International Journal of Toxicology最新文献_第4页

Safety Assessment of Vanilla as Used in Cosmetics. 化妆品中香草的安全性评价。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2025-08-01 Epub Date: 2025-07-17 DOI: 10.1177/10915818251342563

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 M Fiume, Bart Heldreth

{"title":"Safety Assessment of Vanilla as Used in Cosmetics.","authors":"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 M Fiume, Bart Heldreth","doi":"10.1177/10915818251342563","DOIUrl":"10.1177/10915818251342563","url":null,"abstract":"The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of 9 vanilla-derived ingredients as used in cosmetics. These ingredients are reported to function mostly as skin conditioning agents in cosmetic products. Because final product formulations may contain multiple botanicals, each containing the same constituents of concern, formulators are advised to be aware of these constituents, and to avoid reaching levels that may be hazardous to consumers. Industry should continue to use good manufacturing practices to limit impurities. The Panel reviewed data relating to the safety of these ingredients and concluded that 7 ingredients are safe in cosmetics in the present practices of use and concentration when formulated to be non-sensitizing. The Panel further concluded that the available data are insufficient to make a determination of safety under the intended conditions of use in cosmetic formulations for Vanilla Planifolia Flower Extract and Vanilla Planifolia Leaf Cell Extract.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":"44 2_suppl","pages":"19S-37S"},"PeriodicalIF":1.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649440","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

Safety Assessment of Basic Brown 17 as Used in Cosmetics. 碱性棕17在化妆品中的安全性评价。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2025-08-01 Epub Date: 2025-07-17 DOI: 10.1177/10915818251342555

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

Safety Assessment of Scutellaria baicalensis-Derived Ingredients as Used in Cosmetics. 化妆品中黄芩衍生成分的安全性评价。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2025-08-01 Epub Date: 2025-07-17 DOI: 10.1177/10915818251350378

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 M Fiume, Bart Heldreth

引用次数: 0

Preclinical Safety of APG777, A Novel Extended Half-Life Anti-Interleukin-13 Monoclonal Antibody, in Cynomolgus Monkeys. 新型延长半衰期抗白细胞介素-13单克隆抗体APG777在食蟹猴中的临床前安全性

IF 1 4区医学

International Journal of Toxicology Pub Date : 2025-07-30 DOI: 10.1177/10915818251355584

Daniel Rubio, Eric Zhu, Archie Thurston, Kathleen A Funk, Kristina A York, Carl L Dambkowski, Drew Badger

{"title":"Preclinical Safety of APG777, A Novel Extended Half-Life Anti-Interleukin-13 Monoclonal Antibody, in Cynomolgus Monkeys.","authors":"Daniel Rubio, Eric Zhu, Archie Thurston, Kathleen A Funk, Kristina A York, Carl L Dambkowski, Drew Badger","doi":"10.1177/10915818251355584","DOIUrl":"https://doi.org/10.1177/10915818251355584","url":null,"abstract":"Interleukin-13 (IL-13) is a cytokine implicated in the pathophysiology of type 2 inflammatory diseases and is a clinically validated target in atopic dermatitis. APG777 is a humanized IgG1 monoclonal antibody with an optimized pharmacokinetic profile. APG777 has high affinity to IL-13 and includes a triple amino acid modification (the \"YTE\" modification) in its Fc region that is designed to extend its half-life. The current study examined the safety and potential toxicity of APG777 when given by once-weekly subcutaneous injection for 27 weeks to cynomolgus monkeys, and the potential reversibility of any findings following a 2-month recovery period. Toxicokinetic characteristics of APG777 were also determined. APG777 exhibited dose-proportional systemic exposure, with a half-life of approximately 28 days. No APG777-related adverse effects were noted in clinical observations, body weight, ophthalmology, electrocardiogram readings, neurologic parameters, hematology, coagulation, clinical chemistry, urinalysis, organ weights, or histopathology. Anti-drug antibodies were not detected in any APG777-exposed animals. Drug accumulation was evident over the study duration; however, there were no APG777-related adverse findings in any of the parameters analyzed. The no-observed-adverse-effect level (NOAEL) was 150 mg/kg/week. These findings provide preclinical evidence supporting continued clinical development of APG777 for IL-13-mediated diseases. The extended half-life of APG777 suggests potential benefits in reducing dosing frequency compared with existing IL-13-targeting therapies, which could improve treatment adherence and patient outcomes. The safety and efficacy of APG777 are currently being investigated in a Phase 2 clinical trial (NCT06395948) in patients with moderate-to-severe atopic dermatitis.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"10915818251355584"},"PeriodicalIF":1.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753328","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 Commentary: Looking Back and Looking Sideways. 评论：回顾与展望。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2025-07-01 Epub Date: 2025-04-09 DOI: 10.1177/10915818251328037

Anthony Dayan, Peter Pressman, Thomas Blackburn, Norbert Kaminski, Samuel Cohen, A Wallace Hayes

引用次数: 0

Safety Evaluation of N-trans-caffeoyltyramine Derived From a Strain of Yarrowia lipolytica Through Precision Fermentation. 一株解脂耶氏菌精发酵n -反式咖啡乙胺的安全性评价。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2025-07-01 Epub Date: 2025-05-07 DOI: 10.1177/10915818251338788

Sungwon Lee, Srinivas Seekallu, Suresh Babu Venkataramaiah, Chandrashekar Mataguru Doreswamy, Mohan Cheluru Umesh, Sandeep Malleshappa, Sajeev Justin Dev, Ganadhal Puttaramaiah Chethankumara, Nagaraju Lohith, Gajanan Rajpal Deshmukh, Brian Premkumar, Brinda Mahadevan

{"title":"Safety Evaluation of N-trans-caffeoyltyramine Derived From a Strain of Yarrowia lipolytica Through Precision Fermentation.","authors":"Sungwon Lee, Srinivas Seekallu, Suresh Babu Venkataramaiah, Chandrashekar Mataguru Doreswamy, Mohan Cheluru Umesh, Sandeep Malleshappa, Sajeev Justin Dev, Ganadhal Puttaramaiah Chethankumara, Nagaraju Lohith, Gajanan Rajpal Deshmukh, Brian Premkumar, Brinda Mahadevan","doi":"10.1177/10915818251338788","DOIUrl":"10.1177/10915818251338788","url":null,"abstract":"N-trans-caffeoyltyramine (NCT) is a phenolic hydroxycinnamic acid amide naturally present in many plant crop species and is associated with immune response and many development processes. Little research has been done on the potential safety of NCT for use as an ingredient in conventional foods and beverages. This study assessed the safety of NCT derived from caffeic acid and produced using a genetically engineered strain Yarrowia lipolytica strain 3599_7 via precision fermentation through in vitro genotoxicity assays and a 90-day dietary oral toxicity study in rats. The Ames test was performed in bacterial strains and the highest dose tested was 5000.0 μg/plate in the presence and absence of S9. The in vitro mammalian micronucleus test was conducted in human peripheral blood lymphocytes in culture exposed to NCT at predetermined concentrations in the absence (4-hour and 24-hour exposure) and presence (4-hour exposure) of S9. NCT was not genotoxic as evident from the Ames and the in vitro micronucleus assay. NCT exhibited no adverse effects in the 90-day oral toxicity study up to the highest dose tested, where the no-observed-adverse-effect level was 1427 and 1983 mg/kg body weight/day in males and females, respectively.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"328-345"},"PeriodicalIF":1.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002778","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

Comparative Analyses of the Influences of Vehicles on Selected Biological Parameters Following Single-Dose Oral Administration in Sprague-Dawley Rats. Sprague-Dawley大鼠单次口服载药对部分生物学参数影响的比较分析。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2025-07-01 Epub Date: 2025-04-22 DOI: 10.1177/10915818251330516

Tae-Woo Kim, Tae-Kyung Kim, Hye-Joon Park, Mu-Jin Lee, Sung-Jin Park, Laehong Jo, Yong-Hoon Lee, Yong-Seok Kim, Byeongwoo Ahn

{"title":"Comparative Analyses of the Influences of Vehicles on Selected Biological Parameters Following Single-Dose Oral Administration in Sprague-Dawley Rats.","authors":"Tae-Woo Kim, Tae-Kyung Kim, Hye-Joon Park, Mu-Jin Lee, Sung-Jin Park, Laehong Jo, Yong-Hoon Lee, Yong-Seok Kim, Byeongwoo Ahn","doi":"10.1177/10915818251330516","DOIUrl":"10.1177/10915818251330516","url":null,"abstract":"Various types of vehicles are used in non-clinical studies to administer treatment substances to experimental animals. It is recognized that these vehicle substances can influence animal physiology to some extent. Studies are designed to minimize the effects of vehicle substances to ensure reliable results. However, research on the biological effects of these vehicles is still inadequate. This study aims to assess the effects of vehicles on selected biological parameters (body weight, food consumpton, water consumption, functional observational battery, clinical pathology, and organ weights) and to establish reference ranges for these parameters to aid in historical control data. A total of 1,528 Sprague-Dawley rats were used in this study, exposed to commonly utilized vehicles such as distilled water, corn oil, dimethyl sulfoxide (DMSO), polyethylene glycol 400, carboxymethyl cellulose, and methyl cellulose via oral dosing at 5 mL/kg body weight per day, consistent with the dosing regimen employed in the toxicity tests included in this study. Significant changes were observed in the red blood cell counts and organ weights with DMSO treatment, whereas other vehicles induced only minor changes. This study highlights the importance of careful vehicle selection in non-clinical trials to eliminate their biological impact.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"259-286"},"PeriodicalIF":1.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002648","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

Effects of Solvent Dimethyl Sulfoxide Invites a Rethink of Its Application in Amyloid Beta Cytotoxicity. 溶剂二甲亚砜的作用引起对其在β淀粉样蛋白细胞毒性中的应用的重新思考。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2025-07-01 Epub Date: 2025-05-15 DOI: 10.1177/10915818251338235

Yanhong Fu, Jiafa Zhang, Canhong Yang, Yuanyuan Wang, Yunzhu Yang, Pingming Qiu, Weibing Xie, Shufen Zhang, Tianming Lǚ

{"title":"Effects of Solvent Dimethyl Sulfoxide Invites a Rethink of Its Application in Amyloid Beta Cytotoxicity.","authors":"Yanhong Fu, Jiafa Zhang, Canhong Yang, Yuanyuan Wang, Yunzhu Yang, Pingming Qiu, Weibing Xie, Shufen Zhang, Tianming Lǚ","doi":"10.1177/10915818251338235","DOIUrl":"10.1177/10915818251338235","url":null,"abstract":"Dimethyl sulfoxide (DMSO) is commonly used as a solvent for preparing amyloid-beta (Aβ) peptides implicated in Alzheimer's disease. While considered relatively non-toxic at low concentrations, DMSO itself may exert biological effects that could confound experimental outcomes, especially for weakly cytotoxic substances like Aβ. Seven brain cell types (BV-2, N2a, SH-SY5Y, U87, neurons, astrocytes, microglia) were treated with varying DMSO concentrations or Aβ1-42 oligomers/protofibrils/fibrils prepared using DMSO. Cell viability was assessed by CCK-8 and LDH assays. Matched DMSO controls were prepared alongside Aβ treatments to delineate solvent effects. Low DMSO concentrations (0.0625-0.015625%) exhibited hormetic cytoprotective and growth-promoting effects, while higher concentrations (≥2%) were cytotoxic. Importantly, these hormetic solvent effects confounded the measurement of Aβ cytotoxicity. By accounting for matched DMSO controls, the study revealed that Aβ fibril toxicity may have been underestimated due to the cytoprotective solvent effects of low DMSO concentrations used in their preparation. In conclusion, DMSO exhibits complex hormetic dose-responses that can significantly influence experimental outcomes, especially for weakly cytotoxic agents like Aβ. Rigorous solvent controls are crucial to delineate genuine substance effects from potential solvent confounds and avoid erroneous interpretations.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"297-313"},"PeriodicalIF":1.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078081","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

Mechanisms of Apoptosis and Pulmonary Fibrosis Resulting From Sulfur Mustard-Induced Acute Pulmonary Injury in Rats. 硫芥致大鼠急性肺损伤的细胞凋亡和肺纤维化机制。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2025-07-01 Epub 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":"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":"314-327"},"PeriodicalIF":1.2,"publicationDate":"2025-07-01","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

Cardiovascular and Pharmacokinetic Profiles of Intravenous Etripamil in Conscious Telemetered Cynomolgus Monkeys. 静脉注射依曲帕米在有意识遥测食蟹猴体内的心血管和药代动力学特征。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2025-07-01 Epub Date: 2025-04-01 DOI: 10.1177/10915818251327963

Alexis Ascah, Jean-Pierre Moreau, Simon Authier, David B Bharucha, Douglas Wight

{"title":"Cardiovascular and Pharmacokinetic Profiles of Intravenous Etripamil in Conscious Telemetered Cynomolgus Monkeys.","authors":"Alexis Ascah, Jean-Pierre Moreau, Simon Authier, David B Bharucha, Douglas Wight","doi":"10.1177/10915818251327963","DOIUrl":"10.1177/10915818251327963","url":null,"abstract":"Paroxysmal supraventricular tachycardia (PSVT) is a common cardiac arrhythmia associated with substantial health care burden. Etripamil, a fast-acting non-dihydropyridine calcium channel blocker developed for intranasal self-administration, is currently under investigation for acute treatment of PSVT episodes. A novel two-phase study design was used to test a series of five doses of intravenous etripamil (0, 0.025, 0.05, 0.15, and 0.3 mg/kg) in conscious cynomolgus monkeys. The cardiovascular effects (e.g., blood pressure and ECG recordings) were assessed during the first phase, and the pharmacokinetic profile was characterized during the second phase. Animals were dosed remotely to avoid the stress of intranasal dosing and minimize the impact of dose administration on measurements. Results were compared with findings from subsequent intranasal studies in cynomolgus monkeys and humans. Etripamil decreased systolic blood pressure and increased heart rate proportionately in a dose-dependent manner. Etripamil also induced dose-dependent increases in the PR interval. At a dose of 0.3 mg/kg (the highest dose), the mean highest PR prolongation from baseline during 20 minutes after dosing was 27.38%. Systemic exposure to etripamil increased in a dose-dependent manner. Mean area under the curve from administration to when drug was no longer present (AUC0-∞) values ranged from 179 to 2364 ng • min/mL, peak plasma concentration ranged from 13.2 to 176 ng/mL, and mean half-life ranged from 12.3 to 20.8 minutes (Figure 1). Results were consistent with data from subsequent intranasal preclinical and clinical studies. Intravenous etripamil demonstrated the desired targeted pharmacokinetic and pharmacodynamic profiles in conscious cynomolgus monkeys.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"287-296"},"PeriodicalIF":1.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752711","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