Refinement Database

Database on Refinement of Housing, Husbandry, Care, and Use of Animals in Research

This database, created in 2000, is updated every four months with newly published scientific articles, books, and other publications related to improving or safeguarding the welfare of animals used in research.

Tips for using the database:

  • This landing page displays all of the publications in the database.
  • Use the drop-down menus to filter these publications by Animal Type, Setting, and/or Topic.
  • Clicking on a parent category (e.g., Rodent) will include publications relating to all the items in that category (e.g., Chinchilla, Gerbil, Guinea Pig, etc.).
  • You may also add a keyword to further narrow your search.
  • Please note that at this time, only publications dated 2010 or later (with some exceptions) can be filtered by Animal Type and Topic, and only publications dated 2020 or later (with some exceptions) can be filtered by Setting. Most publications older than 2010 can only be searched by keyword. 
Fitzwater, A., Zhang, L. 2024. A cost-effective restraint method for safer subcutaneous scruff injections and reducing stress in mice and handlers. Laboratory Animal Science Professional 12(1) (January/February), 52-53.

Subcutaneous injection is a vital technique in mouse-based biomedical research. Compared to other injections, the subcutaneous method poses fewer technical challenges and reduces acute toxicity risks due to slower absorption. Several suitable subcutaneous injection sites...

Valros, A., Norring, M., Ahlqvist, K. et al. 2024. Effects of repeated intramuscular injections on sow behaviour reactions and stress-related saliva biomarkers – A pilot study. Applied Animal Behaviour Science 271, 106173.

Medicating large production animals, such as sows, individually can be challenging, especially when repeated treatments are needed. Intramuscular (i.m.) injections have been shown to be aversive, and an increased reaction could be expected over consecutive...

Robinson, L. M., Weiss, A. (Eds.) 2023. Nonhuman Primate Welfare: From History, Science, and Ethics to Practice. Springer, Cham, Switzerland. 671 p.

This volume reviews the broad topic of welfare in nonhuman primates under human care. Chapters detail the history of primates in captivity, ethical and legal issues surrounding the use of nonhuman primates as entertainment or...

Bellini, L., Schrank, M., Veladiano, I. A. et al. 2023. Retrospective comparison of the effects of laryngeal mask and endotracheal tube on some cardio-respiratory variables in pet rabbits undergoing anaesthesia for elective gonadectomy. Acta Veterinaria Scandinavica 65(1), 10.

Endotracheal intubation in rabbits is challenging and supraglottic airway devices, such as laryngeal masks (LMA), represent an alternative as they are easy to insert, and do not stimulate the larynx requiring therefore a lighter plane...

Lambertini, C., Grandis, A., De Silva, M. et al. 2023. The spritztube: A new device for extraglottic intubation of rabbits. Animals 13(1), 156.

The Spritztube (ST) is an extraglottic airway device developed for humans. The aim of the study was to design an ST for rabbits and to evaluate its feasibility. The study was divided into two phases...

Mauthe von Degerfeld, M., Serpieri, M., Bonaffini, G. et al. 2023. Intranasal atomization of ketamine, medetomidine and butorphanol in pet rabbits using a mucosal atomization device. Animals 13(13), 2076.

A non-invasive method of drug delivery, intranasal atomization, has shown positive results in human medicine and in some animal species. The objective of this study was to evaluate the effects of intranasal atomization, compared to...

Morton, D. B. 2023. A model framework for the estimation of animal “suffering”: Its use in predicting and retrospectively assessing the impact of experiments on animals. Animals 13(5), 800.

This paper presents and illustrates, with a working example, a hypothesis for the assessment of ongoing severity before and during an experiment that will enable humane endpoints and intervention points to be applied accurately and...

Swan, J., Boyer, S., Westlund, K. et al. 2023. Decreased levels of discomfort in repeatedly handled mice during experimental procedures, assessed by facial expressions. Frontiers in Behavioral Neuroscience 17, 1109886.

Mice are the most commonly used laboratory animal, yet there are limited studies which investigate the effects of repeated handling on their welfare and scientific outcomes. Furthermore, simple methods to evaluate distress in mice are...

Xu, J. J., Lucero, M. Y., Herndon, N. L. et al. 2023. Comparison of a minimally invasive transthoracic approach and a surgical method for intrapleural injection of tumor cells in mice. Comparative Medicine 73(2), 120–126.

Intrapleural injections can be used in mice to deliver therapeutic and diagnostic agents and to model human disease processes (for example, pleural fluid accumulation, malignant pleural disease, and lung cancers). In the context of establishing...

Klabukov, I., Shestakova, V., Krasilnikova, O. et al. 2023. Refinement of animal experiments: Replacing traumatic methods of laboratory animal marking with non-invasive alternatives. Animals 13(22), 3452.

Reliable methods for identifying rodents play an important role in ensuring the success of preclinical studies. However, animal identification remains a trivial laboratory routine that is not often discussed, despite the fact that more than...

Mandour, A. S., Farag, A., Helal, M. A. Y. et al. 2023. Non-invasive assessment of the intraventricular pressure using novel color M-mode echocardiography in animal studies: Current status and future perspectives in veterinary medicine. Animals 13(15), 2452.

The assessment of diastolic function has received great interest in order to comprehend its crucial role in the pathophysiology of heart failure and for the early identification of cardiac events. Silent changes in the intraventricular...

Rogers, L. J. 2023. Knowledge of lateralized brain function can contribute to animal welfare. Frontiers in Veterinary Science 10.

The specialized functions of each hemisphere of the vertebrate brain are summarized together with the current evidence of lateralized behavior in farm and companion animals, as shown by the eye or ear used to attend...

Ferguson, L. T., Rashied, A. A., Liang, Z. et al. 2023. A novel scoring system for humane endpoints in mice with cecal ligation and puncture-induced sepsis. Comparative Medicine 73(6), 446–460.

Animal-based research is essential to the study of sepsis pathophysiology, diagnostics, and therapeutics. However, animal models of sepsis are often associated with high mortality because of the difficulty in predicting imminent death based on premortem...

Chen, D. D., Molk, D. M., Palley, L. S. et al. 2023. Pinna edge biopsy of 7 and 21 day old C57BL/6 mice as a method for identification and genotyping. JAALAS 62(5), 438–448.

Identifying and genotyping mice prior to weaning can be useful for mouse colony management. Mice of an undesired genotype can be identified prior to weaning and removed from further study, resulting in a reduction of...

Williams, W. O., Baneux, P. 2022. Humane Intervention Points: Refining endpoint terminology to incorporate non-euthanasia intervention options to improve animal welfare and preserve experimental outcomes. Laboratory Animals 56(5), 482-489.

Consideration of The Three R’s (Replacement, Reduction, and Refinement) is essential when setting Humane Endpoints; however, a common interpretation assumes that Humane Endpoints are timepoints to perform euthanasia. This interpretation is not always consistent with...

Nuber, M., Gonzalez-Uarquin, F., Neufurth, M. et al. 2022. Development of a 3D simulator for training the mouse in utero electroporation. PLOS ONE 17(12), e0279004.

In utero electroporation (IUE) requires high-level training in microinjection through the mouse uterine wall into the lateral ventricle of the mouse brain. Training for IUE is currently being performed in live mice as no artificial...

Serrano, C., Antonio, J. 2022. Ultrasound guided surgery as a refinement tool in oncology research. Animals 12(23), 3445.

Refinement is one of the ethical pillars of the use of animals in research. Ultrasonography is currently used in human medicine as a surgical tool for guided biopsies and this idea can be applied to...

Brough, D. W., Murkin, J. T., Amos, H. E. et al. 2022. Comparing variability in measurement of subcutaneous tumors in mice using 3D thermal imaging and calipers. Comparative Medicine 72(6), 364–375.

Repeatable tumor measurements are key to accurately assessing tumor growth and treatment efficacy. A preliminary study that we conducted showed that a novel 3D and thermal imaging system (3D-TI) for measuring subcutaneous tumors in rodents...

Burn, C. C., Mazlan, N. H. B., Chancellor, N. et al. 2021. The pen is milder than the blade: Identification marking mice using ink on the tail appears more humane than ear-punching even with local anaesthetic. Animals 11(6), 1664.

Identification marking mice commonly involves ear-punching with or without anaesthetic, or tail-marking with ink. To identify which is most humane, we marked weanling male BALB/c mice using ear-punching (EP), ear-punching with anaesthetic EMLATM cream (EP+A)...

Nunamaker, E. A., Davis, S., O’Malley, C. I. et al. 2021. Developing recommendations for cumulative endpoints and lifetime use for research animals. Animals 11(7), 2031.

Research animals are important for scientific advancement, and therefore, their long-term welfare needs to be monitored to not only minimize suffering, but to provide positive affective states and experiences. Currently, there is limited guidance in...

Koch, A. L., Rusnak, M., Peachee, K. et al. 2021. Comparison of the effects of osmotic pump implantation with subcutaneous injection for administration of drugs after total body irradiation in mice. Laboratory Animals 55(2), 142-149.

The increasing potential for radiation exposure from nuclear accidents or terrorist activities has intensified the need to develop pharmacologic countermeasures against injury from total body irradiation (TBI). Many initial experiments to develop and test these...

Prior, H., Blunt, H., Crossman, L. et al. 2021. Refining procedures within regulatory toxicology studies: Improving animal welfare and data. Animals 11(11), 3057.

During the development of potential new medicines or agrochemicals, an assessment of the safety profile to humans and environmental species is conducted using a range of different in silico and in vitro techniques in conjunction...

Dalmau, A., Sánchez-Matamoros, A., Molina, J. M. et al. 2021. Intramuscular vs. intradermic needle-free vaccination in piglets: Relevance for animal welfare based on an aversion learning test and vocalizations. Frontiers in Veterinary Science 8, 715260.

The aim of the present study was to compare intramuscular injection with a needle and intradermic needle-free vaccinations against porcine reproductive and respiratory syndrome (PRRS) in piglets at 28 days old by studying behavioral and...

Fusco, A., Douglas, H., Barba, A. et al. 2021. V-Gel® guided endotracheal intubation in rabbits. Frontiers in Veterinary Science 8, 684624.

Background: General anesthesia in rabbits is associated with higher morbidity and mortality relative to other mammalian species commonly anesthetized. Unique challenges related to endotracheal intubation (ETI) in rabbits contribute to this risk. Objective: To improve...

Winn, C. B., Hwang, S. K., Morin, J. et al. 2021. Automated monitoring of respiratory rate as a novel humane endpoint: A refinement in mouse metastatic lung cancer models. PLOS ONE 16(9), e0257694.

In oncology research, while xenograft tumor models are easily visualized and humane endpoints can be clearly defined, metastatic tumor models are often based on more subjective clinical observations as endpoints. This study aimed at identifying...