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. 
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...

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...

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...

Hohlbaum, K., Bert, B., Dietze, S. et al. 2018. Impact of repeated anesthesia with ketamine and xylazine on the well-being of C57BL/6JRj mice. PLOS ONE 13(9), e0203559.

Within the scope of the 3Rs of Russel and Burch, the number of laboratory animals can be reduced by repeated use of an animal. This strategy only becomes relevant, if the total amount of pain...

Hohlbaum, K., Bert, B., Dietze, S. et al. 2017. Severity classification of repeated isoflurane anesthesia in C57BL/6JRj mice—Assessing the degree of distress. PLOS ONE 12(6), e0179588.

According to the EU Directive 2010/63, the severity of a procedure has to be classified as mild, moderate or severe. General anesthesia is thought to be mild, but the Directive does not differentiate between single...

Schmitz, S., Tacke, S., Guth, B. et al. 2017. Repeated anaesthesia with isoflurane and medetomidine-midazolam-fentanyl in guinea pigs and its influence on physiological parameters. PLOS ONE 12(3), e0174423.

Repeated anaesthesia may be required in experimental protocols and in daily veterinary practice, but anaesthesia is known to alter physiological parameters in GPs (Cavia porcellus, GPs). This study investigated the effects of repeated anaesthesia with...

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...

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...

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...

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...

Skorupski, A. M., Zhang, J., Ferguson, D. et al. 2017. Quantification of induced hypothermia from aseptic scrub applications during rodent surgery preparation. JAALAS 56(5), 562-569.

Laboratory mice (Mus musculus) are prone to develop hypothermia during anesthesia for surgery, thus potentially impeding anesthetic recovery, wound healing, and future health. The core body temperatures of isoflurane-anesthetized mice are influenced by the choice...

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...

Parkinson, L., Mans, C. 2017. Anesthetic and postanesthetic effects of alfaxalone–butorphanol compared with dexmedetomidine–ketamine in chinchillas (Chinchilla lanigera). JAALAS 56(3), 290-295.

Effective and safe anesthetic protocols are required for a variety of surgical and diagnostic procedures in chinchillas. Alfaxalone, a new anesthetic agent in the United States, can be administered intramuscularly and subcutaneously and is therefore...

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...

Reiter, C. P., Christy, A. C., Olsen, C. H. et al. 2017. Effect of home cage bedding in the induction chamber on serum cortisol and corticosterone levels in response to isoflurane-induced anesthesia in C57BL/6J mice. JAALAS 56(2), 118-121.

Mice are routinely anesthetized with isoflurane in an induction chamber. The AVMA Guidelines for the Euthanasia of Animals states that distress should be minimized during euthanasia but does not address this point in regard to...

Janssen, C. F., Maiello, P., Wright Jr, M. J. et al. 2017. Comparison of atipamezole with yohimbine for antagonism of xylazine in mice anesthetized with ketamine and xylazine. JAALAS 56(2), 142-147.

The α2 adrenergic agonist xylazine produces a sedative effect and is typically combined with ketamine and used for anesthesia or chemical restraint of laboratory mice. Xylazine's sedative effect—and its undesirable side effects of bradycardia, hypotension...

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...

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...

Simpson, D. 2017. Investigation of transportation on rat acclimatisation using novel cage side recording equipment (Rodent Big Brother). Animal Technology and Welfare 16(1), 1-12.

The transportation of animals from supplier to experimental facility is one of the biggest stressors to animals in research. Transportation unavoidably causes stress and when the animals arrive at the testing facility they require a...