Pub Date : 2025-10-30DOI: 10.1016/j.etap.2025.104857
Gabriel O. Ostapchuk , Analía Ale , Victoria S. Andrade , Gisela L. Poletta , Luciana Montalto , Florencia M. Rojas Molina , Martín F. Desimone , Paolo N. Catalano
Silica nanoparticles (SiNP) have a high global production volume, but their toxicity is far from being completely understood. In this study, we synthesized SiNP with distinct morphological features: dense SiNP (dSiNP), conventional mesoporous SiNP (MSN), and two types of flower-like dendritic mesoporous SiNP with a stellate lamellar structure: one using ibuprofen (FLW-IBU) and one using sodium salicylate (FLW-NaSal) as auxiliary templates. To assess their toxicological impact, we conducted a 96-hour bioassay exposing the freshwater bivalve Limnoperna fortunei to 10 µg/mL of these varied SiNP. Exposure to dSiNP increased superoxide dismutase and glutathione S-transferase enzyme activities in the soft tissue of bivalves. Lipid peroxidation levels also augmented following exposure to both dSiNP and MSN. We observed no significant alterations in tissular damage markers across treatments. Neither FLW-IBU nor FLW-NaSal induced any deleterious effect, indicating they are less detrimental to L. fortunei. These findings contribute to the safe-by-design development of nanomaterials.
{"title":"Impact of morphologically tuned silica nanoparticles on the invasive freshwater bivalve Limnoperna fortunei","authors":"Gabriel O. Ostapchuk , Analía Ale , Victoria S. Andrade , Gisela L. Poletta , Luciana Montalto , Florencia M. Rojas Molina , Martín F. Desimone , Paolo N. Catalano","doi":"10.1016/j.etap.2025.104857","DOIUrl":"10.1016/j.etap.2025.104857","url":null,"abstract":"<div><div>Silica nanoparticles (SiNP) have a high global production volume, but their toxicity is far from being completely understood. In this study, we synthesized SiNP with distinct morphological features: dense SiNP (dSiNP), conventional mesoporous SiNP (MSN), and two types of flower-like dendritic mesoporous SiNP with a stellate lamellar structure: one using ibuprofen (FLW-IBU) and one using sodium salicylate (FLW-NaSal) as auxiliary templates. To assess their toxicological impact, we conducted a 96-hour bioassay exposing the freshwater bivalve <em>Limnoperna fortunei</em> to 10 µg/mL of these varied SiNP. Exposure to dSiNP increased superoxide dismutase and glutathione S-transferase enzyme activities in the soft tissue of bivalves. Lipid peroxidation levels also augmented following exposure to both dSiNP and MSN. We observed no significant alterations in tissular damage markers across treatments. Neither FLW-IBU nor FLW-NaSal induced any deleterious effect, indicating they are less detrimental to <em>L. fortunei</em>. These findings contribute to the safe-by-design development of nanomaterials.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104857"},"PeriodicalIF":4.2,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145383645","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 : 2025-10-30DOI: 10.1016/j.etap.2025.104858
Mengya Si , Muhammad Nadeem Khan , Hazrat Bilal , Muhammad Shafiq , Sabir Khan , Xiaoling Guo , Meimei Wang , Jilong Wu , Wang Zhen , Fen Yao , Adela Jing Li , Xiaoyang Jiao
Neonicotinoids (NEOs) and their metabolites impact neuronal function; however, their effects on neurotransmitters remain unexplored. We analyzed cerebrospinal fluid (CSF) from leukemia patients with differing concentrations of N-desmethyl-acetamiprid (N-dm-ACE) for neurotransmitter profiling. Neurotransmitters and biomarkers were measured in CSF, blood, and serum from 39 patients (19 low and 20 high N-dm-ACE) across three age groups: children, adults, and elders. Significant differences (p ≤ 0.05) in neurotransmitters were found among groups, including glutamic acid (253.45 ± 388.16 & 101.11 ± 52.79), aspartic acid (79.64 ± 87.46 & 0.00), tryptophan (325.89 ± 76.47 & 508.09 ± 331.35), and tyrosine (984.41 ± 348.78 ng/mL). Regression analysis indicated that N-dm-ACE is significantly (p < 0.05) positively associated with serum total proteins and negatively with betaine-aldehyde-chloride and ornithine. This suggests that increased accumulation of N-dm-ACE in the CNS may elevate the risk of neurological or neurotoxic conditions. Further studies are needed to better understand the intricate relationship between NEOs, particularly N-dm-ACE, and brain health.
{"title":"Investigation of N-desmethyl-acetamiprid-induced neurotransmitter disturbances in cerebrospinal fluid from leukemia patients","authors":"Mengya Si , Muhammad Nadeem Khan , Hazrat Bilal , Muhammad Shafiq , Sabir Khan , Xiaoling Guo , Meimei Wang , Jilong Wu , Wang Zhen , Fen Yao , Adela Jing Li , Xiaoyang Jiao","doi":"10.1016/j.etap.2025.104858","DOIUrl":"10.1016/j.etap.2025.104858","url":null,"abstract":"<div><div>Neonicotinoids (NEOs) and their metabolites impact neuronal function; however, their effects on neurotransmitters remain unexplored. We analyzed cerebrospinal fluid (CSF) from leukemia patients with differing concentrations of N-desmethyl-acetamiprid (N-dm-ACE) for neurotransmitter profiling. Neurotransmitters and biomarkers were measured in CSF, blood, and serum from 39 patients (19 low and 20 high N-dm-ACE) across three age groups: children, adults, and elders. Significant differences (p ≤ 0.05) in neurotransmitters were found among groups, including glutamic acid (253.45 ± 388.16 & 101.11 ± 52.79), aspartic acid (79.64 ± 87.46 & 0.00), tryptophan (325.89 ± 76.47 & 508.09 ± 331.35), and tyrosine (984.41 ± 348.78 ng/mL). Regression analysis indicated that N-dm-ACE is significantly (p < 0.05) positively associated with serum total proteins and negatively with betaine-aldehyde-chloride and ornithine. This suggests that increased accumulation of N-dm-ACE in the CNS may elevate the risk of neurological or neurotoxic conditions. Further studies are needed to better understand the intricate relationship between NEOs, particularly N-dm-ACE, and brain health.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104858"},"PeriodicalIF":4.2,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145383644","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 : 2025-10-30DOI: 10.1016/j.etap.2025.104859
Wei Zhang , Hui Chen , Yanshu Li , Qian Zhu , Kangtai Liu , Xinran Liu , Yan Wang , Gaochun Zhu
Lead (Pb) facilitates neurological deficits. Silybin is a flavonoid with neuroprotective properties. Heterogeneous nuclear ribonucleoprotein U (hnRNP U) has been implicated in neurodevelopmental disorders and predicted to regulate Repressor Element-1 Silencing Transcription (REST) expression. STAT3 can form a complex with hnRNP U and is inhibited by Silybin. We aim to elucidate the role of hnRNP U/STAT3 in Pb neurotoxicity and the neuroprotective effects of Silybin in Pb-exposed rats. We found that Pb increased the nuclear protein levels of hnRNP U and STAT3 and REST expression, which Silybin can partially reverse. Silencing hnRNP U reduced REST expression. Inhibiting STAT3 blocked hnRNP U nuclear transport. Silybin improves Pb-induced learning and memory impairment. Silybin reduced the expression of hnRNP U and NFκB. Inhibiting NFκB reduced hnRNP U expression. These suggest that Silybin improves Pb-induced learning and memory impairment by antagonizing STAT3/hnRNP U/REST and hnRNP U/NFκB.
{"title":"Silybin ameliorates Pb-induced learning and memory impairment by inhibiting STAT3/hnRNP U/REST and NFκB/hnRNP U","authors":"Wei Zhang , Hui Chen , Yanshu Li , Qian Zhu , Kangtai Liu , Xinran Liu , Yan Wang , Gaochun Zhu","doi":"10.1016/j.etap.2025.104859","DOIUrl":"10.1016/j.etap.2025.104859","url":null,"abstract":"<div><div>Lead (Pb) facilitates neurological deficits. Silybin is a flavonoid with neuroprotective properties. Heterogeneous nuclear ribonucleoprotein U (hnRNP U) has been implicated in neurodevelopmental disorders and predicted to regulate Repressor Element-1 Silencing Transcription (REST) expression. STAT3 can form a complex with hnRNP U and is inhibited by Silybin. We aim to elucidate the role of hnRNP U/STAT3 in Pb neurotoxicity and the neuroprotective effects of Silybin in Pb-exposed rats. We found that Pb increased the nuclear protein levels of hnRNP U and STAT3 and REST expression, which Silybin can partially reverse. Silencing hnRNP U reduced REST expression. Inhibiting STAT3 blocked hnRNP U nuclear transport. Silybin improves Pb-induced learning and memory impairment. Silybin reduced the expression of hnRNP U and NFκB. Inhibiting NFκB reduced hnRNP U expression. These suggest that Silybin improves Pb-induced learning and memory impairment by antagonizing STAT3/hnRNP U/REST and hnRNP U/NFκB.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104859"},"PeriodicalIF":4.2,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145396813","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 : 2025-10-30DOI: 10.1016/j.etap.2025.104860
Claudia Moyano-López, Paula Llorens, Ana Juan-García, Cristina Juan
Beauvericin (BEA) and patulin (PAT) are foodborne mycotoxins with known cytotoxic effects, but their combined impact on neuronal cells is unclear. This study evaluates the individual and interactive neurotoxic effects of BEA and PAT in undifferentiated SH-SY5Y human neuroblastoma cells for 24 h and 48 h, focusing on oxidative stress, lipid peroxidation (LPO), cell cycle progression, and cell death. Both toxins increased reactive oxygen species (ROS), with greater levels under co-exposure, while LPO was mainly elevated by individual treatments. Combined exposure led to cell cycle arrest, characterized by SubG1 accumulation and reduction in S and M phases. Apoptosis and necrosis varied with time and dose, with co-exposure favoring late apoptosis and necrosis. These results demonstrate that BEA and PAT act an enhanced manner through oxidative and cell cycle–related mechanisms, underscoring the importance of considering co-exposures in neurotoxicity risk assessment.
{"title":"ROS-mediated cytotoxicity and cell death pathways in SH-SY5Y cells exposed to beauvericin, patulin, and their combination","authors":"Claudia Moyano-López, Paula Llorens, Ana Juan-García, Cristina Juan","doi":"10.1016/j.etap.2025.104860","DOIUrl":"10.1016/j.etap.2025.104860","url":null,"abstract":"<div><div>Beauvericin (BEA) and patulin (PAT) are foodborne mycotoxins with known cytotoxic effects, but their combined impact on neuronal cells is unclear. This study evaluates the individual and interactive neurotoxic effects of BEA and PAT in undifferentiated SH-SY5Y human neuroblastoma cells for 24 h and 48 h, focusing on oxidative stress, lipid peroxidation (LPO), cell cycle progression, and cell death. Both toxins increased reactive oxygen species (ROS), with greater levels under co-exposure, while LPO was mainly elevated by individual treatments. Combined exposure led to cell cycle arrest, characterized by SubG1 accumulation and reduction in S and M phases. Apoptosis and necrosis varied with time and dose, with co-exposure favoring late apoptosis and necrosis. These results demonstrate that BEA and PAT act an enhanced manner through oxidative and cell cycle–related mechanisms, underscoring the importance of considering co-exposures in neurotoxicity risk assessment.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104860"},"PeriodicalIF":4.2,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145404580","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}
Silver nanoparticles (AgNPs) are widely used for their antimicrobial properties, yet their neurotoxic mechanisms remain under-explored. Ferroptosis, an iron-dependent regulated cell-death pathway implicated in neurological disorders, has not been fully considered in AgNPs-induced neuronal injury. Here, exposures of HT22 mouse hippocampal neurons to AgNPs (2–8 µg/mL) or AgNO3 (0.15–0.6 µg/mL) reduce viability, disrupt iron homeostasis, trigger lipid peroxidation, downregulate GPX4 and upregulate SLC7A11 (system Xc⁻/GPX4 axis), and alter ferroptosis-related proteins (TFRC, FTH1, FTL, ACSL4, COX2). Ferroptosis inhibitors (deferoxamine, Ferrostatin-1) mitigate these effects. Notably, although AgNO3 induced greater Ag+ uptake, AgNPs produced equivalent ferroptotic responses, suggesting nanoparticle-specific mechanisms beyond ionic release. These findings echo our previous in vivo data showing that AgNPs exposure impairs learning and memory in mice. Collectively, our results indicate that AgNPs provoke ferroptosis in hippocampal neurons via iron-dysregulation and antioxidant failure, and our inhibitor-based in vitro study offers mechanistic insight that may guide future therapeutic strategies.
{"title":"Silver nanoparticles induce ferroptosis via iron dyshomeostasis and system Xc⁻/GPX4 axis dysregulation in HT22 cells","authors":"Shuyan Niu, Menghao Guo, Haitao Yang, Xiaoru Chang, Mengting Shang, Chenyu Liu, Mengjing Cui, Tianshu Wu, Yuying Xue","doi":"10.1016/j.etap.2025.104856","DOIUrl":"10.1016/j.etap.2025.104856","url":null,"abstract":"<div><div>Silver nanoparticles (AgNPs) are widely used for their antimicrobial properties, yet their neurotoxic mechanisms remain under-explored. Ferroptosis, an iron-dependent regulated cell-death pathway implicated in neurological disorders, has not been fully considered in AgNPs-induced neuronal injury. Here, exposures of HT22 mouse hippocampal neurons to AgNPs (2–8 µg/mL) or AgNO<sub>3</sub> (0.15–0.6 µg/mL) reduce viability, disrupt iron homeostasis, trigger lipid peroxidation, downregulate GPX4 and upregulate SLC7A11 (system Xc⁻/GPX4 axis), and alter ferroptosis-related proteins (TFRC, FTH1, FTL, ACSL4, COX2). Ferroptosis inhibitors (deferoxamine, Ferrostatin-1) mitigate these effects. Notably, although AgNO<sub>3</sub> induced greater Ag<sup>+</sup> uptake, AgNPs produced equivalent ferroptotic responses, suggesting nanoparticle-specific mechanisms beyond ionic release. These findings echo our previous <em>in vivo</em> data showing that AgNPs exposure impairs learning and memory in mice. Collectively, our results indicate that AgNPs provoke ferroptosis in hippocampal neurons via iron-dysregulation and antioxidant failure, and our inhibitor-based <em>in vitro</em> study offers mechanistic insight that may guide future therapeutic strategies.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104856"},"PeriodicalIF":4.2,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145383662","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 : 2025-10-24DOI: 10.1016/j.etap.2025.104852
Seongmin Kim , Seri Choi , Seung-Yeon Kim , Ji-Won Baek , Chungoo Park , Eun-Mi Kim
The limited ability of animal and cancer cell-based models to recapitulate human-specific responses underscores the need for human-relevant in vitro systems in toxicology. Here, we present a scalable platform for generating human lung organoids from induced pluripotent stem cells (iLOs), providing a physiologically relevant model for respiratory toxicity assessment. To evaluate this model, iLOs were exposed to polyhexamethylene guanidine phosphate (PHMG-p), a disinfectant associated with lung injury. PHMG-p treatment induced fibrotic responses, including upregulation of α-smooth muscle actin and fibronectin. Transcriptomic profiling revealed a coordinated cellular stress response marked by robust induction of metallothionein (MT) genes. Among them, MT1H was highly sensitive and strongly induced, highlighting its potential as an early biomarker of chemically induced lung injury. This human-specific organoid platform enables mechanistic toxicology, early biomarker discovery, and hazard assessment, offering a compelling alternative to animal-based models for evaluating respiratory toxicants.
{"title":"Transcriptomic profiling in human lung organoids uncovers metallothionein response as a signature of PHMG-p-induced lung toxicity","authors":"Seongmin Kim , Seri Choi , Seung-Yeon Kim , Ji-Won Baek , Chungoo Park , Eun-Mi Kim","doi":"10.1016/j.etap.2025.104852","DOIUrl":"10.1016/j.etap.2025.104852","url":null,"abstract":"<div><div>The limited ability of animal and cancer cell-based models to recapitulate human-specific responses underscores the need for human-relevant <em>in vitro</em> systems in toxicology. Here, we present a scalable platform for generating human lung organoids from induced pluripotent stem cells (iLOs), providing a physiologically relevant model for respiratory toxicity assessment. To evaluate this model, iLOs were exposed to polyhexamethylene guanidine phosphate (PHMG-p), a disinfectant associated with lung injury. PHMG-p treatment induced fibrotic responses, including upregulation of α-smooth muscle actin and fibronectin. Transcriptomic profiling revealed a coordinated cellular stress response marked by robust induction of metallothionein (MT) genes. Among them, <em>MT1H</em> was highly sensitive and strongly induced, highlighting its potential as an early biomarker of chemically induced lung injury. This human-specific organoid platform enables mechanistic toxicology, early biomarker discovery, and hazard assessment, offering a compelling alternative to animal-based models for evaluating respiratory toxicants.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104852"},"PeriodicalIF":4.2,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370605","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 : 2025-10-24DOI: 10.1016/j.etap.2025.104854
Laura Camacho-Jiménez, Lilia Leyva-Carrillo, Silvia Gómez-Jiménez, Gloria Yepiz-Plascencia
Polycyclic aromatic hydrocarbons (PAHs) are persistent organic pollutants ubiquitous in coastal areas where the shrimp Penaeus vannamei is farmed. PAHs metabolism increases the production of reactive oxygen species (ROS) and causes oxidative damage. Superoxide dismutases (SODs) are important ROS scavengers. However, SODs regulation in response to PAHs has been scarcely studied in crustaceans. In this work, we report a novel extracellular copper-zinc SOD (CuZnSOD) from P. vannamei with a predicted transmembrane region. To investigate the role of shrimp SODs in the response to PAHs, we analyzed the gene expression of CuZnSOD, cytosolic (cMnSOD) and mitochondrial manganese SOD (mMnSOD) in shrimp hepatopancreas, along with the measurement of total SOD activity and lipid peroxidation. We found that NAP induces a rapid increase in oxidative damage to lipids, while causing differential responses in the SOD gene expression and total SOD activity.
{"title":"The pollutant naphthalene causes changes in superoxide dismutases (SODs) expression, SOD activity and lipid peroxides in the white shrimp Penaeus vannamei","authors":"Laura Camacho-Jiménez, Lilia Leyva-Carrillo, Silvia Gómez-Jiménez, Gloria Yepiz-Plascencia","doi":"10.1016/j.etap.2025.104854","DOIUrl":"10.1016/j.etap.2025.104854","url":null,"abstract":"<div><div>Polycyclic aromatic hydrocarbons (PAHs) are persistent organic pollutants ubiquitous in coastal areas where the shrimp <em>Penaeus vannamei</em> is farmed. PAHs metabolism increases the production of reactive oxygen species (ROS) and causes oxidative damage. Superoxide dismutases (SODs) are important ROS scavengers. However, SODs regulation in response to PAHs has been scarcely studied in crustaceans. In this work, we report a novel extracellular copper-zinc SOD (CuZnSOD) from <em>P</em>. <em>vannamei</em> with a predicted transmembrane region. To investigate the role of shrimp SODs in the response to PAHs, we analyzed the gene expression of CuZnSOD, cytosolic (cMnSOD) and mitochondrial manganese SOD (mMnSOD) in shrimp hepatopancreas, along with the measurement of total SOD activity and lipid peroxidation. We found that NAP induces a rapid increase in oxidative damage to lipids, while causing differential responses in the SOD gene expression and total SOD activity.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104854"},"PeriodicalIF":4.2,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145359320","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}
This study examined the association between ambient air pollution and risk of rheumatoid arthritis (RA). Individuals born 1960–1999 from the nationwide Danish Occupational Cohort with eXposure data were linked to modeled exposure at the home address(es) and RA hospital diagnoses (N = 2,092,596). Recent and 10-years cumulative exposure to particles ≤ 2.5 (PM2.5) and ≤ 10 µm (PM10), nitrogen oxide (NO2) and elemental carbon (EC) were subdivided into quartiles, and risk of incident RA (1997–2018) were calculated using Poisson regression analyses. Recent and cumulative exposure to PM2.5, NO2 and EC increased risk of RA, for all quartiles compared to the lowest quartile, but without a clear exposure-response relationship. Analyses stratified on sex generally showed similar trends, yet small differences were seen for PM2.5 and EC (differences between IRR for men and women in model 2: PM2.5 0.03–0.19, and EC 0.05–0.14). Higher risks were indicated for exposure to PM2.5 and PM10 for age below as compared to above 40 years. In conclusion, exposure to PM2.5, NO2 and EC increased risk of RA, with little influence from sex and some influence of age.
{"title":"Air pollution and risk of rheumatoid arthritis – A Danish register-based cohort study","authors":"Regitze Sølling Wils , Helena Breth Nielsen , Esben Meulengracht Flachs , Astrid Juhl Andersen , Lene Wohlfahrt Dreyer , Matthias Ketzel , Jørgen Brandt , Jibran Khan , Ulla Vogel , Camilla Sandal Sejbaek , Karin Sørig Hougaard","doi":"10.1016/j.etap.2025.104855","DOIUrl":"10.1016/j.etap.2025.104855","url":null,"abstract":"<div><div>This study examined the association between ambient air pollution and risk of rheumatoid arthritis (RA). Individuals born 1960–1999 from the nationwide Danish Occupational Cohort with eXposure data were linked to modeled exposure at the home address(es) and RA hospital diagnoses (N = 2,092,596). Recent and 10-years cumulative exposure to particles ≤ 2.5 (PM<sub>2.5</sub>) and ≤ 10 µm (PM<sub>10</sub>), nitrogen oxide (NO<sub>2</sub>) and elemental carbon (EC) were subdivided into quartiles, and risk of incident RA (1997–2018) were calculated using Poisson regression analyses. Recent and cumulative exposure to PM<sub>2.5</sub>, NO<sub>2</sub> and EC increased risk of RA, for all quartiles compared to the lowest quartile, but without a clear exposure-response relationship. Analyses stratified on sex generally showed similar trends, yet small differences were seen for PM2.5 and EC (differences between IRR for men and women in model 2: PM2.5 0.03–0.19, and EC 0.05–0.14). Higher risks were indicated for exposure to PM<sub>2.5</sub> and PM<sub>10</sub> for age below as compared to above 40 years. In conclusion, exposure to PM<sub>2.5</sub>, NO<sub>2</sub> and EC increased risk of RA, with little influence from sex and some influence of age.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104855"},"PeriodicalIF":4.2,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145359319","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 : 2025-10-20DOI: 10.1016/j.etap.2025.104850
Manel M. Habel , Adrian C. Williams , Vitaliy V. Khutoryanskiy
The principle of the 3Rs—Reduction, Refinement, and Replacement—encourages minimizing animal use, improving experimental design, and developing alternative models for toxicology testing. Among such models, planaria (aquatic flatworms) have gained increasing attention in pharmacology, regenerative medicine, and toxicology because of their simple anatomy, high environmental sensitivity, exceptional regenerative ability, and ease of laboratory maintenance. In this study, we examined the effects of benzalkonium chloride (BAC)—a commonly used pharmaceutical excipient with antimicrobial and permeability-enhancing properties, as well as a known environmental toxicant—on the locomotor activity of Schmidtea mediterranea using both manual assessment and Lolitrack video-tracking software. Six concentrations of BAC (5–1000 μg/mL) and a negative control were tested. Both approaches showed an overall reduction in locomotor activity over time, though manual analysis indicated a transient stimulation at lower concentrations. The software-based method demonstrated greater reliability, precision, and objectivity, making it preferable for toxicity evaluation in planaria.
{"title":"Toxicological assessment of benzalkonium chloride using planaria mobility: A comparison of manual and digital tracking methods","authors":"Manel M. Habel , Adrian C. Williams , Vitaliy V. Khutoryanskiy","doi":"10.1016/j.etap.2025.104850","DOIUrl":"10.1016/j.etap.2025.104850","url":null,"abstract":"<div><div>The principle of the 3Rs—Reduction, Refinement, and Replacement—encourages minimizing animal use, improving experimental design, and developing alternative models for toxicology testing. Among such models, planaria (aquatic flatworms) have gained increasing attention in pharmacology, regenerative medicine, and toxicology because of their simple anatomy, high environmental sensitivity, exceptional regenerative ability, and ease of laboratory maintenance. In this study, we examined the effects of benzalkonium chloride (BAC)—a commonly used pharmaceutical excipient with antimicrobial and permeability-enhancing properties, as well as a known environmental toxicant—on the locomotor activity of <em>Schmidtea mediterranea</em> using both manual assessment and Lolitrack video-tracking software. Six concentrations of BAC (5–1000 μg/mL) and a negative control were tested. Both approaches showed an overall reduction in locomotor activity over time, though manual analysis indicated a transient stimulation at lower concentrations. The software-based method demonstrated greater reliability, precision, and objectivity, making it preferable for toxicity evaluation in planaria.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104850"},"PeriodicalIF":4.2,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338366","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}
Crayfish has been used in biomedical research due to their adaptability and resistance. While genetics, molecular biology, behavior assessments, electrophysiology, and microscopy techniques have been employed to study these crustaceans, in vivo metabolic evaluations using imaging techniques remain scarce. From this perspective, the use of micro positron emission tomography (MicroPET) imaging in crustacean models represents a novel approach to understand metabolic processes in these organisms and evaluating potential environmental impacts on aquatic species.
Objective
To assess the regional uptake of [18F]FDG in male and female crayfish using MicroPET imaging and to find the optimal scan acquisition time.
Methods
Adult male and female crayfish (n = 10/sex, 30–40 g) underwent 1-hour MicroPET scans (6 frames of 10 min) after administration of [18F]FDG (7.4 ± 1.2 MBq). Standardized uptake values (SUV) were calculated for the brain, gonads, green gland, heart, and ganglia of ventral nerve cord.
Results
The brain, green gland, and subesophageal ganglion exhibited the highest metabolic activity. Significant differences in [18F]FDG uptake related to sex were observed only in the gonads, with females showing higher uptake than males. No significant differences were found in other structures; nevertheless, male crayfish showed a higher coefficient of variation (44.33–92.7 %) than females (13.11–46.55 %). Exploratory inter-structure correlation analysis showed uniformly high coupling along the ventral nerve cord in both sexes, with males exhibiting stronger coordination between the heart/green gland and abdominal ganglia (Δρ up to ∼0.8), suggesting sex-dependent metabolic integration.
Conclusions
MicroPET imaging is a valuable tool for assessing metabolic activity and sexual dimorphism in crayfish in a single 10-minute scan (40 min after dose administration). These findings provide a groundwork for further studies investigating the physiological and biochemical basis of these differences.
{"title":"Whole-body glucose uptake in crayfish (Procambarus clarkii): A study of sexual dimorphism via [18F]FDG MicroPET imaging","authors":"Arturo Avendaño-Estrada , Miguel Angel Avila-Rodríguez , Jesús Hernández-Falcón , Karina Mendoza-Ángeles","doi":"10.1016/j.etap.2025.104849","DOIUrl":"10.1016/j.etap.2025.104849","url":null,"abstract":"<div><div>Crayfish has been used in biomedical research due to their adaptability and resistance. While genetics, molecular biology, behavior assessments, electrophysiology, and microscopy techniques have been employed to study these crustaceans, <em>in vivo</em> metabolic evaluations using imaging techniques remain scarce. From this perspective, the use of micro positron emission tomography (MicroPET) imaging in crustacean models represents a novel approach to understand metabolic processes in these organisms and evaluating potential environmental impacts on aquatic species.</div></div><div><h3>Objective</h3><div>To assess the regional uptake of [<sup>18</sup>F]FDG in male and female crayfish using MicroPET imaging and to find the optimal scan acquisition time.</div></div><div><h3>Methods</h3><div>Adult male and female crayfish (n = 10/sex, 30–40 g) underwent 1-hour MicroPET scans (6 frames of 10 min) after administration of [<sup>18</sup>F]FDG (7.4 ± 1.2 MBq). Standardized uptake values (SUV) were calculated for the brain, gonads, green gland, heart, and ganglia of ventral nerve cord.</div></div><div><h3>Results</h3><div>The brain, green gland, and subesophageal ganglion exhibited the highest metabolic activity. Significant differences in [<sup>18</sup>F]FDG uptake related to sex were observed only in the gonads, with females showing higher uptake than males. No significant differences were found in other structures; nevertheless, male crayfish showed a higher coefficient of variation (44.33–92.7 %) than females (13.11–46.55 %). Exploratory inter-structure correlation analysis showed uniformly high coupling along the ventral nerve cord in both sexes, with males exhibiting stronger coordination between the heart/green gland and abdominal ganglia (Δρ up to ∼0.8), suggesting sex-dependent metabolic integration.</div></div><div><h3>Conclusions</h3><div>MicroPET imaging is a valuable tool for assessing metabolic activity and sexual dimorphism in crayfish in a single 10-minute scan (40 min after dose administration). These findings provide a groundwork for further studies investigating the physiological and biochemical basis of these differences.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104849"},"PeriodicalIF":4.2,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338429","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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