# VHP4Safety Glossary This work is licensed under the [CC-BY 4.0 International](https://github.com/VHP4Safety/glossary/blob/main/LICENCE.md).

::: {about=”https://vhp4safety.github.io/glossary/glossary#” typeof=”owl:Ontology”} This [VHP4Safety Glossary]{property=”dc:title”} ontology is collected by (in alphabetical order) [Ozan Çınar]{property=”dc:contributor”}, [Marvin Martens]{property=”dc:contributor”}, [Egon Willighagen]{property=”dc:contributor”}, and others from the VHP4Safety project. :::

## DEVELOPMENT VERSION This glossary is under development. For example, many definitions do not meet the community standards yet [1]. To make new entry queries, please create an issue [here](https://github.com/VHP4Safety/glossary/issues/new/choose) using the [issue template](https://github.com/VHP4Safety/glossary/blob/main/.github/ISSUE_TEMPLATE/ontology-term-request.md). For other issues, suggestions, or problems, please create an issue [here](https://github.com/VHP4Safety/glossary/issues). Experienced GitHub users are encouraged to submit pull requests. More information can be found in the project [README](README.md). ## Toxicology in General

Term Abbreviation Definition [3 Rs Principle]{property=”rdfs:label”} 3Rs Replacement, Reduction, and Refinement. Used in the context of performing more humane animal research. [Benchmark dose]{property=”rdfs:label”} BMD See Benchmark dose modeling [Benchmark dose modeling]{property=”rdfs:label”} BMD An approach to determine the toxicological limit values for human health, such as the acceptable daily intake (ADI), of all chemical substances (e.g., food) regardless of type or origin. BMD modeling (possibly in combination with PBK modeling) analyzes in conjunction with multiple test systems and organ systems, to study how exposure variation has on the outcome of an in vitro test system. [Developmental and Reproductive Toxicology]{property=”rdfs:label”} DART
[Developmental Neurotoxicity]{property=”rdfs:label”} DNT
[(human) Embryonic Stem Cell]{property=”rdfs:label”} (h)ESCs Pluripotent stem cells derived from the inner cell mass of a blastocyst (an early-stage pre-implantation embryo). These cells are characterised by their ability to differentiate into any cell type of the three germ layers: ectoderm, mesoderm, and endoderm. They are also known for their self-renewal capability, meaning they can proliferate indefinitely in culture while maintaining their pluripotency. [induced Embryonic Stem Cell]{property=”rdfs:label”} iPSCs A type of pluripotent stem cell that can be generated directly from adult cells. The process of creating iPSCs involves reprogramming differentiated somatic cells (such as skin or blood cells) by introducing specific genes that reset the cells to a pluripotent state. This reprogramming allows iPSCs to develop into almost any cell type in the body, similarly to hESCs, making them highly valuable for regenerative medicine, disease modelling, and drug discovery. [Lowest Observed Adverse Effect Level]{property=”rdfs:label”} LOAEL The lowest exposure level of a chemical stressor evaluated in a toxicity test that shows harmful effects on a plant or animal. [Monte Carlo Risk Assessment]{property=”rdfs:label”} MCRA See Monte Carlo Risk Assessment calculation model. [Monte Carlo Risk Assessment calculation model]{property=”rdfs:label”} A modeling technique for realistically possible calculation of the intake of risk substances by humans, for example via food, where the exposure can also be linked to the hazard, with which a risk assessment can be carried out. [New Approach Methodology]{property=”rdfs:label”} NAM A collection of various methods (e.g., high-throughput screening and high-content methods) in a wide set of contexts including in chemico and in vitro to improve knowledge over the toxicokinetic or toxicodynamic attributes of chemical substances, and in turn to improve the chemical safety assessment (see also Non-Animal Methodology).^ref1,^ ^ref2^ [Non-Animal Methodology]{property=”rdfs:label”} A collection of methods to evaluate the potential for a chemical to cause systematic toxicity without using tests on animals (see also New Approach Methodology).^ref^ [High Throughput Screening]{property=”rdfs:label”} HTS
[No Observed Adverse Effect Level]{property=”rdfs:label”} NOAEL The highest exposure level of a chemical stressor evaluated in a toxicity test that shows no harmful effects on a plant or animal. [Read accross]{property=”rdfs:label”} A common approach in the risk assessment in order to examine structural similarities between the source and the target substances when there is a lack of information on their physical-chemical, toxicological properties, or environmental fate. [Teratology]{property=”rdfs:label”} Scientific field that studies the causes, mechanisms, and classes of congenital malformations in animals and plants.^ref^ NOEL

## Risk assessment-related terms

Term Abbreviation Definition [Apical Endpoint]{property=”rdfs:label”}
[European Centre for the Validation of Alternative Methods]{property=”rdfs:label”} ECVAM The EU Reference Laboratory for alternatives to animal testing, located in Ispra, Italy. [European Chemical Agency]{property=”rdfs:label”} ECHA An agency of the European Union which manages the technical and administrative aspects of the implementation of the European Union regulation called Registration, Evaluation, Authorisation and Restriction of Chemicals.^ref^ [European Food Safety Authority]{property=”rdfs:label”} EFSA Legislator [Exposure Assessment]{property=”rdfs:label”} The process of assessing the magnitude, frequency and duration of exposure of a certain organism to a certain agent; OF the process of assessing the total external (or internal) exposure following one or more exposure/use scenarios that are described in terms of route, extent, frequency and duration of exposure, including exposure via more than one exposure route (aggregated exposure) and exposure to multiple chemicals (cumulative exposure). [Hazard Assessment]{property=”rdfs:label”} The process of assessing the intrinsic hazard a substance poses to human health and/or the environment. This provides information on potential human health effects such that a safe production and use of a chemical can be assured. Two types can be generally distinguished, i.e. with the purpose to classify the chemical to a certain category of toxicity (mostly qualitative assessment) or to derive an exposure limit, such as a health-based guidance value or product limit, that ensures safe use. [Integrated Approaches to Testing and Assessment]{property=”rdfs:label”} IATA
[Mode of Action]{property=”rdfs:label”} MoA
[The legislation of ‘Registration, Evaluation, Authorisation and Restriction of Chemicals’]{property=”rdfs:label”} REACH Regulation (EC) No 1907/2006 of the European Parliament and of the Council concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH).^ref^ [Risk Assessment]{property=”rdfs:label”} The process of assessing human health risks in a historic, current or emerging exposure scenario for which a concern has risen. [Safety Assessment]{property=”rdfs:label”} The overarching term for hazard and risk assessment in toxicology. For pharmaceuticals, this term is generally used for assessments of the safety of a certain application of pharmaceuticals, including the determination of the therapeutic window and risk/benefit analysis.

## Adverse Outcome Pathway-related terms

Term Abbreviation Definition Adverse Outcome AO A specialised type of key event that is generally accepted as being of regulatory significance on the basis of correspondence to an established protection goal or equivalence to an apical endpoint in an accepted regulatory guideline toxicity test.^ref^ Adverse Outcome Pathway AOP An AOP describes a sequence of events commencing with initial interaction(s) of a stressor with a biomolecule within an organism that causes a perturbation in its biology (i.e., molecular initiating event, MIE), which can progress through a dependent series of intermediate key events (KEs) and culminate in an adverse outcome (AO) considered relevant to risk assessment or regulatory decision-making.^ref^ Bioactivity The affinity and/or potency of a compound for a protein target. Key Event KE A change in biological or physiological state that is both measurable and essential to the progression of a defined biological perturbation leading to a specific adverse outcome.^ref^ Key Event Relationship KER A scientifically-based relationship that connects one key event to another, defines a causal and predictive relationship between the upstream and downstream event, and thereby facilitates inference or extrapolation of the state of the downstream key event from the known, measured, or predicted state of the upstream key event.^ref^ Molecular Adverse Outcome Pathways mAOP Metapathway, similar to conventional AOPs, but connected events as e.g. WikiPathways pathways. Their function is to expand KEs with molecular pathways and allow analyses of omics data. Molecular Initiating Event MIE A specialised type of key event that represents the initial point of chemical/stressor interaction at the molecular level within the organism that results in a perturbation that starts the AOP.^ref^ Quantitative Adverse Outcome Pathway qAOP Quantitative AOPs, “Leiden approach” to connect events using differential equations. Stressor
TXG-MAPr R package TXG-MAPr Statistical quantitative AOP approach using known coexpression changes in tissue toxicity.

## Server-related terms

Term Abbreviation Definition Cloud computing A computer infrastructure that provides access to data resources, analysis software, and computer power to conduct analyses specific to a use case or research community.^ref^ Docker A service to create a virtual computer environment which can include the required software/tools to conduct a scientific work. Dockerfile A file that includes the commands to build a Docker image. Docker container The virtual environment that has been initiated to run based on its Docker image. Docker image A representative file from which a docker container can be run and executed. Kubernetes K8s A computer tool to orchesterize and manage Docker containers. Platform A computer environment where a set of software and tools are hosted and made available for the use of others over the internet.^ref^ Scalability The property of a (cloud) infrastructure to be able to handle a growing amount of data and work related to it with additions.^ref^ Secure Shell ssh A network protocol to access a network service remotely and securely. Strato An internet hosting service provider that supplies the servers where the virtual platform is built.^ref^ VHP server 1 The server provided by Strato where the Docker containers used in the project are deployed. VHP server 2 The server provided by Strato where the Kubernetes structure is formed for orchestration of the Docker containers on VHP server 1. VHP server 3 The server provided by Strato that is used for experimentation, learning, and testing the work that is carried out on VHP servers 1 and 2.

## Tool/service-related terms

Term Abbreviation Definition Absorption, Distribution, Metabolism, and Excretion ADME Absorption, distribution, metabolism, and excretion of a substance (toxic or not) in a living organism, following exposure to this substance Accessible One needs to know how data can be accessed, possibly including authentication and authorisation.^ref^ Application Programming Interface API A type of software interface that provides a way for two or more computer programs to communicate with each other.^ref^ Catalog A systemic collection of items of the same type.^ref^ Data steward A data steward is an oversight or data governance role within an organization, and is responsible for ensuring the quality and fitness for purpose of the organization’s data assets, including the metadata for those data assets.^ref^ Data Management Plan DMP Plans to serve to address the what, how, who, and where of data management by formally outlining the roles, responsibilities, and activities for managing data during and after research in alignment with FAIR principles.^ref^ Data modeling DMP The process of discovering, analyzing, and scoping data requirements, and then representing and communicating these data requirements in a precise form called the data model. This process is iterative and may include a conceptual, logical, and physical model.^ref^ Data stewardship The work performed by a data steward. Findable Metadata and data should be easy to find for both humans and computers. Machine-readable metadata are essential for automatic discovery of datasets and services.^ref^ Findable, Accessible, Interoperable, Reusable FAIR The FAIR principles emphasise machine-actionability (i.e., the capacity of computational systems to find, access, interoperate, and reuse data with none or minimal human intervention) because humans increasingly rely on computational support to deal with data as a result of the increase in volume, complexity, and creation speed of data.^ref^ Identifier The unique identifier for an administered item within a registration authority.^ref^ Hackathon An event in which computer programmers collaborate intensively with one another and sometimes with people in other specialties over a relatively short period of time to create code usually for a new software product or service.^ref^ Human-Readable Data A data or dataset that is in a format that can be naturally read by humans. It usually contrasts with machine-readable data.^ref^ In-vitro-in-vivo extrapolation IVIVE
Interoperable To speed up discovery and uncover new insights, research data should be easily combined with other datasets, applications and workflows by humans as well as computer systems.^ref^ Machine-Readable Data A data or dataset that is in a format that can be read by a computer. It usually contrasts with human-readable data.^ref^ Mathematical Markup Language MathML An Extensible Markup Language (XML) application to encode mathematical notations on the Web to capture their structure and content for their use and re-use.^ref^ Metadata The data that provide information about one or more aspects of the data that is used to summarize basic information about data that can make tracking and working with specific data easier. Model A simplified (generally mathematical) representation of a real system (e.g. of system: an organism, an organ, a cell, etc.) Module [Software Component] An individual component (software, dataset or in vitro method description) that is hosted, or linked to in the VHP4Safety platform.^ref^ Ontology a formal specification of the conceptualization of a set of phenomena naming and defining the elements of the set along with describing relations between the concepts, data, and entities; a way of showing the properties of a subject area and how they are related, by defining a set of concepts and categories that represent the subject.^ref1,ref2^ Open Data A (collection of) data that can be used, studied, and modified without restriction, and which can be copied and redistributed in modified or unmodified form either without restriction, or with restrictions only to ensure that further recipients can also do these things.^ref^ Pharmacokinetics PK see ADME (these terms are equivalent) Physiologically based biokinetic model PBBK see PBPK model (these terms are equivalent) Physiologically based kinetic model PBK model see PBPK model (these terms are equivalent) Physiologically based pharmacokinetic model PBPK Mechanistic representation of ADME processes for a chemical in a living organism, based on physiological and chemical properties Physiologically based toxicokinetic model PBTK see PBPK model (these terms are equivalent) Proteochemometric PCM Mathematical models that can be used to predict the biological properties (mainly bioactivity) of compounds on proteins from the knowledge of their (chemical) structure. Quantitative Structure Activity Relationships QSAR Mathematical models that can be used to predict the physicochemical, biological and environmental fate properties of compounds from the knowledge of their chemical structure. Research Output Management Plan ROMP Descriprion of the process of organising and documenting the diverse range of outputs generated during the research lifecycle.^ref^ Resource Description Framework RDF A globally-accepted framework for data and knowledge representation that is intended to be read and interpreted by machines.^ref^ Reusable Research data should be ready for future research and future processing, making it self-evident that findings can be replicated and that new research effectively builds on already acquired, previous results.^ref^ Sysrev Ortec’s literature reviewer support and curation documentationn storage system. Technology Readiness Levels TRL TRLs are a method for estimating the maturity of technologies during the acquisition phase of a program.^ref^ Template A thing that is used as a model for producing other similar examples.^ref^ Toxicokinetics TK see ADME (these terms are equivalent, although TK is used exclusively for toxic substances) Web Ontology Language OWL RDF standard for making ontologies machine readable. Widget A small software application that is designed to provide a specific piece of information (such as news, weather, or traffic updates) or a specific function (such as taking notes or controlling another application) on demand.^ref^ Workflow An orchestrated and repeatable multi-step process to coordinate multiple tasks and their data dependencies.^ref^

## Project-related terms

Term Abbreviation Definition [Research Line]{property=”rdfs:label”} RL Formal structure within a project to reach some goal. [Research Line 1]{property=”rdfs:label”} RL1 Building the Virtual Human Platform. [Research Line 2]{property=”rdfs:label”} RL2 Feeding the Virtual Human Platform. [Research Line 3]{property=”rdfs:label”} RL3 Implementing the Virtual Human Platform. [Stakeholder]{property=”rdfs:label”} A person or a group of people who hold(s) a stake and/or can influence decision-makin on a specific issue. [Task Force]{property=”rdfs:label”} TF Cross work package effort to reach some goal. [Work Package]{property=”rdfs:label”} WP Formal structure within a project to reach some goal. [Work Package 1.1]{property=”rdfs:label”} WP1.1 Building the ICT infrastructure for the VHP: objectives to develop the technical infrastructure, setting up a predictive platform, developing analysis workflows, making services and data available and interoperable. [Work Package 1.2]{property=”rdfs:label”} WP1.2 In silico toxicokinetics: objectives to define parameters required for PBPK modelling, developing PBK models and providing guidance for in vitro to in vivo extrapolations. [Work Package 1.3]{property=”rdfs:label”} WP1.3 Computational toxicodynamics: objectives to develop QSAR and MIE prediction models, develop qAOPs, testing the platform and generating safety estimates. [Work Package 2.1]{property=”rdfs:label”} WP2.1 In vitro models to provide toxicokinetics & toxicodynamics parameters: objectives to verify in vitro models for ADME and local toxicity, obtaining parameters for PBK modelling, test chemicals on iPSC models. [Work Package 2.2]{property=”rdfs:label”} WP2.2 Disease state - Case study chronic kidney disease: objectives to identify critical physiological pathways, develop AOP networks, test toxicity of selected drugs, and assess the safety of selected drugs. [Work Package 2.3]{property=”rdfs:label”} WP2.3 Life course exposure - Case study neurodegenerative disease and life course exposure to chemicals: objectives to identify critical physiological pathways, model life time exposure, develop AOP networks, test toxicity and assess the safety of selected chemicals. [Work Package 2.4]{property=”rdfs:label”} WP2.4 Age and gender specific safety - Case study Thyroid mediated developmental neurotoxicity: objectives to collect mechanistic physiological data, determine critical pathways, establish quantitative AOP network, identify gender-specific sentitivities and compounds that discriminate, and assess the safety of compound exposure. Work Package 3.1 WP3.1 Technology Assessment of VHP: objectives to perform technology assessment, study and analyse the initiation, development and implementation of VHP, and specify performance criteria. [Work Package 3.2]{property=”rdfs:label”} WP3.2 Acceptance of VHP for safety assessment: objectives to position the VHP in the transition to animal-free safety assessment, raise awareness, investigate uncertainties and acceptance of safety assessments. [Work Package 3.3]{property=”rdfs:label”} WP3.3 Training and Education: objectives to promote collaboration, facilitate transferability of methods and models, implementing new teaching modules, promote capacity building and awareness of stakeholders, improve skills regarding risk communication. [Work Package 4]{property=”rdfs:label”} WP4 Project Coordination, Impact and Data Management: objectives to ensure that project objectives are achieved, deliverables are completed, manage overall knowledge utilisation, and provide effective and sustainable data management.

## Organizations

Term Abbreviation Definition [European Medicines Agency]{property=”rdfs:label”} EMA
CBG
ZIN
CTBG
[European Centre for Ecotoxicology and Toxicology of Chemicals]{property=”rdfs:label”} ECTOC The European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) is a scientific, non-profit, non-commercial and non-governmental association. Established in 1978, ECETOC’s main objective is to identify, evaluate, and through such knowledge help industry to minimise any potentially adverse effects on human health and the environment that may arise from the manufacture and use of chemicals, biomaterials and pharmaceuticals.^ref^

### References 1. Michie, S., West, R. & Hastings, J. Creating ontological definitions for use in science. Qeios (2022). DOI: [10.32388/YGIF9B.2](https://doi.org/10.32388/YGIF9B.2). ### Funding VHP4Safety – the Virtual Human Platform for safety assessment project [NWA 1292.19.272](https://www.nwo.nl/projecten/nwa129219272) is part of the NWA research program ‘Research along Routes by Consortia (ORC)’, which is funded by the Netherlands Organization for Scientific Research (NWO). The project started on June 1, 2021 with a budget of over 10 million Euros and will last for the duration of 5 years.