Altex-Alternatives To Animal Experimentation最新文献_第5页

Elements and development processes for test methods in toxicology and human health-relevant life science research. 毒理学和与人类健康相关的生命科学研究中测试方法的要素和开发流程。

IF 5.6 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-01 DOI: 10.14573/altex.2401041

Eike Cöllen, Yaroslav Tanaskov, Anna-Katharina Holzer, Michelle Dipalo, Jasmin Schäfer, Udo Kraushaar, Marcel Leist

{"title":"Elements and development processes for test methods in toxicology and human health-relevant life science research.","authors":"Eike Cöllen, Yaroslav Tanaskov, Anna-Katharina Holzer, Michelle Dipalo, Jasmin Schäfer, Udo Kraushaar, Marcel Leist","doi":"10.14573/altex.2401041","DOIUrl":"10.14573/altex.2401041","url":null,"abstract":"Many laboratory procedures generate data on properties of chemicals, but they cannot be equated with toxicological \"test methods\". This apparent discrepancy is not limited to in vitro testing, using animal-free new approach methods (NAM), but also applies to animal-based testing approaches. Here, we give a brief overview of the differences between data generation and the setup or use of a complete test method. While there is excellent literature available on this topic for specialists (GIVIMP guidance; ToxTemp overview), a brief overview and easily-accessible entry point may be useful for a broader community. We provide a single figure to summarize all test method elements and processes required in the development (setup and adaptation) of a test method. The exposure scheme, the endpoint, and the test system are briefly outlined as fundamental elements of any test method. A rationale is provided, why they are not sufficient. We then explain the importance and role of purpose definition (including some information on what is modelled) and the prediction model, aka data interpretation procedure, which depends on the purpose definition, as further essential elements. This connection exemplifies that all fundamental elements are interdependent, and none can be omitted. Finally, discussion is provided on validation as a measure to provide confidence in the reliability, performance, and relevance of a test method. In this sense, validation may be considered a sixth fundamental element for practical use of test methods.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":"41 1","pages":"142-148"},"PeriodicalIF":5.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139425974","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

Indian Society for Alternatives to Animal Experiments: Sixth annual meeting and international conference. 印度动物实验替代学会：第六届年会暨国际会议。

IF 5.6 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-01 DOI: 10.14573/altex.2402141

Syed Z Rahman, Alam Anam, Ankita Pandey, Rohit Bisht, Mohammad A Akbarsha

引用次数: 0

Development of a defined approach for eye hazard identification of solid chemicals according to the three UN GHS categories. 根据联合国全球统一制度的三个类别，为固体化学品的眼睛危害识别制定明确的方法。

IF 4.5 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-01 Epub Date: 2024-05-17 DOI: 10.14573/altex.2401191

Nathalie Alépée, Els Adriaens

{"title":"Development of a defined approach for eye hazard identification of solid chemicals according to the three UN GHS categories.","authors":"Nathalie Alépée, Els Adriaens","doi":"10.14573/altex.2401191","DOIUrl":"10.14573/altex.2401191","url":null,"abstract":"Currently there are two OECD-adopted defined approaches (DA) for eye hazard identification of non-surfactant liquids (OECD TG 467). The current study aimed to develop a DA for eye hazard identification of solid chemicals according to the three UN GHS categories (Cat.1, Cat. 2, No Cat.): the DAS. The DAS combines two test methods described in OECD TG 437 and TG 492. The DAS was developed based on in-depth statistical analysis of a database on solids containing in vitro and historically curated in vivo Draize eye test data. The performance of the DAS was assessed by comparing the predictions with the classification based on in vivo Draize eye test data, on the one hand, and with the performance criteria established by the OECD expert group, on the other hand. In a first tier of the DAS, the SkinEthic™ HCE EIT method (TG 492) is used to distinguish No Cat. from classified substances. For classified substances, the BCOP LLBO method (TG 437) is used to identify Cat. 1, and the remaining solids are predicted Cat. 2. In summary, 77.4% Cat. 1 (N=31), 52.3% Cat. 2 (N=18), and 70.0% of No Cat. (N=60) solids were correctly identified compared to the classification based on the Draize eye test. The percentage of correct predictions met the minimum OECD performance values of 75% Cat. 1, 50% Cat. 2, and 70% No Cat., and the percentage of mispredictions was below the established maximum values. Therefore, inclusion of the DAS in OECD TG 467 has been achieved.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"457-468"},"PeriodicalIF":4.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140960843","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

Phase-out planning for animal experimentation. 逐步淘汰动物实验计划。

IF 4.5 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-01 Epub Date: 2024-03-01 DOI: 10.14573/altex.2312041

Nico Müller

引用次数: 0

Risk-based prioritization of PFAS using phenotypic and transcriptomic data from human induced pluripotent stem cell-derived hepatocytes and cardiomyocytes. 利用从人类诱导多能干细胞衍生的肝细胞和心肌细胞中获得的表型和转录组数据，对全氟辛烷磺酸进行基于风险的优先排序。

IF 4.5 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-01 Epub Date: 2024-02-22 DOI: 10.14573/altex.2311031

Han-Hsuan D Tsai, Lucie C Ford, Zunwei Chen, Allison N Dickey, Fred A Wright, Ivan Rusyn

{"title":"Risk-based prioritization of PFAS using phenotypic and transcriptomic data from human induced pluripotent stem cell-derived hepatocytes and cardiomyocytes.","authors":"Han-Hsuan D Tsai, Lucie C Ford, Zunwei Chen, Allison N Dickey, Fred A Wright, Ivan Rusyn","doi":"10.14573/altex.2311031","DOIUrl":"10.14573/altex.2311031","url":null,"abstract":"Per- and polyfluoroalkyl substances (PFAS) are chemicals with important applications; they are persistent in the environment and may pose human health hazards. Regulatory agencies are considering restrictions and bans of PFAS; however, little data exists for informed decisions. Several prioritization strategies were proposed for evaluation of potential hazards of PFAS. Structure-based grouping could expedite the selection of PFAS for testing; still, the hypothesis that structure-effect relationships exist for PFAS requires confirmation. We tested 26 structurally diverse PFAS from 8 groups using human induced pluripotent stem cell-derived hepatocytes and cardiomyocytes, and tested concentration-response effects on cell function and gene expression. Few phenotypic effects were observed in hepatocytes, but negative chronotropy was observed in cardiomyocytes for 8 PFAS. Substance- and cell type-dependent transcriptomic changes were more prominent but lacked substantial group-specific effects. In hepatocytes, we found upregulation of stress-related and extracellular matrix organization pathways, and down-regulation of fat metabolism. In cardiomyocytes, contractility-related pathways were most affected. We derived phenotypic and transcriptomic points of departure and compared them to predicted PFAS exposures. Conservative estimates for bioactivity and exposure were used to derive a bioactivity-to-exposure ratio (BER) for each PFAS; 23 of 26 PFAS had BER > 1. Overall, these data suggest that structure-based PFAS grouping may not be sufficient to predict their biological effects. Testing of individual PFAS may be needed for scientifically-supported decision-making. Our proposed strategy of using two human cell types and considering phenotypic and transcriptomic effects, combined with dose-response analysis and calculation of BER, may be used for PFAS prioritization.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"363-381"},"PeriodicalIF":4.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11305846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013697","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

The Implementation Moonshot Project for Alternative Chemical Testing (IMPACT) toward a Human Exposome Project. 替代化学品检测实施月项目（IMPACT），迈向人类暴露组项目。

IF 4.5 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-01 DOI: 10.14573/altex.2407081

Fenna C M Sillé, Francois Busquet, Suzie Fitzpatrick, Kathrin Herrmann, Lisa Leenhouts-Martin, Thomas Luechtefeld, Alexandra Maertens, Gary W Miller, Lena Smirnova, Katya Tsaioun, Thomas Hartung

{"title":"The Implementation Moonshot Project for Alternative Chemical Testing (IMPACT) toward a Human Exposome Project.","authors":"Fenna C M Sillé, Francois Busquet, Suzie Fitzpatrick, Kathrin Herrmann, Lisa Leenhouts-Martin, Thomas Luechtefeld, Alexandra Maertens, Gary W Miller, Lena Smirnova, Katya Tsaioun, Thomas Hartung","doi":"10.14573/altex.2407081","DOIUrl":"10.14573/altex.2407081","url":null,"abstract":"The Human Exposome Project aims to revolutionize our understanding of how environmental exposures affect human health by systematically cataloging and analyzing the myriad exposures individuals encounter throughout their lives. This initiative draws a parallel with the Human Genome Project, expanding the focus from genetic factors to the dynamic and complex nature of environ-mental interactions. The project leverages advanced methodologies such as omics technologies, biomonitoring, microphysiological systems (MPS), and artificial intelligence (AI), forming the foun-dation of exposome intelligence (EI) to integrate and interpret vast datasets. Key objectives include identifying exposure-disease links, prioritizing hazardous chemicals, enhancing public health and regulatory policies, and reducing reliance on animal testing. The Implementation Moonshot Project for Alternative Chemical Testing (IMPACT), spearheaded by the Center for Alternatives to Animal Testing (CAAT), is a new element in this endeavor, driving the creation of a public-private part-nership toward a Human Exposome Project with a stakeholder forum in 2025. Establishing robust infrastructure, fostering interdisciplinary collaborations, and ensuring quality assurance through sys-tematic reviews and evidence-based frameworks are crucial for the project's success. The expected outcomes promise transformative advancements in precision public health, disease prevention, and a more ethical approach to toxicology. This paper outlines the strategic imperatives, challenges, and opportunities that lie ahead, calling on stakeholders to support and participate in this landmark initiative for a healthier, more sustainable future.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":"41 3","pages":"344-362"},"PeriodicalIF":4.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141629289","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

A proof-of-concept rat toxicity study highlights the potential utility and challenges of virtual control groups. 一项概念验证大鼠毒性研究强调了虚拟对照组的潜在作用和挑战。

IF 4.5 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-01 Epub Date: 2024-08-07 DOI: 10.14573/altex.2404201

Roxanne Andaya, Ruth Sullivan, Tony Pourmohamad, Matt Hayes, Pierre Maliver, Steven Laing, Catrin Hasselgren, Noel Dybdal, Adeyemi O Adedeji, Lennart T Anger

{"title":"A proof-of-concept rat toxicity study highlights the potential utility and challenges of virtual control groups.","authors":"Roxanne Andaya, Ruth Sullivan, Tony Pourmohamad, Matt Hayes, Pierre Maliver, Steven Laing, Catrin Hasselgren, Noel Dybdal, Adeyemi O Adedeji, Lennart T Anger","doi":"10.14573/altex.2404201","DOIUrl":"10.14573/altex.2404201","url":null,"abstract":"The virtual control group (VCG) concept provides a potential opportunity to reduce animal use in drug development by replacing concurrent control groups (CCGs) in nonclinical toxicity studies. This work investigated the feasibility and reliability of using VCGs in place of CCGs. A historical control database (HCD), constructed from Genentech Inc. rat toxicity study data, was reviewed to understand trends and sources of variability in control animals over time, and to identify data curation requirements for assembling VCGs, e.g., alignment of units of measurement. Several endpoints were investigated and stratified against different study design parameters. Sex, route of administration, fasting status, and body weight at study initiation were among the parameters that were indicated as key matching criteria. With a high-level understanding of potential sources of variability, a retrospective proof-of-concept (POC) study was designed, evaluating a historical rat pilot toxicity study for test article-related changes. A masked interpretation of the study was conducted using its CCG and two unique VCGs that were constructed from individual animal data pulled from our HCD. While the results of the microscopic pathology assessment and most endpoints were similar across the different control groups, the POC revealed the risk of using VCGs to interpret subtle test article-related changes in clinical pathology parameters. Within the context of our POC, it appears the use of a VCG is not completely equivalent to the CCG, especially with clinical pathology parameters. Additional work is needed to understand the potential utility, and thus, viability of VCGs in other contexts.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"647-659"},"PeriodicalIF":4.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918018","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 quality control of human and animal tetanus vaccines. 开发用于人类和动物破伤风疫苗质量控制的单克隆抗体夹心酶联免疫吸附试验。

IF 4.5 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-01 Epub Date: 2024-08-23 DOI: 10.14573/altex.2401171

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

{"title":"Development of a monoclonal antibody sandwich ELISA for the quality control of human and animal tetanus vaccines.","authors":"Laura Hassall, Daniel A Yara, Rebecca Riches-Duit, Peter Rigsby, Alexandre Dobly, Maxime Vermeulen, Antoine Francotte, Bart Faber, Paul Stickings","doi":"10.14573/altex.2401171","DOIUrl":"10.14573/altex.2401171","url":null,"abstract":"Antigen identity, quantity and integrity are key factors to be evaluated as part of consistency testing of tetanus vaccines. Here we have developed a monoclonal antibody sandwich ELISA to measure the relative amount and quality of tetanus toxoid (TTxd) in human and animal tetanus vaccines. The ELISA is highly specific, has good dilutional linearity, and is suitable for detecting TTxd in a range of different products. We have demonstrated the ability of the assay to discriminate between batches of different content, using vaccine batches that had been prepared to contain differing amounts of TTxd, and of different quality, using samples of non-adjuvanted TTxd that had been exposed to sonication and final lot vaccines that had been exposed to heat or oxidative stress. We have also demonstrated successful transfer of the method to other laboratories and have shown that different tetanus antigen materials may be able to serve as a reference antigen for standardization of the method. The results show this test has the potential to play a key role in a control strategy no longer including an in vivo potency test.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"588-604"},"PeriodicalIF":4.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127267","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

Revolutionizing developmental neurotoxicity testing - a journey from animal models to advanced in vitro systems. 革命性的发育神经毒性测试--从动物模型到先进体外系统的历程。

IF 4.5 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-01 Epub Date: 2024-04-06 DOI: 10.14573/altex.2403281

Lena Smirnova, Helena T Hogberg, Marcel Leist, Thomas Hartung

{"title":"Revolutionizing developmental neurotoxicity testing - a journey from animal models to advanced in vitro systems.","authors":"Lena Smirnova, Helena T Hogberg, Marcel Leist, Thomas Hartung","doi":"10.14573/altex.2403281","DOIUrl":"10.14573/altex.2403281","url":null,"abstract":"Developmental neurotoxicity (DNT) testing has seen enormous progress over the last two decades. Preceding even the publication of the animal-based OECD test guideline for DNT testing in 2007, a series of non-animal technology workshops and conferences that started in 2005 has shaped a community that has delivered a comprehensive battery of in vitro test methods (DNT IVB). Its data interpretation is now covered by a very recent OECD guidance (No. 377). Here, we overview the progress in the field, focusing on the evolution of testing strategies, the role of emerging technologies, and the impact of OECD test guidelines on DNT testing. In particular, this is an example of the targeted development of an animal-free testing approach for one of the most complex hazards of chemicals to human health. These developments started literally from a blank slate, with no proposed alternative methods available. Over two decades, cutting-edge science enabled the design of a testing approach that spares animals and enables throughput to address this challenging hazard. While it is evident that the field needs guidance and regulation, the massive economic impact of decreased human cognitive capacity caused by chemical exposure should be prioritized more highly. Beyond this, the claim to fame of DNT in vitro testing is the enormous scientific progress it has brought for understanding the human brain, its development, and how it can be perturbed.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":"41 2","pages":"152-178"},"PeriodicalIF":4.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140861361","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

E-validation - Unleashing AI for validation. 电子验证--利用人工智能进行验证。

IF 4.5 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-01 DOI: 10.14573/altex.2409211

Thomas Hartung, Alexandra Maertens, Thomas Luechtefeld

{"title":"E-validation - Unleashing AI for validation.","authors":"Thomas Hartung, Alexandra Maertens, Thomas Luechtefeld","doi":"10.14573/altex.2409211","DOIUrl":"https://doi.org/10.14573/altex.2409211","url":null,"abstract":"The validation of new approach methods (NAMs) in toxicology faces significant challenges, including the integration of diverse data, selection of appropriate reference chemicals, and lengthy, resource-intensive consensus processes. This article proposes an artificial intelligence (AI)-based approach, termed e-validation, to optimize and accelerate the NAM validation process. E-vali-dation employs advanced machine learning and simulation techniques to systematically design validation studies, select informative reference chemicals, integrate existing data, and provide tailored training. The approach aims to shorten current decade-long validation timelines, using fewer resources while enhancing rigor. Key components include the smart selection of reference chemicals using clustering algorithms, simulation of validation studies, mechanistic validation powered by AI, and AI-enhanced training for NAM education and implementation. A centralized dashboard interface could integrate these components, streamlining workflows and providing real-time decision support. The potential impacts of e-validation are extensive, promising to accel-erate biomedical research, enhance chemical safety assessment, reduce animal testing, and drive regulatory and commercial innovation. While the integration of AI and machine learning offers sig-nificant advantages, challenges related to data quality, complexity of implementation, scalability, and ethical considerations must be addressed. Real-world validation and pilot studies are crucial to demonstrate the practical benefits and feasibility of e-validation. This transformative approach has the potential to revolutionize toxicological science and regulatory practices, ushering in a new era of predictive, personalized, and preventive health sciences.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":"41 4","pages":"567-587"},"PeriodicalIF":4.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512490","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