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. 
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...

Head, V., Eshar, D., Nau, M. R. 2017. Techniques for nonterminal blood sampling in black-tailed prairie dogs (Cynomys ludovicianus). JAALAS 56(2), 210-213.

Black-tailed prairie dogs (Cynomys ludovicianus) are used as an animal model for research on gallbladder stones and several infectious diseases. A comprehensive, instructive resource regarding the appropriate techniques for venipuncture and collection of nonterminal blood...

Boivin, G. P., Bottomley, M. A., Schiml, P. A. et al. 2017. Physiologic, behavioral, and histologic responses to various euthanasia methods in C57BL/6NTac male mice. JAALAS 56(1), 69-78.

Rodent euthanasia using exposure to increasing concentrations of CO2 has come under scrutiny due to concerns of potential pain during the euthanasia process. Alternatives to CO2, such as isoflurane and barbiturates, have been proposed as...

Hawkins, P., McNeilly, A., Watson, J. et al. 2017. Report of the 2016 RSPCA/UFAW Rodent and Rabbit Welfare Group meeting. Animal Technology and Welfare 16(2), 77-86.

The RSPCA/UFAW Rodent (and now Rabbit) Welfare Group held a one-day meeting on 1 November 2016 at the University of Edinburgh and was attended by 70 delegates. Presentation topics included refinements in blood sampling rodents...

Guedes, S. R., Valentim, A. M., Antunes, L. M. 2017. Mice aversion to sevoflurane, isoflurane and carbon dioxide using an approach-avoidance task. Applied Animal Behaviour Science 189, 91-97.

Euthanasia of laboratory animals is one of the main concerns for animal welfare, especially the use of carbon dioxide (CO2) which has been described to induce aversive-like behaviours. In order to refine mass euthanasia in...

Pinnell, R. C., Almajidy, R. K., Hofmann, U. G. 2016. Versatile 3-D printed headstage implant for group housing of rodents. Journal of Neuroscience Methods 257, 134-138.

An unfavourable yet necessary side-effect of stereotaxic surgery involves the social isolation of post-surgery rats, in order to protect their wound site or skull-mounted implant from damage. Social isolation can cause a myriad of behavioural...

Miller, A. L., Golledge, H. D. R., Leach, M. C. 2016. The influence of isoflurane anaesthesia on the rat grimace scale. PLOS ONE 11(11), e0166652.

Over 234,000 rats were used in regulated procedures in the UK in 2014, many of which may have resulted in some degree of pain. When using animals in research, there is an ethical and legal...

Schmitz, S., Tacke, S., Guth, B. et al. 2016. Comparison of physiological parameters and anaesthesia specific observations during isoflurane, ketamine-xylazine or medetomidine-midazolam-fentanyl anaesthesia in male guinea pigs. PLOS ONE 11(9), e0161258.

Guinea pigs (GPs) are difficult to anaesthetize successfully, the choices for anaesthesia are limited and physiological parameters are likely to be influenced substantially under anaesthesia. We implanted blood pressure radio-telemetry devices into 16 male GPs...

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...

Karrberg, L., Andersson, L., Kastenmayer, R. J. et al. 2016. Refinement of habituation procedures in diet-induced obese mice. Laboratory Animals 50(5), 397-399.

Orogastric gavage, while a common method for delivering experimental substances in mice, has been shown to induce stress. To minimize the associated stress with this procedure, sham gavage prior to the start of experiment is...

Valentim, A. M., Guedes, S. R., Pereira, A. M. et al. 2016. Euthanasia using gaseous agents in laboratory rodents. Laboratory Animals 50(4), 241-253.

Several questions have been raised in recent years about the euthanasia of laboratory rodents. Euthanasia using inhaled agents is considered to be a suitable aesthetic method for use with a large number of animals simultaneously...

Jang, Y., Park, Y. E., Yun, C.-W. et al. 2016. The vest-collar as a rodent collar to prevent licking and scratching during experiments. Laboratory Animals 50(4), 296-304.

Various types of restraint collars have been used for research animals, and the Elizabethan collar (E-collar) is the most commonly used. However, animals can be choked by the E-collar or they tend to remove it...

Powell, K., Ethun, K., Taylor, D. K. 2016. The effect of light level, CO2 flow rate, and anesthesia on the stress response of mice during CO2 euthanasia. Lab Animal 45(10), 386-395.

Euthanasia protocols are designed to mitigate the stress experienced by animals, and an environment that induces minimal stress helps achieve that goal. A protocol that is efficient and practical in a typical animal research facility...

Hawkins, P., Prescott, M., Carbone, L. et al. 2016. A good death? Report of the second Newcastle meeting on laboratory animal euthanasia. Animals 6(9), 50.

Millions of laboratory animals are killed each year worldwide. There is an ethical, and in many countries also a legal, imperative to ensure those deaths cause minimal suffering. However, there is a lack of consensus...

Hickman, D., Fitz, S., Bernabe, C. et al. 2016. Evaluation of low versus high volume per minute displacement CO2 methods of euthanasia in the induction and duration of panic-associated behavior and physiology. Animals 6(8), 45.

Current recommendations for the use of CO 2 as a euthanasia agent for rats require the use of gradual fill protocols (such as 10% to 30% volume displacement per minute) in order to render the...

Moheban, A. A., Chang, H. H., Havton, L. A. 2016. The suitability of propofol compared with urethane for anesthesia during urodynamic studies in rats. JAALAS 55(1), 89–94.

Urethane anesthesia preserves many reflex functions and is often the preferred anesthetic for urodynamic studies in rats. Because of the toxicity profile of urethane, its use as an anesthetic typically is limited to acute and...

Zatroch, K. K., Knight, C. G., Reime, J. N. et al. 2017. Refinement of intraperitoneal injection of sodium pentobarbital for euthanasia in laboratory rats (Rattus norvegicus). BMC Veterinary Research 13, 60.

Background: The Canadian Council on Animal Care and American Veterinary Medical Association classify intraperitoneal (IP) pentobarbital as an acceptable euthanasia method in rats. However, national guidelines do not exist for a recommended dose or volume...

McEntee, D., Borg, K., Markiewicz, V. 2016. Establishment of a home-cage in vivo method of New Zealand white rabbit urine collection. Laboratory Animal Science Professional 4(4) (December), 44-46.

The most common methods for rabbit urine collection are newborn stroking, cystocentesis, and transfer to a metabolism cage.2 None of these options allow for a significant, quality amount of urine to be collected in vivo...

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...

Wickremsinhe, E. R., Perkins, E. J. 2015. Using dried blood spot sampling to improve data quality and reduce animal use in mouse pharmacokinetic studies. JAALAS. 54(2), 139-144.

Traditional pharmacokinetic analysis in nonclinical studies is based on the concentration of a test compound in plasma and requires approximately 100 to 200 μL blood collected per time point. However, the total blood volume of...

Caron, A., Lelong, C., Pascual, M. H. et al. 2015. Miniaturized blood sampling techniques to benefit reduction in mice and refinement in nonhuman primates: Application to bioanalysis in toxicity studies with antibody-drug conjugates. JAALAS 54(2), 145-152.

Minimizing the number of animals in regulatory toxicity studies while achieving study objectives to support the development of future medicines contributes to good scientific and ethical practices. Recent advances in technology have enabled the development...

Moody, C. M., Makowska, I. J., Weary, D. M. 2015. Testing three measures of mouse insensibility following induction with isoflurane or carbon dioxide gas for a more humane euthanasia. Applied Animal Behaviour Science 163, 183-87.

Laboratory mice are commonly killed via exposure to gradually increasing concentrations of isoflurane and carbon dioxide (CO2) gas. Once rendered insensible using isoflurane or CO2, a high concentration of CO2 is used to decrease time...

Boulanger Bertolus, J., Nemeth, G., Makowska, I. J. et al. 2015. Rat aversion to sevoflurane and isoflurane. Applied Animal Behaviour Science 164, 73-80.

Virtually all rodents used in research are eventually euthanized. Best practice is to anaesthetize these animals before euthanasia using a halogenated anaesthetic such as isoflurane. Exposure to isoflurane is aversive, but less so than exposure...

Bloomsmith, M., Kim, N., Franklin, A. et al. 2015. Positive reinforcement methods to train chimpanzees to cooperate with urine collection. JAALAS 54, 66-69.

Positive reinforcement training can be used in many ways to enhance the welfare of captive primates. Training for biologic sample collection is one application of positive reinforcement training. In this study, 35 adult female chimpanzees...

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...