Pub Date : 2025-12-26DOI: 10.1016/j.etap.2025.104918
Anda R. Gliga , Sarah McCarrick , Vilhelm Malmborg , Pekka Kohonen , Anastasiia Snigireva , Brandon Mills , Pernille Høgh Danielsen , Lena Palmberg , Karin Broberg , Joakim Pagels , Ulla Vogel
Renewable diesel fuels may reduce greenhouse gas emissions and particulate matter compared to fossil diesel, but the toxicity of their combustion products remains unclear. This study assessed pulmonary effects of renewable diesel exhaust particles in female C57BL/6NTac mice after single intratracheal instillation (6, 18, or 54 µg/mouse). Particles were generated from renewable fuels (rapeseed methyl ester, RME; hydrogen-treated vegetable oil, HVO) and petroleum diesel (DEP) using a modern heavy-duty diesel engine. Lung tissue was analysed via RNA sequencing one day post-exposure to identify differentially expressed genes, followed by pathway analysis and benchmark dose (BMD) modelling. Enriched pathways revealed similar toxicological profiles across fuels, involving immune response, extracellular matrix, and cardiovascular signalling. Pathway activation scores and BMDs indicated that HVO and DEP have similar pro-inflammatory potencies whereas RME was less potent. In conclusion, the similarity of the toxicological responses for renewable and traditional diesel exhaust particles raises health concerns for renewable diesels.
{"title":"Similar global transcription patterns in mouse lung tissue following pulmonary exposure to renewable and conventional diesel engine exhaust particles","authors":"Anda R. Gliga , Sarah McCarrick , Vilhelm Malmborg , Pekka Kohonen , Anastasiia Snigireva , Brandon Mills , Pernille Høgh Danielsen , Lena Palmberg , Karin Broberg , Joakim Pagels , Ulla Vogel","doi":"10.1016/j.etap.2025.104918","DOIUrl":"10.1016/j.etap.2025.104918","url":null,"abstract":"<div><div>Renewable diesel fuels may reduce greenhouse gas emissions and particulate matter compared to fossil diesel, but the toxicity of their combustion products remains unclear. This study assessed pulmonary effects of renewable diesel exhaust particles in female C57BL/6NTac mice after single intratracheal instillation (6, 18, or 54 µg/mouse). Particles were generated from renewable fuels (rapeseed methyl ester, RME; hydrogen-treated vegetable oil, HVO) and petroleum diesel (DEP) using a modern heavy-duty diesel engine. Lung tissue was analysed via RNA sequencing one day post-exposure to identify differentially expressed genes, followed by pathway analysis and benchmark dose (BMD) modelling. Enriched pathways revealed similar toxicological profiles across fuels, involving immune response, extracellular matrix, and cardiovascular signalling. Pathway activation scores and BMDs indicated that HVO and DEP have similar pro-inflammatory potencies whereas RME was less potent. In conclusion, the similarity of the toxicological responses for renewable and traditional diesel exhaust particles raises health concerns for renewable diesels.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104918"},"PeriodicalIF":4.2,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145845149","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 : 2025-12-19DOI: 10.1016/j.etap.2025.104907
Xia Wang , Ruixuan Li , Bo Cheng , Yingxue Sun , Xiaolong Yao , Chun Wang
Polyethylene micro/nano plastics (PE-MPs, PE-NPs), being the predominant plastic pollutants in aquaculture environments, frequently coexist with emerging contaminants such as perfluorinated compounds (PFOA) within closed aquaculture systems. Nevertheless, the combined biotoxicological impacts and underlying mechanisms of PE-MPs, PE-NPs, and PFOA co-pollutants remain poorly understood in zebrafish. This study revealed induced oxidative stress in zebrafish, as evidenced by aberrant levels of antioxidant enzymes (CAT, SOD, GST) and lipid peroxidation markers (LPO, GSH) as well as neurotoxicity (AChE) in the targeted organs (gills, intestine, and liver). Specifically, the Integrated Biomarker Responses (IBRv2) revealed that the combined toxic effects exhibited synergism in the gills and liver but antagonism in the gut of zebrafish, showing distinct tissue and organ specificity. The exposure of PFOA to environmental concentrations reduced the richness and diversity of intestinal microbiota, whereas the presence of MPs and NPs increased them. Compared to single exposure to PFOA, the combined-exposure of MPs and PFOA decreased the metabolism of xenobiotics by cytochrome P450 and naphthalene degradation of metabolic pathway. The combined-exposure of NPs and PFOA decreased the abundance of African trypanosomiasis, NOD-like receptor signaling pathway, pathways in cancer, and naphthalene degradation pathway, while increasing the abundance of Wnt signaling pathway. In the combined-exposure group of MPs + NPs and PFOA, the abundance of African trypanosomiasis and naphthalene degradation metabolic pathways decreased, while the ethylbenzene degradation metabolic pathway increased. The present study offers a scientific foundation for conducting comprehensive ecological risk assessments and joint toxicological evaluations of PE-MPs, PE-NPs and PFOA.
{"title":"Combined toxicity of polyethylene micro/nanoplastics and PFOA in zebrafish (Danio rerio): Impacts on antioxidant, neurotransmission, and gut microbiota","authors":"Xia Wang , Ruixuan Li , Bo Cheng , Yingxue Sun , Xiaolong Yao , Chun Wang","doi":"10.1016/j.etap.2025.104907","DOIUrl":"10.1016/j.etap.2025.104907","url":null,"abstract":"<div><div>Polyethylene micro/nano plastics (PE-MPs, PE-NPs), being the predominant plastic pollutants in aquaculture environments, frequently coexist with emerging contaminants such as perfluorinated compounds (PFOA) within closed aquaculture systems. Nevertheless, the combined biotoxicological impacts and underlying mechanisms of PE-MPs, PE-NPs, and PFOA co-pollutants remain poorly understood in zebrafish. This study revealed induced oxidative stress in zebrafish, as evidenced by aberrant levels of antioxidant enzymes (CAT, SOD, GST) and lipid peroxidation markers (LPO, GSH) as well as neurotoxicity (AChE) in the targeted organs (gills, intestine, and liver). Specifically, the Integrated Biomarker Responses (IBRv2) revealed that the combined toxic effects exhibited synergism in the gills and liver but antagonism in the gut of zebrafish, showing distinct tissue and organ specificity. The exposure of PFOA to environmental concentrations reduced the richness and diversity of intestinal microbiota, whereas the presence of MPs and NPs increased them. Compared to single exposure to PFOA, the combined-exposure of MPs and PFOA decreased the metabolism of xenobiotics by cytochrome P450 and naphthalene degradation of metabolic pathway. The combined-exposure of NPs and PFOA decreased the abundance of African trypanosomiasis, NOD-like receptor signaling pathway, pathways in cancer, and naphthalene degradation pathway, while increasing the abundance of Wnt signaling pathway. In the combined-exposure group of MPs + NPs and PFOA, the abundance of African trypanosomiasis and naphthalene degradation metabolic pathways decreased, while the ethylbenzene degradation metabolic pathway increased. The present study offers a scientific foundation for conducting comprehensive ecological risk assessments and joint toxicological evaluations of PE-MPs, PE-NPs and PFOA.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"121 ","pages":"Article 104907"},"PeriodicalIF":4.2,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145785202","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 : 2025-12-18DOI: 10.1016/j.etap.2025.104914
Nivedita Jha , Angshita Das , Megha Prasanth , S. Daisy Precilla , R. Sivachandran , Rajaneesh Anupam , T.S. Anitha
Background
The increasing production of disposable plastic has led to massive plastic waste, much of which is burned, resulting in microplastics (MPs) and other toxic byproducts. This study investigates the smoke-derived MPs from burning polypropylene (PP), their physicochemical properties, and their impact on lung cancer cells.
Methods
Smoke-derived MPs were generated by smoldering PP, and extracted MPs dissolved in methanol, ethanol, and DCM. For physicochemical assessment, DLS, UV–VIS, FTIR NMR, GC-MS, and SEM were performed, followed by in vitro analysis, MTT, AO/EB, and DAPI assays performed using A549 cells.
Result & Discussion
Characterization studies revealed particle size, hazardous compounds such as phthalates, siloxanes, and polyaromatic hydrocarbons. In vitro studies showed increased cell viability in A549 cells with no sign of apoptosis or necrosis.
Conclusion
Proliferation in lung cancer cells through Smoke-derived MPs, implicating combustion MPs in respiratory disease, highlighting urgent control needs.
{"title":"Smoke-derived microplastics of polypropylene In Vitro proliferative impact on human lung adenocarcinoma cells: Physicochemical analysis and biological evaluation","authors":"Nivedita Jha , Angshita Das , Megha Prasanth , S. Daisy Precilla , R. Sivachandran , Rajaneesh Anupam , T.S. Anitha","doi":"10.1016/j.etap.2025.104914","DOIUrl":"10.1016/j.etap.2025.104914","url":null,"abstract":"<div><h3>Background</h3><div>The increasing production of disposable plastic has led to massive plastic waste, much of which is burned, resulting in microplastics (MPs) and other toxic byproducts. This study investigates the smoke-derived MPs from burning polypropylene (PP), their physicochemical properties, and their impact on lung cancer cells.</div></div><div><h3>Methods</h3><div>Smoke-derived MPs were generated by smoldering PP, and extracted MPs dissolved in methanol, ethanol, and DCM. For physicochemical assessment, DLS, UV–VIS, FTIR NMR, GC-MS, and SEM were performed, followed by in vitro analysis, MTT, AO/EB, and DAPI assays performed using A549 cells.</div></div><div><h3>Result & Discussion</h3><div>Characterization studies revealed particle size, hazardous compounds such as phthalates, siloxanes, and polyaromatic hydrocarbons. <em>In vitro</em> studies showed increased cell viability in A549 cells with no sign of apoptosis or necrosis.</div></div><div><h3>Conclusion</h3><div>Proliferation in lung cancer cells through Smoke-derived MPs, implicating combustion MPs in respiratory disease, highlighting urgent control needs.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"121 ","pages":"Article 104914"},"PeriodicalIF":4.2,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145785203","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 : 2025-12-17DOI: 10.1016/j.etap.2025.104910
Natália P.V.M. Faria , Amanda da S. Guerreiro , Giovana S. Branco , Mariana F. de Campos , Renata G. Moreira , Ismael E. Lozano , Renato M. Honji
Phenanthrene (PHE), a polycyclic aromatic hydrocarbon (PAH), poses significant risks to marine biota, yet its behavioral and physiological effects on fish, particularly on Epinephelus marginatus, remain poorly understood. This study therefore aimed to assess the acute (96 h) effects of PHE exposure (0.1 and 1 mg L⁻¹) on juvenile E. marginatus (n = 15 per treatment) compared to an ethanol control (0.004 %). Behavioral endpoints, oxidative stress biomarkers, plasma cortisol levels, and acetylcholinesterase activity were evaluated in the same individuals. PHE-exposed fish exhibited pronounced behavioral disturbances, including reduced agonistic interactions and loss of equilibrium at the highest concentration, which may compromise social hierarchy and predator avoidance. Although acetylcholinesterase and antioxidant enzymes remained unchanged, the higher PHE concentration triggered increased plasma cortisol and hepatic lipid peroxidation, indicating stress axis activation and oxidative damage. These results provide the first integrated evidence of neurobehavioral and physiological disruption in E. marginatus under PHE exposure.
{"title":"Impacts of phenanthrene on juveniles of dusky grouper, Epinephelus marginatus (Perciformes: Serranidae): Behavioral, endocrine and oxidative effects","authors":"Natália P.V.M. Faria , Amanda da S. Guerreiro , Giovana S. Branco , Mariana F. de Campos , Renata G. Moreira , Ismael E. Lozano , Renato M. Honji","doi":"10.1016/j.etap.2025.104910","DOIUrl":"10.1016/j.etap.2025.104910","url":null,"abstract":"<div><div>Phenanthrene (PHE), a polycyclic aromatic hydrocarbon (PAH), poses significant risks to marine biota, yet its behavioral and physiological effects on fish, particularly on <em>Epinephelus marginatus</em>, remain poorly understood. This study therefore aimed to assess the acute (96 h) effects of PHE exposure (0.1 and 1 mg L⁻¹) on juvenile <em>E. marginatus</em> (n = 15 per treatment) compared to an ethanol control (0.004 %). Behavioral endpoints, oxidative stress biomarkers, plasma cortisol levels, and acetylcholinesterase activity were evaluated in the same individuals. PHE-exposed fish exhibited pronounced behavioral disturbances, including reduced agonistic interactions and loss of equilibrium at the highest concentration, which may compromise social hierarchy and predator avoidance. Although acetylcholinesterase and antioxidant enzymes remained unchanged, the higher PHE concentration triggered increased plasma cortisol and hepatic lipid peroxidation, indicating stress axis activation and oxidative damage. These results provide the first integrated evidence of neurobehavioral and physiological disruption in <em>E. marginatus</em> under PHE exposure.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"121 ","pages":"Article 104910"},"PeriodicalIF":4.2,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145785207","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 : 2025-12-17DOI: 10.1016/j.etap.2025.104915
Bozhena Tsyupa , Chiara Emma Campiglio , Elena Carrara , Marta Ripamonti , Alessandro Mancini , Andrea Bonfanti , Micol Introna , Ana Teresa Juarez-Facio , Karine Elihn , Manuela Teresa Raimondi , Andrea Remuzzi
Poor air quality is a significant risk to human health and the environment, with a direct correlation to respiratory diseases and premature death. Ultra fine particles (UFPs) in the atmosphere are particularly hazardous. This study evaluates the toxicological response of epithelial cells (A549) and macrophages (dTHP-1) to particulate matter (PM) emissions from car brake wear, under both submerged and Air-Liquid Interface (ALI) conditions. Toxicity was assessed using cell viability (Resazurin assay) and cytokine assays. Emissions were collected using a dynamometric bench simulating driving and braking conditions. Under ALI, freshly emitted particles were directly deposited onto cells, while in submerged conditions, particles were collected on filters and then deposited onto cells. M1a and M1b materials were tested, both materials are falling into category of ECE R90 Low Metallic pads. M1a showed slight toxicity under ALI and significant immune response in submerged conditions, while M1b showed no toxicity in either condition.
{"title":"On-site ALI versus submerged culture: Chemical and toxicological investigation of brake wear sub-micrometric particles","authors":"Bozhena Tsyupa , Chiara Emma Campiglio , Elena Carrara , Marta Ripamonti , Alessandro Mancini , Andrea Bonfanti , Micol Introna , Ana Teresa Juarez-Facio , Karine Elihn , Manuela Teresa Raimondi , Andrea Remuzzi","doi":"10.1016/j.etap.2025.104915","DOIUrl":"10.1016/j.etap.2025.104915","url":null,"abstract":"<div><div>Poor air quality is a significant risk to human health and the environment, with a direct correlation to respiratory diseases and premature death. Ultra fine particles (UFPs) in the atmosphere are particularly hazardous. This study evaluates the toxicological response of epithelial cells (A549) and macrophages (dTHP-1) to particulate matter (PM) emissions from car brake wear, under both submerged and Air-Liquid Interface (ALI) conditions. Toxicity was assessed using cell viability (Resazurin assay) and cytokine assays. Emissions were collected using a dynamometric bench simulating driving and braking conditions. Under ALI, freshly emitted particles were directly deposited onto cells, while in submerged conditions, particles were collected on filters and then deposited onto cells. M1a and M1b materials were tested, both materials are falling into category of ECE R90 Low Metallic pads. M1a showed slight toxicity under ALI and significant immune response in submerged conditions, while M1b showed no toxicity in either condition.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"121 ","pages":"Article 104915"},"PeriodicalIF":4.2,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145785206","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 : 2025-12-16DOI: 10.1016/j.etap.2025.104913
Martin Staron , Ľubica Rajčáková , Matej Planý , Hossam Abou-Shaara
Nutrition strongly shapes honey bee resilience, especially when bees face multiple environmental stressors. This study examined how different carbohydrate and commercial protein diets influence honey bee responses to residue-level tebuconazole exposure and short-term heat stress (40°C for 48 h). Mortality, food intake, and body water loss were measured under each treatment. Diet had a significant effect on survival: among carbohydrate diets, bees fed the control diet showed the lowest mortality, whereas rapeseed honey caused the highest. For protein diets, sugar candy and the vegetable protein diet yielded the highest survival, in contrast to the pollen-based feed. Food intake varied widely across diets and showed a positive association with mortality. The presence of tebuconazole in diets did not induce avoidance or reduce consumption. Water loss was inversely associated with mortality, suggesting complex physiological trade-offs. Tebuconazole did not cause acute lethal effects, contributing to current evaluations of fungicide risks.
{"title":"Interactive effects of diet, tebuconazole, and elevated temperature on survival and body water loss in honey bee workers","authors":"Martin Staron , Ľubica Rajčáková , Matej Planý , Hossam Abou-Shaara","doi":"10.1016/j.etap.2025.104913","DOIUrl":"10.1016/j.etap.2025.104913","url":null,"abstract":"<div><div>Nutrition strongly shapes honey bee resilience, especially when bees face multiple environmental stressors. This study examined how different carbohydrate and commercial protein diets influence honey bee responses to residue-level tebuconazole exposure and short-term heat stress (40°C for 48 h). Mortality, food intake, and body water loss were measured under each treatment. Diet had a significant effect on survival: among carbohydrate diets, bees fed the control diet showed the lowest mortality, whereas rapeseed honey caused the highest. For protein diets, sugar candy and the vegetable protein diet yielded the highest survival, in contrast to the pollen-based feed. Food intake varied widely across diets and showed a positive association with mortality. The presence of tebuconazole in diets did not induce avoidance or reduce consumption. Water loss was inversely associated with mortality, suggesting complex physiological trade-offs. Tebuconazole did not cause acute lethal effects, contributing to current evaluations of fungicide risks.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"121 ","pages":"Article 104913"},"PeriodicalIF":4.2,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145784054","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 : 2025-12-15DOI: 10.1016/j.etap.2025.104908
Lin Tao , Lulu Dai , Shimin Xiong , Dengqing Liao , Yuan-zhong Zhou , Xubo Shen
Background
This study aimed to comprehensively investigate the associations among maternal immune-inflammatory markers and urinary phthalate (PAE) metabolites during pregnancy, focusing on their potential links with preeclampsia and related reproductive outcomes.
Method
A propensity score-matched case-control design was adopted, enrolling 61 cases and 118 controls matched based on propensity scores. To assess associations, dose-response relationships, and mediating effects, multiple statistical methods were employed, including logistic regression, restricted cubic splines (RCS), Bayesian kernel machine regression (BKMR), and structural equation modeling (SEM).
Results
Maternal urinary metabolites of PAEs (MEHP, MEHHP) and the systemic immune-inflammation index (SII) were significantly higher in the case group than in the control group. Logistic regression analysis revealed positive associations between MEHP, MOP, MEHHP, SII, and preeclampsia (all odds ratios [OR] > 1, P < 0.05). RCS analysis revealed nonlinear dose-response relationships for MOP and SII, with threshold concentrations of 2.57 μg/L creatinine (MOP) and 977.24 μg/L (SII). BKMR results indicated a nonlinear positive correlation between PAE metabolites, immune-inflammatory markers, and spontaneous abortion. SEM models confirmed mediating effects of immune-inflammatory markers: SII mediated the associations between MEHP, MOP, MEHHP and preeclampsia with mediation rates (95 %CI) of 8.73 % [1.33 %–22.34 %], 25.31 % [11.72 %–36.00 %], and 6.50 % [0.36 %–21.39 %], respectively; AISI mediated the MEHP-preeclampsia association (0.27 % [0.20 %–1.19 %]); and MLR and PLR mediated the MEHHP-preeclampsia association (2.54 % [1.53 %–8.80 %] and 7.59 % [1.20 %–12.52 %], respectively).
Conclusion
Maternal urinary PAE metabolites during pregnancy are associated with an increased risk of preeclampsia, and maternal immune-inflammatory markers partially mediate this relationship. These findings provide insights into the potential mechanisms linking prenatal PAE exposure to adverse pregnancy outcomes.
{"title":"Maternal immune-inflammatory markers mediate the association between urinary phthalate metabolites and preeclampsia","authors":"Lin Tao , Lulu Dai , Shimin Xiong , Dengqing Liao , Yuan-zhong Zhou , Xubo Shen","doi":"10.1016/j.etap.2025.104908","DOIUrl":"10.1016/j.etap.2025.104908","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to comprehensively investigate the associations among maternal immune-inflammatory markers and urinary phthalate (PAE) metabolites during pregnancy, focusing on their potential links with preeclampsia and related reproductive outcomes.</div></div><div><h3>Method</h3><div>A propensity score-matched case-control design was adopted, enrolling 61 cases and 118 controls matched based on propensity scores. To assess associations, dose-response relationships, and mediating effects, multiple statistical methods were employed, including logistic regression, restricted cubic splines (RCS), Bayesian kernel machine regression (BKMR), and structural equation modeling (SEM).</div></div><div><h3>Results</h3><div>Maternal urinary metabolites of PAEs (MEHP, MEHHP) and the systemic immune-inflammation index (SII) were significantly higher in the case group than in the control group. Logistic regression analysis revealed positive associations between MEHP, MOP, MEHHP, SII, and preeclampsia (all odds ratios [OR] > 1, P < 0.05). RCS analysis revealed nonlinear dose-response relationships for MOP and SII, with threshold concentrations of 2.57 μg/L creatinine (MOP) and 977.24 μg/L (SII). BKMR results indicated a nonlinear positive correlation between PAE metabolites, immune-inflammatory markers, and spontaneous abortion. SEM models confirmed mediating effects of immune-inflammatory markers: SII mediated the associations between MEHP, MOP, MEHHP and preeclampsia with mediation rates (95 %CI) of 8.73 % [1.33 %–22.34 %], 25.31 % [11.72 %–36.00 %], and 6.50 % [0.36 %–21.39 %], respectively; AISI mediated the MEHP-preeclampsia association (0.27 % [0.20 %–1.19 %]); and MLR and PLR mediated the MEHHP-preeclampsia association (2.54 % [1.53 %–8.80 %] and 7.59 % [1.20 %–12.52 %], respectively).</div></div><div><h3>Conclusion</h3><div>Maternal urinary PAE metabolites during pregnancy are associated with an increased risk of preeclampsia, and maternal immune-inflammatory markers partially mediate this relationship. These findings provide insights into the potential mechanisms linking prenatal PAE exposure to adverse pregnancy outcomes.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"121 ","pages":"Article 104908"},"PeriodicalIF":4.2,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776873","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 : 2025-12-15DOI: 10.1016/j.etap.2025.104911
Phuoc-Cuong Le , Le Van Hao , Tan Nhat , Hoang-Son Le , Thi Xuan Thuy Le
This study assesses seasonal heavy-metal contamination from gold mining in the Bong Mieu River basin (central Viet Nam) and examines its association with human xenobiotic-metabolizing enzyme phenotypes. In sediments, As and Pb consistently exceeded Vietnamese sediment quality limits, by 4.1–25.4 × for As and 2.3–7.8 × for Pb, whereas other metals generally remained within regulatory thresholds. River water exhibited widespread Pb exceedances at all sites and occasional. As exceedances, with higher concentrations in the dry season. Regression analyses indicated strong water–sediment coupling for As, Pb, Hg, Cd, and Zn, supporting shared transport and accumulation processes. Season-resolved Pearson correlations, HCA, PCA, and APCS-MLR source apportionment revealed a dominant mining-derived multi-metal signal year-round, intensified and spatially mixed under monsoon hydrology. Enzyme phenotypes varied with the mixed-metal exposure gradient: sites with higher As/Pb burdens showed higher frequencies of slow NAT2 and intermediate/slow CYP450 phenotypes, and longer residence was associated with higher NAT2 rapid-phenotype frequency.
{"title":"Arsenic and lead exposure in vietnamese gold mining communities: A case study of metabolic enzyme impacts","authors":"Phuoc-Cuong Le , Le Van Hao , Tan Nhat , Hoang-Son Le , Thi Xuan Thuy Le","doi":"10.1016/j.etap.2025.104911","DOIUrl":"10.1016/j.etap.2025.104911","url":null,"abstract":"<div><div>This study assesses seasonal heavy-metal contamination from gold mining in the Bong Mieu River basin (central Viet Nam) and examines its association with human xenobiotic-metabolizing enzyme phenotypes. In sediments, As and Pb consistently exceeded Vietnamese sediment quality limits, by 4.1–25.4 × for As and 2.3–7.8 × for Pb, whereas other metals generally remained within regulatory thresholds. River water exhibited widespread Pb exceedances at all sites and occasional. As exceedances, with higher concentrations in the dry season. Regression analyses indicated strong water–sediment coupling for As, Pb, Hg, Cd, and Zn, supporting shared transport and accumulation processes. Season-resolved Pearson correlations, HCA, PCA, and APCS-MLR source apportionment revealed a dominant mining-derived multi-metal signal year-round, intensified and spatially mixed under monsoon hydrology. Enzyme phenotypes varied with the mixed-metal exposure gradient: sites with higher As/Pb burdens showed higher frequencies of slow NAT2 and intermediate/slow CYP450 phenotypes, and longer residence was associated with higher NAT2 rapid-phenotype frequency.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"121 ","pages":"Article 104911"},"PeriodicalIF":4.2,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776925","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 : 2025-12-15DOI: 10.1016/j.etap.2025.104912
Alice Gabetti , Camilla Mossotto , Francesca Provenza , Serena Anselmi , Alessandra Maganza , Giuseppe Esposito , Maria Vittoria Riina , Alessandra Griglione , Stefania Squadrone , Monia Renzi , Antonia Concetta Elia , Marino Prearo , Paolo Pastorino
The increasing anthropogenic release of gadolinium (Gd) from medical contrast agents raises concern regarding its fate and ecotoxicological effects in freshwater ecosystems. Gd may reach alpine lakes through atmospheric deposition, entering environments already fragile due to extreme conditions. This study examined the sublethal effects of Gd on the alpine copepod Cyclops abyssorum under simulated winter conditions (4 °C, darkness). Organisms were exposed for 14 days to 1–150 µg/L Gd, and oxidative stress biomarkers were measured. Glutathione peroxidase activity increased with concentration, while malondialdehyde indicated lipid peroxidation. Superoxide dismutase and glutathione S-transferase showed non-linear responses, suggesting physiological thresholds or enzyme inhibition. The Threshold-based Integrative Biomarker Response (IBR-T) index revealed progressively higher stress at intermediate and high exposures. Overall, the results indicate that Gd can induce oxidative stress in cold-adapted zooplankton, emphasizing the importance of assessing contaminant risks in alpine lakes using non-model species and realistic exposure scenarios.
{"title":"What lies beneath the ice? How gadolinium affects Cyclops abyssorum during Alpine winters","authors":"Alice Gabetti , Camilla Mossotto , Francesca Provenza , Serena Anselmi , Alessandra Maganza , Giuseppe Esposito , Maria Vittoria Riina , Alessandra Griglione , Stefania Squadrone , Monia Renzi , Antonia Concetta Elia , Marino Prearo , Paolo Pastorino","doi":"10.1016/j.etap.2025.104912","DOIUrl":"10.1016/j.etap.2025.104912","url":null,"abstract":"<div><div>The increasing anthropogenic release of gadolinium (Gd) from medical contrast agents raises concern regarding its fate and ecotoxicological effects in freshwater ecosystems. Gd may reach alpine lakes through atmospheric deposition, entering environments already fragile due to extreme conditions. This study examined the sublethal effects of Gd on the alpine copepod <em>Cyclops abyssorum</em> under simulated winter conditions (4 °C, darkness). Organisms were exposed for 14 days to 1–150 µg/L Gd, and oxidative stress biomarkers were measured. Glutathione peroxidase activity increased with concentration, while malondialdehyde indicated lipid peroxidation. Superoxide dismutase and glutathione S-transferase showed non-linear responses, suggesting physiological thresholds or enzyme inhibition. The Threshold-based Integrative Biomarker Response (IBR-T) index revealed progressively higher stress at intermediate and high exposures. Overall, the results indicate that Gd can induce oxidative stress in cold-adapted zooplankton, emphasizing the importance of assessing contaminant risks in alpine lakes using non-model species and realistic exposure scenarios.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"121 ","pages":"Article 104912"},"PeriodicalIF":4.2,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776899","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 : 2025-12-12DOI: 10.1016/j.etap.2025.104909
Ryan Brownlee , Maria E.A. Galiciolli , Lucy Joshee , Adam M. Kiefer , Caryn S. Seney , Christy C. Bridges
The processing of gold ore with both mercury (Hg) and cyanide (-CN) leads to widespread environmental contamination. Hg and its related compounds form complexes with -CN in the environment, which may result in human exposure through ingestion of contaminated food or water. The kidney is a significant site of Hg accumulation, but the mechanisms by which mercuric cyanide (Hg(CN)n2-n) and methylmercuric cyanide (H3CHg(CN)n1-n) complexes are taken up by renal tubular cells are unknown. We hypothesized that the organic anion transporter (OAT1) is involved in the uptake of these complexes. To test this hypothesis, the time course, temperature-dependence, saturation kinetics, and substrate specificity of Hg uptake were examined in human embryonic kidney cells stably transfected with OAT1. Our data show that these complexes are taken into proximal tubular cells via OAT1. These data are the first to identify a mechanism involved in the uptake of mercuric-cyanide species into proximal tubular cells.
{"title":"Organic anion transporter 1 (OAT1) is a mechanism for uptake of mercuric-cyanide complexes into proximal tubular cells","authors":"Ryan Brownlee , Maria E.A. Galiciolli , Lucy Joshee , Adam M. Kiefer , Caryn S. Seney , Christy C. Bridges","doi":"10.1016/j.etap.2025.104909","DOIUrl":"10.1016/j.etap.2025.104909","url":null,"abstract":"<div><div>The processing of gold ore with both mercury (Hg) and cyanide (<sup>-</sup>CN) leads to widespread environmental contamination. Hg and its related compounds form complexes with <sup>-</sup>CN in the environment, which may result in human exposure through ingestion of contaminated food or water. The kidney is a significant site of Hg accumulation, but the mechanisms by which mercuric cyanide (Hg(CN)<sub>n</sub><sup>2-n</sup>) and methylmercuric cyanide (H<sub>3</sub>CHg(CN)<sub>n</sub><sup>1-n</sup>) complexes are taken up by renal tubular cells are unknown. We hypothesized that the organic anion transporter (OAT1) is involved in the uptake of these complexes. To test this hypothesis, the time course, temperature-dependence, saturation kinetics, and substrate specificity of Hg uptake were examined in human embryonic kidney cells stably transfected with OAT1. Our data show that these complexes are taken into proximal tubular cells via OAT1. These data are the first to identify a mechanism involved in the uptake of mercuric-cyanide species into proximal tubular cells.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"121 ","pages":"Article 104909"},"PeriodicalIF":4.2,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145731818","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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