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- It’s Time to Review the Three Rs, to Make them More Fit for Purpose
in the 21st Century-
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Authors: Jarrod Bailey Pages: 155 - 165 Abstract: Alternatives to Laboratory Animals, Volume 52, Issue 3, Page 155-165, May 2024. The Three Rs have become widely accepted and pursued, and are now the go-to framework that encourages the humane use of animals in science, where no other option is believed to exist. However, many people, including scientists, harbour varying degrees of concern about the value and impact of the Three Rs. This ranges from a continued adherence to the Three Rs principles in the belief that they have performed well, through a belief that there should be more emphasis (or indeed a sole focus) on replacement, to a view that the principles have hindered, rather than helped, a critical approach to animal research that should have resulted in replacement to a much greater extent. This critical review asks questions of the Three Rs and their implementation, and provides an overview of the current situation surrounding animal use in biomedical science (chiefly in research). It makes a case that it is time to move away from the Three Rs and that, while this happens, the principles need to be made more robust and enforced more efficiently. To expedite a shift from animal use in science, toward a much greater and quicker adoption of human-specific New Approach Methodologies (NAMs), some argue for a straightforward focus on the best available science. Citation: Alternatives to Laboratory Animals PubDate: 2024-04-30T02:23:25Z DOI: 10.1177/02611929241241187 Issue No: Vol. 52, No. 3 (2024)
- Editorial
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Authors: Judith C. Madden Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals PubDate: 2024-08-08T02:09:14Z DOI: 10.1177/02611929241274885
- Lessons for the Future of NAMs from History, Philosophy and Social Studies
of Science-
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Authors: Rachel A. Ankeny, Gail F. Davies, Robert G.W. Kirk, Alexandra L. Whittaker, Jane Johnson Abstract: Alternatives to Laboratory Animals, Ahead of Print. This paper explores what we can learn from the humanities and social sciences about how standards operate in and around science, in order to understand more about how ‘the gold standard’ can be shifted away from the use of animals in research and testing, and toward New Approach Methodologies (NAMs). These fields allow us to consider potential futures of NAMs as alternatives, replacements, or complements to animal use in testing and research. As we demonstrate, the questions that we pose and how they are framed are as important as the answers that result. Rather than asking how to ‘redefine the gold standard’, norms and expectations for NAMs must be actively debated and transparently defined. These considerations would be based, in part, on what has been learned in the past from non-human animal models and systems, but also use the norms within the fields from which the NAMs derive in light of the rich broader contexts within which they are being developed. As we argue, notions such as ‘a gold standard’ are limited and must be replaced by contextualised standards that depend on the scientific, sociocultural and other factors that contribute to our understanding of a particular method (new or otherwise) as ‘good’ for a particular purpose. Citation: Alternatives to Laboratory Animals PubDate: 2024-08-06T05:09:44Z DOI: 10.1177/02611929241267763
- Progress and Remaining Opportunities to Increase the Use of Animal-free
Antibodies in the USA-
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Authors: Katherine Groff, David Allen, Warren Casey, Amy J. Clippinger Abstract: Alternatives to Laboratory Animals, Ahead of Print. The scientific and ethical issues associated with the use of animal-derived antibodies in research can be overcome by the use of animal-free, sequence-defined recombinant antibodies, whose benefits are well documented. Here, we describe progress made following a 2019 expert meeting focused on improving the quality and reproducibility of biomedical research by accelerating the production and use of animal-free recombinant antibodies in the USA. In the five intervening years since the meeting, participants have established multifaceted initiatives to tackle the next steps outlined during the meeting. These initiatives include: prioritising the replacement of ascites-derived and polyclonal antibodies; distributing educational materials describing recombinant antibodies; fostering public–private partnerships to increase access to recombinant antibodies; and increasing the availability of funding for recombinant antibody development. Given the widescale use of antibodies across scientific disciplines, a transition to modern antibody production methods relies on a commitment from government agencies, universities, industry and funding organisations, to initiatives such as those outlined here. Citation: Alternatives to Laboratory Animals PubDate: 2024-07-24T07:29:03Z DOI: 10.1177/02611929241266472
- In Silico Phototoxicity Prediction of Drugs and Chemicals by using Derek
Nexus and QSAR Toolbox-
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Authors: Varun Ahuja, Gowrav Adiga Perdur, Zabiullah Aj, Mohan Krishnappa, Helena Kandarova Abstract: Alternatives to Laboratory Animals, Ahead of Print. Phototoxicity testing is crucial for evaluating the potential harmful effects of pharmaceuticals and chemicals on human skin when exposed to sunlight. Traditional in vivo models involving mice, rats, guinea pigs, as well as in vitro assays such as the 3T3 Neutral Red Uptake phototoxicity assay and methods based on the use of reconstructed human epidermis, have been established for phototoxicity testing. While these approaches are extremely valuable, they are costly in terms of both time and resources. Consequently, in silico approaches based on the use of predictive software tools can offer more rapid and cost-effective phototoxicity screening solutions. With this goal in mind, the current study evaluated two in silico tools — Derek Nexus 6.1.0/Derek Knowledge Base 2020 1.0 (Lhasa Limited, UK) and the QSAR Toolbox (v 4.5) developed by the Organisation for Economic Co-operation and Development (OECD) — for their capacity to predict the phototoxicity of several substances from diverse classes. Derek Nexus and the QSAR Toolbox were both found to be very useful for predicting the phototoxicity of drugs and other chemicals. Derek Nexus predicted phototoxicity of the compounds, with a sensitivity of 63%, specificity of 93%, Positive Predictive Values of 90% and Negative Predictive Value of 69%, overall accuracy of 77% and balanced accuracy of 78%. The QSAR Toolbox achieved sensitivity of 73%, specificity of 85%, Positive Predictive Value of 85% and Negative Predictive Value of 74%, overall accuracy of 79% and balanced accuracy of 79%. The results show that Derek Nexus and the QSAR Toolbox can be usefully incorporated in the workflow of phototoxicity testing for pharmaceuticals and chemicals. Citation: Alternatives to Laboratory Animals PubDate: 2024-06-24T06:50:12Z DOI: 10.1177/02611929241256040
- Spotlight on Three Rs Progress
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Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals PubDate: 2024-06-13T10:23:26Z DOI: 10.1177/02611929241260578
- Cigarette Smoke Constituents and Nicotine Differentially Affect Cytokine
Production by Human Macrophages Stimulated by TLR Ligands In Vitro: Considerations for a Standardised Protocol-
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Authors: Abeer Abdullah M. Sharaf, Ian Todd Abstract: Alternatives to Laboratory Animals, Ahead of Print. Chronic obstructive pulmonary disease (COPD) is an inflammatory lung condition associated with cigarette (tobacco) smoking. Numerous in vivo animal studies have been conducted to investigate the links between cigarette smoke, nicotine and infection in lung pathology. As an alternative to animal experiments, we used an in vitro system to investigate the effects of cigarette smoke extract (CSE) or nicotine on TNF-α and IL-10 production by monocyte-derived human macrophages. The macrophages were simultaneously stimulated with either poly-IC (as a chemical surrogate for viral infection) or lipopolysaccharide (as a chemical surrogate for Gram-negative bacterial infection). CSE enhanced TNF-α production, whereas nicotine inhibited IL-10 production by the macrophages, particularly when co-stimulated with the microbial chemical surrogates. A system of this type may help to further our understanding of the immunological and inflammatory effects of smoking, without recourse to in vivo studies. Requirements for the optimisation and standardisation of such an in vitro system are also discussed. Citation: Alternatives to Laboratory Animals PubDate: 2024-06-13T05:15:57Z DOI: 10.1177/02611929241259105
- Conference Diary
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Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals PubDate: 2024-06-12T10:59:38Z DOI: 10.1177/02611929241260577
- Editorial
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Authors: Judith C. Madden Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals PubDate: 2024-06-12T03:14:24Z DOI: 10.1177/02611929241263184
- Resources Round-up
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Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals PubDate: 2024-06-12T01:43:20Z DOI: 10.1177/02611929241260579
- The Accomplishments of KoCVAM in the Development and Implementation of
Alternative Methods in Korea-
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Authors: Nam-Hee Kang, JaeHo Oh Abstract: Alternatives to Laboratory Animals, Ahead of Print. The Korean Center for the Validation of Alternative Methods (KoCVAM), which promotes the Three Rs principles and the use of alternative methods in Korea, has been operating within the Toxicological Screening and Testing Division of the Ministry of Food and Drug Safety (MFDS) since 2009. KoCVAM has exchanged opinions and information on the development and validation of non-animal alternative test methods as part of the International Cooperation on Alternative Test Methods (ICATM), and provided input into draft OECD Test Guidelines (TGs). Several Korean laws (e.g. the Cosmetics Act) encourage the use of alternative test methods for chemical testing and assessment. To promote and support the use of alternative test methods in the country, KoCVAM has published information and provided training on the national guidelines, which are based on the OECD TGs. In addition, KoCVAM has held annual training workshops on alternative test methods, to help Korean research institutions (including GLP test facilities) to implement them. In addition, by helping to develop and validate alternative test methods that were adopted in OECD TG 442B, TG 492 and TG 439, KoCVAM has contributed to the enhanced competitiveness of Korean industry on the worldwide stage. Citation: Alternatives to Laboratory Animals PubDate: 2024-04-16T09:34:16Z DOI: 10.1177/02611929241244520
- Editorial
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Authors: Judith C. Madden Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals PubDate: 2024-04-16T01:58:01Z DOI: 10.1177/02611929241246891
- Resources Round-up
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Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals PubDate: 2024-04-13T08:49:41Z DOI: 10.1177/02611929241245521
- Spotlight on Three Rs Progress
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Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals PubDate: 2024-04-13T08:41:19Z DOI: 10.1177/02611929241245507
- A Novel Ex Vivo Blinking Method for Comparing the Corneal Residence Time
of New Shampoo Formulations-
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Authors: Markus Glaudo, Marc Urbach, Claudia Panfil, Stephanie Herkert, Mark Brown, Norbert Schrage Abstract: Alternatives to Laboratory Animals, Ahead of Print. In the cosmetics sector, many products such as shampoos have a probability of accidental ocular exposure during their routine use. One very specific safety parameter is the residence time of the substance on the corneal surface, as prolonged exposure may cause injury. In this study, we developed a system that simulates corneal exposure to blinking and tear flow, for comparing the corneal clearance times of viscous detergent formulations. The Ex Vivo Eye Irritation Test (EVEIT), which uses corneal explants from discarded rabbit eyes from an abattoir, was used as the basis for the new system. To simulate blinking, we developed a silicone wiping membrane to regularly move across the corneal surface, under conditions of constant addition and aspiration of fluid, to mimic tear flow. Six shampoo formulations were tested and were shown to differ widely in their corneal clearance time. Three groups could be identified according to the observed clearance times (fast, intermediate and slow); the reference shampoo had the shortest clearance time of all tested formulations. With this new system, it is now possible to investigate an important physicochemical parameter, i.e. corneal clearance time, for the consideration of ocular safety during the development of novel cosmetic formulations. Citation: Alternatives to Laboratory Animals PubDate: 2024-04-12T09:05:42Z DOI: 10.1177/02611929241245723
- Conference Diary
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Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals PubDate: 2024-04-10T05:24:05Z DOI: 10.1177/02611929241245506
- Acute Toxicity Assays with the Artemia salina Model: Assessment of
Variables-
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Authors: Gerson Salay, Nádila Lucarelli, Thaís Moura Gascón, Samantha Sanches de Carvalho, Glaucia Raquel Luciano da Veiga, Beatriz da Costa Aguiar Alves Reis, Fernando Luiz Affonso Fonseca Abstract: Alternatives to Laboratory Animals, Ahead of Print. The use of the brine shrimp Artemia salina (Leach) in acute toxicity assays has great potential due to its simplicity, low cost and reproducibility. In the current study, some of the variables that can influence the reliability of the assay in terms of test organism survival, were evaluated as part of its implementation in our laboratory. The quality and type of water used, the buffer components and other parameters (salinity, pH and dissolved oxygen level), were all evaluated for optimisation purposes. DMSO (dimethyl sulphoxide) was used as the test substance in the toxicity assay, to evaluate the concentration limits as a solvent in sample preparation. Regarding the buffer salinity, pH and dissolved oxygen level, we found that a 25% to 30% deviation from the standard values did not affect the survival of the nauplii (the first-instar larval stage) under assay conditions. In summary, we corroborate the potential use of this model for the prediction of the toxic potential of substances, to inform future testing strategies. Citation: Alternatives to Laboratory Animals PubDate: 2024-04-05T01:14:15Z DOI: 10.1177/02611929241242443
- Thanks to Reviewers
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Abstract: Alternatives to Laboratory Animals, Ahead of Print.
Citation: Alternatives to Laboratory Animals PubDate: 2024-02-16T05:53:27Z DOI: 10.1177/02611929241234014
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