Environmental toxicology and pharmacology最新文献

{"title":"Environmental fate of illicit drugs and new psychoactive substances in aquatic systems: Impact, critical insights, and future directions","authors":"Akshita Verma,&nbsp;Samuel Sunday Ogunsola,&nbsp;Kaylyn A. Keith,&nbsp;G.D. Thouli L. Jayawardana","doi":"10.1016/j.etap.2025.104880","DOIUrl":"10.1016/j.etap.2025.104880","url":null,"abstract":"<div><div>Illicit drugs and novel psychoactive substances (NPS) in aquatic environments pose growing ecological and public health concerns due to their persistence and toxicity. Released mainly via wastewater and runoff, their transport and fate are influenced by microbial degradation, hydrology, and bioaccumulation. These compounds have been detected in freshwater and marine ecosystems, causing endocrine disruption and toxicity in aquatic organisms, with potential human exposure through water and food. Advances in high-resolution mass spectrometry (HRMS) have improved their detection, while treatment technologies such as advanced oxidation, membrane filtration, and bioremediation are being developed to remove these residues. This review integrates findings from environmental chemistry, ecotoxicology, and public health to assess the sources, behavior, impacts, and mitigation of illicit drugs and NPS in aquatic systems. It highlights the complexity of these contaminants and identifies critical knowledge gaps that must be addressed to support effective monitoring, risk assessment, and regulatory strategies.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104880"},"PeriodicalIF":4.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145609272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silver nanoparticles induce ferroptosis via iron dyshomeostasis and system Xc⁻/GPX4 axis dysregulation in HT22 cells","authors":"Shuyan Niu,&nbsp;Menghao Guo,&nbsp;Haitao Yang,&nbsp;Xiaoru Chang,&nbsp;Mengting Shang,&nbsp;Chenyu Liu,&nbsp;Mengjing Cui,&nbsp;Tianshu Wu,&nbsp;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 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 <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":"2025-12-01","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}

{"title":"Transcriptomic profiling in human lung organoids uncovers metallothionein response as a signature of PHMG-p-induced lung toxicity","authors":"Seongmin Kim ,&nbsp;Seri Choi ,&nbsp;Seung-Yeon Kim ,&nbsp;Ji-Won Baek ,&nbsp;Chungoo Park ,&nbsp;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":"2025-12-01","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}

{"title":"Impact of morphologically tuned silica nanoparticles on the invasive freshwater bivalve Limnoperna fortunei","authors":"Gabriel O. Ostapchuk ,&nbsp;Analía Ale ,&nbsp;Victoria S. Andrade ,&nbsp;Gisela L. Poletta ,&nbsp;Luciana Montalto ,&nbsp;Florencia M. Rojas Molina ,&nbsp;Martín F. Desimone ,&nbsp;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":"2025-12-01","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}

{"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,&nbsp;Lilia Leyva-Carrillo,&nbsp;Silvia Gómez-Jiménez,&nbsp;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":"2025-12-01","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}

{"title":"Long-term impact of oral gestational PM10 exposure on morris water maze performance and hippocampal gene expression","authors":"Ruiz-Sobremazas Diego ,&nbsp;Coca Mario ,&nbsp;Morales-Navas Miguel ,&nbsp;Nerea Rios Nieto ,&nbsp;Rodulfo-Cárdenas Rocío ,&nbsp;Colomina Maria Teresa ,&nbsp;López-Granero Caridad ,&nbsp;Sanchez-Santed Fernando ,&nbsp;Perez-Fernandez Cristian","doi":"10.1016/j.etap.2025.104874","DOIUrl":"10.1016/j.etap.2025.104874","url":null,"abstract":"<div><div>Environmental exposure to air pollution, specially to particulate matter (PM) during pregnancy, plays a significant role in increasing the risk of neurodevelopmental disorders such as autism. This study investigated the long-term impact of oral gestational PM exposure (200 µg/kg/day) on memory in aged rats using the Morris Water Maze (MWM). After completing MWM, hippocampal tissue was collected and analyzed for gene expression. Our findings indicate that gestational PM exposure caused no major developmental alterations, aside from slightly poorer performance in the adherence test. No differences were detected in standard MWM manipulations, however, PM-offspring showed reduced latency in the test session, suggesting a possible compulsive-like behavior. Additionally, hippocampal gene expression revealed downregulation of several genes, including NMDA and GABAergic subunits. These effects depended on exposure and sex. The behavioral effects might reflect cognitive inflexibility linked to gene alterations. Further research is needed to clarify these outcomes.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104874"},"PeriodicalIF":4.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145575054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adipose tissue cadmium concentrations as potential determinants of serum PON1 status in an adult cohort from Southern Spain","authors":"Maria Cruz Gomez Pellin ,&nbsp;Eduardo Linares-Ruiz ,&nbsp;Javier Esteban ,&nbsp;Inmaculada Salcedo-Bellido ,&nbsp;Gonca Çakmak ,&nbsp;María Eugenia Velasco García ,&nbsp;Jose Barril ,&nbsp;Suylen Galbán-Velázquez ,&nbsp;Celia Pérez-Díaz ,&nbsp;Francisco M. Pérez-Carrascosa ,&nbsp;Petra Vrhovnik ,&nbsp;Željka Fiket ,&nbsp;María de la Cruz Pellín ,&nbsp;Juan P. Arrebola","doi":"10.1016/j.etap.2025.104827","DOIUrl":"10.1016/j.etap.2025.104827","url":null,"abstract":"<div><div>Paraoxonase 1 (PON1) is an antiatherogenic enzyme inhibited by environmental stressors such as cadmium (Cd). Thus, this human study aimed to assess (1) the associations between adipose tissue Cd concentrations and serum PON1 status and (2) the influence of the PON1_Q192R phenotype on the susceptibility of PON1 status to Cd. As a continuation from previous work, a subsample from the GraMo cohort (Granada, Spain) was studied. Three PON1 activities using non-organophosphorous substrates {PALS (phenyl acetate in the absence of NaCl), PAHS (phenyl acetate in 2 M NaCl) and CMPA [4-(chloromethyl)phenyl acetate]} were assayed in serum (n = 296) to obtain the three functional PON1_Q192R phenotypes (QQ, QR and RR). Complementarily, Cd concentrations in adipose tissue (n = 226) and information on socio-demographic characteristics, lifestyle, diet and health status acquired by face-to-face interviews were available. The associations between PON1 activities in serum and Cd concentrations in adipose tissue (subset of n = 138) were explored by using linear regression models, which were adjusted for sex, alcohol consumption and PON1_Q192R phenotype. Additionally, benchmark dose (BMD) modelling was performed. Higher adipose tissue Cd concentrations were associated with lower PON1 activities. PON1_Q192R specific susceptibility to Cd increased in the order QQ &lt; QR &lt; RR. The Cd BMD ranges for an averaged subject were 0.002–0.016 and 0.046–0.115 mg_Cd/kg_{adipose-tissue} for RR and QR, respectively. For QQ cases, the BMD were higher than the Cd concentrations found in adipose tissue. These results suggest that part of the increased susceptibility of the RR cases to cardiovascular diseases might putatively be mediated by its higher sensitivity to Cd, with adipose tissue Cd levels serving as a biomarker of chronic exposure.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104827"},"PeriodicalIF":4.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The agony of choice: Advancing sediment hazard assessment by using avoidance behaviour assays with Lumbriculus variegatus","authors":"Jacqueline Hilgendorf ,&nbsp;Vânia Calisto ,&nbsp;Diogo N. Cardoso ,&nbsp;Joana Fernandes ,&nbsp;Diana L.D. Lima ,&nbsp;José N. Pinto ,&nbsp;Ana Eduardo Rodrigues ,&nbsp;Jesper G. Sørensen ,&nbsp;Érika M.L. Sousa ,&nbsp;Susana Loureiro","doi":"10.1016/j.etap.2025.104871","DOIUrl":"10.1016/j.etap.2025.104871","url":null,"abstract":"<div><div>Sediments play a key role in chemical partitioning in aquatic ecosystems, acting as sinks for lipophilic and persistent compounds. However, sediment hazard assessment is limited, often underestimating risks by focusing on short-term, lethal endpoints. Behavioural assays, although underused for sediment-dwellers, can provide faster, more sensitive assessments. This study adapted soil avoidance methods for sediment, testing avoidance in <em>Lumbriculus variegatus</em> exposed to lead, bixafen, and fluoxetine. We compared survival with conventional one-compartment (contaminated sediment only) and two-compartment (contaminated vs. control) assays. The two-compartment test detected significant avoidance at concentrations up to 428 times lower than survival and showed effects when conventional assays failed to detect any (e.g., for bixafen). It revealed significant responses at environmentally relevant levels (0.19 mg/kg fluoxetine, 550 mg/kg lead) and provided insights into chemical sensing and non-monotonic dose–response curves. Two-compartment avoidance assays are rapid, sensitive, and relevant for future sediment hazard assessments with potential population-level implications.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104871"},"PeriodicalIF":4.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145575020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effects of N-acetylcysteine and its amide derivative against toxic metals in vitro: Potential alternatives/adjuncts to traditional chelators","authors":"Thomas W. Sawyer,&nbsp;Yanfeng Song","doi":"10.1016/j.etap.2025.104825","DOIUrl":"10.1016/j.etap.2025.104825","url":null,"abstract":"<div><div>The protective efficacies of N-acetylcysteine (NAC) and N-acetylcysteine amide (NACA) against the toxicity of compounds containing arsenic, cadmium, cobalt, chromium and mercury, were compared to those of dimercaprol, dimercaptosuccinic acid, 2,3-dimercaptopropanesulphonate, D-penicillamine, and derivatives of ethylenediamine tetraacetic acid and diethylenetriaminepentaacetic in CHO-K1 cells. Both NAC and NACA were found to confer protection against these metals, with comparable or better efficacy than many of the test chelators. Results from studies using the glutathione synthesis inhibitor buthionine sulphoximine were consistent with NAC/NACA protection being mediated through both GSH up-regulation and chelation. Given NAC’s activity against metal toxicity, widespread clinical use, parenteral or oral routes of administration, high clinical safety, low cost and ease of accessibility, it should be given consideration as a broad-spectrum protectant against toxic metal poisoning as a treatment or adjunct/combination treatment. Its more lipophilic derivative NACA, also warrants attention, especially in those cases where brain toxicity is a concern.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104825"},"PeriodicalIF":4.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145180804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of lipid metabolism and peroxisome proliferator activation in mediating pro-cancer phenotypes of poly- and perfluoroalkyl substances in testicular cancer","authors":"Raya I. Boyd ,&nbsp;Doha Shokry,&nbsp;Brayden C. Rennels,&nbsp;Younan Adam,&nbsp;Christine Powell,&nbsp;Samantha Johnson,&nbsp;Michael J. Spinella,&nbsp;Ratnakar Singh","doi":"10.1016/j.etap.2025.104866","DOIUrl":"10.1016/j.etap.2025.104866","url":null,"abstract":"<div><div>Poly- and perfluoroalkyl substances (PFAS) are of human health concern as epidemiological studies show significant associations with testicular germ cell tumors (TGCTs). Here, the effects of perfluorooctanesulfonic acid (PFOS), lithium bis(trifluoromethylsulfonyl)imide (HQ-115), and hexafluoropropylene oxide dimer acid (GenX) on TGCT cells were investigated. Concentrations (10 nM to 1 µM) modelled PFAS doses in relevant human exposure ranges and acute and short-term timepoints (18 h and 4 days) captured proximal mechanisms of action. Metabolomic studies revealed that HQ-115 altered metabolites associated with steroid biosynthesis and lipid metabolism. Peroxisome-proliferator activation receptor (PPAR) target gene expression was altered upon HQ-115 and GenX exposure. Lastly, PFAS exposure altered the activity of PPARs, in TGCT cells, with the most prominent effects being antagonist activity toward PPARγ. These data support that PFAS may act as fatty acid mimics to modulate fatty acid metabolic and steroidogenic endocrine outcome leading to pro-cancer phenotypes in TGCTs.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"120 ","pages":"Article 104866"},"PeriodicalIF":4.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145517419","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}