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. 
Améndola, L., Ratuski, A., Weary, D. M. 2021. Individual differences in rat sensitivity to CO2. PLOS ONE 16(1), e0245347.

Feelings of fear, anxiety, dyspnea and panic when inhaling carbon dioxide (CO2) are variable among humans, in part due to differences in CO2 sensitivity. Rat aversion to CO2 consistently varies between individuals; this variation in...

Brunt, M. W., Améndola, L., Weary, D. M. 2021. Attitudes of laboratory animal professionals and researchers towards carbon dioxide euthanasia for rodents and perceived barriers to change. Laboratory Animals 55(6), 531-539.

Evidence indicates that carbon dioxide (CO2) induces negative affective states (including anxiety, fear and distress) in laboratory rodents, but many countries still accept it for euthanasia. Alternative methods (e.g. inhalant anaesthetic) may represent a refinement...

Locklear, J., Whiteside, T. E. 2021. Optimal colloidal water gel type and novel placement for frequent travelers. Laboratory Animal Science Professional 9(6) (November/December), 38-40.

During transportation, animals must have a water source available to prevent dehydration. Some shipping facilities use potatoes whereas, others use colloidal water gels that provide a uniform water source. The problem occurs when colloidal water...

Botman, J., Hontoir, F., Gustin, P. et al. 2020. Postanaesthetic effects of ketamine–midazolam and ketamine–medetomidine on gastrointestinal transit time in rabbits anaesthetised with isoflurane. Veterinary Record 186(8), 249.

Gastrointestinal stasis is a common perianaesthetic complication in rabbits. The objective of this study was to assess the impact on gastrointestinal transit time of ketamine–midazolam (KMZ) versus ketamine–medetomidine (later antagonised by atipamezole) (KMT-A) in rabbits...

Alemán-Laporte, J., Bandini, L. A., Garcia-Gomes, M. S. et al. 2020. Combination of ketamine and xylazine with opioids and acepromazine in rats: Physiological changes and their analgesic effect analysed by ultrasonic vocalization. Laboratory Animals 54(2), 171–182.

In this study, the effect of four anaesthetic protocols that included the combination of xylazine (X) and ketamine (K) with acepromazine (A) and opioids (methadone (Me), morphine (Mo) or tramadol (T)) was evaluated in laboratory...

Składanowska-Baryza, J., Ludwiczak, A., Pruszyńska-Oszmałek, E. et al. 2020. Effect of two different stunning methods on the quality traits of rabbit meat. Animals 10(4), 700.

The aim of the study was to assess the effect of two different stunning methods on the level of blood stress indicators (cortisol, insulin, glucose) and rabbit meat quality. The experiment was conducted on crossbreds...

Frost, K., Shah, M., Leung , V. S. Y. et al. 2020. Aversion to desflurane and isoflurane in Sprague-Dawley rats (Rattus norvegicus). Animals 10(6), 950.

Carbon dioxide and isoflurane are widely used for killing rats, yet may not truly achieve “euthanasia”, because they elicit aversion. The inhalant anesthetic desflurane is faster acting than isoflurane, representing a potential refinement. Using an...

Ballantine, A., Rodgers, D., Watts, C. et al. 2020. The cotton rat – a new challenge. Animal Technology and Welfare 19(1), 92-95.

This poster describes how the Animal Technologists at Envigo adapted their current practices and procedures for a new species at their laboratory: the cotton rat. The paper describes cotton rat biology and behaviour; housing; environmental...

Améndola, L., Weary, D. M. 2020. Understanding rat emotional responses to CO2. Translational Psychiatry 10, 253.

The aim of this review is to summarize evidence regarding rat emotional experiences during carbon dioxide (CO2) exposure. The studies reviewed show that CO2 exposure is aversive to rats, and that rats respond to CO2...

Chu, D. 2020. Malawi cichlids: A colorful 4th R story. Laboratory Animal Science Professional 8(3) (May/June), 24-25.

This article describes the successful rehoming of 60 Malawi cichlids from a vivarium at Stanford University to San Diego Zoo and the California Academy of Sciences.

Hambrecht, S., Oerke, A.‐K., Heistermann, M. et al. 2020. Diurnal variation of salivary cortisol in captive African elephants (Loxodonta africana) under routine management conditions and in relation to a translocation event. Zoo Biology 39(3), 186–196.

The present study assessed the diurnal variation in salivary cortisol in captive African elephants during routine management (baseline) and in relation to a potential stressor (translocation) to evaluate to what extent acute stress may affect...

Turner, P. V., Hickman, D. L., van Luijk, J. et al. 2020. Welfare impact of carbon dioxide euthanasia on laboratory mice and rats: A systematic review. Frontiers in Veterinary Science 7, 411.

Background: There has been increased concern about the suitability of CO2 as a method for euthanasia of laboratory mice and rats, including the potential discomfort, pain or distress that animals may experience prior to loss...

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...

Shomer, N. H., Allen-Worthington, K. H., Hickman, D. L. et al. 2020. Review of rodent euthanasia methods. JAALAS 59(3), 242–253.

The optimal choice of euthanasia method for laboratory rodents depends on a number of factors, including the scientific goals of the study, the need to minimize animal pain and/or distress, applicable guidelines and laws, the...

Laferriere, C. A., Pang, D. S. 2020. Review of intraperitoneal injection of sodium pentobarbital as a method of euthanasia in laboratory rodents. JAALAS 59(3), 254–263.

Euthanasia is one of the most commonly performed procedures in biomedical research, involving tens of millions of animals in North America and Europe every year. The use of sodium pentobarbital, injected intraperitoneally, for killing rodents...

Kulkarni, S., Hickman, D. 2020. Isoflurane and carbon dioxide elicit similar behavioral responses in rats. Animals 10(8), 1431.

Euthanasia in rodents is an ongoing topic of debate due to concerns regarding the aversive nature of gases with anesthetic properties such as carbon dioxide (CO2) and isoflurane. The aim of this study was to...

West, S. E., Lee, J. C., Johns, T. N. et al. 2020. Intraperitoneal alfaxalone and alfaxalone–dexmedetomidine anesthesia in Sprague–Dawley rats (Rattus norvegicus). JAALAS 59(5), 531-538.

Due to their unpredictability and variable effects, injectable anesthetic regimens in laboratory rodent species warrant refinement. In our study we sought to evaluate alfaxalone, which has gained recent popularity in veterinary medicine, alone and in...

Ambar, N., Eshar, D., Shrader, T. C. et al. 2020. Anesthetic effects of intramuscular alfaxalone–ketamine in naked mole rats (Heterocephalus glaber). JAALAS 59(5), 539-545.

In this study, adult intact male and female (n = 10) naked mole rats (Heterocephalus glaber) were anesthetized by using a combination of ketamine (20 mg/kg IM), and alfaxalone (4.0 mg/kg IM). Induction and recovery...

Klune, C. B., Robbins, H. N. K., Leung, V. et al. 2020. Hypothermia during general anesthesia interferes with pain assessment in laboratory rats (Rattus norvegicus). JAALAS 59(6), 719-725.

Accurate pain assessment methods are necessary to ensure animal welfare and reliable data collection in animal research. The Rat Grimace Scale (RGS), a facial expression pain scale, allows effective identification of pain. However, the potential...

Axiak Flammer, S., Eskes, C., Kohler, I. et al. 2019. Alternatives to carbon dioxide—Taking responsibility for humanely ending the life of animals. Animals 9(8), 482.

Carbon dioxide (CO2) is commonly used to kill rodents. However, a large body of research has now established that CO2 is aversive to them. A multidisciplinary symposium organized by the Swiss Federal Food Safety and...

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...

Steiner, A. R., Axiak Flammer, S., Beausoleil, N. J. et al. 2019. Humanely ending the life of animals: Research priorities to identify alternatives to carbon dioxide. Animals 9(11), 911.

The use of carbon dioxide (CO2) for stunning and killing animals is considered to compromise welfare due to air hunger, anxiety, fear, and pain. Despite decades of research, no alternatives have so far been found...

Krall, C., Glass, S., Dancourt, G. et al. 2019. Behavioural anxiety predisposes rabbits to intra-operative apnoea and cardiorespiratory instability. Applied Animal Behaviour Science 221, 104875.

Rabbits are prone to complications from both anaesthesia and anxiety. Given that anxiety can often impact quality of anaesthesia, we developed a novel cage-side anxiety assessment, and sought to determine whether it correlated to pre-...

Jiron, J. M., Mendieta Calle, J. L., Castillo, E. J. et al. 2019. Comparison of isoflurane, ketamine-dexmedetomidine, and ketamine-xylazine for general anesthesia during oral procedures in rice rats (Oryzomys palustris). JAALAS 58(1), 40-49.

Rice rats (Oryzomys palustris) are an unconventional laboratory species that has been used to study photoperiodicity, periodontitis, and osteonecrosis of the jaw. Interventional procedures that require anesthesia, including oral procedures, are sometimes necessary in preclinical...

Sloman, K, A., Bouyoucos, I. A., Brooks, E. J. et al. 2019. Ethical considerations in fish research. Journal of Fish Biology 94(4), 556-577.

In this review, we focus primarily on the refinement of common methods used in fish research based on emerging knowledge with the aim of improving the welfare of fish used in scientific studies. We consider...