Toxicological Research最新文献

{"title":"The resveratrol-induced apoptosis and/or necroptosis of lung cancer cells is dependent on the activation status of PARP-1 and MLKL under oxidative stress.","authors":"Gwan-Hwan Wi, Seon-Hee Oh","doi":"10.1007/s43188-026-00351-1","DOIUrl":"https://doi.org/10.1007/s43188-026-00351-1","url":null,"abstract":"<p><p>While numerous studies have described the anticancer effects of resveratrol (RES), some aspects of its underlying molecular mechanisms remain to be elucidated. In this study, we investigated the molecular mechanisms by which RES attenuates lung cancer progression. RES inhibited cell growth by blocking G1/S and G2/M transitions in a concentration-dependent manner. It also concentration-dependently increased the number of cells with apoptotic nuclei. This effect was associated with caspase-9-dependent apoptosis and with necroptosis induced by phospho-receptor interacting protein 1 (P-RIP1) and phospho-mixed lineage kinase domain-like protein (P-MLKL) downstream of apoptosis. Furthermore, RES treatment induced poly(ADP-ribose) polymerase-1 (PARP-1) hyperactivation, which was enhanced by NAD⁺ supplementation, leading to increased apoptosis and necroptosis. Conversely, PARP-1 inhibition decreased P-RIP1 and P-MLKL levels, thereby suppressing necroptosis while simultaneously increasing apoptosis. Therefore, the PARP-1 and MLKL activation status plays a crucial role in RES-induced cell death. RES induced the degradation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidants, including heme oxygenase-1 (HO-1) and disrupted the mitochondrial membrane potential. Hemin-induced HO-1 upregulation counteracted RES-induced Nrf2 degradation and increased PARP-1 activation-mediated necroptosis. Compared with RES, <i>N</i>-acetylcysteine (NAC) slightly reduced RES-induced Nrf2 and HO-1, but upregulated catalase and SOD2 and increased PARP-1 cleavage and P-γH2AX level. RES or NAC treatment alone reduced hemin-induced reactive oxygen species (ROS) levels but generated ROS when combined. This suggests that RES scavenges ROS, and their excessive removal by NAC may paradoxically generate more of them. In conclusion, RES exerts anticancer effects through cell cycle arrest, mitochondria-mediated apoptosis, and PARP-1 hyperactivation-mediated necroptosis.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-026-00351-1.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"42 3","pages":"383-393"},"PeriodicalIF":2.3,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13096362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781934","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 oncogenic signalosome: SQSTM1/p62 as a master integrator of signaling, metabolism, and autophagy in cancer.","authors":"Eun-Ji Choi, Sang-Min Jeon","doi":"10.1007/s43188-026-00349-9","DOIUrl":"https://doi.org/10.1007/s43188-026-00349-9","url":null,"abstract":"<p><p>Sequestosome 1 (SQSTM1/p62), long established as a selective autophagy receptor and ubiquitin-binding scaffold, is now recognized as an emerging regulatory hub that integrates signaling, metabolism, and stress adaptation in cancer. Beyond its canonical role in proteostatic cargo degradation, recent advances have revealed that p62 orchestrates nutrient sensing, redox control, innate immune signaling, and metabolic reprogramming through highly dynamic, context-dependent mechanisms. A nascent paradigm emerging from recent studies is that p62 function is specified by a hierarchical post-translational modification (PTM) code, with phosphorylation acting as the primary regulatory layer. Site-specific phosphorylation events-together with modulatory PTMs such as S-acylation, arginine methylation, and O-GlcNAcylation-reshape p62 interaction networks, liquid-liquid phase separation (LLPS) behavior, and signaling output. Through these mechanisms, p62 operates as a sophisticated signal-metabolism interface that couples stress signaling pathways, including NFE2L2/NRF2, AMPK, mTORC1, and NF-κB to the systemic rewiring of glucose, lipid, amino acid, and nucleotide metabolism. Notably, a phosphorylation-dependent positive feedback loop between p62 and AMPK has emerged as a key driver of metabolic plasticity, enabling tumor cells to survive and proliferate under the stringent metabolic stress conditions of the tumor microenvironment. This review integrates recent mechanistic insights into the PTMs, phase behavior, and signaling hub functions of p62, highlighting how these principles manifest in distinct oncogenic contexts, such as lung, prostate, and brain tumors. We further discuss emerging therapeutic strategies that seek to modulate p62-centered assemblies rather than indiscriminately inhibit p62 function. Collectively, these findings position p62 as a phosphorylation-governed oncogenic nexus whose precise manipulation may enable new strategies for context-dependent precision oncology.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"42 3","pages":"325-343"},"PeriodicalIF":2.3,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13096288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781950","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":"Disinfection's impact on the environment, molecular cross-resistance with antibiotics, and modern reduction approaches.","authors":"Mohammed F Hamdi","doi":"10.1007/s43188-026-00340-4","DOIUrl":"https://doi.org/10.1007/s43188-026-00340-4","url":null,"abstract":"<p><p>Industrial disinfectant use has become concerning due to its antimicrobial resistance (AMR)- promoting properties, leading to antibiotic and disinfectant co-resistance. This research investigates the genetic processes by which disinfectants enhance bacterial resistance to antibiotics by analyzing multidrug efflux pumps and mobile genetic elements (MGEs). Bacterial cells that encounter disinfectants tend to increase their production of efflux pumps, which simultaneously protect them against disinfectants and various antibiotics. Multidrug resistance in Pseudomonas aeruginosa arises when the bacterium encounters chlorine disinfectants, which activate the MexEF-OprN efflux pump. Horizontal gene transfer (HGT) is an essential factor for the simultaneous selection of both antibiotic- and disinfectant-resistance genes. Scientific evidence demonstrates that chlorination, along with other disinfectants, increases horizontal gene transfer rates, thereby facilitating the exchange of antibiotic resistance genes among bacterial species. The uptake of foreign genetic material occurs through the combined effects of increased membrane permeability and oxidative stress, which promote the process. The development of resistance results from two main mechanisms: horizontal gene transfer and natural genetic adaptations. Bacteria are exposed to disinfectants, which can cause genetic mutations that activate resistance proteins and other defense systems. The resistance of <i>Pseudomonas aeruginosa</i> bacteria to antibiotics increases due to changes in the pmrB gene. Some experimental results indicate that contact with disinfectants may decrease bacterial antibiotic resistance by either slowing bacterial growth or altering the production of virulence factors. This paper highlights the need for stricter regulations on disinfectant use, given their potential to foster the development of multidrug resistance. Further research into the genetic mechanisms underlying disinfectant-induced resistance is essential to understand better and mitigate its impact on public health.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s43188-026-00340-4.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"42 3","pages":"289-306"},"PeriodicalIF":2.3,"publicationDate":"2026-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13096454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147781062","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":"Sex-dependent neurotoxicity of environmental toxicants: a narrative review.","authors":"Yunkyung Eom, Jaebeom Cho, Ki-Woon Kang, Sung Hoon Lee","doi":"10.1007/s43188-026-00339-x","DOIUrl":"https://doi.org/10.1007/s43188-026-00339-x","url":null,"abstract":"<p><p>Environmental pollutants, whether naturally occurring or manufactured for commercial use, are pervasive in modern ecosystems. Endocrine disruptors, particulate matter, and micro- and nanoplastics are especially concerning because of their ubiquity, persistence, resistance to degradation, and bioaccumulation. Their global dispersal enables widespread human exposure and poses systemic health risks. The brain, with limited antioxidant capacity and a lipid-rich composition, is highly vulnerable to pollutant-induced injury. It exhibits sex-dependent differences in neurotransmission, neuroanatomy, glial populations, and neuroinflammatory responses, which can shape susceptibility to environmental insults. Yet the direct effects of environmental toxicants on the brain remain incompletely defined, partly because many toxicology studies have used only male animals, lacked sex-stratified analyses, or omitted sex altogether. Converging evidence from epidemiological, animal, and cellular studies links pollutant exposure to sex-dependent neurotoxic outcomes spanning neurodevelopmental and neurodegenerative disorders and functional impairments, reflecting intrinsic differences between male and female brains. This review synthesizes current knowledge on sources and exposure routes of key pollutants-endocrine disruptors, particulate matter, and micro- and nanoplastics-along with their sex-dependent neurotoxic effects and underlying mechanisms. Recognizing sex-dependent vulnerabilities is essential to inform public health policies, targeted interventions, and regulatory strategies to prevent pollutant-associated brain diseases.</p>","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"42 2","pages":"127-147"},"PeriodicalIF":2.3,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12946562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147327104","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":"https://doi.org/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":2.3,"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":"https://doi.org/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":2.3,"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":"https://doi.org/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":2.3,"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":"https://doi.org/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":2.3,"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":"https://doi.org/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":2.3,"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}