Journal of Applied Toxicology最新文献

{"title":"Integrated Network Pharmacology and Experimental Study on Shikonin-Induced Male Reproductive Toxicity.","authors":"Ruirui Qian, Houpeng Wang, Jia Li, Yanfan Cui, Yuanqiao He, Houyang Chen, Shimin Liu, Tao Luo","doi":"10.1002/jat.4959","DOIUrl":"https://doi.org/10.1002/jat.4959","url":null,"abstract":"<p><p>Shikonin (SHK), a natural naphthoquinone compound with diverse pharmacological activities, exerts potent inhibitory effects on multiple tumor cell types. However, its impact on the male reproductive system lacks clarity. This investigation applied an integrated network pharmacology and experimental validation strategy to systematically evaluate the potential male reproductive toxicity of SHK. Computational analyses identified 59 overlapping targets between SHK and male infertility-associated genes, with functional enrichment implicating apoptosis regulation and oxidative stress as central mechanisms. To validate these predictions, in vitro experiments were performed to assess the toxicity of SHK on mouse testicular tissues and human sperm. Results demonstrated that SHK reduced testicular tissue viability and disrupted the histological structure of seminiferous tubules by modulating apoptosis-related protein expression and inducing cellular apoptosis. Furthermore, SHK decreased viability, motility, mitochondrial membrane potential (MMP), and B-cell lymphoma-2 (BCL-2)/BCL-2-associated X (BAX) ratios while elevating reactive oxygen species (ROS) levels in human sperm. Critically, co-treatment with ascorbic acid (AA), a potent antioxidant, attenuated SHK-induced ROS overproduction, partially restored sperm motility and viability, and mitigated testicular tissue damage. In summary, SHK triggered mitochondrial apoptosis in the testes and sperm via ROS-mediated oxidative stress, while AA counteracted this toxicity by suppressing oxidative stress.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286191","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":"The Role of the p62-Keap1-Nrf2 Pathway in Protecting Sertoli Cells Against Mono-(2-ethylhexyl)phthalate-induced Ferroptosis.","authors":"Siyuan Wang, Dinggang Li, Wei Deng, Shengde Wu, Yi Wei, Guanghui Wei","doi":"10.1002/jat.4963","DOIUrl":"https://doi.org/10.1002/jat.4963","url":null,"abstract":"<p><p>Di-(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer linked to testicular toxicity. Mono-(2-ethylhexyl) phthalate (MEHP) is the main bioactive metabolite of DEHP. The aim of this study was to investigate the protective role of the p62-Keap1-Nrf2 pathway against ferroptosis in Sertoli cells, which are crucial for normal testicular function, utilizing a cell model of MEHP-induced damage. Sertoli cells were treated with MEHP in vitro to assess the effects of MEHP on cell viability, the occurrence of ferroptosis, and the activation status of the p62-Keap1-Nrf2 pathway. Exposure to MEHP resulted in elevated levels of lipid peroxidation and indicators of iron accumulation in Sertoli cells, indicating oxidative stress and cell death associated with iron overload. Following p62 and Nrf2 gene knockdown in Sertoli cells, MEHP-induced ferroptosis was exacerbated. The p62-Keap1-Nrf2 signaling pathway played a critical role in protecting Sertoli cells from MEHP-induced ferroptosis, potentially mitigating testicular injury in mice. These findings elucidate the molecular mechanisms underlying MEHP toxicity and reveal potential therapeutic strategies for preventing testicular dysfunction associated with MEHP exposure.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280386","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":"Novel Toxicokinetics and Metabolic Insights Into Arsenic in Biological Systems From Realgar-Indigo naturalis Formula.","authors":"Kaifeng Huang, Yunxia Shi, Youhui Xu, Huimin Zeng, Xiang Zhou, Miaolin Li, Yuewen Xu, Zhenhui Wu, Li Zhou, Hao Chen, Yaguo Fan, Zhaohui Ding, Xueqin Yin, Shuijing Hu, James Quinn, Danfeng Wang, Huanhua Xu, Zhenhong Jiang","doi":"10.1002/jat.4954","DOIUrl":"https://doi.org/10.1002/jat.4954","url":null,"abstract":"<p><p>Realgar-Indigo naturalis Formula (RIF) is the only oral arsenic formulation approved globally and serves as a first-line treatment for acute promyelocytic leukemia (APL), and its safety profile remains a critical clinical concern though. Formulated according to the traditional Chinese medicine (TCM) compatibility principle known as \"Jun-Chen-Zuo-Shi,\" the modern toxicokinetic rationale underlying the detoxifying or potentiating effects of its individual constituents on arsenic toxicity remains inadequately elucidated. In this study, we systematically evaluated arsenic toxicokinetic and methylation metabolism patterns in plasma and various tissues using high-performance liquid chromatography coupled with inductively coupled plasma mass spectrometry (HPLC-ICP-MS), supplemented by histopathological examination via hematoxylin and eosin (H&E) staining. Compared with Realgar alone, Salvia miltiorrhiza Bunge and Pseudostellaria heterophylla markedly lowered immediate plasma AsV exposure by 62.8% and 51% and reduced tissue DMA burden by 58% and 23% in 9 days, respectively. In contrast, Indigo naturalis increased AsV exposure by 107% after 7 days and raised DMA burden in tissue by 19%. Overall, these toxicokinetic signatures indicate that S. miltiorrhiza Bunge and P. heterophylla confer a compatibility-dependent detoxifying effect, whereas I. naturalis potentiates arsenic toxicity. These toxicokinetic insights provide critical scientific evidence supporting the traditional compatibility principles, enhancing the safety and rational optimization of arsenic-based TCM formulations.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274519","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":"Toxicological Assessment of Melamine-Functionalized Graphene Oxide and Carbon Nanotubes Using Zebrafish Models.","authors":"Aybek Yiğit, Serkan Yıldırım, Mine Köktürk, Dilek Nazli, Metin Kiliçlioğlu, Gunes Ozhan, Begum Celikkiran, Gonca Alak, Muhammed Atamanalp, Nurettin Menges","doi":"10.1002/jat.4953","DOIUrl":"https://doi.org/10.1002/jat.4953","url":null,"abstract":"<p><p>Graphene oxide (GO) and carbon nanotube (CNT)-based nanomaterials have attracted significant interest in various industrial and biomedical applications due to their unique physicochemical properties; however, concerns about their potential toxicity, especially when modified with additives like melamine (M), remain largely unresolved. This study investigates the toxicological effects and underlying mechanisms of graphene oxide-melamine (GO-M) and carbon nanotube-melamine (CNT-M) nanoparticles in zebrafish (Danio rerio) embryos and larvae. To this end, developmental toxicity, phenotypic and behavioral changes, as well as histopathological and immunofluorescence alterations, were evaluated following acute exposure to GO-M and CNT-M nanoparticles at concentrations of 5, 10, and 20 mg/L. Results showed that both nanoparticles delayed larval hatching, particularly at higher concentrations (10 and 20 mg/L). Malformations were observed at 20 mg/L in the GO-M group and at 10 and 20 mg/L in the CNT-M group. Additionally, significant changes in larval length and eye area were observed at all concentrations for both nanoparticles. Behavioral assessments revealed that CNT-M exposure at 10 and 20 mg/L significantly impaired head sensorimotor reflexes, while all concentrations affected tail reflexes. In contrast, GO-M exposure did not significantly alter sensorimotor responses. These findings suggest differential toxic mechanisms and neurobehavioral effects of GO-M and CNT-M nanoparticles during early zebrafish development.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145274620","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":"Use of the TIPS Technique as a Possible Method of Acute Inhalation Toxicity Assessment.","authors":"Dina Mourad Saleh, Omnia Hosny Mohamed Ahmed, David B Alexander, William T Alexander, Kumiko Ogawa, Min Gi, Aya Naiki-Ito, Salwa Abdallah, Hiroyuki Tsuda","doi":"10.1002/jat.4940","DOIUrl":"https://doi.org/10.1002/jat.4940","url":null,"abstract":"<p><p>Acute inhalation toxicity studies provide crucial information regarding short-term exposure to volatile chemicals and help to ensure the safe handling and use of these chemicals. However, acute inhalation toxicity assessment requires specialized equipment, and most animal facilities are not able to carry out such studies. Consequently, an extremely large number of chemicals remain unassessed. Therefore, we investigated intra-Tracheal Intra-Pulmonary Spraying (TIPS) as a method for testing the acute inhalation toxicity of volatile chemicals. TIPS does not require specialized equipment and consequently is an approach that can be used by essentially all animal facilities. We diluted 12 chemicals in physiological saline and administered the chemicals to test animals using TIPS. When the acute LD50 values obtained by TIPS were converted to LC50 values, there was good agreement between the TIPS LC50 values and the reported inhalation LC50 values of nine of 11 water-soluble chemicals. Two water-soluble chemicals had TIPS LC50 values that were more than 2.5-fold higher than the published inhalation LC50 values, and water-insoluble xylene had an LC50 value that was more than 2.5-fold lower than the published inhalation LC50 value. This strong agreement between TIPS LC50 values and published LC50 values suggests that TIPS has the potential to be used for acute inhalation toxicity testing. However, further studies are needed to establish testing systems that will identify solutes that can and cannot be used for TIPS testing of different water-soluble chemicals and for TIPS testing of water-insoluble chemicals.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258462","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":"Nickel Ferrite Nanoparticles Potentiate the Anticancer Effects of Doxorubicin in Human Lung A549 Cancer Cells.","authors":"Seda Askin, Bahri Avci, Hilal Kiziltunc Ozmen, Esra Palabiyik, Bercem Dilan Oztanrikulu, Melike Sevim, Handan Uguz, Ayse Nurseli Sulumer, Acelya Kardelen Karadag, Kadriye Yalcin, Hakan Askin","doi":"10.1002/jat.4955","DOIUrl":"https://doi.org/10.1002/jat.4955","url":null,"abstract":"<p><p>Nickel ferrite (NiFe₂O₄) nanoparticles, a class of Fe-based magnetic nanoparticles (MNPs), have attracted increasing attention for cancer therapy because of their biocompatibility, magnetic responsiveness, and potential to enhance the efficacy of chemotherapeutic drugs. This study aimed to investigate the in vitro synergistic anticancer effect of NiFe₂O₄ nanoparticles in combination with doxorubicin (Dox) on human lung adenocarcinoma A549 cells. NiFe₂O₄ nanoparticles were synthesized and characterized by X-ray diffraction (XRD), confirming spinel crystallinity; scanning electron microscopy (SEM), revealing nanorod morphology; and energy-dispersive X-ray spectroscopy (EDX), confirming elemental composition. X-ray photoelectron microscope (XPS), Raman scattering, and also Brunauer-Emmett-Teller (BET) analysis were performed to understand the surface. Cytotoxicity was assessed by WST-8 assay, and apoptosis induction was evaluated by mRNA expression analysis of CASP6, BAX, and BCL2 using RT-qPCR. NiFe₂O₄ nanoparticles alone exhibited dose-dependent cytotoxicity with an IC₅₀ of 69.59 μg/mL. When combined with subtoxic Dox (1.485 μM), a strong synergistic effect was observed, reducing the combination IC₅₀ to 15.39 μg/mL. Gene expression results indicated that the combination treatment significantly upregulated CASP6 and BAX, while downregulating BCL2, confirming enhanced apoptosis. NiFe₂O₄ nanoparticles potentiate the anticancer activity of doxorubicin in A549 cells at lower doses, suggesting a promising strategy to enhance efficacy while potentially reducing chemotherapeutic side effects.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258405","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":"Dysregulation of mTOR, GADD45a, and CDKN1A in HepG2/C3A Spheroids Treated With Ursolic Acid.","authors":"Maria Claudia Terkelli de Assis, Luan Vitor Alves de Lima, Liana Martins de Oliveira, Matheus Felipe da Silva, Isabella Cristina Oliveira Carvalho, Isaura Maria Fuzinatto, Mário Sérgio Mantovani","doi":"10.1002/jat.4958","DOIUrl":"https://doi.org/10.1002/jat.4958","url":null,"abstract":"<p><p>Phytochemicals are plant-derived compounds extensively studied for the discovery and development of new drugs. Ursolic acid (UA), a pentacyclic triterpenoid phytochemical extracted from the bark and leaves of plants in the Lamiaceae family, has been the focus of research due to its antiproliferative potential, which has not yet been evaluated in tumor spheroids. This study aimed to analyze the antiproliferative effects and mechanisms of action of UA in 3D cultures (spheroids) of HepG2/C3A cells (human hepatocarcinoma). The analyses in 3D culture included average spheroid volume, genotoxicity using the comet assay, and the influence on mRNA expression, based on the cytotoxicity of UA assessed by the resazurin assay in 2D culture. The data showed that after 24 h of treatment, UA exhibited cytotoxicity at concentrations of 100 and 150 μM, reduced spheroid growth, demonstrated genotoxicity, and induced an increase in MTOR gene expression (2.38×). At 72 h, there was an upregulation of GADD45A (8.8×) and a downregulation of CDKN1A (2×). It is concluded that UA exhibits antiproliferative actions, promoting changes in the expression of genes associated with cell cycle control and DNA damage. This study has contributed to understanding the mechanism of action of this phytochemical for its therapeutic potential.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251235","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":"The Genotoxic Ambiguity of 4-Aminoquinolines: Resolving Hydroxychloroquine's Mechanistic Safety Profile Through Integrated Toxicology Assessment.","authors":"Hatice Yildiz, Hasan Basri İla","doi":"10.1002/jat.4948","DOIUrl":"https://doi.org/10.1002/jat.4948","url":null,"abstract":"<p><p>Hydroxychloroquine sulfate (HCQ), widely prescribed for autoimmune disorders, carries unresolved concerns regarding potential genotoxic risks. This integrated in vitro assessment comprehensively evaluated HCQ's cytogenotoxic profile using bacterial reverse mutation (Ames test in TA98/TA100 strains, 5-80 μg/plate), DNA strand break detection (alkaline Comet assay), chromosomal instability assessment (cytokinesis-block micronucleus test in human lymphocytes, 10-40 μg/mL), oxidative stress biomarkers (TOS/TAR/OSI), plasmid DNA protection (pBR322 under UV/H₂O₂), and molecular docking targeting DNA polymerase δ. Results demonstrated no mutagenicity in TA98. While a statistically significant (p ≤ 0.001) increase in revertants was observed in TA100 at a single concentration, this was transient, nondose-dependent, and biologically insignificant as it remained below the two-fold threshold defined by OECD criteria. No significant DNA damage occurred in mammalian systems, with Genetic Damage Index ≤ 0.14 and micronucleus frequency consistently below 9.75%. Molecular docking revealed weak binding affinity to DNA polymerase δ (ΔG = -5.6 kcal/mol). HCQ induced pronounced dose-dependent cytostasis, evidenced by a 20.5% reduction in Nuclear Division Index at 40 μg/mL, without accompanying genotoxicity. Redox modulation was confirmed through a 15.4% decrease in oxidative stress index. Crucially, HCQ exhibited a complex, biphasic effect on plasmid DNA, paradoxically exacerbating damage at a low concentration (10 μg/mL) while offering significant protection at higher concentrations under combined oxidative stress. These data establish HCQ as a cytostatic agent devoid of genotoxic risk, reinforcing its clinical safety profile while highlighting the necessity for environmental risk validation through in vivo models.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244702","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":"Therapeutic Potential of Phycocyanin in Attenuating Uranium-Induced Neurophysiological Alterations in Adult Male Albino Rats.","authors":"Doaa Mousa, Mohamed M Rezk, Ali Osman, Mahmoud Sitohy","doi":"10.1002/jat.4951","DOIUrl":"https://doi.org/10.1002/jat.4951","url":null,"abstract":"<p><p>Phycocyanin is a pigment-binding protein extracted from different algae for its great antioxidant and protecting properties. Uranium is a naturally radioactive metal showing many hazards effects on living organisms when exposed to it. The present study aims to show the effect of phycocyanin to decrease the ability of uranium to cross, accumulate, and distribute in six brain areas (cortex, cerebellum, hippocampus, striatum, midbrain, and hypothalamus) and demonstrated the expected neuroprotective role of phycocyanin against uranium intoxication in adult male albino rats. One hundred twelve rats are grouped as control, phycocyanin (PC), uranium (U), and PC+U group. Results showed that the daily administration of phycocyanin could decrease the uranium accumulation in the different brain areas. The daily intraperitoneal injection with uranium caused a significant decrease in norepinephrine (NE), dopamine (DA), serotonin (5-HT), and adenosine triphosphate (ATP), and reduced glutathione (GSH) accompanied by a significant increase in disulfide glutathione (GSSH), gamma aminobutyric acid (GABA), and glucose level. On the other hand, phycocyanin administration showed a significant change in malondialdehyde (MDA) and GSH level. The coadministration of phycocyanin in parallel with uranium injection showed that phycocyanin has a neuro-mitigation effect on uranium's adverse effect in all the tested parameters. The ameliorative effect of phycocyanin may be regarded as its high activity of scavenging the free radicals and its highly antioxidant effect.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244712","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":"Urbanization and Water Insecurity in Semi-Arid Regions: A Multi-Index Assessment of Water Quality, Ecological Risk, and Public Health Impacts.","authors":"Muzhda Qasim Qader","doi":"10.1002/jat.4949","DOIUrl":"https://doi.org/10.1002/jat.4949","url":null,"abstract":"<p><p>Degradation of water quality remains a critical environmental and public health issue in semi-arid regions, where limited freshwater resources are increasingly stressed by rapid urbanization, intensive agriculture, and industrial activities. This study assessed the status of surface and groundwater in Erbil City, Kurdistan Region of Iraq, through systematic sampling of 23 sites, including surface water and groundwater sites in 2025. Multiple indices were applied, including the Water Quality Index (WQI), Biochemical Oxygen Demand Index (BI), Nemerow Pollution Index (NPI), Ecological Risk Index (ERI), Index of Geo-Accumulation (Igeo), and human health risk assessment metrics such as Chronic Daily Intake (CDI), Hazard Quotient, Hazard Index (HI), and Incremental Lifetime Cancer Risk (ILCR). WQI values (40.83-76.06) indicated excellent to good water quality, with no sites falling into the poor category, whereas BI (0.28-3.64) revealed moderate organic pollution with localized hotspots. NPI (0.73-14.58) revealed nutrient enrichment at Sites 9, 13, and 16, demonstrated eutrophication risks, while ERI (5.14-276.31) pointed to elevated ecological risks from heavy metals, particularly Pb and Cu at Site 13. Although pH and most ions were within acceptable limits, turbidity, electrical conductivity, and total dissolved solids exceeded thresholds at multiple sites. Health risk assessment revealed noncarcinogenic hazards (HI > 1) at several sites, while carcinogenic risks were primarily driven by arsenic contamination. Specifically, Sites 12, 15, and 19 exceeded the US Environmental Protection Agency (USEPA) threshold of 1 × 10^-3 for ∑ILCR, while the remaining sites were below this level. The findings demonstrated that rapid urbanization and land-use changes substantially impaired water resources in Erbil. These results provide critical evidence for policymakers, underscoring the need for stricter wastewater management, targeted mitigation strategies, and long-term monitoring to ensure water security and safeguard public health in the region.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238720","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}