Altex-Alternatives To Animal Experimentation最新文献

{"title":"Exploring the synergy of CRISPR and microphysiological systems.","authors":"Emanuele Celauro, Amer Saleh, Prathap K Mahalingaiah, Lisa Mohamet, Rhiannon David, Roberto Nitsch","doi":"10.14573/altex.2403251","DOIUrl":"https://doi.org/10.14573/altex.2403251","url":null,"abstract":"<p><p>Since its discovery as an innate bacterial immune system, the Clustered regularly interspaced short palindromic repeats (CRISPR) associated nuclease 9 (CRISPR-Cas9) system has quickly landed on mammalian genomes to become the first-in-class editing technique. CRISPR-Cas9 offered an invaluable approach to correct pathogenic mutations, thus becoming a promising cure for diseases with highly unmet medical needs. To date, several attempts with different degrees of success were done to understand, categorize and predict the outcome of genetic manipulation. The lack of an appropriate and translatable model to test CRISPR/Cas9 effects, both wanted and unwanted, has therefore limited its applications to advance gene therapies. Herein we describe the potential of microphysiological systems (MPS) as an alternative to the classical surrogates used in CRISPR safety studies, such as immortalized cell lines or small mammals (e.g. rodents), to facilitate the progress of new CRISPR medicines to the clinics.</p>","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993904","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 turning point: April 2025 marks historic shift in US animal testing policy.","authors":"Thomas Hartung","doi":"10.14573/altex.2504301","DOIUrl":"https://doi.org/10.14573/altex.2504301","url":null,"abstract":"","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997792","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":"Virtual control groups in non-clinical toxicology - A replicability challenge.","authors":"Thomas Steger-Hartmann, Guillemette Duchateau-Nguyen, Frank Bringezu, Manuela Onidi, Martina Stirn","doi":"10.14573/altex.2503061","DOIUrl":"https://doi.org/10.14573/altex.2503061","url":null,"abstract":"","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025494","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":"Assessment of developmental neurotoxicology-associated alterations in neuronal architecture and function using Caenorhabditis elegans.","authors":"Javier Huayta, Sarah Seay, Joseph Laster, Nelson A Rivera, Abigail S Joyce, P Lee Ferguson, Heileen Hsu-Kim, Joel N Meyer","doi":"10.14573/altex.2501151","DOIUrl":"https://doi.org/10.14573/altex.2501151","url":null,"abstract":"<p><p>Few of the many chemicals that regulatory agencies are charged with assessing for risk have been carefully tested for developmental neurotoxicity (DNT). To speed up assessment, and to reduce the use of vertebrate animals, great effort is being devoted to alternative laboratory models for DNT. A major DNT mechanism is altered neuronal architecture resulting from chemical exposure during neurodevelopment. Caenorhabditis elegans is a nematode that has been extensively studied by neurobiologists and developmental biologists, and to a lesser extent by neurotoxicologists. The development of the nervous system in C. elegans is easily visualized, entirely invariant, and fully mapped. We hypothesized that C. elegans could be a powerful in vivo model to test chemicals for their potential to alter neuronal architecture during development. We developed a novel C. elegans DNT testing paradigm that includes developmental exposure, examines major neurotransmitter neuronal types for architectural alterations, and tests neuron-specific behaviors. We characterized the effects of exposures to the developmental neurotoxicants lead, cadmium, and benzo(a)pyrene on neuronal architecture and specification. We identified no cases in which the apparent neurotransmitter type of the neurons we examined changed, but many in which neuronal morphology was altered. We found that neuron-specific behaviors were altered during C. elegans mid-adulthood for populations with measured morphological neurodegeneration in earlier stages. The functional changes were consistent with the morphological changes in terms of the type of neuron affected. Finally, we identified changes consistent with those reported in the mammalian DNT literature, strengthening the case for C. elegans as a DNT model.</p>","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026012","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":"Considerations from the pharmaceutical industry (IQ MPS affiliate) workshop on animal microphysiological systems and 3Rs in drug development.","authors":"Patrick J Devine, Manti Guha, Jason E Ekert, Anna K Kopec, James R Gosset, May S Freag, Matthew P Wagoner, Philip Hewitt, Kate Harris, Myriam Lemmens, Nakissa Sadrieh, Donna Mendrick, David M Stresser, Leslie Valencia, Paul C Brown, Ronald L Wange, Amy Avila, Kevin Ford, Robert Geiger, Martha Garcia, Jessica A Bonzo, John P Gleeson, Christine C Orozco, Qun Li, Chris Hinckley, Reiner Class, Josephine M McAuliffe, Amy Tran-Guzman, Francesco Nevelli, Gonçalo Gamboa da Costa, Dayton Petibone, Tomomi Kiyota, Qiang Shi, Rhiannon N Hardwick","doi":"10.14573/altex.2503261","DOIUrl":"https://doi.org/10.14573/altex.2503261","url":null,"abstract":"<p><p>Most complex in vitro models (CIVM) and microphysiological systems (MPS) are composed of human cells, with the goal of evaluating diseases, efficacy, safety, and pharmacokinetic questions specifically for humans. The hope with CIVM/MPS is that they will eventually improve our predictivity for clinical responses and reduce or replace animal use in research, supporting the 3Rs concept of only using animals in research when necessary. Given the potential of animal-based models to advance this field by comparing existing in vivo animal data with new animal-based MPS responses, there are currently few CIVM and MPS utilizing animal tissues. Animal-based MPS may also have specific utility for cross-species comparisons or species-specific mechanistic questions on zoonotic diseases, and therapies for animals. Animal-based MPS may help expand in vitro-to in vivo correlations, advance the field and establish confidence in the predictive nature of such platforms. The IQ MPS-FDA workshop provided an interactive venue for pharmaceutical companies and regulatory agencies such as the U.S. Food and Drug Administration (FDA), NC3Rs (UK), Health Canada, NIH/NCATS, NIHS and PMDA (Japan), Danish Medicines Agency, European Commission, NIEHS/ICEATM, HHS, NIST, EURL ECVAM, and the IQ MPS Affiliate, a collaboration of pharmaceutical companies to jointly discuss considerations of animal-based MPS and applications where animal-based MPS are of potential value.</p>","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038505","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":"Animal pilot studies should not be used to estimate sample size if effect size and population variance are unknown.","authors":"Alexander D Bird, Peter Jedlicka, Jochen Wilhelm","doi":"10.14573/altex.2408141","DOIUrl":"https://doi.org/10.14573/altex.2408141","url":null,"abstract":"<p><p>Reducing the number of animals required for a given experiment is part of the 3Rs strategies for animal welfare. Sample size estimation is a critical step in efficient and ethical experimental design. It is generally believed that pilot studies can be used to estimate sample sizes, which could lead to an overall reduction in the number of animals used. As part of the standard approach to ensuring that a planned animal experiment has sufficient statistical power, estimates of effect size and population variance are required. Here we derive the distribution of the sample size estimator when both effect size and variance are unknown. We show that, in this case, it is not feasible to conduct a preliminary pilot study to estimate the required sample size. Our analysis indicates that the sample size of a useful pilot study will often be much larger than that of the main study itself when the effect size is unknown. Therefore, we conclude that performing pilot studies with the aim of estimating sample size will not help to minimize the overall number of animal experiments in basic or pre-clinical research. A practical example is given, and alternative approaches are proposed and discussed.</p>","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026011","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 effect of surfactants and film-forming polymers on pulmonary surfactant function measured in vitro is dose rate dependent.","authors":"Sreyoshee Sengupta, Hugh Barlow, Maria T Baltazar, Jorid B Sørli","doi":"10.14573/altex.2410221","DOIUrl":"https://doi.org/10.14573/altex.2410221","url":null,"abstract":"<p><p>Surfactants and film-forming polymers are common ingredients in consumer spray products such as cleaning products, hair care products, and anti-perspirants. Spraying eases application by creating aerosolized droplets of the product that can distribute evenly over the treated surface. However, these aerosols can potentially be inhaled during their normal application. Droplets that reach the alveoli can interact with the pulmonary surfactant; a complex mixture of phospholipids and proteins that regulates the surface tension at the air-liquid interface. This interaction could elevate the minimum surface tension at maximum compression and change the surface rheology of the pulmonary surfactant at the interface. We tested four surfactants and seven polymers for their ability to inhibit pulmonary surfactant function in vitro and investigated if the inhibition is dose-rate dependent i.e., the product of the concentration (mg/mL) and aerosolization rate (mL/min). We found that independent of chemical class (surfactant or polymer) there was a clear dose-rate dependent inhibition of pulmonary surfactant function and that different chemicals inhibited function at different dose-rates. We compared the points of departure of inhibitory chemicals to a polymer with known dose-rate dependent lung toxicity. When assessing the risk of chemicals that might be inhaled, it is essential to ensure normal use would not inhibit pulmonary surfactant function leading to immediate effects on the lungs.</p>","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144040373","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":"Organizing shipping studies to evaluate the transferability of cell- and tissue-based test systems and reagents: An end user perspective.","authors":"Hans Raabe, Anna van der Zalm, Amy Clippinger, Gertrude-Emilia Costin","doi":"10.14573/altex.2503131","DOIUrl":"https://doi.org/10.14573/altex.2503131","url":null,"abstract":"<p><p>Cell- and tissue-based test systems and reagents (e,g., cells, tissues, organs, reconstructed tissue models, or cell/tissue culture reagents) are increasingly being used in regulatory and non-regulatory testing applications due to their ability to reflect human biology. These test systems and reagents may be shipped long distances, including across international borders, from the vendor to the testing laboratory. To ensure confidence in the data obtained from testing involving these systems and reagents, it is important for the testing laboratory to confirm that quality is maintained during the shipping process and that the materials can be used for their intended application (i.e., that the test method associated with the test system and/or reagent can be effectively transferred between laboratories). This paper describes various types of shipping studies that might be conducted when transferring a method to a new laboratory and key considerations for their design that can help maintain the quality of the test systems and reagents during the shipment process. Furthermore, emphasis is placed on the need for good communication between vendors, shipping agents, and end users to ensure efficient transferability of test methods.</p>","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042762","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":"EU roadmap for phasing out animal testing for chemical safety assessments: Recommendations from a multi-stakeholder roundtable.","authors":"Laurence Walder, Giorgia Pallocca, Luísa F Bastos, Manon Beekhuijzen, Francois Busquet, Helder Constantino, Marco Corvaro, Lilas Courtot, Beate Escher, Rebeca Fernandez, Emeline Gougeon, Love Hansell, Matthias Herzler, Laura Holden, Romana Hornek-Gausterer, Amaia Irizar, Helena Kandarova, Petra Kern, Susanne Kolle, Katia Lacasse, Isabelle Lee, Donna S Macmillan, Gavin Maxwell, Orla Moriarty, Stephanie Nadzialek, Julia Pochat, Kirsty Reid, Marion Revel, Merel Ritskes-Hoitinga, Tomasz Sobanski, Gilly Stoddart, Dylan Underhill, Mandy Veillette, Jelle Vriend, Carl Westmoreland, Julia Baines","doi":"10.14573/altex.2503241","DOIUrl":"https://doi.org/10.14573/altex.2503241","url":null,"abstract":"<p><p>The commitment to develop a roadmap for phasing out the use of animals for chemical safety assessments was part of the European Commission's response to the European Citizens' Initiative \"Save Cruelty-Free Cosmetics - Commit to a Europe Without Animal Testing\". The roadmap aims to outline milestones and specific actions to be implemented in the short to long-term to ultimately phase out animal testing for chemical safety assessments. To advance this goal and help define a structure of the roadmap, a multi-stakeholder roundtable workshop was organised by five animal protection non-governmental organisations in June 2024. The roundtable aimed to explore and define key elements and organisational structures for shaping the roadmap and identify pathways to facilitate the transition to a non-animal testing regulatory framework. Participants discussed a range of critical issues such as revising legislation and guidance, facilitating validation/qualification and regulatory acceptance, strengthening coordination, providing education and training in non-animal approaches, transparency and accessibility to data, establishing metrics to measure progress and securing funding. The importance of a multi-faceted approach integrating scientific, regulatory, policy, ethical, societal, and practical dimensions was emphasised, along with the critical role of transdisciplinary collaboration and combining diverse knowledge, ideas, and technologies to achieve optimal outcomes. This report summarises the main findings and discussion points and provides concrete recommendations. These are intended to facilitate the Commission's work to develop the roadmap and may serve as a valuable resource for similar initiatives worldwide.</p>","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997791","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":"Statistical derivation of cut-off values for in vitro assays.","authors":"Christian T Willenbockel, Mercedes Diez-Cocero, Denise Bloch","doi":"10.14573/altex.2311011","DOIUrl":"https://doi.org/10.14573/altex.2311011","url":null,"abstract":"<p><p>Chemical substances and mixtures are classified based on their toxicological hazard. Today, in vitro methods are more frequently applied for this purpose. The regulatory validation process assesses their relevance by comparing them to standard in vivo test data, which includes transforming continuous read-out data into ordinal data (hazard classes). Existing strategies for developing new methods overlook the constraints associated with small data sets omitting the use of contemporary statistical techniques, such as uncertainty quantification and bootstrapping. To overcome these limitations, we apply bootstrapping, estimates for the out-of-sample error, and uncertainty quantification to the validation dataset of Kaluzhny et al. (2011) and a dataset of plant protection products (PPPs) previously published by Kolle et al. (2015), which have been tested for eye irritation in vitro (OECD TG492) and in vivo (OECD TG 405). Assessment criteria for sensitivity, specificity, and accuracy are proposed, considering uncertainty quantification and estimation of the out-of-sample error. The cut-off value for plant protection products based on the available set of in vitro-in vivo data pairs can be improved by the application of modern cut-off approaches. For PPPs, the OECD recommended cut-off of 60% mean tissue viability based on single substances leads to lower sensitivity than the newly derived cut-off value of 67%. For liquid single substances, the OECD recommended cut-off is confirmed. This case study demonstrates that modern statistical methods for small datasets improve the reliability of in vitro cut-off values and should therefore be used to revise and derive cut-off values for hazard classification in future.</p>","PeriodicalId":51231,"journal":{"name":"Altex-Alternatives To Animal Experimentation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693726","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}