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Alternatives and the 3Rs

Toxicology is the study of poisonous and harmful substances. Toxicity testing allows us to identify the toxicity of chemicals we use and gives information about the potency of their effects. As well as being true for industrial chemicals this is also true of pharmaceuticals and the natural products formed by plants, bacteria and fungi. Knowing whether a chemical can cause cancer, allergic reactions or abnormalities in unborn children is important to human health, and the process of discovering this information is known as assessment of hazard. This process is distinct from assessing risk which determines whether it is likely to actually cause harm in a given situation.


The use of animals must be replaced with alternative techniques, or avoided altogether.

Non-animal techniques are often a spin-off from advances in science and technology. New approaches such as tissue engineering, stem cell technologies and computer modelling show promise for replacing animals in some areas of research. But many alternative methods, such as cell cultures, often give only very limited information about what happens in a whole living animal. Effort devoted to replacing safety tests has produced some notable successes, particularly for assessing substances applied to the skin.

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The number of animals used must be reduced to a minimum, so that information is obtained from fewer animals or more information is gained from the same number of animals. Considerable progress has been made in finding ways to reduce the numbers of animals used in experiments. Further reduction may come from re-examining the findings of studies already conducted (e.g. by systematic reviews), by improving animal models, and by use of good experimental design.

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The way experiments are carried out must be refined to make sure animals suffer as little as possible. This includes better housing, and improvements to procedures which minimise pain and suffering and / or improve animal welfare.


Refinement not only benefits animals, but can also improve the quality of research findings by reducing the level of stress in animals. Any animal suffering must be kept to a minimum, for example, anaesthetics are used for surgery, and painkillers are given as necessary afterwards. If animals have a painful or fatal disease, they can be humanely killed before they show severe symptoms. Laboratory animals spend a lot of time in the animal house not being used in an experiment. Improving their living conditions is called environmental enrichment.

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Alternatives can also mean animals

Although the concept of alternatives is closely allied to the 3Rs, and particularly replacement, alternatives can also mean newer and better animal models. In vivo models may, with advances in methods and technologies, be replaced by in vitro techniques, which do not involve live animals, but still require animals to be bred and killed for scientific purposes.

The National Research Council (NRC) (USA) recently published a report laying out a modernising strategy for future toxicity testing. It recognises many of the problems and limitations with current methods, both in vivo and in vitro, and proposes a plan to address these issues using the current explosion of new technologies, noting that:

"For the foreseeable future, any in vitro strategy will need to include a provision to assess the likely metabolites through whole-animal testing"

And goes on to say that better animal models achieved with new technologies will be an integral part of future toxicology:

"Targeted testing might be conducted in vivo or in vitro, depending on the toxicity tests available. Although targeted [ie animal] testing could be based on existing toxicity-test systems, they will probably differ from traditional tests in the future. They could use transgenic species, isogenic strains, new animal models, or other novel test systems and could include a toxicogenomic evaluation of tissue responses over wide dose ranges. Whatever system is used, testing protocols would maximise the amount of information gained from whole-animal toxicity testing."

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Recent developments

There has recently been debate about acute toxicity testing and whether many of these early drug safety tests can be replaced by other methods. In January 2008, an extensive UK review of pharmaceutical toxicity testing, showed that data from a particular toxicity test can be gathered from other tests. This has already led to a 70% reduction in animal use in acute toxicity tests in the companies involved in the review, with greater reductions in animal use worldwide expected to follow.

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