International Journal of Toxicology最新文献

Isobutane, Isopentane, Butane, and Propane. 异丁烷、异戊烷、丁烷和丙烷。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2025-02-01 Epub Date: 2024-06-14 DOI: 10.1177/10915818241260280

Regina Tucker, Wilma F Bergfeld, Donald V Belsito, David E Cohen, Curtis D Klaassen, Allan E Rettie, David Ross, Thomas J Slaga, Paul W Snyder, Susan Tilton, Monice Fiume, Bart Heldreth

引用次数: 0

Safety Assessment of Mannitol, Sorbitol, and Xylitol as Used in Cosmetics. 化妆品中使用的甘露醇、山梨醇和木糖醇的安全性评估。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2025-02-01 Epub Date: 2024-11-18 DOI: 10.1177/10915818241297097

Priya Cherian, Wilma F Bergfeld, Donald V Belsito, Curtis D Klaassen, Daniel C Liebler, James G Marks, Lisa A Peterson, Ronald C Shank, Thomas J Slaga, Paul W Snyder, Monice Fiume, Bart Heldreth

引用次数: 0

Safety Assessment of Ascorbyl Glucoside and Sodium Ascorbyl Glucoside as Used in Cosmetics. 化妆品中使用的抗坏血酸葡萄糖苷和抗坏血酸葡萄糖苷钠的安全性评估。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2025-02-01 Epub Date: 2024-11-08 DOI: 10.1177/10915818241297075

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

引用次数: 0

Safety Assessment of Wheat-Derived Ingredients as Used in Cosmetics. 化妆品中使用的小麦提取成分的安全性评估。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2025-02-01 Epub Date: 2024-11-08 DOI: 10.1177/10915818241294063

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 Fiume, Bart Heldreth

引用次数: 0

Safety Assessment of Triphenyl Phosphate as Used in Cosmetics. 化妆品中使用的磷酸三苯酯的安全性评估。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2025-02-01 Epub Date: 2024-06-14 DOI: 10.1177/10915818241259692

Christina L Burnett, 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 Fiume, Bart Heldreth

引用次数: 0

Safety Assessment of Soy-Derived Ingredients as Used in Cosmetics. 化妆品中使用的大豆成分安全评估。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2025-02-01 Epub Date: 2024-02-11 DOI: 10.1177/10915818241231249

Priya Cherian, Wilma F Bergfeld, Donald V Belsito, Curtis D Klaassen, Daniel C Liebler, James G Marks, Lisa A Peterson, Ronald C Shank, Thomas J Slaga, Paul W Snyder, Monice Fiume, Bart Heldreth

引用次数: 0

Safety Assessment of Alkyl Amide MIPA Ingredients as Used in Cosmetics. 化妆品中使用的烷基酰胺 MIPA 成分的安全性评估。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2025-02-01 Epub Date: 2024-11-06 DOI: 10.1177/10915818241297089

Alice Akinsulie, Wilma F Bergfeld, Donald V Belsito, Curtis D Klaassen, Daniel C Liebler, James G Marks, Lisa A Peterson, Ronald C Shank, Thomas J Slaga, Paul W Snyder, Monice Fiume, Bart Heldreth

引用次数: 0

Mechanisms of Apoptosis and Pulmonary Fibrosis Resulting From Sulfur Mustard-Induced Acute Pulmonary Injury in Rats.

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2025-01-31 DOI: 10.1177/10915818251315907

Xiaoxuan Hu, Na Zhang, Yuxu Zhong, Tao Liu, Xiaoji Zhu

{"title":"Mechanisms of Apoptosis and Pulmonary Fibrosis Resulting From Sulfur Mustard-Induced Acute Pulmonary Injury in Rats.","authors":"Xiaoxuan Hu, Na Zhang, Yuxu Zhong, Tao Liu, Xiaoji Zhu","doi":"10.1177/10915818251315907","DOIUrl":"https://doi.org/10.1177/10915818251315907","url":null,"abstract":"Sulfur mustard (SM) is a highly toxic bifunctional alkylating agent that inflicts severe damage on the respiratory tract. Although numerous studies have examined the mechanisms underlying SM-induced pulmonary injury, the exact pathways involved remain unclear. This study aims to investigate an acute pulmonary injury model, with SM administered as a single intraperitoneal injection (8 mg/kg) or single intratracheal instillation (2 mg/kg) at equal toxicity doses (1LD50). The results revealed that epithelial cells in the alveolar septa of the intraperitoneal SM group exhibited a significantly higher expression of apoptotic markers, including pro-apoptotic protein Bax, caspase-3, and caspase-9 proteins, than those in the tracheal SM group. Conversely, the expression of the anti-apoptotic protein Bcl-2 was significantly lower in the intraperitoneal SM group than in the tracheal SM group, as confirmed by TUNEL staining and immunohistochemical staining. The intraperitoneal SM group exhibited markedly higher expression of fibrosis-related proteins, including MMP-2, MMP-9, TIMP-1, TIMP-2, collagen type I, collagen type III, TGF-β1, and Smad7, than the tracheal SM group. These markers, detected through immunohistochemical immunolabeling, indicate a more significant fibrotic response in the intraperitoneal group. In summary, this study demonstrates that intraperitoneal exposure to SM results in increased apoptosis, elevated expression of pro-apoptotic proteins, and fibrosis-related proteins in the alveolar epithelial cells compared with intratracheal exposure, even at equivalent toxicity levels. Our findings highlight the suitability of the intraperitoneal route for further investigation and identify apoptotic and fibrosis-related proteins as potential targets for intervention in SM-induced pulmonary injury.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"10915818251315907"},"PeriodicalIF":1.2,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070819","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

The Nonclinical Safety Assessment of a Novel Anti-CEACAM5 Antibody Exatecan Conjugate Predicts a Low Risk for Interstitial Lung Disease (ILD) in Patients-The Putative Mechanism Behind ILD. 新型抗ceacam5抗体Exatecan偶联物的非临床安全性评估预测间质性肺疾病（ILD）患者的低风险- ILD背后的推测机制

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2025-01-04 DOI: 10.1177/10915818241306039

Willem N Sloot, Elisa Bertotti, Manuela Onidi, Andrea Paoletti, Ilse De Salve, Patrizia Tavano, Enrico Vigna, Gundi Mueller

{"title":"The Nonclinical Safety Assessment of a Novel Anti-CEACAM5 Antibody Exatecan Conjugate Predicts a Low Risk for Interstitial Lung Disease (ILD) in Patients-The Putative Mechanism Behind ILD.","authors":"Willem N Sloot, Elisa Bertotti, Manuela Onidi, Andrea Paoletti, Ilse De Salve, Patrizia Tavano, Enrico Vigna, Gundi Mueller","doi":"10.1177/10915818241306039","DOIUrl":"https://doi.org/10.1177/10915818241306039","url":null,"abstract":"The therapeutic window of antibody drug-conjugates (ADC) remains challenging due to safety issues such as interstitial lung disease (ILD) observed with specific deruxtecan-based ADCs. To avoid ILD, we designed M9140 by conjugating the maleimide-containing hydrophilic β-glucuronide linker to exatecan and our anti-CEACAM5 (CarcinoEmbryonic Antigen-related Cell Adhesion Molecule 5) specific antibody. Following repeated iv-infusion at 3 to 30 mg/kg of M9140 every 3 weeks, the pathological findings obtained in cynomolgus monkeys were confined to gastrointestinal and hematolymphoid tissues and resembled the toxicity of exatecan. At 24 mg/kg or higher, transient reductions in neutrophil and reticulocyte counts were observed with each dosing event along with reversible anemia throughout the study. The no observed adverse effect level was 24 mg/kg and the maximum tolerated dose was 30 mg/kg. The difference in toxicity by this small dose increment was correlated with a 2.5-fold difference in plasma exatecan exposure indicating antigen-independent toxicity. As anticipated, no lung toxicity was found with M9140 in these studies that were similar in study design to those used to confirm ILD with trastuzumab-deruxtecan in monkeys. Since the non-human primate model is regarded as predictive for the ILD risk in humans, this result indicates a low risk for ILD when applying M9140 to patients. The current M9140 safety data are discussed with special focus on the absence or presence of ILD with other antibody camptothecin-conjugates, for which a hypothetical pathogenic mechanism is postulated here. The favorable nonclinical profile of M9140 warrants further investigation in patients with CEACAM5-overexpressing tumors.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"10915818241306039"},"PeriodicalIF":1.2,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926988","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

Are Repeat-Dose Toxicity Studies Informative for Safety Assessment of Vaccine Candidates? A Survey of Vaccine Developers. 重复剂量毒性研究是否有助于候选疫苗的安全性评估？疫苗开发人员调查。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2025-01-01 Epub Date: 2024-10-30 DOI: 10.1177/10915818241293371

Cynthia M Rohde, Eric Destexhe, Jan Willem van der Laan, Sarah Gould, Rachel Coe, Bert Haenen

{"title":"Are Repeat-Dose Toxicity Studies Informative for Safety Assessment of Vaccine Candidates? A Survey of Vaccine Developers.","authors":"Cynthia M Rohde, Eric Destexhe, Jan Willem van der Laan, Sarah Gould, Rachel Coe, Bert Haenen","doi":"10.1177/10915818241293371","DOIUrl":"10.1177/10915818241293371","url":null,"abstract":"A BioSafe-sponsored survey investigated how vaccine companies (n = 12) perceive the value of the repeat-dose toxicity studies for safety assessment of vaccine candidates. As all major vaccine developers were part of the survey, it was considered representative for the industry practices up to 2022. Vaccine developers indicated that they see scientific value in performing repeat-dose toxicity studies with vaccines, especially when novel components (e.g., adjuvant) or technology is being used. However, a few (3/12) also indicated that repeat-dose toxicity studies could be replaced by a pharmacology study with additional toxicity parameters. For the majority of companies (9/12), findings from the repeat-dose toxicity studies never prevented or postponed a first-in-human (FIH) trial. In the remaining 3 companies, a total of 4 occurrences of postponement or prevention of clinical development occurred and in only 2 of these cases was the finding considered related to the vaccine. A platform approach has been successfully implemented for influenza vaccines already in 2016, and an outline of the regulatory requirements for a platform approach has been recently documented in the latest infectious disease mRNA-LNP vaccine guideline, as well as in the guidance on the development and licensure of COVID-19 vaccines presented by the FDA. Vaccine developers are seeking to extend this platform approach to the development of new vaccines, building on established technologies and using well-defined manufacturing processes. This approach could support reduction of animal use (a principle of 3Rs) while still providing reassurance of the nonclinical safety of these products.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"3-11"},"PeriodicalIF":1.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545417","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