Altex-Alternatives To Animal Experimentation最新文献_第3页

Characterization of the C17.2 cell line as test system for endocrine disruption-induced developmental neurotoxicity. 将 C17.2 细胞系作为内分泌干扰诱导的发育神经毒性测试系统的特征。

IF 4.5 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2025-01-01 Epub Date: 2024-09-06 DOI: 10.14573/altex.2404131

Andrea Cediel-Ulloa, Roseline Awoga, Arif Dönmez, Ximiao Yu, Anda Gliga, Kristina Attoff, Anna Forsby, Joëlle Rüegg

{"title":"Characterization of the C17.2 cell line as test system for endocrine disruption-induced developmental neurotoxicity.","authors":"Andrea Cediel-Ulloa, Roseline Awoga, Arif Dönmez, Ximiao Yu, Anda Gliga, Kristina Attoff, Anna Forsby, Joëlle Rüegg","doi":"10.14573/altex.2404131","DOIUrl":"10.14573/altex.2404131","url":null,"abstract":"Hormone signaling plays an essential role during fetal life and is vital for brain development. Endocrine-disrupting chemicals can interfere with the hormonal milieu during this critical time-period, disrupting key neurodevelopmental processes. Hence, there is a need for the development of assays that evaluate developmental neurotoxicity (DNT) induced by an endocrine mode of action. Herein, we evaluated the neural progenitor C17.2 cell line as an in vitro test system to aid in the detection of endocrine disruption-induced DNT. For this, C17.2 cells were exposed during 10 days of differentiation to agonists and antagonists of the thyroid hormone (THR), glucocorticoid (GR), retinoic acid (RAR), retinoic x (RXR), oxysterol (LXR), estrogen (ER), androgen (AR), and peroxisome proliferator activated delta (PPARβ/δ) receptors, as well as to the agonist of the vitamin D (VDR) receptor. Upon exposure and differentiation, neuronal morphology (neurite outgrowth and branching) and the percentage of neurons in culture were assessed by immunofluorescence. For this, the cells were stained for βIII-tubulin (neuronal marker). C17.2 cells decreased neurite outgrowth and branching in response to RAR, RXR and PPARβ/δ agonists. Exposure to the GR agonist increased the number of cells differentiating into neurons, while exposure to the RXR agonist had the opposite effect. With this approach, we demonstrate that C17.2 cells are responsive to GR, RAR, RXR, and PPARβ/δ agonists and hence could be useful to develop a test system for hazard assessment of endocrine disruption-induced DNT.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"91-110"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Opportunities and challenges for human microphysiological systems in drug development. 药物开发中人体微生理系统的机遇与挑战。

IF 4.5 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-12-20 DOI: 10.14573/altex.2409221

Shekh M Rahman, Ashok Krishna, Catherine Sullenberger, Ye Eun Jeong, M Iveth Garcia, Bhavya Bhardwaj, Robert M Geiger, Ksenia Blinova, Kevin A Ford

{"title":"Opportunities and challenges for human microphysiological systems in drug development.","authors":"Shekh M Rahman, Ashok Krishna, Catherine Sullenberger, Ye Eun Jeong, M Iveth Garcia, Bhavya Bhardwaj, Robert M Geiger, Ksenia Blinova, Kevin A Ford","doi":"10.14573/altex.2409221","DOIUrl":"https://doi.org/10.14573/altex.2409221","url":null,"abstract":"Microphysiological systems (MPS) are complex in vitro tools that incorporate cells derived from various healthy or disease-state human or animal tissues and organs. While MPS have limitations, including a lack of globally harmonized guidelines for standardization, they have already proven impactful in certain areas of drug development. Further research and regulatory acceptance of MPS will contribute to making them even more effective tools in the future. This review explores the potential applications of human liver, gut, lung, and cardiac MPS in drug development, focusing on disease modeling, safety assessment, and pharmacokinetic studies. Various technical parameters and relevant endpoints for system assessment are discussed alongside challenges such as cell sourcing, reproducibility, and the integration of multiple tissues or organs. The importance of collaborative efforts between academia, industry, and regulatory agencies to develop standardized protocols and validation criteria is emphasized. With ongoing advancements and cooperative initiatives, MPS are poised to play a significant role in enhancing the predictivity and reliability of nonclinical testing, thereby transforming drug development and regulatory processes.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparative evaluation of rat and human in vitro assays for evaluation of thyroid toxicity. 大鼠与人甲状腺毒性体外评价的比较。

IF 4.5 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-12-02 DOI: 10.14573/altex.2405072

Laure Asselin, Audrey Baze, Betty Ory, Lucille Wiss, Amélie Schäfer, Liliia Horbal, Larry Higgins, Lysiane Richert

{"title":"Comparative evaluation of rat and human in vitro assays for evaluation of thyroid toxicity.","authors":"Laure Asselin, Audrey Baze, Betty Ory, Lucille Wiss, Amélie Schäfer, Liliia Horbal, Larry Higgins, Lysiane Richert","doi":"10.14573/altex.2405072","DOIUrl":"https://doi.org/10.14573/altex.2405072","url":null,"abstract":"The effects of ten test chemicals towards thyroid sodium-iodide symporter (NIS), thyroid peroxidase (TPO), and deiodinases (DIOs) type I, II, and III were evaluated in in vitro rat and human systems and compared. Test chemicals known to directly affect TH levels in vivo were confirmed to effectively inhibit at least one of the tested in vitro endpoints, without significant disparities between species, and the tested compounds known to not affect thyroid function, were found ineffective. Interestingly, Iodide Transport Blocker 5, a potent non-competitive iodine uptake inhibitor, exhibited effects beyond direct NIS inhibition, by impacting NIS function through ATP depletion, and also inhibited TPO and DIO1/2 enzymes, although to a lesser extent. Finally, while of the four hepatic inducers known to affect thyroid function indirectly in rats through increased TH metabolism in the liver, dexamethasone, phenobarbital and pregnenolone 16α-carbonitrile were found ineffective in the herein described inhibition tests, rifampicin decreased rat and human TPO activities, highlighting a potential direct effect on thyroid function. This study demonstrates the usefulness of data generated by the rat and human in vitro NIS, TPO and DIOs test systems described here to support risk-based decisions.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Potential value of animal microphysiological systems. 动物微观生理系统的潜在价值。

IF 4.5 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-08-07 DOI: 10.14573/altex.2311141

Paul C Brown, Barry H Hooberman, Brianna L Skinner, Claudia Wrzesinski, Dayton M Petibone, Kevin A Ford, Kristi Muldoon-Jacobs, Kyung E Sung, Luis G Valerio, Nakissa N Sadrieh, Paul C Howard, Peter L Goering, Shelby A Skoog, Suzanne C Fitzpatrick, Tracy Chen, Tracy C MacGill, Donna L Mendrick

{"title":"Potential value of animal microphysiological systems.","authors":"Paul C Brown, Barry H Hooberman, Brianna L Skinner, Claudia Wrzesinski, Dayton M Petibone, Kevin A Ford, Kristi Muldoon-Jacobs, Kyung E Sung, Luis G Valerio, Nakissa N Sadrieh, Paul C Howard, Peter L Goering, Shelby A Skoog, Suzanne C Fitzpatrick, Tracy Chen, Tracy C MacGill, Donna L Mendrick","doi":"10.14573/altex.2311141","DOIUrl":"https://doi.org/10.14573/altex.2311141","url":null,"abstract":"Microphysiological systems (MPS) are designed to recapitulate aspects of tissue/organ physiology in vivo, thereby providing potential value in safety and efficacy assessments of FDA-regulated products and regulatory decision-making. While there have been significant advances in the development, use, and proposals of qualification criteria for human organ MPS, there remains a gap in the development using animal tissues. Animal MPS may be of value in many areas including the study of zoonotic diseases, assessment of the safety and efficacy of animal therapeutics, and possibly reduction of the use of animals in regulatory submissions for animal therapeutics. In addition, the development of MPS from various animal species enables comparison to animal in vivo data. This comparison, while not always critical for all contexts of use, could help gain confidence in the use and application of human MPS data for regulatory decision-making and for the potential identification of species-specific effects. The use of animal MPS is consistent with the replacement, reduction, and refinement (3Rs) principles of animal use by identifying toxic compounds before conducting in vivo studies and identifying the appropriate species for testing.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Development of a monoclonal antibody sandwich ELISA for the determination of antigen content and quality in diphtheria vaccines. 开发用于测定白喉疫苗抗原含量和质量的单克隆抗体夹心酶联免疫吸附试验。

IF 5.6 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-09 Epub Date: 2023-08-07 DOI: 10.14573/altex.2305251

Laura Hassall, Daniel A Yara, Rebecca Riches-Duit, Peter Rigsby, Alexandre Dobly, Maxime Vermeulen, Antoine Francotte, Paul Stickings

{"title":"Development of a monoclonal antibody sandwich ELISA for the determination of antigen content and quality in diphtheria vaccines.","authors":"Laura Hassall, Daniel A Yara, Rebecca Riches-Duit, Peter Rigsby, Alexandre Dobly, Maxime Vermeulen, Antoine Francotte, Paul Stickings","doi":"10.14573/altex.2305251","DOIUrl":"10.14573/altex.2305251","url":null,"abstract":"At present, quality control of diphtheria vaccines by both manufacturers and national control laboratories relies heavily on in vivo assays to confirm potency. As part of the VAC2VAC project we have developed a monoclonal antibody (mAb) enzyme-linked immunosorbent assay (ELISA) to measure the relative amount and quality of diphtheria toxoid (DTxd) in diphtheria-tetanus based vaccines and believe this test has the potential to play a key role in a control strategy no longer including an in vivo potency test. The mAb ELISA is highly specific, has good dilutional linearity, and is suitable for detecting DTxd in a range of different human vaccine products. We demonstrate the ability of the assay to discriminate between batches of different content and quality using vaccine batches that were prepared to contain differing amounts of DTxd or were altered by exposure to heat or oxidative stress. We also demonstrate successful transfer of the method to other laboratories and show that different diphtheria antigen materials may be able to serve as a reference antigen for local standardization of the method. The assay is ideally suited for incorporation into a consistency approach for routine diphtheria vaccine quality control testing and may be suitable to serve as the stability indicating test in replacement of the current in vivo potency test.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"57-68"},"PeriodicalIF":5.6,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10008309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Challenges integrating skin sensitization data for assessment of difficult to test substances. 整合皮肤致敏数据以评估难以测试的物质的挑战。

IF 5.6 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-09 Epub Date: 2023-10-12 DOI: 10.14573/altex.2201122

Allison Greminger, Joseph Frasca, Katy Goyak, Colin North

{"title":"Challenges integrating skin sensitization data for assessment of difficult to test substances.","authors":"Allison Greminger, Joseph Frasca, Katy Goyak, Colin North","doi":"10.14573/altex.2201122","DOIUrl":"10.14573/altex.2201122","url":null,"abstract":"Difficult to test substances, including poorly soluble, mildly irritating, or UVCBs (unknown or variable composition complex reaction products or biological materials), producing weak or borderline in vivo results, face additional challenges in in vitro assays that often necessitate data integration in a weight of evidence (WOE) approach to inform skin sensitization potential. Here we present several case studies on difficult to test substances and highlight the utility of the toxicological priority index (ToxPi) as a data visualization tool to compare skin sensitization biological activity. The case study test substances represent two poorly soluble substances, tetrakis (2-ethylbutyl) orthosilicate and decyl palmitate, and two UVCB substances, alkylated anisole and hydrazinecarboximidamide, 2-[(2-hydroxyphenyl)methylene]-, reaction products with 2 undecanone. Data from key events within the skin sensitization adverse outcome pathway were gathered from publicly available sources or specifically generated. Incorporating the data for these case study test substances as well as data on chemicals of a known sensitization class (sensitizer, irritating non-sensitizer, and non-sensitizer) into ToxPi produced biological activity profiles which were grouped using unsupervised hierarchical clustering. Three of the case study test substances concluded to lack skin sensitization potential by traditional WOE produced biological activity profiles most consistent with non-sensitizing substances, whereas the prediction was less definitive for a substance considered positive by traditional WOE. Visualizing the data using bioactivity profiles can provide further support for WOE conclusions in certain circumstances but is unlikely to replace WOE as a stand-alone prediction due to limitations of the method including the impact of missing data points.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"104-118"},"PeriodicalIF":5.6,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41240754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Developing prototypes of a modernized approach to assess crop protection chemical safety. 开发评估作物保护化学品安全性的现代化方法原型。

IF 5.6 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-09 Epub Date: 2023-08-31 DOI: 10.14573/altex.2307181

Richard A Currie, John Abbott, David A Dreier, Haitian Lu, Tharacad Ramanarayanan, Natalia Ryan, Odette A Watkins, Douglas C Wolf

{"title":"Developing prototypes of a modernized approach to assess crop protection chemical safety.","authors":"Richard A Currie, John Abbott, David A Dreier, Haitian Lu, Tharacad Ramanarayanan, Natalia Ryan, Odette A Watkins, Douglas C Wolf","doi":"10.14573/altex.2307181","DOIUrl":"10.14573/altex.2307181","url":null,"abstract":"In 2019, the US EPA Administrator issued a directive directing the agency away from reliance on vertebrate tests by 2035, whilst maintaining high-quality human health and environmental risk assessments. There is no accepted approach to achieve this. The decade-long duration of the crop protection (CP) chemical R&D process therefore requires both the invention and application of a modernized approach to those CP chemical projects entering corporate research portfolios by the mid-2020s. We conducted problem formulation discussions with regulatory agency scientists which created the problem statement: “Develop, demonstrate, and implement a modern scientifically sound and robust strategy that applies appropriate and flexible exposure and effects characterization without chemical specific vertebrate tests to reliably address risk, uncertainties, and deficiencies in data and its interpretation with equivalent confidence as do the currently accepted test guidelines and meet the regulatory needs of the agencies”. The solution must provide the knowledge needed to confidently conclude human health and environmental protective risk assessments. Exploring this led to a conceptual model involving the creation and parallel submission of a new approach without reliance on chemical-specific vertebrate tests. Assessment in parallel to a traditional package will determine whether it supports some, or all, of the necessary risk management actions. Analysis of any deficiencies will provide valuable feedback to focus development of tools or approaches for subsequent iterations. When found to provide sufficient information, it will form the technical foundation of stakeholder engagement to explore acceptance of a new approach to CP chemical risk assessment.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"119-130"},"PeriodicalIF":5.6,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10148356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Beyond Animal Testing Index: Benchmarking tool for a world beyond animal testing. 超越动物实验指数：超越动物实验世界的基准工具。

IF 5.6 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-09 Epub Date: 2023-08-08 DOI: 10.14573/altex.2304161

Cyrille Krul, Annick De Moor, Koen Stegmeijer, Reinout Stoop, Judith Van Luijk, Jan-Bas Prins

{"title":"Beyond Animal Testing Index: Benchmarking tool for a world beyond animal testing.","authors":"Cyrille Krul, Annick De Moor, Koen Stegmeijer, Reinout Stoop, Judith Van Luijk, Jan-Bas Prins","doi":"10.14573/altex.2304161","DOIUrl":"10.14573/altex.2304161","url":null,"abstract":"While the original definition of replacement focuses on the replacement of the use of animals in science, a more contemporary definition focuses on accelerating the development and use of predictive and robust models, based on the latest science and technologies, to address scientific questions without the use of animals. The transition to animal free innovation is on the political agenda in and outside the European Union. The Beyond Animal Testing Index (BATI) is a benchmarking instrument designed to provide insight into the activities and contributions of research institutes to the transition to animal free innovation. The BATI allows participating organizations to learn from each other and stimulates continuous improvement. The BATI was modelled after the Access to Medicine Index, which benchmarks pharmaceutical companies on their efforts to make medicines widely available in developing countries. A prototype of the BATI was field-tested with three Dutch academic medical centers and two universities in 2020-2021. The field test demonstrated the usability and effectiveness of the BATI as a benchmarking tool. Analyses were performed across five different domains. The participating institutes concluded that the BATI served as an internal as well as an external stimulus to share, learn, and improve institutional strategies towards the transition to animal free innovation. The BATI also identified gaps in the development and implementation of 3R technologies. Hence, the BATI might be a suitable instrument for monitoring the effectiveness of policies. BATI version 1.0 is ready to be used for benchmarking at a larger scale.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"69-75"},"PeriodicalIF":5.6,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9964750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Assessing proarrhythmic potential of environmental chemicals using a high throughput in vitro-in silico model with human induced pluripotent stem cell-derived cardiomyocytes. 使用人诱导多能干细胞衍生的心肌细胞的高通量体外计算机模型评估环境化学物质的致心律失常潜力。

IF 5.6 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-09 Epub Date: 2023-10-19 DOI: 10.14573/altex.2306231

Hsing-Chieh Lin, Ivan Rusyn, Weihsueh A Chiu

{"title":"Assessing proarrhythmic potential of environmental chemicals using a high throughput in vitro-in silico model with human induced pluripotent stem cell-derived cardiomyocytes.","authors":"Hsing-Chieh Lin, Ivan Rusyn, Weihsueh A Chiu","doi":"10.14573/altex.2306231","DOIUrl":"10.14573/altex.2306231","url":null,"abstract":"QT prolongation and the potentially fatal arrhythmia Torsades de Pointes are common causes for withdrawing or restricting drugs; however, little is known about similar liabilities of environmental chemicals. Current in vitro-in silico models for testing proarrhythmic liabilities, using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), provide an opportunity to address this data gap. These methods are still low- to medium-throughput and not suitable for testing the tens of thousands of chemicals in commerce. We hypothesized that combining high-throughput population- based in vitro testing in hiPSC-CMs with a fully in silico data analysis workflow can offer sensitive and specific predictions of proarrhythmic potential. We calibrated the model with a published hiPSC-CM dataset of drugs known to be positive or negative for proarrhythmia and tested its performance using internal cross-validation and external validation. Additionally, we used computational down-sampling to examine three study designs for hiPSC-CM data: one replicate of one donor, five replicates of one donor, and one replicate of a population of five donors. We found that the population of five donors had the best performance for predicting proarrhythmic potential. The resulting model was then applied to predict the proarrhythmic potential of environmental chemicals, additionally characterizing risk through margin of exposure (MOE) calculations. Out of over 900 environmental chemicals tested, over 150 were predicted to have proarrhythmic potential, but only seven chemicals had a MOE < 1. We conclude that a high-throughput in vitro-in silico approach using population-based hiPSC-CM testing provides a reasonable strategy to screen environmental chemicals for proarrhythmic potential.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"37-49"},"PeriodicalIF":5.6,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10898275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71428953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Linking nanomaterial-induced mitochondrial dysfunction to existing adverse outcome pathways for chemicals. 将纳米材料诱导的线粒体功能障碍与现有的化学品不良后果途径联系起来。

IF 5.6 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-09 Epub Date: 2023-08-21 DOI: 10.14573/altex.2305011

Sivakumar Murugadoss, Ivana Vinković Vrček, Alexandra Schaffert, Martin Paparella, Barbara Pem, Anita Sosnowska, Maciej Stępnik, Marvin Martens, Egon L Willighagen, Tomasz Puzyn, Mihaela Roxana Cimpan, Frauke Lemaire, Birgit Mertens, Maria Dusinska, Valérie Fessard, Peter H Hoet

{"title":"Linking nanomaterial-induced mitochondrial dysfunction to existing adverse outcome pathways for chemicals.","authors":"Sivakumar Murugadoss, Ivana Vinković Vrček, Alexandra Schaffert, Martin Paparella, Barbara Pem, Anita Sosnowska, Maciej Stępnik, Marvin Martens, Egon L Willighagen, Tomasz Puzyn, Mihaela Roxana Cimpan, Frauke Lemaire, Birgit Mertens, Maria Dusinska, Valérie Fessard, Peter H Hoet","doi":"10.14573/altex.2305011","DOIUrl":"10.14573/altex.2305011","url":null,"abstract":"The adverse outcome pathway (AOP) framework plays a crucial role in the paradigm shift of toxicity testing towards the development and use of new approach methodologies. AOPs developed for chemicals are in theory applicable to nanomaterials (NMs). However, only initial efforts have been made to integrate information on NM-induced toxicity into existing AOPs. In a previous study, we identified AOPs in the AOP-Wiki associated with the molecular initiating events (MIEs) and key events (KEs) reported for NMs in scientific literature. In a next step, we analyzed these AOPs and found that mitochondrial toxicity plays a significant role in several of them at the molecular and cellular levels. In this study, we aimed to generate hypothesis-based AOPs related to NM-induced mitochondrial toxicity. This was achieved by integrating knowledge on NM-induced mitochondrial toxicity into all existing AOPs in the AOP-Wiki, which already includes mitochondrial toxicity as a MIE/KE. Several AOPs in the AOP-Wiki related to the lung, liver, cardiovascular and nervous system, with extensively defined KEs and key event relationships (KERs), could be utilized to develop AOPs that are relevant for NMs. However, the majority of the studies included in our literature review were of poor quality, particularly in reporting NM physicochemical characteristics, and NM-relevant mitochondrial MIEs were rarely reported. This study highlights the potential role of NM-induced mitochondrial toxicity in human-relevant adverse outcomes and identifies useful AOPs in the AOP-Wiki for the development of AOPs for NMs.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"76-90"},"PeriodicalIF":5.6,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10396093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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