International Journal of Toxicology最新文献_第3页

Safety Assessment of Glucosamine Ingredients as Used in Cosmetics. 化妆品中氨基葡萄糖成分的安全性评价。

IF 1 4区医学

International Journal of Toxicology Pub Date : 2026-02-01 Epub Date: 2026-02-27 DOI: 10.1177/10915818261425571

Priya Ferguson, Wilma F Bergfeld, Donald V Belsito, David E Cohen, Curtis D Klaassen, Daniel C Liebler, Allan E Rettie, David Ross, Lisa A Peterson, Ronald C Shank, Thomas J Slaga, Paul W Snyder, Susan C Tilton, Monice M Fiume, Bart Heldreth

引用次数: 0

5-Methoxy-N,N-Dimethyltryptamine: Functional Safety Pharmacology and Video-EEG Assessment of a Short-Acting Serotonergic Psychedelic in Beagle Canines. 5-甲氧基- n， n -二甲基色胺：短效5-羟色胺能致幻剂对比格犬的功能安全性、药理学和视频脑电图评估。

IF 1 4区医学

International Journal of Toxicology Pub Date : 2026-01-31 DOI: 10.1177/10915818261419429

Amir Lotfi, Samantha Sparapani, Mylene Pouliot, Yifei Zhong, Stephen Montgomery, Simon Authier

{"title":"5-Methoxy-N,N-Dimethyltryptamine: Functional Safety Pharmacology and Video-EEG Assessment of a Short-Acting Serotonergic Psychedelic in Beagle Canines.","authors":"Amir Lotfi, Samantha Sparapani, Mylene Pouliot, Yifei Zhong, Stephen Montgomery, Simon Authier","doi":"10.1177/10915818261419429","DOIUrl":"https://doi.org/10.1177/10915818261419429","url":null,"abstract":"5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a serotonin receptor agonist, in clinical development for the treatment of major depression and other psychiatric disorders. A critical safety concern for serotonergic compounds is their potential to induce seizures, as a severe manifestation of serotonin toxicity. The objective of this study was to evaluate the seizure liability of 5-MeO-DMT in a canine model. Beagle dogs (n = 8) were surgically instrumented for continuous telemetric recording of electroencephalography (EEG) and electromyography (EMG), coupled with behavioral video monitoring. Following a baseline period, animals were intranasally administered with control vehicle or escalating doses of 5-MeO-DMT (0.5, 1.0, and 1.5 mg/kg/day), once daily for nine consecutive days. Plasma samples for determination of pharmacokinetic parameters were collected from a satellite group (n = 3). Intranasal administration of 5-MeO-DMT resulted in centrally mediated and dose-dependent behavioral signs, such as head shaking, salivation, repetitive movements, dilated pupils, increased muscle tone, and tremors. A majority of these signs had a rapid onset and offset, which correlated with the peak plasma levels and resolved within 1 hour post-dose, and they were consistent with serotonergic agonism of 5-MeO-DMT. The continuous EEG recording revealed no evidence of seizures or epileptiform discharges at any dose levels throughout the study. In a canine model, considered sensitive to serotonergic drug-induced seizures, daily intranasal administration of escalating doses of 5-MeO-DMT did not induce seizures or epileptiform activity, even at doses causing significant physiological signs of serotonergic stimulation. These results provide robust critical safety information for a low seizure liability of 5-MeO-DMT.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"10915818261419429"},"PeriodicalIF":1.0,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146092742","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}

引用次数: 0

Preclinical Safety Evaluation of BB106, a Novel Ketamine-Sulfobutylether-Beta-Cyclodextrin Salt, Following Subcutaneous Administration in Rats and Göttingen Minipigs. 新型氯胺酮-磺基丁醚- β -环糊精盐BB106大鼠和Göttingen迷你猪皮下给药的临床前安全性评价

IF 1 4区医学

International Journal of Toxicology Pub Date : 2026-01-20 DOI: 10.1177/10915818251414705

Yuval Ramot, Isabella Andreini, Giuseppe Sacco, Jeffrey Becker, Kevin Bruhn, Rosa Anna Manno, Abraham Nyska

{"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":"https://doi.org/10.1177/10915818251414705","url":null,"abstract":"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.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"10915818251414705"},"PeriodicalIF":1.0,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Subchronic Toxicity and Teratogenicity Studies of Mycoprotein From Fusarium compactum MM-135 in Rats. 压缩镰刀菌MM-135真菌蛋白对大鼠的亚慢性毒性和致畸性研究。

IF 1 4区医学

International Journal of Toxicology Pub Date : 2026-01-09 DOI: 10.1177/10915818251415522

Yibo Xian, Junli Liu, Luqin Yin, Xi Liu, Zebin Wu, Zhenhui Sun, Yuli Sun, Xinyu Hong, Xianzhi Jiang, Lingzhi Tian

{"title":"Subchronic Toxicity and Teratogenicity Studies of Mycoprotein From Fusarium compactum 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":"Traditional food production systems are constrained by limited arable land, climate change, and environmental pressures, necessitating the exploration of alternative protein sources. Mycoprotein from Fusarium compactum (F. compactum) 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 F. compactum 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 F. compactum 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.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"10915818251415522"},"PeriodicalIF":1.0,"publicationDate":"2026-01-09","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}

引用次数: 0

Methylglyoxal Aggregates α-Synuclein by Inhibiting SIRT1-Hif-1α in Intestinal Enteroendocrine Cells. 甲基乙二醛通过抑制小肠内分泌细胞SIRT1-Hif-1α聚集α-突触核蛋白。

IF 1 4区医学

International Journal of Toxicology Pub Date : 2026-01-01 Epub Date: 2025-09-13 DOI: 10.1177/10915818251378724

Eugene Huh, Jin Myeong Kim, Seong Hye Kim, Yujin Choi, Myoung Gyu Park, Myung Sook Oh

{"title":"Methylglyoxal Aggregates α-Synuclein by Inhibiting SIRT1-Hif-1α in Intestinal Enteroendocrine Cells.","authors":"Eugene Huh, Jin Myeong Kim, Seong Hye Kim, Yujin Choi, Myoung Gyu Park, Myung Sook Oh","doi":"10.1177/10915818251378724","DOIUrl":"10.1177/10915818251378724","url":null,"abstract":"Parkinson's disease (PD) is characterized by the abnormal aggregation of α-synuclein, which can originate in the gut and propagate to the brain. Recent evidence suggests a correlation between metabolic disorders, particularly diabetes, and PD pathogenesis through the gut-brain axis. Methylglyoxal (MGO), a glucose-derived metabolite produced by gut bacteria such as Proteus mirabilis, is implicated in protein misfolding and glycation. This study investigated whether MGO induced α-synuclein aggregation in intestinal enteroendocrine cells and explored the underlying mechanisms. Mouse enteroendocrine STC-1 cells were treated with MGO (0.01-1 mM) for 36 h, and changes in α-synuclein aggregation, neuronal markers, and relevant signaling pathways were assessed. MGO at 1 mM significantly reduced cell viability and neuronal marker expression, and concentrations of 0.1 and 1 mM increased α-synuclein aggregation. MGO also inhibited SIRT1 expression, leading to increased Hif-1α transcription and reduced expression of autophagy-related proteins Beclin1 and LC3B. These changes were accompanied by mitochondrial dysfunction, as evidenced by decreased Bcl2, increased cytochrome C expression, and reduced levels of the antioxidant factor HO-1. Our findings provide the first evidence that MGO directly induces α-synuclein aggregation in enteroendocrine cells via the SIRT1-Hif-1α-autophagy pathway dysregulation, establishing a potential mechanistic link between gut microbiome-derived metabolites and PD pathogenesis. These results suggest that intestinal glycation may be a critical target for preventing α-synuclein pathology originating in the gut.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"22-28"},"PeriodicalIF":1.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145053665","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}

引用次数: 0

Incidence of Spontaneous and Urethane-Induced Tumors in a 26-Week Carcinogenicity Study in Tg.rasH2 Mice Sourced From CLEA, Japan. 在一项为期26周的Tg致癌性研究中，自发性和聚氨酯诱导肿瘤的发生率。rasH2小鼠来自日本CLEA。

IF 1 4区医学

International Journal of Toxicology Pub Date : 2026-01-01 Epub Date: 2025-09-27 DOI: 10.1177/10915818251380554

Madhav Paranjpe, Amod Kale, Narendra Deshmukh, Chhaya Magar, Prashant Nalge, Dhrupal Patel

引用次数: 0

Editor's Note. 编者按。

IF 1 4区医学

International Journal of Toxicology Pub Date : 2026-01-01 Epub Date: 2025-12-23 DOI: 10.1177/10915818251409932

引用次数: 0

Incidence of Neoplasms and Selected Non-Neoplastic Findings in Control and Positive Control Groups in CByB6F1-Tg(HRAS)2Jic Hemizygous (rasH2^TM) Mouse Carcinogenicity Studies. CByB6F1-Tg(HRAS)2Jic半合子（rasH2TM）小鼠致癌性研究中对照组和阳性对照组肿瘤发生率和部分非肿瘤发现

IF 1 4区医学

International Journal of Toxicology Pub Date : 2026-01-01 Epub Date: 2025-09-27 DOI: 10.1177/10915818251382087

Mark A Morse, Kimberly L Bonnette, Timothy W Carlson, Bridget S Lewis

{"title":"Incidence of Neoplasms and Selected Non-Neoplastic Findings in Control and Positive Control Groups in CByB6F1-Tg(HRAS)2Jic Hemizygous (rasH2TM) Mouse Carcinogenicity Studies.","authors":"Mark A Morse, Kimberly L Bonnette, Timothy W Carlson, Bridget S Lewis","doi":"10.1177/10915818251382087","DOIUrl":"10.1177/10915818251382087","url":null,"abstract":"The rasH2TM mouse model has become the primary alternative to a 2-year mouse carcinogenicity study in safety testing of human pharmaceuticals. In this publication, we present the neoplastic incidence for 2291 control males, 2191 control females, 575 MNU-treated males, 559 MNU-treated females, and 210 urethane-treated males and females in rasH2TM carcinogenicity studies conducted from 2012 to 2024 as well as survival, body weights, and selected non-neoplastic microscopic findings for control and positive control mice. Inclusion of a positive control group is recommended to ensure regulatory acceptance. Survival of controls at the end of 26 weeks was approximately 96% with similar percentages of survivors in the 13-week urethane-treated positive controls in contrast to a survival percentage of approximately 17% in MNU-treated positive controls. Malignant neoplasms accounted for most early deaths in control and positive control mice. Major neoplasms in control mice included Harderian gland adenomas, bronchioloalveolar adenomas and carcinomas, and splenic hemangiosarcomas, while the predominant neoplasms in MNU-treated mice included squamous cell papillomas and carcinomas of the nonglandular stomach and malignant lymphomas. The percentage of urethane-treated mice developing bronchioloalveolar neoplasms was over 98% in both sexes. When compared to control mice, MNU-treated mice had lower mean body weights while urethane-treated mice had higher mean body weights. Major non-neoplastic findings in control mice were subcapsular cell hyperplasia (51.78% to 89.41%) and skeletal muscle myopathy (77.17% to 80.71%). Other non-neoplastic findings included retinal degeneration in MNU-treated mice (∼87% in both sexes) and bronchioloalveolar hyperplasia in urethane-treated mice (≥53% in both sexes).","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"40-59"},"PeriodicalIF":1.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145175297","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}

引用次数: 0

A 1-Month Exploratory Combination Safety and Toxicity Study of Co-Administration of Sitagliptin and Telmisartan in Male Wistar Han Rats. 西格列汀与替米沙坦在雄性Wistar Han大鼠1个月联合用药安全性及毒性的探索性研究。

IF 1 4区医学

International Journal of Toxicology Pub Date : 2026-01-01 Epub Date: 2025-08-30 DOI: 10.1177/10915818251374566

Chitrang R Shah, Sandip B Patel, Vishal J Patel, Hardikkumar H Savsani, Amit A Joharapurkar, Urvit P Patel, Jitendra H Patel, Ramchandra K Ranvir, Rajesh Sundar, Mukul R Jain

{"title":"A 1-Month Exploratory Combination Safety and Toxicity Study of Co-Administration of Sitagliptin and Telmisartan in Male Wistar Han Rats.","authors":"Chitrang R Shah, Sandip B Patel, Vishal J Patel, Hardikkumar H Savsani, Amit A Joharapurkar, Urvit P Patel, Jitendra H Patel, Ramchandra K Ranvir, Rajesh Sundar, Mukul R Jain","doi":"10.1177/10915818251374566","DOIUrl":"10.1177/10915818251374566","url":null,"abstract":"Diabetes and hypertension often coexist and need complex pharmacological management. Sitagliptin, a dipeptidyl peptidase-4 inhibitor, is widely used for glycemic control, and telmisartan, an angiotensin II receptor blocker, is the preferred treatment for hypertension. Thus, we have conducted a 1-month exploratory combination safety and toxicity study in male Wistar Han rats. Animals were administered 100 mg/kg/day of sitagliptin or telmisartan individually, or in combination by oral gavage. We have evaluated effects on body weight, feed intake, clinical chemistry, and hematology parameters, and microscopic examination of liver, kidney, adrenal glands, heart, lungs, lymphatic organs, and gastrointestinal tract. The combination showed a decrease in body weight gain, feed intake, hematocrit, reticulocytes, WBCs, serum triglycerides, AST, total protein, globulin, and heart weight, and increased serum levels of urea, phosphorous, magnesium, potassium, and kidney weight. Co-administration showed an additive effect on decrease in WBC counts, potentiating the effects on decreased serum triglycerides and increased phosphorous levels and kidney weights, and a synergistic effect on serum AST levels. Sitagliptin attenuated the changes caused by telmisartan on reticulocyte counts, serum creatinine levels, and liver and thymus weights. Administration of the individual compounds caused a reduction in spleen weight, though the combination had no effect. Sitagliptin, telmisartan, or combination dosing showed no significant organ toxicity upon histopathological examination. It appears that co-administration of telmisartan and sitagliptin is well tolerated in rats. Three-month toxicity studies, in both genders, with full toxicokinetic profiling and thorough tissue examination, will be necessary to support the combination's toxicity profile.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"29-39"},"PeriodicalIF":1.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954187","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}

引用次数: 0

Direct Comparison of the Impacts of Bisphenol A, Bisphenol F, and Bisphenol S in a Male Rat 28-Day Oral Exposure Study. 双酚A、双酚F和双酚S在雄性大鼠28天口服暴露研究中的直接比较

IF 1 4区医学

International Journal of Toxicology Pub Date : 2026-01-01 Epub Date: 2025-09-18 DOI: 10.1177/10915818251378990

Guillaume Pelletier, Gen Sheng Wang, Adam Wawrzynczak, Marc Rigden, Rocio Aranda-Rodriguez, Don Caldwell

{"title":"Direct Comparison of the Impacts of Bisphenol A, Bisphenol F, and Bisphenol S in a Male Rat 28-Day Oral Exposure Study.","authors":"Guillaume Pelletier, Gen Sheng Wang, Adam Wawrzynczak, Marc Rigden, Rocio Aranda-Rodriguez, Don Caldwell","doi":"10.1177/10915818251378990","DOIUrl":"10.1177/10915818251378990","url":null,"abstract":"Although Bisphenol A (BPA) is still used in consumer products, concerns about its toxicity led to the adoption of structurally related replacement products such as Bisphenol F (BPF) and Bisphenol S (BPS). Unfortunately, comparing the biological responses to BPA and BPA substitutes in vivo can be challenging, as the available information is often derived from different studies using various animal strains and experimental protocols. To address this issue, we directly compared the impacts of BPA, BPF, and BPS in the same in vivo exposure study. Briefly, 8-week-old male Fischer rats were exposed to BPA, BPF, or BPS (at five different doses) and to 17α-ethinylestradiol (positive control for estrogenicity) by gavage for 28 consecutive days. Rat health, dietary intakes, and weight gains were monitored, 24-hour urine samples were collected, and blood and tissues were harvested at the terminal necropsy. The impacts of BPA, BPF, and BPS on rat weight gains, organ weights and histology, liver enzymatic activities, hematology, clinical chemistry, and serum hormone levels were relatively modest and mostly limited to the highest doses administered. However, bisphenol cross-contamination observed in urine samples from the vehicle control group may have interfered with the evaluation of their effects at lower doses. Although BPA, BPF, and BPS exposures all shared similarities with the 17α-ethinylestradiol positive control group, their impacts on serum hormone levels and endocrine-responsive tissues also presented noticeable differences. This suggests that BPA, BPF, and BPS may interfere with endocrine functions through slightly different molecular mechanisms.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"4-21"},"PeriodicalIF":1.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12783379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086110","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}

引用次数: 0