Pub Date : 2026-03-01Epub Date: 2026-02-03DOI: 10.1016/j.etap.2026.104954
Yanfei Xu , Yan Dong , Min Zhang , Peng Wang
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.
{"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}
Pub Date : 2026-03-01Epub Date: 2026-01-19DOI: 10.1016/j.etap.2026.104942
Kanghee Kim , Yooeun Chae , Yeong-Jin Kim , Seonggeun Zee , Sun-Hyun Park , Chang-Beom Park
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 (th2) and dopamine transporter (dat) 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.
{"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}
Pub Date : 2026-03-01Epub Date: 2026-01-31DOI: 10.1016/j.etap.2026.104951
Andrew Omachoko Onoja , Grace Temitope Obarombi , Ursula Ugonna Odo , Paul Bassey Arikpo , Linus Sule Egwu , Christopher Didigwu Nwani
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 Clarias gariepinus. 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.
{"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}
Pub Date : 2026-03-01Epub Date: 2026-01-15DOI: 10.1016/j.etap.2026.104939
Evren Doruk ENGIN , Ayse Basak ENGIN , Atilla ENGIN
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.
{"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}
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.
{"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}
Pub Date : 2026-03-01Epub Date: 2026-01-23DOI: 10.1016/j.etap.2026.104949
Manuela Cipolletti , Ilaria Campesi , Marco Pellegrini , Marco Fiocchetti , Filippo Acconcia , Maria Marino
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.
{"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}
Pub Date : 2026-03-01Epub Date: 2026-01-21DOI: 10.1016/j.etap.2026.104941
Semra Çi̇çek , Sevda Işık
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 Oncorhynchus mykiss 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 sod1 gene expression at 24°C compared with 23°C and 25°C, respectively. In contrast, sod2 and gpx1a gene expressions at 24°C were 2.3-fold and 7.3-fold lower than that at 23°C, respectively. Similarly, bol 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.
{"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}
Pub Date : 2026-03-01Epub Date: 2026-01-10DOI: 10.1016/j.etap.2026.104938
Jennifer R. McCall , Kathryn T. Sausman , Ralph N. Mead
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 in vitro 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. 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.
{"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}
Pub Date : 2026-03-01Epub Date: 2026-02-04DOI: 10.1016/j.etap.2026.104956
Celia Pérez-Díaz , Axel Raux , Justine Massias , Bruno Le Bizec , Jean Philippe-Antignac , Yann Guitton , Inmaculada Salcedo-Bellido , Eduardo Linares Ruiz , Francisco M. Pérez-Carrascosa , Pilar Requena , Juan Pedro Arrebola , German Cano-Sancho
Several phthalates are considered metabolic-disrupting chemicals since they may alter adipose tissue and lipid metabolism, although human evidence remains limited. This study explored metabolic signatures in adipose tissue associated with phthalate exposure, and their relationship with the 20-year incidence of elevated low-density lipoprotein (LDL) levels in adults from the GraMo cohort. 72 adipose tissue and serum samples were collected from patients in two public hospitals in Granada, Spain. Adipose tissue was analysed using targeted and non-targeted metabolomic and lipidomic approaches. 32 phthalate biomarkers were measured in serum. A meet-in-the-middle approach identified metabolites associated with both exposure and outcome, with pathway analysis conducted using Mummichog. Phthalates were inversely associated with unsaturated phosphatidylcholines and fatty acids, and positively associated with saturated lipids. These lipid changes were, in turn, linked to elevated LDL incidence. Our findings suggest an impact of phthalates on lipid metabolism, but warrant further confirmation.
{"title":"Serum biomarkers of phthalate exposure, adipose tissue metabolites and 20-years incidence of elevated LDL levels: An exploratory exposome study in the GraMo cohort","authors":"Celia Pérez-Díaz , Axel Raux , Justine Massias , Bruno Le Bizec , Jean Philippe-Antignac , Yann Guitton , Inmaculada Salcedo-Bellido , Eduardo Linares Ruiz , Francisco M. Pérez-Carrascosa , Pilar Requena , Juan Pedro Arrebola , German Cano-Sancho","doi":"10.1016/j.etap.2026.104956","DOIUrl":"10.1016/j.etap.2026.104956","url":null,"abstract":"<div><div>Several phthalates are considered metabolic-disrupting chemicals since they may alter adipose tissue and lipid metabolism, although human evidence remains limited. This study explored metabolic signatures in adipose tissue associated with phthalate exposure, and their relationship with the 20-year incidence of elevated low-density lipoprotein (LDL) levels in adults from the GraMo cohort. 72 adipose tissue and serum samples were collected from patients in two public hospitals in Granada, Spain. Adipose tissue was analysed using targeted and non-targeted metabolomic and lipidomic approaches. 32 phthalate biomarkers were measured in serum. A meet-in-the-middle approach identified metabolites associated with both exposure and outcome, with pathway analysis conducted using Mummichog. Phthalates were inversely associated with unsaturated phosphatidylcholines and fatty acids, and positively associated with saturated lipids. These lipid changes were, in turn, linked to elevated LDL incidence. Our findings suggest an impact of phthalates on lipid metabolism, but warrant further confirmation.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104956"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133765","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}
Particulate matter (PM) poses risks to environmental and human health, yet its toxicity mechanisms in aquatic organisms remain unclear. This study investigated the effects of 2 PM types, a standard reference material (S-PM10, NIST, USA) and particulates from the Mae Moh Power Plant, Thailand (MMPS), on zebrafish embryo development and gene expression. Embryos were exposed to various concentrations, and mortality, hatching rates, and morphological abnormalities were assessed. S-PM10, with irregular morphology and broad particle size, induced developmental defects and reduced hatching. MMPS, characterized by uniform, spherical particles, caused higher mortality. qRT-PCR revealed that S-PM10 significantly upregulated oxidative stress (sod1, gstp2) and apoptosis (bax, casp3a) genes. In contrast, MMPS downregulated oxidative stress markers but upregulated apoptosis-related genes. These results suggest particle morphology and size influence toxicity profiles, S-PM10 triggers developmental disruption, while MMPS induces acute lethality. This study underscores the importance of particle characteristics and molecular responses in evaluating PM toxicity.
{"title":"Impact of environmental particulates on zebrafish embryo development and gene expression","authors":"Pinnakarn Techapichetvanich , Varissara Chantho , Siwapech Sillapaprayoon , Chatchai Muanprasat , Phisit Khemawoot , Wittaya Pimtong","doi":"10.1016/j.etap.2026.104948","DOIUrl":"10.1016/j.etap.2026.104948","url":null,"abstract":"<div><div>Particulate matter (PM) poses risks to environmental and human health, yet its toxicity mechanisms in aquatic organisms remain unclear. This study investigated the effects of 2 PM types, a standard reference material (S-PM10, NIST, USA) and particulates from the Mae Moh Power Plant, Thailand (MMPS), on zebrafish embryo development and gene expression. Embryos were exposed to various concentrations, and mortality, hatching rates, and morphological abnormalities were assessed. S-PM10, with irregular morphology and broad particle size, induced developmental defects and reduced hatching. MMPS, characterized by uniform, spherical particles, caused higher mortality. qRT-PCR revealed that S-PM10 significantly upregulated oxidative stress (<em>sod1</em>, <em>gstp2</em>) and apoptosis (<em>bax</em>, <em>casp3a</em>) genes. In contrast, MMPS downregulated oxidative stress markers but upregulated apoptosis-related genes. These results suggest particle morphology and size influence toxicity profiles, S-PM10 triggers developmental disruption, while MMPS induces acute lethality. This study underscores the importance of particle characteristics and molecular responses in evaluating PM toxicity.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104948"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033935","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}
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