Francesca Caloni, Alessandra Cazzaniga, Arno C Gutleb, Thomas Hartung, Helena Kandarova, Giulia Ranaldi, Hassan Rashidi, Doris Wilflingseder, Saliha Moutaharrik
{"title":"Non-animal models: Complexity for interactions…Connecting science.","authors":"Francesca Caloni, Alessandra Cazzaniga, Arno C Gutleb, Thomas Hartung, Helena Kandarova, Giulia Ranaldi, Hassan Rashidi, Doris Wilflingseder, Saliha Moutaharrik","doi":"10.14573/altex.2407181","DOIUrl":"https://doi.org/10.14573/altex.2407181","url":null,"abstract":"","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":"41 4","pages":"666-668"},"PeriodicalIF":4.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480215","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}
Augusto Vitale, Maurilio Calleri, Francesca Caloni, Cristina M Failla, Paola Granata, Laura Gribaldo, Urte Jaeh, Michela Kuan, Stefano Lorenzetti, Francesco Nevelli, Giulia Ranaldi, Irene Ruspantini, Orsola R Salva, Lena Smirnova, Julia Steitz, Luigia Trabace, Zoe Windsor, Isabella De Angelis
{"title":"3 Days for 3Rs 2023: Refinement, reduction, replacement.","authors":"Augusto Vitale, Maurilio Calleri, Francesca Caloni, Cristina M Failla, Paola Granata, Laura Gribaldo, Urte Jaeh, Michela Kuan, Stefano Lorenzetti, Francesco Nevelli, Giulia Ranaldi, Irene Ruspantini, Orsola R Salva, Lena Smirnova, Julia Steitz, Luigia Trabace, Zoe Windsor, Isabella De Angelis","doi":"10.14573/altex.2402121","DOIUrl":"https://doi.org/10.14573/altex.2402121","url":null,"abstract":"","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":"41 2","pages":"329-330"},"PeriodicalIF":5.6,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140871114","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}
Tom Roos, Cathalijn Leenaars, Alexandra Schaffert, Martin Paparella, Sivakumar Murugadoss, Birgit Mertens, Nunzia Linzalone, Gabriele Donzelli, Merel Ritskes-Hoitinga, Ronette Gehring
{"title":"Pollutant exposure and myocardial injury: Protocol and progress report for a toxicological systematic mapping review.","authors":"Tom Roos, Cathalijn Leenaars, Alexandra Schaffert, Martin Paparella, Sivakumar Murugadoss, Birgit Mertens, Nunzia Linzalone, Gabriele Donzelli, Merel Ritskes-Hoitinga, Ronette Gehring","doi":"10.14573/altex.2304111","DOIUrl":"10.14573/altex.2304111","url":null,"abstract":"<p><p>An increasing body of evidence identifies pollutant exposure as a risk factor for cardiovascular disease (CVD), while CVD incidence is rising steadily with the aging population. Although numerous experimental studies are now available, the mechanisms through which lifetime exposure to environmental pollutants can result in CVD are not fully understood. To comprehensively describe and understand the pathways through which pollutant exposure leads to cardiotoxicity, a systematic mapping review of the available toxicological evidence is needed. This protocol outlines a step-by-step framework for conducting this review. Using the National Toxicology Program (NTP) Health Assessment and Translation (HAT) approach for conducting toxicological systematic reviews, we selected 362 out of 8110 in vitro (17%), in vivo (67%), and combined (15%) studies for 129 potential cardiotoxic environmental pollutants, including heavy metals (29%), air pollutants (16%), pesticides (27%), and other chemicals (28%). The internal validity of included studies is being assessed with HAT and SYRCLE risk of bias tools. Tabular templates are being used to extract key study elements regarding study setup, methodology, techniques, and (qualitative and quantitative) outcomes. Subsequent synthesis will consist of an explorative meta-analysis of possible pollutant-related cardiotoxicity. Evidence maps and interactive knowledge graphs will illustrate evidence streams, cardiotoxic effects, and associated quality of evidence, helping researchers and regulators to efficiently identify pollutants of interest. The evidence will be integrated in novel adverse outcome pathways to facilitate regulatory acceptance of non-animal methods for cardiotoxicity testing. The current article describes the progress of the steps made in the systematic mapping review process.</p>","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":"248-259"},"PeriodicalIF":4.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138177951","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}
Marita Meurer, Manasa Nandimandalam, Maren von Köckritz-Blickwede, André Bleich
{"title":"Micro-replace systems.","authors":"Marita Meurer, Manasa Nandimandalam, Maren von Köckritz-Blickwede, André Bleich","doi":"10.14573/altex.2407021","DOIUrl":"10.14573/altex.2407021","url":null,"abstract":"","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":"41 3","pages":"486-488"},"PeriodicalIF":4.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141629287","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}
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":"<p><p>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.</p>","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}
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":"<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}
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":"<p><p>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.</p>","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}
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":"<p><p>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.</p>","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}
{"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}