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Detection of endpoints and biomarkers of repeated dose toxicity using in vitro systems

Objective

Assessment of repeated dose toxicity is a standard requirement in human safety evaluation and relies on animal testing as no alternatives are currently accepted for regulatory purposes. An integrated research strategy for the replacement of animal tests needs to comprise the development of biomarkers of long-term toxicity in human target cells. To this aim, the DETECTIVE project will set up a screening pipeline of high content, high throughput as well as classical functional and “-omics” technologies to identify and investigate human biomarkers in cellular models for repeated dose in vitro testing. In view of industrial use in automated high throughput systems, essential questions of repeated dose toxicity such as stability and robustness of readouts will be investigated in a first phase. This will be the foundation for innovative biomarker development based on integration of multiple data streams derived from “-omics” readouts with traditional toxicological and histopathological endpoint evaluation. Toxicity pathways identified in “-omics” readouts can thus be further investigated by the functional readouts.
DETECTIVE will initially use human hepatic, cardiac and renal models as common target organs of repeated dose toxicity. Ultimately, the strategy for establishing biomarkers will also be applicable to other organs or organ systems affected by systemic toxicants. It is also expected that DETECTIVE will be able to define human toxicity pathways relevant for all organs.
Based on integrative statistical analysis, systematic verification and correlation with in vivo data, the most relevant, highly specific, sensitive and predictive biomarkers will be selected. Within DETECTIVE, partners from academia, industry and research will hence generate pathway- and evidence-based understanding of toxic effects, moving toxicology beyond descriptive science towards mechanism-based prediction.

Field of science

  • /medical and health sciences/basic medicine/toxicology

Call for proposal

FP7-HEALTH-2010-Alternative-Testing
See other projects for this call

Funding Scheme

CP-IP - Large-scale integrating project

Coordinator

KLINIKUM DER UNIVERSITAET ZU KOELN
Address
Kerpener Strasse 62
50937 Koeln
Germany
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 092 420,01
Administrative Contact
Jürgen Hescheler (Prof.)

Participants (14)

JRC -JOINT RESEARCH CENTRE- EUROPEAN COMMISSION
Belgium
EU contribution
€ 315 388
Address
Rue De La Loi 200
1049 Brussels
Activity type
Research Organisations
Administrative Contact
Iain Formosa (Mr.)
UNIVERSITEIT MAASTRICHT
Netherlands
EU contribution
€ 442 026,50
Address
Minderbroedersberg 4-6
6200 MD Maastricht
Activity type
Higher or Secondary Education Establishments
Administrative Contact
René Reijnders (Mr.)
ROCHE DIAGNOSTICS GMBH
Germany
EU contribution
€ 168 655,50
Address
Sandhofer Strasse 116
68305 Mannheim
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Manuel Wölfelschneider (Dr.)
VRIJE UNIVERSITEIT BRUSSEL
Belgium
EU contribution
€ 347 858,80
Address
Pleinlaan 2
1050 Brussel
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Maria Vereeken (Ms.)
PROTEOSYS AG

Participation ended

Germany
EU contribution
€ 147 914,50
Address
Carl Zeissstrasse 51
55129 Mainz
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
André Schrattenholtz (Prof.)
FORSCHUNGSGESELLSCHAFT FUR ARBEITSPHYSIOLOGIE UND ARBEITSSCHUTZ E.V.
Germany
EU contribution
€ 342 556,50
Address
Ardeystrasse 67
44139 Dortmund
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Jan Hengstler (Prof.)
IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE
United Kingdom
EU contribution
€ 307 681,90
Address
South Kensington Campus Exhibition Road
SW7 2AZ London
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Tatjana Palalic (Ms.)
DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG
Germany
EU contribution
€ 153 000
Address
Im Neuenheimer Feld 280
69120 Heidelberg
Activity type
Research Organisations
Administrative Contact
Krischek Ina (Dr.)
ARTTIC
France
EU contribution
€ 354 266,26
Address
Rue Du Dessous Des Berges 58A
75013 Paris
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Annette Ringwald (Ms.)
OU QURETEC
Estonia
EU contribution
€ 72 686,40
Address
Ulikooli 6A
51003 Tartu
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Jaak Vilo (Prof.)
MEDIZINISCHE UNIVERSITAT INNSBRUCK
Austria
EU contribution
€ 137 636
Address
Christoph Probst Platz 1
6020 Innsbruck
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Walter Pfaller (Prof.)
LEIBNIZ-INSTITUT FUR ANALYTISCHE WISSENSCHAFTEN-ISAS-EV
Germany
EU contribution
€ 193 333,50
Address
Bunsen Kirchhoff Strasse 11
44139 Dortmund
Activity type
Research Organisations
Administrative Contact
Albert Sickmann (Prof.)
FRAUNHOFER GESELLSCHAFT ZUR FOERDERUNG DER ANGEWANDTEN FORSCHUNG E.V.
Germany
EU contribution
€ 82 285
Address
Hansastrasse 27C
80686 Munchen
Activity type
Research Organisations
Administrative Contact
Andrea Zeumann (Ms.)
UNIVERSITEIT LEIDEN
Netherlands
EU contribution
€ 179 716,46
Address
Rapenburg 70
2311 EZ Leiden
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Ton Brouwer (Mr.)