Toxicological Sciences最新文献

{"title":"Integrating experimental data and mechanistic modeling to assess potential lead exposure from tampon use.","authors":"Corie A Ellison, Patrick R Doyle, Christina A Haven, Denise M Mcclenathan, Cindy M Obringer, Kara E Woeller","doi":"10.1093/toxsci/kfag052","DOIUrl":"https://doi.org/10.1093/toxsci/kfag052","url":null,"abstract":"<p><p>Trace levels of lead (Pb) have been reported in tampons, prompting concerns about potential exposure during menstrual product use. However, the presence of a chemical in a product does not necessarily translate to biologically relevant exposure. In this study, we characterized the distribution and binding of Pb in menstrual fluid and developed a deterministic, compartmental mass-balance model to evaluate the release and fate of Pb that may be present as an inadvertent trace impurity in tampons. Our experimental measurements demonstrated that Pb preferentially partitions to the red blood cell (RBC) fraction of menstrual fluid. The remaining Pb distributed in the plasma fraction, where the majority was protein-bound. These distribution and binding characteristics were broadly comparable to those reported for systemic blood. Utilizing these data, a mechanistic model was parameterized to describe release of Pb from a tampon into menstrual fluid, partitioning between menstrual fluid compartments, re-absorption into the tampon during fluid uptake, and potential permeation across vaginal tissue. Under the conservative assumptions evaluated here, model simulations for a four-hour tampon wear scenario predicted that the majority of theoretically released Pb is reabsorbed into the tampon, with only a very small fraction (<1 ng; <0.3%) available for potential absorption into vaginal tissue. Sensitivity and alternative release scenario analyses demonstrated that predicted tissue uptake remained minimal across various plausible conditions. Collectively, these findings underscore the importance of integrating chemical presence data with physiological context and mechanistic modeling to inform exposure assessment and support science-based evaluation of product safety.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843165","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":"Contemporary Review: Temporal Dynamics of Neuroinflammation in Response to Environmental Exposure.","authors":"Brenna Baird, Shahani Noor, Shuguang Leng, Andrew Ottens, Matthew J Campen","doi":"10.1093/toxsci/kfag051","DOIUrl":"https://doi.org/10.1093/toxsci/kfag051","url":null,"abstract":"<p><p>Neuroinflammation is the brain's immune response to injury or disease and can negatively impact neurological functions, ranging from mood, cognition, learning and memory, as well as promote neurodegenerative disease and even psychiatric conditions. Different environmental factors may trigger a neuroinflammatory response; the mechanisms of this activation may influence the pattern of activation, the immune subsets involved, and the persistence of the response. The duration of neuroinflammation may significantly outlast exposures, creating a potential unique vulnerability for rare or intermittent exposures. The neuroinflammatory response can be classified into acute, sub-acute and chronic phases, with sub-acute neuroinflammation representing a transient state between acute and chronic inflammation. This phase, lasting from days to weeks, is denoted by metabolic disruptions, cognitive impairments, and peripheral immune activation. Environmental exposures such as such as air pollution, pesticides, heavy metals, and social factors impact oxidative stress, glial activation, and blood-brain barrier disruption leading to neuronal injury and cognitive decline. Notably, exposures like diesel fumes and wildfire smoke have been shown to induce neuroinflammation, subsequently impacting memory and learning, and exacerbating mental health conditions such as PTSD, depression and anxiety. Triggering of reactive astrogliosis via impacts on the blood-brain barrier function may be the most common non-specific manner that environmental toxicants drive neuroinflammation, but direct outcomes from compounds that readily access the brain are also possible.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843189","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":"RENAsym, a Quantitative Systems Toxicology Platform Model, Designed to Predict Drug-Induced Kidney Injury Indicates Polymyxin B and Valproate Overdose Toxicity Potential While Simultaneously Demonstrating Acetaminophen and Valproate Safety at Therapeutic Levels.","authors":"Celeste Vallejo, Pallavi Bhargava, Nader Hamzavi, Matthew McDaniel, Vinal V Lakhani, Timothy Qi, Christina Battista, Lara Clemens, Lisl K M Shoda, Zackary R Kenz, Shailendra Tallapaka, Yeshitila Gebremichael, Jeffrey L Woodhead","doi":"10.1093/toxsci/kfag047","DOIUrl":"https://doi.org/10.1093/toxsci/kfag047","url":null,"abstract":"<p><p>RENAsym is a quantitative systems toxicology (QST) modeling platform designed to predict drug-induced kidney toxicity. The model includes the proximal tubule cell (PTC) life cycle, regeneration of PTCs, sodium reabsorption, nephron death, and drug-induced injury and inflammation within the proximal tubules. The mechanisms of drug-induced toxicity included are overproduction of reactive oxygen species and mitochondrial dysfunction. Inputs into the QST model include the drug's exposure in the kidney and results from in vitro toxicity assays used to parameterize the toxicity mechanisms included in the model. The QST model has a wide array of outputs including fraction of viable PTCs, fraction of viable nephrons, and serum creatinine concentration over time that allow the user to assess the extent of kidney injury induced by a drug. Polymyxin B, valproate, and acetaminophen were three compounds used to test RENAsym's ability to correctly classify compounds as either nephrotoxic or safe. The model successfully identified polymyxin B and valproate as drugs with the potential to cause kidney injury and acetaminophen as a drug that does not cause kidney injury at therapeutic levels, providing increased confidence that the model can be used to indicate kidney injury liability using in vitro inputs before dosing in clinical settings.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843248","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":"RNAseq analysis demonstrates polarization state-dependent responses to ambient particulate matter in a particle composition-specific manner.","authors":"Timothy R Smyth, Stephanie Brocke, Weidong Wu, Zhen An, Ilona Jaspers","doi":"10.1093/toxsci/kfag050","DOIUrl":"https://doi.org/10.1093/toxsci/kfag050","url":null,"abstract":"<p><p>Macrophages are key innate immune cells which exist on a spectrum between pro-inflammatory (M1) and pro-resolutory (M2) states while retaining the ability to reprogram following exposure to new stimuli. Particulate matter (PM) exposure significantly alters macrophage function, leading to increasing respiratory infection morbidity and mortality. However, the influence of macrophage polarization on PM responses remains poorly understood. We hypothesized that human macrophages would demonstrate polarization state- and seasonality-specific responses to airborne PM collected from Xinxiang, China. CD14+CD16- monocytes were differentiated into macrophages and polarized using established methods with or without PM co-exposure followed by RNA sequencing (RNAseq). Macrophage expression profiles were primarily determined by inflammatory (M1) versus naive (M0) and alternative activation (M2), regardless of PM exposure. However, differential expression analysis using polarization state-specific reference groups uncovered distinct gene and pathway expression patterns. Directly polarized M0->M1 macrophages exhibited the fewest unique differentially expressed genes (DEGs) but displayed similar pathway level activity to reprogrammed M2->M1 cells. M2 macrophages showed the highest number of unique DEGs suggesting increased chemotactic pathway activity. Conversely, M0 cells exhibited greater expression of major inflammatory cytokines and chemokines. While polarization state was the primary driver of gene and pathway responses, expression levels varied depending on PM collection dates and correlated strongly with individual PM components in M0 and M2 cells. These findings highlight the need to consider both particle seasonality and macrophage polarization state when studying PM's impact on macrophages as these factors may contribute to the negative health outcomes associated with PM exposure during respiratory infections.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821123","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":"High-concentration MEHP triggers mtDNA depletion in undifferentiated HepaRG and C2C12 cultures and disrupts mitochondrial homeostasis in both HepaRG culture states.","authors":"Md Mostafijur Rahman, Pabitra Khadka, Carolyn K J Young, Jing Wang, Elizabeth M McCormick, Marni J Falk, Matthew J Young","doi":"10.1093/toxsci/kfag049","DOIUrl":"https://doi.org/10.1093/toxsci/kfag049","url":null,"abstract":"<p><p>Phthalates are often called \"everywhere chemicals\" because they are widely used in consumer products and are detectable in the environment and humans. One of the most studied phthalates, di-2-ethylhexyl phthalate (DEHP), is metabolized to mono-(2-ethylhexyl) phthalate (MEHP), which is known to disrupt metabolic processes through peroxisome proliferator-activated receptor (PPAR) signaling. However, accumulating evidence suggests that lipophilic phthalates also affect mitochondria, key regulators of oxidative metabolism, autophagy, and apoptosis. Based on previous observations that undifferentiated cells are more sensitive to a mitotoxic agent, we hypothesized that MEHP differentially affects mitochondrial function and mtDNA maintenance across hepatic cell states. To test this, we used the human HepaRG hepatoma-derived cell line, which can be cultured in undifferentiated and differentiated states, and assessed viability and mitochondrial function following prolonged 6- and 12-day high-concentration MEHP treatments. Prolonged treatments reduced viability and altered bioenergetics in both states. Short treatments (1-3 days) reduced viability only in differentiated cultures and were associated with mtDNA depletion in undifferentiated cultures. In both states, MEHP increased the expression of the low-molecular-weight mitochondrial genome maintenance exonuclease (MGME1) isoform, altered the levels of autophagy-related factors, and induced apoptosis. In another mitochondrial-competent myoblast model (C2C12 cells), a high concentration of MEHP was associated with mtDNA depletion, whereas lower concentrations were associated with modest reductions in cell density without detectable mtDNA loss. These results demonstrate state-dependent mitochondrial responses to MEHP and indicate that a reduced endpoint cell density is a sensitive outcome occurring independently of, and at lower concentrations than, mtDNA depletion in undifferentiated cells.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782029","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":"Omeprazole activation of CD4+ and CD8+ T-cells through off-target covalent modification of cellular proteins.","authors":"Sophie Grice, Sa'd Albashtawy, Georgia Wells, Luisa Hering, Kareena Adair, Joscelyn Sarsby, Philip Brownridge, Megan Ford, Rachel Lloyd, Lucy Hampson, Annette Wagner, Yonghu Sun, Hong Liu, Sean Hammond, Xiaoli Meng, Furen Zhang, Dean Naisbitt","doi":"10.1093/toxsci/kfag046","DOIUrl":"https://doi.org/10.1093/toxsci/kfag046","url":null,"abstract":"<p><p>Targeted covalent inhibition of protein function is increasingly used as a therapeutic mode of action; however, there is a need to characterize off-target binding interactions and to understand whether this represents an immunological risk. Given that the proton-pump inhibitor omeprazole exerts its mechanism of action through covalent inhibition, it serves as an ideal model to investigate the relationship between off-target protein binding and T-cell activation. Binding of omeprazole, omeprazole metabolites and alternative proton-pump inhibitors to antigen presenting cells and GST-pi was characterised by mass spectrometry. Omeprazole-responsive clones were generated and assessed in terms of cytokine secretion, pathways of T-cell activation and crossreactivity with omeprazole metabolites, alternative proton-pump inhibitors and unrelated drugs. Omeprazole stimulated CD4+ and CD8+ T-cell clones to proliferate and secrete cytokines and cytolytic molecules. HLA-restricted T-cell activation was dependent on processing of omeprazole protein adducts by antigen presenting cells. Omeprazole-modified CYS-containing peptides derived from 36 off-target proteins were detected within antigen presenting cells. Omeprazole metabolites and alternative protein pump inhibitors that form protein adducts also activated omeprazole-responsive T-cells. In conclude, T-cells were activated with omeprazole via a hapten mechanism and exhibited considerable promiscuity to metabolites and structurally-related drugs of the same pharmacological class. Similar off-target binding interactions may be a relevant concern for the increasing number of covalent inhibitor drugs receiving regulatory approval.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147780890","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":"An environmentally relevant mixture of organophosphate esters induces cholesterol biosynthesis in THP-1 macrophages.","authors":"Braeden H Giles, Bernard Robaire, Koren K Mann","doi":"10.1093/toxsci/kfag048","DOIUrl":"https://doi.org/10.1093/toxsci/kfag048","url":null,"abstract":"<p><p>Organophosphate esters (OPEs), widely used as flame retardants and plasticizers, are environmental toxicants known to disrupt lipid metabolism. Although most studies have focused on individual OPEs, environmental exposures typically involve complex mixtures. Our previous studies demonstrated that a representative OPE mixture from Canadian household dust promotes cholesterol and lipid droplet accumulation in THP-1 macrophages. However, the molecular mechanisms underlying this lipid dysregulation remain unclear. Here, we employed tandem mass tag (TMT)-based quantitative proteomics to investigate how OPE mixtures alter protein expression and lipid regulation in macrophages. THP-1 macrophages were exposed to vehicle or environmentally relevant dilutions of the OPE mixture for 48 hours. Lysates were subjected to TMT labeling and mass spectrometry. Bioinformatic analyses using STRING and Ingenuity Pathway Analysis identified 162 differentially expressed proteins, with unsupervised clustering highlighting cholesterol biosynthesis as a key pathway. Further validation via qPCR and upstream analysis implicated the sterol regulatory element-binding protein 2 (SREBP2) signaling axis in OPE-induced cholesterol biosynthesis. Functional assays revealed that atorvastatin-mediated HMG-CoA reductase inhibition, the rate limiting enzyme in cholesterol biosynthesis, prevents cholesterol buildup and lipid droplet formation in macrophages. These findings provide the first evidence that an environmentally relevant OPE mixture can induce cholesterol biosynthesis in human macrophages.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147782032","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":"Integration of mechanistic and repeat dose toxicity data in the derivation of an oral reference dose for HFPO-DA.","authors":"Chad M Thompson, Melissa M Heintz, Sarah I Rogers, Melissa J Vincent, Laurie C Haws","doi":"10.1093/toxsci/kfag045","DOIUrl":"https://doi.org/10.1093/toxsci/kfag045","url":null,"abstract":"<p><p>HFPO-DA (ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate) is a short-chain perfluoroether carboxylic acid used as a polymerization aid in the manufacture of some types of fluorinated polymers. Existing toxicity criteria for HFPO-DA include chronic and subchronic oral reference dose (RfD) values based on liver effects in mice. New mechanistic data demonstrate that these liver effects are incontrovertibly linked to rodent-specific peroxisome proliferator-activated receptor alpha (PPARα) signaling pathways that lack human relevance. Therefore, it was critical to reevaluate existing HFPO-DA RfD values. A literature review was conducted to identify human and animal studies that might serve as the basis of updated toxicity criteria. Relevant studies were considered along with a newly completed chronic bioassay in mice. No epidemiological studies were determined acceptable for use in toxicity value development. The only neoplasms in the chronic mouse bioassay were in the liver and were considered PPARα related. The most sensitive extrahepatic noncancer endpoints in rodents involved placental lesions in reproductive and developmental toxicity studies and reduced testicular cellularity in mice following chronic exposure. Both effects resulted in RfD values of 0.001 mg/kg-day. Also presented are probabilistic risk assessment methods that resulted in a similar probabilistic RfD. These results indicate the need to update existing toxicity criteria for HFPO-DA.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676987","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":"Temporal variation in markers of immune signaling and wound repair in primary human airway epithelial cells following acute versus repeated woodsmoke condensate exposure.","authors":"Elise Hickman, Chloe K Chou, Cole Seifert, Jessie Chappel, Yong Ho Kim, Elizabeth Corteselli, Julia E Rager","doi":"10.1093/toxsci/kfag035","DOIUrl":"10.1093/toxsci/kfag035","url":null,"abstract":"<p><p>Wildfire smoke (WFS) exposures are becoming more common, and firefighters and community members are often exposed to WFS for days to weeks. Controlled studies assessing the effects of repeated exposure to WFS and woodsmoke (WS; as a surrogate for WFS) or compared acute versus repeated exposure have evaluated a limited number of timepoints and endpoints using rodent models. Here, we leveraged differentiated primary human bronchial epithelial cells (HBECs) to test the hypothesis that different molecular responses occur upon acute versus repeat exposures to WS. HBECs (n = 4 donors) were exposed to 22 µg/cm2 red oak WS condensate for an acute, 4-h exposure, or repeat exposures of 4 h/d, 3 d/wk, across 2 wk. Membrane permeability, cell viability, and transcriptional responses were measured at the end of each exposure paradigm, and secreted proteins were measured throughout the repeat exposure. Acute exposure significantly increased expression of genes involved in fibrosis and immune response, whereas repeated exposure significantly decreased expression of genes involved in tissue repair and remodeling. Secreted protein responses were similar to transcriptomic responses and demonstrated temporal variation in response to exposure. This study supports the feasibility of using HBECs to evaluate acute and repeat WS exposures and indicates differential responses from these exposures with direct relevance to pulmonary disease processes, including those involved in fibrosis, asthma, and chronic obstructive pulmonary disease. These findings highlight the need for future studies to better understand molecular responses to repeated smoke exposures.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147494467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling toxicological adverse outcomes: toward construction and simulation of large-scale networks.","authors":"Nensi Ikonomi, Natalie Ketter, Mario A A Pepe","doi":"10.1093/toxsci/kfag043","DOIUrl":"10.1093/toxsci/kfag043","url":null,"abstract":"<p><p>Predicting toxicological adverse outcomes is crucial for advancing in silico toxicology strategies. Modern toxicology increasingly relies on systems biology approaches to model and interpret these outcomes. Adverse outcome pathways (AOPs) focus on systems-level descriptions and causal linear relations among initiating, key, and adverse outcome events. Key characteristics (KC)-based topologies capture mechanistic breadth via interconnected property-based modules without assuming linear causality. From another perspective, emerging physiological maps dive deeper into toxicological mechanisms by mapping them at the detailed molecular level. To capture the dynamic nature of toxicological responses, especially their time- and dose-dependent behaviors, there is growing interest in integrating systems biology and mathematical modeling strategies. Although dynamic models have been applied to small-scale AOPs, larger regulatory networks remain largely unexplored from a dynamic perspective. In this review, we highlight recent efforts to combine systems and network biology approaches for predicting toxicological adverse outcomes, covering network construction, analysis, and dynamic predictions. We also explore the aspect of dynamically simulating large-scale molecular networks and its potential contribution to systems toxicology. Specifically, we charter the use of logic-based models (Boolean networks) as an integrative approach to understand molecular crosstalk and cellular phenotypes, highlighting the potential repurpose of existing models. To this end, we show 2 use cases on toxicological applications of Boolean network models. Finally, we prospectively discuss the importance and need of bridging molecular and systemic scales and integrating these modeling strategies with high-dimensional data sources, including omics and multi-omics datasets.</p>","PeriodicalId":23178,"journal":{"name":"Toxicological Sciences","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13120877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147676967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}