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. 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...

Gent, T. C., Detotto, C., Vyssotski, A. L. et al. 2018. Epileptiform activity during inert gas euthanasia of mice. PLOS ONE 13(4), e0195872.

Carbon dioxide (CO2) is one of the most commonly used euthanasia agents for mice, yet it is highly aversive and nociceptive. Inert gases are a possible alternative, however there are qualitative reports of seizures resulting...

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...

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...

Dudley, E. S., Boivin, G. P. 2018. Evaluation of a commercially available euthanasia solution as a voluntarily ingested euthanasia agent in laboratory mice. JAALAS 57(1), 30-34.

All currently accepted methods of euthanasia for laboratory mice involve some degree of stress, fear, anxiety, or pain. We evaluated the voluntary oral administration of a euthanasia drug in 99 male and 81 female mice...

Lahger, C., Laska, M. 2018. Behavioral responses of CD-1 mice to conspecific and heterospecific blood odors and to a blood odor component. Physiology & Behavior 184, 2015-210.

The odor of blood may have both aversive and attractive properties for mammals, depending on the species of the odor donor and the species perceiving the odor. To better understand the informational content of blood...

Galvin, M., Lallo, A., Brown, S. et al. 2018. Refinement of tumour passage by optimisation of the tissue disaggregation protocol. Animal Technology and Welfare 17(2), 101-103.

Surgical implantation of tumour pieces has been used regularly in the passage of tumour models. This involves an invasive surgical procedure, carried out under anaesthesia, ensuring mice have adequate pain relief and peri-operative care. The...

Read, H., Perry, R. 2018. A refinement to Schedule 1. Animal Technology and Welfare 17(2), 117-120.

There are varying methods used for animal restraint and angle of injection. It remains unclear whether one method is more accurate than others. The primary objectives were to examine whether inverted restraint of rats resulted...

Beamish, G., Chapman, C., Lomax, A. 2018. Design by intravenous injection in the Syrian hamster. Animal Technology and Welfare 17(2), 124-125.

Repeated injections in rats and mice are typically done via the tail vein. For hamsters, the tail is not an option. In this paper we explore the development and refinement of IV dosing in the...

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...

Creamer-Hente, M. A., Lao, F. K., Dragos, Z. P. et al. 2018. Sex- and strain-related differences in the stress response of mice to CO₂ euthanasia. JAALAS 57(5), 513–519.

The 2013 edition of the AVMA Guidelines for the Euthanasia of Animals recommends a 10% to 30% volume displacement rate (VDR) per minute for CO2 euthanasia of rodents. Here we sought to evaluate behavior and...

Hickman D. L. 2018. Interpreting neuroendocrine hormones, corticosterone, and blood glucose to assess the wellbeing of anesthetized rats during euthanasia. JAALAS 57(6), 725–728.

Current recommendations for assessing animal wellbeing during euthanasia suggest that measuring neuroendocrine hormones—such as ACTH, noradrenaline, and adrenaline—is preferable to measuring corticosterone and blood glucose because of the sensitivity of neuroendocrine hormones to the acute...

Hickman D. L. 2018. Home cage compared with induction chamber for euthanasia of laboratory rats. JAALAS 57(6), 729–733.

This study compared behavioral and physiologic changes in Sprague–Dawley and Brown Norway rats that were euthanized by using a 30% volume displacement rate of CO2 in either their home cage or an induction chamber; rats...

Byrd, R., Boyd, S., Buckmaster, C. 2018. Rat thunder jacket— A zen experience. Laboratory Animal Science Professional 6(3) (September), 55-57.

Germ-free rats are fairly uncommon, relative to germ-free mice, and restraining these animals safely and effectively for compound administration and blood collection can be challenging. There are many commercially available varieties of restraint devices, but...

Marquardt, N., Feja, M., Hünigen, H. et al. 2018. Euthanasia of laboratory mice: Are isoflurane and sevoflurane real alternatives to carbon dioxide? PLOS ONE 13(9), e0203793.

In the European Union (EU) millions of laboratory mice are used and killed for experimental and other scientific purposes each year. Although controversially discussed, the use of carbon dioxide (CO2) is still permitted for killing...

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...

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...

Tavera-Mendoza, L. E., Brown, M. 2017. A less invasive method for orthotopic injection of breast cancer cells into the mouse mammary gland. Laboratory Animals 51(1), 85-88.

Breast cancer is the most common type of cancer diagnosed in women, and the second most common cause of cancer-related deaths in women in North America. The use of laboratory mice in research is an...

Larsen, R. A., Peveler, J. L., Klutzke, J. B. et al. 2017. Effects of daily restraint with and without injections on skeletal properties in C57BL/6NHsd mice. Lab Animal 46(7), 299-301.

Studies typically involve groups of animals that are injected with placebo compounds. As there are studies that demonstrate that restraint and injection can affect behavior and corticosteroid levels in rodents, the basis of such placebo...

Walsh, J., Percival, A., Turner, P. 2017. Efficacy of blunt force trauma, a novel mechanical cervical dislocation device, and a non-penetrating captive bolt device for on-farm euthanasia of pre-weaned kits, growers, and adult commercial meat rabbits. Animals 7(12), 100.

The commercial meat rabbit industry is without validated on-farm euthanasia methods, potentially resulting in inadequate euthanasia protocols. We evaluated blunt force trauma (BFT), a mechanical cervical dislocation device (MCD), and a non-penetrating captive bolt device...

Hubbard, J. S., Chen, P. H., Boyd, K. L. 2017. Effects of repeated intraperitoneal injection of pharmaceutical-grade and nonpharmaceutical-grade corn oil in female C57BL/6J mice. JAALAS 56(6), 779-785.

Due to potential adverse effects on animal wellbeing, the use of nonpharmaceutical-grade substances in animal research must be scientifically justified in cases where a pharmaceutical-grade version of the substance exists. This requirement applies to all...

Boivin, G. P., Hickman, D. L., Creamer-Hente, M. A. et al. 2017. Review of CO2 as a euthanasia agent for laboratory rats and mice. JAALAS 56(5), 491-499.

Selecting an appropriate, effective euthanasia agent is controversial. Several recent publications provide clarity on the use of CO2 in laboratory rats and mice. This review examines previous studies on CO2 euthanasia and presents the current...

de Souza Dyer, C., Brice, A. K., Marx, J. O. 2017. Intraperitoneal administration of ethanol as a means of euthanasia for neonatal mice (Mus musculus). JAALAS 56(3), 299-306.

The humane euthanasia of animals in research is of paramount importance. Neonatal mice frequently respond differently to euthanasia agents when compared with adults. The AVMA's Guidelines for the Euthanasia of Animals includes intraperitoneal injection of...

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...