Altex-Alternatives To Animal Experimentation最新文献

{"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":"<p><p>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.</p>","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}

{"title":"Editorial.","authors":"Sonja von Aulock","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":"41 1","pages":"U2"},"PeriodicalIF":5.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139405149","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}

{"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":"<p><p>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.</p>","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}

{"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":"<p><p>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.</p>","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}

{"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":"<p><p>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.</p>","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}

{"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":"<p><p>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.</p>","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}

{"title":"Data-driven derivation of an adverse outcome pathway linking vascular endothelial growth factor receptor (VEGFR), endocrine disruption, and atherosclerosis.","authors":"Daniel Ehrlich, Shagun Krishna, Nicole Kleinstreuer","doi":"10.14573/altex.2403211","DOIUrl":"10.14573/altex.2403211","url":null,"abstract":"<p><p>Dysregulation of vascular endothelial growth factor (VEGF) and its receptor (VEGFR) contributes to atherosclerosis and cardiovascular disease (CVD), making it a potential target for CVD risk assessment. High-throughput screening (HTS) approaches have resulted in large-scale in vitro data, providing mechanistic information that can help assess chemical toxicity and identify molecular ini­tiating events (MIEs) of adverse outcome pathways (AOPs). AOPs represent a logical sequence of biological responses contributing to toxicity and are valuable tools to inform chemical risk assessment. Here, we used HTS data to formulate an AOP relating VEGF signaling perturbation to atheroscle­rosis. ToxCast, Tox21, and PubChem data were evaluated to obtain bioprofiles of 4165 compounds active in assays targeting VEGFR. Cheminformatics analysis identified 109 enriched structural fin­gerprints. Applying a subspace clustering approach based on chemical structure bioactivity yielded 12 primary targets, whose relevance to CVD was confirmed by an AI-assisted literature review. An AOP was hypothesized by coupling mechanistic relationships highlighted by HTS data with literature review findings, linking serotonin receptor (HTR), estrogen receptor alpha (ERα), and vasopressin receptor (AVPR) targets with VEGFR activity, angiogenic signaling, and atherosclerosis. Several endocrine disrupting chemicals (EDCs), e.g., bisphenols, triclosan, dichlorodiphenyltrichloroethane (DDT), and polychlorinated biphenyls (PCBs), were identified as relevant chemical stressors. Sub­space clustering of these chemicals evaluated potential MIEs and highlighted associations with use case classes. By applying computational methods to profile HTS data and hypothesize a mechanistic AOP, this study proposes a data-driven approach to evaluating environmental cardiotoxicity, which could eventually supplement and reduce the need for animal testing in toxicological assessments.</p>","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"617-632"},"PeriodicalIF":4.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560307","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}

{"title":"3D bioprinting of human skin and squamous cell tumors (SCCs) as advanced models for precision medicine (BIOSQIN).","authors":"Stefano Lorenzetti, Milena Mikhail, Laura Di Benedetto, Elena Dellambra, Cristina M Failla, Sara M Giannitelli, Riccardo Levato, Alessia Longoni, Valeria Bartolocci, Daniela Lulli, Sofia Raniolo, Isabella De Angelis","doi":"10.14573/altex.2402261","DOIUrl":"https://doi.org/10.14573/altex.2402261","url":null,"abstract":"","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":"41 3","pages":"485-486"},"PeriodicalIF":4.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141629286","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}

{"title":"Trust your gut: Establishing confidence in gastrointestinal models - An overview of the state of the science and contexts of use.","authors":"Susan Debad, David Allen, Omari Bandele, Colin Bishop, Michaela Blaylock, Paul Brown, Maureen K Bunger, Julia Y Co, Lynn Crosby, Amber B Daniel, Steve S Ferguson, Kevin Ford, Gonçalo Gamboa da Costa, Kristin H Gilchrist, Matthew W Grogg, Maureen Gwinn, Thomas Hartung, Simon P Hogan, Ye Eun Jeong, George En Kass, Elaina Kenyon, Nicole C Kleinstreuer, Ville Kujala, Patrik Lundquist, Joanna Matheson, Shaun D McCullough, Angela Melton-Celsa, Steven Musser, Ilung Oh, Oluwakemi B Oyetade, Sarita U Patil, Elijah J Petersen, Nakissa Sadrieh, Christie M Sayes, Benjamin S Scruggs, Yu-Mei Tan, Bill Thelin, M Tyler Nelson, José V Tarazona, John F Wambaugh, Jun-Young Yang, Changwoo Yu, Suzanne Fitzpatrick","doi":"10.14573/altex.2403261","DOIUrl":"10.14573/altex.2403261","url":null,"abstract":"<p><p>The webinar series and workshop titled “Trust Your Gut: Establishing Confidence in Gastrointestinal Models – An Overview of the State of the Science and Contexts of Use” was co-organized by NICEATM, NIEHS, FDA, EPA, CPSC, DoD, and the Johns Hopkins Center for Alternatives to Animal Testing (CAAT) and hosted at the National Institutes of Health in Bethesda, MD, USA on October 11-12, 2023. New approach methods (NAMs) for assessing issues of gastrointestinal tract (GIT)- related toxicity offer promise in addressing some of the limitations associated with animal-based assessments. GIT NAMs vary in complexity, from two-dimensional monolayer cell line-based systems to sophisticated 3-dimensional organoid systems derived from human primary cells. Despite advances in GIT NAMs, challenges remain in fully replicating the complex interactions and pro­cesses occurring within the human GIT. Presentations and discussions addressed regulatory needs, challenges, and innovations in incorporating NAMs into risk assessment frameworks; explored the state of the science in using NAMs for evaluating systemic toxicity, understanding absorption and pharmacokinetics, evaluating GIT toxicity, and assessing potential allergenicity; and discussed strengths, limitations, and data gaps of GIT NAMs as well as steps needed to establish confidence in these models for use in the regulatory setting.</p>","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"402-424"},"PeriodicalIF":5.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11413798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141428266","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}

{"title":"The benefits of validation of methods for toxicity testing outweigh its costs","authors":"Anne Gourmelon, Philippe Hubert, Elise Grignard, Lisa Baumann, Sharon Munn, Cécile Michel","doi":"10.14573/altex.2403051","DOIUrl":"10.14573/altex.2403051","url":null,"abstract":"<p><p>The 4th Annual Forum on Endocrine Disrupters organized by the European Commission brought together the authors of this article around the topic: “From bench to validated test guidelines: (pre)val­idation of test methods”. Validation activities are meant to demonstrate the relevance and reliability of methods and approaches used in regulatory safety testing. These activities are essential to facil­itate regulatory use, still they are largely underfunded and unattractive to the scientific community. In the last decade, large amounts of funding have been invested in European research towards the development of approaches that can be used in regulatory decision-making, including for the identification of endocrine disrupters. There is a vast pool of candidate test methods for potential reg­ulatory applications, but most of them will not be used due to the absence of consideration of their relevance and reliability outside the method developer’s laboratory. This article explains the reasons why such a gap exists between the outputs of research projects and the uptake in a regulatory context. In parallel, there are also increasing expectations from the regulatory science community that validation becomes more efficient with respect to time and resources. This article shares some of the lessons learned and proposes paths forward for validation of new methods that are not intended as one-to-one replacements of animal studies. This includes submitting only mature methods for validation that were developed following good practices and good documentation, proposing a greater emphasis on well-documented transferability studies, and adopting a cost-sharing model among those who benefit from validated methods.</p>","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"395-401"},"PeriodicalIF":4.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140159518","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}