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. 
Liu, P., Roberts, S., Shoemaker, J. T. et al. 2023. Validation of a 3D perfused cell culture platform as a tool for humanised preclinical drug testing in breast cancer using established cell lines and patient-derived tissues. PLOS ONE 18(3), e0283044.

3D cell culture models of cancer are currently being developed to recapitulate in vivo physiological conditions and to assess therapeutic responses. However, most models failed to incorporate the biochemical and biophysical stimuli from fluid flow...

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...

Peruga, M., Kawala, B., Sarul, M. et al. 2023. Are currently selected laboratory animals useful in the research of how female hormones influence orthodontic biomechanics? Animals 13(4), 629.

Animal testing was and remains the only method of introducing a certain treatment and medical procedure on humans. On the other hand, animals have their rights resulting from applicable legal acts, including Directive 2010/63/EU and...

Attokaren, M. K., Jeong, N., Blanpain, L. et al. 2023. BrainWAVE: A flexible method for noninvasive stimulation of brain rhythms across species. ENeuro 10(2) ENEURO.0257-22.2022.

Rhythmic neural activity, which coordinates brain regions and neurons to achieve multiple brain functions, is impaired in many diseases. Despite the therapeutic potential of driving brain rhythms, methods to noninvasively target deep brain regions are...

Martinez-Lopez, S., Angel-Gomis, E., Sanchez-Ardid, E. et al. 2023. The 3Rs in experimental liver disease. Animals 13(14), 2357.

Patients with cirrhosis present multiple physiological and immunological alterations that play a very important role in the development of clinically relevant secondary complications to the disease. Experimentation in animal models is essential to understand the...

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...

Chung, Y. H., Gulumian, M., Pleus, R. C. et al. 2022. Animal welfare considerations when conducting OECD test guideline inhalation and toxicokinetic studies for nanomaterials. Animals 12(23), 3305.

The OECD test guidelines for animal experiments play an important role in evaluating the chemical hazards. Animal tests performed using OECD guidelines, especially when the good laboratory practice (GLP) principle is applied, reduce the duplication...

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...

Weisskopf, M., Glaus, L., Trimmel, N. E. et al. 2022. Dos and don’ts in large animal models of aortic insufficiency. Frontiers in Veterinary Science 9, 949410.

Aortic insufficiency caused by paravalvular leakage (PVL) is one of the most feared complications following transcatheter aortic valve replacement (TAVI) in patients. Domestic pigs (Sus scrofa domestica) are a popular large animal model to study...

Casey, K. M., Gore, F., Vilches-Moure, J. G. et al. 2021. Management of morbidity and mortality in a New Zealand white rabbit model of steroidinduced osteonecrosis of the femoral head. Comparative Medicine 71(1), 86-98.

Steroid-induced osteonecrosis of the femoral head (SONFH) is a condition documented in humans and animals exposed to chronic steroid administration. The rabbit has become a preferred animal model for investigating the pathogenesis and treatment of...

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...

Vis, A., Lammers, J. C. A. M., de Vroege, R. et al. 2021. Strategies to improve survival from surgery for heart valve implantation in sheep. Comparative Medicine 71(3), 235-239.

Sheep are a commonly used and validated model for cardiovascular research and, more specifically, for heart valve research. Implanting a heart valve on the arrested heart in sheep is complex and is often complicated by...

Ellis, T., Katsiadaki, I. 2021. Clarification of early end-points for refinement of animal experiments, with specific reference to fish. Laboratory Animals 55(3), 244-253.

Appropriate end-points are integral to the refinement of laboratory animal experiments. Our recent experience has highlighted that ambiguity around end-points is hampering their adoption in experiments that cause severe suffering to fish. In toxicology, the...

Archibald, W., Glynn, C. 2021. Refining cages for social housing of non-human primates on ADME studies. Animal Technology and Welfare 20(2), 172-174.

The assessment and understanding of Absorption, Distribution, Metabolism and Elimination (ADME) for new pharmaceuticals is required in regulatory submissions. Typically, ADME studies are conducted using metabolism cages designed for the single housing of animals to...

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...

Kinaci, A., Vaessen, K., Redegeld, S. et al. 2021. Minimizing complications in a porcine survival craniotomy model. Laboratory Animals 55(5), 435-442.

A large craniotomy survival porcine model is useful for scientific research. The surgical approaches and complications of craniotomies in pigs have not been published before. This study describes how large craniotomies were performed in 46...

Lomb, J., Mauger, A., von Keyserlingk, M. A. G. et al. 2021. Effects of positive reinforcement training for heifers on responses to a subcutaneous injection. Journal of Dairy Science 104(5), 6146-6158.

Cattle are subjected to routine procedures that require restraint and close contact to humans, which are both potentially aversive to the animal. Positive reinforcement training techniques may affect how animals perceive and respond to these...

Larson, C. M., Wilcox, G. L., Fairbanks, C. A. 2019. Defining and managing pain in stroke and traumatic brain injury research. Comparative Medicine 69(6), 510–519.

Neurologic conditions such as stroke and traumatic brain injury are challenging conditions to study in humans. Animal models are necessary to uncover disease processes and develop novel therapies. When attempting to model these or other...

Hagemeister, K., Ernst, L., Kadaba Srinivasan, P. et al. 2020. Severity assessment in pigs after partial liver resection: Evaluation of a score sheet. Laboratory Animals 54(3), 251–260.

Severity assessment in biomedical research is required by the European authorities. Therefore, a variety of score sheets are available. The first score sheets were designed and introduced by Morton and Griffith (M&G) in 1985, to...

Hedenqvist, P., Trbakovic, A., Mellgren, T. et al. 2020. The effect of housing environment on bone healing in a critical radius defect in New Zealand white rabbits. PLOS ONE 15(5), e0233530.

In animal studies on bone healing, the effect of housing space and physical activity are seldom taken into account. Bone formation was evaluated in New Zealand White rabbits (mean ± SEM BW: 3.9 ± 0.11...

Reinhardt, V. (ed.) 2020. It’s Okay to Cry - Discussions by the Laboratory Animal Refinement & Enrichment Forum [LAREF], Volume V. Animal Welfare Institute, Washington, DC.

This is the 5th volume of selected discussions that took place on the electronic Laboratory Animal Refinement & Enrichment Forum between February 2016 and December 2019. The forum was created in October 2002; it allows...

Rydén, A., Manell, E., Biglarnia, A. et al. 2020. Nursing and training of pigs used in renal transplantation studies. Laboratory Animals 54(5), 469-478.

The pig is commonly used in renal transplantation studies since the porcine kidney resembles the human kidney. To meet the requirements of intense caretaking and examination without stress, a 2-week socialisation and training programme was...

Ober, R. A., Geist, G. E. 2020. Assessment of a noninvasive chronic glucose monitoring system in euglycemic and diabetic swine (Sus scrofa). JAALAS 59(4), 430-437.

Models of type-I diabetes are well-characterized and commonly used in the preclinical evaluation of drugs and medical devices. The diabetic minipig is an excellent example of a translational model. However, chronic glucose monitoring in this...

Raillard, M., Detotto, C., Grepper, S. et al. 2019. Anaesthetic and perioperative management of 14 male New Zealand white rabbits for calvarial bone surgery. Animals 9(11), 896.

Calvarial bone surgery on rabbits is frequently performed. This report aims to document a simple and practical anaesthetic and perioperative management for this procedure. Fourteen male New Zealand white rabbits were included in the study...