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. 
Bertani, S., Donadi, A., Franchi, J. et al. 2023. Blood microsampling in cynomolgus monkey and evaluation of plasma PK parameters in comparison to conventional sampling. Journal of Pharmacological and Toxicological Methods 123, 107298.

Microsampling, a reduced volume sampling method, has successfully gained attention at the International Conference on Harmonization (ICH) level and established benefits support its use in Toxicokinetic (TK) studies. These improved sampling techniques are less invasive...

Gilberto, D., Michener, M., Smith, B. et al. 2022. Chronic collection of cerebrospinal fluid from rhesus macaques (Macaca mulatta) with cisterna magna ports: Update on refinements. Comparative Medicine 72(1), 45-49.

More than 20 y ago, we developed an animal model for chronic and continuous collection of cerebrospinal fluid (CSF) from conscious rhesus macaques. Since our previous publication in 2003, we have successfully implanted 168 rhesus...

Stow, R., Kendrick, J., Ibbotson, N. et al. 2021. A new group housing approach for non-human primate metabolism studies. Journal of Pharmacological and Toxicological Methods 107, 106947.

Understanding the absorption, distribution, metabolism and excretion (ADME) of candidate drugs in preclinical species is an integral part of the safety and efficacy evaluation in drug development. For this purpose, the housing of single animals...

Houser, L. A., Ramsey, C., de Carvalho, F. M. et al. 2021. Improved training and semen collection outcomes using the closed box chair for macaques. Animals 11(8), 2384.

Collaborative semen collection in monkeys is a valuable tool in research, animal collection management, and conservation efforts. To obtain samples, monkeys are often restrained in open restraint chairs (ORC) with the “pole and collar” technique...

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...

Association of Primate Veterinarians. 2019. Association of Primate Veterinarians’ Position Statement: Cerebrospinal fluid aspiration for nonhuman primates in biomedical research. JAALAS 58(4), 428-429.

The Association of Primate Veterinarians (APV) recognizes that CSF collection may be required for both clinical and research purposes in nonhuman primates (NHP). Because there are inherent risks associated with the technique, the laboratory animal...

Gill, M. 2019. The Monkey Business and the UK: To what extent does EU and UK legislation protect long-tailed macaques bred in overseas farms but used for experiments in the UK. Canopy 20(1), 29-34.

Every year around 3,000 long-tailed macaques (Macaca fascicularis) are imported into the UK to satisfy the needs of pharmaceutical contract research organisations (CROs). CITES, and many NGOs suggest that the demand for macaques used globally...

Colby, L. A., Nowland, M. H., Kennedy, L. H. 2019. Clinical Laboratory Animal Medicine: An Introduction (5th ed). Wiley-Blackwell, Ames, IA.

The revised fifth edition of Clinical Laboratory Animal Medicine: An Introduction is an accessible guide to basic information for conducting animal research safely and responsibly. It includes a review of the unique anatomic and physiologic...

Rapp-Santos, K. J., Altamura, L. A., Norris, S. L. et al. 2017. Comparison of saliva collection methods for the determination of salivary cortisol levels in rhesus macaques (Macaca mulatta), cynomolgus macaques (Macaca fascicularis), and African green monkeys (Chlorocebus aethiops). JAALAS 56(2), 181-189.

The ability to quickly and accurately determine cortisol as a biomarker for stress is a valuable tool in assessing the wellbeing of NHP. In this study, 2 methods of collecting saliva (a commercial collection device...

Smedley, J., Macalister, R., Wangari, S. et al. 2016. Laparoscopic technique for serial collection of para-colonic, left colic, and inferior mesenteric lymph nodes in macaques. PLOS ONE 11(6), e0157535.

Unlike peripheral lymph nodes (PLN), the mesenteric lymph nodes (MLN) draining the gastrointestinal (GI) tract are exposed to microbes and microbial products from the intestines and as such, are immunologically distinct. GI draining (MLN) have...

MacAllister, R. P., Lester McCully, C. M., Bacher, J. et al. 2016. Minimally invasive lumbar port system for the collection of cerebrospinal fluid from rhesus macaques (Macaca mulatta). Comparative Medicine 66(4), 349–352.

Biomedical translational research frequently incorporates collection of CSF from NHP, because CSF drug levels are used as a surrogate for CNS tissue penetration in pharmacokinetic and dynamic studies. Surgical placement of a CNS ventricular catheter...

National Health and Medical Research Council [NHMRC]. 2016. Principles and guidelines for the care and use of non-human primates for scientific purposes. National Health and Medical Research Council: Canberra, Australia, 25 pp.

The Principles and guidelines for the care and use of non-human primates for scientific purposes is a revision of NHMRC’s Policy on the care and use of non-human primates for scientific purposes 2003 (the Policy)...

Caron, A., Lelong, C., Pascual, M. H. et al. 2015. Miniaturized blood sampling techniques to benefit reduction in mice and refinement in nonhuman primates: Application to bioanalysis in toxicity studies with antibody-drug conjugates. JAALAS 54(2), 145-152.

Minimizing the number of animals in regulatory toxicity studies while achieving study objectives to support the development of future medicines contributes to good scientific and ethical practices. Recent advances in technology have enabled the development...

Schillaci, T. T., Bishop, B. 2014. Effects of needle gauge on blood quality and potential for bruising with repeated blood collections in cynomolgus macaques. American Association for Laboratory Animal Science [AALAS] Meeting Official Program, 609-610. (Abstract #P226).

Obtaining quality blood samples while minimizing animal trauma related to venipuncture continues to be an important area of focus within the laboratory animal environment as it relates to both animal welfare and sample integrity. A...

Hrapkiewicz, K., Colby, L. A., Denison, P. 2013. Clinical Laboratory Animal Medicine: An Introduction (4th Ed). Wiley-Blackwell, Ames, IA.

Clinical Laboratory Animal Medicine: An Introduction, Fourth Edition offers a user-friendly guide to the unique anatomy and physiology, care, common diseases, and treatment of small mammals and nonhuman primates. Carefully designed for ease of use...

Bloomsmith, M., Franklin, A., Neu, K. et al. 2013. Training time required to collect a variety of biological samples using primarily positive reinforcement training methods. American Journal of Primatology 75(S1), 65. (36th Meeting of the American Society of Primatologists Scientific Program, Abstract #112)

Positive reinforcement training (PRT) methods can be applied to gain the voluntary cooperation of laboratory primates with the collection of biological samples. Information will be provided on training techniques used and the amount of training...

Weissman-Socci, S., Ray, K. D. 2011. Training rhesus macaques for conscious blood sampling in six steps. Tech Talk [The Newsletter for Laboratory Animal Science Technicians] 16(6), 3.

Step 1 Gently squeeze the animal about halfway towards you. Hold the animal in place for about 1 to 2 seconds.We use this time to talk to the animal calmly in a gentle voice. When...

Taylor K. 2010. Reporting the implementation of the three Rs in European primate and mouse research papers: Are we making progress? Alternatives to Laboratory Animals 38(6), 495-517.

It is now more than 20 years since both Council of Europe Convention ETS123 and EU Directive 86/609/EEC were introduced, to promote the implementation of the Three Rs in animal experimentation and to provide guidance...

Schapiro, S. J., Laule, G., Seelig, D. 2007. "Applied behavior" panel discussion. Journal of Applied Animal Welfare Science 10(1), 79-81.

Adriane and Kris just trained eight rhesus monkeys to present their arms in the blood sleeve for blood samples, and it took, on average ... 8 months ... 160 minutes spread out into 40 sessions.

Nelson, R. J., Mandrell, T. D. 2005. Enrichment and nonhuman primates: "First, do no harm". ILAR Journal 46(2), 171-177.

Since the 1998 publication of The Psychological Well-Being of Nonhuman Primates by the National Research Council, and the 1991 implementation of the 1985 Animal Welfare Act Amendment, many formal and informal nonhuman primate enrichment programs...

Kulpa-Eddy, J. A., Taylor, S., Adams, K. M. 2005. USDA perspectives on environmental enrichment for animals. ILAR Journal 46(2), 83-94.

This article provides a brief historical background of the events and circumstances that led to the 1985 Animal Welfare Act (AWA) amendments. It describes the development of the regulations promulgated by the US Department of...

Reinhardt, V. 2004. Flaws in federal regulations pertaining to the welfare of primates kept in research institutions. Journal of Applied Animal Welfare Science 7(4), 273-276.

Federal welfare regulations for primates kept in research laboratories fail (1) to include recommendations pertaining to the legal requirement of the avoidance of stress and unnecessary discomfort during handling procedures, (2) to specify how the...

Reinhardt, V. 2003. Working with rather than against macaques during blood collection. Journal of Applied Animal Welfare Science 6(3), 189-197.

12 adult pair-housed female, 5 adult single-housed male and 10 adult pair-housed male rhesus macaques, and 6 adult pair-housed female stump-tailed macaques were trained to cooperate during in-homecage blood collection. The total number of training...

Reinhardt, V. 2003. Legal loophole for subminimal floor area for caged macaques. Journal of Applied Animal Welfare Science 6(1), 53-56.

The USDA regulations pertaining to the minimum space requirements of nonhuman primates and the fitting of elevated resting surfaces are contradictory. They implicitly condone the prevailing perch design that allows maximal usage of animal room...

National Research Council. 2003. Guidelines for the Care and Use of Mammals in Neuroscience and Behavioral Research. National Academic Press: Washington, DC, 223 pp.

Expanding on the National Research Council’s Guide for the Care and Use of Laboratory Animals, this book deals specifically with mammals in neuroscience and behavioral research laboratories. It offers flexible guidelines for the care of...