Nikola M. Stojanović, Milica M. Todorovska

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Animals were first used for research purposes at the beginning of the development of both biology and medicine. However, the expansion in the use of animals for laboratory purposes began in the 19th century. During an experiment, animals may experience fear, deprivation, disease, and various degrees of pain. Animal Protection activists oppose to animal experiments and it is, therefore, necessary to harmonize the worldwide regulations on the use of animals for scientific purposes. More than 50 years ago, Russell and Burch were the first to define the 3R rule. It consists of the following three principles: Replacement, Reduction and Refinement. Over time, one more R was added to stand for Responsibility, meaning a responsible behavior of those who implement the 3R rule. Replacement means that, if possible, each experimental animal model should be replaced by an in vitro method or be reduced to a smaller number of animals used. Reduction is defined as a reduced number of animals used to obtain certain experimental information, while Refinement is a reduction in the frequency or severity of inhumane procedures applied to animals that have yet to be used. The 3R (+1R) rule has its drawbacks, but it is a very important aspect of animal use regulation, which is essential. These rules are used to direct animal users towards an adequate experimental model, but also to be a reminder of the appropriate use of experimental animals at a given time.


experimental animals, ethics in biomedicine, 3R + 1R rule

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