Toxicology letters最新文献

{"title":"Spilled liquid mercury: case studies, proposition of safety procedures with assessment of commercial cleanup kit and recommendations.","authors":"Łukasz Niżnik, Agnieszka Świdniak, Joanna Toporowska-Kaźmierak, Kamil Jurowski","doi":"10.1016/j.toxlet.2025.06.020","DOIUrl":"https://doi.org/10.1016/j.toxlet.2025.06.020","url":null,"abstract":"<p><p>Mercury, in its elemental form (Hg(0)), has intrigued humanity since antiquity, but its toxicological risks have become more apparent in recent times. Metallic mercury exposure primarily occurs through vapor inhalation, affecting the central nervous system and causing symptoms such as tremors, cognitive impairments, and renal damage. Mercury contamination, often linked to artisanal gold mining and industrial spills, poses environmental and health challenges worldwide. Addressing these hazards requires effective mercury spill management practices. Guidelines from the EPA and WHO emphasize the need for immediate containment, avoiding vacuum cleaners or brooms, and using specialized spill kits. Best practices include isolating contaminated areas, increasing ventilation, and safely disposing of mercury. Large-scale spills may require professional decontamination, including chemical stabilization with sulphur. The manuscript underscores the importance of adopting comprehensive spill management strategies to mitigate both immediate and long-term health risks associated with mercury exposure, offering practical recommendations for handling spills in various environments.</p>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565324","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":"Toxicological Effects of Micro/Nano-plastics on Human Reproductive Health: A Review.","authors":"Amirreza Talaie, Sanaz Alaee, Elham Hosseini, Shahabaldin Rezania, Amin Tamadon","doi":"10.1016/j.toxlet.2025.06.021","DOIUrl":"https://doi.org/10.1016/j.toxlet.2025.06.021","url":null,"abstract":"<p><p>Micro/Nano-plastics (MNPs), including microplastics (MPs; <5mm) and nanoplastics (NPs; <100nm), have become pervasive environmental pollutants due to extensive plastic production and insufficient recycling practices. These particles originate from the degradation of larger plastic materials through processes such as photo-oxidation, thermo-oxidation, and incomplete biodegradation, resulting in chemically reactive fragments that persist in air, water, and food. Once released, MNPs enter the human body primarily via ingestion, inhalation, and dermal absorption, ultimately accumulating in various tissues, including reproductive organs. This review provides a comprehensive summary of current knowledge regarding the toxicological effects of MNPs on male and female reproductive health, with a focus on mammalian models and relevance to human exposure. In males, MNPs have been associated with testicular damage, impaired spermatogenesis, reduced sperm count and motility, and disruptions in the hypothalamic-pituitary-gonadal axis. In females, exposure has been linked to altered folliculogenesis, disrupted ovarian hormone levels, impaired oocyte quality, and placental dysfunction. These effects are largely driven by mechanisms involving oxidative stress, inflammation, endocrine disruption, mitochondrial dysfunction, and apoptosis. Furthermore, MNPs have been shown to disrupt gut microbiota composition, contributing to systemic inflammation and reproductive dysfunction through emerging pathways such as the gut-testis axis. Given their widespread presence and multifaceted modes of action, MNPs pose a serious threat to human reproductive health. Therefore, there is an urgent need for stricter environmental regulations, improved waste management, and further research to understand the long-term and transgenerational consequences of MNP exposure.</p>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144561266","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":"Revolutionizing toxicity predictions of diverse chemicals to protect human health: Comparative QSAR and q-RASAR modeling","authors":"Shubha Das,&nbsp;Probir Kumar Ojha","doi":"10.1016/j.toxlet.2025.06.019","DOIUrl":"10.1016/j.toxlet.2025.06.019","url":null,"abstract":"<div><div>The extensive application of chemicals in the form of pesticides, cosmetics, drugs, etc., has been shown to adversely affect humans and the environment, mainly through food product residues and environmental exposure. Exposure to diverse chemicals through various routes including ingestion, inhalation, and dermal contact is associated with multiple health risks including endocrine disruption, cancer, and neurotoxicity. This study presents an advanced computational approach using quantitative structure-activity relationship (QSAR) and quantitative read-across structure-activity relationship (q-RASAR) models to predict the acute toxicity of diverse chemicals in humans, with the negative logarithm of the lowest published toxic dose (pTDLo) endpoint. We developed the first-ever predictive toxicity models combining QSAR and similarity-based read-across techniques to enhance accuracy, utilizing the TOXRIC database. The q-RASAR model outperformed traditional QSAR approaches, achieving robust statistical performance with internal validation metrics of R² = 0.710, Q² = 0.658, and external validation metrics of Q²_F1 = 0.812, Q²_F2 = 0.812, Δr²_m(test) = 0.087 and <span><math><mover><mrow><msubsup><mrow><mi>r</mi></mrow><mrow><mi>m</mi><mo>(</mo><mi>test</mi><mo>)</mo></mrow><mrow><mn>2</mn></mrow></msubsup></mrow><mo>̅</mo></mover></math></span> = 0.741. The model identified the key structural features, such as high coefficients and variations in similarity values among closely related compounds, the presence of carbon-carbon bonds at specific topological distances (5 and 8), and higher minimum E-state indices, all of which are linked to increased toxicity toward humans. The PLS-based q-RASAR model was further utilized to screen pesticides obtained from the pesticide properties database (PPDB) and 3660 investigational drugs from the DrugBank database for potential toxicants in humans, providing a tool to identify hazardous substances and mitigate risks. The developed models are instrumental in filling eco-toxicological data gaps and facilitating the development of novel, safe, and eco-friendly chemicals.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"411 ","pages":"Pages 16-24"},"PeriodicalIF":2.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144549798","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":"Neurotoxicity of food colorants: Gut dysbiosis and reduced short-chain fatty acids disrupt the enteric nervous system and lead to neurological disability","authors":"Vajagathali Mohammed ,&nbsp;Mariadhas Valan Arasu ,&nbsp;Muthumareeswaran Muthuramamoorthy ,&nbsp;S. Karthick Raja Namasivayam ,&nbsp;Jesu Arockiaraj","doi":"10.1016/j.toxlet.2025.06.022","DOIUrl":"10.1016/j.toxlet.2025.06.022","url":null,"abstract":"<div><div>For centuries, the practice of adding color to food has become deeply ingrained in culinary traditions, evolving into an indispensable aspect of food production today. Major food manufacturing companies extensively use colorants to enhance the visual appeal of their products. However, recent years have seen an increasing number of studies by researchers who have uncovered various health risks associated with food color additives. These studies have predominantly linked food colorants to severe health conditions such as cancer and allergies. Beyond these issues, further investigations have revealed that excessive use of food colorants can also lead to neurological disorders. Specifically, food colorants such as Tartrazine, Allura Red, Indigotine, Erythrosine, and Titanium Dioxide have been identified as significant contributors to bodily harm. Research indicates that these colorants do not directly affect the brain but impact the gut microbiome. They destroy beneficial gut bacteria, creating a pathway for neurological issues. While the direct mechanisms through which these colorants damage the gut and subsequently affect brain health are not yet fully understood, this paper aims to elucidate these pathways. Through comprehensive analysis, we demonstrate how these food colorants compromise gut health and lead to neurological impairments. By highlighting these interactions, this paper seeks to raise awareness and stimulate further research within the scientific community. Such research could pave the way for significant discoveries, providing deeper insights into the long-term effects of food colorants and leading to more informed regulatory decisions and safer food production practices in the future.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"411 ","pages":"Pages 1-15"},"PeriodicalIF":2.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144549838","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":"Corrigendum to “The ameliorative effect of niclosamide on bile duct ligation induced liver fibrosis via suppression of NOTCH and Wnt pathways” [Toxicol. Lett. 347 (2021) 23–35]","authors":"Manar M. Esmail ,&nbsp;Noha M. Saeed ,&nbsp;Haidy E. Michel ,&nbsp;Reem N. El-Naga","doi":"10.1016/j.toxlet.2025.06.016","DOIUrl":"10.1016/j.toxlet.2025.06.016","url":null,"abstract":"","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"410 ","pages":"Pages 197-198"},"PeriodicalIF":2.9,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144502660","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":"Corrigendum to “Dose-dependent effects of chlorpyrifos on liver injury, intestinal dysbiosis, and metabolic perturbations in C57BL/6J mice” [Toxicol. Lett. 407 (2025) 73–82]","authors":"Shuilin Wei ,&nbsp;Mengjing Wu ,&nbsp;Quanzhi Qin ,&nbsp;Chunxia Chen ,&nbsp;Huan Huang ,&nbsp;Zhongqing Wen ,&nbsp;Junli Huang ,&nbsp;Xixiang Xie ,&nbsp;Rixiang Su ,&nbsp;Xing Zhou ,&nbsp;Jian Qin ,&nbsp;Xiaoxia Liu ,&nbsp;Xiaoyu Chen","doi":"10.1016/j.toxlet.2025.06.017","DOIUrl":"10.1016/j.toxlet.2025.06.017","url":null,"abstract":"","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"410 ","pages":"Page 188"},"PeriodicalIF":2.9,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144489684","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":"Autophagy-dependent hepatocyte apoptosis mediates gilteritinib-induced hepatotoxicity","authors":"Yashi Cao ,&nbsp;Zhaozeng Chen ,&nbsp;Yiming Yin ,&nbsp;Xingchen Kang ,&nbsp;Ye Zhang ,&nbsp;Zhifei Xu ,&nbsp;Xiaochun Yang ,&nbsp;Bo Yang ,&nbsp;Qiaojun He ,&nbsp;Hao Yan ,&nbsp;Peihua Luo","doi":"10.1016/j.toxlet.2025.06.018","DOIUrl":"10.1016/j.toxlet.2025.06.018","url":null,"abstract":"<div><div>Gilteritinib, a dual FLT3/AXL inhibitor, is clinically effective for relapsed/refractory FLT3-mutated acute myeloid leukemia (AML) but is limited by severe hepatotoxicity. This study investigates the molecular mechanisms underlying gilteritinib-induced liver injury, focusing on the interplay between autophagy and apoptosis. <em>In vitro</em> and <em>in vivo</em> models, including human hepatocyte HL-7702 cells and C57BL/6 J mice, were employed. Gilteritinib treatment significantly upregulated autophagy markers (LC3-II) and induced autophagosome formation, as confirmed by western blot, TEM, and mCherry-GFP-LC3 reporter assays. Concurrently, apoptosis markers (cleaved-PARP, cleaved-Caspase3, Annexin V/PI staining) increased dose- and time-dependently. Pharmacological inhibition of autophagy with autophagy inhibitor 3-methyladenine (3-MA, 5 mM) or gene silence of <em>Atg7</em> attenuated apoptosis, mitochondrial membrane potential loss, and ROS overproduction, while autophagy induction by Torin1 (100 nM) exacerbated hepatocyte death. <em>In vivo</em>, gilteritinib-treated mice exhibited elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels, alongside histopathological damage, all of which were mitigated in <em>Atg7</em>-deficient mice. These findings demonstrate that gilteritinib triggers excessive autophagy, which drives hepatocyte apoptosis and liver injury. Targeting autophagy pathways, represents a potential therapeutic strategy to alleviate gilteritinib-induced hepatotoxicity, enabling safer clinical use of this vital AML therapy. This study elucidates a critical autophagy-apoptosis axis in drug-induced liver injury and provides actionable insights for managing adverse effects of targeted cancer therapies.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"410 ","pages":"Pages 189-196"},"PeriodicalIF":2.9,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144502659","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":"Arsenic enhances endoplasmic reticulum stress via YTHDC1/AKR1C3 aix to promote the malignant transformation of human urothelial cells","authors":"Chenglin Chen ,&nbsp;Meiting Tong ,&nbsp;Yuanyuan Chang ,&nbsp;Xiaoying Li,&nbsp;Junyu Wang,&nbsp;Lunan Chen,&nbsp;Chuanshu Huang,&nbsp;Haishan Huang,&nbsp;Lingling Zhao","doi":"10.1016/j.toxlet.2025.06.015","DOIUrl":"10.1016/j.toxlet.2025.06.015","url":null,"abstract":"<div><div>Arsenic, a well-established carcinogen, is strongly associated with the development of multiple malignancies, including bladder, skin, and lung cancers. Epidemiological studies have revealed that elevated arsenic concentrations in water sources significantly increase the risk of bladder cancer (BC), which exhibits the highest relative risk among arsenic-induced cancers. Furthermore, patients exposed to arsenic show a greater propensity for developing high-grade malignant tumors. Nevertheless, the precise molecular mechanisms underlying arsenic-induced BC initiation and progression remain incompletely understood. Our experiments revealed a significant upregulation of AKR1C3 expression in human urothelial cells following arsenic exposure. Consistently, rats subjected to long-term arsenic-contaminated drinking water displayed a similar upregulation pattern in bladder epithelial tissues. The overexpression of AKR1C3 showed a pronounced ability to promote arsenic-induced malignant transformation of human urothelial cells, both <em>in vitro</em> and <em>in vivo</em>. Mechanistic studies revealed that arsenic stabilized <em>AKR1C3</em> mRNA by upregulating YTHDC1, resulting in increased AKR1C3 protein levels. Further investigation into downstream mechanisms indicated that AKR1C3 amplifies endoplasmic reticulum (ER) stress by upregulating ER stress-sensing and transducing proteins—PERK, IRE1, and ATF6—thereby exacerbating the unfolded protein response (UPR). This sustained activation of the UPR enhances cellular adaptation to arsenic-induced stress, perpetuating its oncogenic effects and ultimately driving the malignant transformation of urothelial cells. Our findings delineate the specific role and mechanistic basis of AKR1C3 in arsenic-induced bladder carcinogenesis, providing a theoretical framework for developing preventive and therapeutic strategies against this malignancy.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"410 ","pages":"Pages 199-210"},"PeriodicalIF":2.9,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144508432","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":"circ_0000554 promotes macrophage M2 polarization mediated by glycolytic reprogramming and aggravates COPD injury","authors":"Yamei Song ,&nbsp;SiQin Han ,&nbsp;Linlin Liu ,&nbsp;Lifeng Zheng ,&nbsp;Jing Wang ,&nbsp;Zhaobo Cui ,&nbsp;Xixin Yan","doi":"10.1016/j.toxlet.2025.06.014","DOIUrl":"10.1016/j.toxlet.2025.06.014","url":null,"abstract":"<div><div>Environmental pollution, such as fine particulate matter (PM2.5), poses a serious threat to people's health. PM_2.5 can induce lung injury, and the damage to chronic obstructive pulmonary disease (COPD) is more intense. Nevertheless, the regulatory pathways remain unclear, particularly regarding the inflammatory mechanism. Increasing evidence shows that circular RNAs (circRNAs) play important functions in COPD, and dysregulation of macrophage polarization is closely interrelated with the pathogenesis of COPD. In the paper, we screened the GEO database (GSE150251) and found that hsa_circ_0000554 was significantly elevated in COPD patients following exposure to PM_2.5. We further detected circ_0000554 expression in the blood and bronchoalveolar lavage fluid (BALF) of COPD patients after PM_2.5 exposure. To explore the regulatory mechanism of circ_0000554 in COPD injury after PM_2.5 exposure, we first verified it <em>in vitro</em>. We first treated alveolar macrophages MH-S with IL-4 and added PM_2.5 treatment to construct an <em>in vitro</em> model. Then, through flow cytometry and RT-qPCR experiments, it was found that PM_2.5 induced alveolar macrophages to polarize towards the M2 type. It was also found that M2 macrophages play a crucial role in the inflammatory damage associated with COPD. Therefore, we next further elucidated how circ_0000554 regulates M2 polarization of alveolar macrophages. Through bioinformatics prediction and molecular biology assays, we illuminated the targeted regulatory effect of circ_0000554 on the miR-548b-3p-Solute Carrier Family 2 Member 3 (SLC2A3) signaling axis. Mechanistically, we jointly elucidated at the cellular and animal levels that PM_2.5 promotes M2-type polarization induced by metabolic reprogramming of macrophages by activating circ_0000554-mediated SLC2A3 expression, thereby ultimately aggravating COPD injury.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"410 ","pages":"Pages 147-158"},"PeriodicalIF":2.9,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366527","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":"Prenatal microcystin-LR exposure alters pancreatic proteome and impairs insulin secretion in offspring mice","authors":"Yu Chen ,&nbsp;Guofang Chen ,&nbsp;Yijiao Xu ,&nbsp;Xiao Wei ,&nbsp;Xingjia Li ,&nbsp;Yuan Zhou ,&nbsp;Zhaoyao Chen","doi":"10.1016/j.toxlet.2025.06.009","DOIUrl":"10.1016/j.toxlet.2025.06.009","url":null,"abstract":"<div><div>This study examines the toxic effects of microcystin-LR (MC-LR), a cyanobacterial toxin, on glucose metabolism in the pancreatic β cells of offspring following maternal exposure in mice. Female mice were exposed to varying concentrations of MC-LR for 12 weeks and the period of gestation. While no adverse effects were noted in the mothers, the neonates displayed significantly lower blood glucose levels that persisted into puberty, along with elevated fasting insulin levels. The results indicate a differential expression of pancreatic proteins, particularly those involved in the PPAR signaling pathway, which regulates lipid metabolism and insulin secretion. Key proteins affected include Fabp1, Ivd, Acaa1a, Acad11, Acat1, Hmgcs2, Scarb1, Ehhadh, and Hadh. This altered protein expression appears to be the molecular mechanism underlying the metabolic disturbances observed in the offspring. Additionally, the inhibition of pancreatic cell proliferation by MC-LR may have long-term implications for the metabolic health of the offspring. These findings underscore the potential transgenerational effects of environmental toxicants such as MC-LR, which can disrupt metabolic programming during critical developmental periods. The study highlights the need for further research to understand the broader implications of environmental toxins on metabolic health across generations.</div></div>","PeriodicalId":23206,"journal":{"name":"Toxicology letters","volume":"410 ","pages":"Pages 159-168"},"PeriodicalIF":2.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366608","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}