Toxicology Reports最新文献

{"title":"Protective role of baicalin against methylparaben-induced reproductive toxicity: Insights into hormonal and enzymatic regulation","authors":"Daniel Itiza Akaahan ,&nbsp;Augustine Uche Agu ,&nbsp;Nkemjika Chinyere Anyanwu ,&nbsp;Vivian Onyinye Orjiako ,&nbsp;Godson Emeka Anyanwu","doi":"10.1016/j.toxrep.2025.102113","DOIUrl":"10.1016/j.toxrep.2025.102113","url":null,"abstract":"<div><h3>Background</h3><div>Methylparaben is a commonly used preservative in the cosmetics, pharmaceutical, and food industries, valued for its antibacterial and antifungal effects. Numerous in vitro and in vivo studies have investigated its adverse effects on sperm count, testosterone levels, and reproductive organ weight. Baicalin, which comes from the dried roots of the plant Scutellaria baicalensis Georgi, is a natural compound that may have various health benefits, such as reducing fibrosis, itching, bacteria, oxidative stress, inflammation, and cancer. This study investigated the effect of baicalin on the changes in male reproductive hormones and enzyme activity brought about by methylparaben.</div></div><div><h3>Method</h3><div>A total of forty-five adult male Wistar rats were randomly allocated into nine distinct groups, each comprising five rats. Over a period of 28 days, these subjects were administered treatments via gastric gavage, which included distilled water, peanut oil, methylparaben, or differing doses of baicalin, either in isolation or in conjunction with methylparaben. Post-treatment, blood samples were obtained under terminal anesthesia for the purpose of serum analysis. Assays for hormonal levels (FSH, LH, testosterone) and enzymatic activity (17β-HSD3) were performed utilising ELISA and spectrophotometric techniques in accordance with established protocols.</div></div><div><h3>Results</h3><div>Rats treated with methylparaben (Group 3) had much lower levels of FSH, LH, testosterone, and 17β-HSD compared to the other groups, and baicalin was able to reduce these effects in a dose-dependent manner. Higher baicalin doses restored hormone and enzyme levels to near-control values levels indicating its protective benefits.</div></div><div><h3>Conclusion</h3><div>The results indicate that baicalin could mitigate the reproductive toxicity induced by methylparaben, owing to its antioxidant and regulatory characteristics, highlighting its potential as a protective agent against endocrine-disrupting chemicals</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102113"},"PeriodicalIF":0.0,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144865711","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":"In silico toxicological risk assessment of chemical constituents from Curtisia dentata stem-bark extract","authors":"Anna S. van Wyk ,&nbsp;Olusesan Ojo,&nbsp;Olusola Bodede,&nbsp;Gerhard Prinsloo","doi":"10.1016/j.toxrep.2025.102112","DOIUrl":"10.1016/j.toxrep.2025.102112","url":null,"abstract":"<div><div>Herbal products are widely used in healthcare due to their therapeutic potential. However, concerns persist among medicinal chemists and regulatory toxicologists regarding their safety and potential toxicity. Botanical products used in herbal formulations requires rigorous risk assessments. In this study, we applied <em>in silico</em> toxicity testing using natural flavouring complexes (NFCs) approach and Toxtree® v3.1.0 software to assess toxicological risk associated with <em>Curtisia dentata</em>, a widely used medicinal plant for treating diseases. We first conducted experimental analysis of the hexane crude extract of <em>C. dentata</em> using gas chromatography–mass spectrometry (GC-MS) to identify its chemical constituents. A total of 124 compounds were identified from GC-MS analysis and verified using reputable databases, including PubChem, Human Metabolome Database (HMDB), National Institute of Standards and Technology (NIST) database, and scientific literature. The Cramer’s toxicity class of the identified components was determined based on their congeneric groups. The identified constituents were then subjected to in silico toxicity evaluation using Toxtree® v3.1.0. Certain constituents, including aniline, 2,6-dimethoxybenzoquinone, and 1-iodododecane triggered structural alerts for genotoxic carcinogenicity and mutagenicity, while phthalic acid, 4-chloro-3-methylphenyl undecyl ester exhibited alerts for non-genotoxic carcinogenicity. While <em>C. dentata</em> has undoubted proven pharmacological effects, further studies should focus on confirming the <em>in silico</em> predictions through targeted <em>in vitro</em> and <em>in vivo</em> studies, particularly for constituents that fired multiple structural alerts.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102112"},"PeriodicalIF":0.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840833","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":"Chronic lung tissue deposition of inhaled polyethylene microplastics may lead to fibrotic lesions","authors":"Wonkyun Jung ,&nbsp;Mi-Jin Yang ,&nbsp;Min-Sung Kang ,&nbsp;Jin-Bae Kim ,&nbsp;Kyung-Sik Yoon ,&nbsp;Taekyung Yu ,&nbsp;Cheolho Yoon ,&nbsp;Hae Won Yang ,&nbsp;Seong-Jin Choi ,&nbsp;Eun-Jung Park","doi":"10.1016/j.toxrep.2025.102111","DOIUrl":"10.1016/j.toxrep.2025.102111","url":null,"abstract":"<div><div>Given the expected increase in exposure to airborne microplastics, we here aimed to assess the acute and subchronic toxicity of inhaled polyethylene microplastics (PE-MPs). At 24 h post-exposure (0, 125, 250, and 500 μg/lung), PE-MPs were found within alveolar macrophages in the lungs of PE-MP-treated mice, along with an increase in the total number of pulmonary cells and higher pulmonary levels of LDH, CXCL-1, and CCL-2. Similarly, when exposed twice for 14 days (weekly, 0, 125, 250, and 500 μg/lung), the total number of pulmonary cells and the levels of pulmonary chemokines and blood IgE were elevated, whereas the expression of surface proteins related to cell-to-cell interactions was inhibited on the pulmonary cells of mice exposed to PE-MPs. After 90 days of repeated intratracheal instillation (0, 5, 25, and 50 μg/lung), PE-MPs deposited in the lung tissues and increased dose-dependently both the total number of pulmonary cells and inflammatory cytokine levels. Furthermore, infiltration of inflammatory cells, formation of multinucleated giant cells, and thickening of the alveolar wall were noted in the lung tissues of PE-MP-treated male and female mice. While the production of IgA and IgG was inhibited in male and female mice following exposure to PE-MPs, the levels of IgE and IgM tended to increase. In addition, the expression of fibrillar collagens was enhanced in the lung tissues of PE-MP-treated mice. Taken together, we suggest that chronic pulmonary exposure to PE-MPs may cause immune dysregulation by impairing the antigen-presenting function of alveolar macrophages and that PE-MP-induced chronic inflammation may be linked to fibrotic lesions. In addition, we believe that these hypotheses will be clarified by further study of the effects of chronic exposure to PE-MPs on lung function.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102111"},"PeriodicalIF":0.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144852946","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 cutaneous adverse effects of methotrexate: A case report highlighting therapeutic challenges","authors":"Saarthak Miglani,&nbsp;Tanshi Daljit,&nbsp;Anurita Srivastava,&nbsp;Arun Kumar Rathi","doi":"10.1016/j.toxrep.2025.102108","DOIUrl":"10.1016/j.toxrep.2025.102108","url":null,"abstract":"<div><div>Methotrexate (MTX) is a commonly used antimetabolite for managing various autoimmune disorders and cancers. While it is generally well-tolerated at low doses, certain factors may predispose patients to significant toxicity. Here we present a case of 49-year-old male with advanced buccal mucosa squamous cell carcinoma who developed acute severe cutaneous toxicity following low dose of intravenous MTX therapy. After receiving two weekly doses, the patient experienced grade 4 oral mucositis and multiple erythematous plaques. This case highlights the importance of early recognition and prompt management of MTX toxicity, even at low doses, particularly in patients with risk factors such as prior antibiotic use and low serum albumin levels.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102108"},"PeriodicalIF":0.0,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144829718","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":"Health impacts and risk assessment of PM2.5 and PM10 at Suburban Site in Pathum Thani, Thailand","authors":"Dussadee Rattanaphra ,&nbsp;Sittinun Tawkaew ,&nbsp;Wilasinee Kingkam ,&nbsp;Sasikarn Nuchdang ,&nbsp;Kittiwan Kitpakornsanti ,&nbsp;Unchalee Suwanmanee","doi":"10.1016/j.toxrep.2025.102109","DOIUrl":"10.1016/j.toxrep.2025.102109","url":null,"abstract":"<div><div>The aim of this study was to evaluate the carcinogenic and non-carcinogenic health risks associated with heavy metals in PM₂.₅ and PM₁₀ through inhalation exposure among children and adults during both the summer and wet seasons in the Pathum Thani Province, Thailand. PM2.5 and PM10 samples were collected using a Tisch TE-Wilbur sampler, and elemental concentrations were analyzed using Proton-Induced X-Ray Emission (PIXE). Microsoft Excel was employed to determine the statistical values of PM₂.₅ and PM₁₀ concentrations, the concentrations of twelve elements, including Si, S, Cl, K, Ca, Ti, Cr, Mn, Fe, Zn, Ni, and Cu. The enrichment factor (EF), as well as health risk assessment indicators, including target hazard quotient (THQ), hazard index (HI), and carcinogenic risk (CR), were evaluated. The results showed that EF values for Zn, Ni, and Cu ranged from 10 to 100, indicating contributions from anthropogenic sources. Cr exhibited the highest EF values, ranging from 51 to 111, suggesting significant influence from industrial activities and traffic emissions. The mean PM₁₀ concentration (86.0504 µg/m³) during the wet season exceeded the WHO and EU standards but remained below the Thailand standard and the U.S. EPA limit. In contrast, the mean PM₂.₅ concentration (77.5143 µg/m³) during the same period exceeded all referenced standards. The calculated HI values were from 0.0459 to 0.1090 for adults and 0.3285–0.7811 for children. The CR values in PM₂.₅ ranged from 5.0884 × 10⁻⁸ to 7.9544 × 10⁻⁶ for adults and from 5.9364 × 10⁻⁸ to 9.2802 × 10⁻⁶ for children. For PM₁₀, the CR values ranged from 5.1865 × 10⁻⁸ to 1.0412 × 10⁻⁵ for adults and from 6.0509 × 10⁻⁸ to 1.2148 × 10⁻⁵ for children. Although both carcinogenic and non-carcinogenic risks were within acceptable limits, higher risk values were observed in children compared to adults. Therefore, targeted and effective air pollution control policies are recommended, with a particular emphasis on protecting children’s health and strengthening evidence-based air quality management strategies.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102109"},"PeriodicalIF":0.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144810509","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":"Major toxin composition of particulate matter from a coal-fired power plant and its proteomics-associated toxicological profiles in the lungs of balb/c mice","authors":"Pinnakarn Techapichetvanich ,&nbsp;Meng Chieh Yang ,&nbsp;Kran Suknuntha ,&nbsp;Napawan Hirunwiroj ,&nbsp;Paisan Jittorntam ,&nbsp;Apisada Jiso ,&nbsp;Aekkacha Moonwiriyakit ,&nbsp;Arnatchai Maiuthed ,&nbsp;Phisit Khemawoot","doi":"10.1016/j.toxrep.2025.102110","DOIUrl":"10.1016/j.toxrep.2025.102110","url":null,"abstract":"<div><div>This comprehensive study investigated fly ash particulate matter (PM) from Thailand's Mae Moh Coal-fired Power Plant, focusing on its major toxin composition and toxicological effects in mice. Chemical composition analysis using inductively coupled plasma-mass spectrometry identified iron (Fe) as the predominant heavy metal (101,067.31 ± 8246.12 mg/kg). Meanwhile, gas chromatography-mass spectrometry showed acenaphthene as the most abundant polycyclic aromatic hydrocarbon (40.77 ± 0.003 mg/kg). Toxicological profiling was conducted on Balb/c mice via intratracheal instillation at doses of 1 and 10 mg/kg/day for 7 days, with comparisons made to a vehicle negative control and standard PM2.5 as a positive control. Both fly ash PM and standard PM2.5 induced pulmonary inflammation, evidenced by the presence of neutrophils in peribronchial and perivascular areas. Dose-dependent increases in interstitial edema and alveolar macrophages were also observed. Proteomic analysis revealed three inflammation-associated pathways, including leukocyte transendothelial migration, neutrophil extracellular trap formation, and phagosome activity. The increase in pulmonary inflammation may contribute to the pathogenesis of various chronic diseases and promotion of lung cancer. These findings provide valuable insights for academic researchers, electricity enterprises, and policymakers in developing effective strategies to manage air pollution worldwide.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102110"},"PeriodicalIF":0.0,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840832","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":"Antioxidant activity and acute toxicity of ziziphus abyssinica extracts: A comparative study of root and leaf extracts","authors":"Tsegay Beyene Weldemariam ,&nbsp;Abebaye Aragaw Leminie ,&nbsp;Worku Gemechu ,&nbsp;Samuel Woldekidan Hirpesa ,&nbsp;Getahun Tsegaye Dibaba ,&nbsp;Kerat Ali Muhamed ,&nbsp;Beza Tasew Degefu ,&nbsp;Tesfaye Tolessa Dugul","doi":"10.1016/j.toxrep.2025.102103","DOIUrl":"10.1016/j.toxrep.2025.102103","url":null,"abstract":"<div><div>Ziziphus abyssinica Hochst. ex A. Rich., a traditionally valued Ethiopian medicinal plant, was investigated for its phytochemical composition, antioxidant potential, and acute toxicity to validate its ethnopharmacological uses. Through sequential solvent extraction (n-hexane to aqueous), methanol and ethyl acetate fractions of leaves exhibited superior antioxidant activity (DPPH EC50: 12.5 ± 0.8 μg/mL; ABTS EC50: 15.2 ± 1.0 μg/mL), correlating with high phenolic (120.5 ± 0.7 mg GAE/g) and flavonoid (85.6 ± 0.6 mg QE/g) content. Leaves consistently outperformed roots across assays, reflecting tissue-specific metabolic specialization. Comprehensive phytochemical profiling revealed alkaloids, saponins, and glycosides, with quantitative analysis demonstrating solvent-dependent metabolite recovery. Acute toxicity testing using Organization for Economic Co-operation and Development (OECD) Guideline 425, at 2000 mg/kg showed no mortality or significant biochemical alterations, though mild hepatic vacuolization was observed histologically. The study highlights Z. abyssinica’s dual promise as a source of natural antioxidants with a favorable safety profile, while establishing standardized protocols for its evaluation. These findings bridge traditional knowledge with scientific validation, supporting its potential development for nutraceutical or therapeutic applications targeting oxidative stress-related pathologies.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102103"},"PeriodicalIF":0.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144771052","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":"Integrated logistic sigmoid model and graphical analyses of concentration-response relationships of copper sulfate toxicity in aquatic organisms","authors":"Djohan Djohan","doi":"10.1016/j.toxrep.2025.102102","DOIUrl":"10.1016/j.toxrep.2025.102102","url":null,"abstract":"<div><div>The logistic sigmoid model (LSM) of concentration-response relationships (CRRs) of copper sulfate in aquatic organisms encounters three problems, which are diverse types of toxicities, wide ranges of effect concentrations, and various patterns of graphical CRRs. These problems have caused difficulties in evaluating patterns of toxicities from abundant studies, comparing toxicities among various concentration levels, and drawing interpretations from numerous graphical analyses. A study addressing the problems and difficulties is urgently needed to increase the understanding of copper sulfate toxicity and its application in risk assessment and aquaculture. The aquatic organisms used in the present study consisted of fish (Cypriniformes, Cichliformes, and Salmoniformes) and invertebrate parasites (Amyloodinium spp., Icthyobodo spp., and Anacanthorus spp.). In this study, 10 LSM-based effect selection criteria were developed and used, a set of low-medium-high (LMH) and sigmoid-flat-quadrant (SFQ) graphs were created to evaluate a set of sublethal and lethal CRRs, and the usefulness of LSM-LMH-SFQ in aquatic toxicology was discussed. The 10 selection criteria included three concentration types, two slopes, three coefficients of variation, and two data fitness to the model requirements. Out of nine sublethal effects, three selected ones were chosen based on the 10 criteria. Likewise, three selected lethal effects out of seven were chosen. The SFQ graph identified a highly selected sublethal effect (Thiobarbituric Acid Reactive Substances, TBARS) and a highly lethal effect (LC₅₀ of fry), based on ∆ log C (differences between concentrations) ≤ 1 µg. L⁻¹ log scale and k (slope of CRR) ≥ 6. Lastly, the LSM-LMH-SFQ discussion emphasized its significance to applicability in sublethal-lethal and fish-parasite comparability and risk assessment of copper sulfate in aquatic animals.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102102"},"PeriodicalIF":0.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144771046","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":"An evaluation and risk assessment of children’s exposures to water-soluble per- and polyfluoroalkyl substances through winter gloves","authors":"Sarah Berlinski ,&nbsp;Bruce Calder ,&nbsp;Dennis Paustenbach","doi":"10.1016/j.toxrep.2025.102095","DOIUrl":"10.1016/j.toxrep.2025.102095","url":null,"abstract":"<div><div>Winter gloves are often treated with fluoroacrylic surface coatings containing per- and polyfluoroalkyl substances (PFAS) to enhance water resistance. Concern over exposure to water-soluble PFAS, those with the greatest toxicological and regulatory relevance, has grown, particularly for children, who may experience higher relative body burdens due to lower body weight and frequent hand-to-mouth behaviors. In this study, we characterized the PFAS content and migration potential of winter gloves and conducted a screening-level risk assessment of perfluorooctanoic acid (PFOA) and perfluorohexanoic acid (PFHxA) glove exposures in children aged 2–6, considering both hand-to-mouth transfer and dermal absorption. Experimental data were generated through total fluorine analysis, liquid chromatography–tandem mass spectrometry (LC-MS/MS), gas chromatography–tandem mass spectrometry (GC-MS/MS), and leachate testing of individual glove components across eight glove brands. Three fluorotelomer compounds were detected above the limits of detection in 6 out of 173 components, spanning 3 of the 8 brands. No PFAS were detected in leachate samples, suggesting negligible migration under simulated use conditions. The calculated oral, dermal, and cumulative hazard indices, based on conservative, low-exposure scenarios using estimated concentrations below the detection limit, were all well below 0.001. This study contributes to the evidence base for PFAS risk assessment in consumer products and demonstrates that detectable PFAS residues do not necessarily translate to meaningful exposure or health risk. These findings support the use of risk-based regulatory approaches that incorporate realistic exposure scenarios in the evaluation of PFAS in treated textiles.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102095"},"PeriodicalIF":0.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144895630","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":"First case reports of intentional Imepitoin overdose in humans: A case of two patients","authors":"Gerard Ronda-Roca ,&nbsp;Antonio F. Caballero-Bermejo ,&nbsp;José Cantillana-Barrenas ,&nbsp;Belén Ruiz-Antorán","doi":"10.1016/j.toxrep.2025.102098","DOIUrl":"10.1016/j.toxrep.2025.102098","url":null,"abstract":"<div><div>We report two cases of acute imepitoin overdose, a partial GABA-A receptor agonist. The first case involved a caucasian women of 22-year-old patient who ingested 20-24 g of imepitoin in a suicide attempt, presenting with central nervous system depression and mydriasis. The second case involved a caucasian male of 31-year-old patient who ingested 6–8 g of imepitoin along with other psychiatric medication, paracetamol, and ibuprofen. This patient presented with somnolence and bradylalia. Both patients received supportive care, including airway protection, intravenous fluids, activated charcoal, and cardiac monitoring. In the second case, flumazenil was administered and later discontinued. Both patients recovered fully within hours without complications. Imepitoin acts at the benzodiazepine binding site of the GABA-A receptor, approved for canine epilepsy and scarcely studied in humans, producing anxiolytic and anticonvulsant effects with reduced risk of sedation, dependence, or tolerance. It has a rapid absorption profile (T_max 0.5–2 h) and a variable half-life, shorter in smokers due to CYP1A2 induction.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102098"},"PeriodicalIF":0.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144739257","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}