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. 
Higham, J. P., Cooper, E. B., Whalen, C. et al. 2023. Urinary cytokine measurements do not reflect surgery-induced inflammation in rhesus macaques. American Journal of Primatology 85(8), e23506.

Measurement of the health and disease status of free-ranging primates is often limited by a lack of available biomarkers of immune activation and inflammation that can be applied noninvasively via the measurement of urine or...

Brando, S., Norman, M. 2023. Handling and training of wild animals: Evidence and ethics-based approaches and best practices in the modern zoo. Animals 13(14), 2247.

There is an ethical responsibility to provide all animals living in human care with optimal and positive well-being. As animals living in zoos and aquariums frequently interact with their human caregivers as part of their...

Buckmaster, C. L., Levesque, D., LaFollette, M. et al. 2022. Five hot topics in refinement of nonhuman primate neuroscience research. Laboratory Animal Science Professional 10(1) (January/February), 24-26.

Members of the North American 3Rs Collaborative (NA3RsC) refinement initiative have chosen to summarize developments in five hot topics of interest: 1. Tips for welfare-friendly transport, chairing, and restraint; 2. Guidance on refining food and...

Edes, A. N., Zimmerman, D., Jourdan, B. et al. 2022. Value ranges and clinical comparisons of serum DHEA-S, IL-6, and TNF-α in western lowland gorillas. Animals 12(19), 2705.

Physiological data can provide valuable information about the health and welfare of animals. Unfortunately, few validated assays and a lack of information on species-typical levels of circulating biomarkers for wildlife make the measurement, interpretation, and...

Mason, G. J., Lavery, J. M. 2022. What is it like to be a bass? Red herrings, fish pain and the study of animal sentience. Frontiers in Veterinary Science 9, 788289.

Debates around fishes’ ability to feel pain concern sentience: do reactions to tissue damage indicate evaluative consciousness (conscious affect), or mere nociception? Thanks to Braithwaite’s research leadership, and concerns that current practices could compromise welfare...

Prior, H., Holbrook, M. 2021. Strategies to encourage the adoption of social housing during cardiovascular telemetry recordings in non-rodents. Journal of Pharmacological and Toxicological Methods 108, 106959.

The National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) is working with industry to promote social housing during cardiovascular telemetry recordings within non-rodent safety pharmacology and toxicology studies. Following surveys...

Sørensen, D., Cloutier, S., Gaskill, B. (Eds.). 2021. Animal-centric Care and Management - Enhancing Refinement in Biomedical Research. CRC Press, Boca Raton, FL.

The concept of the 3Rs (Refinement, Reduction and Replacement) has been used as a framework for improving the welfare of laboratory animals for the last half century. By establishing an animal-centric view on housing and...

Falendysz, E. A., Calhoun, D. M., Smith, C. A. et al. 2020. Outside the box: Working with wildlife in biocontainment. ILAR Journal 61(1), 72-85.

Research with captive wildlife in Animal Biosafety Level 2 (ABSL2) and 3 (ABSL3) facilities is becoming increasingly necessary as emerging and re-emerging diseases involving wildlife have increasing impacts on human, animal, and environmental health. Utilizing...

Edes, A. N., Brand, C. M. 2021. Age, sex, and inflammatory markers predict chronic conditions, cardiac disease, and mortality among captive western lowland gorillas (Gorilla gorilla gorilla). Primates 62(6), 931-943.

In humans, inflammatory markers predict health risks. As great apes experience many similar conditions, measuring inflammation may provide valuable health information. We examined four serum inflammatory markers in zoo-housed gorillas (n = 48): albumin, CRP, IL-6, and...

Byrnes, E. E., Lear, K. O., Morgan, D. L. et al. 2020. Respirometer in a box: Development and use of a portable field respirometer for estimating oxygen consumption of large‐bodied fishes. Journal of Fish Biology 96(4), 1045-1050.

Respirometry has become the standard method for measuring the metabolic rate of fishes. Traditionally, respirometry has required the fish to be kept in captivity and tested under controlled conditions; however, many species do not readily...

Plangsangmas, T., Brown, J., Thitaram, C. et al. 2020. Circadian rhythm of salivary immunoglobulin A and associations with cortisol as a stress biomarker in captive Asian elephants (Elephas maximus). Animals 10(1), 157.

Salivary immunoglobulin A (sIgA) has been proposed as a potential indicator of welfare for various species, including Asian elephants, and may be related to adrenal cortisol responses. This study aimed to distinguish circadian rhythm effects...

Hambrecht, S., Oerke, A.‐K., Heistermann, M. et al. 2020. Diurnal variation of salivary cortisol in captive African elephants (Loxodonta africana) under routine management conditions and in relation to a translocation event. Zoo Biology 39(3), 186–196.

The present study assessed the diurnal variation in salivary cortisol in captive African elephants during routine management (baseline) and in relation to a potential stressor (translocation) to evaluate to what extent acute stress may affect...

Cloutier Barbour, C., Danforth, M. D., Murphy, H. et al. 2020. Monitoring great ape heart health through innovative electrocardiogram technology: Training methodologies and welfare implications. Zoo Biology 39(6), 443-447.

Assessing and treating cardiovascular disease (or heart disease) is a growing concern for institutions housing great apes, as it is a major cause of mortality in all four taxa managed in human care. As part...

Murphy, A. M., Ross, C. N., Bliss‐Moreau, E. 2019. Noninvasive cardiac psychophysiology as a tool for translational science with marmosets. American Journal of Primatology 81(9), e23037.

The importance of marmosets for comparative and translational science has grown in recent years because of their relatively rapid development, birth cohorts of twins, family social structure, and genetic tractability. Despite this, they remain understudied...

Kumar, V., Pradheeps, M., Kokkiligadda, A. et al. 2019. Non-invasive assessment of physiological stress in captive Asian elephants. Animals 9(8), 553.

Asian elephant (Elephas maximus) populations, both in the wild and in captivity, have been continually declining over the decades. The present study examined the physiological stress response of captive Asian elephants in relation to body...

McIntosh, M. K., Armitage-Brown, B., Levy, R. 2019. Refinements of equipment and methodology to reduce risk during pole-guided chair transfer of nonhuman primates. JAALAS 58(4), 462-468.

Neurophysiologic studies of NHP commonly involve their transfer from a housing enclosure to a laboratory by using a mobile chair. This transfer should be performed in a manner that is safe and minimizes stress for...

McKenzie, D. J., Sadoul, B., Geffroy, B. 2019. Measuring cortisol, the major stress hormone in fishes. Journal of Fish Biology 94(4), 540-555.

Stress in teleosts is an increasingly studied topic because of its interaction with growth, reproduction, immune system and ultimately fitness of the animal. Whether it is for evaluating welfare in aquaculture, adaptive capacities in fish...

Edwards, K. L., Miller, M. A., Carlstead, K. et al. 2019. Relationships between housing and management factors and clinical health events in elephants in North American zoos. PLOS ONE 14(6), e0217774.

Elephants experience a number of health issues that can contribute to their well-being and survival. In managed populations, housing conditions and management practices can influence individual health, so potential risk factors associated with morbidity or...

Broche Jr., N., Takeshita, R. S. C., Mouri, K. et al. 2019. Salivary alpha-amylase enzyme is a non-invasive biomarker of acute stress in Japanese macaques (Macaca fuscata). Primates volume 60(6), 547–558.

Salivary alpha-amylase (sAA) enzyme functions as a digestive enzyme in many species that consume starch in their diet. Human studies have also revealed that sAA enzyme activity levels are positively correlated with the release of...

Cox, R. J., Nol, P., Ellis, C. K. et al. 2019. Research with agricultural animals and wildlife. ILAR Journal 60(1), 66-73.

In fiscal year 2016, agricultural animals such as swine, sheep, goats, and cattle represented 10% of the 820 812 animals used in USDA-regulated research. In addition to traditional agricultural animals, research studies using captive wildlife...

Stevens, C. 2019. Refining handling for small laboratory fishes. Animal Technology and Welfare 18(3), 191-193.

Fishes in captivity, such as those used in laboratory research, may experience handling on a regular basis. In the laboratory, handling is usually done with dip-nets, and involves pursuit, confinement and capture and removal of...

France, L. K., Vermillion, M. S., Garrett, C. M. 2018. Comparison of direct and indirect methods of measuring arterial blood pressure in healthy male rhesus macaques (Macaca mulatta). JAALAS 57(1), 64-69.

Blood pressure is a critical parameter for evaluating cardiovascular health, assessing effects of drugs and procedures, monitoring physiologic status during anesthesia, and making clinical decisions. The placement of an arterial catheter is the most direct...

Ash, H., Smith, T. E., Knight, S. et al. 2018. Measuring physiological stress in the common marmoset (Callithrix jacchus): Validation of a salivary cortisol collection and assay technique. Physiology & Behavior 185, 14-22.

Cortisol levels are often used as a physiological measure of the stress response in captive primates, with noninvasive measures of this being an important step in welfare assessment. We report a method of collecting saliva...

O’Rourke, D. P., Baccanale, C. L., Stoskopf, M. K. 2018. Nontraditional laboratory animal species (cephalopods, fish, amphibians, reptiles, and birds). ILAR Journal 59(2), 168-176.

Aquatic vertebrates and cephalopods, amphibians, reptiles, and birds offer unique safety and occupational health challenges for laboratory animal personnel. This paper discusses environmental, handling, and zoonotic concerns associated with these species.

Fuller, G., Allard, S. 2018. Preliminary data showing potential for salivary C-reactive protein as an indicator of welfare in western lowland gorillas (Gorilla gorilla gorilla). Journal of Veterinary Behavior 28, 58-62.

C-reactive protein (CRP) is an acute phase protein often used as a biomarker for inflammation related to acute trauma or chronic illness. Animal studies showing elevations in CRP following events such as road transport and...