VHP4Safety Glossary

This work is licensed under the CC-BY 4.0 International.

This VHP4Safety Glossary ontology is collected by (in alphabetical order) Ozan Çınar, Marvin Martens, Egon Willighagen, 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 using the issue template. For other issues, suggestions, or problems, please create an issue here. Experienced GitHub users are encouraged to submit pull requests. More information can be found in the project README.

Toxicology in General

Term	Abbreviation	Definition
3 Rs Principle	3Rs	Replacement, Reduction, and Refinement. Used in the context of performing more humane animal research.
Benchmark dose	BMD	See Benchmark dose modeling
Benchmark dose modeling	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	DART
Developmental Neurotoxicity	DNT
(human) Embryonic Stem Cell	(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	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	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	MCRA	See Monte Carlo Risk Assessment calculation model.
Monte Carlo Risk Assessment calculation model		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	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		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	HTS
No Observed Adverse Effect Level	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		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		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
European Centre for the Validation of Alternative Methods	ECVAM	The EU Reference Laboratory for alternatives to animal testing, located in Ispra, Italy.
European Chemical Agency	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	EFSA	Legislator
Exposure Assessment		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		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	IATA
Mode of Action	MoA
The legislation of 'Registration, Evaluation, Authorisation and Restriction of Chemicals'	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		The process of assessing human health risks in a historic, current or emerging exposure scenario for which a concern has risen.
Safety Assessment		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.

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	RL	Formal structure within a project to reach some goal.
Research Line 1	RL1	Building the Virtual Human Platform.
Research Line 2	RL2	Feeding the Virtual Human Platform.
Research Line 3	RL3	Implementing the Virtual Human Platform.
Stakeholder		A person or a group of people who hold(s) a stake and/or can influence decision-makin on a specific issue.
Task Force	TF	Cross work package effort to reach some goal.
Work Package	WP	Formal structure within a project to reach some goal.
Work Package 1.1	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	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	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	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	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	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	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	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	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	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	EMA
	CBG
	ZIN
	CTBG
European Centre for Ecotoxicology and Toxicology of Chemicals	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

Michie, S., West, R. & Hastings, J. Creating ontological definitions for use in science. Qeios (2022). DOI: 10.32388/YGIF9B.2.

Funding

VHP4Safety – the Virtual Human Platform for safety assessment project NWA 1292.19.272 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.

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.

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.