Toxicology Reports最新文献

{"title":"Safety assessment of a proprietary fenugreek mucilage composition (FenuMat®): Acute and subchronic toxicity studies","authors":"Megha Kelenchery Ganesh ,&nbsp;Rani K. Cherian ,&nbsp;Syam Das Sivadasan ,&nbsp;Manu Aryan ,&nbsp;Krishnakumar Illathu Madhavamenon","doi":"10.1016/j.toxrep.2025.102187","DOIUrl":"10.1016/j.toxrep.2025.102187","url":null,"abstract":"<div><div>Fenugreek (<em>Trigonella foenum-graecum</em>) seeds and their extracts are popular culinary ingredients and nutraceuticals. The seed mucilage contains galactomannan, a soluble dietary fiber with prebiotic potential and divergent therapeutic effects. A proprietary fenugreek galactomannan preparation (F-GM), FenuMat®, functions as a natural self-emulsifying hydrogel, enhancing nutrient delivery and bioavailability. Although fenugreek seed safety is well documented, the safety evaluation of FenuMat® is warranted to ensure its compliance with regulatory standards. Hence, the present study evaluated the safety of FenuMat® in adult Wistar rats of both sexes, following OECD guidelines. In the acute oral toxicity study (14 days; OECD Guideline 423), no treatment related adversities were observed, indicating an LD₅₀ above 2000 mg/kg body weight. The subchronic toxicity study (OECD Guideline 408, repeated dose; 90 days) at doses of 250, 500 and 1000 mg/kg b.wt. revealed no significant alterations in hematological or biochemical parameters, or in food and water intake. However, significant reductions in serum glucose levels (at 500 mg/kg and 1000 mg/kg b.wt.) and LDL cholesterol levels (at 1000 mg/kg b.wt.) were observed. Histopathological evaluation revealed no morphological abnormalities in the major organs. Terminal autopsy revealed consistent relative organ weights and no treatment-related histopathological alterations. The high-dose recovery group (1000 mg/kg b.wt.) exhibited no mortality or adverse effects, with hematological and biochemical parameters comparable to controls, indicating a no-observed-adverse-effect level (NOAEL) of 1000 mg/kg b.wt. Further, the Ames test on four <em>Salmonella triphimurium</em> strains, with and without metabolic activation, demonstrated no mutagenic potential, indicating FenuMat®’s suitability for human use.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102187"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Berberine nanoemulsion against nephrotoxicity induced by bisphenol a in rats during pre-puberty stage","authors":"Shahnaz Rajabi ,&nbsp;Atena Mansouri ,&nbsp;Tahora Fakhrtaha ,&nbsp;Parisa Sadighara ,&nbsp;Fariborz Samini ,&nbsp;Saeed Samarghandian ,&nbsp;Tahereh Farkhondeh","doi":"10.1016/j.toxrep.2026.102203","DOIUrl":"10.1016/j.toxrep.2026.102203","url":null,"abstract":"<div><div>This study evaluated the effects of berberine nanoemulsion (BNE) against nephrotoxicity induced by bisphenol A (BPA), a plastic chemical, in rats during the pre-puberty stage. Thirty-six male Wistar rats (23-day-old) were randomly allocated to six groups (n = 6): Group 1 (Control). Group 2 (BPA): BPA (200 mg/kg) and saline. Groups 3 (BNE 5) and 4 (BNE 10): BNE (5 and 10 mg/kg,). Groups 5 (BPA + BNE 5) and 6 (BPA + BNE 10): BPA with BNE (5 and 10 mg/kg). After 30 days, kidney samples were obtained for histopathological and biochemical tests. BPA increased serum urea, uric acid, creatinine (Cr), blood urea nitrogen (BUN), and kidney levels of malondialdehyde (MDA), nitric oxide (NO), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) versus controls. BPA decreased estimated glomerular filtration rate (eGFR), reduced glutathione (GSH), and superoxide dismutase (SOD) activity. BNE (10 mg/kg) reversed these changes to near-control levels. Histopathology showed lumen obliteration of renal tubules, dilated vessels, glomerular atrophy, and large capsular space in the BPA group. Less inflammation and improved glomerular architecture were seen in the BPA + BNE10 group. In conclusion, BNE (10 mg/kg) significantly alleviated BPA-induced oxidative stress, inflammation and histopathological changes in the kidney of rats during the pre-puberty stage due to its antioxidant and anti-inflammatory effects. This finding confirms the safety and efficacy of BNE in nephrotoxic model during pre-puberty stage. It can be suggested to investigate this agent in clinical study as a possible therapeutic approach.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102203"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146173139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute effect of tetracycline on systemic stress markers and organ histopathology in juvenile Nile tilapia, Oreochromis niloticus","authors":"Md Al-Emran ,&nbsp;Md Asad Ud Zahan Siddique ,&nbsp;Md Sayem Sheikh ,&nbsp;Md Ruhul Amin,&nbsp;Most Rifah Tamanna,&nbsp;Purabi Karmoker Puja,&nbsp;Kumari Bristi Rani,&nbsp;AKM Afzal Hossain,&nbsp;Md Abu Rahad,&nbsp;Md Shahjahan","doi":"10.1016/j.toxrep.2026.102215","DOIUrl":"10.1016/j.toxrep.2026.102215","url":null,"abstract":"<div><div>Antibiotic contamination in aquaculture systems frequently encounter severe threat to aquatic life including fish. This study aimed to evaluate acute toxicological effects of tetracycline in juvenile Nile tilapia, <em>Oreochromis niloticus.</em> We exposed ten fish in each tank with nominal tetracycline concentration of 0 μg/L, 10 μg/L, 100 μg/L, 500 μg/L, 1000 μg/L, and 5000 μg/L, under semi-static condition for 96 h. After the exposure periods, six fish per treatment (n = 6) were sampled to evaluate blood glucose, hemoglobin, frequencies of erythrocyte cellular and nuclear abnormalities, and histopathology of gills, intestine, liver, and kidney. Tetracycline induced clear dose-dependent effects in studied fish. Blood glucose increased significantly (p &lt; 0.05) from 100 μg/L and onward, indicating acute metabolic stress, whereas hemoglobin decreased significantly at 500 and 5000 μg/L indicating compromised oxygen transport. Erythrocyte cellular and nuclear abnormalities rose in a threshold manner; twin, tear-drop, elongated, binucleated cells and nuclear buds became significantly more frequent at ≥ 100 μg/L and intensified at higher doses. Gill pathology such as congestion, lamellar degeneration and fusion, epithelial hypertrophy/hyperplasia was appeared from medium doses and was most pronounced at 5000 μg/L. Significant reduction in villus length, vacuolation of enterocyte and fusion of brush-border of intestine was observed at 500 μg/L and higher doses. Liver lesions such as vacuolation, hemorrhage, melanomacrophase centers, and necrosis were intensified with doses. Besides, renal alterations such as mild glomerular expansion at 100 μg/L, dilation of Bowman’s space and tubular changes at 500 μg/L and above concentrations were observed. Our findings highlight sensitive early-warning biomarkers and underscore the need for chronic exposure studies and residual analysis for risk assessments of antibiotic usage in aquaculture.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102215"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146173247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety assessment and gastrointestinal tolerance of a novel highly bioavailable turmeric extract formulation: A randomised, double-blind, placebo controlled clinical trial","authors":"Julie Laval ,&nbsp;Kirt R. Phipps ,&nbsp;Sonia Brinet ,&nbsp;Marie-Cécile Fournier ,&nbsp;Benoit Douillard ,&nbsp;Sa Pham ,&nbsp;Alexandra Lobach ,&nbsp;Severin Mueller ,&nbsp;Pascale Fança-Berthon","doi":"10.1016/j.toxrep.2025.102176","DOIUrl":"10.1016/j.toxrep.2025.102176","url":null,"abstract":"<div><div>Recent advances have led the development of turmeric formulations providing notable blood levels of curcuminoids following ingestion. However, there is a lack of clinical trials confirming the tolerability and safety of these formulations after repeated consumption by healthy subjects, as previous studies have primarily focused on efficacy and safety in subjects with health conditions. This randomised controlled trial assessed the gastrointestinal tolerance and safety of a novel turmeric extract formulation (TF) in healthy adults. Sixty subjects were assigned to either the TF group, receiving 1000 mg or placebo group (maltodextrin), once daily for 5 weeks. The study evaluated: gastrointestinal tolerance [including bloating, abdominal cramping, stomach noises, flatulence, frequency and consistency of stools and perception of Gastrointestinal Quality of Life (GIQLI)], a comprehensive analysis of haematology, clinical biochemistry and urinalysis parameters, vital signs, and a record of adverse events (AEs). No statistically significant differences were observed in gastrointestinal tolerance between the groups. Clinical parameters were not adversely affected by TF consumption, and the incidence and severity of AEs were similar in both groups. In conclusion, daily oral consumption of 1000 mg TF, thus exceeding the recommended 300 mg dose, was well tolerated and safe in healthy adults over the 5-week period.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102176"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145698182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rutin outperforms gallic acid in mitigating carbon tetrachloride-induced nephrotoxicity: Integrated in silico (docking, MD simulations, DFT) and in vivo mechanistic validation","authors":"Hend A. Essa ,&nbsp;Abdallah Ashraf ,&nbsp;Mohamed Elsheikh","doi":"10.1016/j.toxrep.2026.102214","DOIUrl":"10.1016/j.toxrep.2026.102214","url":null,"abstract":"<div><h3>Background</h3><div>Carbon tetrachloride (CCl₄) induces nephrotoxicity via oxidative stress and inflammation.</div></div><div><h3>Aim</h3><div>This novel comparative study evaluated the nephroprotective efficacy of rutin and gallic acid (GA) against CCl₄-induced kidney damage by elucidating their antioxidant and anti-inflammatory mechanisms.</div></div><div><h3>Method</h3><div>In silico, Quantum Mechanics/Molecular Mechanics methods screened rutin and GA's activity against Tumor Necrosis Factor (TNF) by inhibiting TNF-Alpha Convertase Enzyme (TACE) and Interleukin-6 (IL-6) via its receptor IL-6Rα, alongside assessing radical-neutralizing capacity. In vivo, twenty-four male Sprague-Dawley rats were divided into four groups (n = 6): normal control, CCl₄ (1 mL/kg, i.p., twice weekly), CCl₄ + rutin (40 mg/kg/day, oral), and CCl₄ + GA (40 mg/kg/day, oral) for four weeks. Renal function, oxidative stress, inflammation markers, histopathology, and immunohistochemistry were analyzed.</div></div><div><h3>Results</h3><div>In silico, rutin exhibited radical-neutralizing abilities and potential to inhibit TACE and IL-6Rα. GA showed divergence in molecular dynamics simulations for these targets and lower radical neutralization affinity, based on activation energy and reaction enthalpy. In vivo, CCl₄ induced nephrotoxicity, increasing kidney biomarkers, oxidative stress, and inflammatory markers. Both compounds significantly mitigated damage, reducing creatinine, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, urea, uric acid, lipid peroxidation, interleukin-6, tumor necrosis factor-α, p53, and NF-κB expression (p &lt; 0.05). Antioxidant enzymes (reduced glutathione, glutathione S-transferase, superoxide dismutase, catalase) were enhanced. Rutin consistently demonstrated superior efficacy.</div></div><div><h3>Conclusion</h3><div>This first direct comparison confirms rutin’s superior efficacy over GA in mitigating CCl₄-induced nephrotoxicity via antioxidant and anti-inflammatory pathways. The integrated in silico and in vivo approach validates their mechanisms, highlighting rutin's prophylactic potential.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102214"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146173248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute polyneuropathy associated with Kambo poisoning: An unusual case report","authors":"Julio César Mantilla-Pardo ,&nbsp;Juan David García-Valencia ,&nbsp;Juan Pablo Fernández-Cubillos","doi":"10.1016/j.toxrep.2026.102200","DOIUrl":"10.1016/j.toxrep.2026.102200","url":null,"abstract":"<div><div>Kambo is a natural secretion obtained from the Amazonian frog Phyllomedusa bicolor, traditionally used in ritualistic and alternative medicine practices for its purported purifying and immunostimulatory effects. Acute intoxication has been associated with neuropsychiatric manifestations, electrolyte disturbances, and systemic complications; however, involvement of the peripheral nervous system has not been previously confirmed by electrodiagnostic studies. We report the case of a 40-year-old man with no prior medical history who developed rapidly progressive quadriparesis and facial diparesis four days after subcutaneous self-application of Kambo venom. Cerebrospinal fluid analysis demonstrated albuminocytologic dissociation, and nerve conduction studies revealed an acute demyelinating motor polyneuropathy with conduction block and preserved sensory conduction. Due to clinical deterioration and risk of respiratory failure, the patient required intensive care management. He initially underwent five sessions of plasmapheresis with limited improvement, followed by intravenous immunoglobulin at a dose of 0.4 g/kg/day for five days, resulting in partial neurological recovery. At three-month follow-up, he persisted with residual motor deficits without sensory involvement. This case represents, to our knowledge, the first electrodiagnostically confirmed report of acute polyneuropathy associated with Kambo poisoning. Clinicians should be aware that Kambo intoxication may extend beyond central neuropsychiatric effects to involve the peripheral nervous system, and early recognition with consideration of immunomodulatory therapy may be warranted.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102200"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of serum concentration and the type of opioid used in patients with opium poisoning","authors":"Armin Mansouri Sarabbadieh ,&nbsp;Nazir Fattahi ,&nbsp;Mohammad Mehdi Veisi ,&nbsp;Afshin Almasi ,&nbsp;Zahra Shaahmadi ,&nbsp;Toraj Ahmadi Jouybari","doi":"10.1016/j.toxrep.2026.102213","DOIUrl":"10.1016/j.toxrep.2026.102213","url":null,"abstract":"<div><div>Opioid poisoning constitutes a major public health issue in Iran and worldwide, with increasing rates attributed to both traditional opiates and synthetic derivatives such as methadone. Reliable assessment of serum opioid concentrations is essential for clinical management and prognosis. Quantitative measurement of serum opioid concentrations determines local epidemiological patterns and identifies risk factors that guide future prevention and treatment strategies. This descriptive cross-sectional study was conducted at Imam Khomeini Hospital in Kermanshah, Iran, from March to June 2023. Fifty adult patients with confirmed opioid poisoning were clinically diagnosed based on the classic opioid toxidrome (decreased consciousness, miotic pupils, and respiratory depression) documented at emergency department admission. Clinical diagnosis was confirmed by positive response to naloxone administration. Demographic and clinical data, type and route of opioid use, clinical features, laboratory results, and patient outcomes were recorded. Serum concentrations of opioids were measured using gas chromatography–mass spectrometry (GC–MS) after administration of antidotes. Statistical analysis was performed with SPSS 26, using a significance threshold of p &lt; 0.05. Among 50 patients (86 % male, mean age 33.5 ± 9.8 years), methadone was the most common cause of poisoning (72 %), followed by opium and heroin. The principal clinical findings included apnea (44 %), miosis (44 %), and weakness/lethargy (38 %), with severe symptoms observed primarily in methadone cases. Serum methadone concentrations were significantly higher in men than women (p = 0.007), and in rural residents compared to urban (p = 0.005). Higher opioid serum levels were associated with more severe clinical presentations and increased need for intensive care. Most patients recovered with medical management; no in-hospital deaths occurred. Methadone has become the leading cause of opioid poisoning in this region, with high serum concentrations predicting increased clinical severity. Measurement of serum opioid levels is a valuable tool for risk stratification and should be integrated into standard management protocols. Attention must be given to both preventive education and tighter regulation of methadone distribution, particularly among high-risk groups.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102213"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146166801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Runaway uncoupling in 2,4-dinitrophenol poisoning: Clinical and mitochondrial observations from two cases","authors":"Erik Lindeman ,&nbsp;Tine Sommer ,&nbsp;Märta Leffler ,&nbsp;Shusuke Sekine ,&nbsp;Eskil Elmér ,&nbsp;Fredrik Sjövall ,&nbsp;Wilhelm Wallquist","doi":"10.1016/j.toxrep.2025.102183","DOIUrl":"10.1016/j.toxrep.2025.102183","url":null,"abstract":"<div><div>2,4-Dinitrophenol (DNP) is a potent mitochondrial uncoupler briefly marketed in the 1930s as a weight-reducing agent before being banned by the FDA after reports of severe toxicity. Since the early 2000s, DNP has reemerged as an illicit “fat-burner”, causing characteristic metabolic disturbances with a high risk of fatal outcome. We describe two Swedish cases of DNP poisoning: one fatal after suicidal ingestion and one non-fatal after use for weight reduction. Clinical data, mitochondrial respirometry, and analysis of gas exchange and ventilatory dynamics were used to characterize the metabolic disturbances under intensive care. The fatal case progressed within hours to respiratory acidosis, hyperthermia, severe hyperkalemia, and peri-mortem rigidity consistent with catastrophic ATP depletion. The non-fatal case showed similar but reversible toxicity, with sustained yet manageable hypermetabolism lasting more than a week. Serial platelet respirometry demonstrated a marked initial increase in uncoupled respiration, followed by a progressive decline with a functional half-life of 4.9 days. Together, these cases suggest a self-amplifying feedback loop central to DNP toxicity, in which excessive CO₂ production from mitochondrial uncoupling causes local acidosis that enhances mitochondrial DNP uptake. Glucose supplementation and hyperkalemia management are essential supportive measures, whereas active cooling and high minute ventilation may blunt this self-reinforcing metabolic acceleration. Severe poisoning may result in a state of “runaway uncoupling,” a term we propose for the catastrophic progression to death observed in numerous DNP poisonings. This feedback loop illustrates the unpredictable toxicokinetics of DNP and reinforces the FDA’s early conclusion: DNP is “unfit for human consumption”.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102183"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145738777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A meta-analysis on particulate matter-associated heavy metals in rural air: Concentration, seasonal variability, and pollution sources","authors":"Majid Farhadi ,&nbsp;Behrouz Beiranvand","doi":"10.1016/j.toxrep.2025.102194","DOIUrl":"10.1016/j.toxrep.2025.102194","url":null,"abstract":"<div><div>Heavy metals (HMs) bonded to PM (Particulate Matter) are a significant component of rural air pollution. They're primarily released from fossil fuel combustion and the operational decay of automobiles, leading to their considerable presence in roadway dust. This study aims to examine the concentration and seasonal effects on HM emissions in rural air. The pooled mean concentrations for As (7.81 ng m^-³), Cd (4.42 ng m^-³), and Pb (60.97 ng m^-³) were statistically significant. Pb concentrations were exceptionally high in some rural areas of China, with mean values over 500 ng m^-³ reported in two studies. Studies showed notably high levels of Pb, Cu, and Zn, with some sites having exceptional concentrations. The analysis also found significant seasonal variations, with many HMs showing higher concentrations in winter, which is likely due to increased coal combustion for heating. Seasonal analysis in China revealed higher concentrations of several HMs in winter, likely due to increased coal combustion for heating. In spring, road and soil dust from natural phenomena such as dust storms was a primary source of HMs.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102194"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicological safety profiling of Berberis vulgaris hydroethanolic extract using rodent, zebrafish, and in silico models","authors":"Abanti Goswami ,&nbsp;Vara Prasad Saka ,&nbsp;Mahima Sharma ,&nbsp;Narasimha Kumar G.V. ,&nbsp;Pankaj Gupta ,&nbsp;Digvijay Verma ,&nbsp;Subhash Kaushik","doi":"10.1016/j.toxrep.2025.102195","DOIUrl":"10.1016/j.toxrep.2025.102195","url":null,"abstract":"<div><h3>Background</h3><div>The hydroethanolic extract of <em>Berberis vulgaris</em> root bark (BV) is extensively used in traditional medicine, particularly Homoeopathy, for treating renal and hepatic disorders, yet a systematic safety evaluation remains limited.</div></div><div><h3>Objectives</h3><div>This study aimed to establish a comprehensive preclinical safety profile of BV using <em>in vivo</em> rodent and zebrafish models, alongside <em>in silico</em> toxicity predictions.</div></div><div><h3>Methods</h3><div>Phytochemical profiling was conducted using Liquid Chromatography–Mass Spectrometry (LC–MS). Acute and 28-day repeated-dose oral toxicity studies were performed in Wistar rats following OECD guidelines 423 and 407, respectively. Developmental toxicity was assessed in zebrafish embryos (OECD 236), and <em>in silico</em> toxicity predictions for identified phytoconstituents were generated using ProTox 3.0.</div></div><div><h3>Results</h3><div>LC-MS analysis identified 22 bioactive chemical components. In the acute oral toxicity study, BV administered at 2000 µL/kg caused no mortality or toxicity, indicating an LD₅₀ &gt; 2000 µL/kg. The 28-day repeated-dose study showed no significant alterations in haematological, biochemical, or histological parameters at doses up to 1000 µL/kg/day, establishing a No Observed Adverse Effect Level (NOAEL) of ≥ 1000 µL/kg/day. While lower concentrations were safe in zebrafish, high concentrations (4 µL/2 ml) induced developmental abnormalities such as scoliosis and pericardial edema. Computational analysis predicted low-to-moderate toxicity for the majority of phytoconstituents.</div></div><div><h3>Conclusion</h3><div>BV exhibits a wide safety margin in rodent models and is non-toxic at therapeutically relevant doses. However, observed developmental effects in zebrafish suggest caution at high concentrations, supporting the need for adherence to recommended dosages in traditional therapeutic contexts.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102195"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}