Laura N Scott, Monice Fiume, 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, Bart Heldreth
{"title":"Safety Assessment of Zinc Salts as Used in Cosmetics.","authors":"Laura N Scott, Monice Fiume, 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, Bart Heldreth","doi":"10.1177/10915818241227124","DOIUrl":"10.1177/10915818241227124","url":null,"abstract":"<p><p>The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 27 inorganic and organometallic zinc salts as used in cosmetic formulations; these salts are specifically of the <sup>2+</sup> (II) oxidation state cation of zinc. These ingredients included in this report have various reported functions in cosmetics, including hair conditioning agents, skin conditioning agents, cosmetic astringents, cosmetic biocides, preservatives, oral care agents, buffering agents, bulking agents, chelating agents, and viscosity increasing agents. The Panel reviewed the relevant data for these ingredients, and concluded that these 27 ingredients are safe in cosmetics in the present practices of use and concentration described in this safety assessment when formulated to be non-irritating.</p>","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"5S-69S"},"PeriodicalIF":2.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139570305","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}
Laura N Scott, Monice Fiume, 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, Bart Heldreth
{"title":"Safety Assessment of Alkane Diols as Used in Cosmetics.","authors":"Laura N Scott, Monice Fiume, 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, Bart Heldreth","doi":"10.1177/10915818231224234","DOIUrl":"10.1177/10915818231224234","url":null,"abstract":"<p><p>The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 10 alkane diol ingredients as used in cosmetics. The alkane diols are structurally related to each other as small diols, and most are reported to function in cosmetics as solvents. The Panel reviewed the relevant data for these ingredients, and concluded that seven alkane diols are safe in cosmetics in the present practices of use and concentration described in this safety assessment, but that the available data are insufficient to make a determination of safety for three ingredients, namely 1,4-Butanediol, 2,3-Butanediol, and Octanediol.</p>","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"70S-131S"},"PeriodicalIF":2.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139086791","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}
Yusrabbil Amiyati Yusof, Zafarizal Aldrin Azizul Hasan, Zulina Abd Maurad
{"title":"Mutagenicity Assessment of Homologous Series of Methyl Ester Sulphonates (MES) Using the Bacterial Reverse Mutation (Ames) Test.","authors":"Yusrabbil Amiyati Yusof, Zafarizal Aldrin Azizul Hasan, Zulina Abd Maurad","doi":"10.1177/10915818231217041","DOIUrl":"10.1177/10915818231217041","url":null,"abstract":"<p><p>Methyl ester sulphonate (MES) is an anionic surfactant that is suitable to be used as an active ingredient in household products. Four palm-based MES compounds with various carbon chains, namely C<sub>12</sub>, C<sub>14</sub>, C<sub>16</sub> and C<sub>16/18</sub> MES, were assayed by the in vitro bacterial reverse mutation (Ames) test in the <i>Salmonella typhimurium</i> strains TA98, TA100, TA1535, and TA1537 and the <i>Escherichia coli</i> strain WP2 <u>uvrA</u>, with the aim of establishing the safety data of the compounds, specifically their mutagenicity. The test was also carried out on linear alkylbenzene sulphonate (LAS) for comparison. The plate incorporation method was conducted according to the Organization for Economic Cooperation and Development (OECD) Test Guideline 471. All compounds were tested at five analysable non-cytotoxic concentrations, varying from .001 mg/plate to 5 mg/plate, with and without S-9 metabolic activation. All tested concentrations showed no significant increase in the number of revertant colonies compared to revertant colonies of the negative control. The Ames test indicated that each concentration of C<sub>12</sub>, C<sub>14</sub>, C<sub>16</sub>, C<sub>16/18</sub> MES, and LAS used in this study induced neither base-pair substitutions nor frame-shift mutations in the <i>S. typhimurium</i> strains TA98, TA100, TA1535, and TA1537 and the <i>E</i>. <i>coli</i> strain WP2 <u>uvrA</u>. The results showed that C<sub>12</sub>, C<sub>14</sub>, C<sub>16</sub> and C<sub>16/18</sub> MES have no potential mutagenic properties in the presence and absence of S-9 metabolic activation, similarly to LAS. Therefore, the MES is safe to be used as an alternative to petroleum-based surfactants for household cleaning products.</p>","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"157-164"},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138482318","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}
{"title":"Copper Chaperone Atox1 Protected the Cochlea From Cisplatin by Regulating the Copper Transport Family and Cell Cycle.","authors":"Xubo Chen, Weiren Xiang, Lihua Li, Kai Xu","doi":"10.1177/10915818231206665","DOIUrl":"10.1177/10915818231206665","url":null,"abstract":"<p><p>Antioxidant 1 copper chaperone (Atox1) may contribute to preventing DDP cochlear damage by regulating copper transport family and cell cycle proteins. A rat model of cochlear damage was developed by placing gelatin sponges treated with DDP in the cochlea. HEI-OC1 cells were treated with 133 μM DDP as a cell model. DDP-induced ototoxicity in rats was confirmed by immunofluorescence (IF) imaging. The damage of DDP to HEI-OC1 cells was assessed by using CCK-8, TUNEL, and flow cytometry. The relationship between Atox1, a member of the copper transport protein family, and the damage to <i>in vivo</i>/<i>vitro</i> models was explored by qRT-PCR, western blot, CCK-8, TUNEL, and flow cytometry. DDP had toxic and other side effects causing cochlear damage and promoted HEI-OC1 cell apoptosis and cell cycle arrest. The over-expression of Atox1 (oe-Atox1) was accomplished by transfecting lentiviral vectors into <i>in vitro</i>/<i>vivo</i> models. We found that oe-Atox1 increased the levels of Atox1, copper transporter 1 (CTR1), and SOD3 in HEI-OC1 cells and decreased the expression levels of ATPase copper transporting α (ATP7A) and ATPase copper transporting β (ATP7B). In addition, the transfection of oe-Atox1 decreased cell apoptosis rate and the number of G2/M stage cells. Similarly, the expression of myosin VI and phalloidin of cochlea cells <i>in vivo</i> decreased. Atox1 ameliorated DDP-induced damage to HEI-OC1 cells or rats' cochlea by regulating the levels of members of the copper transport family.</p>","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"134-145"},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49677417","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}
Yanxia Peng, Genmeng Yang, Shangwen Wang, Wanrong Lin, Lihua Zhu, Wenjuan Dong, Baoyu Shen, Qianyun Nie, Shijun Hong, Lihua Li
{"title":"Triggering Receptor Expressed on Myeloid Cells 2 Deficiency Exacerbates Methamphetamine-Induced Activation of Microglia and Neuroinflammation.","authors":"Yanxia Peng, Genmeng Yang, Shangwen Wang, Wanrong Lin, Lihua Zhu, Wenjuan Dong, Baoyu Shen, Qianyun Nie, Shijun Hong, Lihua Li","doi":"10.1177/10915818231216397","DOIUrl":"10.1177/10915818231216397","url":null,"abstract":"<p><p>Methamphetamine (METH) is a highly addictive psychostimulant and one of the most widely abused drugs worldwide. The continuous use of METH eventually leads to neurotoxicity and drug addiction. Studies have shown that neurotoxicity is strongly associated with METH-induced neuroinflammation, and microglia are the key drivers of neuroinflammation. Triggering receptor expressed on myeloid cells 2 (TREM2) is reported to play a key role in activation of microglia and neuroinflammation. Yet, the molecular mechanisms by which METH causes neuroinflammation and neurotoxicity remain elusive. In the current study, we investigated the role of TREM2 in neuroinflammation induced by METH in BV2 cells and the wild-type (WT) C57BL/6J mice, CX3CR1<sup>GFP/+</sup> transgenic mice, and TREM2 knockout (KO) mice. Postmortem samples from the frontal cortex of humans with a history of METH use were also analyzed to determine the levels of TREM2, TLR4, IBA1, and IL-1β. The expression levels of TREM2, TLR4, IBA1, IL-1β, iNOS, and Arg-1 were then assessed in the BV2 cells and frontal cortex of mice and human METH users. Results revealed that the expression levels of TREM2, TLR4, IBA1, and IL-1β were significantly elevated in METH-using individuals and BV2 cells. Microglia were clearly activated in the frontal cortex of WT C57BL/6 mice and CX3CR1<sup>GFP/+</sup> transgenic mice, and the protein levels of IBA1, TREM2, TLR4, and IL-1β were elevated in the METH-induced mouse models. Moreover, TREM2-KO mice showed further increased microglial activation, neuroinflammation, and excitotoxicity induced by METH. Thus, these findings suggest that TREM2 may be a target for regulating METH-induced neuroinflammation.</p>","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"165-176"},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138434038","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}
Laxit K Bhatt, Chitrang R Shah, Shital D Patel, Sudhir R Patel, Vipul A Patel, Rajesh J Patel, Nikita M Joshi, Niraj A Shah, Jitendra H Patel, Pankaj Dwivedi, Rajesh Sundar, Mukul R Jain
{"title":"A Retrospective Comparison of Electrocardiographic Parameters in Ketamine and Tiletamine-Zolazepam Anesthetized Indian Rhesus Monkeys (<i>Macaca mulatta</i>).","authors":"Laxit K Bhatt, Chitrang R Shah, Shital D Patel, Sudhir R Patel, Vipul A Patel, Rajesh J Patel, Nikita M Joshi, Niraj A Shah, Jitendra H Patel, Pankaj Dwivedi, Rajesh Sundar, Mukul R Jain","doi":"10.1177/10915818231221276","DOIUrl":"10.1177/10915818231221276","url":null,"abstract":"<p><p>Electrocardiographic evaluation is performed in rhesus monkeys to establish the cardiovascular safety of candidate molecules before progressing to clinical trials. These animals are usually immobilized chemically by ketamine (KTM) and tiletamine-zolazepam (TZ) to obtain a steady-state heart rate and to ensure adequate human safety. The present study aimed to evaluate the effect of these anesthetic regimens on different electrocardiographic parameters. Statistically significant lower HR and higher P-wave duration, RR, QRS, and QT intervals were observed in the KTM-anesthetized group in comparison to TZ-anesthetized animals. No significant changes were noticed in the PR interval and p-wave amplitude. Sex-based significance amongst these parameters was observed in male and female animals of TZ- and KTM-anesthetized groups. Regression analysis of four QTc formulas in TZ-anesthetized rhesus monkeys revealed that QTcNAK (Nakayama) better corrected the QT interval than QTcHAS (Hassimoto), QTcBZT (Bazett), and QTcFRD (Fridericia) formulas. QTcNAK exhibited the least correlation with the RR interval (slope closest to zero and r = .01) and displayed no statistical significance between male and female animals. These data will prove useful in the selection of anesthetic regimens for chemical restraint of rhesus monkeys in nonclinical safety evaluation studies.</p>","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"184-195"},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138804301","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}
Miranda J Baran, Rebecca Hof, Angelique Groot, Irene Eurlings, Jet Gijsbrechts, Britt de Jong, Jeremy E Wulff
{"title":"Safety Evaluation of a Prototypical Diazirine-Based Covalent Crosslinker and Molecular Adhesive.","authors":"Miranda J Baran, Rebecca Hof, Angelique Groot, Irene Eurlings, Jet Gijsbrechts, Britt de Jong, Jeremy E Wulff","doi":"10.1177/10915818231215692","DOIUrl":"10.1177/10915818231215692","url":null,"abstract":"<p><p><i>bis</i>-Diazirine reagents are increasingly being used as polymer crosslinkers, adhesives, and photopatterning agents in the materials sciences literature, but little effort has been made thus far to document their chemical safety profile. Here, we describe the results of a detailed toxicity assessment of a representative <i>bis</i>-diazirine. Safety was evaluated by a series of in vitro assays, which found the product to be non-mutagenic in bacterial tester strains TA98 and TA100, non-corrosive and non-irritating to skin, and requiring no classification for eye irritation or serious damage. While in vitro tests do not capture the integrated whole animal system, and thus cannot completely rule out the possibility of adverse responses, the results of this study suggest a desirable safety profile for <i>bis</i>-diazirine reagents and provide a solid foundation upon which to add in vivo assessment of safety risk and dose-response studies.</p>","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"146-156"},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10916352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138176155","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}
Susan Hall, Jane Grayson, Gary Grant, Christopher Vertullo, Shailendra Anoopkumar-Dukie
{"title":"In Vitro Evaluation of Vancomycin-Induced Toxicity in Human Primary Knee Chondrocytes.","authors":"Susan Hall, Jane Grayson, Gary Grant, Christopher Vertullo, Shailendra Anoopkumar-Dukie","doi":"10.1177/10915818231216413","DOIUrl":"10.1177/10915818231216413","url":null,"abstract":"<p><p>Septic arthritis as a complication of orthopaedic joint surgery can have catastrophic outcomes for patients. To minimise infection risk associated with elective orthopaedics, topical vancomycin during surgery has become increasingly common. Evidence suggests that high concentrations of vancomycin, following direct application of the drug to the joint, are toxic towards various local cell types in the joint, including chondrocytes. However, the mechanism of this vancomycin tissue toxicity is yet to be determined. The aim of this study was to evaluate the toxicity of vancomycin on chondrocytes and the mechanisms of cell death involved. Human primary knee chondrocytes were exposed to vancomycin (1.25-10 mg/mL) for 24 h and their viability assessed using the resazurin reduction assay in vitro. Specific cell death mechanisms and their contributors, including reactive oxygen species (ROS) production and apoptosis, were measured. This study showed that high concentrations of vancomycin (5 and 10 mg/mL) were toxic towards human primary knee chondrocyte cells, while lower concentrations (1.25 and 2.5 mg/mL) were not. Cell death studies found that this occurred through an apoptotic pathway. This study provides additional support that vancomycin in high doses is toxic towards chondrocytes and preliminary evidence that this toxicity occurs via apoptotic cell death mechanisms.</p>","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"177-183"},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10916344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138290887","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}
{"title":"A Commentary on Fasting of Nonclinical Research Animals.","authors":"David V Gauvin, Margaret McComb, Ryan Farero","doi":"10.1177/10915818231218975","DOIUrl":"10.1177/10915818231218975","url":null,"abstract":"<p><p>This commentary discusses the implementation of fasting in nonclinical animal experimental subjects. The short-term removal of food from cages of experimental animals is in all respects innocuous. The term \"stress\" is ill-defined and the statutes and regulations governing animal research laboratories that exert their authority in the performance of their operations do so without substantive grounds to base compliance. The legislative and administrative history of the implementation of the Animal Welfare Act (AWA) has evolved into the development of laboratory management strategies that focus on the reduction of the biological cost of stress to the animals and the determination of when subclinical stress (eustress) becomes distress. Animal welfare is based on the tenet that in laboratories conducting animal research in compliance with Good Laboratory Practices (Title 21 USC, Chapter 13,§58), it is the study protocol and the study director that establish procedures and processes that are approved by each Institutional Animal Care and Use Committee to ensure the humane care and use of animals in research, teaching, and testing and to ensure compliance with guidelines and regulations. This approval process establishes the justification of eustress in the environment that do not rise to the threshold of distress under the AWA.</p>","PeriodicalId":14432,"journal":{"name":"International Journal of Toxicology","volume":" ","pages":"196-208"},"PeriodicalIF":2.2,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048691","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}