Altex-Alternatives To Animal Experimentation最新文献_第7页

Qualitative and quantitative concentration-response modelling of gene co-expression networks to unlock hepatotoxic mechanisms for next generation chemical safety assessment. 基因共表达网络的定性和定量浓度反应模型，为下一代化学品安全评估揭示肝毒性机制。

IF 5.6 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-01 Epub Date: 2024-02-20 DOI: 10.14573/altex.2309201

Steven J Kunnen, Emma Arnesdotter, Christian Tobias Willenbockel, Mathieu Vinken, Bob van de Water

{"title":"Qualitative and quantitative concentration-response modelling of gene co-expression networks to unlock hepatotoxic mechanisms for next generation chemical safety assessment.","authors":"Steven J Kunnen, Emma Arnesdotter, Christian Tobias Willenbockel, Mathieu Vinken, Bob van de Water","doi":"10.14573/altex.2309201","DOIUrl":"10.14573/altex.2309201","url":null,"abstract":"Next generation risk assessment of chemicals revolves around the use of mechanistic information without animal experimentation. In this regard, toxicogenomics has proven to be a useful tool to elucidate the underlying mechanisms of adverse effects of xenobiotics. In the present study, two widely used human in vitro hepatocyte culture systems, namely primary human hepatocytes (PHH) and human hepatoma HepaRG cells, were exposed to liver toxicants known to induce liver cholestasis, steatosis or necrosis. Benchmark concentration-response modelling was applied to transcriptomics gene co-expression networks (modules) to derive benchmark concentrations (BMCs) and to gain mechanistic insight into the hepatotoxic effects. BMCs derived by concentration-response modelling of gene co-expression modules recapitulated concentration-response modelling of individual genes. Although PHH and HepaRG cells showed overlap in deregulated genes and modules by the liver toxicants, PHH demonstrated a higher responsiveness, based on the lower BMCs of co-regulated gene modules. Such BMCs can be used as transcriptomics point of departure (tPOD) for assessing module-associated cellular (stress) pathways/processes. This approach identified clear tPODs of around maximum systemic concentration (Cmax) levels for the tested drugs, while for cosmetics ingredients the BMCs were 10-100-fold higher than the estimated plasma concentrations. This approach could serve next generation risk assessment practice to identify early responsive modules at low BMCs, that could be linked to key events in liver adverse outcome pathways. In turn, this can assist in delineating potential hazards of new test chemicals using in vitro systems and used in a risk assessment when BMCs are paired with chemical exposure assessment.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"213-232"},"PeriodicalIF":5.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139906868","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

Alternative methods go green! Green toxicology as a sustainable approach for assessing chemical safety and designing safer chemicals 绿色替代方法！绿色毒理学是评估化学品安全性和设计更安全化学品的可持续方法

IF 5.6 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-01 DOI: 10.14573/altex.2312291

Alexandra Maertens, Thomas Luechtefeld, Jean Knight, Thomas Hartung

{"title":"Alternative methods go green! Green toxicology as a sustainable approach for assessing chemical safety and designing safer chemicals","authors":"Alexandra Maertens, Thomas Luechtefeld, Jean Knight, Thomas Hartung","doi":"10.14573/altex.2312291","DOIUrl":"10.14573/altex.2312291","url":null,"abstract":"Green toxicology is marching chemistry into the 21st century. This emerging framework will transform how chemical safety is evaluated by incorporating evaluation of the hazards, exposures, and risks associated with chemicals into early product development in a way that minimizes adverse impacts on human and environmental health. The goal is to minimize toxic threats across entire supply chains through smarter designs and policies. Traditional animal testing methods are replaced by faster, cutting-edge innovations like organs-on-chips and artificial intelligence predictive models that are also more cost-effective. Core principles of green toxicology include utilizing alternative test methods, applying the precautionary principle, considering lifetime impacts, and emphasizing risk prevention over reaction. This paper provides an overview of these foundational concepts and describes current initiatives and future opportunities to advance the adoption of green toxicology approaches. Chal-lenges and limitations are also discussed. Green shoots are emerging with governments offering carrots like the European Green Deal to nudge industry. Noteworthy, animal rights and environ-mental groups have different ideas about the needs for testing and their consequences for animal use. Green toxicology represents the way forward to support both these societal needs with sufficient throughput and human relevance for hazard information and minimal animal suffering. Green toxi-cology thus sets the stage to synergize human health and ecological values. Overall, the integration of green chemistry and toxicology has potential to profoundly shift how chemical risks are evaluated and managed to achieve safety goals in a more ethical, ecologically-conscious manner.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":"41 1","pages":"3-19"},"PeriodicalIF":5.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139405148","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

Sensitivity analysis and quality indicators for an in vitro oral irritation assay. 体外口腔刺激性测定的灵敏度分析和质量指标。

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.2405071

Robert Gutierrez, Blaza Toman, Yong Ma, John T Elliott, Elijah J Petersen

{"title":"Sensitivity analysis and quality indicators for an in vitro oral irritation assay.","authors":"Robert Gutierrez, Blaza Toman, Yong Ma, John T Elliott, Elijah J Petersen","doi":"10.14573/altex.2405071","DOIUrl":"10.14573/altex.2405071","url":null,"abstract":"Biocompatibility testing using in vivo tests is often one of the final evaluations of new dental materials. To reduce the likelihood of failure at this late stage, predictive biocompatibility testing using in vitro methods is needed. In this study, we describe a sensitivity analysis of an oral irritation test by evaluating changes in the viability, using the MTT assay, of 3-D models with EpiOral constructs as a case study. Experiments that tested sources of variability in the assay led to recommendations regarding the storage of the constructs after arrival, pipetting procedure, use of MTT reagents from different vendors, use of transepithelial electrical resistance measurements, and statistical analyses. A statistical model was proposed to evaluate whether test substances yield a positive or negative result and the associated statistical confidence. Testing several test compounds such as the Y-4 polymer, which contains a known irritant, and dentally relevant substances such as sodium dodecyl sulfate (SDS) at varying concentrations revealed statistically significant results as expected. Lastly, a software app was designed to support a multiwell culture plate layout design. Overall, the findings and suggestions documented here will support the further development and potential standardization of this assay system and may be useful for the development of other assays using 3-D constructs.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"633-646"},"PeriodicalIF":4.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918020","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

60 Years of the 3Rs symposium: Lessons learned and the road ahead. 3Rs 专题讨论会 60 周年：经验教训与未来之路。

IF 4.5 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-01 DOI: 10.14573/altex.2403061

Michael Balls, Rolf Bass, Rodger Curren, Julia Fentem, Alan Goldberg, Thomas Hartung, Kathrin Herrmann, Nicole C Kleinstreuer, Lisa Libowitz, John Parascandola, Andrew Rowan, Horst Spielmann, Martin L Stephens, Russell S Thomas, Katya Tsaioun

{"title":"60 Years of the 3Rs symposium: Lessons learned and the road ahead.","authors":"Michael Balls, Rolf Bass, Rodger Curren, Julia Fentem, Alan Goldberg, Thomas Hartung, Kathrin Herrmann, Nicole C Kleinstreuer, Lisa Libowitz, John Parascandola, Andrew Rowan, Horst Spielmann, Martin L Stephens, Russell S Thomas, Katya Tsaioun","doi":"10.14573/altex.2403061","DOIUrl":"10.14573/altex.2403061","url":null,"abstract":"When The Principles of Humane Experimental Technique was published in 1959, authors William Russell and Rex Burch had a modest goal: to make researchers think about what they were doing in the laboratory – and to do it more humanely. Sixty years later, their groundbreaking book was celebrated for inspiring a revolution in science and launching a new field: The 3Rs of alternatives to animal experimentation. On November 22, 2019, some pioneering and leading scientists and researchers in the field gathered at the Johns Hopkins Bloomberg School of Public Health in Baltimore for the 60 Years of the 3Rs Symposium: Lessons Learned and the Road Ahead. The event was sponsored by the Johns Hopkins Center for Alternatives to Animal Testing (CAAT), the Foundation for Chemistry Research and Initiatives, the Alternative Research & Development Foundation (ARDF), the American Cleaning Institute (ACI), the International Fragrance Association (IFRA), the Institute for In Vitro Sciences (IIVS), John “Jack” R. Fowle III, and the Society of Toxicology (SoT). Fourteen presentations shared the history behind the groundbreaking publication, international efforts to achieve its aims, stumbling blocks to progress, as well as remarkable achievements. The day was a tribute to Russell and Burch, and a testament to what is possible when people from many walks of life – science, government, and industry – work toward a common goal.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":"41 2","pages":"179-201"},"PeriodicalIF":4.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140854798","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

International STakeholder NETwork (ISTNET) Workshop for creating a developmental and reproductive toxicity (DART) testing roadmap for regulatory purposes. 国际利益相关者网络（ISTNET）研讨会，为监管目的制定发育和生殖毒性（DART）测试路线图。

IF 4.5 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-01 DOI: 10.14573/altex.2410081

Ellen Fritsche, Lucia Selfa Aspiroz, Michael Arand, Elaine Faustman, Iris Müller

引用次数: 0

The validation of regulatory test methods - Conceptual, ethical, and philosophical foundations. 监管测试方法的验证--概念、伦理和哲学基础。

IF 4.5 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-01 DOI: 10.14573/altex.2409271

Thomas Hartung

{"title":"The validation of regulatory test methods - Conceptual, ethical, and philosophical foundations.","authors":"Thomas Hartung","doi":"10.14573/altex.2409271","DOIUrl":"https://doi.org/10.14573/altex.2409271","url":null,"abstract":"Validation establishes the reproducibility and relevance of regulatory test methods, particularly for new approach methods (NAMs) as alternatives to animal testing. While validation concepts provide a framework to assess method suitability, they rarely undergo method-critical assessment. This paper explores the philosophical and ethical foundations of the validation process, drawing from various philosophical traditions and contemporary ethical frameworks. How validation intersects with utilitarian principles, ethics of responsibility, and post-modern critiques is examined, offering a multifaceted perspective on its role in scientific progress and societal values. The paper argues for a paradigm shift in validation, moving beyond traditional animal-based comparisons towards more flexible, fit-for-purpose approaches that embrace emerging technologies and ethical con-siderations. Key ethical principles guiding NAM validation are discussed, including beneficence, non-maleficence, justice, and respect for animal welfare. Integrating these principles with scientific rigor can create a more holistic validation framework that balances human safety, animal welfare, and technological innovation. By critically examining the philosophical underpinnings of validation, this paper aims to stimulate dialogue on reforming the process to better align with contemporary scientific knowledge, ethical standards, and societal expectations. It calls for a more adaptive, transparent, and ethically grounded approach to validation that can accelerate the adoption of innovative and human-relevant toxicological methods while maintaining scientific integrity and public trust.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":"41 4","pages":"525-544"},"PeriodicalIF":4.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512494","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

The road to virtual control groups and the importance of proper body-weight selection. 通往虚拟对照组之路以及正确选择体重的重要性。

IF 4.5 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-01 Epub Date: 2024-05-22 DOI: 10.14573/altex.2403141

Alexander Gurjanov, Lea A I Vaas, Thomas Steger-Hartmann

{"title":"The road to virtual control groups and the importance of proper body-weight selection.","authors":"Alexander Gurjanov, Lea A I Vaas, Thomas Steger-Hartmann","doi":"10.14573/altex.2403141","DOIUrl":"10.14573/altex.2403141","url":null,"abstract":"Virtual control groups (VCGs) created from historical control data (HCD) can reduce the number of concurrent control group animals needed in regulatory toxicity studies by up to 25%. This study investigates the performance of VCGs on statistical outcomes of body weight development between treatment and control groups in legacy studies. The objective is to reproduce the statistical outcomes of 28-day sub-chronic studies (legacy studies) after replacing the concurrent control group with virtual ones. In rodent toxicity studies initial body weight is used as surrogate for the age of animals. For the assessment of VCG-sampling methods, three different approaches were explored: (i) sampling VCGs from the entire HCD, ignoring initial body weight information of the legacy study, (ii) sampling from HCD by matching the legacy study’s initial body weights, and (iii) sampling from HCD with assigned statistical weights derived from legacy study initial body weight information. The ability to reproduce statistical outcomes using virtual controls was determined by the congruence between the legacy study and the HCD weight distribution: regardless of the chosen approach, the ability to reproduce statistical outcomes was high for VCGs when the legacy study’s initial body weight distribution was similar to the HCD’s. When the initial body weight range of the legacy study was at the extreme ends of the HCD’s distribution, the weighted sampling approach was superior. This article demonstrates the importance of proper HCD matching by the legacy study’s initial body weight and discusses conditions to accurately reproduce body weight development.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"660-665"},"PeriodicalIF":4.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141162743","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

Editorial. 社论

IF 5.6 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-01

Sonja von Aulock

引用次数: 0

Have the non-technical summaries of animal experiments in Europe improved? An update 欧洲动物实验的非技术性总结是否有所改进？最新情况。

IF 4.5 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-01 Epub Date: 2024-03-14 DOI: 10.14573/altex.2310181

Katy Taylor, Tilo Weber, Laura Rego Alvarez

{"title":"Have the non-technical summaries of animal experiments in Europe improved? An update","authors":"Katy Taylor, Tilo Weber, Laura Rego Alvarez","doi":"10.14573/altex.2310181","DOIUrl":"10.14573/altex.2310181","url":null,"abstract":"Following a review of Directive 2010/63/EU on the protection of animals used for scientific purposes in the European Union (EU), non-technical project summaries (NTS) of all approved projects must be published in a central database using a standard template. Our initial review of the NTS reported in ALTEX in 2018 had found the NTS to be deficient in their accessibility and quality, notably the “adverse effects” section where the harms to the animals are meant to be described. Here we repeat our review to see if these legislative changes have improved the accessibility and quality of the NTS. As before, we focused on the NTS from the United Kingdom (UK) and Germany; even though the UK has left the EU, it is using the same template. We found significant improvement in the reporting of five of the six elements we identified as essential to the “predicted harms” section. However, there was no significant improvement in the reporting of adverse effects. Only 41% of German NTS and 48% of UK NTS are fully reporting this important element of the “predicted harms” section. In our view, researchers need support in describing the impact of their research on the animals and to assist here we include a checklist for competent authorities and a list of suggested terminology for standard administration and sampling procedures. Unless the NTS improve further, their utility as a tool for sharing of good practices in the 3Rs or to support evidence-based policymaking will remain limited.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"382-394"},"PeriodicalIF":4.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140141096","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

Toward implementing virtual control groups in nonclinical safety studies. 在非临床安全性研究中实施虚拟控制组。

IF 4.5 2区医学

Altex-Alternatives To Animal Experimentation Pub Date : 2024-01-01 Epub Date: 2023-12-01 DOI: 10.14573/altex.2310041

Emily Golden, David Allen, Alexander Amberg, Lennart T Anger, Elizabeth Baker, Szczepan W Baran, Frank Bringezu, Matthew Clark, Guillemette Duchateau-Nguyen, Sylvia E Escher, Varun Giri, Armelle Grevot, Thomas Hartung, Dingzhou Li, Laura Lotfi, Wolfgang Muster, Kevin Snyder, Ronald Wange, Thomas Steger-Hartmann

{"title":"Toward implementing virtual control groups in nonclinical safety studies.","authors":"Emily Golden, David Allen, Alexander Amberg, Lennart T Anger, Elizabeth Baker, Szczepan W Baran, Frank Bringezu, Matthew Clark, Guillemette Duchateau-Nguyen, Sylvia E Escher, Varun Giri, Armelle Grevot, Thomas Hartung, Dingzhou Li, Laura Lotfi, Wolfgang Muster, Kevin Snyder, Ronald Wange, Thomas Steger-Hartmann","doi":"10.14573/altex.2310041","DOIUrl":"10.14573/altex.2310041","url":null,"abstract":"Historical data from control groups in animal toxicity studies are currently mainly used for comparative purposes to assess validity and robustness of study results. Due to the highly controlled environment in which the studies are performed and the homogeneity of the animal collectives it has been proposed to use the historical data to build so-called virtual control groups, which could partly or entirely replace the concurrent control group. This would constitute a substantial contribution to the reduction of animal use in safety studies. Before the concept can be implemented, the prerequisites regarding data collection, curation, and statistical evaluation together with a validation strategy need to be identified to avoid any impairment of the study outcome and subsequent consequences for human risk assessment. To further assess and develop the concept of virtual control groups, the transatlantic think tank for toxicology (t4) sponsored a workshop with stakeholders from the pharmaceutical and chemical industry, academia, FDA, contract research organizations (CROs), and non-governmental organizations in Washington, which took place in March 2023. This report summarizes the current efforts of a European initiative to share, collect, and curate animal control data in a centralized database and the first approaches to identify optimal matching criteria between virtual controls and the treatment arms of a study as well as first reflections about strategies for a qualification procedure and potential pitfalls of the concept.","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"282-301"},"PeriodicalIF":4.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138479251","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