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. 
Wallace, C. K., Bright, L. A., Marx, J. O. et al. 2018. Effectiveness of rapid cooling as a method of euthanasia for young zebrafish (Danio rerio). JAALAS 57(1), 58-63.

Despite increased use of zebrafish (Danio rerio) in biomedical research, consistent information regarding appropriate euthanasia methods, particularly for embryos, is sparse. Current literature indicates that rapid cooling is an effective method of euthanasia for adult...

Hocking, A. J., Elliot, D., Hua, J. et al. 2018. Administering fixed oral doses of curcumin to rats through voluntary consumption. JAALAS 57(5), 508–512.

Curcumin, a polyphenol derived from turmeric, has a wide variety of therapeutic benefits including antiinflammatory, antioxidative, and chemopreventative effects. Oral gavage is widely performed to administer curcumin in laboratory rodents in several experimental models. Although...

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...

Raya, J., Neves Girardi , C. E., Hipólide, D. C. 2019. Corticosterone assimilation by a voluntary oral administration in palatable food to rats. Journal of Applied Animal Welfare Science 22(1), 37-41.

Drug delivery in research on nonhuman animals in the laboratory is still challenging because it is usually invasive and stressful. Stress-free voluntary oral drug administration in water lacks precise control of dose and timing of...

Hankenson, F. C., Marx, J. O., Gordon, C. J. et al. 2018. Effects of rodent thermoregulation on animal models in the research environment. Comparative Medicine 68(6), 425–438.

To best promote animal wellbeing and the efficacy of biomedical models, scientific, husbandry, and veterinary professionals must consider the mechanisms, influences, and outcomes of rodent thermoregulation in contemporary research environments. Over the last 2 decades...

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...

Köhler, A., Collymore, C., Finger-Baier, K. et al. 2017. Report of Workshop on Euthanasia for Zebrafish—A Matter of welfare and science. Zebrafish 14(6), 547-551.

The increasing importance of zebrafish as a biomedical model organism is reflected by the steadily growing number of publications and laboratories working with this species. Regulatory recommendations for euthanasia as issued in Directive 2010/63/EU are...

Zhang, E. Q., Knight, C. G., Pang, D. S. J. 2017. Heating pad performance and efficacy of 2 durations of warming after isoflurane anesthesia of Sprague–Dawley rats (Rattus norvegicus). JAALAS 56(6), 786-791.

Anesthetic agents depress thermoregulatory mechanisms, causing hypothermia within minutes of induction of general anesthesia. The consequences of hypothermia include delayed recovery and increased experimental variability. Even when normothermia is maintained during anesthesia, hypothermia may occur...

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 Lombaert, M. C. M., Rick, E. L., Krugner-Higby, L. A. et al. 2017. Behavioral characteristics of adult zebrafish (Danio rerio) after MS222 anesthesia for fin excision. JAALAS 56(4), 377-381.

The health of laboratory animals is an ethical responsibility of researchers and a critical determinant of experimental outcome. Therefore, all Husbandry & Management procedures should be evaluated for their effects on mortality, behavior, and physiology...

Chatigny, F., Kamunde, C., Creighton, C. M. et al. 2017. Uses and doses of local anesthetics in fish, amphibians, and reptiles. JAALAS 56(3), 244-253.

Local anesthetics are an integral part of routine pain management in mammals, yet their use is relatively limited in fish, amphibians and reptiles. These animals frequently undergo potentially painful surgical procedures and therefore could possibly...

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...

Lidster, K., Readman, G. D., Prescott, M. J. et al. 2017. International survey on the use and welfare of zebrafish Danio rerio in research. Journal of Fish Biology 90(5), 1891-1905.

A survey was conducted regarding zebrafish Danio rerio use for scientific research with a focus on: anaesthesia and euthanasia; housing and husbandry; breeding and production; refinement opportunities. A total of 98 survey responses were received...

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...

Martins, T., Valentim, A. M., Pereira, L. N. et al. 2016. Anaesthesia and analgesia in laboratory adult zebrafish: a question of refinement. Laboratory Animals 50(6), 476-488.

Anaesthesia is used daily in fish experimental procedures; however, the use of an inadequate anaesthetic protocol can compromise not only the animal’s welfare but also the reliability of results. The use of zebrafish (Danio rerio)...

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...

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...

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...

Reinhardt, V. (ed.) 2013. Compassion Makes a Difference - Discussions by the Laboratory Animal Refinement & Enrichment Forum [LAREF], Volume III. Animal Welfare Institute, Washington, DC.

This is the third volume of discussions that took place on the Laboratory Animal Refinement & Enrichment Forum (LAREF). This forum is dedicated to the exchange of personal experiences of refining the conditions under which...

Lambeth, S. P., Schapiro, S. J., Bernacky, B. J. et al. 2013. Establishing 'quality of life' parameters using behavioural guidelines for humane euthanasia of captive non-human primates. Animal Welfare 22(4) 429-435.

Chronic pain and distress are universally accepted conditions that may adversely affect an animal’s quality of life (QOL) and lead to the humane euthanasia of an animal. At most research institutions and zoological parks in...

Wong, D., Makowska, I. J., Weary, D. M. 2013. Rat aversion to isoflurane versus carbon dioxide. Biology Letters 9(1), 20121000.

Some experts suggest that sedation of laboratory rodents with isoflurane before euthanasia with carbon dioxide (CO2) is a humane alternative to euthanasia with CO2 alone, but little research has compared aversion with these agents. Albino...