Archives of Toxicology

, Volume 90, Issue 6, pp 1529–1539 | Cite as

“Watching the Detectives” report of the general assembly of the EU project DETECTIVE Brussels, 24–25 November 2015

  • Ruani N. Fernando
  • Umesh Chaudhari
  • Sylvia E. Escher
  • Jan G. Hengstler
  • Jürgen Hescheler
  • Paul Jennings
  • Hector C. Keun
  • Jos C. S. Kleinjans
  • Raivo Kolde
  • Laxmikanth Kollipara
  • Annette Kopp-Schneider
  • Alice Limonciel
  • Harshal Nemade
  • Filomain Nguemo
  • Hedi Peterson
  • Pilar Prieto
  • Robim M. Rodrigues
  • Agapios Sachinidis
  • Christoph Schäfer
  • Albert Sickmann
  • Dimitry Spitkovsky
  • Regina Stöber
  • Simone G. J. van Breda
  • Bob van de Water
  • Manon Vivier
  • René P. Zahedi
  • Mathieu Vinken
  • Vera Rogiers
Meeting Report

Abstract

SEURAT-1 is a joint research initiative between the European Commission and Cosmetics Europe aiming to develop in vitro- and in silico-based methods to replace the in vivo repeated dose systemic toxicity test used for the assessment of human safety. As one of the building blocks of SEURAT-1, the DETECTIVE project focused on a key element on which in vitro toxicity testing relies: the development of robust and reliable, sensitive and specific in vitro biomarkers and surrogate endpoints that can be used for safety assessments of chronically acting toxicants, relevant for humans. The work conducted by the DETECTIVE consortium partners has established a screening pipeline of functional and “-omics” technologies, including high-content and high-throughput screening platforms, to develop and investigate human biomarkers for repeated dose toxicity in cellular in vitro models. Identification and statistical selection of highly predictive biomarkers in a pathway- and evidence-based approach constitute a major step in an integrated approach towards the replacement of animal testing in human safety assessment. To discuss the final outcomes and achievements of the consortium, a meeting was organized in Brussels. This meeting brought together data-producing and supporting consortium partners. The presentations focused on the current state of ongoing and concluding projects and the strategies employed to identify new relevant biomarkers of toxicity. The outcomes and deliverables, including the dissemination of results in data-rich “-omics” databases, were discussed as were the future perspectives of the work completed under the DETECTIVE project. Although some projects were still in progress and required continued data analysis, this report summarizes the presentations, discussions and the outcomes of the project.

Abbreviations

AFB1

Aflatoxin B1

ANOVA

Analysis of variance

AOP

Adverse outcome pathway

BSEP

Bile salt export pump

CsA

Cyclosporin A

DEG

Differentially expressed genes

DE-miRs

Differentially expressed miRNAs

DILI

Drug-induced liver injury

DKFZ

Deutsches Krebsforschungszentrum—Department of Biostatistics

DMG

Differentially methylated genes

DOX

Doxorubicin

ER

Endoplasmic reticulum

hiPSC-CMs

Human-induced pluripotent stem cell-derived cardiomyocytes

IC

Imperial College of Science, Technology and Medicine

IFADO

Leibniz Research Centre for Working Environment and Human Factors

IMU

Medizinische Universität Innsbruck

ISAS

Leibniz-Institut für Analytische Wissenschaften-ISAS-EV

ITEM

Fraunhofer-Gesellschaft zur Förderung der Angewandten Forschung E.V.

iTRAQ

Isobaric tags for relative and absolute quantification

JRC

Joint Research Centre

KBrO3

Potassium bromate

LC–MS/MS

Liquid chromatography-tandem mass spectrometry

LIMMA

Linear models for microarray data

LOEC

Lowest observed effect concentration

OTA

Ochratoxin A

PHH

Primary human hepatocytes

QURE

QURE Ltd

RTCA

Real-time cell analyser

TF

Transcription factors

UKK

Klinikum der Universität zu Köln

UL

Universiteit Leiden

UM

Universiteit Maastricht

VPA

Valproic acid

VUB

Vrije Universiteit Brussel

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Ruani N. Fernando
    • 1
  • Umesh Chaudhari
    • 2
  • Sylvia E. Escher
    • 3
  • Jan G. Hengstler
    • 4
  • Jürgen Hescheler
    • 2
  • Paul Jennings
    • 5
  • Hector C. Keun
    • 6
  • Jos C. S. Kleinjans
    • 7
  • Raivo Kolde
    • 8
  • Laxmikanth Kollipara
    • 9
  • Annette Kopp-Schneider
    • 10
  • Alice Limonciel
    • 5
  • Harshal Nemade
    • 2
  • Filomain Nguemo
    • 2
  • Hedi Peterson
    • 8
  • Pilar Prieto
    • 11
  • Robim M. Rodrigues
    • 1
  • Agapios Sachinidis
    • 2
  • Christoph Schäfer
    • 2
  • Albert Sickmann
    • 9
    • 12
    • 13
  • Dimitry Spitkovsky
    • 2
  • Regina Stöber
    • 4
  • Simone G. J. van Breda
    • 7
  • Bob van de Water
    • 14
  • Manon Vivier
    • 1
  • René P. Zahedi
    • 9
  • Mathieu Vinken
    • 1
  • Vera Rogiers
    • 1
  1. 1.Department of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and PharmacyVrije Universiteit BrusselBrusselsBelgium
  2. 2.Centre of Physiology and Pathophysiology, Institute of NeurophysiologyCentre for Molecular Medicine Cologne (CMMC)CologneGermany
  3. 3.Fraunhofer Institute for Toxicology and Experimental MedicineHannoverGermany
  4. 4.Leibniz Research Centre for Working Environment and Human Factors (IFADO)Technical University of DortmundDortmundGermany
  5. 5.The Division of Physiology, Department of Physiology and Medical PhysicsMedical University of InnsbruckInnsbruckAustria
  6. 6.Biomolecular Medicine, Department of Surgery and CancerImperial College LondonLondonUK
  7. 7.Department of ToxicogenomicsMaastricht UniversityMaastrichtThe Netherlands
  8. 8.QURE Ltd.TartuEstonia
  9. 9.Leibniz-Institut für Analytische Wissenschaften-ISAS-e.V.DortmundGermany
  10. 10.Division of BiostatisticsGerman Cancer Research Center (DKFZ)HeidelbergGermany
  11. 11.EURL ECVAM (The European Union Reference Laboratory for Alternatives to Animal Testing), Systems Toxicology Unit, Institute for Health and Consumer Protection, European CommissionJoint Research CentreIspraItaly
  12. 12.Department of Chemistry, College of Physical SciencesUniversity of AberdeenAberdeenScotland, UK
  13. 13.Medizinische Fakultät, Medizinische Proteom-Center (MPC)Ruhr-Universität BochumBochumGermany
  14. 14.Division of Toxicology, Leiden/Academic Centre for Drug ResearchLeiden UniversityLeidenThe Netherlands

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