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Veterinary › Small Animals

Animal testing and alternatives

Works Count: 36208

Description

This cluster of papers focuses on improving the reporting and conduct of animal research studies, with an emphasis on the use of ARRIVE guidelines, cytotoxicity assays, ethical considerations, systematic reviews, in vitro testing methods, and addressing publication bias. It also discusses the challenges in translating findings from animal studies to human applications and the determination of sample sizes for preclinical studies.

Keywords

ARRIVE Guidelines; Animal Research Reporting; Cytotoxicity Assays; Preclinical Studies; Translation to Humans; Ethical Considerations; Systematic Reviews; In Vitro Testing; Publication Bias; Sample Size Determination

Biology of the Laboratory Mouse

1941-11-01
Earl L. Green

Casarett and Doull's Toxicology: The Basic Science of Poisons

1992-09-01
Curtis D. Klaassen
The most trusted all-in-one overview of the biomedical and environmental aspects of toxicology - Now more complete, up-to-date, and in full color. It is a Doody's Core Title for 2015! … The most trusted all-in-one overview of the biomedical and environmental aspects of toxicology - Now more complete, up-to-date, and in full color. It is a Doody's Core Title for 2015! New to the Eighth Edition Full-Color design to allow for a clearer interpretation of the basic components of toxicology featured throughout the text. Expanded tables, illustrations, and other visuals are updated with state-of-the-art standards that makes this edition even more current and relevant DVD with image bank features all tables and illustrations from the text in presentation-ready format. New Chapters include Toxic Effects of Calories and Toxic Effects of Nanoparticles. The world's leading and most authoritative textbook on poisons has more to offer students, toxicologists, and pharmacologists than ever before. Now in full color, and thoroughly revised, the eighth edition of Casarett & Doull's Toxicology: The Basic Science of Poisons not only delivers a comprehensive review of the essential components of toxicology, it offers the most up-to-date, revealing, and in-depth look at the systemic responses of toxic substance available anywhere. Combined with the latest thinking by the field's foremost scholars plus solid coverage of general principles, modes of action, and chemical-specific toxicity, this landmark text continues to set the standard for toxicology references.

Animal tissue techniques

1962-01-01
Gretchen L. Humason
Animal tissue techniques , Animal tissue techniques , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی Animal tissue techniques , Animal tissue techniques , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی
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Animal research: Reporting <i>in vivo</i> experiments: The ARRIVE guidelines

2010-07-06
Carol Kilkenny , William J. Browne , Innes C. Cuthill +2 more
The NC3Rs gratefully acknowledges the expertise and advice that all the contributors have given to developing the guidelines. We would particularly like to acknowledge the contribution of the NC3Rs Reporting … The NC3Rs gratefully acknowledges the expertise and advice that all the contributors have given to developing the guidelines. We would particularly like to acknowledge the contribution of the NC3Rs Reporting Guidelines Working Group-– Professor Doug Altman, Centre for Statistics in Medicine, University of Oxford UK, Professor David Balding, Department of Epidemiology & Public Health, Imperial College, London UK, Professor William Browne, Department of Clinical Veterinary Science, University of Bristol UK, Professor Innes Cuthill, School of Biological Sciences, University of Bristol UK, Dr Colin Dunn, Editor Laboratory Animals (Royal Society of Medicine press), Dr Michael Emerson, National Heart and Lung Institute, Imperial College, London UK, Dr Stella Hurtley, Senior Editor Science, Professor Ian McGrath, Editor-in-Chief British Journal of Pharmacology (Wiley Blackwell Publishers) and Dr Clare Stanford, Department of Psychopharmacology, University College, London UK. We would also like to thank NC3Rs grant holders, the Medical Research Council, Biotechnology and Biological Sciences Research Council (BBSRC), Wellcome Trust, Parkinson's Disease Society, British Heart Foundation and their grant holders and funding committee members who provided feedback on the guidelines; and Kathryn Chapman and Vicky Robinson (both NC3Rs) for their help with the manuscript. -Please note: that the working group members who contributed to these guidelines were advising in their personal capacity and their input does not necessarily represent the policy of the organisations they are associated with. The reporting guidelines project was funded by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs). These guidelines are excerpted (as permitted under the Creative Commons Attribution License [CCAL], with the knowledge and approval of PLoS Biology and the authors) from Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Animal research: reporting in vivo experiments: ARRIVE guidelines. PLoS Biol 2010; 8(6): e1000412. doi: 10.1371/journal.pbio.1000412. These guidelines are licensed under the Creative Commons Attribution 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/ or send a letter to Creative Commons, 171 Second Street, Suite 300, San Francisco, California, 94105, USA.
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The Laboratory Rat

2006-01-01
Mark A. Suckow , Steven H. Weisbroth , Craig L. Franklin

Implementing guidelines on reporting research using animals (<scp>ARRIVE</scp> etc.): new requirements for publication in <scp>BJP</scp>

2015-05-12
J.C. McGrath , Elliot Lilley
The ARRIVE guidelines have been implemented in BJP for 4 years with the aim of increasing transparency in reporting experiments involving animals. BJP has assessed our success in implementing them … The ARRIVE guidelines have been implemented in BJP for 4 years with the aim of increasing transparency in reporting experiments involving animals. BJP has assessed our success in implementing them and concluded that we could do better. This editorial discusses the issues and explains how we are changing our requirements for authors to report their findings in experiments involving animals. This is one of a series of editorials discussing updates to the BJP Instructions to Authors Linked Editorials This Editorial is part of a series. To view the other Editorials in this series, visit: http://onlinelibrary.wiley.com/doi/10.1111/bph.12956/abstract ; http://onlinelibrary.wiley.com/doi/10.1111/bph.12954/abstract ; http://onlinelibrary.wiley.com/doi/10.1111/bph.13112/abstract and http://onlinelibrary.wiley.com/doi/10.1111/bph.12856/abstract . Video To view the video on the ARRIVE guidelines, visit: https://www.youtube.com/watch?v=DYXoUAnhoPM
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Guidelines for reporting experiments involving animals: the ARRIVE guidelines

2010-07-06
J.C. McGrath , G.B. DRUMMOND , Elspeth M. McLachlan +2 more
British Journal of Pharmacology (BJP) is pleased to publish a new set of guidelines for reporting research involving animals, simultaneously with several other journals; the ‘ARRIVE’ guidelines (Animals in Research: … British Journal of Pharmacology (BJP) is pleased to publish a new set of guidelines for reporting research involving animals, simultaneously with several other journals; the ‘ARRIVE’ guidelines (Animals in Research: Reporting In Vivo Experiments). This editorial summarizes the background to the guidelines, gives our view of their significance, considers aspects of specific relevance to pharmacology, re‐states BJP's guidelines for authors on animal experiments and indicates our commitment to carrying on discussion of this important topic. We also invite feedback via the British Pharmacological Society website.
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Disposition of Toxic Drugs and Chemicals in Man

2014-12-01
Donald G. Barceloux
Congratulations to Dr. Baselt for the publication of his 10th edition and the expansion of his classic toxicology text to cover over 1,500 medications and chemicals. This enduring work provides … Congratulations to Dr. Baselt for the publication of his 10th edition and the expansion of his classic toxicology text to cover over 1,500 medications and chemicals. This enduring work provides a c...

Neutral red uptake assay for the estimation of cell viability/cytotoxicity

2008-06-12
Guillermo Repetto , Ana del Peso , Jorge L. Zurita

Guidelines on the recognition of pain, distress and discomfort in experimental animals and an hypothesis for assessment

1985-04-20
David B. Morton , Paul Griffiths
Under the 1876 Cruelty to Animals Act it is necessary to recognise pain so that an assessment may be made to determine if it is 'an experiment calculated to give … Under the 1876 Cruelty to Animals Act it is necessary to recognise pain so that an assessment may be made to determine if it is 'an experiment calculated to give pain' and 'to prevent the animal feeling pain'. Under the conditions of the licence it is also necessary to recognise 'severe pain which is likely to endure' and 'suffering considerable pain'. In the White Paper May 1983 (Command 8883) it is stated that: 'in the application of controls the concept of pain should be applied in a wide sense' and 'the Home Secretary's practice has been to interpret the concept of pain to include disease, other disturbances of normal health, adverse change in physiology, discomfort and distress'. The draft European Convention for the Protection of Vertebrate Animals used for Experimental and other Purposes, aims to control, subject to specific exceptions, any experimental or other scientific procedure which 'may cause pain, suffering, distress or lasting harm'. (The White Paper states that UK control will be stricter than the Council of Europe proposals.) Thus, there is a considerable onus on the experimenter to recognise pain (not to define it) and to alleviate it. It is intended that this article should be of help, not only to newcomers inexperienced in the recognition of pain, but also possibly to those relatively experienced workers who may be called upon to evaluate the pain involved in a new model or an individual animal.(ABSTRACT TRUNCATED AT 250 WORDS)

Toxicity testing in the 21st century: A vision and a strategy

2007-11-14
Steven Gibb

Blood sample collection in small laboratory animals

2010-11-10
Subramani Parasuraman , R Raveendran , Kesavan Ramasamy

Forced swimming test in mice: a review of antidepressant activity

2004-11-17
Benoit Petit‐Demoulière , Franck Chenu , Michel Bourin

Animal Research: Reporting <i>in vivo</i> Experiments—The ARRIVE Guidelines

2011-01-05
Carol Kilkenny , William J. Browne , Innes C. Cuthill +2 more
The following guidelines are excerpted (as permitted under the Creative Commons Attribution License (CCAL), with the knowledge and approval of PLoS Biology and the authors) from Kilkenny et al (2010). … The following guidelines are excerpted (as permitted under the Creative Commons Attribution License (CCAL), with the knowledge and approval of PLoS Biology and the authors) from Kilkenny et al (2010). ​ Table
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A simple quantitative procedure using monolayer cultures for cytotoxicity assays (HTD/NR-90)

1985-03-01
Ellen Borenfreund , James A. Puerner

Policy: NIH plans to enhance reproducibility

2014-01-24
Francis S. Collins , Lawrence A. Tabak
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Improving bioscience research reporting: The ARRIVE guidelines for reporting animal research.

2010-07-01
Carol Kilkenny , William J. Browne , Innes C. Cuthill +2 more
animals used (i.e., species/strain, sex, and age/weight). Most of the papers surveyed did not report using randomisation (87%) or blinding (86%) to reduce bias in animal selection and outcome assessment. … animals used (i.e., species/strain, sex, and age/weight). Most of the papers surveyed did not report using randomisation (87%) or blinding (86%) to reduce bias in animal selection and outcome assessment. Only 70% of the publications that used statistical methods fully described them and presented the results with a measure of precision or variability [5]. These findings are a cause for concern and are consistent with reviews of many research areas, including clinical studies, published in recent years [2–22].
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SYRCLE’s risk of bias tool for animal studies

2014-03-25
Carlijn R. Hooijmans , Maroeska M. Rovers , Rob BM de Vries +3 more
Systematic Reviews (SRs) of experimental animal studies are not yet common practice, but awareness of the merits of conducting such SRs is steadily increasing. As animal intervention studies differ from … Systematic Reviews (SRs) of experimental animal studies are not yet common practice, but awareness of the merits of conducting such SRs is steadily increasing. As animal intervention studies differ from randomized clinical trials (RCT) in many aspects, the methodology for SRs of clinical trials needs to be adapted and optimized for animal intervention studies. The Cochrane Collaboration developed a Risk of Bias (RoB) tool to establish consistency and avoid discrepancies in assessing the methodological quality of RCTs. A similar initiative is warranted in the field of animal experimentation.We provide an RoB tool for animal intervention studies (SYRCLE's RoB tool). This tool is based on the Cochrane RoB tool and has been adjusted for aspects of bias that play a specific role in animal intervention studies. To enhance transparency and applicability, we formulated signalling questions to facilitate judgment.The resulting RoB tool for animal studies contains 10 entries. These entries are related to selection bias, performance bias, detection bias, attrition bias, reporting bias and other biases. Half these items are in agreement with the items in the Cochrane RoB tool. Most of the variations between the two tools are due to differences in design between RCTs and animal studies. Shortcomings in, or unfamiliarity with, specific aspects of experimental design of animal studies compared to clinical studies also play a role.SYRCLE's RoB tool is an adapted version of the Cochrane RoB tool. Widespread adoption and implementation of this tool will facilitate and improve critical appraisal of evidence from animal studies. This may subsequently enhance the efficiency of translating animal research into clinical practice and increase awareness of the necessity of improving the methodological quality of animal studies.
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How to calculate sample size in animal studies?

2013-10-10
Jaykaran Charan , N. D. Kantharia
Calculation of sample size is one of the important component of design of any research including animal studies. If a researcher select less number of animals it may lead to … Calculation of sample size is one of the important component of design of any research including animal studies. If a researcher select less number of animals it may lead to missing of any significant difference even if it exist in population and if more number of animals selected then it may lead to unnecessary wastage of resources and may lead to ethical issues. In this article, on the basis of review of literature done by us we suggested few methods of sample size calculations for animal studies.
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A new specific, sensitive and non-carcinogenic reagent for the demonstration of horseradish peroxidase

1977-11-01
Jacob S. Hanker , Peggy E. Yates , Charles B. Metz +1 more

A good practice guide to the administration of substances and removal of blood, including routes and volumes

2001-01-01
Karl‐Heinz Diehl , Robin Hull , David B. Morton +5 more
Abstract This article is the result of an initiative between the European Federation of Pharmaceutical Industries Associations (EFPIA) and the European Centre for the Validation of Alternative Methods (ECVAM). Its … Abstract This article is the result of an initiative between the European Federation of Pharmaceutical Industries Associations (EFPIA) and the European Centre for the Validation of Alternative Methods (ECVAM). Its objectives are to provide the researcher in the safety evaluation laboratory with an up‐to‐date, easy‐to‐use set of data sheets to aid in the study design process whilst at the same time affording maximum welfare considerations to the experimental animals. Although this article is targeted at researchers in the European Pharmaceutical Industry, it is considered that the principles underpinning the data sets and refinement proposals are equally applicable to all those who use these techniques on animals in their research, whether in research institutes, universities or other sectors of industry. The implications of this article may lead to discussion with regulators, such as those responsible for pharmacopoeial testing. There are numerous publications dealing with the administration of test substances and the removal of blood samples, and many laboratories also have their own ‘in‐house’ guidelines that have been developed by custom and practice over many years. Within European Union Directive 86/609EEC1 we have an obligation to refine experiments to cause the minimum amount of stress. We hope that this article will provide background data useful to those responsible for protocol design and review. This guide is based on peer‐reviewed publications whenever possible, but where this is not possible we have used ‘in‐house’ data and the experience of those on the working party (as well as helpful comments submitted by the industry) for a final opinion. The guide also addresses the continuing need to refine the techniques associated with the administration of substances and the withdrawal of blood, and suggests ways of doing so. Data‐sharing between laboratories should be encouraged to avoid duplication of animal work, as well as sharing practical skills concerning animal welfare and scientific problems caused by ‘overdosing’ in some way or another. The recommendations in this guide refer to the ‘normal’ animal, and special consideration is needed, for instance, during pregnancy and lactation. Interpretation of studies may be confounded when large volumes are administered or excessive sampling employed, particularly if anaesthetics are used. Copyright © 2001 John Wiley &amp; Sons, Ltd.
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Guidelines for the Design and Statistical Analysis of Experiments Using Laboratory Animals

2002-01-01
Michael F. W. Festing , Douglas G. Altman
For ethical and economic reasons, it is important to design animal experiments well, to analyze the data correctly, and to use the minimum number of animals necessary to achieve the … For ethical and economic reasons, it is important to design animal experiments well, to analyze the data correctly, and to use the minimum number of animals necessary to achieve the scientific objectives---but not so few as to miss biologically important effects or require unnecessary repetition of experiments. Investigators are urged to consult a statistician at the design stage and are reminded that no experiment should ever be started without a clear idea of how the resulting data are to be analyzed. These guidelines are provided to help biomedical research workers perform their experiments efficiently and analyze their results so that they can extract all useful information from the resulting data. Among the topics discussed are the varying purposes of experiments (e.g., exploratory vs. confirmatory); the experimental unit; the necessity of recording full experimental details (e.g., species, sex, age, microbiological status, strain and source of animals, and husbandry conditions); assigning experimental units to treatments using randomization; other aspects of the experiment (e.g., timing of measurements); using formal experimental designs (e.g., completely randomized and randomized block); estimating the size of the experiment using power and sample size calculations; screening raw data for obvious errors; using the t-test or analysis of variance for parametric analysis; and effective design of graphical data.

Ethical guidelines for investigations of experimental pain in conscious animals

1983-06-01
M. Zimmermann

Toxicity determined in vitro by morphological alterations and neutral red absorption

1985-02-01
Ellen Borenfreund , James A. Puerner

Measurement of Cell Growth in Tissue Culture with a Phenol Reagent (Folin-Ciocalteau)

1956-02-01
Vance I. Oyama , Harry Eagle
SummaryAn analytical method for the measurement of cell growth in tissue culture is described, based on the Lowry method for the determination of protein, and employing a phenol reagent (Folin-Ciocalteau) … SummaryAn analytical method for the measurement of cell growth in tissue culture is described, based on the Lowry method for the determination of protein, and employing a phenol reagent (Folin-Ciocalteau) for color development. The results, referred to a bovine serum albumin standard, may be converted to dry weight, nitrogen or cell count by appropriate conversion factors. Those factors are here given for 7 human cell lines and 1 mouse line.

Concordance of the Toxicity of Pharmaceuticals in Humans and in Animals

2000-08-01
Harry M. Olson , Graham R. Betton , Denise E. Robinson +7 more

Swine as Models in Biomedical Research and Toxicology Testing

2011-03-25
M. Michael Swindle , Andy Makin , Alan J. Herron +2 more
Swine are considered to be one of the major animal species used in translational research, surgical models, and procedural training and are increasingly being used as an alternative to the … Swine are considered to be one of the major animal species used in translational research, surgical models, and procedural training and are increasingly being used as an alternative to the dog or monkey as the choice of nonrodent species in preclinical toxicologic testing of pharmaceuticals. There are unique advantages to the use of swine in this setting given that they share with humans similar anatomic and physiologic characteristics involving the cardiovascular, urinary, integumentary, and digestive systems. However, the investigator needs to be familiar with important anatomic, histopathologic, and clinicopathologic features of the laboratory pig and minipig in order to put background lesions or xenobiotically induced toxicologic changes in their proper perspective and also needs to consider specific anatomic differences when using the pig as a surgical model. Ethical considerations, as well as the existence of significant amounts of background data, from a regulatory perspective, provide further support for the use of this species in experimental or pharmaceutical research studies. It is likely that pigs and minipigs will become an increasingly important animal model for research and pharmaceutical development applications.

Guidelines for the welfare and use of animals in cancer research

2010-05-01
Paul Workman , Eric O. Aboagye , Frances R. Balkwill +7 more
Animal experiments remain essential to understand the fundamental mechanisms underpinning malignancy and to discover improved methods to prevent, diagnose and treat cancer. Excellent standards of animal care are fully consistent … Animal experiments remain essential to understand the fundamental mechanisms underpinning malignancy and to discover improved methods to prevent, diagnose and treat cancer. Excellent standards of animal care are fully consistent with the conduct of high quality cancer research. Here we provide updated guidelines on the welfare and use of animals in cancer research. All experiments should incorporate the 3Rs: replacement, reduction and refinement. Focusing on animal welfare, we present recommendations on all aspects of cancer research, including: study design, statistics and pilot studies; choice of tumour models (e.g., genetically engineered, orthotopic and metastatic); therapy (including drugs and radiation); imaging (covering techniques, anaesthesia and restraint); humane endpoints (including tumour burden and site); and publication of best practice.
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A call for transparent reporting to optimize the predictive value of preclinical research

2012-10-01
Story C. Landis , Susan Amara , Khusru Asadullah +7 more
Deficiencies in methods reporting in animal experimentation lead to difficulties in reproducing experiments; the authors propose a set of reporting standards to improve scientific communication and study design. Animal studies … Deficiencies in methods reporting in animal experimentation lead to difficulties in reproducing experiments; the authors propose a set of reporting standards to improve scientific communication and study design. Animal studies have contributed immensely to our understanding of diseases and assist the development of new therapies, but inadequate experimental reporting can sometimes render such studies difficult to reproduce and to translate into the clinic. This year, a US National Institute of Neurological Disorders and Stroke workshop addressed this issue, and its conclusions are discussed in a Perspective piece in this issue of Nature. The main workshop recommendation is that at a minimum, studies should report on randomization, blinding, sample-size estimation and how the data were handled. The US National Institute of Neurological Disorders and Stroke convened major stakeholders in June 2012 to discuss how to improve the methodological reporting of animal studies in grant applications and publications. The main workshop recommendation is that at a minimum studies should report on sample-size estimation, whether and how animals were randomized, whether investigators were blind to the treatment, and the handling of data. We recognize that achieving a meaningful improvement in the quality of reporting will require a concerted effort by investigators, reviewers, funding agencies and journal editors. Requiring better reporting of animal studies will raise awareness of the importance of rigorous study design to accelerate scientific progress.
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Guide for the Care and Use of Laboratory Animals (8th edn)

2012-06-23
Udo Albus
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CELL DEATHS IN NORMAL VERTEBRATE ONTOGENY

1951-02-01
A. Glücksmann
Summary i. Degenerations of embryonic cells have either been reported as such or have been misinterpreted by various authors as ‘mitotic metabolites’ or blood cells. 2. There is ample support … Summary i. Degenerations of embryonic cells have either been reported as such or have been misinterpreted by various authors as ‘mitotic metabolites’ or blood cells. 2. There is ample support for the morphological identification of dying cells from the following considerations: the degeneration ‘granules’ are initially Feulgen‐positive and have thus originated from nuclear constituents; the stages of cell deaths seen in normal embryos are identical with those produced experimentally and with those observed directly in tissue cultures; degenerating cells react in the same manner to supravital stains in vivo and in vitro. 3. The process of degeneration varies with the degree of specialization of the cell, with its functional state (e.g. mitosis), with the type of animal and under experimental conditions with the causative agents. 4. Cell death may take from less than 1 hr. to about 7 hr. when only a small proportion of a living tissue dies, but may be prolonged to days when numerous cells die simultaneously and their resorption is delayed. 5. Degenerations have been found during the normal development in embryos of all vertebrate animals examined. The occurrence of necrosis in embryos of pure genetical lines is excluded from this article. 6. The incidence of embryonic cell deaths according to site, tissue, developmental stage or process and type of animal is summarized in Table 1. 7. While some degenerations have no obvious function in embryonic development, others seem to play a significant role in embryonic processes, e.g. the morphogenesis and histogenesis of tissues and organs, and the representation and regression of phylogenetic steps (Table 2). 8. Morphogenetic degenerations precede changes in the form of epithelial organs, e.g. during the invagination of the optic cup, the formation of the crystalline lens, the olfactory pit, the neural tube, etc. They bring about the separation of rudiments such as that of the neural tube and the lens from the ectoderm. They reduce the excessive thickening of uniting edges such as those of the body wall and of the mandibles. They are involved in the production of lumina in the solid rudiments of glands and the intestinal tract. In the mesenchyme they precede and make possible the influx of specialized tissue such as the sternal plates or the ingrowth of myogenic tissue in the mandible. 9. Histiogenetic degenerations are related to the differentiation of tissues and organs. The differentiation of the three cell layers of the frog tadpole retina, for instance, is accompanied by three waves of degeneration. Similar cell deaths of early neuroblasts are found in the spinal ganglia outside the limb regions. In amphibia a partial sarcolysis during metamorphosis provides a blastema for the permanent musculature. Sex differentiation of the individual involves the partial degeneration of the Mullerian or Wolffian ducts. Cell deaths also occur in relation to fibre formation and to the appearance of bone and cartilage matrix. Their role in these and in evocatory processes needs further elucidation. Whether cell deaths in the central nervous system and the sense organs at the time of vascularization and neurotization are related to these phenomena remains to be further investigated. 10. Phylogenetic cell deaths are of two types: those which represent a vestigial organ such as the paraphysis or the second muscle stage in higher vertebrates, and those concerned with the regression of larval structures such as the conjunctival papilla, parts of the ganglia of branchial nerves, of the pro‐ and mesonephros. Some of these larval organs have a function in embryonic development, viz. the apical ridge on the limb buds. 11. The causation of the distinctly localized morphogenetic degenerations is obscure. Vascular or nutritional disturbances are unlikely to be responsible for these cell deaths which precede changes in form and appear in the same localizations and amounts in the vascularized tissue of the intact embryo and after explantation in tissue cultures. . Most of the histiogenetic and phylogenetic cell deaths, as well as some of the not strictly localized morphogenetic degenerations, may be due to the fading out of stimuli for their proliferation or for the completion of their differentiation. If such cells fail to divide, they age and die on reaching the end of their normal life span. This conception assumes that stimuli for the formation of embryonic tissues and organs act for limited periods only and extend over a field of cells. Some of these cells respond fully to stimulation, while others are late to react or do so only partially or receive only a fraction of the whole stimulus. The partial differentiation of cells unfits them for division, for dedifferentiation and redifferentiation in another direction. 12. The localized morphogenetic degenerations are correlated with the incidence and orientation of mitosis and of cell movements, and changes in the form of embryonic organs are brought about by the integration of these three cellular activities. Cell deaths are abundant wherever the regular arrangement and close packing of cells prevent free cell movements; they are rare or absent when, as, for instance, in the tadpole eye, a loose arrangement of cells and a decrease in cell volume (by resorption of yolk) allow of free cell movements. 14. Cell degeneration in vertebrate ontogeny is an important mechanism of integration of cells into tissues and organs by helping to shape the form of organs, by the removal of superfluous cells or by the preparation of a dedifferentiated blastema in histio‐ and phylogenesis.

Can Animal Models of Disease Reliably Inform Human Studies?

2010-03-29
H. Bart van der Worp , David W. Howells , Emily S. Sena +4 more
Animal experiments have contributed much to our understanding of mechanisms of disease, but their value in predicting the effectiveness of treatment strategies in clinical trials has remained controversial [1-3].In fact, … Animal experiments have contributed much to our understanding of mechanisms of disease, but their value in predicting the effectiveness of treatment strategies in clinical trials has remained controversial [1-3].In fact, clinical trials are essential because animal studies do not predict with sufficient certainty what will happen in humans.In a review of animal studies published in seven leading scientific journals of high impact, about one-third of the studies translated at the level of human randomised trials, and one-tenth of the interventions, were subsequently approved for use in patients [1].However, these were studies of high impact (median citation count, 889), and less frequently cited animal research probably has a lower likelihood of translation to the clinic.Depending on one's perspective, this attrition rate of 90% may be viewed as either a failure or as a success, but it serves to illustrate the magnitude of the difficulties in translation that beset even findings of high impact.Recent examples of therapies that failed in large randomised clinical trials despite substantial reported benefit in a range of animal studies include enteral probiotics for the prevention of infectious complications of acute pancreatitis, NXY-059 for acute ischemic stroke, and a range of strategies to reduce lethal reperfusion injury in patients with acute myocardial infarction [4][5][6][7].In animal models of acute ischemic stroke, about 500 ''neuroprotective'' treatment strategies have been reported to improve outcome, but only aspirin and very early intravenous thrombolysis with alteplase (recombinant tissueplasminogen activator) have proved effec-tive in patients, despite numerous clinical trials of other treatment strategies [8,9].Research in Translation discusses health interventions in the context of translation from basic to clinical research, or from clinical evidence to practice.
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1,026 Experimental treatments in acute stroke

2006-02-01
Victoria O’Collins , Malcolm Macleod , Geoffrey A. Donnan +3 more
Preclinical evaluation of neuroprotectants fostered high expectations of clinical efficacy. When not matched, the question arises whether experiments are poor indicators of clinical outcome or whether the best drugs were … Preclinical evaluation of neuroprotectants fostered high expectations of clinical efficacy. When not matched, the question arises whether experiments are poor indicators of clinical outcome or whether the best drugs were not taken forward to clinical trial. Therefore, we endeavored to contrast experimental efficacy and scope of testing of drugs used clinically and those tested only experimentally.We identified neuroprotectants and reports of experimental efficacy via a systematic search. Controlled in vivo and in vitro experiments using functional or histological end points were selected for analysis. Relationships between outcome, drug mechanism, scope of testing, and clinical trial status were assessed statistically.There was no evidence that drugs used clinically (114 drugs) were more effective experimentally than those tested only in animal models (912 drugs), for example, improvement in focal models averaged 31.3 +/- 16.7% versus 24.4 +/- 32.9%, p > 0.05, respectively. Scope of testing using Stroke Therapy Academic Industry Roundtable (STAIR) criteria was highly variable, and no relationship was found between mechanism and efficacy.The results question whether the most efficacious drugs are being selected for stroke clinical trials. This may partially explain the slow progress in developing treatments. Greater rigor in the conduct, reporting, and analysis of animal data will improve the transition of scientific advances from bench to bedside.

A simple practice guide for dose conversion between animals and human

2016-01-01
Anroop B. Nair , Shery Jacob
Understanding the concept of extrapolation of dose between species is important for pharmaceutical researchers when initiating new animal or human experiments.Interspecies allometric scaling for dose conversion from animal to human … Understanding the concept of extrapolation of dose between species is important for pharmaceutical researchers when initiating new animal or human experiments.Interspecies allometric scaling for dose conversion from animal to human studies is one of the most controversial areas in clinical pharmacology.Allometric approach considers the differences in body surface area, which is associated with animal weight while extrapolating the doses of therapeutic agents among the species.This review provides basic information about translation of doses between species and estimation of starting dose for clinical trials using allometric scaling.The method of calculation of injection volume for parenteral formulation based on human equivalent dose is also briefed.
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The 1996 Guide for the Care and Use of Laboratory Animals

1997-01-01
J. Derrell Clark , Gerald F. Gebhart , Janet C. Gonder +2 more
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Experimental design and analysis and their reporting II: updated and simplified guidance for authors and peer reviewers

2018-03-09
Michael J. Curtis , S P H Alexander , Giuseppe Cirino +7 more
Abstract This article updates the guidance published in 2015 for authors submitting papers to British Journal of Pharmacology (Curtis et al. , 2015) and is intended to provide the rubric … Abstract This article updates the guidance published in 2015 for authors submitting papers to British Journal of Pharmacology (Curtis et al. , 2015) and is intended to provide the rubric for peer review. Thus, it is directed towards authors, reviewers and editors. Explanations for many of the requirements were outlined previously and are not restated here. The new guidelines are intended to replace those published previously. The guidelines have been simplified for ease of understanding by authors, to make it more straightforward for peer reviewers to check compliance and to facilitate the curation of the journal's efforts to improve standards.
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Guide for the Care and Use of Laboratory Animals

2011-12-27
National Research Council

Guide for the Care and Use of Laboratory Animals

2011-04-30

ARRIVE 2.0 and the British Journal of Pharmacology: Updated guidance for 2020

2020-07-14
Elliot Lilley , S. Clare Stanford , David Kendall +7 more
The BJP has been and remains an active advocate of the ARRIVE (Animal Research: Reporting of in vivo Experiments) guidelines (Kilkenny, Browne, Cuthill, Emerson, & Altman, 2010a) that were established … The BJP has been and remains an active advocate of the ARRIVE (Animal Research: Reporting of in vivo Experiments) guidelines (Kilkenny, Browne, Cuthill, Emerson, & Altman, 2010a) that were established by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) in 2010. The ARRIVE guidelines need no introduction and we will not rehearse the arguments in depth here, other than to restate that the lack of key in vivo experimental details has been identified as a major contributing factor to the poor reproducibility of pre-clinical research. This fact was the primary driver for establishment by the NC3Rs of the first version of the ARRIVE guidelines. ARRIVE provided a 20-point checklist, specifying all of the experimental details (procedures and fixed factors) that should be included in manuscripts for proper reporting of animal research. The guidelines were rapidly endorsed internationally by funding bodies, universities, learned societies and, importantly, Life Science journals. Currently there are 1,046 journals endorsing ARRIVE including BJP, which was one of the original six influential journals that published the guidelines in full in 2010 (Kilkenny, Browne, Cuthill, Emerson, & Altman, 2010b). However, ARRIVE has not had the effect that was originally hoped for, despite this widespread support and endorsement. In 2016 and in 2018 assessments of adherence of articles published in endorsing journals identified a lack of engagement. As an example, one systematic review of reports of studies investigating acute lung injury revealed that, of the items expected for ARRIVE compliance, only 45% of those advised for inclusion in the Methods, and only 29% of those for inclusion in the Results section, were present (Avey et al., 2016). Moreover, formal endorsement of the ARRIVE guidelines by journals did not necessarily improve compliance (Leung, Rousseau-Blass, Beauchamp, & Pang, 2018). Such disappointing reports of outcome triggered a reappraisal of the guidelines led by the NC3Rs who, in 2018, established a new, international Working Group to review and update the ARRIVE guidelines to generate ARRIVE 2.0 (Percie du Sert et al., 2018). As with the team of experts brought together to establish the first iteration of ARRIVE, the Editor in Chief of the BJP is a member of the new team that was assembled. As such, the BJP has been well-placed to influence the content, testing and final publication of both iterations of the guidelines. In 2015, the BJP published an editorial reporting findings from a survey of compliance with ARRIVE in articles published in 2014 in two issues of the journal (McGrath & Lilley, 2015). The results were not as had been hoped for, as was also evident from assessments elsewhere, and revealed scope for improving compliance in respect of both the design of the (animal) experiments and the description of experimental procedures. To help remedy this problem, a checklist was developed that provided an aide memoire of the details of the animals and research procedures that should be reported in manuscripts submitted to the journal. A further editorial focussed on experimental design and data analysis (Curtis et al., 2018) for all types of experimental data published in the journal, including those emanating from experiments with animals, was also published. A key issue with many of the studies reported in BJP prior to this related to inadequate experimental design and inappropriate statistical analysis. At the same time, the Instructions to Authors were revised, to include the new rubric, and the editorial scrutiny of these aspects of the peer review process was tightened up. As a further prompt, in 2016, authors were required to make a Declaration as part of the submission process, to confirm that their manuscript was ARRIVE compliant. In addition to these measures, two new 'specialist' editors were appointed: a Design & Analysis Advisor and a Consulting Editor in ARRIVE Guidelines and Animal Welfare. The brief of the latter was to monitor ARRIVE compliance in BJP publications and to assist Senior Editors with their appraisal of manuscripts. All these changes still remain in place with the addition of a Consulting Editor in Statistical Analysis to ensure that the research reports match BJP criteria and so qualify for publication. ARRIVE 2.0 together with an 'Explanation and Elaboration' document was loaded onto the NC3Rs website in July 2019 as a preprint (i.e., before peer review (Percie du Sert et al., 2019)), and is now published in full in PLOS Biology (Percie du Sert et al., 2020), with simultaneous publication in several international journals, including this issue of the BJP (Percie du Sert et al., 2020). In preparation for the publication of the new guidelines we conducted surveys assessing compliance to ARRIVE in the BJP over 4 years, the results of which can be seen in Table 1. These data together with the July 2019 preprint of ARRIVE 2.0 were discussed extensively by the Senior Editorial Board of the BJP in December 2019. This editorial explains the ensuing changes in the journal's editorial policy as a result of those discussions and how they relate to ARRIVE 2.0. The principle of full disclosure lies at the heart of what we expect from authors wishing to publish in the BJP and in support of this principle is the absence of a word restriction for the Methods section. Judging from articles surveyed, between July 2014 and October 2019, most authors are conscientious about compliance with our 'Instructions to Authors' in respect of confirming ethical approval of the research, specifying the source, species and strain of animals and the inclusion of a statement on the translational relevance of the research study (Table 1). However, a general observation is that, although many manuscripts include lengthy details of the molecular biological or biochemical techniques that were used in the study, when experiments involved the use of animals, both the design of experiments and the description of the experimental procedures are often inadequately detailed making reproducibility challenging. Reporting of the method for killing animals has improved over the years but is still inconsistent, despite the need for manuscripts to be clear about when and how animals were killed. Information on housing and husbandry is often provided but, again, the level of detail is highly variable. Important elements, such as stocking density, configuration of group-housed animals (in respect of littermates, genotypes, or randomised mixed-caging, for example) provision of food (including, ideally, the composition of the laboratory diet) and water and environmental enrichment are not always disclosed, despite increasing recognition that these factors can affect the research findings (Finney et al., 2020; Reardon, 2016). The poor reporting of the provision of analgesia in the surgical context is particularly worrying. Of course, a lack of any mention of analgesia in the manuscript does not mean that none was provided; there could also be a strong scientific justification for withholding analgesia in some experiments. However, that did not apply to any of the manuscripts that were reviewed: in all those cases, analgesia could and should have been provided. Two options were considered by the Senior Editorial Board in December 2019: (i) endorse ARRIVE 2.0 guidelines and adopt them verbatim as official BJP policy or (ii) endorse ARRIVE 2.0 but devise our own reporting policy, which would be particularly relevant for pharmacologists. In considering the results of our surveys and the content of the ARRIVE 2.0 preprint, the Board decided on the latter approach. Authors should be reassured that nothing major has changed in practice. This journal has always taken inspiration from ARRIVE, while adopting a 'bespoke' approach to the reporting of the types of animal research carried out by pharmacologists. Authors should also note that requirements in respect of experimental design and analysis in articles published in BJP have not changed at all and can be found at: https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.14153 (Curtis et al., 2018). That said, we strongly advise authors to use the NC3Rs Experimental Design Assistant (https://www.nc3rs.org.uk/experimental-design-assistant-eda) (Percie du Sert et al., 2017) when planning the experimental design and the data analysis of their work. The most striking change in the updated ARRIVE guidelines is the subdivision of the original checklist into two tables/checklists: the 'Essential 10' and the 'Recommended set'. The former focuses mainly on aspects of the experimental design that are essential for reducing bias (subjective or systematic), whereas the latter deals with points that pertain to the factors that authors are advised to disclose in order to enable others to replicate the experiment. Our current guidelines for experimental design and statistical analysis address many of the 'Essential 10', and for our modified approach we concentrate on many of the items in the 'Recommended set'. Our updated'BJP Declaration of Transparency and Scientific Rigour: Checklist for Animal Experimentation' is shown in Table 2, along with indicators of how each element connects with ARRIVE 2.0. These amendments do not challenge the importance of either version of ARRIVE. On the contrary, we strongly recommend that all authors read ARRIVE 2.0 (Percie du Sert, Hurst, et al., 2020) and familiarise themselves with the complementary 'Explanation and Elaboration' document (Percie du Sert et al., 2020). Essential 8 Essential 9 Recommended Recommended 12 Recommended 14 Recommended 15 Recommended 16 In terms of the details that should be included in every manuscript submitted to the BJP, the new checklist for reporting animal research will consist of the following six mandatory elements (see also Table 2): Details of the source, species, strain, sex, age and/or weight range of the animals used in the study must be given. A comprehensive account of the experimental procedure with particular attention to the use of any pharmacologically active agents at any stage of the study, including: anaesthesia, analgesia, antibiotics or any veterinary treatment administered for welfare purposes. Authors should also confirm that, for all surgical procedures, precautions to ensure aseptic conditions were applied throughout. Details of post-surgical analgesia and care of the animals should be provided, as should any procedures for monitoring the animals during post-operative recovery: e.g., the frequency and duration of the observations, temperature control etc. If analgesia cannot be given, this needs to be justified scientifically. A statement to confirm that the animals were killed by an individual trained to do this procedure, together with a description of how and when animals are killed, must also be included. In this context, authors should bear in mind that only certain methods for humane killing are permitted in the UK (and other countries governed by Directive 2010/63/EU) and these are stringently regulated. As a consequence, it might not be possible to consider a manuscript for publication in this journal if euthanasia has been carried out using a procedure that is regarded as unacceptable in the UK.One notable change to our policy is that whenever welfare assessments, or other precautions, were necessary during any stage of the research, these must now be reported, together with a clear definition of humane end-points. We acknowledge that these aspects of experimental conduct may well be implemented routinely in individual laboratories but, hitherto, they have not been perceived as an essential aspect of the research report. We want authors to include this information, as a matter of course, not least because other researchers in the field would find it important and helpful. Full details of the specific animal model that was used and the scientific justification for the choice of that model in the context of achieving the research objectives should be provided. This aspect of the report can be challenging, but we hope to encourage authors to be conservative and realistic when claiming to have used an animal 'model' of a complex human disorder (see next section). A statement to confirm that the research reported in the manuscript obtained local ethical approval is essential. BJP seeks to publish research on animals that conforms to standards upheld in the UK. Some elements should always be included, for example: type of housing, type of cage (open or individually ventilated) stocking density, food and water provision, bedding material, environmental enrichment, lighting regimen. For fish, details of the tank and the number of fish in each one should be included. Information on other elements should be included if they are crucial for the study or if they could affect the experimental results: e.g., the time of day the study took place, nature of handling/capture. The configuration of animals within cages should also be specified for instance, mixed or separate housing of genetically-altered/wildtypes or disease-susceptible/normal animals should be provided. Any welfare-related assessments, measurements and interventions that were carried out before, during, or after the study, especially if these were intended to ameliorate or limit the harms to the animals (e.g., humane end-points) must be reported. Another change is that both ARRIVE 2.0 and our revised BJP Declaration have removed the obligation to report any advance in the 3Rs (Replacement, Reduction and Refinement) that has emerged from the research. This is partly because compliance with this has been negligible. Nevertheless, the BJP Senior Editorial Board recognises the importance of the 3Rs as part of the ethical framework for all research that uses animals and so we encourage authors to include this information whenever their findings have made a useful contribution to any of the 3Rs. The ARRIVE 2.0 guidelines are certainly viewed as an important step in helping to address the problem of poor reproducibility and translation of research findings in the biomedical sciences. However, successful translation also depends on a sound rationale for the research. So far, the attempts to improve reproducibility have somewhat overshadowed the growing scepticism about the validity of 'animal models' of some human disorders. In many cases, the creation of an animal model in order to carry out experiments, which would not be permitted in humans, is an entirely reasonable objective. That would be the case for human disorders that have an established link with a single genetic abnormality, such as cystic fibrosis, Down syndrome and hypertrophic cardiomyopathy. Even in cases where a specific genetic mutation is a common, but not invariable, cause of the disorder (e.g., Fragile X syndrome, amyotrophic lateral sclerosis), it is still reasonable to back-translate the mutation to create an animal model to investigate the underlying biological abnormalities and potential treatments. Few people would argue that those research findings are not instructive or that the description of the animal as a 'model' of the human disorder is scientifically unjustified. Even when there is no such clear causal link, it is valid to describe an animal as a 'model' when it expresses an abnormality that is convincingly analogous to the diagnostic biomarker(s) in humans. Examples of these would include: neoplasia, Cushing's/Addison's disease, diabetes, skin pigmentation diseases, myasthenia gravis. Even though treatment strategies that are effective in the animals often do not translate into humans, it is still reasonable to regard them as 'models' of the human condition and such research has contributed a great deal to our understanding of the illnesses. It is far more difficult to be confident about the validity of animal models of complex, multifactorial human illnesses, which can comprise a mixture of any of several pathological, physiological and behavioural abnormalities, which can be primary or secondary features of the illness. These would include conditions such as: hypertension, heart failure, renal failure, metabolic syndrome, neurological and psychiatric disorders. In all these cases, the profile and/or severity of the underlying problems can differ substantially from patient to patient, but still meet the criteria for the same broad clinical diagnosis. In such cases, we hope to encourage authors to be more cautious about claims that their 'animal model' is analogous to the human condition. This is especially important for 'models' that are based on evidence from procedures that are normally used as drug screens to predict therapeutic efficacy in humans (see, for example: Stanford, 2017). In such cases, authors should justify their assumption that the abnormality that is being evaluated in the baseline condition (i.e, with no experimental intervention such as drug treatment or genetic alteration) is a valid model of the human illness or a particular aspects of that illness. On the other hand, we want to discourage non-committal descriptions such as 'cirrhosis-like', 'epilepsy-like' or 'autism-like', or vague terms, such as 'asthma' instead of 'respiratory allergy'. Instead, our aim is to encourage authors to be precise about the extent to which aspect(s) of the human disorder are expressed in the animal model, and also to acknowledge its limitations. Where these questions have been very well analysed for any particular model, it is appropriate for authors to cite the relevant literature explaining why the animal model is appropriate. We believe this is timely advice because there is burgeoning interest in research of 'endophenotypes' in which a specific aspect of an animal's normal/abnormal physiology or behaviour can be mapped onto an underlying genetic mutation or physiological system (e.g., neuronal network, or other physiological feedback loop) – and which are often not confined to a single human disorder. This approach further acknowledges that some human illnesses are better regarded as assemblies of endophenotypes, rather than unitary disorders. Obviously, the definition of an endophenotype also needs scrupulous validation, but this change of mindset will be essential for successful progress in stratified and personalised medicine. A final point, addressed only indirectly by ARRIVE 2.0, concerns the validity of some research procedures that are used to produce the 'model' (see: Stanford, 2020). Examples include some experimental interventions to induce end-stage heart failure, or the use of environmental stressors that are intended to alter the physiology and/or behaviour of the animals. Examples include the use of environmental stressors, such as electric shocks or a series of unpredictable stressors that change from day to day, sometimes for several weeks. In most cases, the individual stressors are mild and can arguably be regarded as analogous to challenges faced by some humans and which impair their mental health, but this is not always the case. Some of these experiments involve prolonged bouts of stressors, which would be regarded as severe, especially when their cumulative harm is taken into account. In such cases, the BJP will require authors to provide assurance that the severity and duration of the aversive stimuli was the minimum required to meet the scientific objectives of the study, particularly when using a series of unpredictable stressors, for instance. Also, in order to underpin the validity of such animal 'models', authors should include a statement to clarify the ways in which the aversive stimuli used in the research are relevant to the manifestation of the disorder of interest, which is being modelled in the animals. In response to the publication of the revised ARRIVE guidelines (ARRIVE 2.0), the Senior Editorial Board of this journal has revised the policy on reporting of animal research. The primary principle remains the same as before, which is to encourage full disclosure of all relevant information and to expect to see evidence for high standards of animal welfare. It is important to remember that this is not simply for the benefit of the animals. High standards of experimental design, reporting and animal welfare are crucial if the research is to be reproducible and translatable. In that context, we encourage authors to read Drummond and Vowler (2013). The BJP has, for some time, taken the view that the prevailing standards expected by the regulatory framework in the UK should be reflected in the journal's publications. For example, studies of proprietary tobacco products are not permitted in the UK and the BJP will not publish them. Similarly, death as an endpoint, in non-regulatory studies would not normally be acceptable (with the exception of studies of anti-cancer and certain antimicrobial drugs, for example), but when current regulatory guidelines still mandate mortality endpoints, we expect humane endpoints to be described fully and implemented. Some experiments that involve procedures that would be regarded as 'severe' but can, nonetheless, be scientifically justified. However, the justification for some such procedures might not be clear. In most of these cases, a discussion between the editor(s) and the authors would seek to confirm whether or not there was a robust justification for using such procedures, or humane endpoints, regardless of any local ethical approval for the study. If this turns out to be the case, the manuscript may be published. Finally, raising the standard of research reporting will certainly help to improve reproducibility but, to improve translation will also require a more realistic, evidence-based appraisal of the validity of the experimental procedures and research 'models'. To that end, we want to encourage authors to consider the extent to which the models they have investigated really do offer insight into the causes, pathology and treatment of multifactorial human disorders. In cases where there is any doubt, authors should be assured that more modest objectives and clarity about the specific features of the disorder that have been 'modelled' would attract even more confidence and scientific merit. The authors declare no conflicts of interest.
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Reporting animal research: Explanation and elaboration for the ARRIVE guidelines 2.0

2020-07-14
Nathalie Percie du Sert , Amrita Ahluwalia , Sabina Alam +7 more
Improving the reproducibility of biomedical research is a major challenge. Transparent and accurate reporting is vital to this process; it allows readers to assess the reliability of the findings and … Improving the reproducibility of biomedical research is a major challenge. Transparent and accurate reporting is vital to this process; it allows readers to assess the reliability of the findings and repeat or build upon the work of other researchers. The ARRIVE guidelines (Animal Research: Reporting In Vivo Experiments) were developed in 2010 to help authors and journals identify the minimum information necessary to report in publications describing in vivo experiments. Despite widespread endorsement by the scientific community, the impact of ARRIVE on the transparency of reporting in animal research publications has been limited. We have revised the ARRIVE guidelines to update them and facilitate their use in practice. The revised guidelines are published alongside this paper. This explanation and elaboration document was developed as part of the revision. It provides further information about each of the 21 items in ARRIVE 2.0, including the rationale and supporting evidence for their inclusion in the guidelines, elaboration of details to report, and examples of good reporting from the published literature. This document also covers advice and best practice in the design and conduct of animal studies to support researchers in improving standards from the start of the experimental design process through to publication.
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The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research

2020-07-14
Nathalie Percie du Sert , Viki Hurst , Amrita Ahluwalia +7 more
Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of … Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and reproduce the methods and results. Despite considerable levels of endorsement by funders and journals over the years, adherence to the guidelines has been inconsistent, and the anticipated improvements in the quality of reporting in animal research publications have not been achieved. Here, we introduce ARRIVE 2.0. The guidelines have been updated and information reorganised to facilitate their use in practice. We used a Delphi exercise to prioritise and divide the items of the guidelines into 2 sets, the "ARRIVE Essential 10," which constitutes the minimum requirement, and the "Recommended Set," which describes the research context. This division facilitates improved reporting of animal research by supporting a stepwise approach to implementation. This helps journal editors and reviewers verify that the most important items are being reported in manuscripts. We have also developed the accompanying Explanation and Elaboration document, which serves (1) to explain the rationale behind each item in the guidelines, (2) to clarify key concepts, and (3) to provide illustrative examples. We aim, through these changes, to help ensure that researchers, reviewers, and journal editors are better equipped to improve the rigour and transparency of the scientific process and thus reproducibility.
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The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research

2020-07-14
Nathalie Percie du Sert , Viki Hurst , Amrita Ahluwalia +7 more
Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of … Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and reproduce the methods and results. Despite considerable levels of endorsement by funders and journals over the years, adherence to the guidelines has been inconsistent, and the anticipated improvements in the quality of reporting in animal research publications have not been achieved. Here, we introduce ARRIVE 2.0. The guidelines have been updated and information reorganised to facilitate their use in practice. We used a Delphi exercise to prioritise and divide the items of the guidelines into 2 sets, the "ARRIVE Essential 10," which constitutes the minimum requirement, and the "Recommended Set," which describes the research context. This division facilitates improved reporting of animal research by supporting a stepwise approach to implementation. This helps journal editors and reviewers verify that the most important items are being reported in manuscripts. We have also developed the accompanying Explanation and Elaboration (E&E) document, which serves (1) to explain the rationale behind each item in the guidelines, (2) to clarify key concepts, and (3) to provide illustrative examples. We aim, through these changes, to help ensure that researchers, reviewers, and journal editors are better equipped to improve the rigour and transparency of the scientific process and thus reproducibility.
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The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research*

2020-07-14
Nathalie Percie du Sert , Viki Hurst , Amrita Ahluwalia +7 more
Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of … Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and reproduce the methods and results. Despite considerable levels of endorsement by funders and journals over the years, adherence to the guidelines has been inconsistent, and the anticipated improvements in the quality of reporting in animal research publications have not been achieved. Here, we introduce ARRIVE 2.0. The guidelines have been updated and information reorganised to facilitate their use in practice. We used a Delphi exercise to prioritise and divide the items of the guidelines into 2 sets, the "ARRIVE Essential 10," which constitutes the minimum requirement, and the "Recommended Set," which describes the research context. This division facilitates improved reporting of animal research by supporting a stepwise approach to implementation. This helps journal editors and reviewers verify that the most important items are being reported in manuscripts. We have also developed the accompanying Explanation and Elaboration document, which serves (1) to explain the rationale behind each item in the guidelines, (2) to clarify key concepts, and (3) to provide illustrative examples. We aim, through these changes, to help ensure that researchers, reviewers, and journal editors are better equipped to improve the rigour and transparency of the scientific process and thus reproducibility.
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Frontiers in Catecholamine Research

1973-01-01

Improving Bioscience Research Reporting: The ARRIVE Guidelines for Reporting Animal Research

2010-06-29
Carol Kilkenny , William J. Browne , Innes C. Cuthill +2 more
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The Guide for the Care and Use of Laboratory Animals

2016-03-31
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Guide for the care and use of laboratory animals

1997-02-01

Lost in translation: animal models and clinical trials in cancer treatment.

2014-01-01
Isabella W.Y. Mak , Nathan Evaniew , Michelle Ghert
Due to practical and ethical concerns associated with human experimentation, animal models have been essential in cancer research. However, the average rate of successful translation from animal models to clinical … Due to practical and ethical concerns associated with human experimentation, animal models have been essential in cancer research. However, the average rate of successful translation from animal models to clinical cancer trials is less than 8%. Animal models are limited in their ability to mimic the extremely complex process of human carcinogenesis, physiology and progression. Therefore the safety and efficacy identified in animal studies is generally not translated to human trials. Animal models can serve as an important source of in vivo information, but alternative translational approaches have emerged that may eventually replace the link between in vitro studies and clinical applications. This review summarizes the current state of animal model translation to clinical practice, and offers some explanations for the general lack of success in this process. In addition, some alternative strategies to the classic in vivo approach are discussed.

[10] Superoxide dismutase assays

1984-01-01
Leopold Flohé , Fritz Ötting

From traditional medicine to modern medicine: the importance of TCM regulatory science (TCMRS) as an emerging discipline

2025-06-26
Hua Hua , Jianyuan Tang , Junning Zhao +6 more | Chinese Medicine
Abstract Traditional Chinese medicine (TCM) has become a standardized medical system through systematic development across global healthcare practices. However, concerns persist regarding the safety, efficacy and quality of traditional medicinal … Abstract Traditional Chinese medicine (TCM) has become a standardized medical system through systematic development across global healthcare practices. However, concerns persist regarding the safety, efficacy and quality of traditional medicinal products. Traditional Chinese medicine regulatory science (TCMRS) has emerged as an interdisciplinary field to address these challenges. This discipline integrates multidisciplinary knowledge to develop new tools, standards and approaches for systematic evaluation of benefit-risk profiles. This approach aims to ensure the quality, safety, and efficacy of TCM products, while also supporting the development of scientifically grounded regulatory frameworks that accommodate traditional medicine’s distinctive characteristics. Through comprehensive quality management from raw material sourcing to production processes and clinical validation, developing and adopting TCMRS is entrusted to significantly strengthen its regulatory oversight. This review examines the critical scientific challenges in the modernization process of TCM, analyzes the conceptual foundations of TCMRS, evaluates its pivotal role in pharmaceutical transformation, and highlights its essential function in preserving traditional knowledge while fostering therapeutic innovation. Key challenges for TCMRS implementation include reconciling traditional epistemologies with modern pharmaceutical paradigms, standardizing complex herbal formulations, and developing rigorous evaluation protocols for decoctions and compound preparations. The integration of advanced methodologies, including systems biology, network pharmacology, artificial intelligence, and nanotechnology, into regulatory frameworks, combined with enhanced international cooperation, remains a crucial strategy for tackling global public health challenges. Future development trajectories for TCMRS will prioritize lifecycle management strategies, technology-driven innovation systems, and global knowledge-sharing initiatives, propelled by advancements in life sciences and information technology. This evolution requires careful balancing of three fundamental elements: theoretical development in traditional medicine, integration of emerging technologies, and maintenance of regulatory system stability. It is crucial to innovate the working mechanisms of the TCMRS researcher alliance and the global policy-coordination mechanism for TCM regulation, enhance the conversion of basic disciplines into regulatory applications, and support the establishment of an excellent TCM regulatory system with scientific decision-making. These efforts are essential for promoting the high-quality development of the TCM industry and boosting its international influence and presence.

Impact of CONCEA's normative resolutions on animal use in regulatory testing in Brazil: a quantitative assessment

2025-06-24
Lilia Serodio , Carolina de Oliveira , Charles Alves Nogueira +2 more | Caderno Pedagógico
Introduction: Alternative testing methods based on the 3Rs principles (Replacement, Reduction, and Refinement) have increasingly been incorporated into regulatory toxicology. In Brazil, the creation of the National Council for the … Introduction: Alternative testing methods based on the 3Rs principles (Replacement, Reduction, and Refinement) have increasingly been incorporated into regulatory toxicology. In Brazil, the creation of the National Council for the Control of Animal Experimentation (CONCEA) in 2008, has driven the recognization of validated alternative methods. Since 2014, CONCEA has published Normative Resolutions (NRs) recognizing alternative methods aligned with replacing or reducing traditional animal-based tests. Objective: This study aimed to quantitatively assess the impact of NRs 18/2014, 31/2016, 45/2019, and 56/2022 on animal use in regulatory testing. A detailed comparison was made between traditional and alternative methods referenced in OECD TGs and Brazilian Pharmacopoeia monographs. Materials and Methods: A quantitative analysis evaluated the impact of CONCEA’s NRs (18/2014, 31/2016, 45/2019, and 56/2022) by comparing animal-based toxicological tests and species used with alternative methods recognized. Results and Discussion: Before the adoption of alternative methods, up to 534 animals could be used per batch. The recognition of 34 alternative methods through CONCEA’s NRs is projected to result in a 78% reduction in animals up to 2027. Conclusions: The implementation of CONCEA’s Normative Resolutions has significantly advanced the application of the 3Rs principles in Brazil, demonstrating a measurable reduction in animal use for regulatory safety testing. The study underscores the role of CONCEA’s NRs and international harmonization in promoting ethical and scientifically robust testing practices in Brazil. While progress is evident, the continued reliance on certain in vivo methods highlights the need for ongoing development, validation, and broader regulatory recognition of alternative approaches to ensure ethical and effective testing practices.

Letter to the editor: a commentary on “exploring the toxicological network in diabetic microvascular disease: the role of endocrine disrupting chemicals”

2025-06-24
Junqi Gou , Chaohui Liu , Fengyou Yao | International Journal of Surgery

Correction: Mertz et al. Interdisciplinary Animal Research Ethics—Challenges, Opportunities, and Perspectives. Animals 2024, 14, 2896

2025-06-19
Marcel Mertz , Tatiana Hetzel , Karla Alex +7 more | Animals
In the original version [...]. In the original version [...].

From animal testing to in Silico models: a systematic review and practical guide to cosmetic assessment

2025-06-16
Tamara G. Vasiljev , Lucia Salvioni , Miriam Colombo +2 more | Statistical Methods & Applications

Quantifying Misuse of Color in Biological Research

2025-06-15
Teng-Jui Lin , Kylee Hillman , Laura Kim +3 more | bioRxiv (Cold Spring Harbor Laboratory)
Colors are widely used to report biological research data. Effective interpretation of colors relies on accurate, intuitive, and accessible colormaps that are properly labeled. Misuse of colormaps, such as using … Colors are widely used to report biological research data. Effective interpretation of colors relies on accurate, intuitive, and accessible colormaps that are properly labeled. Misuse of colormaps, such as using rainbow, mismatched, and other inaccessible colormaps, hinders reader interpretation. Despite their ubiquitous use to represent biological data, the prevalence of colormap misuse has not been quantified. Using established guidelines, we analyzed over 6,000 articles in 10 high-impact biological journals spanning 2020-2024 to quantify the prevalence of colormap use and misuse. Over 67% of articles contain at least one colormap, of which 81% contain some form of misuse. Among the over 11,000 acquired colormap-associated figures, 60% contain some form of misuse. Heatmaps, scatter plots, images, and image overlays are the most commonly used figures with colormaps. These statistics vary by journal but remain constant over time, demonstrating the urgent need to increase awareness and education about color-based data reporting guidelines.

The (re)turn of the 3Rs: an inquiry into the normative nature of Russell and Burch’s principles of humane experimental technique – their misunderstanding, reform and implementation through an ethics tool

2025-06-12
Herwig Grimm , Marc Dusseldorp | Laboratory Animals
The 3Rs strongly shape the practice of laboratory animal use, as well as related policies worldwide. This success should not obscure the fact that implementing the 3Rs comes with challenges. … The 3Rs strongly shape the practice of laboratory animal use, as well as related policies worldwide. This success should not obscure the fact that implementing the 3Rs comes with challenges. A major problem is that it is fundamentally unclear under which conditions the 3Rs may be considered fulfilled in specific contexts. We argue that this lack of clarity is largely a result of the fact that the normative nature of the 3Rs has so far been disregarded. Hence, this paper seeks to answer the following research question: how is the normative nature of the 3Rs to be understood, and how can this understanding transparently guide their implementation? Based on a distinction between different types of norms, we show that the 3Rs, which have been called ‘principles’ since their origin, are indeed to be understood as principles in a substantive (norm-theoretical) sense. That is, they are norms that command the highest possible realization of their content. This understanding of the normative nature of the 3Rs has a significant effect on their implementation in practical contexts. As we will argue, it turns the orthodox idea of implementation strategies upside down. Building on this theoretical claim, we propose an ethics tool designed to help applicants, review committee members and authorities to apply the 3Rs transparently and, above all, in accordance with a reflected understanding of the relevant EU Directive’s intention (Directive 2010/63/EU) and of the work of Russell and Burch, the pioneers of this milestone in the promotion of animal welfare in research.

McGreal [née Pollitt], Shirley (1934–2021), primate conservationist

2025-06-09
Susan M. Cheyne | Oxford Dictionary of National Biography

Animal Models in Biomedical Research: Ethics and Alternatives

2025-06-06
Arun Kumar | Stallion Journal for Multidisciplinary Associated Research Studies
Animal models have long been central to biomedical research, providing critical insights into disease mechanisms, pharmacological responses, and therapeutic outcomes. However, the ethical concerns surrounding animal experimentation have grown substantially, … Animal models have long been central to biomedical research, providing critical insights into disease mechanisms, pharmacological responses, and therapeutic outcomes. However, the ethical concerns surrounding animal experimentation have grown substantially, leading to debates over the necessity, justification, and humane treatment of animals in laboratories. This paper explores the role of animal models in modern biomedical science, scrutinizes ethical concerns, and evaluates emerging alternatives such as organoids, computer simulations, and in vitro systems. The study emphasizes the importance of adhering to the 3Rs principle—Replacement, Reduction, and Refinement—and assesses current global trends aimed at replacing animal models with more humane and technologically advanced methods.

Simultaneous determination of mixture mineralization &amp; constituent specific primary degradation in a modified ready biodegradability test

2025-06-05
Heidi Birch , Karen Scharling Dyhr , Ann Flemming Nielsen +1 more | Environmental Toxicology and Chemistry
Abstract Ready biodegradability screening tests are the first step in regulatory persistence assessments of chemicals. However, current ready biodegradability tests are not applicable to UVCBs (substances of Unknown and Variable … Abstract Ready biodegradability screening tests are the first step in regulatory persistence assessments of chemicals. However, current ready biodegradability tests are not applicable to UVCBs (substances of Unknown and Variable composition, Complex reaction products, and Biological materials), since they cannot demonstrate the degradation of all UVCB constituents. The mineralization of the majority of constituents could mask the lack of degradation of persistent constituents. The aim of this study was to develop and apply a new whole UVCB ready biodegradability test, where oxygen depletion is applied to determine whole UVCB mineralization, and Solid Phase Microextraction coupled to GC-MS to determine constituent specific primary degradation. The method development and design optimization addressed oxygen-related and UVCB-related challenges. The designed test system consisted of 100 mL clear injection flasks with oxygen sensor spots mounted inside, closed with crimp caps and butyl/PTFE septa. The new test was applied to black pepper essential oil as a model UVCB. The composition of black pepper essential oil is well defined and contains a balance of monoterpenes and sesquiterpenes permitting validation of the approach across a broad spectrum of naturally occurring components. The essential oil test concentration was lowered to 10 mg/L to avoid substrate inhibition, and a headspace ratio of 25% ensured aerobic conditions. Mineralization of black pepper essential oil reached the pass level of 60% within less than 12 days, and primary degradation was rapid and consistent for all measured constituents. The mineralization of the UVCB and the primary degradation of its constituents provide two lines of evidence for black pepper essential oil being readily biodegradable. The developed approach is a modified rather than an enhanced OECD 301 method, since substance specific test challenges motivated and justify the test modifications. This approach seems now applicable for an improved biodegradation testing and persistence assessment of UVCBs.

Small animal review

2025-06-02
Alex Gough | Companion animal
Chronic kidney disease is very common in older cats, and poses challenges to the clinician because of difficulties of early diagnosis and limited effective treatment options. Chronic kidney disease is very common in older cats, and poses challenges to the clinician because of difficulties of early diagnosis and limited effective treatment options.

POS0480 ACR70 Response and Its Dependence on Deep Tissue Efficacy

2025-06-01
A.C. Bay-Jensen , M.A. Karsdal , Christian S. Thudium +1 more | Annals of the Rheumatic Diseases

Toxicology and safety pharmacology investigations on the nervous system: 2024 industry survey

2025-06-01
Simon Authier , Marcus S. Delatte , Alison Wakeford +7 more | Journal of Pharmacological and Toxicological Methods

There is no replacement for animal models in medical research

2025-06-01
Carole LaBonne | Developmental Biology

Thermal effects of the anovo® instrument arms hook electrode and curved scissors: an ex vivo study of safety and precision in monopolar electrosurgery

2025-05-29
Yuval Ramot , Sapir Hillel , Maor Mussan +2 more | BMC Surgery
Thermal damage during surgical procedures is a critical factor influencing patient safety and outcomes, particularly in minimally invasive laparoscopic surgeries. Advanced robotic-assisted surgical systems, such as the Anovo® Surgical System, … Thermal damage during surgical procedures is a critical factor influencing patient safety and outcomes, particularly in minimally invasive laparoscopic surgeries. Advanced robotic-assisted surgical systems, such as the Anovo® Surgical System, incorporate monopolar electrosurgical tools designed to optimize precision while minimizing collateral tissue damage. This study evaluates the thermal effects of the Anovo® Hook Electrode and Curved Scissors compared to conventional off-the-shelf (OTS) tools. An ex vivo study was conducted using 288 tissue samples from a swine model, including liver, kidney, and muscle tissues. Thermal effects during monopolar cutting and coagulation were evaluated at three power settings (low, medium, high) and durations (5, 10, 15 s). Histological analysis was performed on all samples to assess coagulation necrosis and thermal spread. Statistical equivalence testing was applied to compare the Anovo® devices with OTS tools. The Anovo® devices achieved precise and consistent thermal effects, meeting equivalence criteria in 97.57% of samples. Histological analysis confirmed well-defined coagulation zones with no unintended necrosis beyond the treated areas. Thermal spread increased proportionally with power settings and activation durations, but remained within clinically acceptable limits. The Anovo® devices demonstrated performance comparable to, and occasionally superior to, OTS tools. The Anovo® Hook Electrode and Curved Scissors provide safe and effective monopolar electrosurgical performance with precise thermal effects. These findings support their use in robotic-assisted laparoscopic surgeries and highlight their potential to enhance surgical precision and patient outcomes.

Application of a 3D Human Cornea‐Like Epithelium for Eye Irritation Assessment of Contact Lens Solutions

2025-05-27
Xian He , Fang Li , Xianhua Chen +7 more
ABSTRACT Currently, medical device eye irritation testing relies on the Draize eye test in rabbits, which presents significant challenges regarding animal welfare and variations across laboratories. This research explores the … ABSTRACT Currently, medical device eye irritation testing relies on the Draize eye test in rabbits, which presents significant challenges regarding animal welfare and variations across laboratories. This research explores the application of the commercially available three‐dimensional reconstructed human corneal epithelial tissue (Skinovo‐Ocular) in eye irritation evaluation. The model is developed by culturing immortalized human corneal epithelial cells at a liquid‐air interface, resembling the morphology and induction of biological indicators found in human corneal tissue. We evaluated the eye irritation effect of 30 minimum reference chemicals according to OECD Performance Standards. The results revealed a sensitivity of 100%, specificity of 66.7%, and accuracy of 83.3%, indicating predictive performance comparable to other reference methods. Furthermore, we conducted analyses including trans‐epithelial electrical resistance, cytokine secretion, and histology, thereby enhancing our understanding of the mechanisms underlying eye irritation assessment in this model. Additionally, we tested various contact lens solutions and compared the results with rabbit in vivo experiments, demonstrating the model's potential for analyzing the eye irritation of mixtures. This model shows promise as an alternative for eye irritation analysis of medical devices, further reducing the reliance on experimental animals.

Long-Term Experiences of Basic Education in Laboratory Animal Science

2025-05-25
Valeria Küller , Johannes Schenkel
Adequate education in laboratory animal science and subsequently the attendance of relevant courses are mandatory prerequisites for animal experimentation. The course content for different stakeholders is stipulated by European and … Adequate education in laboratory animal science and subsequently the attendance of relevant courses are mandatory prerequisites for animal experimentation. The course content for different stakeholders is stipulated by European and national regulations. If all of this content is covered, accreditation by competent bodies is possible and recommended. Here, we present our experiences with an EU-Function A/C/D accredited course (practical training with mice and rats) and an introductory seminar for undergraduate students, which have been running for more than ten years. All courses were organized in-house and were very relevant to the students and their needs but were also very labor intensive. The courses were systematically (and retrospectively) evaluated, showing a high degree of satisfaction and a great acquisition of knowledge, and the organizer was able to re-adjust the courses as needed over the years. Tests demonstrated the students’ progress and highlighted some parts of the lessons that were difficult to convey, such as those on legal regulations, housing and feeding, transport, GM animals, breeding, and the classification of severity. Dummies were proven to be very helpful at the beginning of the training but could not fully replace training with live animals. On-site lectures were favored over online sources, which were needed due to the pandemic. High standards in education are mandatory, and the accreditation process allows for the transferal of certificates to other institutions.

Workshop Report: Implementation of the 3Rs – Regulatory Animal Testing and Current Debates on Transparency in Animal Experimentation

2025-05-23
Nicole Lüthi , Katerina Styokova , Sara Faizee +1 more
This workshop report summarizes the key findings and discussions from the event “Implementation of the 3Rs in Swiss Law – Regulatory Animal Testing and Current Debates on Transparency in Animal … This workshop report summarizes the key findings and discussions from the event “Implementation of the 3Rs in Swiss Law – Regulatory Animal Testing and Current Debates on Transparency in Animal Experimentation”, held on March 20, 2025, in Zurich. The workshop brought together experts from academia, regulatory bodies, and NGOs to address two central topics in animal research: regulatory chemical safety assessments and transparency as a legal requirement.

Advancements in Peripheral Nerve Injury Research Using Lab Animals

2025-05-23
Natalia Pluta , Manuela Gaviria , Casey M. Sabbag +1 more
Peripheral nerve injuries (PNIs) commonly result from trauma, compression, or iatrogenic causes, leading to functional deficits. Despite the peripheral nervous system’s regenerative capacity, current treatments yield inconsistent outcomes. Basic science … Peripheral nerve injuries (PNIs) commonly result from trauma, compression, or iatrogenic causes, leading to functional deficits. Despite the peripheral nervous system’s regenerative capacity, current treatments yield inconsistent outcomes. Basic science and translational research supporting nerve repair remain underdeveloped, partly due to the absence of standardized protocols, limiting reproducibility. Animal models are essential for studying injury mechanisms, repair strategies, and therapeutic development. This review examines commonly used animal models in PNI research, from non-mammalian species to rodents and large mammals. We discuss the relevance of injury types, experimental variables (i.e., age, sex, nerve type), and study design elements (i.e., nerve gap size, injury induction methods). Assessing these models’ strengths and limitations, this review aims to guide researchers in selecting appropriate models that enhance preclinical relevance. It also addresses the need for standardized protocols and future directions for improving PNI research and patient outcomes. Various PNI treatments—including microsurgery, nerve grafts, scaffolds, stem cells, immunomodulators, nerve augmentation strategies, and polyethylene glycol-mediated fusion—have been developed using animal models. These models are essential for driving innovation and translating emerging therapies to improve outcomes across a broad range of peripheral nerve injuries.

Introduction: Animal welfare

2025-05-22
Enrique Font , Pau Carazo
The idea that some lives are less important or deserve less respect than others is at the root of many of the worst disasters our society has endured. Xenophobia, homophobia, … The idea that some lives are less important or deserve less respect than others is at the root of many of the worst disasters our society has endured. Xenophobia, homophobia, racism, sexism, ageism and other -isms make the headlines with alarming frequency. Not to mention the way we treat other species with which we share the planet. We slaughter billions of animals around the world every year for food, clothing, scientific research, and other purposes. Before they are slaughtered, many of these animals live in conditions that we would consider cruel if they were humans. Although insufficient and subject to constant revision, the available scientific evidence suggests that animals are sentient beings, capable of suffering and feeling pain, which for some should be reason enough to reconsider the way we treat them. Only a few decades ago, concern for animals and animal welfare was considered a frivolous matter without any sort of practical consequence. Today, the situation is very different. Animal welfare is becoming an increasingly important issue. It is the basis for debates, conferences and university courses, and even for changes in legislation with important implications at various levels. The new animal welfare law recently passed in Spain is a perfect example of the debate and controversy surrounding this issue.

Medicina veterinária legal na criação e experimentação de animais de laboratório

2025-05-22
Jackson Barros do Amaral , Vinícius José Moreira Nogueira , Laura Nataly Garcia‐Oliveros
Animal models in research are widely used in teaching and scientific research. However, there is no way to trust scientific data in activities that use animals whose health and welfare … Animal models in research are widely used in teaching and scientific research. However, there is no way to trust scientific data in activities that use animals whose health and welfare are affected, as they compromise the validity of scientific research data. This review is based on articles, research from the PubMed and Google Scholar platforms, and relevant books. It aims to identify and discuss the criteria and regulations for animal breeding and experimentation within the Legal Veterinary Medicine (MVL) context. In some cases, there is a need for legal and forensic investigations to assist with the legal issues involved in animal breeding and experimentation. In recent years, the MVL in Brazil has grown, reaching significant technical and scientific advancements which play an important role in guiding legal and forensic issues. Regulation and legislation for the use of animals in the laboratory, teaching, and research includes guidelines for animal health services, public health, environmental health, and biosafety. They are ruled by government actions, among which the following stand out: Law No. 11,794/2008, the Ministry of Agriculture, Livestock and Supply-MAPA, the Ministry of Science, Technology and Innovation-MCTI, together with the National Council for the Control of Animal Experimentation-CONCEA and the Federal Council of Veterinary Medicine-CFMV. Regulatory requirements challenge MVL and the law. Intense discussions still relate to the health and well-being of laboratory animals, since some facilities do not meet the obligations for the animals, the public, and environmental health control, in addition to the fact that there are risks affecting workers' health, indicating the need for increased attention to biosafety and public health. To comply with regulations, legislation, and humanitarian obligations regarding the use of animals in teaching and research, MVL and veterinary forensics emerge as important technical and scientific support in guiding legal matters related to the breeding and experimentation of laboratory animals.

Histology-Based Sub-chronic Toxicity Assessment of Target Heavy Metals from a Crude Oil Spill Using Testicular Histo-morphometry in Wistar Rats

2025-05-20
Allison Theodore Athanasius , O Richard
Toxicology studies the harmful effects of chemical, biological and physical agents in biological systems, which establishes the extent of damage in living organisms. Toxicity tests can measure lethal and/or sublethal … Toxicology studies the harmful effects of chemical, biological and physical agents in biological systems, which establishes the extent of damage in living organisms. Toxicity tests can measure lethal and/or sublethal effects. This study was aimed at evaluating, in histological terms, the sub-chronic toxicity of some target crude oil contaminants on the histo-morphometry of the testes of exposed Wistar rats. The following target chemicals (TCs; cadmium (Cd), chromium (Cr), copper (Cu), lead (Pb) and nickel (Ni)) were selected based on findings from the literature review of chemical analysis done on the crude oil spill site. In estimation of the rat exposure dose (RED) for the study, OEDC (2001) reference oral LD50 dose for Wistar Rat (in mg/Kg of body weight) of the TCs – Cd (63mg/kg); Cr (46 mg/kg), Cu (481 mg/kg); Nickel (300 mg/kg) and Pb (600 mg/kg), was used as a guideline standard for the upper limits of dose administration. Thirty (30) inbred male Wistar rats of average weight 150-200g (5 for control and 25 for experimental – 5 for each of the five TC- treated groups) were obtained from the animal house of the Department of Anatomy, Faculty of Basic Medical Sciences, University of Benin for this study. Rats were later sacrificed, and the target organ (testis) excised and used for qualitative histological evaluation. Gross anatomical assessment showed that there was no significant difference (P&gt; 0.05) when correlating weight gain between the treated and control groups. This implies that the RED does not have a significant effect on the weight of Wistar Rats, which is consistent with other studies in which Wistar Rats were exposed to heavy metals. Histological evaluation showed the following major lesions: glomerular congestion, degeneration and necrosis; tubular degeneration and necrosis; Interstitial inflammation, haemorrhage and necrosis. This study gives credence to the fact that histology-based evidence is a veritable tool for assessing sublethal levels of environmental stressors in the certification of toxicity.

External Validation of STopTox – Novel Alternative Method (NAM) for Acute Systemic and Topical Toxicity

2025-05-20
Ricardo Scheufen Tieghi , Cleber C. Melo‐Filho , Holli‐Joi Martin +7 more

How Toxic Is It to Bacteria?

2025-05-19
Michael Duchêne

Is the FDA’s plan to phase out animal toxicity testing realistic?

2025-05-15
Asher Mullard

Innovative cage-based technique for mouse urine collection

2025-05-15
J. S. Huang , Yan Wang , Yan Gao +5 more
Accurate and humane collection of mouse urine samples is crucial for research studies and health monitoring of laboratory mouse colonies. Conventional methods may stress animals and compromise sample quality. To … Accurate and humane collection of mouse urine samples is crucial for research studies and health monitoring of laboratory mouse colonies. Conventional methods may stress animals and compromise sample quality. To address these challenges, we developed a natural and animal-friendly approach using a specially designed urine collection device. This innovative technique involved individual transparent compartments with 96-well collection plates, allowing C57BL/6NTac mice to urinate freely for up to 2 h. Our study found that the optimal collection period was from 7 AM to 9 AM, during which the mice produced urine quantities ranging from 80 μl to 810 μl, with a substantial majority (85%) producing over 150 μl. The use of 96-well plates minimized stress, sample evaporation and contamination from fecal material. This cage-based non-invasive technique provides a user-friendly solution for obtaining accurate and high-quality mouse urine samples, benefiting animal welfare and facilitating rodent health surveillance and research studies.

Preclinical Safety Assessment: General and Genetic Toxicology

2025-05-15
Bruce E. LeRoy , Eric A.G. Blomme

Defined approaches to predict GHS and EPA classifications for ocular irritation potential of agrochemical formulations

2025-05-15
Amber B. Daniel , Anna J. van der Zalm , Hans Raabe +5 more
Regulations require that agrochemicals be labeled to indicate potential harmful effects caused by exposure. The in vivo Draize rabbit eye test has historically been the standard method used to assess … Regulations require that agrochemicals be labeled to indicate potential harmful effects caused by exposure. The in vivo Draize rabbit eye test has historically been the standard method used to assess the eye irritation or corrosion potential of chemical substances. However, as scientific confidence has been established for certain in chemico, in vitro, and ex vivo methods developed for this purpose, regulators are increasingly accepting data from such methods in lieu of the in vivo test. Defined approaches (DAs) may also be used to derive hazard and potency predictions by applying fixed data interpretation procedures to results from multiple methods, thereby leveraging strengths of different methods. Currently, the DAs accepted by regulators to predict eye irritation or corrosion potential do not specifically list agrochemical formulations within their applicability domains. To address this gap, we conducted testing to confirm the applicability of in vitro methods to agrochemical formulations and to develop DAs to predict eye irritation hazard labeling according to the Globally Harmonized System of Classification and Labeling (GHS) and the U.S. Environmental Protection Agency (EPA) classification system. Twenty-nine formulations were tested in up to four methods: bovine corneal opacity and permeability (BCOP; OECD TG 437) including histopathology, EpiOcular Eye Irritation Test (EO; OECD TG 492), SkinEthic time-to-toxicity for liquids (TTL; OECD TG 492B), and EyeIRR-IS. We propose four DAs comprising BCOP with histopathology alone, and combined with EO, TTL, or EyeIRR-IS. Instead of evaluating direct concordance of the four individual DAs with historical in vivo rabbit eye test data, for each formulation, we assessed orthogonal concordance of GHS and EPA classifications predicted across all five approaches. Predictions were considered orthogonally concordant when they aligned with the prediction of at least two other approaches (i.e. a majority, or at least 3 of the 5 approaches, achieved the same prediction), referred to as the 'majority prediction.' We also evaluated hazard labeling and PPE labeling associated with the GHS and EPA predictions, respectively. Relative to the hazard and PPE labeling associated with the majority predictions, each of the four DAs were as, or more, protective of human health than the rabbit test; hence, we conclude that these DAs can be used to predict the GHS and EPA classifications of agrochemical formulations.

Bayesian Refinement of a Physiologically Based Pharmacokinetic Model for Ethylbenzene Pharmacokinetics in Mice, Rats, and Humans

2025-05-15
Yu-Sheng Lin , Nan‐Hung Hsieh , Paul M. Schlosser +2 more
Abstract Although several physiologically based pharmacokinetic (PBPK) models exist for ethylbenzene (EB), a systematic evaluation of variability and uncertainty across species is still missing. This study aims to develop and … Abstract Although several physiologically based pharmacokinetic (PBPK) models exist for ethylbenzene (EB), a systematic evaluation of variability and uncertainty across species is still missing. This study aims to develop and validate a universal population-based, Bayesian PBPK model to study EB inhalation kinetics for mice, rats, and humans using a Markov Chain Monte Carlo (MCMC) approach to enhance model parameterization and its predictions. A comprehensive database was used for calibration and evaluation. This refined model demonstrates a superior or comparable fit to the data when contrasted with earlier published PBPK models for EB. Except for mouse fat and lung tissues, the concentrations of EB in tissues and its metabolites were generally within residual errors of 3-fold across species. Specifically, urinary concentrations of mandelic acid (MA), the primary downstream metabolite of EB, are generally well predicted in both rats and humans. Our approach offers a better characterization of pharmacokinetic variability and uncertainty than previous EB models, with strong agreement between predictions and experimental data. This supports efforts to adopt PBPK modeling for data extrapolation from animal studies to inform human health assessments, thereby greatly promoting public health. The confidence in applying the current refined PBPK model could be increased by confirming the predictions made by our analysis with additional targeted data collection.

2024 International Academy of Toxicologic Pathology (IATP) Satellite Symposium: New Approach Methodologies (NAMs) for Neurotoxicity Assessment and Regulatory Perspectives

2025-05-15
Helena T. Högberg , Ellen Fritsche , Sibylle Gröters +4 more
The International Academy of Toxicologic Pathology (IATP) Satellite Symposium on “New Approach Methodologies (NAMs) for Neurotoxicity Assessment and Regulatory Perspectives,” organized in Spain, addressed the growing need for improved assessment … The International Academy of Toxicologic Pathology (IATP) Satellite Symposium on “New Approach Methodologies (NAMs) for Neurotoxicity Assessment and Regulatory Perspectives,” organized in Spain, addressed the growing need for improved assessment of neurotoxicity. Traditional neurotoxicity assessment using in vivo animal studies are impractical for testing the substantial number of environmental chemicals that currently lack data and in the early detection of neuro-related adverse reactions in drug discovery. The NAMs, including human in vitro assays and small model organisms, have been developed for faster and cost-effective assessment of neurotoxic potential. While NAMs offer improved practicality, utility, and valuable mechanistic insights, their integration into regulatory decision-making requires robust scientific validation and technical characterization. Confidence in and regulatory application of NAMs data can be supported by mapping cellular outcomes to neuropathological findings in mammals, including humans, through the Adverse Outcome Pathway (AOP) framework, and the Integrated Approach to Testing and Assessment (IATA). Case studies presented demonstrated the application of NAMs in chemical and drug safety evaluations, focusing on developmental neurotoxicity (DNT), Parkinson’s disease, and drug-induced seizures. In conjunction with in vivo toxicology studies, NAMs represent a significant step toward advancing chemical and drug toxicity assessment via hazard identification and drug screening safety assessments.

Can Applied Ethics Lead to Justice for Animals?

2025-05-14
Alice Crary , Lori Gruen
In the summer of 2023, approximately 2,000 young, dead penguins washed up on the beaches across Uruguay. The birds were thin, their stomachs empty, and scientists suggest that this mass … In the summer of 2023, approximately 2,000 young, dead penguins washed up on the beaches across Uruguay. The birds were thin, their stomachs empty, and scientists suggest that this mass death was due to starvation. Without fat, the penguins can’t keep warm in the colder waters that they now have to navigate to find food. Food shortages due to overfishing in South America may have contributed to their demise. This die-off was unprecedented for the species, although the magellanic penguin population has been consistently dropping, and the species is now considered near threatened. Impacts of climate change, which contributed to these penguins’ precarity, were also likely the cause of the mass deaths of penguins in New Zealand in 2022, when hundreds of little blue penguins washed up dead. They probably died because warming oceans forced them to venture into deeper and colder waters in search of food, causing them to dive to distances that are not sustainable. These birds were also found to be thinner than they should have been. An even more drastic penguin die-off occurred in Antarctica in 2022—over 10,000 emperor penguin chicks perished when the sea-ice they were growing up on melted before they had the fat and waterproofed feathers needed to survive in the cold waters. Most of the birds drowned or froze to death. These sorts of large-scale group deaths have led scientists to suggest that the emperor penguins will be extinct by the end of the century.

Ethical considerations and challenges associated with euthanasia in laboratory animal research

2025-05-13
Raheleh Rafaiee , Hamid Kalalian Moghaddam , Fahimeh Mohseni
The Article Abstract is not available. The Article Abstract is not available.

Human Activities and Their Effects on Animal Populations

2025-05-12
Masroor Elahi Babar , Muhammad Ashraf

OCR: College mishandled request for service animal

2025-05-12
Case name: Letter re: Pikes Peak State College , No. 08‐24‐2149 (OCR 08/02/24). Case name: Letter re: Pikes Peak State College , No. 08‐24‐2149 (OCR 08/02/24).

5. Animal Ethics and Animal Experimentation

2025-05-12
COMPOST Collective
In this chapter 5, we introduce animal ethics and different views on the ethical permissibility of animal experimentation. The chapter highlights two aspects of discussions on animal experimentation ethics can, … In this chapter 5, we introduce animal ethics and different views on the ethical permissibility of animal experimentation. The chapter highlights two aspects of discussions on animal experimentation ethics can, namely, the moral status of other-than-human animals and the moral theories, consequentialism and deontology, on which the argumentation is built. Along these dimensions, we provide students and researchers with a brief overview of some arguments in favor or against animal experimentation. Finally, we also lay out the hybrid approach to animal experimentation ethics, which underpins current evaluation policies and EU regulation on the ethical acceptability of animal studies.