Pub Date : 2026-03-01Epub Date: 2026-01-21DOI: 10.1016/j.etap.2026.104944
Mohamed Abdeltawab , Abdel-Hameed Ebid , Osama Ahmed , Mohamed A. Mobarez , Mahmoud Ibrahim
Linezolid-associated thrombocytopenia (LAT) limits its use in critically ill patients. This double-blind, randomized, placebo-controlled trial evaluated intravenous N-acetylcysteine (IV NAC) for LAT prevention in 250 critically ill adults receiving linezolid for ≥ 48 h. Patients received IV NAC (600 mg every 12 h) or placebo. The primary endpoint was LAT incidence (platelet count <150 × 10 ³/mm³ or >50 % reduction from baseline). NAC significantly reduced LAT incidence (16.8 % vs. 41.6 %; p < 0.001), platelet transfusions (1.6 % vs. 11.2 %; p = 0.003), and linezolid discontinuations (6.4 % vs. 32.0 %; p < 0.001). NAC delayed LAT onset (adjusted hazard ratio 0.24; p < 0.001) and accelerated platelet recovery (adjusted hazard ratio 3.88; p = 0.011), with greatest benefit in moderate-severity cases. These findings suggest IV NAC may offer a preventive benefit against LAT in critically ill patients, though multicenter validation is needed to confirm generalizability across diverse clinical settings.
Clinical Trial Registration
https://clinicaltrials.gov/study/NCT05944458. Registered on July 6, 2023.
{"title":"N-acetylcysteine reduces incidence and duration of linezolid-associated thrombocytopenia in critically ill patients: A randomized controlled trial","authors":"Mohamed Abdeltawab , Abdel-Hameed Ebid , Osama Ahmed , Mohamed A. Mobarez , Mahmoud Ibrahim","doi":"10.1016/j.etap.2026.104944","DOIUrl":"10.1016/j.etap.2026.104944","url":null,"abstract":"<div><div>Linezolid-associated thrombocytopenia (LAT) limits its use in critically ill patients. This double-blind, randomized, placebo-controlled trial evaluated intravenous N-acetylcysteine (IV NAC) for LAT prevention in 250 critically ill adults receiving linezolid for ≥ 48 h. Patients received IV NAC (600 mg every 12 h) or placebo. The primary endpoint was LAT incidence (platelet count <150 × 10 ³/mm³ or >50 % reduction from baseline). NAC significantly reduced LAT incidence (16.8 % vs. 41.6 %; p < 0.001), platelet transfusions (1.6 % vs. 11.2 %; p = 0.003), and linezolid discontinuations (6.4 % vs. 32.0 %; p < 0.001). NAC delayed LAT onset (adjusted hazard ratio 0.24; p < 0.001) and accelerated platelet recovery (adjusted hazard ratio 3.88; p = 0.011), with greatest benefit in moderate-severity cases. These findings suggest IV NAC may offer a preventive benefit against LAT in critically ill patients, though multicenter validation is needed to confirm generalizability across diverse clinical settings.</div></div><div><h3>Clinical Trial Registration</h3><div><span><span>https://clinicaltrials.gov/study/NCT05944458</span><svg><path></path></svg></span>. Registered on July 6, 2023.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104944"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033386","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: 2026-01-20DOI: 10.1016/j.etap.2026.104943
Rahul Kumar , Ashwin Chinala , Rama R. Gullapalli
Cadmium (Cd) is an anthropogenic toxic heavy metal pollutant with a biological half-life on the order of decades. Chronic Cd exposures through industrial sources, cigarette smoke (1° and 2°), and contaminated food and/or water sources lead to progressive bioaccumulation, particularly in the human liver and kidneys. In hepatocytes, Cd is a potent inducer of mitochondrial dysfunction and oxidative stress. Cd exposures initiate a cascade of reactive oxygen species (ROS) production, triggering redox imbalances, acute and chronic inflammation, and, in extreme exposures, cellular death. While mitochondria are well recognized as central targets of Cd toxicity, the precise mechanisms linking Cd-induced mitochondrial damage driving chronic liver and metabolic diseases remains incompletely understood. Emerging evidence implicates Cd exposure as a direct inhibitor of the mitochondrial electron transport chain (ETC) complexes and disruption of calcium homeostasis as key, converging pathways of hepatocellular injury. And yet, their specific molecular underpinnings are still unknown. This review focuses on how Cd exposures perturb mitochondrial bioenergetics, calcium signaling, and lipid signaling and metabolism within the hepatocytes specifically. Subsequently, we examine how these molecular-level alterations may contribute to the pathogenesis of chronic liver disease. In this review article, we present a cohesive framework to highlight Cd exposures as a critical (and a model) environmental heavy metal driver of chronic hepatocellular mitochondrial injury. Prolonged heavy metal exposures (such as Cd) have significant implications for long-term human hepatic health and metabolic disorders, such as metabolic (dysfunction) associated liver injury (MASLD), a key emerging pandemic of chronic human liver disease.
{"title":"Understanding molecular mechanisms driving cadmium-induced mitochondrial dysfunction in human metabolic liver disease","authors":"Rahul Kumar , Ashwin Chinala , Rama R. Gullapalli","doi":"10.1016/j.etap.2026.104943","DOIUrl":"10.1016/j.etap.2026.104943","url":null,"abstract":"<div><div>Cadmium (Cd) is an anthropogenic toxic heavy metal pollutant with a biological half-life on the order of decades. Chronic Cd exposures through industrial sources, cigarette smoke (1° and 2°), and contaminated food and/or water sources lead to progressive bioaccumulation, particularly in the human liver and kidneys. In hepatocytes, Cd is a potent inducer of mitochondrial dysfunction and oxidative stress. Cd exposures initiate a cascade of reactive oxygen species (ROS) production, triggering redox imbalances, acute and chronic inflammation, and, in extreme exposures, cellular death. While mitochondria are well recognized as central targets of Cd toxicity, the precise mechanisms linking Cd-induced mitochondrial damage driving chronic liver and metabolic diseases remains incompletely understood. Emerging evidence implicates Cd exposure as a direct inhibitor of the mitochondrial electron transport chain (ETC) complexes and disruption of calcium homeostasis as key, converging pathways of hepatocellular injury. And yet, their specific molecular underpinnings are still unknown. This review focuses on how Cd exposures perturb mitochondrial bioenergetics, calcium signaling, and lipid signaling and metabolism within the hepatocytes specifically. Subsequently, we examine how these molecular-level alterations may contribute to the pathogenesis of chronic liver disease. In this review article, we present a cohesive framework to highlight Cd exposures as a critical (and a model) environmental heavy metal driver of chronic hepatocellular mitochondrial injury. Prolonged heavy metal exposures (such as Cd) have significant implications for long-term human hepatic health and metabolic disorders, such as metabolic (dysfunction) associated liver injury (MASLD), a key emerging pandemic of chronic human liver disease.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104943"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014950","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: 2025-12-30DOI: 10.1016/j.etap.2025.104920
Enzo de Oliveira Novaes , Adriano Teixeira de Oliveira , Paloma de Almeida Rodrigues , Letícia Torrão Araruna , Júlia Vianna de Pinho , Flavia Dayana Felix Farias , Lucas Maia Garcês , Barbara Franz , Carlos Adam Conte-Junior
The present study aimed to determine the mercury (Hg) levels and risk analysis of consumption of tambaqui Colossoma macropomum in fish farms in the Amazon region. In total 212 tambaqui muscle samples were collected from 10 fish farms in 5 states (Amazonas, Pará, Amapá, Roraima, and Rondônia). The Hg in tambaqui muscles in the Amazon region revealed that Amazonas and Amapá had the highest values. The monthly estimate of tambaqui consumption per month showed that children had the highest values compared to young people and adults. Meanwhile, in the states of Amazonas and Amapá, especially among children, the maximum monthly intake of tambaqui should be lower than in other localities. For the hazard quality, only tambaqui evaluated in fish farms in the states of Roraima, Rondônia and Pará presented safety levels. Therefore, routine biomonitoring of fish farms is crucial, especially tambaqui farms, as the main fish species farmed in Brazil.
{"title":"Evaluation of mercury and risk analysis of consumption of the Amazonian tambaqui fish Colossoma macropomum from the production system of the Amazon region","authors":"Enzo de Oliveira Novaes , Adriano Teixeira de Oliveira , Paloma de Almeida Rodrigues , Letícia Torrão Araruna , Júlia Vianna de Pinho , Flavia Dayana Felix Farias , Lucas Maia Garcês , Barbara Franz , Carlos Adam Conte-Junior","doi":"10.1016/j.etap.2025.104920","DOIUrl":"10.1016/j.etap.2025.104920","url":null,"abstract":"<div><div>The present study aimed to determine the mercury (Hg) levels and risk analysis of consumption of tambaqui <em>Colossoma macropomum</em> in fish farms in the Amazon region. In total 212 tambaqui muscle samples were collected from 10 fish farms in 5 states (Amazonas, Pará, Amapá, Roraima, and Rondônia). The Hg in tambaqui muscles in the Amazon region revealed that Amazonas and Amapá had the highest values. The monthly estimate of tambaqui consumption per month showed that children had the highest values compared to young people and adults. Meanwhile, in the states of Amazonas and Amapá, especially among children, the maximum monthly intake of tambaqui should be lower than in other localities. For the hazard quality, only tambaqui evaluated in fish farms in the states of Roraima, Rondônia and Pará presented safety levels. Therefore, routine biomonitoring of fish farms is crucial, especially tambaqui farms, as the main fish species farmed in Brazil.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104920"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890664","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: 2026-01-27DOI: 10.1016/j.etap.2026.104950
F.J. Hernández-Fernández , J. Hernández-Fernández , L.J. Lozano , E. Iniesta-López , A. Hernández-Fernández , J. Quesada-Medina , V. Caballero , A.P. de los Ríos
The increasing interest in ionic liquids (ILs) as alternative solvents for biocatalytic and industrial applications is limited by concerns regarding their potential toxicity. In this study, we compiled one of the most comprehensive ecotoxicity datasets to date for Vibrio fischeri, Daphnia magna, and Pseudokirchneriella subcapitata. Using Partial Least Squares (PLS)-based Quantitative Structure–Activity Relationship (QSAR) models, we established predictive correlations between IL structural features and ecotoxicity. The models demonstrated high robustness and predictive power, enabling identification of key molecular descriptors driving toxicity. Results consistently indicate that longer alkyl side chains in cations, higher hydrophobicity, and aromatic ring structures are associated with increased toxicity, whereas the incorporation of heteroatoms (O, OH, CN) or non-aromatic rings reduces toxicity. Anions generally exert a lower influence compared to cations, although certain highly fluorinated species substantially increase toxicity. The comparative analysis across microorganisms highlights both shared and species-specific structural determinants. These findings provide valuable insights into IL toxicity mechanisms, particularly the role of membrane accumulation and disruption, and establish design rules for the development of safer, environmentally benign ionic liquids suitable for green chemistry and biotechnological processes.
{"title":"Comparing qsar models of ionic liquid toxicity for different microorganisms to design environmentally friendly ionic liquids and elucidate mechanisms of toxicity","authors":"F.J. Hernández-Fernández , J. Hernández-Fernández , L.J. Lozano , E. Iniesta-López , A. Hernández-Fernández , J. Quesada-Medina , V. Caballero , A.P. de los Ríos","doi":"10.1016/j.etap.2026.104950","DOIUrl":"10.1016/j.etap.2026.104950","url":null,"abstract":"<div><div>The increasing interest in ionic liquids (ILs) as alternative solvents for biocatalytic and industrial applications is limited by concerns regarding their potential toxicity. In this study, we compiled one of the most comprehensive ecotoxicity datasets to date for Vibrio fischeri, Daphnia magna, and Pseudokirchneriella subcapitata. Using Partial Least Squares (PLS)-based Quantitative Structure–Activity Relationship (QSAR) models, we established predictive correlations between IL structural features and ecotoxicity. The models demonstrated high robustness and predictive power, enabling identification of key molecular descriptors driving toxicity. Results consistently indicate that longer alkyl side chains in cations, higher hydrophobicity, and aromatic ring structures are associated with increased toxicity, whereas the incorporation of heteroatoms (O, OH, CN) or non-aromatic rings reduces toxicity. Anions generally exert a lower influence compared to cations, although certain highly fluorinated species substantially increase toxicity. The comparative analysis across microorganisms highlights both shared and species-specific structural determinants. These findings provide valuable insights into IL toxicity mechanisms, particularly the role of membrane accumulation and disruption, and establish design rules for the development of safer, environmentally benign ionic liquids suitable for green chemistry and biotechnological processes.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"122 ","pages":"Article 104950"},"PeriodicalIF":4.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146072576","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}
Recognition of bisphenol A’s toxicity has meant substitution by new analogues, which are poorly investigated. We determined the impact of bisphenol A and 8 of its analogues on platelet aggregation, coagulation, and their toxicity to erythrocytes. Erythrocyte lysis assays revealed bisphenol toxicity towards both human and rat erythrocytes with high TC50s > 100 μM. Bisphenol A and bisphenol PH acted as antiplatelet compounds. Bisphenol PH was particularly potent (IC50 of 0.42 ± 0.14 μM; 0.16 ± 0.05 μg/ml) in arachidonic acid-based platelet aggregation. Mechanistically, bisphenol PH blocked cyclooxygenase 1, in a similar manner to the antiplatelet drug acetylsalicylic acid. In terms of the coagulation cascade, only weak effects were found for some of the selected compounds, and the tested bisphenols did not impact coagulation or demonstrate erythrocytic toxicity at biologically achievable concentrations. Contrarily, the negative impact of bisphenol PH on platelets, with a possible subsequent risk of bleeding, might have biological relevance.
{"title":"The effect of bisphenol PH and seven other bisphenol A alternatives on human haemostasis in vitro","authors":"Marcel Hrubša , Alina Soloviova , Patrícia Harčárová , Catherine Gunaseelan , Zuzana Lomozová , Eduard Jirkovský , Alejandro Carazo , Marija Sollner Dolenc , Lucija Peterlin Mašič , Přemysl Mladěnka","doi":"10.1016/j.etap.2025.104897","DOIUrl":"10.1016/j.etap.2025.104897","url":null,"abstract":"<div><div>Recognition of bisphenol A’s toxicity has meant substitution by new analogues, which are poorly investigated. We determined the impact of bisphenol A and 8 of its analogues on platelet aggregation, coagulation, and their toxicity to erythrocytes. Erythrocyte lysis assays revealed bisphenol toxicity towards both human and rat erythrocytes with high TC<sub>50</sub>s > 100 μM. Bisphenol A and bisphenol PH acted as antiplatelet compounds. Bisphenol PH was particularly potent (IC<sub>50</sub> of 0.42 ± 0.14 μM; 0.16 ± 0.05 μg/ml) in arachidonic acid-based platelet aggregation. Mechanistically, bisphenol PH blocked cyclooxygenase 1, in a similar manner to the antiplatelet drug acetylsalicylic acid. In terms of the coagulation cascade, only weak effects were found for some of the selected compounds, and the tested bisphenols did not impact coagulation or demonstrate erythrocytic toxicity at biologically achievable concentrations. Contrarily, the negative impact of bisphenol PH on platelets, with a possible subsequent risk of bleeding, might have biological relevance.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"121 ","pages":"Article 104897"},"PeriodicalIF":4.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145688782","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 : 2026-01-01Epub Date: 2025-12-11DOI: 10.1016/j.etap.2025.104903
Ana Caroline Pimentel de Oliveira , Letícia Ramos Molica , Karen C.M. Moraes
Pesticides are used worldwide and cause several pathologies as metabolic dysfunction-associated steatotic liver disease. Steatosis is a mark of the disease beginning; however, the mechanisms by which pesticides act on this dysfunction require further understanding. Thus, this work presents a sensitive and responsive low-cost hepatic multicellular spheroid useful to detail metabolic routes in hepatic dysfunction. Using those spheroids, the effects of pesticides bromacil and terbacil were assessed. Pesticides doses near the acceptable daily intake in Brazil changes energetic, oxidative and the one-carbon metabolism. Moreover, pesticide-specific effects were observed as increased expression of FASN, PPARs, CYP1A1, AHR, DNMTs among others, and changes in the methylation pattern of DNA, RNA and histones. Combined, the results were alarming, considering the long-lasting effects of the evaluated pesticides in agriculture fields. In addition, we can suggest that our spheroid model could be useful for large scale investigation of the effects of pesticides in liver metabolism.
{"title":"Assessing the effects of uracil-based pesticides on hepatic metabolic dysfunctions in low-cost three-dimensional multicellular spheroids","authors":"Ana Caroline Pimentel de Oliveira , Letícia Ramos Molica , Karen C.M. Moraes","doi":"10.1016/j.etap.2025.104903","DOIUrl":"10.1016/j.etap.2025.104903","url":null,"abstract":"<div><div>Pesticides are used worldwide and cause several pathologies as metabolic dysfunction-associated steatotic liver disease. Steatosis is a mark of the disease beginning; however, the mechanisms by which pesticides act on this dysfunction require further understanding. Thus, this work presents a sensitive and responsive low-cost hepatic multicellular spheroid useful to detail metabolic routes in hepatic dysfunction. Using those spheroids, the effects of pesticides bromacil and terbacil were assessed. Pesticides doses near the acceptable daily intake in Brazil changes energetic, oxidative and the one-carbon metabolism. Moreover, pesticide-specific effects were observed as increased expression of <em>FASN</em>, <em>PPAR</em>s, <em>CYP1A1</em>, <em>AHR</em>, <em>DNMT</em>s among others, and changes in the methylation pattern of DNA, RNA and histones. Combined, the results were alarming, considering the long-lasting effects of the evaluated pesticides in agriculture fields. In addition, we can suggest that our spheroid model could be useful for large scale investigation of the effects of pesticides in liver metabolism.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"121 ","pages":"Article 104903"},"PeriodicalIF":4.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145731817","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 : 2026-01-01Epub 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":"2026-01-01","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 : 2026-01-01Epub Date: 2025-12-11DOI: 10.1016/j.etap.2025.104906
Humaira H. Rahman , Weston R. Stokey , Stuart H. Munson-McGee
Human exposure to per- and poly-fluoroalkyl substances (PFAS) occurs from environmentally contaminated food and water. PFAS are a health concern because they are associated with various neurological, developmental, and endocrine disorders. Despite causes of infertility being equal, male causes are less studied, with etiologies ranging from genetic to anatomic to physiologic dysfunctions. This study aimed to investigate a correlation between six subtypes of PFAS with low male testosterone levels. Data from the National Health and Nutrition Examination Survey (NHANES) cycles 2013–2016 were utilized to assess serum PFAS and testosterone levels. This study observed age, marital status, body mass index, smoking status, alcohol consumption, and diabetic status being significantly correlated with low testosterone levels. PFNA exposure was observed to have a strong inverse relationship with male testosterone levels in low/medium (ORs 0.518, 0.571, 0.322, 0.455) and low/high-medium exposure levels (ORs 0.262, 0.262, 0.321, and 0.310), indicating exposure-dependent effects on testosterone levels.
{"title":"Correlation of per- and poly-fluoroalkyl substances (PFAS) exposure with testosterone levels in the male population","authors":"Humaira H. Rahman , Weston R. Stokey , Stuart H. Munson-McGee","doi":"10.1016/j.etap.2025.104906","DOIUrl":"10.1016/j.etap.2025.104906","url":null,"abstract":"<div><div>Human exposure to per- and poly-fluoroalkyl substances <strong>(</strong>PFAS) occurs from environmentally contaminated food and water. PFAS are a health concern because they are associated with various neurological, developmental, and endocrine disorders. Despite causes of infertility being equal, male causes are less studied, with etiologies ranging from genetic to anatomic to physiologic dysfunctions. This study aimed to investigate a correlation between six subtypes of PFAS with low male testosterone levels. Data from the National Health and Nutrition Examination Survey (NHANES) cycles 2013–2016 were utilized to assess serum PFAS and testosterone levels. This study observed age, marital status, body mass index, smoking status, alcohol consumption, and diabetic status being significantly correlated with low testosterone levels. PFNA exposure was observed to have a strong inverse relationship with male testosterone levels in low/medium (ORs 0.518, 0.571, 0.322, 0.455) and low/high-medium exposure levels (ORs 0.262, 0.262, 0.321, and 0.310), indicating exposure-dependent effects on testosterone levels.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"121 ","pages":"Article 104906"},"PeriodicalIF":4.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145731819","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 : 2026-01-01Epub Date: 2025-12-07DOI: 10.1016/j.etap.2025.104899
Patricia Rolo , João L.T. Pestana , Diana Campos
UV filters are contaminants of emerging concern, acting as endocrine disruptors, and altering the normal development of living organisms. Due to their lipophilic properties, they accumulate in aquatic sediments, endangering epibenthic organisms such as planarians. We aimed to assess the sensitivity of Girardia tigrina to two organic UV filters, 2-hydroxy-4-methoxybenzophenone (BP-3, Benzophenone-3) and 4-methylbenzylidene camphor (4-MBC, Enzacamene), by evaluating mortality, behavioural activity, cephalic regeneration after decapitation, and biochemical endpoints. A 96-hour LC50 s of 1483 µg/L and 1653 µg/L were estimated for BP-3 and 4-MBC, respectively. Sublethal concentrations of both compounds impaired planarian cephalic regeneration; BP-3 induced a delay in auricles regeneration, while 4-MBC delayed both photoreceptors and auricles regeneration. Locomotion significantly decreased in planarians exposed to 4-MBC, while BP-3 exposure did not induce locomotion alterations in G. tigrina. Moreover, induced phase II detoxifying enzyme (measured through Glutathione-S-transferase activity) was also observed in 4-MBC exposure, possibly mitigating oxidative damage, while BP-3 exposure caused oxidative damage (increased lipid peroxidation levels). Exposure to both compounds led to a reduction in acetylcholinesterase activity, showing evidence of neurotoxicity. Even though this study reported deleterious effects in exposed G. tigrina, the concentrations at which effects were reported are still higher than those usually reported in the freshwater environment. However, we would like to emphasise the importance of such studies in supporting the regulation and environmentally safe use of sunscreen products.
紫外线过滤器是新兴关注的污染物，作为内分泌干扰物，并改变生物体的正常发育。由于它们的亲脂性，它们积聚在水生沉积物中，危及像涡虫这样的底栖生物。我们旨在通过评估死亡率、行为活性、斩首后头再生和生化终点来评估虎Girardia tigrina对2-羟基-4-甲氧基二苯甲酮（BP-3，二苯甲酮-3）和4-甲基苄基樟脑（4-MBC, Enzacamene）两种有机紫外线过滤器的敏感性。BP-3和4-MBC的96小时lc50分别为1483µg/L和1653µg/L。这两种化合物的亚致死浓度损害了涡虫的头再生；BP-3诱导耳廓再生延迟，而4-MBC同时延迟光感受器和耳廓再生。暴露于4-MBC的涡虫的运动能力显著降低，而BP-3暴露未引起大鼠的运动能力改变。此外，在4-MBC暴露中也观察到诱导II期解毒酶（通过谷胱甘肽- s -转移酶活性测量），可能减轻氧化损伤，而BP-3暴露引起氧化损伤（增加脂质过氧化水平）。暴露于这两种化合物导致乙酰胆碱酯酶活性降低，显示出神经毒性的证据。尽管本研究报告了暴露的绿螺旋藻的有害影响，但报告的影响浓度仍然高于通常在淡水环境中报告的浓度。然而，我们想强调这些研究在支持防晒霜产品的监管和环境安全使用方面的重要性。
{"title":"Toxicity assessment of organic UV filters Benzophenone-3 (BP-3) and Enzacamene (4-MBC) using the freshwater planarian Girardia tigrina","authors":"Patricia Rolo , João L.T. Pestana , Diana Campos","doi":"10.1016/j.etap.2025.104899","DOIUrl":"10.1016/j.etap.2025.104899","url":null,"abstract":"<div><div>UV filters are contaminants of emerging concern, acting as endocrine disruptors, and altering the normal development of living organisms. Due to their lipophilic properties, they accumulate in aquatic sediments, endangering epibenthic organisms such as planarians. We aimed to assess the sensitivity of <em>Girardia tigrina</em> to two organic UV filters, 2-hydroxy-4-methoxybenzophenone (BP-3, Benzophenone-3) and 4-methylbenzylidene camphor (4-MBC, Enzacamene), by evaluating mortality, behavioural activity, cephalic regeneration after decapitation, and biochemical endpoints. A 96-hour LC<sub>50 s</sub> of 1483 µg/L and 1653 µg/L were estimated for BP-3 and 4-MBC, respectively. Sublethal concentrations of both compounds impaired planarian cephalic regeneration; BP-3 induced a delay in auricles regeneration, while 4-MBC delayed both photoreceptors and auricles regeneration. Locomotion significantly decreased in planarians exposed to 4-MBC, while BP-3 exposure did not induce locomotion alterations in <em>G. tigrina</em>. Moreover, induced phase II detoxifying enzyme (measured through Glutathione-<em>S</em>-transferase activity) was also observed in 4-MBC exposure, possibly mitigating oxidative damage, while BP-3 exposure caused oxidative damage (increased lipid peroxidation levels). Exposure to both compounds led to a reduction in acetylcholinesterase activity, showing evidence of neurotoxicity. Even though this study reported deleterious effects in exposed <em>G. tigrina</em>, the concentrations at which effects were reported are still higher than those usually reported in the freshwater environment. However, we would like to emphasise the importance of such studies in supporting the regulation and environmentally safe use of sunscreen products.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"121 ","pages":"Article 104899"},"PeriodicalIF":4.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145697229","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 : 2026-01-01Epub 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":"2026-01-01","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}
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