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. 
Nosaka, N., Crother, T. R., Chen, S. et al. 2019. Optimal tube length of orotracheal intubation for mice. Laboratory Animals 53(1), 79–83.

Endotracheal tube (ETT) management is an essential technique in handling mice with mechanical ventilators. Malposition into bronchi causes not only lethal complications for them but also less efficient mechanical ventilation. However, in general, it is...

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...

Mather, J. A., Carere, C. 2019. Consider the individual: Personality and welfare in invertebrates. In: The Welfare of Invertebrate Animals. Carere, C., Mather, J. (eds), 229-245. Springer, Cham.

Personality, defined as consistent between-individual variation in clusters of behavioral traits independent of factors such as age or sex, emerges in most animal species tested so far. The number of invertebrate species discovered to have...

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...

Grist, A., Lines, J., Knowles, T. et al. 2018. Use of a non-penetrating captive bolt for euthanasia of neonate goats. Animals 8(4), 58.

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 goats (Capra aegagrus hircus) of mean...

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...

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...

Weineck, K., Ray, A. J., Fleckenstein, L. J. et al. 2018. Physiological changes as a measure of crustacean welfare under different standardized stunning techniques: Cooling and electroshock. Animals 8(9), 158.

Stunning of edible crustaceans to reduce sensory perception prior and during slaughter is an important topic in animal welfare. The purpose of this project was to determine how neural circuits were affected during stunning by...

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...

Collymore, C., Kent, L., Ahn, S. K. et al. 2018. Humane endpoints for guinea pigs used for Mycobacterium tuberculosis vaccine research. Comparative Medicine 68(1), 41–47.

Guinea pigs are a commonly used model for tuberculosis vaccine research. Loss of body weight is the most frequently described humane endpoint for animals used in these studies. During a chronic study, we noted labored...

Wolfe, A. M., Rahman, M., McFadden, D. G. et al. 2018. Refinement and successful implementation of a scoring system for myxomatosis in a susceptible rabbit (Oryctolagus cuniculus) model. Comparative Medicine 68(4), 280–285.

Myxoma virus is a member of Leporipoxviridae whose tropism is tightly restricted to lagomorphs. In susceptible Oryctolagus rabbits, the virus causes a highly lethal disease known as myxomatosis, which begins as a localized infection but...

Toth, L. A. 2018. Identifying and implementing endpoints for geriatric mice. Comparative Medicine 68(6), 439–451.

The types of changes in physical appearance and behavior that occur in elderly people similarly develop in elderly animals. Signs and symptoms that might cause concern in younger people or mice may be normal in...

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...

Sutherland, M. A., Watson, T. J., Millman, S. T. 2017. Technical contribution: evaluation of the efficacy of a non-penetrating captive bolt to euthanase dairy goat kids up to 30 days of age. Animal Welfare 26(3), 277-280.

The objective of this study was to evaluate the effectiveness of a non-penetrating captive bolt (NPCB) to euthanase previously disbudded Saanen dairy goat kids (Capra hircus) up to 30 days of age and 9 kg...

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...

Otano-Rivera, V., Boakye, A., Grobe, N. et al. 2017. A highly efficient strategy to determine genotypes of genetically-engineered mice using genomic DNA purified from hair roots. Laboratory Animals 51(2), 138-146.

Genotyping of genetically-engineered mice is necessary for the effective design of breeding strategies and identification of mutant mice. This process relies on the identification of DNA markers introduced into genomic sequences of mice, a task...

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...

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...

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...