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. 
Williams, E., Hunton, V., Hosey, G. et al. 2023. The impact of visitors on non-primate species in zoos: A quantitative review. Animals 13(7), 1178.

Visitors are a prominent feature in the lives of zoo animals, and their presence can cause a range of impacts on zoo animals (typically classed as positive, negative or neutral impacts), commonly referred to as...

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...

Luisi, B., Micheletta, J., Julle-Danière, E. et al. 2023. Monkeying around: Non-human primate behavioural responses to humans reproducing their facial expressions. Applied Animal Behaviour Science 265, 105990.

People are often observed mimicking animals’ facial expressions in an attempt to communicate with them. However, to date, there is limited understanding of how animals respond to humans reproducing their facial displays, or if this...

Bertrand, D. A., Berman, C. M., Heistermann, M. et al. 2023. Effects of tourist and researcher presence on fecal glucocorticoid metabolite levels in wild, habituated Sulawesi crested macaques (Macaca nigra). Animals 13(18), 2842.

Ecotourism managers and researchers often assume that apparently habituated primate groups no longer experience adverse consequences of prolonged exposure to tourists or researchers. We examined the effects of tourists and researchers on fecal glucocorticoid metabolite...

Alizadeh, E. A., Graf, K., Schiwon, J. et al. 2023. Thirty years of telemetry-based data acquisition for cardiovascular drug safety evaluation: Applications and optimization. Journal of Pharmacological and Toxicological Methods 122, 107279.

Conducting safety evaluations of new drugs using conscious animals has been a specialty of our working group for thirty years. In this article, we review the various technical challenges and solutions dealt with over the...

Broche, N., Mouri, K., Suzumura, T. et al. 2023. Measuring short-term changes in stress-associated salivary analytes in free-ranging Japanese macaques (Macaca fuscata). Primates 64(4), 439–449.

Monitoring short-term changes of endocrine responses in non-human primates living in wild populations is a challenge. Saliva contains enzymes, steroids, and various analytes that can be broadly useful for helping us understand physiological responses to...

Sharma, S., Khanal, L., Shrestha, S. et al. 2023. Zoo visitors as a source of enrichment to reduce abnormal behavior in captive rhesus macaques (Macaca mulatta) in the Central Zoo, Kathmandu, Nepal. Journal of Animal Behaviour Biometeorology 11(1), e2023005.

Overexpression of abnormal behavior among captive primates indicates poor management practices. The type, frequency, and contributing factors of abnormal behaviors vary highly across individual animals in captive settings. This study explored if sex, rearing history...

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...

Kishida, T., Motokawa, Y., Yokoi, R. et al. 2022. Less invasive, simultaneous, and continuous measurements of locomotor activity and body temperature using the nano tag® small accelerometer device in cynomolgus monkeys. Journal of Pharmacological and Toxicological Methods 118, 107224.

Locomotor activity and body temperature evaluations of cynomolgus monkeys are useful to understand the effects of drugs on the central nervous system. Here, we describe a simple, inexpensive, and less invasive evaluation method using the...

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...

Tölgyesi, B., Bakker, J., Nagy, K. et al. 2021. Refined acquisition of high-resolution chest CTs in macaques by free breathing. Laboratory Animals 55(6), 551-559.

The use of medical imaging as a non-invasive or minimally invasive method to assess disease or treatment response continues to grow. A similar trend is observed in pre-clinical research, in general, and more specifically in...

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...

Sharpe, S. A., Scott, S., Taylor, I. et al. 2020. Use of high frequency jet ventilation as a refinement for imaging macaques with respiratory disease. Laboratory Animals 54(4), 386–390.

Imaging is used in human medicine to diagnose disease and monitor treatment efficacy. Computed tomography (CT) positron emission tomography (PET) and magnetic resonance (MR) are applied to animal models of infectious diseases to increase data...

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...

Reinhardt, V. (ed.) 2020. It’s Okay to Cry - Discussions by the Laboratory Animal Refinement & Enrichment Forum [LAREF], Volume V. Animal Welfare Institute, Washington, DC.

This is the 5th volume of selected discussions that took place on the electronic Laboratory Animal Refinement & Enrichment Forum between February 2016 and December 2019. The forum was created in October 2002; it allows...

Baker, K. C. 2020. Cage position and response to humans in singly-housed rhesus macaques (Macaca mulatta). JAALAS 59(5), 503-507.

Traditional laboratory caging for nonhuman primates is typically configured in a 2-tiered manner, with caging arranged in 2 horizontal rows stacked vertically. Studies of the effects of cage row have yielded inconsistent results with respect...

Carlstead, K., Paris, S., Brown, J. L. et al. 2019. Good keeper-elephant relationships in North American zoos are mutually beneficial to welfare. Applied Animal Behaviour Science 211, 103-111.

Relationships between animals and their human caretakers can have profound impacts on animal welfare in farms, laboratories and zoos, while human attitudes are important predictors of caretaker behavior towards livestock. In this study, we examined...

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...

Sherwen, S. L., Hemsworth, P. H. The visitor effect on zoo animals: Implications and opportunities for zoo animal welfare. Animals 9(6), 366.

Achieving and maintaining high standards of animal welfare is critical to the success of a modern zoo. Research has shown that an animal's welfare is highly dependent on how various individual animal factors (e.g., species...

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...

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...

Crawley, J. A. H., Lahdenperä, M., Seltmann, M. W. et al. 2019. Investigating changes within the handling system of the largest semi-captive population of Asian elephants. PLOS ONE 14(1), e0209701.

The current extinction crisis leaves us increasingly reliant on captive populations to maintain vulnerable species. Approximately one third of Asian elephants (Elephas maximus) are living in semi-captive conditions in range countries. Their relationship with humans...

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...

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...