We work to nuture the aspiration for change and give the general public as well as the scientific community and NAMs stakeholders a wider and deeper understanding of what exists today – what tomorrow could be – and how to get there.
TATABOX is an edutainment game meant to open a conversation about NAMs and validation process in a fun and convivial environment. During a meeting, as a team building activity, or during a training, TATABOX gathers players around a common goal and fosters exchanges about research methods.
2 to 4 players – 30min per game
TATABOX tiles are not meant to be exhaustive in terms of content as well as persona but rather a starting point for discussion with concrete items within a team on the process towards alternatives to animal testing. Moreover, through brainstorming the participants can create synergy and common goals on a personalized validation path based on the institution technology/models to illustrate their work as well as better understanding of the critical steps necessary for regulatory acceptance.
You are a scientist who dreams of developing and validating a new research method without using laboratory animals. What a good idea! ALTERTOX team is here to help you understand the specific steps allowing you to do and validate your research in the most rigorous way!
With in silico or in vitro methods, create the most suitable path to validation. In TaTaBox, all players build the deck, each game is different.
Using your sector power strategically and skillfully collaborating with other scientists will be essential to succeed and save as many animals as possible!
Will you be able to validate your method and thus participate in the shift of science towards alternatives to animal experimentation?
A project supported by the team SeriouslyFun!
- Artificial intelligence is used in toxicology to predict the effect of a chemical on a living organism. The main applications are machine learning and deep learning. (tile n6)
- Attend a congress. Even without a poster or a lecture to give, a congress is a perfect way to share with experts and cultivate your network. (tile n60)
- Case studies in toxicology are in-depth analysis on a specific subset of chemicals or exposure situations which can prove or strengthen a scientific conclusion. For example, suppose a theory claims that chemicals in water lead to neurological defects in fish. In that case, a case study on a specific water region where such chemicals are present in known concentrations could support that theory and explain why. Case studies are particularly useful to support the validation of a method. (tile n39) validation of a method.
- A 2D cell system is the classical method of cultivating cells on a flat surface. Cells from many human/animal organs can be grown and used to test chemical/substance toxicity. (tile n8)
- A 3D cell system is a modern technique where cells can grow in all directions thanks to the presence of specific scaffolds in the dish. In such a setting, cells create structures similar to real organs, which can be used to test chemical/substance toxicity. (tile n9)
- Collaboration with national regulatory agencies: When developing a new method, it is beneficial to include the regulatory agencies in the process since they will be the ones deciding whether the technique can be used. (tile n44)
- Data analysis is the process of systematically applying statistical and/or logical techniques to describe,illustrate, condense,recap and evaluate data. (tile n29)
- Data curation and cleaning is the process of collecting all the information related to these data, such as how they have been collected, where they have been stored and how others can reuse them. (tile n16)
- A data management plan is a series of procedures to collect and store scientific data in a standardised way. Detailed information on how the data have been generated and catalogued help other scientists exploit them for new studies which improves scientific reproducibility. (tile n12)
- A defined unambiguous algorithm refers to an algorithm that is both clear and straightforward to the point that any person can follow its steps and reach the correct conclusions. (tile n30)
- A defined endpoint in toxicology is the result of a study conducted to determine how dangerous a substance is. The data collected are often used to report the substance’s toxicity to regulatory agencies. Endpoints can include mortality/lethality, behaviour, reproductive status or physiological and biochemical changes. (tile n14)
- Define acceptance criteria is the process of specifying which characteristics/parameters/results a method must present to be accepted and used. For example, in toxicology, it could mean being able to detect a substance at a specific concentration or to predict a number of effects on the human body for a chemical. (tile n26)
- Defined domain of applicability refers to an essential step in mathematical models such as QSAR during which the chemicals and situations that the model can work on are specified. It is based on the information used to create the model itself; for example, if a QSAR is developed from data on chemicals found in water, it cannot be used to predict chemicals found in the air. (tile n35)
- Defined mechanistic interpretation refers to a direct causal link between a chemical and an observed toxic effect on organisms or the environment. This is of great importance when considering regulatory toxicology. (tile n36)
- Deep learning is a machine learning method which uses artificial neural networks to mimic human brain processes. In toxicology, it is used to predict the effect of substances on living organisms. (tile n3)
- Endpoint-specific control (EC) shows that pathways considered to be relevant for test endpoints are indeed affecting the test endpoint. EC helps correlate (by concentration and time) compound effect on pathway (activity measure to be established) and on test endpoint (standard test readout). (tile n23)
Endorsement of an AOP (Adverse Outcome Pathway). An AOP describes the various steps, from exposure to a particular chemical, leading to a final toxic adverse effect on an organism or the environment. Each step is usually a molecular event (chemical binding a receptor or damage to the DNA), which is necessarily triggered in order to move to the next step, like the domino effect. (tile n40)
- EU Parliament meeting. Elected policy makers have the power to co-design policies that affect how chemicals are regulated and assessed. These decisions can be based on scientific evidence, and it is crucial to learn how to discuss with policy makers to understand what they need and expect. (tile n46)
- EU Agency meeting: Several agencies in the European Union work on the implementation of the chemical regulations (e.g: ECHA, EFSA, EMA). Discussing with their experts and desk officers can helpdesigning a better method. (tile n47)
- An external validation consists of assessing whether a test method developed in the historical laboratory will generate the same results for the same substances in another laboratory with a different team of scientists. (tile n19).
- Guidance documents are prepared by regulatory agencies to illustrate how an endpoint should be assessed. For example, how to report information on a new chemical for industries to national and international agencies. (tile n41)
- Guidance document EFSA – ECHA: see “Guidance documents”above. (tile n42)
- In vitro in vivo extrapolation (IVIVE) means translating an experimental result obtained in vitro into an in vivo setting. An example is to measure how fast a chemical is eliminated by human liver cells to estimate how long it will stay in the human body. (tile n27)
- In vitro & in vivo data can be extracted from existing data set and being used to build in silico models or during a validation study.
In vitro methods are laboratory techniques based on the use of cells and other biological materials which do not involve the use of entire living organisms such as animals.
In silico methods in toxicology are technologies based on software, algorithms and mathematical models used to predict the effect of chemicals on living organisms.
- A lecture in a conference is where scientific research is presented in front of peers (scientists and experts). Communicating on your method development is a great way to challenge it and reach better results or spring collaborations. (tile n49)
- Machine learning is used in toxicology to predict how a substance will affect various organisms, such as humans and animals based on the physical and chemical characteristics of the substance in question combined with the results of in vitro and in silico methods. (tile n2)
- Medium FBS-free is a cell culture reagent which does not contain animal-derived foetal bovine serum (FBS). FBS is still an important component of the laboratory solutions used to grow cells. However, it is extracted from bovine foetuses and its composition varies from batch to batch, introducing potential reproducibility issues. (tile n11)
- A workflow model (modelling workflow) is the sequential series of steps that make up a process. For example, in toxicology, it can describe how various computational and statistical methods, such as QSAR or PBPK, work. (tile n17)
Model verification and validation starts after functional specifications have been documented and initial model development has been completed. Model verification and validation is an iterative process that takes place throughout the development of a model.(tile n31)
- NAM’s training. Once your method is developed, you will need as many people as possible to use it. Hosting training sessions to showcase your methods, share your know-how and explain your work to peers is a great way to support the uptake of your method. (n50,59)
- Non-sentient organisms or in vivo alternatives are a group of animals considered unable to perceive pain, some organisms are non-sentient only during a particular stage of their life cycle (e.g: embryonic stage). Examples are invertebrates such as worms (C. Elegans), fruit flies (Drosophila melanogaster), embryos of fishes and frogs (Danio rerio and Xenopus laevis). They represent a way to replace the use of mammals in toxicology. (tile n7)
- The OECD national coordinator meeting is where it is decided if a test can be accepted for regulatory purposes in OECD member countries. It is composed of experts in the field of toxicology and regulatory toxicology and representatives of national and international regulatory agencies. (tile n45)
- Organ on a chip is a cell culture technique aiming to recreate specific organs’ micro-environment on a synthetic platform. Rather than mimic the entire organ, it focuses on smaller critical parts, such as blood vessels or lung alveoli and simulates their physiological role in the living organisms. (tile n10)
- Physiological-based pharmacokinetic (PBPK) is a mathematical modelling able to predict the absorption, distribution, metabolism and excretion (ADME) of a particular substance in humans and other animals. (tile n1)
- Peer-reviewed submission is the process by which external and independent experts double-check a scientific article to ensure its method is sound and its conclusion plausible and valuable enough for the scientific community to be published. (tile n48
- Programming languages are used to design algorithms on which mathematical modelling, such as PBPK and IVIVE, are based. (tile n21)
- Physiological-based pharmacokinetic modelling is a mathematical modelling able to predict the absorption, distribution, metabolisms and extraction of a particular substance in humans and other animals.
- Positive & negative controls are used in science to reduce experimental variability. For example, in toxicology, a positive control assures that your test always detects the right chemical toxicity, while negative control ensures that your test also properly detects lack of toxicity. (tile n25)
- A poster at a conference is a visual representation and summary of all your results in an A0 format. It is the perfect support to discuss with the rest of the community and increase your network. (n52-57)
- Preprint (e.g. bioRxiv) is a manuscript prepared for publication prior to peer review and publication by a scientific paper. Since the peer review process can be extremely lengthy, publishing preprints enables the immediate sharing of the research results with the scientific community (n53)
- A peer review article is a scientific publication which has gone through the process of peer review.
- Post on social networks. Let everyone know about your amazing method, maybe with a “meme” or a key message/takeaway in 280 characters. (n 55 – 56)
- A peer review is the evaluation of a scientific study by one or more peers with similar expertise and knowledge as the producers of the evaluated research. It functions as a form of self-regulation by qualified members of a profession within a scientific field of research. (n54)
- The quantitative structure-activity relationship (QSAR) is a mathematical modelling technique that predicts a substance’s mode of action based on its chemical structure. (tile n4)
- QSAR: Quantitative structure-activity relationship in a mathematical modelling technique which predict the mode of action of a substance based on its chemical composition.
Repeatability measures if a particular test or assay can be repeated in similar but not identical conditions, for example, in a different laboratory or by another person, multiple times, and generating the same result: the greater the repeatability, the stronger the assay. (tile n28)
- Reproducibility within the lab is the process of making sure a specific assay can be reproduced in the same laboratory but by different operators at different moments. It is the first step to validate a method. (tile n34)
- Relevance answers the following question: Will the chosen test method cover a key human component in toxicity or disease pathway, or why is it thought to reflect a key human component, mechanism or tissue? (tile n37)
- Sensitivity analysis is a tool used in the context of a mathematical model to evaluate how the changes in the input values can affect the output values. For example, a model usedas output the effect of chemicals on the reproductive system and as input the number of such chemicals in the environment. Sensitivity analysis allows measuring the change in the reproductive system when the number of chemicals in the environment increases or decreases. (tile n32)
- Standard Operating Procedure (SOP) is a document describing a series of detailed steps necessary to complete a specific activity (such as a laboratory test) following particular regulations. Using SOP means that your method can be accepted by regulatory agencies more easily. (tile n38)
- Systems Toxicology combines information deriving from several sources, such as in vitro experiments, informatic analysis and population studies, to create a quantitative map able to predict how substances affect molecules, cells, organs, organisms and the environment. (tile n5)
- Software is a set of instructions, data or programs used to operate computers and execute specific tasks. It is the opposite of hardware, which describes the physical aspects of a computer. (tile n18)
- Test with a list of reference chemicals is a practice to assess the quality of a new test with a large number of chemicals whose toxicity is already known. By comparing how much correct chemical toxicity information the new test can generate, it is possible to evaluate its accuracy. (tile n24)
- Test guideline OECD accurately describes how to perform a test, which regulatory agencies internationally accepted under the Mutual Acceptance Data (MAD) concept. (tile n43)
- Transferability to other labs is a procedure by which a test or assay developed in a laboratory is made available and reproducible? in another laboratory. This means reaching the same results in both settings, even with different operators/person, materials and equipment. (tile n33)
- Test method definition should include a series of critical information such as purpose, scientific principle, metabolic competence, quality control criteria, technical limitations and strengths provided by the scientists. (tile n13)
- Unspecified control is a type of negative control for functional assays: not inactive, but only toxic for the cells (cytotoxic). (tile n22)
- Video about your results is one of the best ways to disseminate your results and let others know about your method. (n51,58)