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. 
National Academies of Sciences, Engineering, and Medicine. 2019. Care, Use, and Welfare of Marmosets as Animal Models for Gene Editing-Based Biomedical Research: Proceedings of a Workshop. The National Academies Press: Washington, DC, 122 pp.

The marmoset, a type of small monkey native to South America, is a research model of increasing importance for biomedical research in the United States and globally. Marmosets offer a range of advantages as animal...

Nosaka, N., Crother, T. R., Chen, S. et al. 2019. Optimal tube length of orotracheal intubation for mice. Laboratory Animals 53(1), 79–83.

Endotracheal tube (ETT) management is an essential technique in handling mice with mechanical ventilators. Malposition into bronchi causes not only lethal complications for them but also less efficient mechanical ventilation. However, in general, it is...

Bauer, C., Schillinger, U., Brandl, J. et al. 2019. Comparison of pre-emptive butorphanol or metamizole with ketamine +medetomidine and s-ketamine + medetomidine anaesthesia in improving intraoperative analgesia in mice. Laboratory Animals 53(5), 459–469.

In accordance with the ‘refinement’ component of the 3Rs, the primary aim of this study was to investigate and compare ketamine + medetomidine (KM) and s-ketamine + medetomidine (SKM) anaesthetic protocols in C57BL/6J mice (both sexes). We sought to...

Gjendal, K., Lund Ottesen, J., Olsson, I. A. S. et al. 2019. Burrowing and nest building activity in mice after exposure to grid floor, isoflurane or ip injections. Physiology & Behavior 206, 59-66.

Burrowing and nest building are examples of highly motivated innate behaviours in rodents. Assessments based on these behaviours can be used as non-invasive indicators of pain, distress and suffering. In this study, we investigated the...

Mechelinck, M., Kupp, C., Krüger, J. C. et al. 2019. Oxygen inhalation improves postoperative survival in ketamine-xylazine anaesthetised rats: An observational study. PLOS ONE 14(12), e0226430.

A simple but reliable and safe anaesthetic procedure is required for surgical interventions in small rodents. Combined ketamine and xylazine injections are often used in rats for less invasive surgery, possibly with spontaneous breathing and...

Shelton, K. A., Nehete, B. P., Chitta, S. et al. 2019. Effects of transportation and relocation on immunologic measures in cynomolgus macaques (Macaca fascicularis). JAALAS 58(6), 774–782.

NHP are a small, but critical, portion of the animals studied in research laboratories. Many NHP are imported or raised at one facility and subsequently moved to another facility for research purposes. To improve our...

Peric, T., Comin, A., Corazzin, M., et al. 2018. Hair cortisol concentrations in New Zealand white rabbits subjected to surgery. Animal Welfare 27(1), 13-20.

The aim of this study was to assess hair cortisol concentrations in New Zealand white rabbits (Oryctolagus cuniculus) that were subjected to relocation and surgery to evaluate HPA-axis activity; in addition, we used this marker...

ter Horst, E. N., Krijnen, P. A. J., Flecknell, P. et al. 2018. Sufentanil–medetomidine anaesthesia compared with fentanyl/fluanisone–midazolam is associated with fewer ventricular arrhythmias and death during experimental myocardial infarction in rats and limits infarct size following reperfusion. Laboratory Animals 52(3), 271-279.

To improve infarct healing following myocardial infarction in humans, therapeutic interventions can be applied during the inflammatory response. Animal models are widely used to study this process. However, induction of MI in rodents is associated...

Schuster, C. J., Pang, D. S. J. 2018. Forced-air pre-warming prevents peri-anaesthetic hypothermia and shortens recovery in adult rats. Laboratory Animals 52(2), 142-151.

General anaesthesia disrupts thermoregulation in mammals, which can cause hypothermia. Decreases in core body temperature of 1℃ cause significant postoperative complications in humans, and peri-anaesthetic hypothermia in mice increases data variability, which can potentially increase...

Khoo, S. Y.-S., Lay, B. P. P., Joya, J. et al. 2018. Local anaesthetic refinement of pentobarbital euthanasia reduces abdominal writhing without affecting immunohistochemical endpoints in rats. Laboratory Animals 52(2), 152-162.

Sodium pentobarbital is a commonly used agent for euthanizing laboratory rats, however its high pH can cause abdominal discomfort after intraperitoneal injection. Previous studies suggest that the addition of a local anaesthetic may alleviate this...

van Wijk, H., Crossman, L., Adjin-Tettey, G. et al. 2018. Advances in animal welfare and scientific outcomes of the bile duct cannulated rat model utilised in ADME studies. Animal Technology and Welfare 17(1), 64-67.

Since rats lack a gall bladder, they are an ideal model for investigating continuous biliary excretion and biotransformation. The design and implementation of a modified tail cuff and cannula system introduced at Covance permits the...

Gottlieb, D. H., Del Rosso, L, Sheikhi, F. et al. 2018. Personality, environmental stressors, and diarrhea in Rhesus macaques: An interactionist perspective. American Journal of Primatology 80(12), e22908.

Previous research has repeatedly shown both personality and psychological stress to predict gastrointestinal disorders and chronic diarrhea in humans. The goal of the present research was to evaluate the role of personality, as well as...

Hankenson, F. C., Marx, J. O., Gordon, C. J. et al. 2018. Effects of rodent thermoregulation on animal models in the research environment. Comparative Medicine 68(6), 425–438.

To best promote animal wellbeing and the efficacy of biomedical models, scientific, husbandry, and veterinary professionals must consider the mechanisms, influences, and outcomes of rodent thermoregulation in contemporary research environments. Over the last 2 decades...

Benedict, D., Megrath, B. 2018. Upgrades to nonhuman primate tethered infusion system. Laboratory Animal Science Professional 6(3) (September), 62-64.

Continuous tethered infusions in any animal model pose a unique set of problems. These problems are amplified when nonhuman primates are the model. A high tolerance to the tether system by an animal model is...

Coursodon, P., Cox, L., Largent-Milnes, T. M. et al. 2018. Enhanced environmental enrichment strategies for retired rhesus macaques. Laboratory Animal Science Professional 6(2) (June), 41-43.

One challenge in providing enrichment to NHP arises following completion of their assigned studies (retired) when there tends to be a sudden decrease in provision of daily human interaction and overall stimulation that results from...

Hohlbaum, K., Bert, B., Dietze, S. et al. 2018. Impact of repeated anesthesia with ketamine and xylazine on the well-being of C57BL/6JRj mice. PLOS ONE 13(9), e0203559.

Within the scope of the 3Rs of Russel and Burch, the number of laboratory animals can be reduced by repeated use of an animal. This strategy only becomes relevant, if the total amount of pain...

Hohlbaum, K., Bert, B., Dietze, S. et al. 2017. Severity classification of repeated isoflurane anesthesia in C57BL/6JRj mice—Assessing the degree of distress. PLOS ONE 12(6), e0179588.

According to the EU Directive 2010/63, the severity of a procedure has to be classified as mild, moderate or severe. General anesthesia is thought to be mild, but the Directive does not differentiate between single...

Nehete, P. N., Shelton, K. A., Nehete, B. P. et al. 2017. Effects of transportation, relocation, and acclimation on phenotypes and functional characteristics of peripheral blood lymphocytes in rhesus monkeys (Macaca mulatta). PLOS ONE 12(12), e0188694.

Nonhuman primates from domestic sources constitute a small, but critical, proportion of animals studied in research laboratories. Many of these nonhuman primates are raised at one facility and subsequently transported/relocated to another facility for research...

Burden, N., Kendrick, J., Knight, L. et al. 2017. Maximizing the success of bile duct cannulation studies in rats: Recommendations for best practice. Laboratory Animals 51(5), 457-464.

Bile duct cannulation (BDC) studies are usually carried out in the rat to support the absorption, distribution, metabolism and excretion profiling of novel agrochemicals and pharmaceuticals. The different aspects of these studies (e.g. surgical preparation...

Jensen, V. F. H., Mølck, A.-M., Martensson, M. et al. 2017. Assessment of implantable infusion pumps for continuous infusion of human insulin in rats: Potential for group housing. Laboratory Animals 51(3), 273-283.

Group housing is considered to be important for rats, which are highly sociable animals. Single housing may impact behaviour and levels of circulating stress hormones. Rats are typically used in the toxicological evaluation of insulin...

Reupke, V., Walliser, K., Perl, T. et al. 2017. Total intravenous anaesthesia using propofol and sufentanil allows controlled long-term ventilation in rabbits without neuromuscular blocking agents. Laboratory Animals 51(3), 284-291.

The aim of this study was to evaluate a total intravenous anaesthesia (TIVA) protocol using propofol and sufentanil without neuromuscular blocking agents (NBAs) for a non-recovery lung pathology study in rabbits including 10 h of...

Miranda, A., Pego, J. M., Correia-Pinto, J. 2017. Animal facility videoendoscopic intubation station: Tips and tricks from mice to rabbits. Laboratory Animals 51(2), 204-207.

Endotracheal intubation of laboratory animals is a common procedure shared by several research fields for different purposes, such as mechanical ventilation of anaesthetized animals, instillation of cytotoxic nanoparticles, infectious agents or tumour cells for induction...

Peric, T., Comin, A., Corazzin, M. et al. 2017. Relocation and hair cortisol concentrations in New Zealand White rabbits. Journal of Applied Animal Welfare Science 20(1), 1-8.

To investigate how long relocation modified hair cortisol concentrations in New Zealand white rabbits, 19 rabbits were subjected to a change in their breeding facility at the beginning of the trial and then were kept...

Zhang, E. Q., Knight, C. G., Pang, D. S. J. 2017. Heating pad performance and efficacy of 2 durations of warming after isoflurane anesthesia of Sprague–Dawley rats (Rattus norvegicus). JAALAS 56(6), 786-791.

Anesthetic agents depress thermoregulatory mechanisms, causing hypothermia within minutes of induction of general anesthesia. The consequences of hypothermia include delayed recovery and increased experimental variability. Even when normothermia is maintained during anesthesia, hypothermia may occur...

Skorupski, A. M., Zhang, J., Ferguson, D. et al. 2017. Quantification of induced hypothermia from aseptic scrub applications during rodent surgery preparation. JAALAS 56(5), 562-569.

Laboratory mice (Mus musculus) are prone to develop hypothermia during anesthesia for surgery, thus potentially impeding anesthetic recovery, wound healing, and future health. The core body temperatures of isoflurane-anesthetized mice are influenced by the choice...