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., 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...

van Dijk, R. M., Koska, I., Bleich, A. et al. 2020. Design of composite measure schemes for comparative severity assessment in animal-based neuroscience research: A case study focussed on rat epilepsy models. PLOS ONE 15(5): e0230141.

Comparative severity assessment of animal models and experimental interventions is of utmost relevance for harm-benefit analysis during ethical evaluation, an animal welfare-based model prioritization as well as the validation of refinement measures. Unfortunately, there is...

Helgers, S., Talbot, S. R., Riedesel, A. K. et al. 2020. Body weight algorithm predicts humane endpoint in an intracranial rat glioma model. Scientific Reports 10, 9020.

Humane endpoint determination is fundamental in animal experimentation. Despite commonly accepted endpoint criteria for intracranial tumour models (20% body weight loss and deteriorated clinical score) some animals still die before being euthanized in current research...

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...

Zude, B. P., Jampachaisri, K., Pacharinsak, C. 2020. Use of flavored tablets of gabapentin and carprofen to attenuate postoperative hypersensitivity in an incisional pain model in rats (Rattus norvegicus). JAALAS 59(2), 163–169.

Providing postoperative analgesia to rats by oral administration, compared with injections, reduces stress from frequent handling and is technically easier for investigators. The purpose of this study was to investigate whether bacon-flavored tablets containing gabapentin...

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...

Thoré, E. S. J., Brendonck, L., Pinceel, T. 2020. Conspecific density and environmental complexity impact behaviour of turquoise killifish (Nothobranchius furzeri). Fish Biology 97(5), 1448–1461.

Fish models are essential for research in many biological and medical disciplines. With a typical lifespan of only 6 months, the turquoise killifish (Nothobranchius furzeri) was recently established as a time- and cost-efficient model to...

Zieglowski, L., Kümmecke, A., Ernst, L. et al. 2020. Severity assessment using three common behavioral or locomotor tests after laparotomy in rats: A pilot study. Laboratory Animals 54(6), 525-535.

The aim of this pilot study was to evaluate whether behavioral or locomotor tests (Open Field (OF), rotarod (RR), and CatWalk (CW)) can help assess the severity of laparotomy in rats. The new EU Directive...

Berke, M. S., Abelson, K. S. P. 2020. The adjuvant-induced rat model of monoarthritis: Welfare implications and possible refinement strategies. Scandinavian Journal of Laboratory Animal Science 46(1), 39-50.

This study investigated welfare, mechanical hyperalgesia and model specific parameters (mobility, stance, joint stiffness and ambulation impairment) during a three-week period in a rat model of monoarthritis. The objective was to identify possible targets for...

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...

Pedrazzani, A. S., Quintiliano, M. H., Bolfe, F. et al. 2020. Tilapia on-farm welfare assessment protocol for semi-intensive production systems. Frontiers in Veterinary Science 7, 606388.

The aim of this study was to develop and test a tilapia on-farm welfare assessment protocol, based on Brazilian semi-intensive production systems. The study included two mains steps: the elaboration of tilapia welfare protocol and...

Do, J. P., Defensor, E. B., Ichim, C. V. et al. 2020. Automated and continuous monitoring of animal welfare through digital alerting. Comparative Medicine 70(4), 313-327.

A primary goal in preclinical animal research is respectful and responsible care aimed toward minimizing stress and discomfort while enhancing collection of accurate and reproducible scientific data. Researchers use hands-on clinical observations and measurements as...

Stanger, K. J., Kells, N. J., Fisher, A. D. et al. 2019. Evaluation of euthanasia of sheep with intravenous saturated salt solutions to enable the collection of whole, intact brains. Animal Welfare 28(4), 397-406.

Captive bolts or firearms are unsuitable for euthanasia of livestock when an intact brain is required for diagnostics. Injectable barbiturates can be used, but this method carries risk of poisoning animals eating the carcase. Intravenous...

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...

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...

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...

Anders, N., Roth, B., Grimsbø, E. et al. 2019. Assessing the effectiveness of an electrical stunning and chilling protocol for the slaughter of Atlantic mackerel (Scomber scombrus). PLOS ONE 14(9), e0222122.

Inducing unconsciousness in fish using electrical stunning prior to slaughter may improve fish welfare and fillet quality if such practises can be disseminated into wild capture fisheries. The objectives of this study were to: 1)...

Harikrishnan, V. S., Krishnan, L. K., Abelson, K. S. P. 2019. A novel technique to develop thoracic spinal laminectomy and a methodology to assess the functionality and welfare of the contusion spinal cord injury (SCI) rat model. PLOS ONE 14(7), e0219001.

This study reports the advantage of a novel technique employing a motorised dental burr to assist laminectomy over the conventional manual technique at T10-T11 vertebra level in a rat model of spinal cord injury. Twenty-four...

Améndola, L., Ratuski, A., Weary, D. M. 2019. Variation in the onset of CO2-induced anxiety in female Sprague Dawley rats. Scientific Reports 9, 19007.

Carbon dioxide (CO2) is commonly used to kill laboratory rats. Rats find CO2 aversive and aversion varies between individuals, indicating that rats vary in CO2 sensitivity. Healthy humans experience feelings of anxiety at concentrations similar...

Santurtun, E., Broom, D. M., Phillips, C. J. C. 2018. A review of factors affecting the welfare of Atlantic salmon (Salmo salar). Animal Welfare 27(3), 193-204.

In the expanding salmon industry, many farmers use production methods that could result in poor welfare of the fish at various points of their lifecycle. We have reviewed methods used for producing salmon for food...

Kells, N. J., Beausoleil, N. J., Sutherland, M. A. et al. 2018. Electroencephalographic responses of anaesthetised rats to carbon dioxide inhalation. Animal Welfare 27(3), 215-223.

Exposure to high concentrations of CO2 is a common means of stunning and killing laboratory rodents. However, there is concern regarding the potential for animals to have aversive experiences, such as pain or breathlessness, prior...

Golledge, H., Carter, E. 2018. Welfare of fish farmed in the EU during transport and at slaughter. Animal Welfare 27(3), 287-288.

This Report, commissioned by the European Commission, summarises the current state of transport and slaughter practices in the aquaculture industry within eleven case-study countries in the European Economic Area (EAA). Comparisons are also made with...

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...

Grist, A., Lines, J., Knowles, T. et al. 2018. The use of a mechanical non-penetrating captive bolt device for the euthanasia of neonate lambs. Animals 8(4), 49.

A non-penetrating captive bolt device, powered by a 1-grain 0.22″ cartridge delivering a calculated kinetic energy of 47 Joules was tested as a euthanasia method on 200 neonate lambs (Ovis aries) of 4.464 kg (SD...