Frontiers in toxicology最新文献

{"title":"Elucidating the mechanistic relationships between peroxisome proliferator-activated receptors and hepatic fibrosis using the ROBOKOP knowledge graph.","authors":"Karamarie Fecho, Nyssa Tucker, Jon-Michael Beasley, Scott S Auerbach, Chris Bizon, Alexander Tropsha","doi":"10.3389/ftox.2025.1549268","DOIUrl":"https://doi.org/10.3389/ftox.2025.1549268","url":null,"abstract":"<p><p>We developed the Reasoning Over Biomedical Objects linked in Knowledge Oriented Pathways (ROBOKOP) application as an open-source knowledge graph system to support evidence-based biomedical discovery and hypothesis generation. This study aimed to apply ROBOKOP to suggest biological mechanisms that might explain the hypothesized relationship between exposure to the herbicide and lipid-lowering drug clofibrate, an activator of peroxisome proliferator-activated receptor-α (PPARA), and hepatic fibrosis. We queried ROBOKOP to first establish that it could demonstrate a relationship between clofibrate and PPARA as a validation test and second to identify intermediary genes and biological processes or activities that might relate the activation of PPARA by clofibrate to hepatic fibrosis. Queries of ROBOKOP returned several paths relating clofibrate, PPARA, and hepatic fibrosis. One path suggested the following: <i>clofibrate - affects / increases_ expression_ of / increases_ activity_ of / increases_ response_ to / decreases_ response_ to / is_ related_ to - PPARA - is_ actively_ involved_ in - cellular response to lipid - actively_ involves - CCL2 - is_ genetically_ associated_ with - hepatic fibrosis</i>. This result established a relationship between clofibrate and PPARA and further suggested that PPARA is actively involved in the cellular response to lipids, which actively involves the chemokine ligand CCL2, a gene genetically associated with hepatic fibrosis; thus, we can infer that PPARA, upon activation by clofibrate, plays a role in hepatic fibrosis. We conclude that ROBOKOP can be used to derive insights into biological mechanisms that might explain relationships between environmental exposures and liver toxicity.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1549268"},"PeriodicalIF":3.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Critical values for dimensional parameters of mesotheliomagenic mineral fibers: evidence from the dimensions and rigidity of MWCNT.","authors":"Ann G Wylie, Andrey A Korchevskiy","doi":"10.3389/ftox.2025.1568513","DOIUrl":"https://doi.org/10.3389/ftox.2025.1568513","url":null,"abstract":"<p><p>MWCNT (multi-walled carbon nanotubes) used in 72 animal instillation or inhalation studies were classified by average length, average width, Young's modulus, Rigidity Index (RI), and potency for mesothelioma in animals. The RI is based on the Euler buckling theory. MWCNT that induce mesothelioma have average lengths >2 µm and widths >37 nm, and average RI > 0.05 (µm² x GPa x 10⁴). Many noncarcinogenic MWCNT materials have RI < 0.05 and lack biological rigidity. In comparison, Elongate Mineral Particle (EMP) populations with one exception have RI > 0.05. Mineral particles likely to have RI < 0.05 include chrysotile fibrils with lengths >5 μm, amosite and crocidolite fibers with widths <60 nm, and sheet silicate fibers with widths <200 nm. The product of percent EMPA, average RI, and biosolubility among silicates correlates with known mesothelioma potency. The derived models reproduce published values of R_M with high statistical significance (P < 0.05). Average RI, length, and width are critical parameters for mesotheliomagenicity for both MWCNT and EMPA mineral fiber.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1568513"},"PeriodicalIF":3.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing a predictive model for blood-brain-barrier permeability to explore relevance of <i>in vitro</i> neurotoxicity data for <i>in vivo</i> risk assessment.","authors":"Siena E Illa, Yumei Feng Earley, Li Li, Dingsheng Li","doi":"10.3389/ftox.2025.1535112","DOIUrl":"https://doi.org/10.3389/ftox.2025.1535112","url":null,"abstract":"<p><strong>Introduction: </strong>Despite recent rapid advancements in <i>in vitro</i> toxicology, its application to whole-body health outcomes remains limited. Incorporating factors like internal exposure, such as permeability across biomembranes, could improve its relevance. Notably, there is a lack of data and predictive models for blood-brain barrier (BBB) permeability, a proxy for the exposure of target organs to neurotoxicity. We developed a predictive model for BBB permeability to investigate whether it can strengthen the correlation between <i>in vitro</i> and <i>in vivo</i> neurotoxicity data.</p><p><strong>Methods: </strong>We collected permeability data from parallel artificial membrane permeability assays for brain membranes (PAMPA-BBB) for 106 compounds with varied physicochemical properties. This was utilized to develop an empirical model to expand the potential coverage of chemicals. A list of 23 chemicals with available <i>in vivo</i> and <i>in vitro</i> neurotoxicity data from EPA IRIS and ToxCast was curated to analyze the correlation in toxicity rankings with the Spearman correlation coefficient, with and without the consideration of permeability from our predictive model.</p><p><strong>Results: </strong>The PAMPA-BBB predictive model showed promising results, with an R2 of 0.71 (measured vs predicted permeabilities). Considering permeability did not improve the correlation between <i>in vitro</i> and <i>in vivo</i> neurotoxicity (0.01 vs -0.11).</p><p><strong>Discussion: </strong>This weak correlation may stem from model uncertainty and the exclusion of other toxicokinetic processes, along with interspecies toxicodynamics differences. Our results indicate more detailed information on how neurotoxic substances behave inside the body is essential to better utilize the <i>in vitro</i> neurotoxicity data for predicting <i>in vivo</i> toxicity and assessing the risk to the central nervous system.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1535112"},"PeriodicalIF":3.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure to deltamethrin leads to gill liver damage, oxidative stress, inflammation, and metabolic disorders of Japanese flounder (<i>Paralichthys olivaceus</i>).","authors":"Bingbu Li, Guixing Wang, Xinyu Zheng, Mingyang Liu, Yucong Yang, Yuqin Ren, Yitong Zhang, Yufeng Liu, Zhongwei He, Jiangong Ren, Hailong Wan, Wei Cao, Yufen Wang, Xiaoyan Zhang, Jilun Hou","doi":"10.3389/ftox.2025.1560192","DOIUrl":"https://doi.org/10.3389/ftox.2025.1560192","url":null,"abstract":"<p><strong>Introduction: </strong>Deltamethrin is a pyrethroid insecticide commonly used to kill animal parasites in aquaculture. However, increasing evidence suggests that deltamethrin affects the health of aquatic animals by causing tissue damage and even death.</p><p><strong>Methods: </strong>In this study, the damage caused by deltamethrin to the gill and liver tissues, as well as its effects on oxidative stress and immune metabolism, were studied in <i>Paralichthys olivaceus</i>.</p><p><strong>Results: </strong>We observed a positive correlation between the residual levels of deltamethrin (Del) and the exposure concentrations, with the highest residue detected in the 0.28 μg/L concentration group (0.0684 mg/kg at 7 days). Then, we observed different degrees of damage to the gill and liver tissues of the Paralichthys olivaceus, including swelling, apical fusion, shedding of gill secondary lamellae, liver cell necrosis, and nuclear vacuolization, by observing tissue sections. Lysozyme enzyme activity increased, whereas catalase and alkaline phosphatase enzyme activities decreased. The liver transcriptome results of the control and high-concentration (0.28 μg/L) groups showed that there were 697 differentially expressed genes, including 390 upregulated and 307 downregulated genes. These differentially expressed genes were significantly enriched in oxidation-reduction, ferroptosis, steroid biosynthesis, and apoptosis pathways.</p><p><strong>Discussion: </strong>In summary, we found that deltamethrin induces oxidative stress and metabolic disorders in <i>P. olivaceus</i> and leads to inflammation. However, the fish body resists such damage through a complex regulatory network. These experimental results provide a theoretical reference for the safe use of deltamethrin in <i>P. olivaceus</i>.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1560192"},"PeriodicalIF":3.6,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing a feasible fast-track testing method for developmental neurotoxicity studies: alternative model for risk assessment of micro- and nanoplastics.","authors":"Xian Wu, TinChung Leung, Dereje D Jima, Majemite Iyangbe, John Bang","doi":"10.3389/ftox.2025.1567225","DOIUrl":"https://doi.org/10.3389/ftox.2025.1567225","url":null,"abstract":"<p><p>Micro- and nanoplastics (MNPs) are widespread environmental pollutants that pose significant health risks. They originate from industrial processes, consumer products, and environmental degradation, inducing oxidative stress through cellular dysfunctions such as membrane interaction, internalization, mitochondrial damage, inflammation, metal ion leaching, and impaired antioxidant defense. Despite increasing evidence of their toxicity-particularly developmental neurotoxicity (DNT) and mitochondrial impairment-our understanding remains limited due to the high costs of animal studies, which reduce the overall size of experimental data. This underscores the urgent need for alternative test methods that are cost-effective, rapid, and translational. This review examines new approach methodologies (NAMs) for DNT assessment, addressing the ethical, financial, and translational limitations of animal models. NAMs integrate three complementary non-animal models that enhance conventional testing. First, zebrafish models provide organismal insights into behavioral and neurodevelopmental outcomes at minimal cost. Second, neuronal organoids replicate human-specific neurodevelopmental processes in a 3D system, offering mechanistic insights. Lastly, human cell lines enable high-throughput screening, integrating findings from zebrafish and organoid studies. Establishing a new paradigm for DNT testing is crucial for faster and more efficient toxicity and risk assessments, ultimately protecting public health. Standardizing and gaining regulatory acceptance for NAMs will improve predictive accuracy and broaden their application in environmental toxicology. Advancing these methodologies is essential to addressing the risks of MNP exposure while promoting ethical and sustainable research practices.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1567225"},"PeriodicalIF":3.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12037614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144054751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute cannabis intoxication among the paediatric population.","authors":"Ginevra Malta, Giuseppe Davide Albano, Gianluca Lavanco, Anna Brancato, Carla Cannizzaro, Antonina Argo, Simona Contorno, Fulvio Plescia, Stefania Zerbo","doi":"10.3389/ftox.2025.1558721","DOIUrl":"https://doi.org/10.3389/ftox.2025.1558721","url":null,"abstract":"<p><p>This narrative review synthesizes the toxicological, clinical and medico-legal aspects of paediatric cannabis intoxication. By providing a comprehensive overview, it aims to inform future research, guide policymaking, and enhance clinical and toxicological practice in addressing this growing public health concern. The pharmacokinetics of cannabinoid ingestion in children are significantly influenced by the immaturity of their gastrointestinal tract and metabolic enzyme systems, resulting in altered oral bioavailability. Clinical data indicate that Δ9-tetrahydrocannabinol (THC)-related effects in paediatricpaediatric patients typically emerge within 2 hours of ingestion, with more severe symptoms developing within 4 hours. The endocannabinoid system (ECS) undergoes significant developmental changes, with marked differences in cannabinoid receptor expression and distribution across fetal, neonatal, and adult brains. During neurodevelopment, CB1 receptors exhibit unique expression patterns, including transient localization in brainstem regions critical for neurovegetative functions. These developmental dynamics likely explain children's heightened sensitivity to THC's neurological and neurovegetative effects, often resulting in more severe outcomes compared to adults. The reliable detection of cannabinoids involves integrating screening methods with confirmatory analytical techniques. Urine immunoassay testing is widely considered an helpful toolto assess a previous exposure, becoming positive within 3-4 h of ingestion. However, this method is prone to false positives. Plasma THC concentration, when measured close to the event, offers valuable insights into the quantity ingested and the correlation between exposure and clinical outcomes in the impairment window. Hair analysis, while useful for distinguishing between acute and chronic use, is susceptible to various biases. The rising incidence of acute cannabis intoxication in children underscores the urgent need for targeted public health interventions and stricter regulatory frameworks. Preventive measures such as child-resistant packaging, public education campaigns, and cannabis use screening during pregnancy are essential to mitigate risks. Clinicians should consider THC exposure in the differential diagnosis of children presenting with unexplained neurological, immune, or metabolic symptoms.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1558721"},"PeriodicalIF":3.6,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12034656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: \"Unravelling micro-/nano-plastics toxicity profiling: can we link associated effects to intrinsic characteristics?\"","authors":"Sebastian Beggel, Valentina Helen Pauna, Vanessa Modesto, Marisa Sárria Pereira de Passos","doi":"10.3389/ftox.2025.1605402","DOIUrl":"https://doi.org/10.3389/ftox.2025.1605402","url":null,"abstract":"","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1605402"},"PeriodicalIF":3.6,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12034682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144060478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lupin poisoning: a review.","authors":"Meye Bloothooft, Pien Cremers, Sükriye Güven, Stijn J Stoutjesdijk, Mara Jiron, Mark Wessel, Marcel A G Van Der Heyden","doi":"10.3389/ftox.2025.1547535","DOIUrl":"https://doi.org/10.3389/ftox.2025.1547535","url":null,"abstract":"<p><strong>Introduction: </strong>Lupin beans are the seeds of plants from the Fabaceae family. These beans are rich in protein and used for human consumption for several millennia. Their popularity is still increasing. Some species produce beans with high alkaloid contents, specifically of spartaine and lupanine. Without proper processing, consuming these beans can result in lupin poisoning that causes anticholinergic syndrome. We systematically analyzed all case reports describing lupin poisoning in humans in order to define most observed clinical findings, treatment options and outcome.</p><p><strong>Methods: </strong>We screened Pubmed and Google scholar for human case reports on lupin poisoning. Obtained full-text papers in any language were screened for eligibility. Demographics, time-to-symptoms, treatment and outcome were analyzed. Symptoms were categorized using the ICD11 classification.</p><p><strong>Results: </strong>Twenty-seven case reports describing 33 patients were obtained. Poisoning occurred in all age groups and sexes equally. Most frequent symptoms were bilateral mydriasis (n = 25), xerostomia (n = 25), blurred vision (n = 17), lightheadedness (n = 14), weakness (n = 11). Onset of symptoms was typically within 60 min. In most cases no treatment was required, and symptoms resolved within 24 h after which patients were discharged. Two of four children in the cohort required ICU admission and one died.</p><p><strong>Discussion: </strong>Lupin poisoning is rare and requires most often a conservative clinical approach. However, in children the effects are more severe than in adults. Frequency of lupin poisoning may rise due to increased popularity of the beans as an alternative protein source.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1547535"},"PeriodicalIF":3.6,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12014556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144013634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Promising protective potential of MiR-103a-3p against polystyrene microplastic neurotoxicity in rats.","authors":"Leila Mohammadi, Tourandokht Baluchnejadmojarad, Mina Goudarzi, Vahid Khodashenas, Roya Khoshravesh, Mehrdad Roghani","doi":"10.3389/ftox.2025.1560980","DOIUrl":"https://doi.org/10.3389/ftox.2025.1560980","url":null,"abstract":"<p><p><b>Introduction:</b> Microplastics are ubiquitous environmental pollutants with potential neurotoxic effects that can impair learning and memory. MicroRNAs are essential regulators of a number of physiological and pathological processes, but detailed information on the impact of miRNAs on the neurotoxic effects of microplastics is lacking. <b>Methods:</b> In the present study, polystyrene microplastics (PS-MPs) were administered orally and miR-103a-3p was injected intracerebroventricularly as a treatment for PS-MPs-induced neurotoxicity. <b>Results and Discussion:</b> Performance in the novel object discrimination Y-maze and Barnes maze tests indicated that miR-103a-3p mitigates the deleterious effects of PS-MPs on learning and memory. Oxidative stress, pyroptosis, apoptosis and inflammation induced by PS-MPs were modulated after miR- 103a-3p injection by reducing malondialdehyde, protein carbonyl, nitrite, caspase 3, caspase 1, TNFα, and NLRP3 levels in hippocampal tissue. Our results also showed that miR-103a-3p can reverse the impact of PS-MPs on astrocytic reaction and SIRT1 and BDNF levels. MiR-103a-3p alleviated PS-MPs-induced endoplasmic reticulum (ER) stress through reducing the levels of PERK, CHOP and GRP78. These findings imply that miR-103a-3p exerts a neuroprotective influence against cognitive deficits induced by exposure to PS-MPs. This is achieved by reducing inflammation, oxidative stress, apoptosis and endoplasmic reticulum stress.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1560980"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11996803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing humanized 3D tumor modeling using an open access xeno-free medium.","authors":"Atena Malakpour-Permlid, Manuel Marcos Rodriguez, Kinga Zór, Anja Boisen, Stina Oredsson","doi":"10.3389/ftox.2025.1529360","DOIUrl":"https://doi.org/10.3389/ftox.2025.1529360","url":null,"abstract":"<p><p>Despite limitations like poor mimicry of the human cell microenvironment, contamination risks, and batch-to-batch variation, cell culture media with animal-derived components such as fetal bovine serum (FBS) have been used <i>in vitro</i> for decades. Moreover, a few reports have used animal-product-free media in advanced high throughput three-dimensional (3D) models that closely mimic <i>in vivo</i> conditions. To address these challenges, we combined a high throughput 3D model with an open access, FBS-free chemically-defined medium, Oredsson Universal Replacement (OUR) medium, to create a more realistic 3D <i>in vitro</i> drug screening system. To reach this goal, we report the gradual adaptation procedure of three cell lines: human HeLa cervical cancer cells, human MCF-7 breast cancer cells, and cancer-associated fibroblasts (CAFs) from FBS-supplemented medium to OUR medium, while closely monitoring cell attachment, proliferation, and morphology. Our data based on cell morphology studies with phase contrast and real-time live imaging demonstrates a successful adaptation of cells to proliferate in OUR medium showing sustained growth kinetics and maintaining population doubling time. The morphological analysis demonstrates that HeLa and MCF-7 cells displayed altered cell morphology, with a more spread-out cytoplasm and significantly lower circularity index, while CAFs remained unaffected when grown in OUR medium. 3D fiber scaffolds facilitated efficient cell distribution and ingrowth when grown in OUR medium, where cells expand and infiltrate into the depths of 3D scaffolds. Drug toxicity evaluation of the widely used anti-cancer drug paclitaxel (PTX) revealed that cells grown in 3D cultures with OUR medium showed significantly lower sensitivity to PTX, which was consistent with the FBS-supplemented medium. We believe this study opens the way and encourages the scientific community to use animal product-free cell culture medium formulations for research and toxicity testing.</p>","PeriodicalId":73111,"journal":{"name":"Frontiers in toxicology","volume":"7 ","pages":"1529360"},"PeriodicalIF":3.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11979229/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144013757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}