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. 
Lambert, H., Cornish, A., Waley, D. 2024. The value of regulating stocking densities in aquaculture must not be dismissed: A reply to Saraiva et al. 2022. Frontiers in Veterinary Science 10.

We would like to rebut the argument made by Saraiva et al. (1) in their paper “Finding the “golden stocking density”: a balance between fish welfare and farmers' perspectives,” that stocking densities should not be...

Diao, W., Jia, R., Hou, Y. et al. 2023. Effects of stocking density on the growth performance, physiological parameters, antioxidant status and lipid metabolism of Pelteobagrus fulvidraco in the integrated rice-fish farming system. Animals 13(11), 1721.

Pelteobagrus fulvidraco is a freshwater fish commonly raised in rice fields, yet the optimal stocking density for this species remains unknown. Therefore, this study aimed to investigate the appropriate stocking density of P. fulvidraco in...

Farag, A., Mandour, A. S., Hendawy, H. et al. 2023. A review on experimental surgical models and anesthetic protocols of heart failure in rats. Frontiers in Veterinary Science 10, 1103229.

Heart failure (HF) is a serious health and economic burden worldwide, and its prevalence is continuously increasing. Current medications effectively moderate the progression of symptoms, and there is a need for novel preventative and reparative...

Mauthe von Degerfeld, M., Serpieri, M., Bonaffini, G. et al. 2023. Intranasal atomization of ketamine, medetomidine and butorphanol in pet rabbits using a mucosal atomization device. Animals 13(13), 2076.

A non-invasive method of drug delivery, intranasal atomization, has shown positive results in human medicine and in some animal species. The objective of this study was to evaluate the effects of intranasal atomization, compared to...

Morton, D. B. 2023. A model framework for the estimation of animal “suffering”: Its use in predicting and retrospectively assessing the impact of experiments on animals. Animals 13(5), 800.

This paper presents and illustrates, with a working example, a hypothesis for the assessment of ongoing severity before and during an experiment that will enable humane endpoints and intervention points to be applied accurately and...

Silva-Reis, R., Faustino-Rocha, A. I., Silva, J. et al. 2023. Studying and analyzing humane endpoints in the fructose-fed and streptozotocin-injected rat model of diabetes. Animals 13(8), 1397.

This work aimed to define a humane endpoint scoring system able to objectively identify signs of animal suffering in a rat model of type 2 diabetes. Sprague-Dawley male rats were divided into control and induced...

Baßmann, B., Hahn, L., Rebl, A. et al. 2023. Effects of stocking density, size, and external stress on growth and welfare of African catfish (Clarias gariepinus Burchell, 1822) in a commercial RAS. Fishes 8(2), 74.

The effects of semi-intensive (100 kg m−3), intensive (200 kg m−3), and super-intensive (400 kg m−3) stocking densities on the growth and welfare of African catfish (Clarias gariepinus) were investigated under commercial production conditions. Plasma...

Ruíz-López, P., Cuypers, C., Schauvliege, S. 2023. Xylazine infusion during equine colic anesthesia with isoflurane and lidocaine: A retrospective study. Animals 13(18), 2902.

This retrospective study investigated the effect of a xylazine infusion on heart rate; mean arterial pressure; blood gases; anesthetic and dobutamine requirements; recovery quality and duration; percentage of death/survival; and days to die/discharge in horses...

Williams, W. O., Baneux, P. 2022. Humane Intervention Points: Refining endpoint terminology to incorporate non-euthanasia intervention options to improve animal welfare and preserve experimental outcomes. Laboratory Animals 56(5), 482-489.

Consideration of The Three R’s (Replacement, Reduction, and Refinement) is essential when setting Humane Endpoints; however, a common interpretation assumes that Humane Endpoints are timepoints to perform euthanasia. This interpretation is not always consistent with...

Farag, A., Mandour, A. S., Hamabe, L. et al. 2022. Novel protocol to establish the myocardial infarction model in rats using a combination of medetomidine-midazolam-butorphanol (MMB) and atipamezole. Frontiers in Veterinary Science 9, 1064836.

Myocardial infarction (MI) is one of the most common cardiac problems causing deaths in humans. Previously validated anesthetic agents used in MI model establishment are currently controversial with severe restrictions because of ethical concerns. The...

Saraiva, J. L., Rachinas-Lopes, P., Arechavala-Lopez, P. 2022. Finding the “golden stocking density”: A balance between fish welfare and farmers’ perspectives. Frontiers in Veterinary Science 9, 930221.

The effects of stocking density on fish welfare are complex and involve many interacting parameters. This complex relationship between fish welfare, stocking density and influencing factors make it challenging to define a specific optimal (“golden”)...

Wahltinez, S. J., Stacy, N. I., Hadfield, C. A. et al. 2022. Perspective: Opportunities for advancing aquatic invertebrate welfare. Frontiers in Veterinary Science 9, 973376.

Welfare considerations and regulations for invertebrates have lagged behind those for vertebrates, despite invertebrates comprising more than 95% of earth’s species. Humans interact with and use aquatic invertebrates for exhibition in zoos and aquaria, as...

Anderson, M. G., Campbell, A. M., Kuhn, D. D. et al. 2022. Impact of environmental complexity and stocking density on affective states of rainbow trout (Oncorhynchus mykiss). Animal Cognition 25(5), 1331–1343.

Environmental condition, such as environmental complexity or stocking density, can directly or indirectly influence animal emotion and ultimately, affective state. Affective states of animals can be assessed through judgement bias tests, evaluating responses to ambiguous...

Oliveira, A. R., Gozalo-Marcilla, M., Ringer, S. K. et al. 2021. Development, validation, and reliability of a sedation scale in horses (EquiSed). Frontiers in Veterinary Science 8, 611729.

The lack of standardization of sedation scales in horses limits the reproducibility between different studies. This prospective, randomized, blinded, horizontal and controlled trial aimed to validate a scale for sedation in horses (EquiSed). Seven horses...

Silva-Reis, R., Faustino-Rocha, A. I., Gonçalves, M. et al. 2021. Refinement of animal model of colorectal carcinogenesis through the definition of novel humane endpoints. Animals 11(4), 985.

This study aimed to define appropriate humane endpoints (HEs) for an animal model of colorectal carcinogenesis (CRC). Twenty-nine male Wistar rats were divided into two control groups (CTRL1 and CTRL2) injected with ethylenediamine tetraacetic acid...

Nunamaker, E. A., Davis, S., O’Malley, C. I. et al. 2021. Developing recommendations for cumulative endpoints and lifetime use for research animals. Animals 11(7), 2031.

Research animals are important for scientific advancement, and therefore, their long-term welfare needs to be monitored to not only minimize suffering, but to provide positive affective states and experiences. Currently, there is limited guidance in...

Ellis, T., Katsiadaki, I. 2021. Clarification of early end-points for refinement of animal experiments, with specific reference to fish. Laboratory Animals 55(3), 244-253.

Appropriate end-points are integral to the refinement of laboratory animal experiments. Our recent experience has highlighted that ambiguity around end-points is hampering their adoption in experiments that cause severe suffering to fish. In toxicology, the...

Kälin, I., Henze, I. S., Ringer, S. K. et al. 2021. Comparison of recovery quality following medetomidine versus xylazine balanced isoflurane anaesthesia in horses: A retrospective analysis. Animals 11(8), 2440.

Medetomidine partial intravenous anaesthesia (PIVA) has not been compared to xylazine PIVA regarding quality of recovery. This clinical retrospective study compared recoveries following isoflurane anaesthesia balanced with medetomidine or xylazine. The following standard protocol was...

Abbo, L. A., Himebaugh, N. E., DeMelo, L. M. et al. 2021. Anesthetic efficacy of magnesium chloride and ethyl alcohol in temperate octopus and cuttlefish species. JAALAS 60(5), 556-567.

Cephalopods are important in biologic and biomedical research, yet relatively little objective information is available to guide researchers and veterinarians regarding the best methods for anesthetizing these animals for various experimental procedures. Recent studies demonstrate...

White, K. L., Hird, J. F. R., Taylor, P. M. 2021. Sevoflurane or isoflurane anaesthesia? A prospective, randomised blinded clinical trial in horses undergoing elective surgery. Veterinary Record 189(3), e507.

Background: Isoflurane is the only volatile anaesthetic agent licensed for equine use in the United Kingdom, but sevoflurane is also commonly used. The two agents have rarely been compared for use in clinical elective surgery...

Botman, J., Hontoir, F., Gustin, P. et al. 2020. Postanaesthetic effects of ketamine–midazolam and ketamine–medetomidine on gastrointestinal transit time in rabbits anaesthetised with isoflurane. Veterinary Record 186(8), 249.

Gastrointestinal stasis is a common perianaesthetic complication in rabbits. The objective of this study was to assess the impact on gastrointestinal transit time of ketamine–midazolam (KMZ) versus ketamine–medetomidine (later antagonised by atipamezole) (KMT-A) in rabbits...

Yaw, T. J., Mans, C., Johnson,S. et al. 2020. Evaluation of subcutaneous administration of alfaxalone-midazolam and dexmedetomidine-midazolam for sedation of ball pythons (Python regius). Journal of the American Veterinary Medical Association 256(5), 573-579.

OBJECTIVE: To evaluate SC administration of alfaxalone-midazolam and dexmedetomidine-midazolam for sedation of ball pythons (Python regius). ANIMALS: 12 healthy juvenile ball pythons. PROCEDURES: In a randomized crossover study, each snake was administered a combination of...

Alemán-Laporte, J., Bandini, L. A., Garcia-Gomes, M. S. et al. 2020. Combination of ketamine and xylazine with opioids and acepromazine in rats: Physiological changes and their analgesic effect analysed by ultrasonic vocalization. Laboratory Animals 54(2), 171–182.

In this study, the effect of four anaesthetic protocols that included the combination of xylazine (X) and ketamine (K) with acepromazine (A) and opioids (methadone (Me), morphine (Mo) or tramadol (T)) was evaluated in laboratory...

Talbot, S. R., Biernot, S., Bleich, A. et al. 2020. Defining body-weight reduction as a humane endpoint: A critical appraisal. Laboratory Animals 54(1), 99–110.

In many animal experiments scientists and local authorities define a body-weight reduction of 20% or more as severe suffering and thereby as a potential parameter for humane endpoint decisions. In this study, we evaluated distinct...

Hempstead, M. N., Waas, J. R., Stewart, M. et al. 2020. Can isoflurane and meloxicam mitigate pain associated with cautery disbudding of 3-week-old goat kids? Animals 10(5), 878.

We evaluated the effect of pain mitigation strategies (isoflurane and meloxicam) on the behaviour and physiology of 3-week-old disbudded goat kids. Fifty Saanen does (mean ± SD, 21 ± 3 days old) were randomly allocated...