International Journal of Toxicology最新文献

DEHP and Its Metabolite MEHP Alter the Insr and Glut4 Gene Expression by Blunting the Interaction of Transcription Factors in L6 Myotubes.

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2024-12-10 DOI: 10.1177/10915818241305090

Mangala Priya Viswanathan, Vigneswari Mullainadhan, Balasubramanian Karundevi

{"title":"DEHP and Its Metabolite MEHP Alter the Insr and Glut4 Gene Expression by Blunting the Interaction of Transcription Factors in L6 Myotubes.","authors":"Mangala Priya Viswanathan, Vigneswari Mullainadhan, Balasubramanian Karundevi","doi":"10.1177/10915818241305090","DOIUrl":"https://doi.org/10.1177/10915818241305090","url":null,"abstract":"Endocrine-disrupting chemicals (EDCs) play an important role in the incidence of type-2 diabetes. Di-2-ethyl hexyl Phthalate (DEHP) is one of the endocrine-disrupting chemicals used as a plasticizer to impart flexibility and softness to plastic-containing materials. Mono-2-ethylhexyl Phthalate (MEHP), a DEHP's primary metabolite, is preferentially absorbed once metabolized. A previous study from our laboratory showed that DEHP and MEHP altered the key proteins such as insulin receptor (INSR) and glucose transporter-4 (GLUT4) in L6 myotubes. In a sequel to the previous study, the present study hypothesized that DEHP and its metabolite MEHP may alter the Insr and Glut4 gene expression in L6 myotubes. Therefore, to find out the molecular mechanism behind the decreased INSR and GLUT4 protein levels in the previous study, the direct effect of DEHP and its metabolite MEHP in regulating Insr and Glut4 gene transcription in L6 myotubes was studied. The L6 myotubes were exposed to 50 and 100 μM DEHP and MEHP for 24 h, followed by insulin stimulation for 20 min. We observed decreased Insr and Glut4 mRNA levels in DEHP and MEHP-treated groups. Western blot data showed decreased protein levels of MEF2A and MyoD in treated groups. ChIP assay detected a decreased association of MEF2A and MyoD to the Glut4 gene promoter and HMGA1 to the Insr gene promoter. The study revealed that DEHP and MEHP diminished the Insr and Glut4 gene expression through weakened interaction of their transcription factors on the respective promoter.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"10915818241305090"},"PeriodicalIF":1.2,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800583","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

Exploring the Biological Effects of Polystyrene Nanoplastics on Spermatogenesis: Insights From Transcriptomic Analysis in Mouse Spermatocytes.

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2024-12-08 DOI: 10.1177/10915818241305086

Ying Jiang, Kexuan He, Qianyi Shen, Can Yang, Xin Huang, Junjie Fan, Miaomiao Du, Jianrong Wu, Huajuan Ruan, Jun Yang, Yeting Hong

{"title":"Exploring the Biological Effects of Polystyrene Nanoplastics on Spermatogenesis: Insights From Transcriptomic Analysis in Mouse Spermatocytes.","authors":"Ying Jiang, Kexuan He, Qianyi Shen, Can Yang, Xin Huang, Junjie Fan, Miaomiao Du, Jianrong Wu, Huajuan Ruan, Jun Yang, Yeting Hong","doi":"10.1177/10915818241305086","DOIUrl":"https://doi.org/10.1177/10915818241305086","url":null,"abstract":"The presence of polystyrene plastics in the human testis has raised concerns, yet their biological activity remains poorly characterized. This study aimed to investigate the biological effects and potential regulatory genes of polystyrene nanoplastics on spermatocyte line, GC-2spd(ts). After a 24-h exposure to polystyrene nanoplastics, the results indicated cell membrane disruption, impairment of mitochondrial membrane potential, increased levels of reactive oxygen species (ROS), and induced DNA damage. Furthermore, a comprehensive transcriptomic analysis was conducted, revealing differential gene expression patterns in GC-2spd(ts) cells in response to polystyrene nanoplastics. A total of 134 differentially expressed genes (DEGs) were identified, with 48 genes upregulated and 86 genes downregulated. The Gene Ontology analysis highlighted the involvement of these genes in various spermatogenesis-related biological processes, including acrosome reaction, sperm mitochondrial organization, sperm annulus, and outer acrosomal membrane. Subsequently, the quantification of gene expression through qRT-PCR identified five key genes (NSUN7, SEPTIN4, TRIM36, EQTN, and SYT8) screened from the DEGs. In conclusion, this study provides valuable insights into the biological effects of polystyrene nanoplastics on mouse spermatocytes using comprehensive transcriptomic analysis, contributing to the establishment of a foundation for future investigations into these relevant pathways.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"10915818241305086"},"PeriodicalIF":1.2,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794422","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

Editor's note. 编者注

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2024-12-01 Epub Date: 2024-10-03 DOI: 10.1177/10915818241286420

Mary Beth Genter

引用次数: 0

Inclusion of Histopathology in Dose Range-Finding Nonclinical Studies for Inhaled Drug Products. 将组织病理学纳入吸入药物产品的剂量范围探索非临床研究。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2024-12-01 Epub Date: 2024-08-29 DOI: 10.1177/10915818241276439

Emily A Resseguie, Helen Palmer

{"title":"Inclusion of Histopathology in Dose Range-Finding Nonclinical Studies for Inhaled Drug Products.","authors":"Emily A Resseguie, Helen Palmer","doi":"10.1177/10915818241276439","DOIUrl":"10.1177/10915818241276439","url":null,"abstract":"Drug development is a lengthy process that promotes and protects the health and safety of future patients. Nonclinical safety studies follow essentially similar designs that fulfill regulatory requirements but are amended based on factors including the mechanism of action, class of molecule, and route of administration. Clinical observations, clinical pathology, and macroscopic pathology in dose range-finding (DRF) studies generally provide sufficient information to select doses for pivotal studies by most delivery routes. Inhaled drug candidates are recognized for producing adverse effects on the respiratory system at the microscopic level that may otherwise be unpredictable; therefore, unlike other routes of administration, inhalation DRF studies typically include histopathology of the respiratory tract. Histopathology evaluations can add several weeks to the Investigational New Drug (IND) application timeline along with additional costs but have been considered necessary to support accurate dose selection for adequate safety margins, thereby potentially avoiding additional studies and animal usage by ensuring achievement of a NOAEL in the pivotal studies. Therefore, DRF inhalation studies initiated from 2018 to 2021 at Labcorp were reviewed to determine whether inclusion of histopathology on preliminary inhalation studies was necessary for subsequent dose selection. Histopathology findings in the DRF impacted dose selection in pivotal inhalation studies for approximately 45% of rat and dog studies. This review identified histopathology findings in rat and dog that support continued inclusion of respiratory tract histopathology in DRF studies. Future investigations will evaluate potential surrogate endpoints for these findings, which could reduce nonclinical drug development timelines by several weeks.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"540-548"},"PeriodicalIF":1.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142107455","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

Twelfth Triennial Toxicology Salary Survey. 第十二次三年期毒理学薪酬调查。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2024-12-01 Epub Date: 2024-09-26 DOI: 10.1177/10915818241284800

Shayne C Gad, Dexter Sullivan, Danika A Pitts

引用次数: 0

Temperature Is a Key Factor Governing the Toxic Impact of Ultra-Violet Radiation-Emitting Nail Dryers When Used on Human Skin Cells. 温度是影响紫外线辐射指甲干燥器对人类皮肤细胞毒性影响的关键因素

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2024-12-01 Epub Date: 2024-08-03 DOI: 10.1177/10915818241268617

Elijah Finn, Lucia Dussan, Scott Rosenthal, Cynthia Simbulan-Rosenthal, Dean Rosenthal, Peter Sykora

{"title":"Temperature Is a Key Factor Governing the Toxic Impact of Ultra-Violet Radiation-Emitting Nail Dryers When Used on Human Skin Cells.","authors":"Elijah Finn, Lucia Dussan, Scott Rosenthal, Cynthia Simbulan-Rosenthal, Dean Rosenthal, Peter Sykora","doi":"10.1177/10915818241268617","DOIUrl":"10.1177/10915818241268617","url":null,"abstract":"The skin is the largest organ in the body and the only one to come into contact with solar UV radiation (UVR). UVA (320-400 nm) is a significant contributor to UV-related skin damage. The UVA spectrum makes up over 95% of solar-UV energy reaching the earth's surface causing the majority of the visible signs of skin photoaging. Many consumer products also emit UVA, including nail dryers. There have been sporadic reports suggesting that these units may be contributing to skin cancer incidence. This notion was recently bolstered by a finding that nail dryer-irradiated mammalian skin cells develop a mutational signature consistent with UVA exposure. This report was surprising considering the comparatively low level of UVA to which the skin is exposed during nail treatments. In this research, we investigated how UVA-emitting devices caused cytotoxic/genotoxic impact after only low levels of UVA exposure. Our data showed that levels of UVA in the unit are highly variable and location dependent. We confirm previous reports that using prolonged exposure protocols could induce significant levels of DNA damage. It was also determined that UV-induced DNA damage only partially correlated with the level of UVA fluency. On investigation, we found that the unit had a rapid increase in internal temperature when in use. Exposing human cells to these elevated temperatures acted synergistically with UVA to magnify the cytotoxic and genotoxic impact of UV irradiation.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"549-560"},"PeriodicalIF":1.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889226","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

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 : 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

Four-Week GLP Immunotoxicity Assessment of Lactoferrin Alpha Produced by Komagataella phaffii in Sprague-Dawley Rats. 在 Sprague-Dawley 大鼠体内对 Komagataella phaffii 产生的 Alpha 乳铁蛋白进行为期四周的 GLP 免疫毒性评估。

IF 1.2 4区医学

International Journal of Toxicology Pub Date : 2024-11-13 DOI: 10.1177/10915818241299344

Ross Peterson, Robert B Crawford, Lance K Blevins, Norbert E Kaminski, Anthony J Clark, Carrie-Anne Malinczak

{"title":"Four-Week GLP Immunotoxicity Assessment of Lactoferrin Alpha Produced by Komagataella phaffii in Sprague-Dawley Rats.","authors":"Ross Peterson, Robert B Crawford, Lance K Blevins, Norbert E Kaminski, Anthony J Clark, Carrie-Anne Malinczak","doi":"10.1177/10915818241299344","DOIUrl":"https://doi.org/10.1177/10915818241299344","url":null,"abstract":"Oral toxicity and toxicokinetic properties of human lactoferrin (LF) alpha produced in Komagataella phaffii (effera™) were investigated in adult Sprague-Dawley rats over a 28-day period under good laboratory practice conditions. Main study dosing used groups of 10 rats/sex/dose, and a secondary study evaluating toxicokinetic parameters used 6 rats/sex/dose. The vehicle control group received sodium citrate buffer, test groups received daily doses of 200, 600, and 2000 mg of effera™ per kg body weight, and the comparative control group received 2000 mg bovine LF (bLF)/kg body weight per day. T-cell-dependent antibody response against keyhole limpet hemocyanin and immunophenotyping of the spleen were performed as measures of immunotoxicity. Clinical observations, body weight, hematology, coagulation, clinical chemistry, urinalysis, immunotoxicity, gross necropsy, and histopathology were assessed. Toxicokinetic parameters were analyzed as an indication of LF bioavailability, and anti-LF antibody assays were conducted to detect antibodies produced against LF to measure immunogenicity. No treatment related toxicologically significant changes were observed. Based on the absence of toxicologically relevant changes, effera™ is well tolerated in rats at doses up to 2000 mg rhLF/kg/day, an amount ∼400 times that of the estimated daily intake at the 90th percentile proposed for human adult use.","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"10915818241299344"},"PeriodicalIF":1.2,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620664","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 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 : 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 : 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