Agrochemical active ingredients are among the most toxicologically evaluated chemical substances, and genetically modified (GM) crops must be evaluated for safety and nutritional adequacy. Traditionally, these evaluation...Agrochemical active ingredients are among the most toxicologically evaluated chemical substances, and genetically modified (GM) crops must be evaluated for safety and nutritional adequacy. Traditionally, these evaluations are conducted There are concerted efforts in the agrochemical sector to reduce animal testing, but there is also an emphasis on updating test guidelines and fulfilling new data package requirements, which can both result in increased animal testing. The purpose of this project was to generate benchmarks for the numbers of vertebrate animals used in: a) evaluating agrochemical pesticidal active ingredients for human health hazards; and b) assessing GM crops for safety and nutritional adequacy, based on guideline studies for data package requirements. To achieve this, guideline studies employing vertebrates, as required by regulatory bodies for developing global data packages for new active ingredients and for GM crops, were listed. These listed guideline studies were reviewed, in terms of the study details and the required animal-use, which was determined based on best testing practices. For historical animal-use benchmarking, Corteva's six most recent agrochemical pesticidal active ingredients and four most recent GM crop events were evaluated. Across the six most recently developed active ingredients, an average of approximately 10,000 mammals were used for the testing of each (range: 5500-19,000); across the four most recently developed GM crops, the average number of vertebrates similarly used for each was approximately 1200 (range: 1000-1500). Though regulatory testing requirements are likely to change with time, as new technologies become available, this project has established a theoretical minimum requirement to help drive aspirational animal reduction goals, identified regulatory challenges associated with the reduction of animal-use, and helped to refine Corteva's vertebrate animal-use tracking approaches.
Increasing the use of microphysiological systems (MPS) in Three Rs and regulatory applications is a nuanced but important goal, which would also help increase their scientific impact. There are three distinct and importa...Increasing the use of microphysiological systems (MPS) in Three Rs and regulatory applications is a nuanced but important goal, which would also help increase their scientific impact. There are three distinct and important stakeholder groups that each play a unique role in expediting the use of MPS for regulatory purpose - namely, commercial MPS developers, end-users and regulators. Additionally, non-profit organisations, such as the 3Rs Collaborative (3RsC), can help coordinate these efforts. This paper introduces the MPS Initiative, as organised by the 3RsC, and clarifies the potential for MPS to benefit all Three Rs. Key differences in the use of MPS-derived data for regulatory evidence of efficacy versus safety, and for various other contexts of use, are discussed. Finally, the results are presented from a survey of primarily commercial MPS developers, that collected their views on the realistic responsibilities of each stakeholder group. The results also highlight their key perspectives on the use of MPS, in the context of Three Rs and regulatory applications.
The first ONTOX Hackathon of the EU Horizon 2020-funded ONTOX project was held on 21-23 April 2024 in Utrecht, The Netherlands (https://ontox-project.eu/hackathon/). This participatory event aimed to collectively advance...The first ONTOX Hackathon of the EU Horizon 2020-funded ONTOX project was held on 21-23 April 2024 in Utrecht, The Netherlands (https://ontox-project.eu/hackathon/). This participatory event aimed to collectively advance innovation for human safety through the use of Artificial Intelligence (AI), and hence significantly reduce reliance on animal-based testing. Expert scientists, industry leaders, young investigators, members of animal welfare organisations and academics alike, joined the hackathon. Eight teams were stimulated to find innovative solutions for challenging themes, that were selected based on previous discussions between stakeholders, namely: How to drive the use of AI in chemical risk assessment?; To predict or protect?; How can we secure human health and environmental protection at the same time?; and How can we facilitate the transition from animal tests to full implementation of human-relevant methods? The hackathon ended with a pitching contest, where the teams presented their solutions to a jury. The most promising solutions will be presented to regulatory authorities, industry, academia and non-governmental organisations at the next ONTOX Stakeholder Network meeting and taken up by the ONTOX project in order to tackle the above-mentioned challenges further. This report comprises two parts: The first part highlights some of the lessons learnt during the planning and execution of the hackathon; the second part presents the outcome of the ONTOX Hackathon, which resulted in several innovative and promising solutions based on New Approach Methodologies (NAMs), and outlines ONTOX's intended way forward.
Currently for engineered nanomaterials (ENMs), there are no alternatives to bioaccumulation testing in fish as prescribed by OECD TG 305. New approaches are being sought, in order to reduce the numbers of animals used an...Currently for engineered nanomaterials (ENMs), there are no alternatives to bioaccumulation testing in fish as prescribed by OECD TG 305. New approaches are being sought, in order to reduce the numbers of animals used and address the ethical concerns associated with the use of vertebrates in such testing. This study aimed to demonstrate the value of an alternative method - the digestibility assay - as a tool to assess the bioaccumulation potential of ENMs. Titanium dioxide ENMs, or their equivalent bulk form, were incorporated onto a commercial fish diet and the fish digestion process was simulated at pH 2 (simulated stomach phase) and pH 7.8 (simulated intestinal phase). Only the 1000 mg/kg dry weight feed treatment showed measurable Ti release in the stomach phase, with the results being similar for the TiO ENM and the bulk form. More Ti from TiO was released from the feed during the intestinal phase of digestion compared to the stomach phase, but there were no statistically significant differences between either the ENM or bulk form. There was higher incidental Ti release from untreated control feed in the intestinal phase compared to the stomach phase. On a percentage basis, the stomach generally showed a statistically significant digestibility of around 3% of the total Ti in the feed, compared to around 7% in the intestine. The digestibility assay shows potential for use in the determination of the bioaccessible fraction of ENMs, and could be a useful screening tool to identify ENMs of concern for bioaccumulation.
The acquisition of skills to perform an ovariohysterectomy (OVH) is crucial for veterinary medicine students. It has been demonstrated that the most effective way to develop these skills is through repetitive training on...The acquisition of skills to perform an ovariohysterectomy (OVH) is crucial for veterinary medicine students. It has been demonstrated that the most effective way to develop these skills is through repetitive training on simulators. Unfortunately, commercial simulators are expensive, limiting their use and highlighting the need for the development of more cost-effective alternatives. This study aimed to assess the effectiveness of a low-cost, easily constructed textile-based simulator for the canine ovaries and uterus in training veterinary students on the OVH technique. The impact of tutor guidance on student learning was also assessed. Participants were divided into two groups: simulator and tutor guidance (SG) and simulator only (SO). Each student performed 20 repetitions of the three-clamp OVH technique, and the number of errors and execution time were quantified. The SG group reached the learning curve plateau in terms of minimum errors on the 7th repetition and attained the fastest time on the 6th repetition. The SO group reached the learning curve plateau in terms of minimum errors and attained the fastest time both on the 15th repetition. From individuals in the SG group, there were no requests for tutor guidance from the 11th attempt. This low-cost simulator is ideal for training veterinary students in the early stages of surgical learning, as it effectively facilitates learning the OVH procedure without the use of live animals.
The use of adverse effect data from animals as the gold standard in regulatory toxicology has a long tradition dating back to the 1960s. It has also been increasingly criticised, based on both scientific and animal welfa...The use of adverse effect data from animals as the gold standard in regulatory toxicology has a long tradition dating back to the 1960s. It has also been increasingly criticised, based on both scientific and animal welfare concerns, and yet, animal studies remain the gold standard in most areas of toxicology to this very day. In the 1980s, when the first generation of non-animal methods were evaluated as alternatives to animal testing, it was logical to compare the 'new' data obtained with historical animal data. This worked reasonably well for simple endpoints, such as skin and eye irritation, but became problematic for the more complex systemic endpoints, since in these cases, the effects are not directly comparable to those observed in systems. While the need to redefine the gold standard is not new, there is still no consensus on how to do so. We propose a consistent principle that avoids the need for animal reference data, while also ensuring an equivalent or better level of protection. We argue that the gold standard can be redefined, or rather bypassed, by focusing on risk management outcomes rather than the outputs of animal methods. This allows us to more efficiently protect human health and the environment, ensuring the safe use of chemicals while also identifying less hazardous chemicals for use as substitutes. We describe how this might work out for two main contexts of use: classification and labelling, and risk assessment. This has implications for the implementation of the EU Commission Roadmap toward the phasing out of animal testing in chemical safety assessments.
The data on the number of animals used for experimental purposes, with a particular focus on regulatory toxicity studies, in Turkey and EU member states plus Norway (EU+), were compared for the period 2015 to 2020 (UK da...The data on the number of animals used for experimental purposes, with a particular focus on regulatory toxicity studies, in Turkey and EU member states plus Norway (EU+), were compared for the period 2015 to 2020 (UK data after Brexit for 2020 were included too). The total number of listed vertebrates used for regulatory toxicity testing in the full 6-year reporting period in Turkey was 3.6% of that reported for the EU+. However, these numbers showed an increasing trend over the reporting period in Turkey, while the trend decreased in the EU+. In the top three most-used species for regulatory toxicology purposes in Turkey, 41% were fish (68,758 animals), followed by rats (29%; 49,975 animals), and then mice (20%; 33,292 animals). Turkey used low numbers of cats and dogs, while the corresponding number for the EU+ was more than 70-fold higher. Non-human primates were not used at all in Turkey, whereas about 34,000 were used in EU+ laboratories. The majority of toxicity tests (57%) performed in Turkey were categorised as 'Other' toxicity tests, and 27% were acute and sub-acute toxicity tests. Successful replacement alternatives (e.g. and approaches) are already used in a wide range of research areas. However, although this new research and testing paradigm is underpinned by scientific evidence, the legislation and pace of acceptance of these new techniques in Turkey is considerably lagging behind other countries.
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 scie...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 , to a view that the principles have hindered, rather than helped, a critical approach to animal research that should have resulted in 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.
Kitsara M, Smajlhodžić-Deljo M, Gurbeta Pokvic L
… +19 more, Bert B, Bubalo N, Erden S, Franco NH, Chirico G, Gómez Raja J, Gonzalez-Uarquin F, Lang A, Linklater N, Mojsova S, Olsson IAS, Sandvig I, Schaffert A, Schmit M, Schober S, Sevastre B, Wilflingseder D, Ahluwalia A, Neuhaus W
Publication is essential to share new ideas, knowledge, or recent findings with those who have an interest in a particular area. Selecting the most appropriate format and timing for dissemination is critical to ensuring...Publication is essential to share new ideas, knowledge, or recent findings with those who have an interest in a particular area. Selecting the most appropriate format and timing for dissemination is critical to ensuring the long-term impact of research. However, many researchers, particularly those in the early stages of their career, are unaware of how the publication process works and the different options available for promoting research to maximum effect. Understanding how to maximise impact is particularly important for research using animal models or alternative methods, to make the best use of any animal data generated and reduce animal testing in future. Herein, different publishing models are explained, including anonymised peer review, open review and data sharing initiatives. An overview is given of key resources available to assist authors, reviewers and editors in the process of writing, presenting, reviewing and publishing research. New challenges and opportunities in publishing are discussed, including the potential influence of Artificial Intelligence. A list of 'ten top tips' in publishing for early career researchers is presented, providing advice and recommendations for ensuring a successful and impactful publication record.
Altern Lab Anim
· 2024 Sep · PMID 39262033
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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...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.