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

Leveraging biomarkers and translational medicine for preclinical safety - Lessons for advancing the validation of alternatives to animal testing. 利用生物标志物和转化医学促进临床前安全性--推动动物试验替代品验证的经验教训。

IF 4.5 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-01 DOI: 10.14573/altex.2410011

Thomas Hartung, Nicholas M P King, Nicole Kleinstreuer, Marcel Leist, Danilo A Tagle

{"title":"Leveraging biomarkers and translational medicine for preclinical safety - Lessons for advancing the validation of alternatives to animal testing.","authors":"Thomas Hartung, Nicholas M P King, Nicole Kleinstreuer, Marcel Leist, Danilo A Tagle","doi":"10.14573/altex.2410011","DOIUrl":"https://doi.org/10.14573/altex.2410011","url":null,"abstract":"This article explores the potential of principles established in translational medicine for the use of bio-markers to advance the validation of alternatives to animal testing in preclinical safety assessment. It examines especially how such principles can enhance the predictive power, mechanistic under-standing, and human relevance of new approach methodologies (NAMs). Key concepts from translational medicine, such as fit-for-purpose validation, evidence-based approaches, and inte-grated testing strategies, are already being applied to the development and validation of NAMs. The article discusses challenges in implementing biomarker-based approaches, including standardi-zation, demonstration of relevance, regulatory acceptance, and addressing biological complexity. It also highlights opportunities for advancement through collaborative efforts, technological inno-vations, and regulatory evolution. Case studies demonstrate successful applications of biomarkers in preclinical safety, while future perspectives explore emerging trends like multi-omics integration, microphysiological systems, and artificial intelligence. The article emphasizes the potential of bio-markers and translational science approaches in creating more predictive, efficient, and ethical preclinical safety assessment paradigms in the use of NAMs. Use of biomarkers can enable the mechanistic validation of human-relevant models and provide a means to relate changes in NAMs to animal or clinical study results. By leveraging these tools, the field can work towards reducing reliance on animal testing while improving the accuracy and human relevance of safety predictions.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":"41 4","pages":"545-566"},"PeriodicalIF":4.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512492","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

Characterization and optimization of variability in a human colonic epithelium culture model. 人类结肠上皮细胞培养模型的特征和变异性优化。

IF 4.5 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-01 Epub Date: 2024-04-18 DOI: 10.14573/altex.2309221

Colleen M Pike, Bailey Zwarycz, Bryan E McQueen, Mariana Castillo, Catherine Barron, Jeremy M Morowitz, James A Levi, Dhiral Phadke, Michele Balik-Meisner, Deepak Mav, Ruchir Shah, Danielle L Cunningham Glasspoole, Ron Laetham, William Thelin, Maureen K Bunger, Elizabeth M Boazak

{"title":"Characterization and optimization of variability in a human colonic epithelium culture model.","authors":"Colleen M Pike, Bailey Zwarycz, Bryan E McQueen, Mariana Castillo, Catherine Barron, Jeremy M Morowitz, James A Levi, Dhiral Phadke, Michele Balik-Meisner, Deepak Mav, Ruchir Shah, Danielle L Cunningham Glasspoole, Ron Laetham, William Thelin, Maureen K Bunger, Elizabeth M Boazak","doi":"10.14573/altex.2309221","DOIUrl":"10.14573/altex.2309221","url":null,"abstract":"Animal models have historically been poor preclinical predictors of gastrointestinal (GI) directed therapeutic efficacy and drug-induced GI toxicity. Human stem and primary cell-derived culture systems are a major focus of efforts to create biologically relevant models that enhance preclinical predictive value of intestinal efficacy and toxicity. The inherent variability in stem cell-based cultures makes development of useful models a challenge; the stochastic nature of stem cell differentiation interferes with the ability to build and validate reproducible assays that query drug responses and pharmacokinetics. In this study, we aimed to characterize and reduce sources of variability in a complex stem cell-derived intestinal epithelium model, termed RepliGut® Planar, across cells from multiple human donors, cell lots, and passage numbers. Assessment criteria included barrier formation and integrity, gene expression, and cytokine responses. Gene expression and culture metric analyses revealed that controlling cell passage number reduces variability and maximizes physiological relevance of the model. In a case study where passage number was optimized, distinct cytokine responses were observed among four human donors, indicating that biological variability can be detected in cell cultures originating from diverse human sources. These findings highlight key considerations for designing assays that can be applied to additional primary cell-derived systems, as well as establish utility of the RepliGut® Planar platform for robust development of human-predictive drug-response assays.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"425-438"},"PeriodicalIF":4.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140861390","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

National workshop on alternatives to higher animals in toxicology and biomedical science. 关于毒理学和生物医学科学中高等动物替代品的国家研讨会。

IF 4.5 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-01 DOI: 10.14573/altex.2403151

Yasir H Siddique, Tanveer Beg, Himanshi Varshney, Iqra Subhan, Kajal Gaur, Javeria Fatima, Mohammad A Akbarsha

引用次数: 0

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