Questions and answers on animal experiments at the German Federal Institute for Risk Assessment (BfRshort forGerman Federal Institute for Risk Assessment)

As the home of the German Centre for the Protection of Laboratory Animals (Bf3R), the BfRshort forGerman Federal Institute for Risk Assessment applies the principle, also stipulated by law, of avoiding the use of living animals, using the smallest possible number of animals to carry out testing, and ensuring their greatest possible comfort and reducing stress as far as possible. This principle is also known as the 3R principle (see: ‘What is the 3R principle?’). For this reason, all planned animal experiments are thoroughly examined before starting in order to determine whether alternative methods (replacement) can be used instead of live animals. If this is not possible, complex statistical methods are used to determine the smallest possible number of animals that need to be used to answer the research question (reduction). All animals are kept and cared for at the BfRshort forGerman Federal Institute for Risk Assessment under the best possible conditions before, during and, if necessary, after being used for animal experiments, so as to meet the needs of each species and improve their welfare (refinement).

As part of its statutory responsibilities, animals are used at the BfRshort forGerman Federal Institute for Risk Assessment to develop replacement methods and establish better welfare and testing conditions which can be used internationally. The second major area for which animals are used in experiments is research into the safety of food and animal feed. The aim of these tests is to identify and assess the risks for humans as well as animals used for food production.

In accordance with its broad range of activities the BfRshort forGerman Federal Institute for Risk Assessment keeps mice, rats, guinea pigs, hamsters, rabbits, chickens, pigs, sheep, goats, cattle, shrimps, farmed fish and danios and uses them for scientific research. Some animal species, such as chickens or guinea pigs, are only used in individual experiments and are therefore not kept every year. Other animal species, such as mice, are used in various projects every year.

Refinement: In accordance with Article 4 of European Directive 2010/63/EU on the protection of animals used for scientific purposes, particular emphasis is given to ‘refinement’ by the Member States. This means that any pain, suffering, distress or lasting harm to an animal needs to be avoided or minimised as far as possible. The units set up at the BfRshort forGerman Federal Institute for Risk Assessment to focus on ‘laboratory animal science’ and animal husbandry research how to determine pain and distress of laboratory animals as objectively as possible as well as how to reduce them. The aim is to establish better welfare, preparation and testing conditions.

Safety of food products and animal feed: As part of its statutory responsibilities, the BfRshort forGerman Federal Institute for Risk Assessment conducts animal experiments to assess the safety and possible contamination of animal feed. Cattle, pigs or chickens are used in animal experiments to determine whether, for example, substances from the environment or feed are absorbed by the animals and whether they make their way into food products.

Preparation of reference material: The statutory responsibilities of the BfRshort forGerman Federal Institute for Risk Assessment include the development and improvement of methods for detecting pathogens that may be transmitted to humans via food products and for detecting undesirable or prohibited substances in food products. In addition, the National Reference Laboratories regularly verify the methodological competence of the official testing authorities. This necessitates animal reference material. It is either taken from untreated animals that are proven to be free of the pathogens or substances in question, or from animals that have been specifically infected with certain pathogens or treated with substances. Depending on the specific method, faeces, spontaneous urine, hair or feathers, eggs, milk, blood or meat are used as reference material.

Training: The German Animal Welfare Act and the Ordinance on the Protection of Laboratory Animals stipulate that only persons with proven expertise are allowed to be involved in the care of laboratory animals and in animal experiments. For this reason, the BfRshort forGerman Federal Institute for Risk Assessment trains animal care staff that specialise in research and clinical care and is part of the Berlin training association for this specialisation. Initially, many different training methods are used that do not require the use of animals, such as theoretical instructions, training videos, working with artificial models, and practical training in day-to-day tasks. Only when these methods have reached their limit, certain procedures are allowed to be practised on live animals, so that they can be applied safely in experiments and the laboratory animals are exposed to as little stress as possible.

Reduction: One project showed that the reproducibility of test results can be increased by familiarising the animals with the test apparatus beforehand (habituation). This is primarily achieved by reducing the random variability of the data in favour of stable behavioural patterns that develop through habituation. The targeted use of such habituation measures can significantly reduce the number of laboratory animals required.

In 2024, 8 animals were used in experiments at the BfRshort forGerman Federal Institute for Risk Assessment. A total of 4 pigs and 4 cattle were used in two approved projects. Both projects were associated with low stress levels for the animals. In addition to the animals used in experiments, 15 mice were killed to use their organs to develop methods for replacing animal experiments. 77 chickens were killed so that their organs could be analysed for studies into food safety. These animals were not subjected to any stress before their death and were killed painlessly. The same applied to 244 danios, which were used for breeding and killed at an advanced age to avoid stress and suffering.

The BfRshort forGerman Federal Institute for Risk Assessment is authorised by the Berlin State Office for Health and Social Affairs to keep up to 70 cattle, 90 sheep, 60 goats, 65 turkeys, 300 chickens, 170 pigs, 50 rabbits, 20 guinea pigs, 10 hamsters, 100 rats, 1,000 mice, 600 edible fish, 2,500 danios and 70 cephalopods on its premises.

These numbers, which need to be reapplied for every five years in accordance with the current rules on keeping laboratory animals, are the maximum permissible number of each species of animal that may be kept in suitable rooms and pens at the same time. The actual numbers of animals that are kept and used in animal experiments depend on the projects and the numbers deemed essential for the individual animal experiments. At no time may these be higher than the total authorised number for the premises.

The Berlin State Office for Health and Social Affairs provides further information on the requirements for keeping laboratory animals on its website: External Link:https://www.berlin.de/lageso/gesundheit/veterinaerwesen/tierschutz/versuchstierhaltung/.

The 3R principle was published in 1959 by the British scientists William Russell and Rex Burch and enshrined in law in the 2010 European Directive 2010/63/EU on the protection of animals used for scientific purposes. The aim of the 3R principle is to completely avoid animal experiments (replacement) or to limit the number of animals (reduction) and their suffering (refinement) in experiments to the absolute minimum. All persons and organisations that carry out animal experiments are legally obliged to act in accordance with this principle.

Further information on the 3R principle can be found on the Bf3R website: External Link:https://www.bf3r.de/en/.

Various research projects are being planned and carried out continuously at the BfRshort forGerman Federal Institute for Risk Assessment to replace animal experiments. Some examples are given below. The list is by no means exhaustive.

Cell and tissue culture methods are being developed at the BfRshort forGerman Federal Institute for Risk Assessment to completely replace an experimental method that uses animals with an alternative method. They should form the foundation of new, animal-free alternative methods for basic research and toxicological assessment. For example, research projects for basic biomedical research include:

• Bone-on-a-chip / organ-on-a-chip systems
• Development of an in vitro implantation model (MIVI)
• A search engine for alternatives to animal experiments (SMAFIRA)

Research projects for toxicological risk assessment

• Development of an alternative method for testing the carcinogenic potential of hormonally active substances
• Alternative methods to animal experiments for the detection of hormonally active effects in vitro
• Influence of circadian regulatory systems on in vitro test methods
• Toxicological in vitro studies on the combination effect of fungicides
• Computational toxicology: Role and importance of novel methodological approaches in health risk assessment
• Establishment of integrated approaches to testing and assessment (IATAs) to support nanomaterial groupings and for other toxicological issues
• Prediction of the sensitising potential of chemicals and products in vitro in the human system as a substitute for animal experiments
• Development of ‘tattooed’ 3D skin models
• Establishment of co-culture models consisting of microbially colonised 3D skin models to determine the microbial-induced modulation of the toxicity of pesticides
• Development of colonised melanoma models to determine the microbial influence on human tumour progression.
• In silico methods for predicting the adverse health effects of pesticides
• Development of an animal-free test strategy for the risk assessment of pesticides as complex mixtures
• Use of in vitro methods, e.g. to understand the fermentation processes in the rumen of cows (e.g. in the breakdown and conversion of plant toxins) or the digestive processes in the gastrointestinal tract of pigs

In addition, the BfRshort forGerman Federal Institute for Risk Assessment is involved in several international projects in which alternative methods are being developed, such as External Link:PARC or External Link:RISK-HUNT3R.

Further information on the projects can be found on the Bf3R website: External Link:https://www.bf3r.de/en/research/replace/.

Various research projects are being planned and carried out continuously at the BfRshort forGerman Federal Institute for Risk Assessment to reduce the number of laboratory animals used in experiments. Some examples are given below. The list is by no means exhaustive.

For example, in order to find ways of reducing the number of laboratory animals used in research, the BfRshort forGerman Federal Institute for Risk Assessment is researching new statistical and bioinformatic analysis models. The aim is to use them to determine which methodological and institutional changes to research and the publication process could contribute to fewer animal experiments being carried out. At the same time, the BfRshort forGerman Federal Institute for Risk Assessment is using new biometric approaches to make the statistical planning of experiments more efficient with and without the use of laboratory animals. This should reduce to the minimum the number of animals required for planned research projects involving laboratory animals. In a further project, it was shown that the reproducibility of test results can be increased by familiarising the animals with the test apparatus beforehand (habituation). This is primarily achieved by reducing the random variability of the data in favour of stable behavioural patterns that develop through habituation. The targeted use of such habituation measures can significantly reduce the number of laboratory animals required.

Further information on the projects can be found on the Bf3R website: External Link:https://www.bf3r.de/en/research/replace/.

Various research projects are being planned and carried out continuously at the BfRshort forGerman Federal Institute for Risk Assessment to minimise the pain and suffering of laboratory animals. Some examples are given below. The list is by no means exhaustive.

In order to reduce conditions such as pain, suffering or distress in laboratory animals and at the same time increase the quality of test results, measures to reduce stress and improve welfare are being researched. In addition, evaluation criteria are being developed for assessing the levels of stress. Examples of previous research projects include:

• Improving the housing conditions of laboratory animals
• Effect on the animals of alternative housing systems with enriched environments
• Development of choice experiments to determine needs from the perspective of the laboratory animals - which food, rewards and enrichment activities are preferred?
• Development of home cage-based testing methods in which animals voluntarily participate in the tests (e.g. learning experiments integrated into the housing system)
• Influence of chronic monotony and boredom on the psychoemotional behaviour and cognition of laboratory animals
• Automated recognition of stress based on facial features
• ‘Animal personality’ - personality traits and their effect on experiment results and their reproducibility
• Pain perception in fish (using the danio as a model organism)
• Methodology and efficacyClose dialogefficacyPositive Predictive ValueTo glossary of training measures for laboratory animals.

Further information on the projects can be found on the Bf3R website: External Link:https://www.bf3r.de/en/research/refine/.

The State Office for Health and Social Affairs is responsible for the inspection and authorisation of animal experiments in the German federal state (“Land”) of Berlin. Every experiment planned at the BfRshort forGerman Federal Institute for Risk Assessment requires a written application which is submitted to the Berlin State Office for Health and Social Affairs. Beforehand, the BfRshort forGerman Federal Institute for Risk Assessment discusses and plans each experimental project in detail internally with the animal welfare officers, and the BfRshort forGerman Federal Institute for Risk Assessment Animal Welfare Committee is also involved. We adhere strictly to the 3R principle: First of all, we check whether the objective of the experiment can also be achieved using animal-free methods (‘replace’). If this is not the case, the number of animals to be used is selected to ensure that the lowest possible number of animals is used (‘reduce’). This is achieved by careful statistical calculation when planning the animal experiments. In addition, the experimental conditions are intentionally designed such that pain, suffering and harm are reduced to the absolute minimum (‘refinement’). Examples include the continuous improvement of the conditions in which the animals are kept, the design of their environment and the handling of the animals. Training laboratory animals for certain procedures reduces stress and results in less pressure. If painful procedures are carried out, an appropriate painkiller is administered.

The experiments may only be carried out by specifically trained staff. These staff members are named in the application. The Berlin State Office for Health and Social Affairs checks the application documents for completeness and clarity and consultation is provided by an independent commission for animal experiments. All questions about the experimental project that are brought up during this process are answered in writing and checked again by the Berlin State Office for Health and Social Affairs. Once all of the questions have been adequately answered, a notice of authorisation can be issued for the requested experiment for a maximum of five years.

The authorising authority, in Berlin the State Office for Health and Social Affairs, is responsible for monitoring animal experiments. The Berlin State Office for Health and Social Affairs monitors the experiments by making announced or unannounced visits. Internally, all animal experiments are monitored by the BfR’s animal welfare officers. In addition to their veterinary training, these officers have a specific qualification in the field of laboratory animal science. It is in the interest of all persons involved in the experiment that the experiments are carried out in accordance with the regulations and are documented accordingly. The BfR’s Animal Welfare Committee discusses ongoing and completed animal experiments with the project leaders and all persons involved in the experiment and makes recommendations for future projects, in particular to improve animal welfare. It also continuously checks whether the living conditions of the animals and their welfare can be improved both during and outside of animal experiments.

Some species are bred specifically at the BfRshort forGerman Federal Institute for Risk Assessment for its own experiments. Other animals are purchased from specialised laboratory animal breeders or from selected farms according to legal requirements.

When an application is made to conduct an animal experiment, the maximum level of stress that the experiment may cause an animal is determined. All procedures are defined to minimise the stress as far as possible. This includes suitable painkillers as well as sufficient recovery time and a species-appropriate environment (including factors such as suitable toys or lighting conditions). The German Animal Welfare Act requires animals to be constantly monitored during the experiment. The animals are systematically and regularly examined for signs of stress. When a defined stress limit is reached, the experiment is discontinued for the animal affected. The monitoring of signs and the point at which the animal needs to be removed from the experiment are authorised in advance by the competent authority, which checks compliance. All those involved in the animal experiment are required to continually apply veterinary and care measures to improve the well-being of the animals and to reduce any stress.

What happens to the animals after the experiment depends mainly on the type of experiment. For some experimental purposes, it is necessary to euthanise the animal in accordance with animal welfare regulations to be able to carry out further examinations of the organs. If it is possible for animals to live on without impairments to their welfare and without posing a hazard for humans, other animals or the environment, they either remain at the BfRshort forGerman Federal Institute for Risk Assessment or an attempt is made to place the animals with competent private individuals.

As part of the German Animal Welfare Initiative of the German Federal Ministry of Agriculture, Food and Regional Identity (BMLEH), the German Centre for the Protection of Laboratory Animals (Bf3R) was founded at the BfRshort forGerman Federal Institute for Risk Assessment in 2015. The centre coordinates nationwide activities with the aim of limiting animal experiments to the minimum necessary and ensuring the best possible protection for laboratory animals.

Selected questions and answers can be found here: External Link:https://www.bfr.bund.de/en/service/frequently-asked-questions/topic/questions-and-answers-about-the-german-centre-for-the-protection-of-laboratory-animals-bf3r/.

On 7 January 2019, the German Centre for the Protection of Laboratory Animals at the BfRshort forGerman Federal Institute for Risk Assessment launched the digital animal study registry External Link:www.animalstudyregistry.org. The registry was set up in response to the reproducibility crisis and gives scientists a platform for registering an exact study plan before starting their studies and thus prevents selective reporting. In addition, more transparency is provided worldwide by the animalstudyregistry.org. New fields of research and development for greater animal welfare can thus be identified.

Further information on this can be found in our FAQs: External Link:https://www.animalstudyregistry.org/asr_web/asr.web.static.action?name=asr.links.faq.

The legislator has also assigned the BfRshort forGerman Federal Institute for Risk Assessment the task of publishing generally understandable project summaries (NTP) of approved animal experiments projects in Germany in anonymised form. The investigators submit these summaries to the competent authorities together with the authorisation application. The BfRshort forGerman Federal Institute for Risk Assessment publishes them in the online database AnimalTestInfo (External Link:www.animaltestinfo.de), to inform the public about animal experiments. In addition, the BfRshort forGerman Federal Institute for Risk Assessment sends NTPs to the European database ALURES.

Explanatory background information on this can be found here: External Link:https://www.bf3r.de/en/offers/for-private-citizens/animaltestinfo/.

In accordance with Section 15a of the German Animal Welfare Act, the BfRshort forGerman Federal Institute for Risk Assessment also performs the role of the ‘National Committee for the Protection of Animals Used for Scientific Purposes’ - or National Committee for short - for the Federal Republic of Germany. The National Committee advises the competent German authorities and animal welfare committees on matters relating to the acquisition, breeding, housing, care and use of animals in procedures according to the German Animal Welfare Act. It ensures that there is an exchange of best practice in Germany and also shares information with other national committees within the European Union on the functioning of animal welfare committees, project assessment and best practice.

More background information as well as the statements and recommendations of the National Committee can be found here:

External Link:https://www.bf3r.de/en/offers/for-national-authorities/national-committee/ .

In 2021, the BfRshort forGerman Federal Institute for Risk Assessment was commissioned by the BMLEH to report the number of laboratory animals used annually. The data collected annually by laboratory animal facilities and submitted to the BfRshort forGerman Federal Institute for Risk Assessment by the relevant authorities was published on the Bf3R website for the first time for the reporting year 2020. The BfR’s legal mandate has since been enshrined in the German Laboratory Animal Reporting Ordinance (Section 2 VersTierMeldV). In this context, the BfRshort forGerman Federal Institute for Risk Assessment also sends the German laboratory animal numbers to the European Commission.

Current laboratory animal statistics can be found on the Bf3R website: External Link:https://www.bf3r.de/en/offers/laboratory-animal-numbers/.

The ‘Transparent Animal Experiments Initiative’ is a joint project of the Senate Commission on Animal Experimental Research of the German Research Foundation (DFG) and the ‘Understanding Animal Experiments’ initiative of the Alliance of Science Organisations in Germany, which was launched on 1 July 2021.

The BfRshort forGerman Federal Institute for Risk Assessment not only supports this initiative, but was also one of the first signatories. The declared goals include transparent information and open communication about animal experiments in research. The BfRshort forGerman Federal Institute for Risk Assessment and its German Centre for the Protection of Laboratory Animals (Bf3R) have been active in this area for many years. The BfRshort forGerman Federal Institute for Risk Assessment is committed to ensuring that animal experiments are transparent to the public. The BfR’s AnimalTestInfo and AnimalStudyRegistry databases are intended to make studies more comprehensible and avoid unnecessary animal experiments.