International Journal of Toxicology最新文献_第8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 1.3 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

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 1.3 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

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

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

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

Thank you to our ad hoc reviewers! 感谢我们的特别审稿人！

IF 1 4区医学

International Journal of Toxicology Pub Date : 2025-12-18 DOI: 10.1177/10915818251407133

引用次数: 0

Amended Safety Assessment of Silicates as Used in Cosmetics. 修订了化妆品用硅酸盐的安全性评价。

IF 1 4区医学

International Journal of Toxicology Pub Date : 2025-12-01 Epub Date: 2025-10-21 DOI: 10.1177/10915818251375461

Christina L Burnett, Wilma F Bergfeld, Donald V Belsito, David E Cohen, Curtis D Klaassen, Daniel C Liebler, James G Marks, Lisa A Peterson, Ronald C Shank, Thomas J Slaga, Paul W Snyder, Monice M Fiume, Bart Heldreth

引用次数: 0

Amended Safety Assessment of Salicylic Acid and Salicylates as Used in Cosmetics. 修订水杨酸和水杨酸盐在化妆品中的安全性评估。

IF 1 4区医学

International Journal of Toxicology Pub Date : 2025-12-01 Epub Date: 2025-11-16 DOI: 10.1177/10915818251389456

Wilbur Johnson, Jinqiu Zhu, Wilma F Bergfeld, Donald V Belsito, Ronald A Hill, Curtis D Klaassen, Daniel C Liebler, James G Marks, Ronald C Shank, Thomas J Slaga, Paul W Snyder, Monice M Fiume, Bart Heldreth

引用次数: 0