Animal testing policy

Safe and healthy food, medicine, consumer products, and household chemicals, both at home and at work, are important to all of us. Research at TNO contributes to the development of these products and helps us predict whether substances are safe and effective. Sometimes animal testing is a necessary part of this research. Partly due to legal requirements and partly because there are no alternatives yet.

Our animal testing policy

We have formulated a meticulous animal testing policy, based on the following principles:

  • we only carry out animal testing if required by law or if no reliable alternatives are available
  • we actively contribute to the development and application of alternatives to animal testing (the three Rs: Reduction, Refinement, Replacement)
  • of course, we strictly adhere to the legal rules and regulations

Intrinsic value of animals

We attach great importance to the intrinsic value of each individual animal. That is why all experiments are subject to ethical review and careful treatment of the laboratory animals is paramount. Animal testing is only permissible when there is no suitable alternative and the purpose of the research outweighs any inconvenience to the animal. This decision is taken for each individual study, weighing up the ethical necessity. Animal welfare is ensured under strict legislation by an independent Animal Experiments Committee.

In addition, we actively participate in the social debate on the use of laboratory animals. We are well aware of developments in the field of animal testing that contribute to fewer animals or better living conditions and are keen to apply them ourselves.

Our policies

Our policy on the use of laboratory animals is part of our TNO Corporate Social Responsibility policy and is the official guideline for the TNO management and employees. A working group on animal testing and alternatives evaluates the policy annually and reports directly to TNO's Executive Board.

Animal welfare

Laboratory animals have the right to optimal care throughout their lives. We agree with the view that certain circumstances justify the use of laboratory animals. We also realise that by carrying out animal experiments, the researcher and TNO’s Executive Board are responsible for the ethical considerations and animal welfare. TNO's Animal Welfare department and our employees together ensure a 'culture of care' for laboratory animals.

Reduction, replacement, and refinement

Animal testing is only permissible when there is no suitable alternative and the purpose of the research outweighs the animals’ potential distress. The main principles are the reduction, refinement, and replacement of animal testing (3R). We operate within the boundaries of relevant legislation and, where applicable, according to quality criteria such as those of the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC).

Continuous improvement of methods

Animal testing has enabled progress in science and in human health and welfare. Despite this, there is a need in the field for methods for which the predictive value for people, i.e., patients, is better substantiated. Improvements of current methods are possible by developing and applying innovative 3R methods. This idea is embedded in our policies, research programmes, and communications.

Policy document

The TNO policy document on animal testing and alternatives also contains instructions on related topics, such as staff training, education, facilities, transparency, and accountability. In January 2018, we revised the policy to be in line with TNO’s 2018 - 2021 strategy period.

Download the policy document on laboratory animals and animal testing (pdf)

Evaluations and annual reports

Since 1985, a dedicated, independent animal testing committee has evaluated all tests involving animals. At the end of 2014, the Experiments on Animals Act was amended and since then this committee has been advising the Central Authority for Scientific Procedures on Animals. This makes the 2014 annual report the last report that the animal experiments committee submitted to TNO.

Our ambition

Our ambition is to conduct excellent biomedical research to improve human health. Both clinical and pre-clinical technologies are developed and applied for this purpose. In preclinical techniques, such as in silico, in vitro, and laboratory animals, the predictive value for humans is central.

New 3R methods

It is our ambition to develop new innovative 3R methods and to have these methods accepted for application more quickly. We are, therefore, engaging and collaborating with all relevant parties including academics, legislators and regulators, governments, and industry. We use our own research tools to replace, reduce, and certainly refine animal testing.

Transparency and communication

For us, transparency and communication are essential. We provide clear information about our activities and position on animal testing in order to establish a dialogue based on mutual respect.

This dialogue is strengthened by the objective exchange of information (without compromising the safety of researchers and laboratory animals or the confidentiality of research data), and maximum transparency.

In 2010, we committed ourselves to the Code for Transparency in Animal Testing and, in 2021, TNO signed the Dutch Transparency Agreement on Animal Testing. Central to both the code and the transparency agreement is that TNO engages with the various stakeholders on all aspects of animal testing. Openness about laboratory animal use and animal testing is one of the key issues in the corporate social responsibility (CSR) policy.

This year saw the completion of the 'Open-by-Design' pilot to which TNO also contributed. Following this, a start will be made in 2022 to actively publish granted animal testing applications on the TNO website.

Publications

We publish transparently and systematically about our animal testing, as recently laid down in the ARRIVE guideline (Animal Research: Reporting of In Vivo Experiments) and the 'golden standard checklist'. Our staff have also endorsed the 'Montreal Declaration on the Synthesis of Evidence to Advance the 3Rs Principles in Science (pdf, 582 kB). In addition, our animal testing-based publications contain the information essential according to international guidelines in order to prevent the repetition of animal testing and to enable meta-analysis.

Innovations to which we contribute

The Netherlands wants to be at the forefront of the international transition to non-animal innovation. We work together with companies, governments, academic institutions, and civil society organisations on this transition by developing and applying technologies that contribute to this goal. For example, we are working with our partners on the Transition to Non-Animal Innovation (TPI) project initiated by the Dutch government, with the aim of speeding it up.

Transition to non-animal research

We want to accelerate the transition to non-animal research and are working on new technologies to do so:

  • Organ-on-a-chip': human stem cells are cultured on a chip to mimic specific human organ functions.
  • ‘Microtracing: also known as 'microdosing', this is a highly specialised technique involving the administration of very small, non-harmful quantities of drugs to humans. It can help to study what the human body does with the drug and vice versa.
  • In Silico systems.
  • Research using ex-vivo human material.

Han van de Sandt, Head of Metabolic Health Research at TNO, explains: ‘Our role at TNO is to look beyond the hype, by tackling the scientific foundations of new research. And to match the supply of innovations with industrial demands through contacts with industry in order to achieve practical implementation.’

Microdosing

With advanced technology, it is possible to collect the kinetic data of new drugs and innovative food ingredients more quickly than is currently the case. This greatly reduces the need for animal testing prior to the clinical phase. We carry out this research using an Accelerator Mass Spectrometer (AMS). This is an instrument that supports microdosing studies in humans and is available at TNO. In Europe, TNO is the first organisation to make AMS services available to pharmaceutical, biotech, and innovative food companies.

Animal testing alternatives

We aim to reduce, refine, and replace animal testing and have established a research programme for this purpose. Once we have found ways to improve research methods, it becomes our top priority to gain wide acceptance and actually implement these 3R improvements.

Reduction

We aim to reduce the number of animals used for testing. We regularly evaluate our testing methods and implement integrated testing strategies. This is how we determine whether animal testing is necessary or whether the same information can be obtained by other means. In addition, for experiments in which only tissue from laboratory animals is needed (but not the intact animal), animals from other experiments or from control groups (within or outside TNO) are used, so that laboratory animals are used as optimally as possible.

Refinement

We strive to develop and adapt testing methods to minimise discomfort and stress to laboratory animals. We do this by using state-of-the-art techniques and continuously optimising suitable human and experimental endpoints.

Replacement

We aim to replace animal testing with other methods, preferably using human tissue and cells. Wherever possible, we use human samples. Examples include:

  • TIM: TNO’s unique gastrointestinal models for research on digestion of food or drug kinetics. We are trying to use this to replace animal testing with alternative research methods.
  • A test to determine the effects of (chemical) substances on eye irritation. This method uses unused tissue from slaughterhouse chickens instead of live animals. This has been formally accepted by the OECD, an international organisation for cooperation and economic development.

Encouraging employees

At TNO, we foster a stimulating environment in which our employees are encouraged to contribute their own ideas to make research more animal friendly. If a method offers improvement while maintaining the same research results, we make the new method available to others.

Award-winning

In 2010, we received our first award from the Dutch Committee for the Replacement, Reduction, and Refinement of Animal Testing. This was prior to our efforts to reduce discomfort in animals during inhalation tests. Our modified design helps to reduce the distress of 50 to 70% of the 500 to 700 rats annually exposed to inhalation at TNO (distress is reduced particularly in young and female animals).

This is an improvement on the commercially available materials. The manufacturer has joined us to look at the possibilities of making the adapted materials available to other users.

Encouraging employees to contribute ideas is also paying off. In 2021, we were once again given an award for refinement of animal testing at the DALAS symposium. This was before all optimisations made by the animal testing researchers to the diabetic renal failure model. These optimisations included the introduction of ‘tube-handling’ which eliminates lifting the animals by the tail, heated racks, and improved measuring methods. All these aspects enabled the animals’ distress in these tests to be significantly reduced.

Imaging

Imaging is used as a diagnostic tool in hospitals to monitor changes over time. But it is developing all the time, and our scientists are studying how imaging can refine or reduce animal testing. Imaging allows a laboratory animal to be followed over a period of time. This allows the effects of a disease or treatment to be viewed at different stages. In addition, imaging is usually minimally invasive, which reduces stress and discomfort in laboratory animals and improves study results. More extensive research is needed on the application of imaging and the additional benefits.

Our collaborative partnerships

In order for parties involved in legislation and regulation to think differently about animal testing and alternatives, it is essential to consider a broader perspective. The whole area needs to change its mindset. An organisation can be a catalyst for change. That is why we are participating in various groups to encourage dialogue and find ways to make the 3R principles work.

Intensive interaction between industry, academia, governments, and regulatory authorities is needed to accelerate the acceptance and validation of alternatives. We proactively provide information through scientific publications and lectures. Here are some examples of our network.

National platforms

We participate in:

  • The National Knowledge Centre for Alternatives (Het Nationaal Kenniscentrum Alternatieven or NKCA).
  • Dialogue and TRAIN (Three Rs Alternatives Initiating Network).
  • Discussion groups with other interested parties, including animal welfare organisations and political parties, with the aim of sharing our views on animal testing, creating respect, and exploring common goals.

International platforms

Our employees are also active within various international platforms:

  • European and national authorities, such as the European Food Safety Authority (EFSA) and the Health Council.
  • The Organisation for Economic Cooperation and Development (OECD) sets international requirements for safety testing, among other things. Our employees are involved in various working groups. Regarding the 3Rs, the OECD has officially recognised alternative tests, such as the Inoculated Chicken Eye test (ICE).
  • European and national associations that promote the development and use of alternatives to animal testing, such as IVTIP, INVITROM, and ESTIV.

Collaborative projects

We work with various links in the chain on a range of projects. For example, on the Peaks in the Delta project called SLIM (‘Sneller van Innovatie naar Mens’, or Faster from Innovation to People). This was commissioned by the Municipality and Province of Utrecht and the Ministry of Economic Affairs, Agriculture, and Innovation and aims to bring innovative food and drugs from the laboratory to the clinic more quickly. The goal is to develop good practices to speed up acceptance of alternative testing methods.

Education

Young scientists are the key to the future of science and 3R research. To extend the training of young scientists, we support two university chairs: Alternatives to Animal Testing at Utrecht University of Applied Sciences and Translational Toxicology at Wageningen University.

Facts and figures

Animal testing is carried out with the utmost care. Over the past 35 years, the use of laboratory animals in the Netherlands has been more than halved. Also, at TNO, the number of animals used for testing has been significantly reduced. After a sharp decline in 2013, thanks to a revised breeding policy, our number of laboratory animals has remained stable in recent years, although a decrease in the number of laboratory animals was seen in 2020 as a result of Covid-19, which continued in 2021.

Species

Summary of total number of animal tests per year from 2015
2015 2016 2017 2018 2019 2020 2021
3247 3032 2636 3180 2758 2102 1217

The choice of an animal species for use in an animal experiment depends on its predictive value for humans. They mainly include rodents (mice, rats, and guinea pigs) due to the wide availability of historical data and proven translatability of the models used.

However, rodents are not always the best model for humans and, therefore, other animal species are sometimes used. For example, a small number of pigs were used as animal models in 2021. The use of improved translatable models prevents unnecessary animal testing.

Rodents

Animal species used for experimental research within TNO
Type of animal Number of animals Percentage
Mice 919 75.5%
Rats 118 9.7%
Guinea pigs 178 14.6%
Pigs 2 0,2%
Total 1217 100%

In 2021, we used mainly rodents in research, namely mice (76%), guinea pigs (15%), and rats (10%). More than three quarters of the mice are transgenic. These animals are implanted with a human gene, so the disease development in these animals is very similar to humans. Much research has been done with these transgenic mice so that we know which aspects of human diseases they are suitable for, and which they are not.

Focus on efficiency

We breed the special mice ourselves, making sure that the animals that are born are used as efficiently as possible. One of the ways in which we do this is by coordinating breeding centrally and by joining a national network of breeding coordinators in order to match supply and demand as closely as possible. This prevents a breeding surplus as much as possible.

Effective partnerships

If animal organs or tissues are required for research, we do everything we can to avoid killing animals specifically for this purpose. For example, we have a collaboration agreement with several slaughterhouses for the supply of fresh pig tissue. We also have a collaboration agreement with Utrecht University and other institutes in the Netherlands to obtain organs and tissue from animals that have been killed for veterinary training or have been used in studies.

Through these collaborations, we obtained tissue for testing without killing any additional animals. This has been used, for example, for research into the absorption of substances by the intestine, for which, among other things, fresh intestinal material is needed.

In addition, we collaborate with hospitals, which allows us to regularly use fresh human material for research. We are active within the national VitalTissue project, an initiative that helps researchers in the Netherlands to obtain vital remnant human tissue. In addition to the improved translatability of research results, this method contributes to the reduction of animal testing.

Objectives of animal testing

At TNO, we conduct research into social issues. The results are used to cure and prevent conditions and diseases such as metabolic syndromes, obesity or cardiovascular diseases. We also study recovery from acute intoxications and the reduction of possible consequential damage. The purposes of animal testing are:

applied and translational research (85%), basic scientific research (13%), education (2%).

Applied research

The majority of animal tests (97%) concern the efficacy (effectiveness) of medicines or therapies. Our applied research is largely into metabolic diseases and protection against intoxication.

Basic scientific research

In addition to applied research, we also conduct basic scientific research into the mechanisms of diseases (0.2%).

Education

For the education and continuous training of staff, the refinement of research techniques, and the implementation of new research techniques and models, laboratory animals are used on a small scale (educational purposes): 3%).

Number of animals used for the various research objectives within TNO
Objective Number of animals Percentage
Basic scientific research 2 0.2%
Applied and translational research 1179 96.8%
Education 36 3.0%
Total 1217 100%

Expertly trained staff contribute directly to the responsible use of laboratory animals. It is important to note that, for the training of staff, animals can usually be used that are not purchased specifically for this purpose, but which were present in the facility and could no longer be used in other experiments.

Prior to animal testing

Before animals are used, a replacement solution is sought. Is the use of animals unavoidable? We will then look into whether the study can be carried out with fewer animals, or whether methods can be refined. TNO also complies with the frameworks laid down in the  Experiments on Animal Act regarding the internal supervision of animal testing.

Animal Welfare Department

An Animal Welfare Department (IvD) has been set up within TNO. This department assesses whether the experiments contribute to the goal defined in the licences. The IvD also supervises the workplace and is a source of information for all animal-related research. The chairperson of IvD is not part of the departments that carry out animal experiments. This establishes an additional independence step.

Preventing distress

If animal testing is necessary, we strive for the least possible distress for animals and the least possible number of animals required. In most cases, the test animals experience mild or moderate distress. Where possible, we reduce this, for example by earlier humane endpoints, better living conditions (such as cage enrichment), better testing methods or the use of pain relief.

Classifications

In a limited number of studies, an animal is anaesthetised for the purpose of the experiment, and waking the animals is not necessary to achieve the results. In this way, the animals experience as little distress as possible. Internationally, such studies are therefore classified separately as 'terminal'.

At TNO, this concerns about 1.6% of animal experiments. Other animal experiments are classified as mild, moderate or severe distress according to the general guidelines.

Mild distress

In 61% of animal experiments, mild distress is involved. An example type of experiment that falls into the 'mild distress' category is feeding animals a specific diet, for example a high or low fat diet. The animals are not bothered by this, but they are weighed from time to time, for example.

Moderate distress

In 35% of the animal experiments, there is moderate distress. In this case, it is necessary, for example, to inject the animals weekly and over a longer period with a substance to be studied, to take regular blood samples or to subject the animals to a light intervention under anaesthesia. Where possible, procedures are combined to reduce the number of interventions per animal. Pain management is also applied to animals undergoing minor surgery.

Severe distress

Severe distress is caused in 3% of animal experiments. This involves testing the efficacy of drugs, where animals have certain symptoms. Inducing these symptoms in an animal can lead to ‘severe distress’.

We test drugs for, among others, pulmonary fibrosis and to combat the effects of intoxications. In these studies, we choose the earliest possible experimental endpoint, so that the experiment can be stopped as soon as acceptable results are obtained and the animals are in distress for the shortest possible period of time.

Monitoring

All animals are monitored daily for distress, and there is a special procedure if an animal requires additional attention.

Importance of animal welfare

We value animal welfare and therefore have an AAALAC accreditation for our Leiden location. AAALAC stands for Association for Assessment and Accreditation of Laboratory Animal Care and is a globally accepted organisation that aims to optimise animal welfare through a voluntary accreditation and assessment programme. This goes beyond the minimum legal requirements for animal testing.