Journal of Applied Toxicology最新文献

{"title":"Effects of Lithium and Verapamil on Thyroid and Kidney Function in Mice: A Preclinical Study.","authors":"Mohammad Salem Hareedy, Mahmoud Hamdy Abdelrahem, Samar Sayed Hassan, Heba Hassan Elkaliny","doi":"10.1002/jat.70172","DOIUrl":"10.1002/jat.70172","url":null,"abstract":"<p><p>Lithium (Li) salts are still one of the basic therapies for manic-depressive illness, which has a double-edged nature where the good efficacy is threatened by possible toxicity if Li levels are elevated. The effects of verapamil and N-acetylcysteine (NAC) on Li levels and Li-related toxicity in the thyroid gland and kidneys were studied. Five groups of mice (normal control, Li, verapamil, Li + verapamil, and Li + NAC) were evaluated for levels of urea, creatinine, thyroid hormones (T3 and T4), thyroid-stimulating hormone (TSH), sodium, and potassium after 6 weeks. Li levels were measured in all groups that received Li. Renal and thyroid tissues were assessed histologically. T4 and T3 were significantly elevated in the Li, Li + verapamil, and Li + NAC groups compared to the normal control (p < 0.0001), while TSH was significantly decreased (p < 0.001). Levels of Li, potassium, and urea were elevated by the co-administration of verapamil or NAC, while serum creatinine was significantly decreased compared to the Li-treated group. Verapamil and NAC elevated the serum levels of Li and augmented the effects of Li on the thyroid gland, urea, and potassium levels.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":"4044-4056"},"PeriodicalIF":3.1,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147491069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concentration-Dependent Cytotoxicity and DNA Damage Responses of Iohexol in MCF-7 Breast Cancer Cells: An In Vitro and In Silico Study.","authors":"Ferhat Aslan, İbrahim Halil Kenger","doi":"10.1002/jat.70340","DOIUrl":"10.1002/jat.70340","url":null,"abstract":"<p><p>Iohexol is a nonionic, low-osmolarity iodinated contrast agent that is widely used in clinical imaging applications. This study evaluated the cytotoxic effects and DNA damage responses of iohexol on the human breast adenocarcinoma cell line (MCF-7) in vitro using MTS and alkaline comet assays. Additionally, molecular docking analyses were performed to complement this approach and investigate the potential interactions of iohexol with DNA, the anti-apoptotic protein BCL-XL, and the metabolic enzyme NUDT5. Iohexol administration caused a concentration-dependent decrease in cell viability, with significant cytotoxicity observed at concentrations of ≥ 18.26 mM (p < 0.0001). Comet assay results showed increased DNA damage responses at concentrations above clinical doses, with significant increases detected from 22.8 mM onwards (p < 0.05) and the highest damage levels observed at 91.3-182.6 mM (p < 0.01). Molecular docking analyses revealed that iohexol exhibited weak binding affinity with DNA (-3.57 kcal/mol), showing relatively more pronounced, albeit still moderate, interactions with BCL-XL (-5.25 kcal/mol) and NUDT5 (-5.40 kcal/mol). These findings suggest that iohexol may indirectly interact via pathways associated with cellular stress. In general, the obtained data indicate that iohexol can cause cytotoxicity and DNA damage responses in MCF-7 cells under supra-clinical in vitro exposure conditions. These findings suggest that these effects develop through indirect cellular mechanisms rather than direct DNA binding. This emphasizes the need for careful interpretation of high-dose in vitro data, as well as the need for further mechanistic studies, in order to better understand the cellular effect profile of iohexol. Therefore, the present findings should not be interpreted as direct evidence of genotoxic risk under clinically relevant exposure conditions.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":"4223-4230"},"PeriodicalIF":3.1,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148446991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tannic Acid Mitigates Monosodium Glutamate-Induced Cortical Damage by Modulating Synaptic and Calcium-Related Gene and Protein Expression.","authors":"Medine Sibel Karagac, Enver Fehim Koçpinar, Hamid Ceylan","doi":"10.1002/jat.70185","DOIUrl":"10.1002/jat.70185","url":null,"abstract":"<p><p>Neurotoxicity induced by excessive glutamatergic signaling is associated with synaptic dysfunction, calcium imbalance, and oxidative stress, which are key molecular events implicated in several neurodegenerative conditions. Monosodium glutamate (MSG), a common flavor enhancer, may exert neurotoxic effects, particularly on synaptic integrity, though mechanisms remain unclear. Tannic acid (TA), a natural polyphenol, has been proposed as a neuroprotective compound. This study investigated the impact of MSG on synaptic components beyond classical AD markers and assessed the protective potential of TA. Rats were randomly divided into four groups (n = 6 per group) and treated with MSG (2 g/kg) and/or TA (50 mg/kg) by oral gavage for 21 consecutive days. Gene and protein expression levels of the synaptic markers (GRIN2A, GRIN2B, DLG2, SNAP25, SCN2A, and ATP2B2) in the cerebral cortex were analyzed using qPCR and western blot. MSG treatment significantly downregulated SNAP25, GRIN2B, DLG2, and SCN2A at both mRNA and protein levels, indicating synaptic dysfunction. GRIN2A and ATP2B2 showed reduced mRNA expression, but protein levels were inconsistent. MSG+TA group showed no significant difference compared with the control group, while TA alone produced minimal changes, suggesting that its role is primarily protective under toxic stress. These findings suggest that chronic MSG exposure disrupts synaptic molecular architecture, whereas the restorative effect of TA may be attributed to its ability to modulate MSG-induced molecular alterations. The data emphasize synaptic pathways as alternative neurotoxicity targets and highlight TA's potential in mitigating diet-related excitotoxic synaptic alterations. Further functional and pathway-based studies are needed to confirm the underlying mechanisms.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":"4099-4111"},"PeriodicalIF":3.1,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147529339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lethal and Sublethal Effects of Three Novel Insecticides on Biological Parameters of Pink Bollworm, Pectinophora gossypiella (Lepidoptera: Gelechiidae).","authors":"Tadagavadi Nagaraju Madhu, Kamanur Muralimohan, Vakudavth Chinnababu Naik, Manikyanahalli Chandrashekara Keerthi, Tenguri Prabhulinga, Kadanakuppe Thammaiah Shivakumara","doi":"10.1002/jat.70173","DOIUrl":"10.1002/jat.70173","url":null,"abstract":"<p><p>Pink bollworm (Pectinophora gossypiella) is a serious pest of cotton that causes huge economic losses in major cotton-growing regions. The development of resistance to transgenic Cry1Ac and Cry2Ab in India has led to long-term reliance on insecticides, thus enables the larvae to experience sublethal effects due to its concealed feeding behavior. This study investigated the impact of sublethal concentrations (LC₁₀ and LC₃₀) of emamectin benzoate, spinetoram, and spinosad on P. gossypiella. The results showed that emamectin benzoate was more toxic to P. gossypiella (LC₅₀-2.12 mgL^-1) than spinetoram (LC₅₀-3.52 mgL^-1) and spinosad (LC₅₀-7.44 mgL^-1). The developmental time and adult preoviposition period (APOP) were extended, while fecundity, egg hatchability, and ovipositional days were reduced at sublethal concentrations in treated populations than the control group. Among treated insecticides, mean fecundity of P. gossypiella was significantly reduced in emamectin benzoate LC₁₀ (91.03 ± 3.87/female) and LC₃₀ (62.89 ± 3.22/female) treated population than spinetoram and spinosad. Further, the biological parameters including the intrinsic rate of increase (r), finite rate of increase (λ), and net reproductive rate (R₀) were also significantly decreased in the treated population as compared with untreated insects. Our results indicated that emamectin benzoate was effective against P. gossypiella and highlighted the importance of sublethal effects of insecticides on target insects to ensure the comprehensive evaluation and rational use of insecticides under field conditions.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":"4000-4010"},"PeriodicalIF":3.1,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147480695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety Assessment and Hypoglycemic Effect of Moringa oleifera Lam. Seed Lectin (WSMoL) in Alloxan-Induced Diabetic Mice.","authors":"Alícia Natalie Silva Dos Santos, Matheus Cavalcanti de Barros, Cleidiane Silva Vieira de Souza, Ryan Cristian da Silva, Luana Cassandra Breitenbach Barroso Coelho, Maria Tereza Dos Santos Correia, Fernanda das Chagas Ângelo Mendes Tenório, Alisson Macário de Oliveira, Thiago Henrique Napoleão, Robson Raion de Vasconcelos Alves, Patrícia Maria Guedes Paiva","doi":"10.1002/jat.70161","DOIUrl":"10.1002/jat.70161","url":null,"abstract":"<p><p>Moringa oleifera Lam. seeds contain WSMoL, a lectin previously studied for toxicity and pharmacological effects. In this study, we investigated WSMoL (10, 25, or 50 mg/kg i.p.) for acute and 14-day repeated-dose toxicity, as well as genotoxicity, in Swiss mice. In addition, the hypoglycemic activity of WSMoL (25 and 50 mg/kg i.p.) was evaluated in alloxan-treated mice. Animals were monitored for body weight, water and food consumption, behavioral changes, hematological and biochemical parameters, and histological patterns of the liver, spleen, and kidneys. Acute toxicity assay showed that WSMoL did not cause mortality or changes in behavior, food and water intake, or body weight. However, its administration resulted in monocytopenia, and histological changes consistent with an inflammatory process. The repeated-dose assay also indicated no significant alterations in body weight, water, or food intake. Hematological analyses, however, revealed monocytopenia and lymphocytopenia, and histological changes consistent with inflammation were observed. The micronucleus test in bone marrow cells indicated that WSMoL was not genotoxic. Administration of WSMoL (25 and 50 mg/kg) significantly reduced fasting blood glucose levels and improved oral glucose tolerance in both male and female animals after 10 days of treatment. Interestingly, WSMoL at 50 mg/kg reduced blood glucose to levels comparable to insulin. Histological analyses suggest that WSMoL prevented liver and kidney damage induced by hyperglycemia. Overall, our results indicate that WSMoL is a promising natural alternative for diabetes treatment, but its use should be approached with caution due to potential subclinical toxicity.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":"3973-3988"},"PeriodicalIF":3.1,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147473993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure to Zinc Oxide and Selenium Nanoparticles in Japanese Quail: Oxidative Stress, Inflammatory Responses, and Histopathological Outcomes.","authors":"Tuba Noreen, Muhammad Mansha, Jibran Hussain","doi":"10.1002/jat.70158","DOIUrl":"10.1002/jat.70158","url":null,"abstract":"<p><p>This study investigated the effects of green-synthesized zinc oxide (ZnO-NPs) and selenium nanoparticles (Se-NPs) on oxidative stress, inflammation, and histopathology in Japanese quail. The NPs were synthesized using extracts from Moringa oleifera (MrOl) and Agaricus bisporus (AaBi). One-day-old quails (six per group) were assigned to a control and each of 16 treatment groups receiving dietary supplementation with varying doses of ZnO-NPs (20-80 mg/kg) and Se-NPs (0.05-0.30 mg/kg) for 5 weeks. Biochemical, hematological, oxidative stress biomarkers, and gene expression (Nrf-2, IL-6) were analyzed, and histopathological examinations of the liver, kidney, and spleen were conducted. Results showed that optimal doses of MrOl-synthesized NPs, particularly Se-MrOl, significantly improved antioxidant status (reduced MDA, increased GSH), upregulated Nrf-2, downregulated IL-6, and enhanced lipid profiles (increased HDL) without causing significant histopathological damage. In contrast, higher doses, especially of AaBi-synthesized NPs, induced oxidative stress, inflammation, and mild tissue alterations. The study concludes that green-synthesized ZnO and Se-NPs, particularly from MrOl at optimized doses, can enhance antioxidant defenses and modulate immune responses in quail, highlighting their potential as effective nutritional supplements in poultry production.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":"4025-4043"},"PeriodicalIF":3.1,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147486144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Branched-Chain Amino Acids Alleviate Carbon Tetrachloride-Induced Kidney Fibrosis and Splenic Hemorrhage in Rat Models.","authors":"Zeinab Al-Amgad, Elsayed S I Mohammed, Hend Al-Amgad, Enas A Noseer, Amany Ahmed Abd El-Aziz, Heba A Mohammed, Abeer Madkour Mahmoud, Mariam M Jad, Fatma A Madkour","doi":"10.1002/jat.70179","DOIUrl":"10.1002/jat.70179","url":null,"abstract":"<p><p>Branched-chain amino acids (BCAAs) are recognized for their roles in protein synthesis, mitigation of oxidative stress, and maintenance of cellular health in models of carbon tetrachloride (CCl4) toxicity, which is associated with industrial chlorofluorocarbon emissions. Male Wistar rats were randomly assigned to four groups: control, CCl4, CCl4 plus 10 g BCAAs, and CCl4 plus 20-g BCAAs. Each rat received 1 mL/kg of CCl4. After 10 weeks, kidney function biomarkers, including glutathione peroxidase (GPX) and malondialdehyde (MDA), were assessed in kidney homogenates. Histomorphological changes in the kidneys and spleens were also evaluated. CCl4 exposure resulted in significant alterations in kidney markers, indicating nephrotoxicity, as evidenced by elevated creatinine and urea levels in the CCl4-treated group (p < 0.05). Coadministration of BCAAs with CCl4 increased glutathione peroxidase (GPX) activity and produced a dose-dependent decrease in malondialdehyde (MDA) levels compared to the CCl4 group. These biochemical outcomes were consistent with histological observations in both kidneys and spleens. Tissue damage was more pronounced in CCl4-exposed rats than in those receiving both CCl4 and BCAAs. The incidence of fibrosis was higher in the CCl4-only group, accompanied by a notable reduction in intracellular protein granules. Collectively, these results indicate that BCAAs exert dose-dependent reparative and antioxidant effects on kidney and spleen pathology. BCAAs significantly restored parameters altered by CCl4, ameliorating renal and splenic disorders. The results of the current study suggest that oral administration of BCAAs is recommended to reduce kidney fibrosis and improve spleen injury.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":"4011-4024"},"PeriodicalIF":3.1,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147480755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paraquat Dichloride Induced Cytotoxicity in Primary Hepatocytes via an Antioxidative and Mitochondrial-Dependent Pathway.","authors":"Irfan Ashraf Badroo, Hemlata Pradeep Nandurkar, Vinod K Nagale, Saba Khursheed Khan, Ashiq Hussain Khanday, Zahid Ahmad Wani, Mohd Amin Lone","doi":"10.1002/jat.70162","DOIUrl":"10.1002/jat.70162","url":null,"abstract":"<p><p>The liver serves as the primary detoxification organ, playing a crucial role in protecting against environmental toxicants. Paraquat (PQ), a widely used herbicide in agricultural and domestic applications, has been extensively documented to induce severe toxicity in various tissues and disrupt multiple cellular signaling pathways. This study investigates the cytotoxic and genotoxic effects of PQ on isolated primary rat hepatocytes, obtained via the collagenase perfusion method. A comprehensive toxicity assessment was conducted, including cell viability at different PQ concentrations, reactive oxygen species (ROS) generation, reduced (GSH) and oxidized glutathione (GSSG) levels, mitochondrial membrane potential (MMP) collapse, lysosomal integrity, and lipid peroxidation (MDA) content. A significant increase in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) leakage indicated hepatocellular membrane disruption. PQ exposure resulted in excessive ROS generation, mitochondrial dysfunction, oxidative stress, and apoptosis activation through the caspase-9/-3 signaling cascade. Notably, coincubation with the ROS scavenger N-acetylcysteine (NAC) significantly attenuated ROS generation, apoptosis, and hepatocyte damage, underscoring the role of oxidative stress in PQ-induced hepatotoxicity. These findings provide mechanistic insights into PQ-induced cytotoxicity, demonstrating that ROS overproduction and mitochondrial impairment are the primary drivers of hepatocyte injury. Given the extensive use of PQ and its potential environmental and human health risks, these findings are critical for understanding its toxicological impact and exploring antioxidant-based therapeutic strategies to mitigate liver damage.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":"4057-4075"},"PeriodicalIF":3.1,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147521076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How Synthetic Pyrethroid 1-Trans Phenothrin Affects Freshwater Mussel, Unio delicatus: Biochemical and Histological Responses.","authors":"Zehra Sarı, Gülbin Feridun, Pınar Arslan Yüce, Göktuğ Gül, Beran Feridun, Aysel Çağlan Günal","doi":"10.1002/jat.70152","DOIUrl":"10.1002/jat.70152","url":null,"abstract":"<p><p>1-Trans phenothrin (CAS no: 26046-85-5;3-phenoxybenzyl (1R,3R)-2,2-dimethyl-3-(2-methylprop-1-enyl)) cyclopropanecarboxylate, a synthetic pyrethroid insecticide, is widely used in agriculture for crop protection, household insects, and human louse infestation. Freshwater mussels (Unio delicatus Lea, 1863) were exposed to 1-trans phenothrin at concentrations of 1/10 (814 μ/L) and 1/100 (81.4 μ/L) of the 96-h LC₅₀ value for 96 h and 21 days. Total hemocyte counts (THCs), total antioxidant status (TAS), total oxidant status (TOS), sodium-potassium adenosine triphosphatase (Na⁺/K⁺-ATPase), and acetylcholinesterase (AChE) activities of the gill and digestive gland tissues of freshwater mussels were measured. Biochemical responses did not show any significant change in the solvent control group relative to the control (p > 0.05). Na⁺/K⁺-ATPase activity of the gills decreased at both low and high concentrations of 1-trans phenothrin at the end of both experimental periods compared to the control group. Additionally, AChE activity decreased in the gills and digestive glands at all experimental concentrations by the end of the trial periods compared to the control group (p < 0.05). Under the effect of 1-trans phenothrin, TAS levels decreased in the gills, while they increased in the digestive glands during both exposure periods (p < 0.05). In both tissues, TOS levels increased at 814 μg/L 1-trans phenothrin on the 21st day compared to the control group (p < 0.05). The gill and digestive gland tissues were affected histopathologically. THCs increased at 96 h under exposure to 81.4 μg/L and 814 μg/L 1-trans phenothrin compared to the control group, whereas they decreased on the 21st day. This study demonstrated that 1-trans phenothrin causes toxicity by affecting the biochemical parameters of freshwater mussels (U. delicatus).</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":"3961-3972"},"PeriodicalIF":3.1,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147473941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure-Associated Metabolic Changes in Electronic-Waste Recycling Workers: An Exploratory Untargeted Metabolomics Study.","authors":"Ozan Kaplan, Sonia Sanajou, Emine Koc, Sara Muhammetli, Canan Demir, Gözde Girgin, Mustafa Celebier, Terken Baydar","doi":"10.1002/jat.70421","DOIUrl":"10.1002/jat.70421","url":null,"abstract":"<p><p>Electronic-waste (e-waste) recycling is an important source of occupational exposure to complex mixtures of heavy metals, yet the broader metabolic consequences remain insufficiently characterized. Untargeted metabolomics provides a hypothesis-generating approach for identifying systemic biochemical alterations associated with such exposure. A cross-sectional serum metabolomics study was performed using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) in negative electrospray ionization mode, including 30 e-waste recycling workers and 46 non-exposed controls. After preprocessing, 2305 metabolic features were retained. Multivariate analysis indicated separation between exposed workers and controls. Univariate filtering identified 44 putatively annotated discriminatory features (p < 0.05, fold change > 1.5), of which 20 also showed VIP scores > 1.0. Steroid-related metabolites (pregnenolone, 17-hydroxyprogesterone, corticosterone, and tetrahydrocorticosterone) and eicosanoid/oxylipin-related features (thromboxane B2, prostaglandin H2, prostaglandin B2, 15-HETE, and 5,6-DHET) were among the main contributors to group discrimination. Pathway analysis indicated steroid-related metabolism as the strongest pathway-level signal, whereas arachidonic acid metabolism and several additional pathways showed exploratory trends. Overall, no statistically significant associations between individual blood metal levels and discriminatory metabolites remained after correction for multiple testing. These findings indicate that the observed metabolic differences are more appropriately characterized as exposure group associated rather than directly attributable to any single measured metal. Occupational e-waste exposure was associated with a distinct serum metabolic profile, with the strongest differences involving steroid-related metabolites and additional variation in eicosanoid/oxylipin-related features. These findings support the utility of untargeted metabolomics for characterizing exposure-associated metabolic signatures and provide a basis for future targeted and longitudinal studies.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":"4231-4241"},"PeriodicalIF":3.1,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}