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. 
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...

Ruberto, T., Clément, R. J. G., Spinello, C. et al. 2018. The tagging procedure of visible implant elastomers influences zebrafish individual and social behavior. Zebrafish 15(5), 433-444.

One commonly used method to preserve individual identity in the study of social behavior of zebrafish is through silicone-based visible implant elastomers (VIEs), which represent a safe and durable tagging procedure. While the effects of...

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...

Wever, K. E., Geessink, f. J., Brouwer, M. A. E. et al. 2017. A systematic review of discomfort due to toe or ear clipping in laboratory rodents. Laboratory Animals 51(6), 583-600.

Toe clipping and ear clipping (also ear notching or ear punching) are frequently used methods for individual identification of laboratory rodents. These procedures potentially cause severe discomfort, which can reduce animal welfare and distort experimental...

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...

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...

De Lombaert, M. C. M., Rick, E. L., Krugner-Higby, L. A. et al. 2017. Behavioral characteristics of adult zebrafish (Danio rerio) after MS222 anesthesia for fin excision. JAALAS 56(4), 377-381.

The health of laboratory animals is an ethical responsibility of researchers and a critical determinant of experimental outcome. Therefore, all Husbandry & Management procedures should be evaluated for their effects on mortality, behavior, and physiology...

Williams, M. D., Long, C. T., Durrant, J. R. et al. 2017. Oral transmucosal detomidine gel in New Zealand White rabbits (Oryctolagus cuniculus). JAALAS 56(4), 436-442.

Handling and restraining rabbits for routine procedures may be impossible without prior sedation, result in unnecessary stress or injury to the rabbit or handler, and increase experimental variability. Parenteral administration of sedatives can cause stress...

Chatigny, F., Kamunde, C., Creighton, C. M. et al. 2017. Uses and doses of local anesthetics in fish, amphibians, and reptiles. JAALAS 56(3), 244-253.

Local anesthetics are an integral part of routine pain management in mammals, yet their use is relatively limited in fish, amphibians and reptiles. These animals frequently undergo potentially painful surgical procedures and therefore could possibly...

Reiter, C. P., Christy, A. C., Olsen, C. H. et al. 2017. Effect of home cage bedding in the induction chamber on serum cortisol and corticosterone levels in response to isoflurane-induced anesthesia in C57BL/6J mice. JAALAS 56(2), 118-121.

Mice are routinely anesthetized with isoflurane in an induction chamber. The AVMA Guidelines for the Euthanasia of Animals states that distress should be minimized during euthanasia but does not address this point in regard to...

Janssen, C. F., Maiello, P., Wright Jr, M. J. et al. 2017. Comparison of atipamezole with yohimbine for antagonism of xylazine in mice anesthetized with ketamine and xylazine. JAALAS 56(2), 142-147.

The α2 adrenergic agonist xylazine produces a sedative effect and is typically combined with ketamine and used for anesthesia or chemical restraint of laboratory mice. Xylazine's sedative effect—and its undesirable side effects of bradycardia, hypotension...

Wilding, L. A., Hampel, J. A., Khoury, B. M. et al. 2017. Benefits of 21% oxygen compared with 100% oxygen for delivery of isoflurane to mice (Mus musculus) and rats (Rattus norvegicus). JAALAS 56(2), 148-154.

At research institutions, isoflurane delivered by precision vaporizer to a face mask is the standard for rodent surgery and for procedures with durations that exceed a few minutes. Pure oxygen is often used as the...

Lidster, K., Readman, G. D., Prescott, M. J. et al. 2017. International survey on the use and welfare of zebrafish Danio rerio in research. Journal of Fish Biology 90(5), 1891-1905.

A survey was conducted regarding zebrafish Danio rerio use for scientific research with a focus on: anaesthesia and euthanasia; housing and husbandry; breeding and production; refinement opportunities. A total of 98 survey responses were received...

Martins, T., Valentim, A. M., Pereira, L. N. et al. 2016. Anaesthesia and analgesia in laboratory adult zebrafish: a question of refinement. Laboratory Animals 50(6), 476-488.

Anaesthesia is used daily in fish experimental procedures; however, the use of an inadequate anaesthetic protocol can compromise not only the animal’s welfare but also the reliability of results. The use of zebrafish (Danio rerio)...

Norton, W. B., Scavizzi, F., Smith, C. D. et al. 2016. Refinements for embryo implantation surgery in the mouse: Comparison of injectable and inhalant anesthesias – tribromoethanol, ketamine and isoflurane – on pregnancy and pup survival. Laboratory Animals 50(5), 335-343.

An essential aspect of genetically-engineered mice (GEM) is the ability to produce live animals after the appropriate injection procedure. Animals are produced by implantation of manipulated embryos into pseudopregnant females for gestation, parturition, and growth...

O'Connell, C. P., Leurs, G. 2016. A minimally invasive technique to assess several life-history characteristics of the endangered great hammerhead shark Sphyrna mokarran. Journal of Fish Biology 88(3), 1257-1264.

A dorsal-fin photo-identification technique paired with a non-invasive parallel laser photogrammetry technique was used to non-invasively identify individual Sphyrna mokarran over time. Based on the data collected over a duration of 59 days, 16 different...

Miller, A., Kitson, G., Skalkoyannis, B. et al. 2015. The effect of isoflurane anaesthesia and buprenorphine on the mouse grimace scale and behaviour in CBA and DBA/2 mice. Applied Animal Behaviour Science 172, 58-62.

Prevention or alleviation of pain in laboratory mice is a fundamental requirement of in vivoresearch. The mouse grimace scale (MGS) has the potential to be an effective and rapid means of assessing pain and analgesic...

Miller, A. L., Leach, M. C. 2015. Using the mouse grimace scale to assess pain associated with routine ear notching and the effect of analgesia in laboratory mice. Laboratory Animals 49(2), 117-120.

Social housing is recommended where possible for laboratory mice. In order to achieve this, mice must be individually identifiable. Although, various methods are available, permanent identification is often required, such as ear notching. This method...

Bayne, K. A., Beaver, B. V., Mench, J. A. et al. 2015. Laboratory animal behavior. In: Laboratory Animal Medicine, 3rd edition. Fox, J. G., Anderson, L., Otto, G., et al. (eds). Elsevier, Inc., Amsterdam, NL. pp. 1617-1651.

The study of laboratory animal behavior has increased steadily over the last decade, with expanding emphasis on a variety of commonly used species. In the United States, this trend was initially focused on species for...

Cesarovic, N., Arras, M., Jirkof, P. 2014. Impact of inhalation anaesthesia, surgery and analgesic treatment on home cage behaviour in laboratory mice. Applied Animal Behaviour Science. 157, 137-145.

Anaesthesia and analgesia are used frequently in laboratory routine to ensure animal welfare and good scientific outcomes in experiments that may elicit pain or require immobilisation of the animal. However, there is concern regarding the...

Young, M., Lawson, G. W., Duarte-Vogel, S. et al. 2014. Minimizing symptoms and stress in seizure-prone mice by using acupressure during routine handling. American Association for Laboratory Animal Science [AALAS] Meeting Official Program, 555 (Abstract #P29).

Many laboratory mice used in research experience spontaneous seizures during cage changing and routine handling. The triggers are usually the abrupt sound and sudden motion of the cage. These seizures can range from mild to...

Nicholson, G., Sheldon, E. L., Hamilton, J. et al. 2014. Sand pools as a novel enrichment for rabbits. American Association for Laboratory Animal Science [AALAS] Meeting Official Program, 571. (Abstract #P83).

For anyone who has housed rabbits in an artificial plastic environment, what to provide as a nonfood enrichment can be an issue. Nonfood enrichment, or environmental enrichment, can be any toy, engaging sights or sounds...

Readman, G. D., Owen, S. F., Murrell, J. C. et al. 2013 Do fish perceive anaesthetics as aversive? PLOS ONE. 8(9), e73773.

This study addresses a fundamental question in fish welfare: are the anaesthetics used for fish aversive? Despite years of routine general use of many agents, within both scientific research and aquaculture, there is a paucity...

Swennes, A. G., Alworth, L. C., Harvey, S. B. et al. 2011. Human handling promotes compliant behavior in adult laboratory rabbits. JAALAS 50(2), 41-45.

Routine laboratory procedures can be stressful for laboratory animals. We wanted to determine whether human handling of adult rabbits could induce a degree of habituation, reducing stress and facilitating research-related manipulation. To this end, adult...

Coleman, K. 2011. Caring for nonhuman primates in biomedical research facilities: Scientific, moral and emotional considerations. American Journal of Primatology 73(3), 220-225.

Animal care for nonhuman primates (NHPs) in biomedical facilities has undergone major changes in the past few decades. Today, most primate facilities have dedicated and highly trained animal care technicians who go to great efforts...