Archives of Toxicology最新文献

{"title":"PET microplastics alter the transcriptome profile and oxidative stress markers in the liver of immature piglets: an in vivo study","authors":"Monika Golubska,&nbsp;Aleksandra Kurzyńska,&nbsp;Karol Mierzejewski,&nbsp;Ismena Gałęcka,&nbsp;Jarosław Całka,&nbsp;Iwona Bogacka","doi":"10.1007/s00204-025-04151-8","DOIUrl":"10.1007/s00204-025-04151-8","url":null,"abstract":"<div><p>The increasing global contamination with microplastics (MPs) poses a significant threat to human and animal health. Recent studies suggest that exposure to microplastics contributes to various detrimental hepatic effects, including oxidative stress and metabolic dysregulation. The aim of the present study was to investigate the global liver transcriptome, oxidative stress and selected liver function markers in immature piglets (<i>n</i> = 15) exposed to polyethylene terephthalate (PET) MPs for 4 weeks. The animals were divided into three groups: a low-dose MPs exposure group (0.1 g PET MPs/day), a high-dose MPs exposure group (1 g PET MPs/day), and a control group that did not receive MPs. The transcriptome profile of the liver was assessed using RNA-Seq. In addition, markers of oxidative stress (catalase, superoxide dismutase, glutathione peroxidase, glutathione transferase, and malondialdehyde) were determined using specific enzymatic assays, and the levels of selected liver function markers (bilirubin, collagen IV, alanine transaminase and aspartate aminotransferase) were measured by ELISA. The results showed that exposure to MPs, especially at a high dose, significantly altered the hepatic transcriptome profile. A low dose of PET MPs changed the expression of 5 genes, while a high dose affected the expression of 24 genes. The differentially expressed genes were associated with several biological processes such as cholesterol metabolism, transferase activity, and oxidation. Moreover, consumption of MPs resulted in increased catalase activity and decreased activity of superoxide dismutase and glutathione peroxidase in the liver. We also observed an increase in bilirubin and a decrease in collagen type IV, alanine aminotransferase, and aspartate aminotransferase content in the liver. These results suggest that PET MPs ingestion may disrupt systemic homeostasis and contribute to liver dysfunction.</p></div>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":"99 11","pages":"4595 - 4609"},"PeriodicalIF":6.9,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00204-025-04151-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Occurrence and environmental fate/behaviors of tire wear particles and their human and ecological health: an emerging global issue","authors":"Xin Li,&nbsp;Shiyu Zhou,&nbsp;Tao Zhang,&nbsp;Lei Bai,&nbsp;Fangru Chen,&nbsp;Xia Yan,&nbsp;Lei Luo,&nbsp;Kunming Tian","doi":"10.1007/s00204-025-04147-4","DOIUrl":"10.1007/s00204-025-04147-4","url":null,"abstract":"<div><p>Rapid societal and urban development has driven a surge in tire production, generating tire wear particles (TWPs), a pervasive environmental pollutant. Upon environmental release, TWPs interact with physio-chemical factors, altering their fate and amplifying toxicity. Available evidence indicates that TWPs mainly enter the organism body through inhalation and dermal contact. Toxicokinetic studies reveal that TWPs and additives penetrate biological barriers, accumulating in the liver and metabolizing via P450 enzymes, producing detoxified compounds or more toxic derivatives like N-(1,3-dimethylbutyl)-N’-phenyl-p-phenylenediamine-quinone(6PPD-q). Currently, the adverse ecological and health effects have gained increasingly public concerns. A series of advances have been achieved to address their ecological and human risks across aquatic, terrestrial, and mammal models, even at population level. Their toxicological effects span across respiratory diseases, metabolic disorders, and reproductive toxicology. Considering the challenges arising from the large-scale production and mismanagement of TWPs, this review synthesizes the latest knowledge on their generation, environmental fate, toxicokinetic, and ecological and human health effects. However, critical gaps remain in long-term low-dose effects, cross-generational toxicity, and biomarker validation. This review highlights the urgent need for global regulatory frameworks and interdisciplinary strategies to mitigate the cascading ecological and health impacts originated from TWPs.</p></div>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":"99 11","pages":"4353 - 4366"},"PeriodicalIF":6.9,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platelets mediate neutrophil infiltration and exacerbate liver injury and sinusoidal endothelial cell damage after a severe acetaminophen overdose in mice","authors":"Olamide B. Adelusi,&nbsp;Caitlin Schneider,&nbsp;Caylie McKimens,&nbsp;James P. Luyendyk,&nbsp;Anup Ramachandran,&nbsp;Hartmut Jaeschke","doi":"10.1007/s00204-025-04144-7","DOIUrl":"10.1007/s00204-025-04144-7","url":null,"abstract":"<div><p>Acetaminophen (APAP) overdose, the leading cause of acute liver failure in the US, is accompanied by hepatocyte necrosis and liver sinusoidal endothelial cell (LSEC) damage, with hepatic neutrophil infiltration and platelet deposition. However, the exact role played by platelets in the pathophysiology is not fully understood. To investigate this, we depleted platelets in C57Bl/6 J mice by injecting 2 mg/kg anti-CD41 antibody or IgG control 12 and 2 h before a moderate (300 mg/kg) or severe (600 mg/kg) APAP overdose. Platelet depletion did not affect liver injury as measured by plasma ALT levels and hepatic areas of necrosis 24 h after a moderate APAP overdose, but reduced hepatic neutrophil infiltration. After a severe overdose, platelet depletion caused a significant reduction in hepatic neutrophil infiltration, but contrary to the moderate overdose, it also significantly reduced liver injury. These findings were confirmed with a second platelet-depleting antibody (CD42b antibody). These results corroborate our previous findings, which showed that neutrophils exacerbate liver injury only after a severe APAP overdose but not a moderate one. Furthermore, severe APAP overdose induced LSEC injury 24 h after APAP, which was significantly reduced in platelet-depleted mice as measured by intrahepatic hemorrhage, increased hepatic von Willebrand factor deposition, and elevated plasma levels of hyaluronan. Thus, platelets contribute to endothelial cell injury and mediate neutrophil recruitment, which aggravates liver injury after a severe APAP overdose, underscoring the role of platelets in the pathophysiology.</p></div>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":"99 11","pages":"4575 - 4594"},"PeriodicalIF":6.9,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polychlorinated biphenyls (PCBs) interact with drug metabolism in vivo","authors":"Julian Peter Müller,&nbsp;Jens Rengelshausen,&nbsp;Salah Laieb,&nbsp;Maryam Safavi,&nbsp;Andrea Kaifie,&nbsp;Andre Esser,&nbsp;Thomas Schettgen,&nbsp;Jens Bertram,&nbsp;Julia Krabbe,&nbsp;Elke Schaeffeler,&nbsp;Jens Sarömba,&nbsp;Katja S. Just,&nbsp;Roman Tremmel,&nbsp;Matthias Schwab,&nbsp;Julia C. Stingl,&nbsp;Thomas Kraus,&nbsp;Patrick Ziegler","doi":"10.1007/s00204-025-04145-6","DOIUrl":"10.1007/s00204-025-04145-6","url":null,"abstract":"<div><p>Polychlorinated biphenyls (PCBs) are widespread environmental contaminants that interfere with xenobiotic metabolism, primarily by modulating cytochrome P450 (CYP) enzymes. However, their pharmacokinetic consequences in exposed individuals remain poorly defined. Here, we investigated the impact of PCB exposure on CYP enzyme activity using a combined clinical pharmacokinetic and in vitro mechanistic approach. Ten occupationally PCB-exposed individuals from the German HELPcB cohort and ten controls received a CYP phenotyping cocktail to assess enzyme function (Clinical Trial Registry: DRKS00028922). Plasma drug and metabolite concentrations were quantified to evaluate CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A activity, considering genetically defined metabolizer status. PCB118 exposure was significantly associated with reduced CYP1A2 activity (R² = 0.155, t = − 2.115, p = 0.049, β = − 0.446), indicating a decrease in CYP1A2 activity with higher PCB118 levels. This was further supported by in vitro assays demonstrating dose-dependent inhibition. In addition, PCB74 exposure showed a trend toward increased CYP2C9 activity, suggesting a potential inductive effect. Mechanistic studies revealed that PCB118 acts as both an inhibitor and a substrate of CYP1A2, generating reactive arene oxide intermediates that may contribute to mechanism-based inhibition. These findings challenge the traditional view of PCBs as merely chronic toxicants, showing that they can acutely alter drug metabolism and potentially impact drug efficacy and safety. Given the widespread presence of PCBs and other persistent organic pollutants, these results highlight the need to integrate environmental toxicant exposure into pharmacokinetic models to optimize drug therapy and minimize adverse effects.</p></div>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":"99 11","pages":"4423 - 4437"},"PeriodicalIF":6.9,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00204-025-04145-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nutrient environment improves drug metabolic activity in human iPSC-derived hepatocytes and HepG2","authors":"Victoria Pozo Garcia,&nbsp;Tuğçe S. Çobanoğlu,&nbsp;Helen Sophie Hammer,&nbsp;Rita Carlota,&nbsp;Kasper Holm,&nbsp;Catherine Verfaillie,&nbsp;Oliver Poetz,&nbsp;Paul Jennings,&nbsp;Sofia Moco","doi":"10.1007/s00204-025-04139-4","DOIUrl":"10.1007/s00204-025-04139-4","url":null,"abstract":"<div><p>Induced pluripotent stem cells (iPSCs) have emerged as a transformative tool in regenerative medicine, in liver research. The perspective of a stable and functional source of hepatocytes has led to developing protocols for human iPSC-derived hepatocytes-like cells (HLCs). Yet, hepatic models remain one of most challenging systems to functionally reproduce with iPSCs, due to its resulting limited metabolic function. Using an adapted nutrient regimen, two human hepatocyte models were characterized: HLCs (derived from iPSCs) and metabolically active HepG2 (mHepG2, derived from the cell line HepG2), for their drug metabolism activity. In these cell systems, the transcriptome, proteome, and metabolome of 11 drug-relevant cytochrome P450 (CYP) isoenzymes were studied. A liquid chromatography–mass spectrometry (LC–MS)-based metabolomics approach, using model drugs as isoenzyme reporters, was applied, achieving a comprehensive overview of mHepG2 and HLCs drug metabolism. Drugs used in this study to characterize xenobiotic machinery were: bupropion (25 µM), phenacetin (30 µM), rosiglitazone (10 µM), diclofenac (75 µM), dextromethorphan (15 µM), chlorzoxazone (60 µM), midazolam (15 µM), benzydamine (15 µM), coumarin (250 µM) and 7-ethoxycoumarin (60 µM). Being HepG2 notorious for its limited metabolic capacity, our study raises mHepG2 as a highly performant cell model, with activity on 8 drug-metabolizing CYPs. Modulation by nutrient environment in improving metabolic function of in vitro models is here proven as a key determinant. Likewise, HLCs hold the widest CYP coverage at the transcript level and were able to cope with a wide variety of chemical insults, making them a promising model for personalized metabolic studies.</p></div>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":"99 11","pages":"4493 - 4511"},"PeriodicalIF":6.9,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00204-025-04139-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Critical discussion of recently published claims of a causal relationship between bat decline and infant mortality","authors":"Philip Marx-Stoelting,&nbsp;Tewes Tralau,&nbsp;Veronika Städele,&nbsp;Stefanie Rotter,&nbsp;Vera Ritz,&nbsp;Jörg Rahnenführer,&nbsp;Jan G. Hengstler","doi":"10.1007/s00204-025-04142-9","DOIUrl":"10.1007/s00204-025-04142-9","url":null,"abstract":"","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":"99 9","pages":"3859 - 3862"},"PeriodicalIF":6.9,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00204-025-04142-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Time course of lung retention and toxicity of inhaled particles: short-term exposure to nano-Ceria","authors":"Jana Keller,&nbsp;Wendel Wohlleben,&nbsp;Lan Ma‑Hock,&nbsp;Volker Strauss,&nbsp;Sibylle Gröters,&nbsp;Karin Küttler,&nbsp;Karin Wiench,&nbsp;Christiane Herden,&nbsp;Günter Oberdörster,&nbsp;Bennard van Ravenzwaay,&nbsp;Robert Landsiedel","doi":"10.1007/s00204-025-04127-8","DOIUrl":"10.1007/s00204-025-04127-8","url":null,"abstract":"","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":"99 9","pages":"3863 - 3864"},"PeriodicalIF":6.9,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term TCDD oral exposure changes gut microbial glycosylation patterns in female but not male C57BL/6 mice","authors":"Doreen Reichert,&nbsp;Stefan Janssen,&nbsp;Andrea Rossi,&nbsp;Charlotte Esser","doi":"10.1007/s00204-025-04137-6","DOIUrl":"10.1007/s00204-025-04137-6","url":null,"abstract":"<div><p>2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) at high doses damages the liver and disrupts gut microbiota in mice. We investigated whether very low TCDD doses also cause dysbiosis and if sex-specific differences exist. Male and female C57BL/6 mice received 1 µg TCDD/kg body weight initially and maintenance doses biweekly for 12 weeks; controls received DMSO/corn oil. Fecal pellets were collected throughout, and cecal, liver, and gut samples at euthanasia. Mice did not suffer weight loss, and the liver weight to body weight ratio remained normal in all groups. Barrier genes’ expression was unaffected in all groups. 16S sequencing of fecal pellets revealed an increase in α-diversity over the 12-week treatment period, regardless of TCDD exposure or sex. No significant differences in α-diversity were observed between control and TCDD-treated groups. Analysis of β-diversity indicated differences in microbiota composition between male and female mice, as well as over time. However, probably due to low sample numbers, we could not detect significant differences using UniFrac or other ß-diversity metrics. However, our flow cytometry-based analysis tool, FlowSoFine™, identified significantly distinct microbial signatures in TCDD-treated female mice compared to control females. We hypothesized that this could be due to the formation of bacterial clusters or to different glycosylation patterns, both undetectable by sequencing. We therefore stained the cecal material with a panel of seven fluorescent lectins, which detect typical bacterial sugar structures, i.e., glycans. Significant changes were detected for concanavalin A, soybean agglutinin, and <i>Dolichos biflorus</i> agglutinin binding in the gut microbiota in female but not in male mice. We isolated bacteria by fluorescence-activated cell sorting (FACS), which differed between TCDD-treated and control female mice. 16S sequencing of these bacteria revealed a high frequency of <i>Lachnospiraceae</i> and reduced amount of <i>Lactobacillaceae, CAG-508</i>, and <i>Oscillospiraceae</i> in the TCDD-exposed samples. Glycoconjugates govern biofilm formation, infectious behavior of bacteria, and host immune responses, but little is known about diet or xenobiotic induced changes in glycosylation. We conclude that assessing glycosylation parameters in studies of dysbiosis is relevant, as well as stratifying for sex-specific differences.</p></div>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":"99 11","pages":"4467 - 4480"},"PeriodicalIF":6.9,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00204-025-04137-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NAD(P)+-dependent alcohol oxidoreductases oxidize 7-hydroxycannabidiol to a reactive formyl metabolite","authors":"Qiangen Wu,&nbsp;Jia-Long Fang,&nbsp;Suresh K. Nagumalli,&nbsp;Xiaoqing Guo,&nbsp;Frederick A. Beland","doi":"10.1007/s00204-025-04140-x","DOIUrl":"10.1007/s00204-025-04140-x","url":null,"abstract":"<div><p>Cannabidiol (CBD) undergoes oxidation to 7-hydroxy-CBD in the liver via cytochrome P450 enzymes. 7-Hydroxy-CBD can be further oxidized to 7-carboxy-CBD, the principal circulating metabolite in humans. An aldehyde intermediate, 7-formyl-CBD, is hypothesized to be the precursor of 7-carboxy-CBD; however, the formation of 7-formyl-CBD and the enzymes leading to its formation and metabolism have not been thoroughly investigated. Upon incubating 7-hydroxy-CBD with human liver S9 or microsomes, and using <i>O</i>-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine (PFBHA) as a trapping agent, we demonstrated the formation of 7-formyl-CBD as its oxime derivative 7-pentafluorobenzyl oxime-CBD (7-PFBO-CBD). The transformation of 7-hydroxy-CBD to 7-formyl-CBD in S9 or microsomes required NAD⁺ or NADP⁺. Trapping 7-formyl-CBD with PFBHA decreased the formation of 7-carboxy-CBD, indicating that the formation of 7-carboxy-CBD depends on the availability of 7-formyl-CBD. The flavonoid kaempferol, which inhibits xanthine oxidoreductase and hydroxysteroid dehydrogenases, suppressed the formation of 7-PFBO-CBD and 7-carboxy-CBD in human liver S9 and microsomes incubated with 7-hydroxy-CBD. The xanthine oxidoreductase inhibitor allopurinol and its substrate xanthine did not affect the metabolism of 7-hydroxy-CBD. The hydroxysteroids estradiol and dehydroepiandrosterone reduced the formation of 7-carboxy-CBD in liver microsomes and S9. These results suggest that alcohol oxidoreductases associated with hydroxysteroid metabolism may play a role in the conversion of 7-hydroxy-CBD to 7-formyl-CBD. The irreversible aldehyde dehydrogenase inhibitors, disulfiram and WIN 18,446, inhibited the formation of 7-carboxy-CBD and led to a significant accumulation of 7-PFBO-CBD in the S9 and microsomal incubations. The accumulation of the aldehyde intermediate may play a role in the enhanced cytotoxicity of 7-hydroxy-CBD in HepG2 cells when co-treated with disulfiram. These findings indicate that NAD(P)⁺-dependent alcohol oxidoreductases may catalyze the conversion of 7-hydroxy-CBD to 7-formyl-CBD in human liver S9 and microsomes. The potentially toxic aldehyde intermediate is further oxidized by aldehyde dehydrogenase to 7-carboxy-CBD.</p></div>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":"99 11","pages":"4411 - 4421"},"PeriodicalIF":6.9,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144740984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The important role of standards for the uptake of transcriptomics and metabolomics based in vitro methods in regulatory toxicology","authors":"Julia M. Malinowska,&nbsp;Maurice Whelan","doi":"10.1007/s00204-025-04119-8","DOIUrl":"10.1007/s00204-025-04119-8","url":null,"abstract":"<div><p>Driven by increasing regulatory interest in applying omics-based methods and reducing animal testing, this study reviewed existing documentary standards for transcriptomics and metabolomics, focusing on those applicable to in vitro test systems. Investigation revealed the landscape to be heterogeneous: for transcriptomics (using RNA-seq), some documentary standards have been produced by formal standardisation bodies (e.g., International Organization for Standardization), whilst for metabolomics (using MS), these were primarily driven by the work of the scientific community developing best practices. The value of reference materials is also highlighted since they enable characterisation of both (analytical) intra-laboratory repeatability and reproducibility as well as inter-laboratory reproducibility. Leveraging standards within omics-based in vitro methods that enter the OECD Test Guideline Programme will ensure their reliability, accessibility across jurisdictions, and sustainability for their long-term use. These benefits are explained with practical examples and make the case for better use of existing standards and initiating targeted development of new standards for efficient and effective development of international Test Guidelines based on in vitro transcriptomics and metabolomics methods.</p></div>","PeriodicalId":8329,"journal":{"name":"Archives of Toxicology","volume":"99 10","pages":"3865 - 3875"},"PeriodicalIF":6.9,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s00204-025-04119-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}