Environmental toxicology and pharmacology最新文献

{"title":"Persistent environmental toxicants PCP, TCHQ, and HCB drive PANoptosis and RNA granule remodeling in human lung epithelial cells","authors":"R. Kondati ,&nbsp;M. Thakur ,&nbsp;D. Mutyala ,&nbsp;W. Dorsey ,&nbsp;S. Batra","doi":"10.1016/j.etap.2025.104862","DOIUrl":"10.1016/j.etap.2025.104862","url":null,"abstract":"<div><div>Pentachlorophenol (PCP), its metabolite tetrachlorohydroquinone (TCHQ), and the co-occurring pollutant hexachlorobenzene (HCB) remain a toxicological concern due to their environmental persistence and bioaccumulation. Both PCP and TCHQ exhibit well-documented toxicities and have likely contributed to substantial occupational and environmental exposures worldwide, owing to their efficient absorption through multiple routes. While HCB, although not a PCP metabolite, similarly poses long-term toxicological risks. These toxicants exhibit distinct toxicological profiles, underscoring their relevance as environmental health hazards. Our previous studies have demonstrated that PCP exposure activates the Hsp70-ROS-autophagy axis in submerged lung alveolar epithelial (A549) monolayers, highlighting its role in initiating early cellular stress responses. Building on our prior investigations, this study evaluates the cellular mechanisms activated by PCP, its metabolite TCHQ, and the co-occurring pollutant HCB at a higher occupationally relevant concentration using submerged monolayer (2D) and 3D air-liquid interface (ALI) models. The computational insights from the STITCH-based network prompted us to validate these links in A549 cells exposed to PCP, TCHQ, and HCB. All tested compounds induced the expression of PANoptosis and RNA granule markers, alongside inflammatory cytokine/chemokine production, implicating integrated cell death pathways and post-transcriptional regulatory mechanisms jointly mediate cellular responses under these conditions. Remarkably, wound healing (in vitro scratch) assays indicated preserved epithelial cell migration capacity despite robust inflammatory and PANoptotic signaling, highlighting a dynamic balance between cellular stress and regenerative resilience. Overall, this study elucidates the role of PANoptosis and RNA granule dynamics as central mediators of toxicant-induced inflammation, providing a mechanistic framework for evaluating the cellular effects of chlorinated environmental pollutants such as PCP and related compounds.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"121 ","pages":"Article 104862"},"PeriodicalIF":4.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145441642","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":"Smoke-derived microplastics of polypropylene In Vitro proliferative impact on human lung adenocarcinoma cells: Physicochemical analysis and biological evaluation","authors":"Nivedita Jha ,&nbsp;Angshita Das ,&nbsp;Megha Prasanth ,&nbsp;S. Daisy Precilla ,&nbsp;R. Sivachandran ,&nbsp;Rajaneesh Anupam ,&nbsp;T.S. Anitha","doi":"10.1016/j.etap.2025.104914","DOIUrl":"10.1016/j.etap.2025.104914","url":null,"abstract":"<div><h3>Background</h3><div>The increasing production of disposable plastic has led to massive plastic waste, much of which is burned, resulting in microplastics (MPs) and other toxic byproducts. This study investigates the smoke-derived MPs from burning polypropylene (PP), their physicochemical properties, and their impact on lung cancer cells.</div></div><div><h3>Methods</h3><div>Smoke-derived MPs were generated by smoldering PP, and extracted MPs dissolved in methanol, ethanol, and DCM. For physicochemical assessment, DLS, UV–VIS, FTIR NMR, GC-MS, and SEM were performed, followed by in vitro analysis, MTT, AO/EB, and DAPI assays performed using A549 cells.</div></div><div><h3>Result &amp; Discussion</h3><div>Characterization studies revealed particle size, hazardous compounds such as phthalates, siloxanes, and polyaromatic hydrocarbons. <em>In vitro</em> studies showed increased cell viability in A549 cells with no sign of apoptosis or necrosis.</div></div><div><h3>Conclusion</h3><div>Proliferation in lung cancer cells through Smoke-derived MPs, implicating combustion MPs in respiratory disease, highlighting urgent control needs.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"121 ","pages":"Article 104914"},"PeriodicalIF":4.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145785203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"On-site ALI versus submerged culture: Chemical and toxicological investigation of brake wear sub-micrometric particles","authors":"Bozhena Tsyupa ,&nbsp;Chiara Emma Campiglio ,&nbsp;Elena Carrara ,&nbsp;Marta Ripamonti ,&nbsp;Alessandro Mancini ,&nbsp;Andrea Bonfanti ,&nbsp;Micol Introna ,&nbsp;Ana Teresa Juarez-Facio ,&nbsp;Karine Elihn ,&nbsp;Manuela Teresa Raimondi ,&nbsp;Andrea Remuzzi","doi":"10.1016/j.etap.2025.104915","DOIUrl":"10.1016/j.etap.2025.104915","url":null,"abstract":"<div><div>Poor air quality is a significant risk to human health and the environment, with a direct correlation to respiratory diseases and premature death. Ultra fine particles (UFPs) in the atmosphere are particularly hazardous. This study evaluates the toxicological response of epithelial cells (A549) and macrophages (dTHP-1) to particulate matter (PM) emissions from car brake wear, under both submerged and Air-Liquid Interface (ALI) conditions. Toxicity was assessed using cell viability (Resazurin assay) and cytokine assays. Emissions were collected using a dynamometric bench simulating driving and braking conditions. Under ALI, freshly emitted particles were directly deposited onto cells, while in submerged conditions, particles were collected on filters and then deposited onto cells. M1a and M1b materials were tested, both materials are falling into category of ECE R90 Low Metallic pads. M1a showed slight toxicity under ALI and significant immune response in submerged conditions, while M1b showed no toxicity in either condition.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"121 ","pages":"Article 104915"},"PeriodicalIF":4.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145785206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crotonaldehde oral exposure disrupt cardiac energy metabolism and induces oxidative stress via down-regulation of nrf-2 and up-regulation of PPARα","authors":"Olufemi I. Oluranti ,&nbsp;Bernard O. Adele ,&nbsp;Abayomi O. Ige ,&nbsp;Elsie O. Adewoye","doi":"10.1016/j.etap.2025.104892","DOIUrl":"10.1016/j.etap.2025.104892","url":null,"abstract":"<div><div>Alterations in cardiac energy metabolic pathways have been linked to cardiac dysfunction. This study investigated cardiac energy metabolism in male rats exposed to crotonaldehyde. Thirty-six male Wistar rats (150–170 g; n = 9) were grouped into 4 (I-IV): Control (normal saline 10 mL/kg), crotonaldehyde (0.75, 1.5, and 2.5 mg/kg, p.o) for 28 days. Levels of creatinine-kinase-myocardial-band, cardiac-troponin-I, glucose increased significantly, while triglyceride, free-fatty-acid, and insulin reduced significantly in all groups compared with control. Cardiac Pyruvate level, hexokinase and pyruvate dehydrogenase activities increased significantly in all crotonaldehyde-treated groups compared with control. Cardiac levels of malondialdehyde and hydrogen-peroxide increased significantly, while glutathione and nuclear-factor-erythroid-2-related-factor-2 reduced; superoxide-dismutase and catalase activities decreased following crotonaldehyde exposure compared with control. Cardiac glucose-transporter-4 and peroxisome-proliferator-activated-receptor-alpha expression increased in groups III and IV, while carnitine-palmitoyltransferase1β expression decreased in group II but increased in groups III and IV compared with control. Crotonaldehyde exposure exerts cardio-toxic effects by altering cardiac energy metabolism.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"121 ","pages":"Article 104892"},"PeriodicalIF":4.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145689828","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":"Effects of consumer-grade and commercial acetamiprid formulations on the embryonic development of the South African clawed frog Xenopus laevis","authors":"Hannah Flach,&nbsp;Marlen Kerner,&nbsp;Mert Tosun,&nbsp;Paolina Maier,&nbsp;Petra Dietmann,&nbsp;Karin Botzenhart,&nbsp;Susanne J. Kühl","doi":"10.1016/j.etap.2025.104905","DOIUrl":"10.1016/j.etap.2025.104905","url":null,"abstract":"<div><div>The insecticide acetamiprid is a neonicotinoid still approved for outdoor use worldwide. For active use, there are formulations that contain other often unpublished co-formulants in addition to acetamiprid. This study investigated effects of four different acetamiprid formulations (Careo Rosenspray, Careo, Mospilan, Danjiri) in a concentration range of 0.01–100 mg a.i./L on embryonic development of <em>Xenopus laevis</em>. The formulations led to an increase in embryo mortality with LC₅₀-values between 0.5 and 53.2 mg a.i./L depending on the formulation. At sublethal acetamiprid concentrations in Mospilan and Danjiri, the external appearance (body length, oedemas), the early neural development (eyes, heads, brains, cranial nerves) as well as the heart morphology and function were disturbed. Our results show that strict adherence to recommended handling and application conditions of acetamiprid formulations is essential to protect <em>X. laevis</em>. Therefore, pesticide risk assessment and approval renewal procedures must include commercially available combined formulations rather than solely evaluating the active ingredient.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"121 ","pages":"Article 104905"},"PeriodicalIF":4.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145731243","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":"Ecotoxicological impacts of imazethapyr herbicide on amphibian larvae: Evidence from Physalaemus cuvieri","authors":"Alexandre Folador ,&nbsp;Inete Cleide Bau ,&nbsp;Guilherme Felicioni ,&nbsp;Bruna Caprini ,&nbsp;Aline Pompermaier ,&nbsp;Wagner Antonio Tamagno ,&nbsp;Carla Alves ,&nbsp;Paulo Afonso Hartmann ,&nbsp;Marilia Hartmann","doi":"10.1016/j.etap.2025.104878","DOIUrl":"10.1016/j.etap.2025.104878","url":null,"abstract":"<div><div>Aquatic environments are amongst the ecosystems most impacted by pesticides, with amphibians being a particularly vulnerable group. This study investigated the cytotoxic, body condition and biochemical effects of a commercial formulation of imazethapyr-based herbicide (IBH), on <em>Physalaemus cuvieri</em> tadpoles at developmental stage 25 exposed to a broad concentration gradient (0–500 µg/L) for 14 days. Notably, even the lowest concentration (1 µg/L) significantly reduced body weight, body mass index, and scaled mass index, while inducing multiple erythrocyte nuclear abnormalities (ENAs). All tested concentrations caused these effects in ENAs (e.g., micronuclei, lobed nuclei) and impaired energy allocation patterns. IBH was also neurotoxic and induced oxidative stress at higher concentrations (400–500 µg/L). The cellular damage observed suggests the difficulty for tadpoles in maintaining energy reserves for growth and metamorphosis, as evidenced by significant body weight loss. Together, these results indicate that IBH is cytotoxic at environmentally relevant concentrations and may consequently compromise the health of <em>P. cuvieri</em> populations.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"121 ","pages":"Article 104878"},"PeriodicalIF":4.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145609270","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":"Histopathological and toxicogenomic evaluation of 1,4-dioxane toxicity after a 14-day repeated oral administration","authors":"Hiroshi Honda ,&nbsp;Kentaro Yamamoto ,&nbsp;Mutsumi Shiraishi","doi":"10.1016/j.etap.2025.104875","DOIUrl":"10.1016/j.etap.2025.104875","url":null,"abstract":"<div><div>1,4-dioxane (DON) has been widely used as a pharmaceutical ingredient, a solvent in organic synthesis reactions, and a stabilizer in chlorinated organic solvents. Although DON shows hepatocarcinogenicity in mice and rats, the mode of action has not fully been elucidated. Therefore, to understand the toxicological potential of DON in high doses after repeated oral administration and the adverse effects on the liver in terms of molecular mechanisms, we analyzed a results of repeated dose 14-day oral toxicity test integrating a gene expression analysis using DNA microarray. Rats were orally administered a dose of DON (0, 150, 500 and 1500 mg/kg/day) and examinations on hematology, blood biochemistry, organ weights and histopathology were conducted. Surplus liver was harvested to gene expression analysis to identify genes and molecular pathways related to the adverse effect of DON. As a result, centrilobular hypertrophy of hepatocytes (liver), tubular vacuolation/basophilic change (kidney), and vacuolation (pituitary posterior lobe) were observed as pathological findings. Gene expression analysis revealed genes related to oxidative stress, xenobiotic receptor response, immune response, and hepatocellular carcinoma were significantly enriched. Under middle dose group, DNA damage response related genes were not significantly enriched and histopathological change in liver was not observed suggesting a threshold. Continuous alteration of these gene expression profiles related to hepato-carcinogenesis may have an important role in the non-genotoxic mode of action of DON. Our results would be useful in further understanding the general toxicity of DON and in considering early changes in the liver which lead to carcinogenesis.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"121 ","pages":"Article 104875"},"PeriodicalIF":4.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145598653","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":"Mutual oral administration of wood/plastic smoke PM and heavy metals Pb2+/Cd2+: General toxicity effects and ACE2 expression in rats","authors":"Nataliya Dziubenko ,&nbsp;Iryna Byelinska ,&nbsp;Taisa Dovbynchuk ,&nbsp;Arsen Ishchuk ,&nbsp;Viktoriia Velmyk ,&nbsp;Mariia Korbush ,&nbsp;Konstantin Paliienko ,&nbsp;Liliia Kalynovska ,&nbsp;Nataliya Krisanova ,&nbsp;Nataliya Pozdnyakova ,&nbsp;Tatiana Borisova ,&nbsp;Ganna Tolstanova","doi":"10.1016/j.etap.2025.104881","DOIUrl":"10.1016/j.etap.2025.104881","url":null,"abstract":"<div><div>Carbonaceous air pollution particulate matter (PM) and xenobiotic heavy metals, Pb²⁺ and Cd²⁺, are hazardous toxicants. PM-associated Pb²⁺ and Cd²⁺ are substantial metal components of PM_2.5. Here, we analysed general toxicity and ACE2 concentration/expression in rats after combined oral administration of water-suspended smoke PM preparations from wood (WS) or polypropylene (PS) and Pb²⁺/Cd²⁺. After combined exposure to Pb²⁺/Cd² and WS/PS, turnover of erythrocytes increased (an increase in volume of MCV erythrocytes). The combined effect of Cd²⁺ and PS had a lymphosuppressive effect. Pb²⁺/Cd²⁺ with WS/PS increased the level of myeloperoxidase activity in the mucous membrane of rat colon in all groups. ACE2 concentrations in the blood plasma were not changed in all groups. WS and PS reduced the intensity of positive staining of ACE2 receptors in the mucous membrane of the colon of rats. Therefore, multipollutant heavy metal- and PM-induced effects on general toxicity parameters and ACE2 concentration/expression were revealed.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"121 ","pages":"Article 104881"},"PeriodicalIF":4.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145609271","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":"Evaluation of THC-induced neurotoxicity via oxidative stress in undifferentiated SH-SY5Y cells","authors":"A. Sanz-Pérez ,&nbsp;B.J. Anaya ,&nbsp;A.I. Fraguas-Sánchez ,&nbsp;D.R. Serrano ,&nbsp;T. Pérez ,&nbsp;P. Basilicata ,&nbsp;M. Pieri ,&nbsp;E. González-Burgos","doi":"10.1016/j.etap.2025.104891","DOIUrl":"10.1016/j.etap.2025.104891","url":null,"abstract":"<div><div>The increasing global consumption of cannabis, particularly high-THC products, has raised public health concerns due to potential neurotoxic effects, although its association with oxidative stress remains a subject of debated. Some studies link THC-rich cannabis to increased oxidative damage, while others highlight antioxidant properties of cannabinoids. This study aimed to evaluate whether THC concentrations observed in real-world scenarios, specifically in the blood of drivers involved in traffic accidents, can induce neuronal damage through oxidative stress in vitro. Human undifferentiated SH-SY5Y neuroblastoma cells were exposed to 0.66, 20, 73.75, and 150 ng/mL THC. High concentrations (73.75 and 150 ng/mL) significantly reduced cell viability (to 76.5 % and 64.6 % at 48 h) and caused morphological changes. THC exposure increased ROS, peaking at 116.5 % at 150 ng/mL, disrupted glutathione balance (GSH/GSSG ratio decreased by 69.2 %), and moderately increased lipid peroxidation (34.5 %). Activities of antioxidant enzymes (CAT, SOD, GR, GPx) declined concentration-dependently. Additionally, nuclear condensation and mitochondrial membrane depolarization indicated early apoptosis. These findings suggest that high THC levels can trigger neurotoxicity via oxidative stress and mitochondrial dysfunction.</div></div>","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"121 ","pages":"Article 104891"},"PeriodicalIF":4.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145683445","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":"Corrigendum to “In vitro enantioselective inhibition of key human CYP450 enzymes by the chiral fungicide penconazole” [Environ. Toxicol. Pharmacol. 118 (2025) 104790]","authors":"Maike Felipe Santos Barbetta ,&nbsp;Giovanni Stoppa Baviera ,&nbsp;Icaro Salgado Perovani ,&nbsp;Leandro Oka Duarte ,&nbsp;Anderson Rodrigo Moraes de Oliveira","doi":"10.1016/j.etap.2025.104890","DOIUrl":"10.1016/j.etap.2025.104890","url":null,"abstract":"","PeriodicalId":11775,"journal":{"name":"Environmental toxicology and pharmacology","volume":"121 ","pages":"Article 104890"},"PeriodicalIF":4.2,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145688786","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}