mercury accumulated in the spinal cord dorsal horn increased depending on the duration of exposure. These results suggest that gradual dysfunction of spinal dorsal horn neurons, dependent on the amount of methylmercury accumulated, is involved in the observed biphasic change in pain sensitivity. This study is the first to examine dynamic changes in pain sensitivity due to methylmercury exposure in a mouse model and provides important information for investigating the molecular mechanisms involved in methylmercury-induced sensory impairment.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"42 3","pages":"361-369"},"PeriodicalIF":3.3,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13096254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The future of toxicity testing: the emerging role of organ-on-a-chip platforms.","authors":"Kumsal Kocadal, Dilek Battal, Sahan Saygi","doi":"10.1007/s43188-025-00327-7","DOIUrl":"https://doi.org/10.1007/s43188-025-00327-7","url":null,"abstract":"<p><p>The 3Rs are guiding principles that must be followed when designing studies and conducting toxicity research. There is ongoing controversy regarding the use of animals in research. Moreover, the European Union outlawed animal experimentation in cosmetic products on 11 March 2013. More recently, the FDA Modernization Act 2.0 removed the requirement to use animal studies as part of the process for obtaining a licence for a biological product. These moral, ethical, and legal constraints have increased the need for alternative testing procedures. 3D cell cultures have gained popularity in recent years. Small microfluidic platforms known as \"organs-on-chips\" are dynamic cell cultures that mimic specific microenvironments. These microchips allow scientists to collect in vivo-like data. Organs-on-chips are considered a promising replacement for animal testing, and toxicity research is rapidly adopting this novel approach, much like other scientific fields, such as neuroscience, stem cell research, and cancer investigations. Therefore, the purpose of this review is to discuss the areas of toxicology where these platforms are currently being used, summarise the most recent toxicological applications of the aforementioned platforms, discuss the opportunities and challenges they present for toxicological research, and explore the interdisciplinary approaches applied within the field of toxicology.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"42 2","pages":"149-170"},"PeriodicalIF":2.3,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12946558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147327102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro metabolism and inhibitory effect of vonifimod on drug-metabolizing enzymes in human liver preparations.","authors":"Eun Jeong Kim, Min Seo Lee, Yang Hae Park, Bongyong Lee, Hye Suk Lee","doi":"10.1007/s43188-025-00329-5","DOIUrl":"10.1007/s43188-025-00329-5","url":null,"abstract":"<p><p>Vonifimod is a novel sphingosine-1-phosphate receptor (S1PR) modulator with selectivity for S1PR1 and S1PR4 that is under development for the treatment of autoimmune disease. No reports on vonifimod metabolism exist except for the formation of active vonifimod-phosphate in rats. The in vitro metabolic pathways and drug interaction potentials of vonifimod were characterized by identifying the metabolites of vonifimod in human hepatocytes via liquid chromatography-high-resolution mass spectrometry and determining the inhibitory effects of vonifimod on major cytochrome P450 (CYP) and UDPGA-glucuronosyltransferase (UGT) enzyme activities in human liver microsomes. The incubation of vonifimod with human hepatocytes resulted in the formation of nine metabolites, including hydroxy-vonifimod (M1 and M2), inactive carboxylic acids (M3 - M6), active vonifimod-phosphate (M7), and M3 glucuronides (M3-G1 and M3-G2). ω-Hydroxylation of vonifimod to M2 at the methyl terminus of the decyl chain was catalyzed mainly by CYP4F2 enzymes, which were further oxidized to four carboxylic acid metabolites (M3 - M6). UGT1A7, UGT1A8, UGT1A9, and UGT1A10 catalyzed the formation of M3-G2 from M3. Vonifimod revealed the negligible and weak inhibition of major CYP and UGT enzyme activities at 50 µM in human liver microsomes, suggesting that vonifimod has low potential for drug-drug interactions. These findings suggest hepatic metabolism to be the primary elimination pathway for vonifimod.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"42 3","pages":"345-359"},"PeriodicalIF":3.3,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13096377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phloroglucinol protects skin cells from particulate matter 2.5-induced oxidative stress and apoptosis.","authors":"Pincha Devage Sameera Madushan Fernando, Kyoung Ah Kang, Mei Jing Piao, Herath Mudiyanselage Udari Lakmini Herath, Herath Mudiyanselage Maheshika Madhuwanthi Senavirathna, Mee Jung Ahn, Changlim Hyun, Jin Won Hyun","doi":"10.1007/s43188-025-00324-w","DOIUrl":"https://doi.org/10.1007/s43188-025-00324-w","url":null,"abstract":"<p><p>Particulate matter 2.5 (PM_2.5) is an air pollutant that causes skin inflammation and aging. Phloroglucinol (PG) is a naturally occurring polyphenol with strong antioxidant potential that is widely used in pharmaceutical production. Information regarding the protective effect of PG against PM_2.5-induced cellular damage is lacking; therefore, this study evaluated the protective effect of PG against the detrimental effects of PM_2.5. PG reduced cellular reactive oxygen species levels in a dose-dependent manner. Furthermore, PG reduced PM_2.5-induced 8-hydroxydeoxyguanosine, protein carbonylation, 8-isoprostane, interleukin (IL)-6, and IL-1β levels. PG reduced PM_2.5-induced apoptosis by inhibiting the expression of pro-apoptotic proteins and mitochondrial membrane depolarization. PG restored PM_2.5-impaired nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (Ho-1) protein expression. Furthermore, PG reduced PM_2.5-induced mitogen-activated protein kinase pathway-related protein expression. Assessment of mouse skin tissue further confirmed that PG could restore PM_2.5-reduced Nrf2 and Ho-1 expression and reduce PM_2.5-induced thickening of the mouse epidermis. Overall, PG exhibited a strong potential to reduce PM_2.5-mediated skin cell damage by activating the antioxidant defense system.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"42 2","pages":"251-260"},"PeriodicalIF":2.3,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12945859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147327086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence‑based quantitative analysis of hepatic fibrosis in carbon tetrachloride-induced mouse model of metabolic dysfunction-associated steatohepatitis.","authors":"Jin-Hee Lee, Myung-Hwa Yang, Gyeongjin Han, Won Hoon Jung, Myung Ae Bae, Ji-Seok Han, Tae-Sung Koo, Jae-Woo Cho","doi":"10.1007/s43188-025-00326-8","DOIUrl":"10.1007/s43188-025-00326-8","url":null,"abstract":"<p><p>Liver fibrosis, a major histopathological indicator of chronic liver injury, is also a key feature of metabolic dysfunction-associated steatohepatitis. Its quantitative assessment in preclinical toxicology is frequently inconsistent and subjective. This study aimed to develop and validate multi-scale, patch-based convolutional neural network classification algorithms for automated fibrosis quantification in a carbon tetrachloride (CCl₄)-induced mouse model. We sought to determine the optimal patch size for accurate predictions. Accordingly, male C57BL/6 mice (n = 19) were categorized into the following three groups: vehicle control (n = 5), high-fat diet (HFD) and CCl₄ positive control (n = 9), and HFD and CCl₄ with elafibranor (ELA) treatment (n = 5). Liver tissues were stained with Sirius-red, digitized as whole slide images, and cropped into patches of 32 × 32, 64 × 64, or 128 × 128 pixels. Each algorithm was trained, validated, and tested in an 8:1:1 ratio over 40 epochs with a batch size of 32 to classify fibrotic, normal, and background regions. All models performed robustly, with validation accuracies exceeding 98% and F1-scores above 0.96. Particularly, the 32 × 32 model exhibited the highest correlation with pathologist's measurements (Spearman's <i>r</i> = 0.9609; <i>p</i> < 0.05) and the most accurate estimation of absolute fibrotic area compared to expert assessments. This model also accurately detected the antifibrotic effects of ELA. These findings establish that the 32 × 32 patch-based classification approach provides a rapid, reproducible, and objective method for liver fibrosis quantification in preclinical toxicology, with strong potential for integration into digital pathology workflows.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-025-00326-8.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"42 2","pages":"235-250"},"PeriodicalIF":3.3,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12945867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147327098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}