International Journal of Toxicology最新文献

{"title":"Safety Assessment of Radish Root - Derived Ingredients as Used in Cosmetics.","authors":"Preethi S Raj, Wilma F Bergfeld, Donald V Belsito, David E Cohen, Curtis D Klaassen, Daniel C Liebler, Lisa A Peterson, Allan E Rettie, David Ross, Ronald C Shank, Thomas J Slaga, Paul W Snyder, Susan C Tilton, Monice M Fiume, Bart Heldreth","doi":"10.1177/10915818261455269","DOIUrl":"10.1177/10915818261455269","url":null,"abstract":"<p><p>The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 7 radish root-derived ingredients, most of which are reported to function as hair and skin conditioning agents in cosmetic products. Because final product formulations may contain multiple botanicals, each containing similar constituents of concern, formulators are advised to be aware of these constituents and to avoid reaching levels that may be hazardous to consumers. With radish root-derived ingredients, the Panel was concerned about the presence of anthocyanins and isothiocyanates in cosmetics. Industry should use current good manufacturing practices to minimize impurities that could be present in botanical ingredients. The Panel reviewed the available data and concluded that these ingredients are safe in cosmetics in the present practices of use and concentration described in this safety assessment when formulated to be non-sensitizing.</p>","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"112S-123S"},"PeriodicalIF":1.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148360737","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":"Subchronic Toxicity and Teratogenicity Studies of Mycoprotein From <i>Fusarium compactum</i> MM-135 in Rats.","authors":"Yibo Xian, Junli Liu, Luqin Yin, Xi Liu, Zebin Wu, Zhenhui Sun, Yuli Sun, Xinyu Hong, Xianzhi Jiang, Lingzhi Tian","doi":"10.1177/10915818251415522","DOIUrl":"10.1177/10915818251415522","url":null,"abstract":"<p><p>Traditional food production systems are constrained by limited arable land, climate change, and environmental pressures, necessitating the exploration of alternative protein sources. Mycoprotein from <i>Fusarium compactum</i> (<i>F. compactum</i>) MM-135 has shown promise due to its balanced amino acid profile, high dietary fiber, and low-fat content. Previous studies, including a 14-day dietary exposure study, have shown safety at high doses up to 150,000 ppm. This study further evaluated the subchronic toxicity and teratogenicity of mycoprotein from <i>F. compactum</i> MM-135, testing higher doses than previously reported. In the 90-day oral toxicity study, rats were fed diets containing 50,000, 100,000, or 200,000 ppm of mycoprotein with no adverse effects. The NOAEL was 200,000 ppm (15.26 g/kg/day in males and 16.20 g/kg/day in females). In the teratogenic study, pregnant rats were exposed to the same doses from gestation days 6 to 15. No adverse effects on maternal pregnancy or fetal development were observed, with an NOAEL of 200,000 ppm (16.53 g/kg/day). These results confirm that mycoprotein from <i>F. compactum</i> MM-135 is safe at the tested dose of 200,000 ppm, exceeding the safety threshold established in prior studies, and support its potential as a sustainable alternative protein source.</p>","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"362-377"},"PeriodicalIF":1.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145944017","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":"Pair-Feeding Differentiates Feed-Dependent and Pharmacodynamic Effects of Telmisartan in Wistar Rats.","authors":"Chitrang R Shah, Sandip B Patel, Vishal J Patel, Maulik Patel, Amit A Joharapurkar, Urvit P Patel, Jitendra H Patel, Shekhar B Kadam, Ramchandra K Ranvir, Rajesh Sundar, Mukul R Jain","doi":"10.1177/10915818261429056","DOIUrl":"10.1177/10915818261429056","url":null,"abstract":"<p><p>Telmisartan, an angiotensin II receptor blocker with partial PPAR-γ agonist activity, exhibits pleiotropic effects beyond its antihypertensive action, including modulation of lipid metabolism, erythropoiesis, and renal function. However, its anorexigenic properties complicate interpretation of systemic outcomes in toxicology studies. This study employed a pair-feeding design to differentiate feed-dependent effects from direct pharmacodynamic actions in male Wistar rats treated with telmisartan (100 mg/kg/day) for 28 days. Both telmisartan and pair-fed groups showed reduced body weight and hepatic triglyceride levels, confirming feed-dependent metabolic effects. In contrast, telmisartan-specific changes included suppression of erythroid indices; reduced serum triglycerides; elevated urea, creatinine, potassium, and inorganic phosphate levels; and mild gastric submucosal inflammation, none of which were observed in pair-fed controls. These findings demonstrate that telmisartan's hematological, renal, and lipid-lowering effects are feed-independent and mechanistically distinct from caloric restriction.</p>","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"330-338"},"PeriodicalIF":1.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147305980","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":"Corrigendum to Subchronic Toxicity and Teratogenicity Studies of Mycoprotein From <i>Fusarium compactum</i> MM-135 in Rats.","authors":"","doi":"10.1177/10915818261444880","DOIUrl":"10.1177/10915818261444880","url":null,"abstract":"","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"391"},"PeriodicalIF":1.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837626","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":"Aldose Reductase Inhibitor, Epalrestat, Suppresses Colorectal Cancer Cell Proliferation Through Complement-Dependent Cytotoxicity.","authors":"Dongxu Peng, Zhengsheng Yi, Yidan Chen, Yanxia Xu, Nan Zhang, Liping Zheng, Zhuocheng He","doi":"10.1177/10915818261465349","DOIUrl":"https://doi.org/10.1177/10915818261465349","url":null,"abstract":"<p><p>Complement-dependent cytotoxicity (CDC) is critical for tumor cell proliferation. Previous work has revealed that epalrestat (EPA), an inhibitor of aldose reductase, plays a crucial role in tumor cell proliferation. However, whether CDC is involved in EPA-mediated inhibition of cancer cell proliferation remains unclear. This study evaluates reactive oxygen species (ROS) levels, 5-ethynyl-2'-deoxyuridine (EdU) incorporation, and Cell Counting Kit-8 assay to determine the effect of EPA on cell proliferation in colorectal cancer cells. Quantitative real-time PCR, immunoblotting, rescue experiments combined with luciferase reporter assay, and chromatin immunoprecipitation (ChIP) assay were performed to explore the mechanism of EPA on CDC. In the present study, we observed that EPA significantly downregulates cell proliferation characterized by enhanced ROS levels and reduced EdU⁺ positive cells, which was attributed to the decreased CD46 expression. Ectopic CD46 expression reversed the above EPA-induced phenomenon. Mechanistically, EPA treatment suppressed protein kinase D (PKD)/signal transducer and activator of transcription 3 (STAT3) phosphorylation, leading to reduce the binding ability of STAT3 to the CD46 promoter, further attenuating CD46 transactivation. Activation of PKD by phorbol 12-myristate 13-acetate largely blocked the effect of EPA-mediated CD46 transactivation. Together, the current findings revealed a novel mechanism whereby EPA modulates CDC to inhibit the proliferation of cancer cells, broadening the pharmacological functions of EPA in anti-tumor therapy.</p>","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"10915818261465349"},"PeriodicalIF":1.3,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148351911","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":"Nonclinical Safety Profiles of mRNA Therapeutics Comprising Unmodified or N1-Methyl-Pseudouridine-Modified Nucleosides Are Similar Following Repeated Administration.","authors":"Albena Draycheva, Joske Millecam, Ebru Caba","doi":"10.1177/10915818261446630","DOIUrl":"https://doi.org/10.1177/10915818261446630","url":null,"abstract":"<p><p>mRNA, either with unmodified or modified nucleosides, has become an important modality in medicines and vaccines. Despite the inclusion of N1-methyl-pseudouridine (N1mѰ)-modified mRNA in approved coronavirus 2019 (COVID-19) vaccines and the various ongoing clinical studies with both N1mѰ-modified and unmodified mRNA therapeutics, there are limited nonclinical data directly comparing unmodified and N1mѰ-modified mRNA safety and tolerability. Here we present data from a repeat-dose toxicity study in Wistar Han rats, which were intramuscularly administered mRNA (either with unmodified or N1mѰ-modified nucleosides) encapsulated into lipid nanoparticles (LNPs). The study evaluated systemic toxicity, local tolerance, and immune responses after once-weekly intramuscular injections for 3 weeks, followed by a final injection 2 weeks later. Additionally, a subgroup of animals was maintained for a 2-week dose-free period following the last dose to assess recovery from any findings. Repeat IM administration of unmodified and N1mѰ-modified mRNA rabies vaccine to male and female Wistar Han rats was well tolerated at doses of 10 μg and 40 μg, with similar non-adverse findings irrespective of the test article used, confirming that the N1mѰ nucleoside modification does not impact the nonclinical safety of mRNA when encapsulated into the same LNP. As the field of RNA medicines evolves and matures, the ability to use existing knowledge of unmodified or N1mѰ-modified mRNA to support mRNA therapeutic development in a nonclinical safety context will allow for a more streamlined and rapid process when developing or improving mRNA therapeutics.</p>","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"10915818261446630"},"PeriodicalIF":1.3,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148277340","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":"Evaluation of the <i>in vitro</i> Toxicity of Novel Oxime Acetylcholinesterase Reactivators.","authors":"Janice E Chambers","doi":"10.1177/10915818261431761","DOIUrl":"10.1177/10915818261431761","url":null,"abstract":"<p><p>War and terrorism demonstrate the need for an improved antidote against nerve agents that cause brain damage following inhibition of acetylcholinesterase (AChE). Our laboratories invented substituted phenoxyalkyl pyridinium oxime AChE reactivators (US patent 9,227,937) that demonstrate the ability to cross the blood-brain barrier in <i>in vivo</i> rat tests with a sarin surrogate by reducing time to cessation of seizure-like behaviors, glial fibrillary acidic protein levels, and neuropathology, compared to the FDA-approved oxime, 2-pyridine aldoxime methyl chloride (2-PAM). This study investigated the safety profile of novel oximes through evaluation of their cytotoxicity and genotoxicity. Cytotoxicity was evaluated in mouse areolar fibroblasts using a lactate dehydrogenase (LDH) assay and an MTS assay. All novel oximes showed no toxicity in the LDH assay from 1.25 nM to 5 mM, whereas 2-PAM did; novel oximes were significantly different from 2-PAM (<i>P</i> < .00001). The MTS assay demonstrated that novel oximes at 2 µM to 500 µM significantly reduced the metabolic activity of fibroblasts compared to 2-PAM (<i>P</i> = .00001). A modified Ames assay using 5 bacterial strains with and without S9 assessed the genotoxicity of the lead compound, Oxime 20, at concentrations from 100 µM to 10 mM. No concentration, whether with S9 or without, showed any genotoxicity. The LDH and Ames results indicated no cytotoxicity or genotoxicity was caused by the novel oximes.</p>","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"10915818261431761"},"PeriodicalIF":1.3,"publicationDate":"2026-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148251450","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":"Investigating the Impact of Bisphenol A on Gastric Cancer Through Network Toxicology and Molecular Docking.","authors":"Wen-Yan Yu, Yue Zhang","doi":"10.1177/10915818261451203","DOIUrl":"10.1177/10915818261451203","url":null,"abstract":"<p><p>The extensive application of bisphenol A (BPA), an endocrine-disrupting substance in polymer-based products and consumer commodities, has sparked concerns over its carcinogenic potential. However, the molecular mechanisms underlying BPA-induced gastric carcinogenesis remain poorly understood. We used network toxicology and molecular docking analysis to uncover the pivotal targets and mechanisms underlying BPA-associated gastric carcinogenesis. Potential BPA-related targets and differentially expressed genes in gastric cancer (GC) were collected from publicly available databases to identify hub genes. A prognostic risk assessment model utilizing hub genes, with molecular docking simulations, was performed to confirm the binding interactions between BPA and target proteins. A total of 27 potential targets associated with both BPA exposure and GC were identified. The protein-protein interaction network analysis revealed 19 hub genes, with core targets including MMP9, ADRB2, PTGS1, SLC6A4, ERBB2, MAPT, AR, SLC6A3, CNR1, PDE5A, DRD2, KCNH2, MC4R, CALCR, CHRM1, ADRB3, CXCR2, MMP1, and SHBG. Enrichment analysis demonstrated these hub genes were significantly involved in neuroactive ligand-receptor interaction, calcium signaling pathway, cGMP-PKG signaling pathway, and chemical carcinogenesis-receptor activation pathways. Prognostic analysis identified six hub genes (CALCR, ADRB3, CNR1, HRH2, KCNH2, and AR) significantly associated with patient survival. Molecular docking simulations demonstrated robust interaction affinities of BPA with the identified core target proteins. This study reveals that BPA may influence GC development and progression through multiple targets and signaling pathways, particularly involving G protein-coupled receptor signaling, hormone regulation, and neurological pathways.</p>","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"10915818261451203"},"PeriodicalIF":1.0,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147941343","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":"Microplastics: A Narrative Review on Modes of Exposure and Impact on Human Health.","authors":"Sandhya Jinesh, Rajan Radhakrishnan","doi":"10.1177/10915818251392140","DOIUrl":"10.1177/10915818251392140","url":null,"abstract":"<p><p>BackgroundPlastics have been widely used for several decades, but their persistence in the environment has resulted in the widespread presence of microplastics (MPs) in the air, water, and soil. With particle sizes smaller than 5 mm, MPs are now recognized as emerging contaminants of concern owing to their potential impact on human health.ObjectiveThis study aimed to conduct a critical narrative umbrella review of published reviews and primary studies on microplastic exposure and human health. Specifically, the objective was to synthesize evidence across the major exposure pathways (ingestion, inhalation, and dermal), summarize the associated health outcomes, and critically appraise common themes, inconsistencies, and knowledge gaps. This review provides guidance for future research and policy directions by aligning findings with methodological strengths and limitations.ResultsMPs are consistently detected in food, water, air, human stool, blood, placenta, and breast milk. Reported outcomes include gastrointestinal inflammation, gut microbiota disruption, respiratory diseases, endocrine and reproductive dysfunction, and possible neurotoxicity. Inhalation is increasingly recognized as significant, and ingestion remains the most studied, whereas dermal exposure is underexplored.ConclusionMicroplastics represent a pervasive and complex public health challenge. This umbrella review underscores the need for harmonized methodologies, epidemiological investigations, and mechanistic studies that reflect real-world exposure. Strengthening this evidence base is essential for risk assessment, regulation, and public awareness of the health impacts of microplastics.</p>","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"287-302"},"PeriodicalIF":1.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145426543","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":"Preclinical Safety Evaluation of BB106, a Novel Ketamine-Sulfobutylether-Beta-Cyclodextrin Salt, Following Subcutaneous Administration in Rats and Göttingen Minipigs.","authors":"Yuval Ramot, Isabella Andreini, Giuseppe Sacco, Jeffrey Becker, Kevin Bruhn, Rosa Anna Manno, Abraham Nyska","doi":"10.1177/10915818251414705","DOIUrl":"10.1177/10915818251414705","url":null,"abstract":"<p><p>BackgroundConventional ketamine hydrochloride solutions are acidic and hyperosmotic, limiting their tolerability for subcutaneous (SC) delivery. BB106 is a novel ketamine formulation using the multitude of sulfobutylether-beta-cyclodextrin (SBECD) anionic substitutions as ionic counterions to achieve a new ketamine-SBECD salt in solution at near-physiologic pH and isotonicity, thereby enabling SC administration. To support its development for pain and neuropsychiatric indications, we conducted nonclinical toxicology studies in rats and minipigs.MethodsA 2-week repeated-dose SC injection study in rats and a 4-week continuous SC infusion study in Göttingen minipigs were performed, each with a 2-week recovery phase. Assessments included clinical observations, body weights, food consumption, ophthalmology, electrocardiography, clinical pathology, toxicokinetics (TK), and histopathology.ResultsBB106 was well-tolerated in both species. No mortality or dose-limiting systemic toxicity occurred. Clinical signs were consistent with ketamine pharmacology (eg, transient ataxia) and resolved after dosing. Local site reactions were minimal, histologically mild, and reversible. No treatment-related lesions were observed in any of the systemic tissues examined (including liver, kidney, bladder, and brain). TK analyses confirmed consistent systemic exposure without accumulation. SBECD itself produced no adverse effects at the exposure levels tested.ConclusionRepeated SC bolus injections in rats and continuous SC infusion in minipigs demonstrated favorable local and systemic safety profiles for BB106. These findings support its feasibility as an alternative to intravenous ketamine for pain and psychiatric disorders. To our knowledge, this is the first toxicology report of SC administration of an SBECD salt formulation and the results support continued consideration as a potential medicine.</p>","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"232-246"},"PeriodicalIF":1.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146010323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}