首页 > 最新文献

Chemical Research in Toxicology最新文献

英文 中文
The Toxicity of Poly(acrylonitrile-styrene-butadiene) Microplastics toward Hyalella azteca Is Associated with Biofragmentation and Oxidative Stress.
IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-01-20 Epub Date: 2024-12-29 DOI: 10.1021/acs.chemrestox.4c00300
Lucas Gonçalves Queiroz, Caio César Achiles do Prado, Paulo Filho Marques de Oliveira, Daniel Farinha Valezi, Marcelo Cecconi Portes, Beatriz Rocha de Moraes, Rômulo Augusto Ando, Eduardo Vicente, Teresa Cristina Brazil de Paiva, Marcelo Pompêo, Bárbara Rani-Borges

Acrylonitrile-butadiene-styrene (ABS) is a thermoplastic copolymer commonly used in the electronics, automotive, and construction industries. In the aquatic environment, the formation of microplastics from larger-sized plastic waste occurs naturally, induced by physical, chemical, and biological processes that promote the aging of these particles. Here, we investigated the interactions between the freshwater amphipod Hyalella azteca and ABS microplastics (10-20 μm) (pristine and after accelerated aging) over 7 days of exposure. At the end of the exposure period, we evaluated the ability of H. azteca to fragment the ABS particles, as well as the changes in its oxidative stress biomarkers (SOD, CAT, MDA, and GST) as the result of ABS exposure. H. azteca promoted a significant fragmentation of ABS particles. The ratio of this biofragmentation was more pronounced in pristine particles. Despite the absence of significant changes in the mortality of exposed organisms, alterations in the oxidative stress biomarkers were observed. The results demonstrate the ability of H. azteca to fragment pristine and aged ABS microplastics and, the consequent susceptibility of these organisms to the effects of microplastic exposure.

{"title":"The Toxicity of Poly(acrylonitrile-styrene-butadiene) Microplastics toward <i>Hyalella azteca</i> Is Associated with Biofragmentation and Oxidative Stress.","authors":"Lucas Gonçalves Queiroz, Caio César Achiles do Prado, Paulo Filho Marques de Oliveira, Daniel Farinha Valezi, Marcelo Cecconi Portes, Beatriz Rocha de Moraes, Rômulo Augusto Ando, Eduardo Vicente, Teresa Cristina Brazil de Paiva, Marcelo Pompêo, Bárbara Rani-Borges","doi":"10.1021/acs.chemrestox.4c00300","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00300","url":null,"abstract":"<p><p>Acrylonitrile-butadiene-styrene (ABS) is a thermoplastic copolymer commonly used in the electronics, automotive, and construction industries. In the aquatic environment, the formation of microplastics from larger-sized plastic waste occurs naturally, induced by physical, chemical, and biological processes that promote the aging of these particles. Here, we investigated the interactions between the freshwater amphipod <i>Hyalella azteca</i> and ABS microplastics (10-20 μm) (pristine and after accelerated aging) over 7 days of exposure. At the end of the exposure period, we evaluated the ability of <i>H. azteca</i> to fragment the ABS particles, as well as the changes in its oxidative stress biomarkers (SOD, CAT, MDA, and GST) as the result of ABS exposure. <i>H. azteca</i> promoted a significant fragmentation of ABS particles. The ratio of this biofragmentation was more pronounced in pristine particles. Despite the absence of significant changes in the mortality of exposed organisms, alterations in the oxidative stress biomarkers were observed. The results demonstrate the ability of <i>H. azteca</i> to fragment pristine and aged ABS microplastics and, the consequent susceptibility of these organisms to the effects of microplastic exposure.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"38 1","pages":"91-101"},"PeriodicalIF":3.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Activation of V-Domain Immunoglobulin Suppressor of T-Cell Activation by Baloxavir Marboxil Ameliorates Systemic Lupus Erythematosus through Inhibiting Lysophosphatidylcholine/CD40 Ligand. Baloxavir Marboxil通过抑制溶血磷脂酰胆碱/CD40配体激活t细胞活化的v域免疫球蛋白抑制因子改善系统性红斑狼疮
IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-01-20 Epub Date: 2025-01-08 DOI: 10.1021/acs.chemrestox.4c00449
Zhijie Luo, Tingting Zhang, Penglu Wang, Dingyi Yuan, Shasha Jin, Jianwen Di, Ruixue Ma, Lu Yang, Xinzhi Wang, Jun Liu

Deficiency of the V-domain immunoglobulin suppressor of T-cell activation (VISTA) accelerates disease progression in lupus-prone mice, and activation of VISTA shows therapeutic effects in mouse models of a lupus-like disease. Metabolic reprogramming of T cells in systemic lupus erythematosus (SLE) patients is important in regulating T-cell function and disease progression. However, the mechanism by which VISTA affects the immunometabolism in SLE remains unclear. Here, we demonstrated that the deficiency of VISTA promoted the synthesis of the metabolite lysophosphatidylcholine (LPC) using untargeted metabolomics and increased the protein expression of the CD40 ligand (CD40L). Furthermore, baloxavir marboxil (BXM), a small molecule agonist of VISTA, significantly ameliorated autoantibody production, renal damage, and imbalance of immune cell subpopulations in the models of a lupus-like disease in mice (chronic graft-versus-host disease and MRL/MpJ-Faslpr/J mice) possibly by inhibiting LPC synthesis to downregulate CD40L protein expression and inhibiting aberrant activation of noncanonical nuclear factor-κB pathway. Our results indicated that BXM targeting VISTA ameliorated lupus-like symptoms by altering lipid metabolism and CD40L expression, which offers novel mechanisms and a promising therapy for SLE.

v域免疫球蛋白t细胞激活抑制因子(VISTA)的缺乏加速了狼疮易感小鼠的疾病进展,VISTA的激活在狼疮样疾病的小鼠模型中显示出治疗效果。系统性红斑狼疮(SLE)患者T细胞的代谢重编程在调节T细胞功能和疾病进展中是重要的。然而,VISTA影响SLE免疫代谢的机制尚不清楚。在这里,我们利用非靶向代谢组学证明了VISTA的缺乏促进了代谢物溶磷脂酰胆碱(LPC)的合成,并增加了CD40配体(CD40L)的蛋白质表达。此外,VISTA小分子激动剂baloxavir marboxil (BXM)可能通过抑制LPC合成下调CD40L蛋白表达和抑制非规范核因子-κB通路异常激活,显著改善狼疮样疾病小鼠(慢性移植物抗宿主病和MRL/MpJ-Faslpr/J小鼠)模型中自身抗体的产生、肾损伤和免疫细胞亚群失衡。我们的研究结果表明,靶向VISTA的BXM通过改变脂质代谢和CD40L表达来改善狼疮样症状,这为SLE提供了新的机制和有希望的治疗方法。
{"title":"Activation of V-Domain Immunoglobulin Suppressor of T-Cell Activation by Baloxavir Marboxil Ameliorates Systemic Lupus Erythematosus through Inhibiting Lysophosphatidylcholine/CD40 Ligand.","authors":"Zhijie Luo, Tingting Zhang, Penglu Wang, Dingyi Yuan, Shasha Jin, Jianwen Di, Ruixue Ma, Lu Yang, Xinzhi Wang, Jun Liu","doi":"10.1021/acs.chemrestox.4c00449","DOIUrl":"10.1021/acs.chemrestox.4c00449","url":null,"abstract":"<p><p>Deficiency of the V-domain immunoglobulin suppressor of T-cell activation (VISTA) accelerates disease progression in lupus-prone mice, and activation of VISTA shows therapeutic effects in mouse models of a lupus-like disease. Metabolic reprogramming of T cells in systemic lupus erythematosus (SLE) patients is important in regulating T-cell function and disease progression. However, the mechanism by which VISTA affects the immunometabolism in SLE remains unclear. Here, we demonstrated that the deficiency of VISTA promoted the synthesis of the metabolite lysophosphatidylcholine (LPC) using untargeted metabolomics and increased the protein expression of the CD40 ligand (CD40L). Furthermore, baloxavir marboxil (BXM), a small molecule agonist of VISTA, significantly ameliorated autoantibody production, renal damage, and imbalance of immune cell subpopulations in the models of a lupus-like disease in mice (chronic graft-versus-host disease and MRL/MpJ-Faslpr/J mice) possibly by inhibiting LPC synthesis to downregulate CD40L protein expression and inhibiting aberrant activation of noncanonical nuclear factor-κB pathway. Our results indicated that BXM targeting VISTA ameliorated lupus-like symptoms by altering lipid metabolism and CD40L expression, which offers novel mechanisms and a promising therapy for SLE.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"193-205"},"PeriodicalIF":3.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Physical and Chemical Characterization of Aerosols Produced from Commercial Nicotine Salt-Based E-Liquids. 商用烟碱盐基电子烟液生产气溶胶的物理化学特性。
IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-01-20 Epub Date: 2024-12-09 DOI: 10.1021/acs.chemrestox.4c00315
Trevor Harris

Nicotine salt e-liquids are widely used in pod-style and disposable electronic nicotine delivery systems (ENDS). Studying the physical and chemical properties of their emissions can inform their toxicological impact. A prior companion study reported the harmful and potentially harmful constituents (HPHCs) and aerosol particle sizes produced from laboratory-made nicotine salt and freebase nicotine e-liquids to assess the effects of varying nicotine salts and nicotine protonation. This study reports the HPHCs and aerosol particle sizes for commercial brand nicotine salt and freebase nicotine formulations. Several tobacco, fruit, mint, and menthol flavored e-liquids of varying nicotine concentrations were tested with open and closed pod-style ENDS and a disposable ENDS. The nicotine yields showed a positive correlation with aerosol output, and the aerosol nicotine mass fractions reflected the e-liquid nicotine quantities. Benzene, crotonaldehyde, and 2,3-pentanedione were not detected or quantified in any of the aerosols, whereas acetaldehyde, acrolein, diacetyl, and formaldehyde were each quantified in at least one of the tested conditions. The aerosol particle number concentrations indicated that 97-99% of the aerosols for all the ENDS tested were composed of ultrafine (<0.1 μm) and fine (0.1-1.0 μm) aerosol particle sizes, and the mass median aerodynamic diameters ranged from 1.0 to 1.4 μm. The estimated regional deposition fractions and total respiratory depositions were calculated for all the ENDS conditions using a dosimetry modeling program. The calculations predicted depositions would predominantly occur in the pulmonary and head regions with a low total respiratory deposition (≤41%) calculated for all ENDS tested. This study broadens the availability of high-quality and reliable testing data of popular commercial nicotine salt-based ENDS for the scientific and regulatory communities. In conjunction with the previous work on the model e-liquids, these studies offer an extensive examination of the HPHCs and physical aerosol parameters of nicotine salt e-liquids.

尼古丁盐电子液体广泛应用于豆荚式和一次性电子尼古丁输送系统(ENDS)。研究其排放物的物理和化学性质可以了解其毒理学影响。先前的一项配套研究报告了实验室制造的尼古丁盐和自由碱尼古丁电子液体产生的有害和潜在有害成分(HPHCs)和气溶胶颗粒大小,以评估不同尼古丁盐和尼古丁质子化的影响。本研究报告了商业品牌尼古丁盐和自由碱尼古丁配方的HPHCs和气溶胶颗粒大小。几种不同尼古丁浓度的烟草、水果、薄荷和薄荷味电子液体分别用开放式和封闭式豆荚式终端和一次性终端进行了测试。烟碱得率与气溶胶输出量呈正相关,气溶胶烟碱质量分数反映了烟液烟碱量。苯、巴豆醛和2,3-戊二酮在任何气溶胶中均未被检测或定量,而乙醛、丙烯醛、二乙酰和甲醛在至少一种测试条件下均被定量。气溶胶粒子数浓度表明,所有被测终端的气溶胶中有97-99%由超细(
{"title":"Physical and Chemical Characterization of Aerosols Produced from Commercial Nicotine Salt-Based E-Liquids.","authors":"Trevor Harris","doi":"10.1021/acs.chemrestox.4c00315","DOIUrl":"10.1021/acs.chemrestox.4c00315","url":null,"abstract":"<p><p>Nicotine salt e-liquids are widely used in pod-style and disposable electronic nicotine delivery systems (ENDS). Studying the physical and chemical properties of their emissions can inform their toxicological impact. A prior companion study reported the harmful and potentially harmful constituents (HPHCs) and aerosol particle sizes produced from laboratory-made nicotine salt and freebase nicotine e-liquids to assess the effects of varying nicotine salts and nicotine protonation. This study reports the HPHCs and aerosol particle sizes for commercial brand nicotine salt and freebase nicotine formulations. Several tobacco, fruit, mint, and menthol flavored e-liquids of varying nicotine concentrations were tested with open and closed pod-style ENDS and a disposable ENDS. The nicotine yields showed a positive correlation with aerosol output, and the aerosol nicotine mass fractions reflected the e-liquid nicotine quantities. Benzene, crotonaldehyde, and 2,3-pentanedione were not detected or quantified in any of the aerosols, whereas acetaldehyde, acrolein, diacetyl, and formaldehyde were each quantified in at least one of the tested conditions. The aerosol particle number concentrations indicated that 97-99% of the aerosols for all the ENDS tested were composed of ultrafine (<0.1 μm) and fine (0.1-1.0 μm) aerosol particle sizes, and the mass median aerodynamic diameters ranged from 1.0 to 1.4 μm. The estimated regional deposition fractions and total respiratory depositions were calculated for all the ENDS conditions using a dosimetry modeling program. The calculations predicted depositions would predominantly occur in the pulmonary and head regions with a low total respiratory deposition (≤41%) calculated for all ENDS tested. This study broadens the availability of high-quality and reliable testing data of popular commercial nicotine salt-based ENDS for the scientific and regulatory communities. In conjunction with the previous work on the model e-liquids, these studies offer an extensive examination of the HPHCs and physical aerosol parameters of nicotine salt e-liquids.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"115-128"},"PeriodicalIF":3.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11752517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Phototoxic Effects on Skin Biomolecules Induced by a Domestic Nail Polish Dryer Device. 国产指甲油干燥器对皮肤生物分子的光毒性作用。
IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-01-20 Epub Date: 2025-01-06 DOI: 10.1021/acs.chemrestox.4c00401
Carlos A Ardila Padilla, Mariana Vignoni, Mariana P Serrano, M Laura Dántola

UVA radiation and visible light can lead to indirect damage to DNA, proteins, and lipids through photosensitized reactions, where a molecule undergoes a photochemical alteration by the initial absorption of radiation by another molecular entity called photosensitizer (Sens). The chemical changes undergone by biomolecules in photosensitized reactions can trigger important adverse processes such as photoallergy, phototoxicity, and skin cancer, among others. Despite the knowledge about photosensitized reactions and the fact that many endogenous compounds present in the skin can act as Sens, UVA, and visible light are widely used in several devices for domestic and general use without a thorough evaluation of their possible harmful effects; one prominent example is UV-nail polish dryers. The information in the literature about the possible damage that can be caused by using this type of radiation source is controversial. In this work, we demonstrate that the radiation dose emitted by the nail polish dryer device during a typical gel nail manicure session effectively degrades molecules present in the skin under physiological and pathological conditions. Additionally, it may induce damage to biomolecules such as proteins and lipids due to the photosensitization process, leading to the loss of their biological functions.

UVA辐射和可见光可通过光敏反应间接损害DNA、蛋白质和脂质,其中分子通过另一种称为光敏剂(Sens)的分子实体最初吸收辐射而发生光化学改变。生物分子在光敏反应中发生的化学变化可引发重要的不良反应,如光过敏、光毒性、皮肤癌等。尽管人们了解光敏反应,并且皮肤中存在的许多内源性化合物可以起到Sens的作用,但在没有对其可能的有害影响进行彻底评估的情况下,UVA和可见光被广泛用于家庭和一般用途的几种设备中;一个突出的例子是紫外线指甲油烘干机。文献中关于使用这种辐射源可能造成的损害的信息是有争议的。在这项工作中,我们证明了在生理和病理条件下,在典型的凝胶美甲过程中,指甲油干燥器发出的辐射剂量有效地降解了皮肤中存在的分子。此外,它还可能由于光敏化过程而引起蛋白质和脂质等生物分子的损伤,导致其生物学功能的丧失。
{"title":"Phototoxic Effects on Skin Biomolecules Induced by a Domestic Nail Polish Dryer Device.","authors":"Carlos A Ardila Padilla, Mariana Vignoni, Mariana P Serrano, M Laura Dántola","doi":"10.1021/acs.chemrestox.4c00401","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00401","url":null,"abstract":"<p><p>UVA radiation and visible light can lead to indirect damage to DNA, proteins, and lipids through photosensitized reactions, where a molecule undergoes a photochemical alteration by the initial absorption of radiation by another molecular entity called photosensitizer (Sens). The chemical changes undergone by biomolecules in photosensitized reactions can trigger important adverse processes such as photoallergy, phototoxicity, and skin cancer, among others. Despite the knowledge about photosensitized reactions and the fact that many endogenous compounds present in the skin can act as Sens, UVA, and visible light are widely used in several devices for domestic and general use without a thorough evaluation of their possible harmful effects; one prominent example is UV-nail polish dryers. The information in the literature about the possible damage that can be caused by using this type of radiation source is controversial. In this work, we demonstrate that the radiation dose emitted by the nail polish dryer device during a typical gel nail manicure session effectively degrades molecules present in the skin under physiological and pathological conditions. Additionally, it may induce damage to biomolecules such as proteins and lipids due to the photosensitization process, leading to the loss of their biological functions.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"38 1","pages":"182-192"},"PeriodicalIF":3.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 Cheminformatics Workflow to Select Representative TSCA Chemicals for New Approach Methodology (NAM) Screening. 选择具有代表性的TSCA化学品用于新方法方法学(NAM)筛选的化学信息学工作流。
IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-01-20 Epub Date: 2024-12-10 DOI: 10.1021/acs.chemrestox.4c00367
Grace Patlewicz, Antony J Williams, Matthew Adams, Imran Shah, Katie Paul-Friedman

The Toxic Substances Control Act (TSCA) requires the US EPA to evaluate the hazard and exposure of new and existing chemicals. New chemical notifications are typically data-poor and EPA has historically relied upon approaches including chemical categories to fill data gaps. As part of a multi-year Research Program, opportunities are being explored to leverage New Approach Methods (NAMs) in hazard and exposure assessments. Data from a battery of in vitro NAMs will be generated to form a case study for an adaptable approach to inform new chemical assessments. Herein, a cheminformatics workflow was developed to identify a set of ∼300 representative candidate chemicals for in vitro screening from the TSCA non-confidential active inventory. The freely available web application ClassyFire was used to categorize all discrete organic structures from the TSCA inventory into one of 68 primary structural categories. Large primary categories were subcategorized into smaller categories using hierarchical agglomerative clustering, ultimately yielding 180 structural terminal categories. The inventory was filtered to substances that lacked previous ToxCast bioactivity screening, were associated with physicochemical property predictions indicating non-volatile solids or liquids, and had a higher chance of procurement. Amenability predictions for liquid chromatography-mass spectrometry were also generated to provide an indication of which chemicals lent themselves to aqueous-based screening and analytical verification in solvated samples. Structures associated with transformation in solvent, potentially explosive or highly reactive, were excluded. Potential candidate substances were selected on the basis of being structurally representative of the terminal category and meeting other screenability conditions. A final set of 318 candidate chemicals were proposed to undergo analytical quality control and screening in a range of broad and targeted biological technologies for human health-relevant end points. Finally, in silico tools were applied to explore predicted hazard profiles of these candidate substances relative to the full inventory.

有毒物质控制法(TSCA)要求美国环境保护署评估新的和现有化学品的危害和暴露。新化学品通报通常缺乏数据,EPA历来依赖包括化学品类别在内的方法来填补数据空白。作为多年研究计划的一部分,正在探索利用危害和暴露评估的新方法(NAMs)的机会。将生成一系列体外nama的数据,以形成一种适应性方法的案例研究,为新的化学品评估提供信息。本文开发了一个化学信息学工作流程,从TSCA非机密活性清单中确定一组约300种具有代表性的候选化学物质进行体外筛选。使用免费的web应用程序ClassyFire将TSCA清单中的所有离散有机结构分类为68个主要结构类别之一。大的主要类别被细分为较小的类别,使用分层聚集聚类,最终产生180个结构终端类别。该清单经过筛选,筛选出了之前没有进行ToxCast生物活性筛选的物质,这些物质与物理化学性质预测相关,表明是非挥发性固体或液体,并且有更高的采购机会。还生成了液相色谱-质谱分析的适应性预测,以提供哪些化学物质适合在溶剂化样品中进行基于水的筛选和分析验证的指示。与溶剂转化有关的结构,潜在的爆炸性或高度反应性,被排除在外。根据在结构上代表终端类别和满足其他筛选条件来选择潜在的候选物质。最后提出了一套318种候选化学品,在一系列与人类健康相关的广泛和有针对性的生物技术中进行分析质量控制和筛选。最后,应用计算机工具来探索这些候选物质相对于完整清单的预测危害概况。
{"title":"A Cheminformatics Workflow to Select Representative TSCA Chemicals for New Approach Methodology (NAM) Screening.","authors":"Grace Patlewicz, Antony J Williams, Matthew Adams, Imran Shah, Katie Paul-Friedman","doi":"10.1021/acs.chemrestox.4c00367","DOIUrl":"10.1021/acs.chemrestox.4c00367","url":null,"abstract":"<p><p>The Toxic Substances Control Act (TSCA) requires the US EPA to evaluate the hazard and exposure of new and existing chemicals. New chemical notifications are typically data-poor and EPA has historically relied upon approaches including chemical categories to fill data gaps. As part of a multi-year Research Program, opportunities are being explored to leverage New Approach Methods (NAMs) in hazard and exposure assessments. Data from a battery of <i>in vitro</i> NAMs will be generated to form a case study for an adaptable approach to inform new chemical assessments. Herein, a cheminformatics workflow was developed to identify a set of ∼300 representative candidate chemicals for <i>in vitro</i> screening from the TSCA non-confidential active inventory. The freely available web application ClassyFire was used to categorize all discrete organic structures from the TSCA inventory into one of 68 primary structural categories. Large primary categories were subcategorized into smaller categories using hierarchical agglomerative clustering, ultimately yielding 180 structural terminal categories. The inventory was filtered to substances that lacked previous ToxCast bioactivity screening, were associated with physicochemical property predictions indicating non-volatile solids or liquids, and had a higher chance of procurement. Amenability predictions for liquid chromatography-mass spectrometry were also generated to provide an indication of which chemicals lent themselves to aqueous-based screening and analytical verification in solvated samples. Structures associated with transformation in solvent, potentially explosive or highly reactive, were excluded. Potential candidate substances were selected on the basis of being structurally representative of the terminal category and meeting other screenability conditions. A final set of 318 candidate chemicals were proposed to undergo analytical quality control and screening in a range of broad and targeted biological technologies for human health-relevant end points. Finally, <i>in silico</i> tools were applied to explore predicted hazard profiles of these candidate substances relative to the full inventory.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"129-144"},"PeriodicalIF":3.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 Photoinducible DNA Cross-Linking Agent with Potent Cytotoxicity and Selectivity Toward Triple-Negative Breast Cancer Cell Line. 一种对三阴性乳腺癌细胞系具有强细胞毒性和选择性的光诱导DNA交联剂。
IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-01-20 Epub Date: 2024-12-25 DOI: 10.1021/acs.chemrestox.4c00499
Qi Zhang, Taufeeque Ali, Thilini Nimasha Fernando Ponnamperumage, Zechao Lin, Nurul Islam Setu, Wasiu Olaniyi Awoyera, Regina Titilayo Oddiri, Adam Davis Rasmussen, Mary Collette Felli, David N Frick, Xiaohua Peng

DNA interstrand cross-links (ICLs) are the sources of the cytotoxicity of many anticancer agents. Selenium compounds showed great potential as anticancer drugs. In this work, we synthesized a binaphthalene analog 1 containing phenyl selenide (-SePh) as the leaving group and investigated its photochemical reactivity toward DNA as well as its cytotoxicity and selectivity. DNA ICLs were not observed with binaphthalene phenyl selenide 1 without UV irradiation, while ∼15% DNA ICL products were detected with UV irradiation, indicating a photoresponsive property of 1. The trapping reactions with TEMPO and MeONH2, respectively, suggested that free radicals and carbocations are involved in the DNA cross-linking process induced by the photoirradiation of 1. The photochemical reactivity of 1 toward DNA was sequence-dependent. DNA interstrand cross-linking occurred mainly at dG/dC base pairs, while monoalkylations occurred at dGs and dAs. Additionally, we have demonstrated that 1 alone without UV irradiation did not inhibit cancer cell growth even with a concentration of 100 μM, while the cytotoxicity of 1 toward cancer cells was significantly enhanced upon 350 nm irradiation with an IC50 of 1.7 μM. No cytotoxicity was observed toward normal epithelial MCF 10A cells, regardless of UV exposure, in the presence or absence of 1. The alkaline comet assay suggested that the photoinduced cytotoxicity of 1 is correlated to cellular DNA damage. Normal cells showed higher levels of GSH than cancer cells and exhibited efficient DNA repair mechanisms, which can both prevent and repair potential DNA damage induced by 1, contributing to the selective cytotoxicity of the prodrug toward triple-negative breast cancer cells.

DNA链间交联(ICLs)是许多抗癌药物的细胞毒性来源。硒化合物作为抗癌药物具有很大的潜力。本文合成了一种以硒化苯(-SePh)为离去基的二萘类似物1,并研究了其对DNA的光化学反应性、细胞毒性和选择性。在没有紫外线照射的情况下,双萘苯硒化物1没有观察到DNA ICL,而在紫外线照射下检测到约15%的DNA ICL产物,表明其光响应特性为1。分别与TEMPO和MeONH2的捕获反应表明,自由基和碳正离子参与了1。1对DNA的光化学反应性依赖于序列。DNA链间交联主要发生在dG/dC碱基对上,而单烷基化主要发生在dG和dAs碱基对上。此外,我们已经证明,即使在100 μM的紫外线照射下,单独使用1也不会抑制癌细胞的生长,而在350 nm的紫外线照射下,1对癌细胞的细胞毒性显著增强,IC50为1.7 μM。无论是否暴露在紫外线下,均未观察到对正常上皮MCF 10A细胞的细胞毒性。碱性彗星试验表明,1的光致细胞毒性与细胞DNA损伤有关。正常细胞GSH水平高于癌细胞,并表现出有效的DNA修复机制,可以预防和修复1诱导的潜在DNA损伤,这有助于前药对三阴性乳腺癌细胞的选择性细胞毒性。
{"title":"A Photoinducible DNA Cross-Linking Agent with Potent Cytotoxicity and Selectivity Toward Triple-Negative Breast Cancer Cell Line.","authors":"Qi Zhang, Taufeeque Ali, Thilini Nimasha Fernando Ponnamperumage, Zechao Lin, Nurul Islam Setu, Wasiu Olaniyi Awoyera, Regina Titilayo Oddiri, Adam Davis Rasmussen, Mary Collette Felli, David N Frick, Xiaohua Peng","doi":"10.1021/acs.chemrestox.4c00499","DOIUrl":"10.1021/acs.chemrestox.4c00499","url":null,"abstract":"<p><p>DNA interstrand cross-links (ICLs) are the sources of the cytotoxicity of many anticancer agents. Selenium compounds showed great potential as anticancer drugs. In this work, we synthesized a binaphthalene analog <b>1</b> containing phenyl selenide (-SePh) as the leaving group and investigated its photochemical reactivity toward DNA as well as its cytotoxicity and selectivity. DNA ICLs were not observed with binaphthalene phenyl selenide <b>1</b> without UV irradiation, while ∼15% DNA ICL products were detected with UV irradiation, indicating a photoresponsive property of <b>1</b>. The trapping reactions with TEMPO and MeONH<sub>2</sub>, respectively, suggested that free radicals and carbocations are involved in the DNA cross-linking process induced by the photoirradiation of <b>1</b>. The photochemical reactivity of <b>1</b> toward DNA was sequence-dependent. DNA interstrand cross-linking occurred mainly at dG/dC base pairs, while monoalkylations occurred at dGs and dAs. Additionally, we have demonstrated that <b>1</b> alone without UV irradiation did not inhibit cancer cell growth even with a concentration of 100 μM, while the cytotoxicity of <b>1</b> toward cancer cells was significantly enhanced upon 350 nm irradiation with an IC<sub>50</sub> of 1.7 μM. No cytotoxicity was observed toward normal epithelial MCF 10A cells, regardless of UV exposure, in the presence or absence of <b>1</b>. The alkaline comet assay suggested that the photoinduced cytotoxicity of <b>1</b> is correlated to cellular DNA damage. Normal cells showed higher levels of GSH than cancer cells and exhibited efficient DNA repair mechanisms, which can both prevent and repair potential DNA damage induced by <b>1</b>, contributing to the selective cytotoxicity of the prodrug toward triple-negative breast cancer cells.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"216-228"},"PeriodicalIF":3.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Dried Matrix Spots: An Underutilized and Unexplored Technology in India. 干基质斑点:印度未充分利用和未开发的技术。
IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-01-20 Epub Date: 2025-01-08 DOI: 10.1021/acs.chemrestox.4c00408
Divya Pulivarthi, Jasmin Chovatiya, Ravikumar Jagani, Syam S Andra

Dried Matrix Spot (DMS) is a cost-effective and stable sampling technique used in population-based studies, clinical research, and noninvasive chemical and biomarker screening. DMS is especially useful in developing countries like India, where collaborative initiatives are required for its improved applications.

干基质斑点(DMS)是一种经济、稳定的采样技术,用于基于人群的研究、临床研究和无创化学和生物标志物筛选。DMS在印度这样的发展中国家尤其有用,在这些国家需要合作倡议来改进其应用。
{"title":"Dried Matrix Spots: An Underutilized and Unexplored Technology in India.","authors":"Divya Pulivarthi, Jasmin Chovatiya, Ravikumar Jagani, Syam S Andra","doi":"10.1021/acs.chemrestox.4c00408","DOIUrl":"10.1021/acs.chemrestox.4c00408","url":null,"abstract":"<p><p>Dried Matrix Spot (DMS) is a cost-effective and stable sampling technique used in population-based studies, clinical research, and noninvasive chemical and biomarker screening. DMS is especially useful in developing countries like India, where collaborative initiatives are required for its improved applications.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"1-3"},"PeriodicalIF":3.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Environmental Stability Determines the Cytotoxicity of Metal-Organic Frameworks to a Nitrogen-Fixing Bacterium Azotobacter vinelandii. 环境稳定性决定了金属有机框架对固氮菌 "醋兰氮杆菌 "的细胞毒性。
IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-01-20 Epub Date: 2024-11-18 DOI: 10.1021/acs.chemrestox.4c00385
Ziqi Tang, Chengzhuang Liang, Qinmei Zhong, Jinwei Yang, Yusen Ma, Yue Yuan, Yiming Zeng, Xian Wu, Sheng-Tao Yang

During widespread applications of metal-organic frameworks (MOFs), the environmental hazards and risks of MOFs have aroused great concerns. In this study, we aimed to reveal the importance of the environmental stability of MOFs on their toxicity. Two Zn-MOFs, namely, ZIF-8 with high aqueous stability and Zn-BDC with low aqueous stability, were compared directly in the toxicological evaluations of a nitrogen-fixing bacterium Azotobacter vinelandii. Zn-BDC showed strong cytotoxicity at 100 mg/L and higher, inducing growth inhibition, cell apoptosis, structural changes, oxidative damage, and, consequently, loss of nitrogen fixation ability. In contrast, ZIF-8 was nearly nontoxic to A. vinelandii. The transcriptome analysis showed that Zn-BDC directly disturbed the ribosome pathway and lowered the expression level of nitrogen-fixing nif cluster genes. On the other hand, ZIF-8 stress could regulate the flagellar assembly, siderophore group nonribosomal peptide biosynthesis, bacterial chemotaxis, and amino sugar and nucleotide sugar metabolism pathways to promote the cell growth of A. vinelandii. Beyond that, the toxicity of Zn-MOFs to A. vinelandii was associated with the release of Zn2+, but Zn-MOFs were less toxic than the mixtures of their starting materials. Overall, our results suggested that the environmental stability of Zn-MOFs determined their environmental toxicity through different molecular pathways. Designing stable MOFs is preferred due to environment-friendly considerations.

在金属有机框架(MOFs)广泛应用的过程中,MOFs 的环境危害和风险引起了人们的极大关注。本研究旨在揭示 MOFs 的环境稳定性对其毒性的重要影响。在对固氮菌 Azotobacter vinelandii 进行毒理学评价时,我们直接比较了两种 Zn-MOFs (即水稳定性高的 ZIF-8 和水稳定性低的 Zn-BDC)。Zn-BDC 在 100 毫克/升或更高浓度时表现出强烈的细胞毒性,会导致生长抑制、细胞凋亡、结构变化、氧化损伤,进而丧失固氮能力。相比之下,ZIF-8 对 A. vinelandii 几乎无毒。转录组分析表明,Zn-BDC 直接干扰了核糖体途径,降低了固氮 nif 簇基因的表达水平。另一方面,ZIF-8胁迫可调控鞭毛组装、苷元组非核糖体肽生物合成、细菌趋化、氨基糖和核苷酸糖代谢途径,从而促进醋酸菌的细胞生长。此外,Zn-MOFs 对醋栗酵母菌的毒性与 Zn2+ 的释放有关,但 Zn-MOFs 的毒性低于其起始材料的混合物。总之,我们的研究结果表明,Zn-MOFs 的环境稳定性通过不同的分子途径决定了其环境毒性。出于对环境友好的考虑,人们更倾向于设计稳定的 MOFs。
{"title":"Environmental Stability Determines the Cytotoxicity of Metal-Organic Frameworks to a Nitrogen-Fixing Bacterium <i>Azotobacter vinelandii</i>.","authors":"Ziqi Tang, Chengzhuang Liang, Qinmei Zhong, Jinwei Yang, Yusen Ma, Yue Yuan, Yiming Zeng, Xian Wu, Sheng-Tao Yang","doi":"10.1021/acs.chemrestox.4c00385","DOIUrl":"10.1021/acs.chemrestox.4c00385","url":null,"abstract":"<p><p>During widespread applications of metal-organic frameworks (MOFs), the environmental hazards and risks of MOFs have aroused great concerns. In this study, we aimed to reveal the importance of the environmental stability of MOFs on their toxicity. Two Zn-MOFs, namely, ZIF-8 with high aqueous stability and Zn-BDC with low aqueous stability, were compared directly in the toxicological evaluations of a nitrogen-fixing bacterium <i>Azotobacter vinelandii</i>. Zn-BDC showed strong cytotoxicity at 100 mg/L and higher, inducing growth inhibition, cell apoptosis, structural changes, oxidative damage, and, consequently, loss of nitrogen fixation ability. In contrast, ZIF-8 was nearly nontoxic to <i>A. vinelandii</i>. The transcriptome analysis showed that Zn-BDC directly disturbed the ribosome pathway and lowered the expression level of nitrogen-fixing <i>nif</i> cluster genes. On the other hand, ZIF-8 stress could regulate the flagellar assembly, siderophore group nonribosomal peptide biosynthesis, bacterial chemotaxis, and amino sugar and nucleotide sugar metabolism pathways to promote the cell growth of <i>A. vinelandii</i>. Beyond that, the toxicity of Zn-MOFs to <i>A. vinelandii</i> was associated with the release of Zn<sup>2+</sup>, but Zn-MOFs were less toxic than the mixtures of their starting materials. Overall, our results suggested that the environmental stability of Zn-MOFs determined their environmental toxicity through different molecular pathways. Designing stable MOFs is preferred due to environment-friendly considerations.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"151-162"},"PeriodicalIF":3.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Human Monocyte-Derived Macrophages Demonstrate Distinct Responses to Ambient Particulate Matter in a Polarization State- and Particle Seasonality-Specific Manner. 人类单核细胞来源的巨噬细胞在极化状态和颗粒季节性特异性的方式下对环境颗粒物质表现出不同的反应。
IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-01-20 Epub Date: 2024-12-20 DOI: 10.1021/acs.chemrestox.4c00291
Timothy R Smyth, Stephanie Brocke, Yong Ho Kim, Cara Christianson, Kasey D Kovalcik, Joseph Patrick Pancras, Michael D Hays, Weidong Wu, Zhen An, Ilona Jaspers

Macrophages are professional phagocytic immune cells that, following activation, polarize on a spectrum between the proinflammatory M1 and the proresolution M2 states. Macrophages have further been demonstrated to retain plasticity, allowing for the reprogramming of their polarization states following exposure to new stimuli. Particulate matter (PM) has been repeatedly shown to modify macrophage function and polarization while also inducing worsening respiratory infection morbidity and mortality. However, limited work has considered the impact of the initial macrophage polarization state on subsequent responses to PM exposure. PM composition can demonstrate seasonality-specific compositional changes based on differences in seasonal weather patterns and energy needs, introducing the need to consider the seasonality-specific effects of airborne PM when investigating its impact on human health. This study sought to determine the impact of airborne PM collected during different seasons of the year in Xinxiang, China, on macrophage function in a polarization state-dependent manner. Macrophages were differentiated using the macrophage colony-stimulating factor (M-CSF) on CD14+CD16- monocytes isolated from the blood of healthy human volunteers. The resulting macrophages were polarized into indicated states using well-characterized polarization methods and assessed for phagocytic function, bioenergetic properties, and secretory profile following exposure to PM collected during a single day during each season of the year. Macrophages demonstrated clear polarization state-dependent phagocytic, bioenergetic, and secretory properties at the baseline and following PM exposure. Specific PM seasonality had a minimal impact on phagocytic function and a minor effect on bioenergetic properties but had clear impacts on the secretory profile as demonstrated by the enriched secretion of well-characterized mediator clusters by particle season. Together, these data suggest that both particle seasonality and macrophage polarization state must be considered when investigating the impact of PM on macrophage function. These factors may contribute to the negative outcomes linked to PM exposure during respiratory infections.

巨噬细胞是专业的吞噬免疫细胞,在激活后,在促炎M1和促炎M2状态之间极化。巨噬细胞已被进一步证明保持可塑性,允许其极化状态在暴露于新的刺激后重新编程。颗粒物质(PM)多次被证明可以改变巨噬细胞的功能和极化,同时也会导致呼吸道感染发病率和死亡率的恶化。然而,有限的研究考虑了巨噬细胞初始极化状态对PM暴露的后续反应的影响。根据季节天气模式和能源需求的差异,颗粒物组成可显示出季节性特定的成分变化,因此在调查空气中颗粒物对人类健康的影响时,需要考虑其季节性特定影响。本研究旨在确定中国新乡市不同季节收集的空气中PM对巨噬细胞功能的影响,并以极化状态依赖的方式进行研究。利用巨噬细胞集落刺激因子(M-CSF)在健康志愿者血液中分离的CD14+CD16-单核细胞上分化巨噬细胞。使用特性良好的极化方法将所得巨噬细胞极化成指示状态,并在暴露于一年中每个季节的一天内收集的PM后评估吞噬功能,生物能量特性和分泌谱。巨噬细胞在基线和PM暴露后表现出明显的极化状态依赖性吞噬、生物能量和分泌特性。特定的PM季节对吞噬功能的影响很小,对生物能量特性的影响也很小,但对分泌谱有明显的影响,这一点可以通过颗粒季节丰富的分泌来证明。综上所述,这些数据表明,在研究PM对巨噬细胞功能的影响时,必须考虑颗粒季节性和巨噬细胞极化状态。这些因素可能导致呼吸道感染期间接触PM的负面结果。
{"title":"Human Monocyte-Derived Macrophages Demonstrate Distinct Responses to Ambient Particulate Matter in a Polarization State- and Particle Seasonality-Specific Manner.","authors":"Timothy R Smyth, Stephanie Brocke, Yong Ho Kim, Cara Christianson, Kasey D Kovalcik, Joseph Patrick Pancras, Michael D Hays, Weidong Wu, Zhen An, Ilona Jaspers","doi":"10.1021/acs.chemrestox.4c00291","DOIUrl":"10.1021/acs.chemrestox.4c00291","url":null,"abstract":"<p><p>Macrophages are professional phagocytic immune cells that, following activation, polarize on a spectrum between the proinflammatory M1 and the proresolution M2 states. Macrophages have further been demonstrated to retain plasticity, allowing for the reprogramming of their polarization states following exposure to new stimuli. Particulate matter (PM) has been repeatedly shown to modify macrophage function and polarization while also inducing worsening respiratory infection morbidity and mortality. However, limited work has considered the impact of the initial macrophage polarization state on subsequent responses to PM exposure. PM composition can demonstrate seasonality-specific compositional changes based on differences in seasonal weather patterns and energy needs, introducing the need to consider the seasonality-specific effects of airborne PM when investigating its impact on human health. This study sought to determine the impact of airborne PM collected during different seasons of the year in Xinxiang, China, on macrophage function in a polarization state-dependent manner. Macrophages were differentiated using the macrophage colony-stimulating factor (M-CSF) on CD14+CD16- monocytes isolated from the blood of healthy human volunteers. The resulting macrophages were polarized into indicated states using well-characterized polarization methods and assessed for phagocytic function, bioenergetic properties, and secretory profile following exposure to PM collected during a single day during each season of the year. Macrophages demonstrated clear polarization state-dependent phagocytic, bioenergetic, and secretory properties at the baseline and following PM exposure. Specific PM seasonality had a minimal impact on phagocytic function and a minor effect on bioenergetic properties but had clear impacts on the secretory profile as demonstrated by the enriched secretion of well-characterized mediator clusters by particle season. Together, these data suggest that both particle seasonality and macrophage polarization state must be considered when investigating the impact of PM on macrophage function. These factors may contribute to the negative outcomes linked to PM exposure during respiratory infections.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":" ","pages":"73-90"},"PeriodicalIF":3.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Characterizing the Transient Emission of Particles and Gases from a Single Puff of Electronic Cigarette Smoke
IF 3.7 3区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2025-01-17 DOI: 10.1021/acs.chemrestox.4c0042010.1021/acs.chemrestox.4c00420
Kashala Fabrice Kapiamba, Steven Achterberg, Ta-Chun Lin, Philip D. Whitefield, Yue-Wern Huang and Yang Wang*, 

This study employed high-time-resolution systems to examine the transient properties of aerosols and gases emitted from electronic cigarette (EC) puffs. Using a fast aerosol sizer, we measured particle size distributions (PSDs) across various EC brands (JUUL, VUSE, VOOPOO), revealing sizes ranging from 5 to 1000 nm at concentrations of 107 to 1010 cm–3. Most aerosols were found to be in the ultrafine range (below 100 nm), with JUUL-, VUSE-, and VOOPOO-producing aerosols with geometric mean sizes of 19.9, 47.3, and 29.4 nm, respectively. Applying the International Commission on Radiological Protection (ICRP) deposition model and assuming no further evolution of aerosols in the respiratory system, we estimated particle deposition in different respiratory regions: 45–60% in the alveolar region, 10–25% in the tracheobronchial region, and 20–35% in the extrathoracic region. The highest single-puff deposition was observed with the VOOPOO device at 60 W, depositing 180.1 ± 7.6 μg in the alveolar region. The gas emissions (CO2, NOx, CO, and total hydrocarbons) were measured at different power settings of the VOOPOO EC. Single-puff NOx and CO levels exceeded the permissible exposure limits of the Occupational Safety and Health Administration, indicating potential acute exposure risks. Higher power settings were correlated with increased gas mixing ratios, suggesting more e-liquid vaporization and possible chemical transformations at higher temperatures. These findings demonstrated significant health risks associated with ultrafine particles from high-power ECs and emphasize the need for advanced measurements to accurately assess their physicochemical properties and potential health implications.

{"title":"Characterizing the Transient Emission of Particles and Gases from a Single Puff of Electronic Cigarette Smoke","authors":"Kashala Fabrice Kapiamba,&nbsp;Steven Achterberg,&nbsp;Ta-Chun Lin,&nbsp;Philip D. Whitefield,&nbsp;Yue-Wern Huang and Yang Wang*,&nbsp;","doi":"10.1021/acs.chemrestox.4c0042010.1021/acs.chemrestox.4c00420","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00420https://doi.org/10.1021/acs.chemrestox.4c00420","url":null,"abstract":"<p >This study employed high-time-resolution systems to examine the transient properties of aerosols and gases emitted from electronic cigarette (EC) puffs. Using a fast aerosol sizer, we measured particle size distributions (PSDs) across various EC brands (JUUL, VUSE, VOOPOO), revealing sizes ranging from 5 to 1000 nm at concentrations of 10<sup>7</sup> to 10<sup>10</sup> cm<sup>–3</sup>. Most aerosols were found to be in the ultrafine range (below 100 nm), with JUUL-, VUSE-, and VOOPOO-producing aerosols with geometric mean sizes of 19.9, 47.3, and 29.4 nm, respectively. Applying the International Commission on Radiological Protection (ICRP) deposition model and assuming no further evolution of aerosols in the respiratory system, we estimated particle deposition in different respiratory regions: 45–60% in the alveolar region, 10–25% in the tracheobronchial region, and 20–35% in the extrathoracic region. The highest single-puff deposition was observed with the VOOPOO device at 60 W, depositing 180.1 ± 7.6 μg in the alveolar region. The gas emissions (CO<sub>2</sub>, NO<i><sub>x</sub></i>, CO, and total hydrocarbons) were measured at different power settings of the VOOPOO EC. Single-puff NO<i><sub>x</sub></i> and CO levels exceeded the permissible exposure limits of the Occupational Safety and Health Administration, indicating potential acute exposure risks. Higher power settings were correlated with increased gas mixing ratios, suggesting more e-liquid vaporization and possible chemical transformations at higher temperatures. These findings demonstrated significant health risks associated with ultrafine particles from high-power ECs and emphasize the need for advanced measurements to accurately assess their physicochemical properties and potential health implications.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":"38 2","pages":"270–280 270–280"},"PeriodicalIF":3.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143418743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
期刊
Chemical Research in Toxicology
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1