3Rs TOXICITY TESTING AND DISEASE MODELING PROJECTS IN THE EUROPEAN HORIZON 2020 RESEARCH AND INNOVATION PROGRAM - LRSS
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EXCLI Journal 2020;19:775-784 – ISSN 1611-2156
Received: May 23, 2020, accepted: June 08, 2020, published: June 09, 2020
Review article:
3Rs TOXICITY TESTING AND DISEASE MODELING PROJECTS IN
THE EUROPEAN HORIZON 2020 RESEARCH AND INNOVATION
PROGRAM
Mathieu Vinken
Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel,
Laarbeeklaan 103, 1090 Brussels, Belgium
Correspondence: Prof. Mathieu Vinken, Ph.D., E.R.T., Pharm. D., Department of In Vitro
Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090
Brussels, Belgium; Tel: +32 2 477 45 87. E-mail: mathieu.vinken@vub.be
ORCID ID: https://orcid.org/0000-0001-5115-8893
http://dx.doi.org/10.17179/excli2020-2450
This is an Open Access article distributed under the terms of the Creative Commons Attribution License
(http://creativecommons.org/licenses/by/4.0/).
ABSTRACT
The 3Rs concept, calling for replacement, reduction and refinement of animal experimentation, is receiving in-
creasing attention around the world, and has found its way to legislation, in particular in the European Union. This
is aligned by growing efforts of the European Commission to support development and implementation of 3Rs
methods. The present paper gives an overview of European 3Rs initiatives as part of the different pillars of the
Horizon 2020 framework program for research and innovation. Focus is hereby put on projects that address the
3Rs concept in the context of toxicity testing, chemical risk assessment and disease modeling.
Keywords: 3Rs, animal-free, in vitro, in silico, Europe, Horizon 2020
SETTING THE SCENE FOR 3Rs 3Rs concept served as a basis for the Euro-
RESEARCH AND INNOVATION IN pean legislation on the protection of animals
THE EUROPEAN UNION for experimental and other scientific pur-
Driven by ethical and scientific con- poses, first introduced in 1986 as laid down in
straints that emerged a number of decades ago Directive 86/609/EEC (EEC, 1986), and re-
already, there is a clear tendency worldwide vised a decade ago in Directive 2010/63/EU
to increasingly employ animal-free methods, (EU, 2010). This has been reinforced in the
in particular for toxicological and safety eval- past few years by a number of more explicit
uation of chemicals. This mindset has been European legislative changes, in particular in
majorly inspired by the seminal book entitled the cosmetics field, where animal testing and
“The principles of humane experimental tech- marketing bans have been imposed (EU,
2009). An increasing number of countries
nique” published by William Russell and Rex
worldwide have followed the ban on animal
Burch in 1959, introducing the 3Rs, calling
testing for cosmetics. In fact, Europe is a
for replacement, reduction and refinement of
world pioneer regarding animal welfare and
animal testing (Russell and Burch, 1959). The
775EXCLI Journal 2020;19:775-784 – ISSN 1611-2156
Received: May 23, 2020, accepted: June 08, 2020, published: June 09, 2020
spearheads the global 3Rs alternative meth- Table 1: Pillars of the H2020 program
ods field. The European Commission follows (https://ec.europa.eu/programmes/hori-
zon2020/en)
a number of strategies in order to do so. In this
respect, the European Union Reference La- Pillar 1: excellent science
boratory for Alternatives to Animal Testing European Research Council
Marie Skłodowska-Curie Actions
(EURL ECVAM), mandated under Directive
Future and Emerging Technologies
2010/63/EU, is not only responsible for vali- Research Infrastructures
dation of 3Rs alternative methods, but also for Pillar 2: industrial leadership
promoting their regulatory acceptance and Leadership in Enabling and Industrial Technol-
disseminating information regarding 3Rs al- ogies
ternative methods. Through EURL ECVAM, Access to Risk Finance
Innovation in Small-sized and Medium-sized
the European Commission plays an active
Enterprises
role at the level of the Organization for Eco- Pillar 3: societal challenges
nomic Co-operation and Development Health
(OECD) in the regulatory acceptance of 3Rs Food
alternative methods as well as their interna- Energy
tional adoption (https://ec.eu- Transport
ropa.eu/jrc/en/eurl/ecvam). Furthermore, the Climate
Society
European Commission teamed up with 8 Eu- Security
ropean trade associations and 36 individual
companies from relevant business sectors in a
unique public-private partnership called the The present paper gives an overview of
European Partnership for Alternative Ap- relevant completed and ongoing research pro-
proaches to Animal Testing (EPAA). EPAA jects in the H2020 program focused on the de-
is committed to pool knowledge and re- velopment of 3Rs alternative methods. The
sources in order to accelerate the develop- major resource consulted in order to do so was
ment, validation and acceptance of 3Rs alter- the Community Research and Development
native approaches for regulatory testing Information Service (CORDIS)
(https://ec.europa.eu/growth/sectors/chemi- (https://cordis.europa.eu/), which is the pri-
cals/epaa_en). The European Commission mary public repository and portal of the Eu-
also strongly supports research and develop- ropean Commission to disseminate infor-
ment of 3Rs alternative methods as part of its mation on all funded European research pro-
framework program for research and innova- jects.
tion called Horizon 2020 (H2020). The
H2020 program, which is the successor of the
7th framework program (FP7), has a budget of 3Rs PROJECTS IN H2020 PILLAR 1
80 billion Euro available spread over 7 years (EXCELLENT SCIENCE)
i.e. from 2014 to 2020. The core of the H2020
program relies on 3 pillars, namely excellent VESCEL: vascular engineering-on-chip us-
science (pillar 1), industrial leadership (pillar ing differentiated stem cells
2) and societal challenges (pillar 3), each that The VESCEL project (2015-2020;
consist of specific funding programs (Table 1) https://www.utwente.nl/en/eemcs/bios/re-
(https://ec.europa.eu/programmes/hori- search/) was funded by the European Re-
zon2020/en). search Council and has developed a technol-
ogy to enable the use of differentiated human
induced pluripotent stem cells to engineer
blood vessels-on-chip that constitute disease
models for thrombosis and neurodegenerative
776EXCLI Journal 2020;19:775-784 – ISSN 1611-2156
Received: May 23, 2020, accepted: June 08, 2020, published: June 09, 2020
diseases. Such models serve translational re- TOXANOID: pharmacological safety test-
search purposes and replace animal testing. ing in human adult stem cell-derived organ-
oids
CryoProtect: a new cryoprotectant formula- The TOXANOID project (2017-2018;
tion for the next generation of high- https://www.fabiodisconzi.com/open-
throughput screening toxicology tests h2020/projects/209165/index.html) was
The CryoProtect project (2016-2017; funded by the European Research Council
https://environment.leeds.ac.uk/see-re- and developed a 3D culture system that al-
search/dir-record/research-projects/788/cryo- lows to expand human tissue stem cells from
protect-erc-proof-of-concept) was funded by intestine and liver as organoids and differen-
the European Research Council and devel- tiate them to the respective functional adult
oped a strategy for cryopreservation of cells tissue in vitro. Besides alleviating costs,
within multiwell plates, allowing them be TOXANOID helped to overcome practical
shipped to laboratories around the world and and ethical pitfalls in animal-based testing.
thawed only when they are needed. This helps
to optimize in vitro testing, which in turn re- NeMatrix: nematode-based screening tech-
duces animal experimentation. nology for next-generation drug discovery
The NeMatrix project (2017-2018;
OCLD: tracking the dynamics of human https://www.epfl.ch/research/) was funded by
metabolism using spectroscopy-integrated the European Research Council and devel-
liver-on-chip microdevices oped a microfluidic platform for fully auto-
The OCLD project (2016-2021; mated culture and analysis of the roundworm
https://www.nahmias-lab.com/) is funded by Caenorhabditis elegans tailored for drug
the European Research Council and generates screening applications. NeMatrix has set an
a liver-on-chip device capable of tracking the example for alternative model organisms for
metabolism of tissue engineered livers in real 3Rs testing in biomedical research and phar-
time, enabling an accurate assessment of maceutical industries.
chronic liver toxicity and the deconstruction
of complex metabolic regulation during nutri- INSITE: development and use of an inte-
tional events. OCLD will replace animal stud- grated in silico-in vitro mesofluidics system
ies in toxicity testing. for tissue engineering
The INSITE project (2018-2023;
Mini Brains: cerebral organoids: human https://www.kuleuven.be/english/research/)
mini brains in a dish open up new possibili- is funded by the European Research Council
ties for drug development in neurodegener- and establishes a new mesofluidics set-up for
ative and developmental diseases in vitro testing of tissue engineering con-
The Mini Brains project (2017-2018; structs through development of multiscale
https://www.imba.oeaw.ac.at/) was funded by and multiphysics models that aggregate the
the European Research Council and yielded a available data and use these to design com-
human pluripotent stem cell-derived 3D or- plex constructs and proper mesofluidics set-
ganoid culture system. This cerebral organoid tings for in vitro testing. This system will al-
system can be used for investigating brain dis- low for a maximum of relevant in vitro re-
orders and testing new drugs, thereby offering search prior to the in vivo phase, thus comply-
a 3Rs alternative to animal experiments. ing with the 3Rs concept.
777EXCLI Journal 2020;19:775-784 – ISSN 1611-2156
Received: May 23, 2020, accepted: June 08, 2020, published: June 09, 2020
Design2Flow: disposable well-plate inserts contributed to organs-on-chip technology by
and perfusion chambers for easy-to-use and combining cell biology with microfluidics
generic microchannel creation in 3D tissue and chip-based techniques for high-through-
culture put drug screening and basic research.
The Design2Flow project (2020-2021; MIMIC combined research activities with
https://www.ukw.de/startseite/) is funded by 3Rs training of early-stage researchers.
the European Research Council and generates
perfusable 3D cell culture products for phar- In3: an integrated interdisciplinary
maceutical industry. This allows to mimic in approach to animal-free chemical and
vivo blood flow and hence provides a suitable nanomaterial safety assessment
in vitro alternative for animal experimenta- The In3 project (2017-2020;
tion. https://www.estiv.org/in3/) was funded by the
Marie Skłodowska-Curie Actions program
ORCHID: organ-on-chip in development and aimed at the synergistic development and
The ORCHID project (2017-2019; application of in vitro and in silico tools for
https://h2020-orchid.eu/) was funded by the human chemical and nanomaterial safety as-
Future and Emerging Technologies program sessment. In3 focused on human induced plu-
and created a roadmap for organ-on-chip ripotent stem cell-derived tissues and utilized
technology and the framework to build a net- mechanistic toxicology, quantitative adverse
work of relevant stakeholders. In this way, outcome pathways, biokinetics, chemo-infor-
ORCHID has facilitated drug development, matics and modeling approaches to derive
assisted in developing personalized medicine testable prediction models. While having a
and contributed to reducing animal experi- strong research core, In3 mainly aspired train-
ments. ing of young researchers in the 3Rs field.
TISuMR: integrated tissue slice culture and ChromaFish: chromatographic micro-
nuclear magnetic resonance metabolomics: column development for pharmaceutical
a novel approach towards systemic under- applications in zebraFish
standing of liver function and disease The ChromaFish project (2018-2022;
The TISuMR project (2017-2020; https://www.kuleuven.be/english/research/)
http://tisumr.soton.ac.uk/) was funded by the is funded by the Marie Skłodowska-Curie Ac-
Future and Emerging Technologies program tions program and aims at optimizing and ap-
and produced new technology that combines plying methods to measure whole-body up-
microfluidic lab-on-chip tissue culture with take of drugs in zebrafish, in particular in
advanced nuclear magnetic resonance spec- brain. ChromaFish is another example of al-
troscopy. TISuMR focused on liver tissue cul- ternative model organisms for 3Rs testing in
ture and drug-induced cholestatic liver injury. biomedical research and pharmaceutical in-
By doing so, TISuMR not only increased the dustries.
efficiency and specificity of drug safety test-
ing, but also provided a 3Rs alternative to an- uKNEEversal: a miniaturized 3D in vitro
imal testing. model of human joint to gain new
knowledge on osteoarthritis pathophysiol-
MIMIC: mimicking organs-on-chips for ogy
high-throughput drug screening and basic The uKNEEversal project (2019-2021;
research https://www.polimi.it/en/) is funded by the
The MIMIC project (2016-2019; Marie Skłodowska-Curie Actions program
https://www.sheffield.ac.uk/itn- and aims to generate a comprehensive in vitro
mimic#gsc.tab=0) was funded by the Marie human model of osteoarthritis to fill gaps of
Skłodowska-Curie Actions program and has existing preclinical tools as well as to function
778EXCLI Journal 2020;19:775-784 – ISSN 1611-2156
Received: May 23, 2020, accepted: June 08, 2020, published: June 09, 2020
as a tool for mechanistic and translational re- OpenRiskNet: open e-infrastructure to sup-
search. Furthermore, uKNEEversal provides port data sharing, knowledge integration
a solution for ethical issues regarding animal and in silico analysis and modeling in risk
experimentation by providing a 3Rs replace- assessment
ment alternative. The OpenRiskNet project (2016-2019;
https://openrisknet.org/) was funded by the
ChOLLATERAL: generation of an adverse Research Infrastructures program and has de-
outcome pathway network on cholestatic veloped an open e-infrastructure providing re-
liver injury for mechanism-based in vitro sources and services to a variety of communi-
testing of chemicals ties requiring risk assessment, including
The ChOLLATERAL project (2019- chemicals, cosmetic ingredients, therapeutic
2021; https://www.vub.be/en/re- agents and nanomaterials. A number of case
search#home) is funded by the Marie studies demonstrated the applicability of the
Skłodowska-Curie Actions program and aims infrastructure in supporting research and in-
at elucidating the mechanisms of cholestatic novation in safer product design and risk as-
liver injury. This knowledge is used for set- sessment, and concomitantly, in replacing the
ting up advanced human-based in vitro testing use of animal testing in toxicology.
batteries, which help to better predict liver in-
sults induced by chemicals and that avoid the
3Rs PROJECTS IN H2020 PILLAR 2
use of animals.
(INDUSTRIAL LEADERSHIP)
PTOoC: plug-n-play tool-kit of organ-on- HISENTS: high-level integrated sensor for
chips nanotoxicity screening
The PTOoC project (2019-2021; The HISENTS project (2016-2019;
https://www.elveflow.com/) is funded by the https://hisents.eu/) was funded by the Leader-
Marie Skłodowska-Curie Actions program ship in Enabling and Industrial Technologies
and aims at building modular organ model program, and delivered an advanced
systems. PTOoC establishes a library of com- nanosafety platform capable of providing
ponents to produce tissue testing systems in a high-throughput toxicity screening for the
plug-and-play fashion. This will produce a risk assessment of novel nanomaterials. This
tool for testing potential therapies in physio- screening tool enhanced efficiency of hazard
logically relevant systems and will thus mini- profiling of nanomaterials and reduced the
mize animal use. use of animals for safety testing.
SiGNATURE: selection of human iPSC-de- DifMATRIX: ground breaking 3D cell cul-
rived cardiomyocytes by single cell gene ex- ture platform to eliminate animal testing in
pression and patch clamp for a mature car- pharmaceuticals
diac model The DifMATRIX project (2018;
The SiGNATURE project (2020-2022; https://inocure.cz/) was funded by the Innova-
https://www.lumc.nl/research/) is funded by tion in Small-sized and Medium-sized Enter-
the Marie Skłodowska-Curie Actions pro- prises program and has produced a 3D scaf-
gram and provides a functionally relevant folding platform with drug delivery embed-
gene signature of human induced pluripotent ded system for cell culture, which simulates
stem cell-derived cardiomyocytes of use for the in vivo tissue phenotype in vitro. While
the modeling of cardiomyocyte autonomous improving preclinical-to-clinical translation
cardiac diseases for personalized drug screen- efficiency, DifMATRIX also provided a 3Rs
ing. SiGNATURE will enhance rates of drug alternative to animal testing models.
discovery and safety, and, at least in part, will
replace the use of animal models.
779EXCLI Journal 2020;19:775-784 – ISSN 1611-2156
Received: May 23, 2020, accepted: June 08, 2020, published: June 09, 2020
HypoSkin: unique breakthrough ex vivo MOOD: feasibility study for the introduc-
human skin model to predict efficacy and tion into preclinical study domain of the
toxicity of subcutaneous drugs first-of-a-kind multi-organ-on-device tech-
The HypoSkin project (2018; nology
https://www.genoskin.com/) was funded by The MOOD project (2018-2019;
the Innovation in Small-sized and Medium- https://www.react4life.com/) was funded by
sized Enterprises program and has generated the Innovation in Small-sized and Medium-
an in vitro testing kit containing living ex vivo sized Enterprises program and generated a
human skin biopsies with subcutaneous fat. multi-organ-on-device, being an advanced
HypoSkin enabled to reliably predict the local fluidic multichamber bioreactor and a 3D
human’s response to the injection of drugs model of breast cancer tissue cultured onto a
and replaced animal testing. membrane mimicking the blood vessel bar-
rier. This device reduced time, costs and use
mP-CSE: microphysiological circadian of animals in drug development.
platform for safety and efficacy assessment
of drugs and cosmetics uHeart: a beating heart-on-chip for
The mP-CSE project (2018; preclinical early detection of drugs
https://www.tissuedynamics.com/) was cardiac safety
funded by the Innovation in Small-sized and The uHeart project (2019-2020;
Medium-sized Enterprises program and has http://www.biomimx.com/) was funded by
generated a multi organ-on-chip platform that the Innovation in Small-sized and Medium-
uses real-time sensing of tissue function, in- sized Enterprises program and has produced a
cluding mimicking of circadian rhythms, to beating heart-on-chip by integrating a 3D cell
detect the effect of drug-induced physiologi- culture and mechanical stimulation. While
cal stress in multiple 3D vascular organs. This providing a tool for rapid screening in early
device reduced cost of drug development, but drug development, uHeart also provided a
also established a 3Rs alternative for safety 3Rs alternative to animal testing models.
testing.
OrganoPlate Graft: organ-on-a-chip
QSAREACH: QSAR computational mod- technology for in vitro grafting and
els’ self-using platform for EC Regulation vascularization of 3D tissues
REACH The OrganoPlate Graft project (2019-
The QSAREACH project (2018-2019; 2021; https://mimetas.com/) is funded by the
https://protoqsar.com/en/european-comis- Innovation in Small-sized and Medium-sized
sion-sme-instrument/) was funded by the In- Enterprises program and will deliver a high-
novation in Small-sized and Medium-sized throughput in vitro culture method for vascu-
Enterprises program and generated an in sil- larized tissue. OrganPlate Graft will enable
ico platform consisting of quantitative struc- design of novel types of experiments in re-
ture-activity relationship models for (eco)tox- search, development and clinical settings, and
icological investigation of chemicals, includ- will replace animal tests.
ing nanomaterials, in line with European leg-
islation. This forms a full 3Rs replacement al- Droplet Microarray: miniaturized system
ternative for animal testing. for screening of primary cells based on
droplet microarray
The Droplet Microarray project (2020-
2022; http://www.aquarray.com/) is funded
by the Innovation in Small-sized and Me-
dium-sized Enterprises program and focuses
on the miniaturization of microplates using
780EXCLI Journal 2020;19:775-784 – ISSN 1611-2156
Received: May 23, 2020, accepted: June 08, 2020, published: June 09, 2020
primary cells for drug discovery purposes. InSilc: in silico trials for drug-eluting BVS
This will enable personalized medicine and design, development and evaluation
will reduce use of animals in pharmaceutical The InSilc project (2017-2020;
industry. https://insilc.eu/) was funded under the Health
topic and aimed at delivering an in silico clin-
ical trial platform for designing, developing
3Rs PROJECTS IN H2020 PILLAR 3
and assessing drug-eluting bioresorbable vas-
(SOCIETAL CHALLENGES)
cular scaffolds by building on the comprehen-
EuroMix: a tiered strategy for risk assess- sive biological and biomedical knowledge
ment of mixtures of multiple chemicals and advanced modeling approaches to simu-
The EuroMix project (2015-2019; late their implantation performance in indi-
https://www.euromixproject.eu/) was funded vidual cardiovascular physiology. InSilc con-
under the Food topic and developed a tiered tributed to reduction of development costs
strategy for the risk assessment of mixtures of and shorting of time-to-market, and the im-
multiple chemicals derived from several plementation of the 3Rs.
sources across different life stages. EuroMix
abundantly used in vitro assays and in silico HBM4EU: European human
tools, and hence led to a reduction of the use biomonitoring initiative
of animals for safety testing of chemicals. The HBM4EU project (2017-2021;
https://www.hbm4eu.eu/) is funded under the
EDC-MixRisk: integrating epidemiology Health topic and aims at generating
and experimental biology to improve risk knowledge to inform the safe management of
assessment of exposure to mixtures of chemicals by using human biomonitoring to
endocrine disruptive compounds understand human exposure to chemicals and
The EDC-MixRisk project (2015-2019; resulting health impacts. HBM4EU will adapt
https://edcmixrisk.ki.se/) was funded under chemical risk assessment methodologies to
the Health topic and focused on effects of use human biomonitoring data, thereby avoid-
mixtures of endocrine disrupting chemicals ing reliance on animal experimentation.
on children. EDC-MixRisk developed an ap-
propriate mixture risk assessment methodol- EURION: European cluster to improve
ogy implemented in an interoperational data identification of endocrine disruptors
and model platform and relied on animal-free EURION (2019-2024; https://eurion-
research. cluster.eu/) is a cluster group of 8 research
projects (ATHENA, ERGO, SCREENED,
EU-ToxRisk: an integrated European flag- ECDMET, GOLIATH, OBERON, END-
ship program driving mechanism-based poiNTS and FREIA) under the Health topic
toxicity testing and risk assessment for the focused on testing and screening methods to
21st century identify endocrine disrupting chemicals. Each
The EU-ToxRisk project (2016-2021; project in the cluster addresses a different as-
http://www.eu-toxrisk.eu/) is funded under pect of new testing and screening methods to
the Health topic and establishes a mechanism- identify endocrine disrupting chemicals,
based testing strategy for animal-free chemi- thereby embracing the 3Rs concept as much
cal safety assessment of chemicals of diverse as possible.
sectors. It is considered the flagship 3Rs pro-
ject in Europe, as it integrates all concepts of
21st century toxicity testing, including hu- CONCLUSIONS AND PERSPECTIVES
man-based testing devoid of animals by fully According to the most recent report of the
relying on in vitro and in silico experimenta- European Commission on the statistics on the
tion. number of animals used for experimental and
781EXCLI Journal 2020;19:775-784 – ISSN 1611-2156
Received: May 23, 2020, accepted: June 08, 2020, published: June 09, 2020
other scientific purposes in the member states association Cosmetics Europe and the Euro-
of the European Union, 2.18 million animals pean Federation of Pharmaceutical Industries
were used for regulatory testing purposes in and Associations, respectively. Some of those
2017, which is roughly one fourth of all ani- initiatives, in particular IMI, are continued in
mals used during that year. A total of 8 % of the H2020 program, with projects such as
all animals was used for toxicological and eTRANSAFE (https://etransafe.eu/), focused
other safety evaluation purposes. Although on the use of in silico tools in the pharmaceu-
this number slightly decreased compared to tical sector, and VAC2VAC
previous years, this still implies a considera- (http://www.vac2vac.eu/), which addresses in
ble number of animals (EU, 2020). Intensive vitro method development for vaccine testing.
efforts worldwide try to reduce and replace In fact, the 3Rs are fully intertwined in the 3
the use of animals, in particular for toxicity pillars of the H2020 program. While pillar 1
testing of chemicals. In this respect, the US (excellent science) and pillar 2 (industrial
Environmental Protection Agency (US EPA) leadership) focus in general on the develop-
issued a memorandum in 2019 announcing ment of new animal-free methodologies, such
that it will reduce its requests for and funding as advanced in vitro models and in silico
of mammal studies by 30 % towards 2025, tools, multidisciplinary and intersectoral pro-
and eliminate all mammal study requests and jects in pillar 3 (societal challenges) rather ad-
funding by 2035. Furthermore, the US EPA dress the integration of such new technical
stated that the regulatory requirements for risk know-how in view of setting up human-based
assessment will be refined and an increased strategies and workflows for next generation
flexibility in risk assessment framework will toxicity testing and risk assessment of chemi-
be implemented to facilitate the incorporation cals fully devoid animals. Such pillar 3 pro-
of non-animal methods (US EPA, 2019). In jects are increasingly being encouraged to
2016, the Netherlands National Committee team up in clusters in order to maximize
for the Protection of Animals used for Scien- cross-fertilization of knowledge and hence to
tific Purposes published a strategy to phase create synergistic outcome. In this context, a
out animal experiments by 2025 (NCad, new call for pillar 3 projects under the Health
2016). Although the ambition was later on topic was published in 2019 (https://ec.eu-
loosened to making research largely free of ropa.eu/info/funding-tenders/opportuni-
animal testing, the Netherlands still aspire to ties/portal/screen/opportunities/topic-de-
become world leader in innovations without tails/sc1-bhc-11-2020) and is expected to re-
laboratory animals in 2025. At the European sult in 3-4 projects that will intensively col-
level, a multitude of instruments is being used laborate under the theme “advancing the
since many years to implement the 3Rs prin- safety assessment of chemicals without the
ciples, not only in toxicology and risk assess- use of animal testing” as of 2021. Also in
ment, but in life science research and educa- 2019, the European Commission published
tion in general. In FP7, the European Com- the proposal for the H2020 follow-up research
mission spent about 200 million Euro on sup- and innovation program called Horizon Eu-
porting animal-free toxicology projects rope for the period 2021-2027 (https://ec.eu-
(https://ec.europa.eu/environment/chemi- ropa.eu/info/horizon-europe-next-research-
cals/lab_animals/3r/research_en.htm). A con- and-innovation-framework-programme_en).
siderable part of this budget was dedicated to With some changes compared to its H2020
public-private partnerships, including the predecessor, the Horizon Europe program has
Safety Evaluation Ultimately Replacing Ani- kept a 3-pillar structure and foresees ample
mal Testing consortium (SEURAT; opportunities for 3Rs research, innovation,
http://www.seurat-1.eu/) and the Innovative collaboration and education. This will not
Medicines Initiative (IMI; only consolidate Europe’s world-leading 3Rs
https://www.imi.europa.eu/), with the trade position, but first and foremost will save the
782EXCLI Journal 2020;19:775-784 – ISSN 1611-2156
Received: May 23, 2020, accepted: June 08, 2020, published: June 09, 2020
lives of millions of animals, while meeting the http://tisumr.soton.ac.uk/
ever increasing regulatory human safety re- http://www.aquarray.com/
quirements of chemicals.
http://www.biomimx.com/
Funding
http://www.eu-toxrisk.eu/
No funding was received for this paper.
http://www.seurat-1.eu/
Conflict of interest
No conflicts of interest are to report. http://www.vac2vac.eu/
https://cordis.europa.eu/
Author’s contributions
Mathieu Vinken is the sole author of this https://ec.europa.eu/environment/chemicals/lab_ani-
mals/3r/research_en.htm
paper.
https://ec.europa.eu/growth/sectors/chemi-
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783EXCLI Journal 2020;19:775-784 – ISSN 1611-2156
Received: May 23, 2020, accepted: June 08, 2020, published: June 09, 2020
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