Yubeen Kim , Jisoo Song , Seung-Min Bae , Fuller W. Bazer , Gwonhwa Song , Wooyoung Jeong , Whasun Lim
{"title":"Tolylfluanid induces mitochondrial dysfunction through excessive ROS generation and inhibits cell growth in bovine mammary epithelial cells","authors":"Yubeen Kim , Jisoo Song , Seung-Min Bae , Fuller W. Bazer , Gwonhwa Song , Wooyoung Jeong , Whasun Lim","doi":"10.1016/j.etap.2026.104945","DOIUrl":"10.1016/j.etap.2026.104945","url":null,"abstract":"<div><div>Tolylfluanid is a phenylsulfamide fungicide commonly used to manage fungal diseases in crops; however, evidence has shown its unintended toxicity in non-target organisms. To elucidate its cellular impact, we investigated how tolylfluanid affects bovine mammary epithelial (MAC-T) cells. The results revealed that exposure to tolylfluanid suppressed MAC-T cell viability, enhanced apoptotic responses, and disrupted 3D spheroid development compared with the control group. The treatment provoked excessive generation of ROS, elevated mitochondrial calcium accumulation, and triggered a reduction in mitochondrial membrane potential. These alterations were accompanied by oxidative stress–mediated mitochondrial depolarization, which was alleviated when cells were co-treated with N-acetyl-<span>L</span>-cysteine. Western blotting and RT-qPCR further demonstrated that tolylfluanid activated PI3K and MAPK signaling and upregulated inflammation-related genes. Additionally, real-time oxygen consumption measurements reveal mitochondrial dysfunction following tolylfluanid. Altogether, these findings indicate that tolylfluanid exerts cytotoxic and pro-oxidative effects on MAC-T cells, suggesting possible implications for milk production efficiency in cattle.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104945"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tzu-Hsin Yen , Sheng-Han Lee , Hao-Jan Liang , Zou-Xiao Huang , Chi-Tsung Chen , Christopher Li , Ching-Yu Lin
{"title":"Metabolomics-based investigation of PFOS-induced molecular perturbations across multiple rat organs","authors":"Tzu-Hsin Yen , Sheng-Han Lee , Hao-Jan Liang , Zou-Xiao Huang , Chi-Tsung Chen , Christopher Li , Ching-Yu Lin","doi":"10.1016/j.etap.2026.104957","DOIUrl":"10.1016/j.etap.2026.104957","url":null,"abstract":"<div><div>This study aimed to investigate the perfluorooctane sulfonic acid (PFOS)-induced metabolic alterations in several organs and establish the potential mechanisms underlying the organ toxicity. A nuclear magnetic resonance-based metabolomics approach was employed to analyze metabolic alterations in multiple organs and serum of male rats exposed to varying doses of PFOS. We observed significant alterations in metabolites associated with inflammation (e.g., uridine diphosphate glucose), energy metabolism (e.g., adenosine monophosphate and adenosine triphosphate), amino acid (e.g., branched-chain amino acids), carbohydrate metabolism, and oxidative stress modulation (e.g., glutathione and taurine) in several organs. These alterations could be linked to inflammation, fibrosis, mitochondrial dysfunction, insulin resistance, and oxidative stress. Succinate accumulation was observed in the heart and liver, suggesting the susceptibility of these organs to mitochondrial dysfunction. Overall, our findings revealed potential key molecular events triggered by PFOS exposure, contributing to a deeper understanding of the possible adverse effects on multiple organs.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104957"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146135161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Assessment of the toxicity of acrolein on an alveolus microphysiological system","authors":"Yanfei Xu , Yan Dong , Min Zhang , Peng Wang","doi":"10.1016/j.etap.2026.104954","DOIUrl":"10.1016/j.etap.2026.104954","url":null,"abstract":"<div><div>With the advancement of industrialization, public concerns about air pollution have been increasing. As the primary site of gas exchange in the respiratory system, the human lung is highly susceptible to the toxic effects of environmental pollutants. Among these, acrolein, an ubiquitous environmental contaminant, poses significant health risks to humans. In this study, we evaluated the impact of acrolein exposure using a novel alveolus microphysiological system (MPS), which mimics the key alveolar-capillary unit via the co-culturing of human alveolar epithelial cells and microvascular endothelial cells under fluid flow conditions. Following acrolein exposure, marked injuries were observed on the chip, including disrupted alveolar-capillary barrier, increased pro-inflammatory cytokine release, disruption of metabolic function, and mitochondrial impairment. Furthermore, we performed a drug screening on the alveolus MPS, which showed dexamethasone and prednisolone could partially mitigate acrolein-induced alveolar injury in the model. Together, these findings demonstrate that the alveolus MPS can quickly probe human lung responses to acrolein exposure, providing a human-relevant alternative for the rapid assessment of health risks posed by environmental pollutants.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104954"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146110288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kanghee Kim , Yooeun Chae , Yeong-Jin Kim , Seonggeun Zee , Sun-Hyun Park , Chang-Beom Park
{"title":"6PPD and its metabolites induce locomotor dysfunction in zebrafish through dopaminergic disruption with brain accumulation","authors":"Kanghee Kim , Yooeun Chae , Yeong-Jin Kim , Seonggeun Zee , Sun-Hyun Park , Chang-Beom Park","doi":"10.1016/j.etap.2026.104942","DOIUrl":"10.1016/j.etap.2026.104942","url":null,"abstract":"<div><div>Tire wear particles release the antioxidant N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine (6PPD) and its oxidative products, notably 4-hydroxydiphenylamine (4-HDPA) and 6PPD-quinone (6PPD-Q), which pose unrecognized neurotoxic hazards to aquatic life. This study demonstrates that seven-day exposure of zebrafish larvae to environmentally relevant concentrations (30 and 300 µg/L) of these compounds leads to dose-dependent locomotor deficits, with up to a 42 % reduction in swimming speed at 300 µg/L. LC-MS/MS analysis confirmed accumulation of 6PPD, 4-HDPA, and 6PPD-Q in brain tissue, where they provoked oxidative stress, elevated reactive oxygen species, and dysregulated key antioxidant enzymes. Critically, dopaminergic dysfunction emerged as a central mechanism: downregulation of tyrosine hydroxylase (<em>th2</em>) and dopamine transporter (<em>dat</em>) expression coincided with depletion of brain dopamine and behavioral impairments. Suppression of corticotropin-releasing hormone further indicated broad neuroendocrine disruption. Despite preserved motor neuron morphology, apoptotic neuronal death increased, triggering compensatory neurotrophic and anti-apoptotic gene responses. By delineating this adverse outcome pathway, from chemical exposure and brain accumulation to oxidative injury, dopaminergic collapse, and locomotor impairment, our findings provide the mechanistic evidence of tire-derived antioxidant neurotoxicity in fish. These results underscore the urgent need to reassess 6PPD use in tire formulations, inform regulatory policies on tire wear particle emissions, and guide the design of safer alternative antioxidants to protect aquatic ecosystems.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104942"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrew Omachoko Onoja , Grace Temitope Obarombi , Ursula Ugonna Odo , Paul Bassey Arikpo , Linus Sule Egwu , Christopher Didigwu Nwani
{"title":"Chemical profiling, cytogenotoxic effect and systemic alterations in Clarias gariepinus exposed to a municipal dumpsite soil simulated leachate","authors":"Andrew Omachoko Onoja , Grace Temitope Obarombi , Ursula Ugonna Odo , Paul Bassey Arikpo , Linus Sule Egwu , Christopher Didigwu Nwani","doi":"10.1016/j.etap.2026.104951","DOIUrl":"10.1016/j.etap.2026.104951","url":null,"abstract":"<div><div>Solid waste dumpsites are significant sources of emerging contaminants with ecological and public health implications. This study assessed the cytogenotoxic and systemic effects of simulated leachate from the Obajana dumpsite, Kogi State, Nigeria, using juvenile <em>Clarias gariepinus</em>. Leachate physicochemical properties, metal concentrations, and leachate pollution index (LPI) were determined using inductively coupled plasma mass spectrometry (ICP-MS) while organic pollutants were quantified using gas chromatography coupled with a flame ionization detector (GC–FID). Fifty fish were assigned to five groups (n = 10) and exposed to 0, 15, 25, 50, and 75 % (v/v) leachate under semi-static conditions for 28 days with 48 h renewal. Bioaccumulation of pollutants in gills was quantified by ICP-MS and GC-FID. Haematological, biochemical, oxidative stress, genotoxic, and histopathological responses were also evaluated following standard protocols. The leachate exhibited elevated biochemical oxygen demand (BOD) (112.33 mg/L), chemical oxygen demand (COD; 186.58 mg/L), turbidity (28.9 NTU), alkalinity (2800 mg/L), Manganese (Mn; 291.34 mg/L), and iron (Fe; 65.79 mg/L), with a high LPI (53.99). Exposure caused concentration dependent increases in metals accumulation in gills, accompanied by altered blood indices, elevated liver enzymes, oxidative stress, micronuclei formation, and severe gill lesions. These findings demonstrate significant toxicity of Obajana dumpsite leachate, highlighting risks associated with unmanaged solid waste disposal.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104951"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146095881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Toxic effects of nanoplastics on a model of dog aortic cells","authors":"Giuseppina Basini , Martina Tambassi , Simona Bussolati , Francesca Grasselli , Anna Scalori , Erika Scaltriti , Stefano Grolli , Roberto Ramoni , Fausto Quintavalla , Melissa Berni","doi":"10.1016/j.etap.2026.104940","DOIUrl":"10.1016/j.etap.2026.104940","url":null,"abstract":"<div><div>Nanoplastic fragments (NP) are a growing concern and using dog aortic endothelial cells (CnAEOC) and fluorescence microscopy, we observed an interaction between NP and cells, demonstrating a localization at the cytoplasmic level. Furthermore, the data collected show a disruption of both cell proliferation and metabolic activity. The results also show the induction of oxidative stress. In detail, NP caused an increase in the levels of ROS production and an inhibition of enzymatic defence systems. On the contrary, there was no alteration of the non-enzymatic defence mechanism. The analysis conducted to evaluate a possible induction of autophagy, a survival mechanism implemented by cells, following exposure to NP reported the absence of autophagy involvement in the model analysed. Finally, investigations were conducted regarding the involvement of NP in gene expression processes. Both RNA-seq and RT-PCR did not highlight differentially expressed genes in treated cells.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104940"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145995620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Evren Doruk ENGIN , Ayse Basak ENGIN , Atilla ENGIN
{"title":"Bidirectional effect of intestinal microbiome and host in circadian rhythm disruption: Environmental factors and breast cancer development","authors":"Evren Doruk ENGIN , Ayse Basak ENGIN , Atilla ENGIN","doi":"10.1016/j.etap.2026.104939","DOIUrl":"10.1016/j.etap.2026.104939","url":null,"abstract":"<div><div>Suppression of nocturnal circadian melatonin signaling amplitude, disruption of the host's circadian clock through diet or phase shifts, and imbalances in the gut microbiome are significant factors that increase the incidence of breast cancer. After host-derived mature microRNAs (miRNAs) are secreted from intestinal epithelial cells, they pass to the microbiota as faecal or exosomal miRNAs and modify the epigenetic profile of the microbiome. Subsequently, the profile of host miRNAs is altered by metabolites, which are derived from intestinal bacteria. Bidirectional epigenetic modulations of host and microbiota trigger the activation of oncogenic transcriptional pathways in extraintestinal tissues. However, the effect of the mutual epigenetic interactions between the gut microbiota and the host on the development of extraintestinal cancer is not clear. The aim of this review is to discuss the factors influencing bidirectional epigenetic regulation mechanisms between microbial dysbiosis and the host in breast cancer.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104939"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145994698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of nickel oxide nanoparticles and minor temperature changes on cytotoxic, antioxidant, reproductive, and genotoxic responses in gonadal Oncorhynchus mykiss cells","authors":"Semra Çi̇çek , Sevda Işık","doi":"10.1016/j.etap.2026.104941","DOIUrl":"10.1016/j.etap.2026.104941","url":null,"abstract":"<div><div>Understanding the combined effects of nickel oxide nanoparticles (NiO NPs) and minor temperature changes is urgent for assessing the possible risks to aquatic organisms under global climate change and nanoparticle-associated environmental stressors. This study investigated the cytotoxic, antioxidant, reproductive and genotoxic responses of <em>Oncorhynchus mykiss</em> gonadal (RTG-2) cells following exposure to NiO NPs (25–250 µg/mL) under minor temperature changes (23°C, 24°C, and 25°C) for 24 and 48 h. Our results show that the toxicity induced by cubic crystal NiO NPs (10–40 nm) was strongly modulated by both temperature and exposure time. The highest toxicity (83.49 % cell death) was observed at 100 µg/mL after 48 h at 25°C. After 48 h of exposure, NiO NP treatment led to 4.7-fold and 4.4-fold increases in <em>sod1</em> gene expression at 24°C compared with 23°C and 25°C, respectively. In contrast, <em>sod2</em> and <em>gpx1a</em> gene expressions at 24°C were 2.3-fold and 7.3-fold lower than that at 23°C, respectively. Similarly, <em>bol</em> gene expression was decreased by 12.4-fold and 11.4-fold at 24°C and 25°C, respectively, compared with that at 23°C. Compared with the control treatment, the NiO NP treatment increased the tail DNA percentage by 46.29 %, 42.61 % and 37.75 % compared to the control groups at 23°C, 24°C and, 25℃, respectively. These results indicate that minor environmental temperature changes can significantly alter nanoparticle toxicity by disrupting oxidative and genetic defense pathways and highlight the need for revised nanoparticle risk assessments under climate change scenarios.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104941"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jennifer R. McCall , Kathryn T. Sausman , Ralph N. Mead
{"title":"Per- and polyfluoroalkyl substances (PFAS) alter immune responses from THP-1 human monocytes","authors":"Jennifer R. McCall , Kathryn T. Sausman , Ralph N. Mead","doi":"10.1016/j.etap.2026.104938","DOIUrl":"10.1016/j.etap.2026.104938","url":null,"abstract":"<div><div>Per- and Polyfluoroalkyl substances (PFAS) are widespread environmental contaminants linked to various adverse health conditions, including immune dysregulation and inflammation, though cellular mechanisms remain poorly understood. In this study, we investigated the direct <em>in vitro</em> impact of long-chain/legacy PFOA and PFOS, byproduct NBP2, PFO4DA, and PFMOAA, and next generation HFPO-DA/”GenX” on THP-1 human monocyte function at the cellular level<em>.</em> While all PFAS activated THP-1 cells and altered immune function, it is important to note that they did so in very different and often contrasting ways. PFOS suppressed inflammatory cytokine release, while NBP2 and PFO4DA activated uncoordinated and simultaneous inflammatory and anti-inflammatory immune responses. PFOA, HFPO-DA/”GenX”, and PFMOAA increased markers of suppressive phenotypes often associated with tumor-associated macrophages. Taken together, our findings demonstrate that PFAS, even at non-lethal concentrations, can directly interfere with functional immune responses in cellular models by altering cytokine profiles and immune activation states.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104938"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145956536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Manuela Cipolletti , Ilaria Campesi , Marco Pellegrini , Marco Fiocchetti , Filippo Acconcia , Maria Marino
{"title":"Exploring novel biomarkers for endocrine disruptor exposure: insights into extra-nuclear signaling pathways of estrogen and androgen receptors","authors":"Manuela Cipolletti , Ilaria Campesi , Marco Pellegrini , Marco Fiocchetti , Filippo Acconcia , Maria Marino","doi":"10.1016/j.etap.2026.104949","DOIUrl":"10.1016/j.etap.2026.104949","url":null,"abstract":"<div><div>Synthetic chemicals classified as endocrine disruptors (EDs) pose health risks by interfering with sex-steroid hormone signaling. This study evaluated bisphenol A (BPA) for its effects on ERα, ERβ, and AR expression and extranuclear signaling, including ERα phosphorylation, in human monocytes from healthy male and female donors, and assessed ten additional chemicals in ERα-positive breast cancer cell lines (MCF-7, T47D). BPA increased ERα phosphorylation in both male and female monocytes without altering receptor levels, while modulating downstream signaling in a sex-dependent manner and attenuating DHT- or E2-induced effects. The ten other chemicals similarly enhanced ERα phosphorylation, often independently of direct receptor binding. These findings indicate that ERα phosphorylation is a sensitive, early marker of ED activity across immune and epithelial cells and support its use as a receptor-proximal endpoint to complement conventional transcription-based assays in next-generation ED screening strategies.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104949"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}