Toxicology Reports最新文献

{"title":"Investigation of alpha smooth muscle actin changes in the liver of cholestatic rats following the consumption of L-theanine","authors":"Mobina Daneshnia ,&nbsp;Pejman Mortazavi ,&nbsp;Mahsa Ale-Ebrahim ,&nbsp;Razieh Hosseini","doi":"10.1016/j.toxrep.2025.102193","DOIUrl":"10.1016/j.toxrep.2025.102193","url":null,"abstract":"<div><div>Cholestatic liver disease represents a major global health threat, resulting in significant morbidity and mortality. Cholestasis can be induced in laboratory animals using Bile Duct Ligation (BDL) technique. Activated Hepatic Stellate Cells (aHSCs) express Alpha Smooth Muscle Actin (α-SMA), which is correlated with experimental liver fibrogenesis. The <em>Camellia sinensis</em> plant produces <span>L</span>-Theanine, an amino acid (AA), in its roots. This research endeavored to conduct a comprehensive assessment of the anti-fibrotic effects of <span>L</span>-Theanine alongside α-SMA changes in the liver of cholestatic rats. Rats were classified into eight experimental groups, each consisting of five animals, including; (1) normal control group, (2) BDL control group, (3–5) healthy experimental groups, 6–8) BDL + <span>L</span>-Theanine groups. <span>L</span>-Theanine solution (100, 200 or 400 mg kg⁻¹) was administered to the animals by Intragastric gavage (once a day) for 30 successive days. BDL significantly elevated the enzymatic activity of Gamma-glutamyl transferase (GGT), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), Aspartate aminotransferase (AST) and elevated the amount of total bilirubin. These biochemical alterations were ameliorated when <span>L</span>-Theanine was administered. Masson`s Trichrome and Immunohistochemical (IHC) staining revealed that BDL expanded the collagen deposition and α-SMA expression in hepatic tissue. Administration of <span>L</span>-Theanine, remarkably alleviated these alterations. <span>L</span>-Theanine attenuates hepatic fibrosis through decreasing the production of α-SMA.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102193"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925976","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":"Clinical evaluation of oral fluid point-of-care testing for drugs of abuse compared to urinary point-of-care testing at a large-scale music festival","authors":"Frantzen MGM ,&nbsp;Gresnigt FMJ ,&nbsp;Litsenburg van RTH ,&nbsp;Franssen EJF","doi":"10.1016/j.toxrep.2025.102192","DOIUrl":"10.1016/j.toxrep.2025.102192","url":null,"abstract":"<div><h3>Background</h3><div>Urinary point-of-care testing for recreational drugs is commonly used in clinical settings. An oral fluid-based point-of-care test is a less invasive alternative, but the reliability and clinical applicability in a real-life acute care setting is unclear.</div></div><div><h3>Aim</h3><div>To assess the concordance of oral fluid point-of-care testing compared to urine point-of-care testing for recreational drugs in a prehospital clinical setting.</div></div><div><h3>Methods</h3><div>This study was conducted during a large-scale dance music festival in October 2023. Urine and oral fluid samples were collected at the event medical station from volunteers with a suspected drug intoxication. Participants aged 18 years and older were included if both samples were provided and at least one substance tested positive. The percentage of positive oral fluid test results per recreational drug were compared with those of the urine point-of-care test.</div></div><div><h3>Results</h3><div>A total of 78 patients were included. For most drug substances, positivity rates were similar between the two test types. Methamphetamine/3,4-methylenedioxymethamphetamine was the only substance that showed significantly more positive results in oral fluid compared to urine (p &lt; 0.001). For all other substances, the differences between the two tests were small, with slightly higher positivity rates (on average 3.9 %) detected in oral fluid.</div></div><div><h3>Conclusion</h3><div>Oral fluid point-of-care testing shows potential in specific scenarios but requires further validation. It is a less invasive alternative to urine point-of-care testing for recreational drugs in a clinical setting. Nevertheless, it is important to consider the differences in test characteristics, such as detection window. Further research is needed to evaluate the reliability in other populations and settings.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102192"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926068","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":"Genotoxicity risk assessment of a 7-hydroxymitragynine-enriched Kratom preparation: An integrated in silico and in vitro approach","authors":"Nathaphat Harnkit ,&nbsp;Tiyanee Sahad ,&nbsp;Ittiya Noonate ,&nbsp;Phatiphan Primpai ,&nbsp;Sarayut Radapong ,&nbsp;Weerachai Pipatrattanaseree ,&nbsp;Pornchai Sincharoenpokai ,&nbsp;Pramote Chamnanpuen","doi":"10.1016/j.toxrep.2026.102206","DOIUrl":"10.1016/j.toxrep.2026.102206","url":null,"abstract":"<div><div>The increasing global use of <em>Mitragyna speciosa</em> (Kratom) necessitates a thorough safety assessment, particularly regarding the genotoxic potential of its key alkaloids. This study employed an integrated in silico and in vitro approach to evaluate the genotoxicity of a well-characterized, semi-synthetically enhanced Kratom preparation (SKP) enriched in 7-hydroxymitragynine (7-OHMG; 56.31 % of total composition). Computational predictions using the OECD QSAR Toolbox and VEGA-QSAR platform indicated a lack of genotoxic activity for the major Kratom alkaloids (mitragynine, paynantheine, speciogynine, 7-hydroxymitragynine, and speciociliatine) across various in vitro and in vivo endpoints. However, several DNA-binding structural alerts were identified, particularly under metabolic activation, and prediction reliability ranged from low to moderate. To empirically verify these findings, an in vitro cytokinesis-block micronucleus (CBMN) assay was conducted in human TK6 cells following OECD Test Guideline 487. The extract induced concentration-dependent cytotoxicity. A statistically significant increase in micronucleus frequency was observed only at the highest concentration tested (125 µg/mL) under short-term (4 h) exposure conditions, both with and without S9 metabolic activation. Excessive cytotoxicity prevented analysis at high concentrations during long-term (24 h) exposure. Importantly, a complementary bacterial reverse mutation assay (Ames test) conducted on the identical extract showed no mutagenic activity up to 5000 µg/plate across five strains. In conclusion, while a weak positive chromosomal effect was noted at a highly cytotoxic concentration, the overall weight of evidence—including negative in silico predictions, negative Ames results, and limited in vitro micronucleus response—suggests that this 7-OHMG-enriched Kratom preparation does not present a significant genotoxic hazard under the conditions tested. This study underscores the value of a combined computational and experimental workflow for the robust genotoxicity assessment of complex natural products.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102206"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977348","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":"Toxicity and health effects of delta-8, delta-9, and delta-10-tetrahydrocannabinol and unregulated cannabinoids in vaping products","authors":"Karen Lin,&nbsp;Yehao Sun,&nbsp;Rhea Raghu,&nbsp;Parth Suharu,&nbsp;Felix Effah,&nbsp;Irfan Rahman","doi":"10.1016/j.toxrep.2026.102202","DOIUrl":"10.1016/j.toxrep.2026.102202","url":null,"abstract":"<div><div>Hemp-derived cannabinoids (CBDs) such as Δ8- and Δ10-tetrahydrocannabinol (THC) in cannabis e-cigarettes have been growing in popularity among youth, causing great concern for their health effects. Previous novel lung injury outbreaks, such as E-cigarette or Vaping Use-Associated Lung Injury (EVALI), were associated with the rising use of e-cigarettes and vaping products. Toxicological studies have revealed that chronic exposure to cannabis vapor can cause adverse brain and pulmonary effects. Hemp products are classified as cannabis and set a limit of no more than 0.3 % Δ9-THC, while products containing more than 0.3 % are defined as ‘marijuana.’ This has led to the proliferation of hemp-derived intoxicating cannabinoids, such as Δ8- and Δ10-THC, in addition to cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), and Δ9-THC appearing in combination products. CBD frequently serves as a significant component of hemp-derived formulations, making it a central consideration for toxicological and regulatory evaluation as well. This phenomenon poses significant health risks to youth because these newer THC isomers and products are currently unregulated and not well-researched, yet they are still widely available. Therefore, we have examined the pharmacology, toxicity, potential therapeutic uses and possible health risks of several THC and hemp-derived cannabinoids. This review draws insightful highlights to the public health consequences of secondary exposures to CBD and THC, and their molecular mechanisms of action. It underscores the urgency for a regulatory oversight over unregulated cannabinoid markets to prevent toxicity of vaping-related health crises and other rapidly emerging cannabis health disorders, like the cannabinoid hyperemesis syndrome (CHS).</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102202"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977347","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":"Synthesis, characterization, and anticancer evaluation of N-Heterocyclic entities: ADME profiling and In Silico predictions","authors":"Zakariae Abbaoui ,&nbsp;Oussama Khibech ,&nbsp;Hüseyin Karci ,&nbsp;Muhammed Dündar ,&nbsp;İlknur Özdemir ,&nbsp;Nevin Gürbüz ,&nbsp;Ahmet Koç ,&nbsp;Wilson Agerico Dino ,&nbsp;İsmail Özdemir ,&nbsp;Naifa Alenazi ,&nbsp;Rachid Touzani ,&nbsp;Hanan Alghibiwi","doi":"10.1016/j.toxrep.2025.102184","DOIUrl":"10.1016/j.toxrep.2025.102184","url":null,"abstract":"<div><div>This study aimed to synthesize a novel series of <em>N</em>-heterocyclic compounds and evaluate their integrated pharmacological potential by coupling <em>in vitro</em> selective cytotoxicity on tumor and normal cell lines with predictive <em>in silico</em> ADME-Tox profiling. This research highlights the anti-cancer potential of twelve synthesized compounds, five of which are new chemical entities never before described in the literature. Their detailed structural characterization (NMR ¹H, ¹³C, IR), combined with <em>in silico</em> predictions (ADME-Tox), confirmed their ability to cross essential biological barriers, in particular the intestinal membrane and, for certain derivatives, the BBB. Biological evaluations conducted on SH-SY5Y (neuroblastoma) and HCT116 (colorectal carcinoma) cell lines revealed several compounds with IC₅₀ values lower than those of cisplatin while exhibiting reduced cytotoxicity towards the normal human epithelial BEAS-2B cell line. In particular, the compound (<em>1H</em>-imidazol-1-yl)methanol (designated as Compound <strong><u>6</u></strong>) stands out with IC₅₀ values of 6.97 ± 0.06 µM on SH-SY5Y and 10.70 ± 0.33 µM on HCT116, significantly lower than those of cisplatin under the same experimental conditions. This profile, combined with virtually no toxicity on normal BEAS-2B cells (IC₅₀ &gt; 800 µM), highlights its remarkable selectivity. These results highlight optimized pharmacological properties and suggest the potential for developing selective therapeutic agents against different types of cancer, particularly neuronal and colorectal tumors. Future research will focus on in-depth mechanistic studies and <em>in vivo</em> validation to optimize the efficacy, pharmacokinetics, and safety of these promising molecules.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102184"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145791726","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":"Pharmacokinetics and metabolism of siamenoside I in rats","authors":"Ashley Roberts ,&nbsp;Nicole Cuellar-Kingston ,&nbsp;Steven Townley ,&nbsp;Terence Ormsby ,&nbsp;Shaun Johnson ,&nbsp;Jennifer L.G. van de Ligt ,&nbsp;Alex K. Eapen","doi":"10.1016/j.toxrep.2025.102185","DOIUrl":"10.1016/j.toxrep.2025.102185","url":null,"abstract":"<div><div>The pharmacokinetics and metabolism of [¹⁴C]-siamenoside I were studied following single oral doses of 5 mg/kg bodyweight with intact and bile duct-cannulated rats. Elimination of radioactivity was rapid and essentially complete by the end of the sample collection period (0–168 h), with the primary excretion route being the feces (101 % males and 92 % females). The estimate of absorption determined from the level of radiolabel in the bile of bile duct-cannulated rats was approximately 43 % in males and 42 % in females. The resultant systemic exposure as determined via urinary as well as blood and plasma radioactivity levels was low relative to the administered dose with only 1–1.5 % eliminated in intact and bile duct-cannulated male and female urine. Blood, plasma and tissue radioactivity levels were rapidly and widely distributed with the overall distribution low relative to administered dose. Metabolism of siamenoside I, to mogrol following cleavage of the sugar groups was the major component of feces (53–59 %), which appears to occur in the gastrointestinal tract prior to absorption. This was supported by mogrol being a significant component of radioactivity in plasma and tissues. The biotransformation of absorbed radioactivity also involved formation of several oxidized metabolites of mogrol, generally addition of oxygen and/or dehydrogenation. Overall absorption and subsequent excretion of [¹⁴C]-siamenoside I was similar in male and female rats as determined by the levels of radioactivity present in the urine and bile with no evidence of accumulation or retention observed in any tissue.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102185"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145791812","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":"Heated tobacco product aerosol emission compared to cigarette smoke: A scoping review","authors":"Stefano Bellosta ,&nbsp;Alberto Corsini ,&nbsp;Gabriele Catena","doi":"10.1016/j.toxrep.2026.102209","DOIUrl":"10.1016/j.toxrep.2026.102209","url":null,"abstract":"<div><div>Heated tobacco products (HTPs) are promoted as reduced-risk alternatives to combustible tobacco cigarettes (TCs), yet toxicant exposure reduction and associated health benefits remain uncertain. We evaluated preclinical and interventional clinical studies comparing HTPs with TCs, focusing on aerosol composition, toxicological exposure, and harm biomarkers. A systematic PubMed search identified 1105 peer-reviewed articles published between January 2017 and October 2024. Studies were screened using validated MeSH terms and commercial brand names. Forty-three articles met inclusion criteria, reporting standardized aerosol characterization, <em>in vivo</em> or <em>in vitro</em> toxicology, or biomarker assessments. Data were extracted by independent reviewers. Clinical studies were categorized by exposure duration (acute, short, medium, or long-term). HTP aerosols contained up to 95 % lower levels of regulated toxicants and exhibited substantially reduced mutagenic, toxic, genotoxic, carcinogenic, and proinflammatory activities (85–95 % reduction) compared with TC smoke. Among 24 interventional clinical studies, 20 reported 40–97 % reductions in toxicant biomarkers of exposure (BoE)—including tobacco-specific nitrosamines, carboxyhemoglobin, volatile organic compounds, and mutagenic metabolites—among smokers who switched completely to HTPs. These reductions were observed from minutes to 24 months and occurred largely independently of systemic nicotine concentrations. Four independent studies reported no significant improvement or detected adverse effects. International health authorities acknowledge that HTP aerosols contain carcinogenic and mutagenic constituents, albeit at substantially lower concentrations than TC smoke, suggesting a potential—though unconfirmed—risk reduction. Overall, HTP users experience lower toxicant exposure than TC smokers; however, additional independent, long-term investigations are required to determine the actual health impact of sustained HTP use.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102209"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077717","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":"Methotrexate toxicity due to a medication dispensing error compounded by an interaction with proton pump inhibitors","authors":"Ankita Chakrabarti ,&nbsp;Murlidhar Pamarthi ,&nbsp;Raman Bansal ,&nbsp;Sankha Shubhra Chakrabarti ,&nbsp;Upinder Kaur","doi":"10.1016/j.toxrep.2026.102281","DOIUrl":"10.1016/j.toxrep.2026.102281","url":null,"abstract":"<div><div>Methotrexate at a low weekly dose is used for immunomodulation in autoimmune conditions such as rheumatoid arthritis and psoriasis. With an elimination half-life of a few hours, the drug is primarily cleared through the renal route. Elimination of the drug is delayed in the presence of polypharmacy or deranged renal function. Here, we present a case of a 55-year-old lady who was on chronic once-weekly methotrexate therapy for rheumatoid arthritis. A recent change in the branded generic formulation of methotrexate by her pharmacist led to confusion with another prescription medication she was receiving (duloxetine), as the packaging resembled each other. As a result, she accidentally consumed methotrexate tablets (5 mg) for 6 consecutive days. This resulted in severe mucositis and moderate hematological changes, necessitating hospitalization. The patient recovered significantly with the use of intravenous fluid support, folinic acid, and alkaline diuresis. However, measurable higher levels of methotrexate were detectable in her serum for ten days after her last dose. In retrospect, the possibility of a pharmacokinetic interaction with a concurrent proton pump inhibitor was suspected. Our case also highlights the complications resulting from dispensing errors for drugs with a narrow margin of safety, especially in a less educated population.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102281"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148167734","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":"Can in silico models predict drug-induced cardiac risk in vulnerable populations?","authors":"Paula Dominguez-Gomez ,&nbsp;Pablo Gonzalez-Martin ,&nbsp;Laura Baldo-Canut ,&nbsp;Eva Casoni ,&nbsp;Ani Amar ,&nbsp;Jose M. Pozo ,&nbsp;Constantine Butakoff ,&nbsp;Mariano Vazquez ,&nbsp;Jazmin Aguado-Sierra","doi":"10.1016/j.toxrep.2025.102179","DOIUrl":"10.1016/j.toxrep.2025.102179","url":null,"abstract":"<div><div>This study evaluates virtual cardiac populations for preclinical assessment of drug-induced QT interval prolongation and arrhythmic risk. Traditional predictions often rely on small, healthy cohorts, excluding vulnerable populations. Using computational models of realistic heart anatomies and electrophysiology, we generated a virtual cohort of 512 subjects across healthy and diseased hearts (heart failure, dilated and hypertrophic cardiomyopathy, ischaemia, and myocardial infarction). We assessed QT prolongation and arrhythmic events following administration of moxifloxacin (benchmark antibiotic) and contraindicated drugs including quinidine, bepridil, and flecainide.</div><div>Patients with heart failure, hypertrophic and dilated cardiomyopathy showed greater QT prolongation to moxifloxacin, unlike ischaemia and myocardial infarction, which resembled healthy subjects. Females exhibited consistently higher QT prolongation than males. Contraindicated drugs markedly increased arrhythmia risk in populations with heart failure, dilated and hypertrophic cardiomyopathy, and ischaemia, frequently leading to lethal arrhythmias such as Torsades des Pointes or ventricular fibrillation, particularly in females.</div><div>These findings demonstrate that computational models capture variability in drug response across pathologies and sexes, offering a predictive framework for preclinical safety evaluations and supporting safer, more personalized drug development strategies.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102179"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145738700","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":"Concomitant food intake markedly alters plasma glutamic acid kinetics after oral monosodium glutamate administration in rats: Relevance to dietary safety evaluation","authors":"Ryosei Sakai,&nbsp;Risa Motoi,&nbsp;Yusuke Amino,&nbsp;Kohsuke Hayamizu","doi":"10.1016/j.toxrep.2025.102191","DOIUrl":"10.1016/j.toxrep.2025.102191","url":null,"abstract":"<div><h3>Background</h3><div>Monosodium glutamate (MSG) is widely used as a flavor enhancer and has been evaluated as safe by international authorities. However, some toxicological studies have employed oral bolus dosing of MSG without food, an approach that is unlikely to reflect physiological dietary exposure.</div></div><div><h3>Objectives</h3><div>To determine how concomitant food intake modifies plasma glutamic acid kinetics following oral MSG administration in rats, thereby improving the interpretation of toxicological data.</div></div><div><h3>Methods</h3><div>Male Wistar rats received graded oral doses of MSG (150, 300, or 600 mg/kg) with or without a liquid diet (Sustagen®). Plasma glutamic acid concentrations were measured by LC-MS/MS, and pharmacokinetic parameters were determined.</div></div><div><h3>Results</h3><div>Bolus MSG administration alone caused rapid, dose-dependent increases in plasma glutamic acid, with peak concentrations occurring 20–30 min post-dose. Co-administration of Sustagen® markedly reduced both C_max and AUC and also delayed T_max, indicating that food intake substantially attenuated systemic glutamic acid exposure.</div></div><div><h3>Conclusions</h3><div>Concomitant food intake profoundly alters plasma glutamic acid kinetics after oral MSG administration in rats. These findings emphasize the importance of considering realistic dietary exposure conditions when interpreting toxicological studies of MSG and related glutamate salts and underscore the need for physiologically relevant dosing regimens.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102191"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926065","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}