International Journal of Toxicology最新文献_第9页

Safety Assessment of Tetrasodium Glutamate Diacetate and Beta-Alanine Diacetic Acid as Used in Cosmetics. 化妆品用谷氨酸四钠和丙氨酸四钠的安全性评价。

IF 1 4区医学

International Journal of Toxicology Pub Date : 2025-12-01 Epub Date: 2025-10-17 DOI: 10.1177/10915818251344597

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 Anhydrogalactose, Anhydroglucitol, Anhydroxylitol, Arabinose, Psicose, Saccharide Hydrolysate, and Saccharide Isomerate as Used in Cosmetics. 化妆品中使用的无水半乳糖、无水葡萄糖醇、无水糖醇、阿拉伯糖、糖、糖水解物和糖异构物的安全性评价。

IF 1 4区医学

International Journal of Toxicology Pub Date : 2025-12-01 Epub Date: 2025-11-16 DOI: 10.1177/10915818251384580

Wilbur Johnson, 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 Saccharum officinarum (Sugarcane)-Derived Ingredients as Used in Cosmetics. 化妆品用甘蔗衍生成分的安全性评价。

IF 1 4区医学

International Journal of Toxicology Pub Date : 2025-12-01 Epub Date: 2025-11-16 DOI: 10.1177/10915818251384589

Priya Ferguson, Wilma F Bergfeld, Donald V Belsito, David E Cohen, Curtis D Klaassen, Daniel C Liebler, 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 1.3 4区医学

International Journal of Toxicology Pub Date : 2025-11-01 Epub 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":"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":"443-450"},"PeriodicalIF":1.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12589665/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Comprehensive Toxicological Safety Evaluation of Anaerostipes caccae. 厌氧菌疫苗的毒理学安全性综合评价。

IF 1.3 4区医学

International Journal of Toxicology Pub Date : 2025-11-01 Epub Date: 2025-08-29 DOI: 10.1177/10915818251367353

Vickie Modica, Róbert Glávits, Amy Clewell, John R Endres, Gábor Hirka, Adél Vértesi, Erzsébet Béres, Ilona Pasics Szakonyiné

{"title":"A Comprehensive Toxicological Safety Evaluation of Anaerostipes caccae.","authors":"Vickie Modica, Róbert Glávits, Amy Clewell, John R Endres, Gábor Hirka, Adél Vértesi, Erzsébet Béres, Ilona Pasics Szakonyiné","doi":"10.1177/10915818251367353","DOIUrl":"10.1177/10915818251367353","url":null,"abstract":"Anaerostipes caccae CLB101 (CLB101) is an obligate, anaerobic bacteria that was isolated from the stool of a healthy infant. Due to its ability to produce butyrate and its potential promotion of microbiome health through multiple homeostatic interactions there is interest in its consumption by humans. No toxicity data are publicly available for any strain of A. caccae. Therefore, its genotoxic and toxicological potential was investigated in the current study. Due to its anaerobic nature, a genotoxicity evaluation was performed using the in vivo comet assay and the in vivo mammalian micronucleus assay, which found no evidence of clastogenicity or aneugenicity. General toxicity and potential target organs were assessed in a 90-day, repeated-dose, oral toxicity study using 0, 250, 500, and 1000 mg/kg bw/day in Wistar rats. CLB101 exposure did not result in adverse effects in male or female rats when evaluated for clinical signs, body weight, food consumption, clinical pathology, organ weight, and histopathology after administration, at any dose. Therefore, a NOAEL of 1000 mg/kg bw/day, equivalent to 1.9 × 1011 CFU/kg bw/day for all cells and, based on ∼32% cell viability in the buffer used (Mitsuoka), ∼6.1 × 1010 CFU/kg bw/d for living cells.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"471-487"},"PeriodicalIF":1.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954223","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

Evaluation of Repeat Dose Toxicity and Embryo-Fetal Developmental Toxicity of Novel Glucokinase Activator ZYGK1 in Wistar Rats. 新型葡萄糖激酶激活剂ZYGK1对Wistar大鼠重复剂量毒性及胚胎-胎儿发育毒性评价。

IF 1.3 4区医学

International Journal of Toxicology Pub Date : 2025-11-01 Epub Date: 2025-06-27 DOI: 10.1177/10915818251353718

Kalpesh Patani, Sudhir Patel, Amit Joharapurkar, Rajesh Sundar, Mukul Jain

{"title":"Evaluation of Repeat Dose Toxicity and Embryo-Fetal Developmental Toxicity of Novel Glucokinase Activator ZYGK1 in Wistar Rats.","authors":"Kalpesh Patani, Sudhir Patel, Amit Joharapurkar, Rajesh Sundar, Mukul Jain","doi":"10.1177/10915818251353718","DOIUrl":"10.1177/10915818251353718","url":null,"abstract":"ZYGK1 is a novel small molecule glucokinase (GK) activator. The purpose of this study was to assess the repeated dose toxicity of ZYGK1 in male and female Wistar rats and its effect on pregnancy and embryo-fetal development in pregnant female Wistar rats. ZYGK1 was administered by oral gavage to rats at 15, 30, 60, and 120 mg/kg, once a day, for 28 consecutive days. For studying the effect on pregnancy and embryo-fetal development, ZYGK1 was administered by oral gavage at 60 and 120 mg/kg from gestation day (GD) 6 to 15, to presumed pregnant female Wistar rats. Hypoglycemia was observed at all doses of ZYGK1 in male and female rats in the general toxicity study, but no toxic effects were observed, except partially reversible axonal degeneration in peripheral nerves. ZYGK1 treatment in pregnant female rats caused hypoglycemia and decreased the fetal body weight. Treatment from GD 6 to 15 caused no significant fetal abnormalities, except incidental fetal skeleton anomalies. Thus, ZYGK1 may lead to maternal hypoglycemia, but no significant developmental toxicity was observed.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"458-470"},"PeriodicalIF":1.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505677","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

Mitochondria: Key Mediator for Environmental Toxicant-Induced Neurodegeneration. 线粒体：环境毒物诱导的神经变性的关键媒介。

IF 1.3 4区医学

International Journal of Toxicology Pub Date : 2025-11-01 Epub Date: 2025-08-28 DOI: 10.1177/10915818251369414

Nishi Shah, Bhagawati Saxena, Richa Gupta

{"title":"Mitochondria: Key Mediator for Environmental Toxicant-Induced Neurodegeneration.","authors":"Nishi Shah, Bhagawati Saxena, Richa Gupta","doi":"10.1177/10915818251369414","DOIUrl":"10.1177/10915818251369414","url":null,"abstract":"Compiling evidence strongly suggests the involvement of environmental toxicants, including heavy metals (aluminum, arsenic, lead, copper, cadmium, mercury, and manganese), pesticides, and solvents, as the prime culprits of neurodegenerative disorders, including Alzheimer's disease and Parkinson's disease. The pathogenesis of environmental toxicant-induced neurodegenerative disease remains elusive. Studies carried out in the last decade suggest that dysfunctional mitochondria are increasingly recognized as a key factor in the progression of neurodegenerative diseases. Mitochondria, the essential organelles that regulate cellular energy production, are particularly vital in neurons, which have high energy demands and depend on proper mitochondrial function for survival. Environmental toxicants have been shown to impair mitochondrial membranes, disrupt the electron transport chain, increase oxidative stress, and damage mitochondrial DNA, leading to progressive neurodegeneration, with mitochondrial fragmentation and oxidative stress that worsens neurodegeneration. There are currently no disease-modifying treatments available for most neurodegenerative disorders, largely due to the lack of suitable molecular targets. Targeting mitochondria presents a rational strategy for neuroprotective therapy, with the potential to slow or halt disease progression. In view of this, this review highlights the central role of mitochondria in environmental toxicant-induced neurodegeneration, emphasizing how environmental exposures drive mitochondrial dysfunction and accelerate disease progression. Understanding these mechanisms is crucial for identifying environmental risk factors and developing targeted interventions. This will provide a foundation for future research targeting mitochondria and developing suitable therapeutic interventions for neurodegenerative diseases.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"507-525"},"PeriodicalIF":1.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954210","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

Evaluation of Plasma Polyethylene Glycol (PEG) Levels in a Healthy Adult Population. 健康成人血浆聚乙二醇（PEG）水平的评价

IF 1.3 4区医学

International Journal of Toxicology Pub Date : 2025-11-01 Epub Date: 2025-09-07 DOI: 10.1177/10915818251371966

Klaus Kubesch, Christian Lubich, Daniel Mascher, Srilatha Tangada, Peter L Turecek

{"title":"Evaluation of Plasma Polyethylene Glycol (PEG) Levels in a Healthy Adult Population.","authors":"Klaus Kubesch, Christian Lubich, Daniel Mascher, Srilatha Tangada, Peter L Turecek","doi":"10.1177/10915818251371966","DOIUrl":"10.1177/10915818251371966","url":null,"abstract":"Polyethylene glycols (PEGs) are amphiphilic polymers that are used extensively in consumer products and PEGylated biotherapeutics. Although PEGs are considered biologically inert with a low toxicity, anti-PEG antibodies have been detected in patients receiving treatment with PEGylated biotherapeutics as well as in healthy individuals. Despite continual exposure in daily life, the prevalence of PEGs within the general population remains unclear. This study aimed to evaluate a healthy population for the presence of PEGs. A validated enzyme-linked immunosorbent assay (ELISA) platform was used to analyze 200 plasma samples from healthy adults for the presence of PEGs. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was also used to analyze the samples for the presence of four PEG analytes: PEG3350; PEG4000; PEG10000; and PEG2ru20K COOH, a 20 kDa PEG used to modify therapeutic proteins. The detection limit for PEG3350 calculated by extrapolation with linear regression was assumed to be 3.60 ng/mL. PEG levels above the lower limit of quantification (LLOQ) (21.6 ng/mL) were detected in 41 plasma samples, range 22.1-43.9 ng/mL, using the ELISA platform. None of the samples were found to contain detectable levels of PEG4000, PEG10000, or PEG2ru20K COOH. Following extrapolation, PEG3350 levels above the LLOQ (3.60 ng/mL) were detected in 154 plasma samples, range 3.69-46.0 ng/mL. Using an ELISA platform and HPLC-MS/MS analysis, PEGs were detected in the plasma of 77.4% of healthy adults. The findings are suggestive that expanding worldwide exposure to PEGs may have resulted in a much higher incidence of detectable plasma burdens of PEG than was previously realized.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"451-457"},"PeriodicalIF":1.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12589669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015368","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

Integrin αvβ3 Antagonist Ameliorates Atherosclerotic Progression by Reducing Platelet Hyperactivation. 整合素αvβ3拮抗剂通过降低血小板过度活化改善动脉粥样硬化进展。

IF 1.3 4区医学

International Journal of Toxicology Pub Date : 2025-11-01 Epub Date: 2025-09-08 DOI: 10.1177/10915818251375887

Mengyun Xu, Xurui Zhang, Feng Qi, Jihong Zou, Cheng Xiao, Guangsheng Cai, Xiaojuan Pan

{"title":"Integrin αvβ3 Antagonist Ameliorates Atherosclerotic Progression by Reducing Platelet Hyperactivation.","authors":"Mengyun Xu, Xurui Zhang, Feng Qi, Jihong Zou, Cheng Xiao, Guangsheng Cai, Xiaojuan Pan","doi":"10.1177/10915818251375887","DOIUrl":"10.1177/10915818251375887","url":null,"abstract":"Platelet hyperactivation represents a significant risk factor for atherosclerotic cardiovascular diseases. This study investigated the expression and functional roles of integrin αvβ3 and (Multimerin 1) MMRN1 in platelets from atherosclerotic conditions and evaluated the therapeutic potential of integrin αvβ3 antagonism in atherosclerotic progression. We examined the expression patterns of αvβ3 and MMRN1 in platelets from healthy controls, patients with coronary heart disease (CHD), and patients with acute myocardial infarction (AMI) using qRT-PCR and ELISA techniques. The correlation between αvβ3 and MMRN1 expression levels with platelet counts and aggregation was analyzed. Additionally, we established a mouse model of atherosclerosis to investigate the effects of an αvβ3 antagonist (SB273005) and MMRN1 knockdown on platelet activation and atherosclerosis progression. Our findings revealed positive correlations between MMRN1 and αvβ3 expression levels with both platelet counts and aggregation. Notably, elevated platelet counts and aggregation observed in CHD and AMI patient samples were effectively reduced by the αvβ3 antagonist treatment. Furthermore, both αvβ3 antagonist treatment and MMRN1 knockdown significantly ameliorated disease severity in the mouse atherosclerosis model. These results demonstrate that upregulation of αvβ3 integrin and MMRN1 contributes to platelet hyperactivation in atherosclerotic vascular diseases, and targeting the αvβ3/MMRN1 axis may serve as a promising intervention strategy for the clinical management of atherosclerotic vascular diseases.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"488-498"},"PeriodicalIF":1.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023285","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

Validating and Using Cardiac NAMs for Toxicity Screening and Drug Development. 心脏名称在毒性筛选和药物开发中的验证和使用。

IF 1.3 4区医学

International Journal of Toxicology Pub Date : 2025-11-01 Epub Date: 2025-09-09 DOI: 10.1177/10915818251375348

Jennifer Beck Pierson, Anthony Bahinski, Brian Berridge, Daniel Bramham, Todd Bourcier, Khuram W Chaudhary, Sandy Eldridge, Yasunari Kanda, William B Mattes, Jessica Oliphant, Li Pang, Alex Savtchenko, Jeffery Siegel, Natalie Simpson, Chengyi Tu, Ronald Wange, Joseph C Wu, Xi Yang

{"title":"Validating and Using Cardiac NAMs for Toxicity Screening and Drug Development.","authors":"Jennifer Beck Pierson, Anthony Bahinski, Brian Berridge, Daniel Bramham, Todd Bourcier, Khuram W Chaudhary, Sandy Eldridge, Yasunari Kanda, William B Mattes, Jessica Oliphant, Li Pang, Alex Savtchenko, Jeffery Siegel, Natalie Simpson, Chengyi Tu, Ronald Wange, Joseph C Wu, Xi Yang","doi":"10.1177/10915818251375348","DOIUrl":"10.1177/10915818251375348","url":null,"abstract":"Technological advances and the desire to reduce dependence on animal models have brought human-relevant models to the forefront of drug development. This paradigm shift is leveraging the advances in in vitro systems and new approach methodologies (NAMs), which was the focus of a workshop convened by the Health and Environmental Sciences Institute (HESI) in May 2024. Highlights included discussions on predicting cardiac failure modes and the utility of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), microfluidic systems like BioFlux™, and engineered heart tissues in enhancing early-stage drug safety assessments. Regulatory perspectives underscored the challenges and potential for integrating NAMs into submissions, advocating for standardized reporting and validation protocols. Case studies where NAMs offered superior predictivity compared to traditional methods are emerging and offer insights into a roadmap forward. However, there remains a need for collaboration among academia, industry, and regulatory bodies to ensure robust validation and adoption. These efforts aim to refine cardiovascular drug discovery, reduce attrition rates, and accelerate the transition toward more ethical and efficient preclinical testing paradigms.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"499-506"},"PeriodicalIF":1.3,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029755","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