Word
Action number 15018 Last updated 20/09/2011 08:20:27 Year 2012
Title Systems Toxicology
Acronym ST
Type Action
Url
Institute JRC.I Institute for Health and Consumer Protection (Ispra)
Leader BERGGREN Katarina JRC.I.5   E-Mail
Thematic Area TA4 - Safety of Food and Consumer Products
TA4.HLO1 - To ensure EU-wide harmonised approaches via the provision of validated analytical methods for identification, characterisation, detection and quantification of substances in food and consumer products falling under EU legislative and consumer concern
TA4.HLO3 - To develop improved systems, frameworks, and tools for assessing human-health risk from factors including manufactured chemicals, chemical emissions, nanomaterials, and environmental noise; and to co-ordinate consensus-reaching processes of EU Member State national risk assessment bodies and to operate the European Union Reference Laboratory for Alternatives to Animal Testing (ECVAM)
TA4.HLO5 - To provide evidence-based and scientifically circumspect opinion on the impact of food and dietary choices in health and quality of life, as an information source for the general public and to feed into the policy and regulatory processes
1 Prosperity in a Knowledge intensive society
1.5 Life Sciences and biotechnology

AGRI - Agriculture and Rural Development
ENTR - Enterprise and Industry
ENV - Environment
JRC KB - JRC Knowledge Base
RTD - Research and Innovation
SANCO - Health and Consumers


Cosmetics Europe - European Cosmetics Association
ECHA - European Chemicals Agency (ECHA)
ILSI - Europe - International Life Science Institute Europe
OECD - Organisation for Economic Co-operation and Development (OECD)
WHO - World Health Organization



EFSA - European Food Safety Agency
US-EPA - US Environmental Protection Agency
toxicology, risk assessment, mode of action, adverse outcome pathway, key event, in vitro method, non-testing method, computational modelling, structure-activity relationship, QSAR, chemical category, read-across, molecular modelling, toxicokinetics, toxicodynamics, PBBK, PBPK, metabonomics, high-throughput screening, high content imaging, electrophysiology, neurotoxicity, hepatotoxicity, combined exposure, mixture, statistics, chemometrics, biological model, cell model, endocrine active substance, EAS, endocrine disruption, nanomaterial, OHT, nanohub, nutrition, standardisation
Rationale
Systems Toxicology (ST) is one of the Actions implementing the work programe of JRC's Thematic Area 4 (TA4 - Safety of Food ad Consumer Products). In particular, it addresses the TA's strategic objective in relation to developing improved methods and tools for risk assessment in order to make them more informative, intelligent and cost- and time-effective.

The common basic idea of the ST activities is to understand the toxicological mode of actions of chemicals, aiming on the identification of key events leading to an adverse systemic outcome. Chemicals can then be classified based on the initial key events detected through in vitro testing rather than on the final disease observed in the organism. Through further development of computational prediction models and in combination with in vitro data, also predictions of quantified risk assessment necessary for regulatory purpose will be further investigated.

ST focuses on: (1) improvement of the biological models used, always aiming on the best fit for purpose, (2) implementation and further development of technologies for detection and prediction of adverse effects on cellular level, (3) implementation of in vitro assays also in high throughput screening for sophisticated classification of tested materials based on their organelle and cellular effects, (4) development of computational models to better understand molecular initiating events and predict metabolic activity, (5) prediction of in vivo concentrations from in vitro dose-response curves (Physiologically Based Pharmacokinetic - PBPK modelling), and (6) development of data and knowledge bases to enable an efficient exchange of information with the entire research community and use this as a tool for building further strategies.

ST is multi-disciplinary in nature enabling the merging of different fields of expertise for a sustainable way forward towards an animal-free risk assessment with the emphasis on the paradigm shift towards a completely new approach for assessing chemicals. ST is a collaboration partner within the US EPA Tox 21 initiative and is a main contributor to the FP7 SEURAT-1 (Safety Evaluation Replacing Animal Testing – phase one) projects, and as well participates in related activities (including support to standardisation) at the OECD and WHO, especially in the context of Intergovernmental Programme on Chemical Safety (IPCS).

ST serves EU policies on safety of food and consumer products, in relation to endocrine disruption, combined exposure and mixtures, nanomaterials, alternative methods, and in the implementation of the REACH and CLP.
Summary of the activity
In 2012 ST aims to further implement a mode of action strategy for the assessment of chemicals combining technologies already applied within the action, such as High Throughput Screening, High Content Imaging, metabonomics, in vitro electrophysiology measurements and computational methods. The focus of the work will be to set up testing strategies focussed on hepatotocicity and neurotoxicity. The number of tested chemicals will be limited and dependent on the method used, to facilitate the possibility to maximise outcome through repeated and improved testing conditions and also directly related to computational predictions or statistical evaluations. Combination effects of chemicals will also be further investigated. The expected outcome is described in the deliverables under Objectives 1 and 2.

Objective 3 includes several initiatives related to chemicals with endocrine disrupting activities supporting the correspondent DG ENV policy area. The current ST activities for Endocrine Active Substances (EAS) are partly new and substantially enlarged in the WP 2012. The development of EAS database, supported by an Administrative Agreement (AA) with DG ENV, already started will be finalised. Further a new AA with DG ENV is set up to support the activities of an expert working group for the development of an EU criteria for identification of Endocrine Disruption to be applied horizontally within EU chemicals legislation. In addition to these activities the ST is scaling up and collecting data for estrogen and androgen receptor in vitro assays for profiling chemicals known to have endocrine activities (this activity is cross-linking to Objective 1).

Objective 4 is related to the Commission policy in the area of nanomaterials. Within this area, ST is closely collaborating with the NBS action (15024). Specific ST activities are related to profiling of nanomaterials to their mode of action (again cross-linking to Objective 1) both using the High Throughput Screening laboratory as well as computational prediction models by testing a large set of nanomaterials. In addition, the enhanced Nanohub database will be completed in 2012.

In the field of the strategic objective 3.1, ST is closely collaborating with the IVM action (15015). ST is supporting ECVAM (European Centre for Validation of Alternative Methods) with innovation related projects, and those are collected under Objective 5. In 2012 there is an emphasised activity on the standardisation and characterisation of stem cell models. Further in vitro cardiomyocyte testing is evaluated. ST is also contributing as a trial laboratory to an on-going ECVAM validation study on CYP induction, planned to be concluded in 2012.

In addition there is also an activity within the ST Action dedicated to nutrition and policy advice related to issues concerning health and food.

ST contributes to the following FP7 Indirect Actions through WP 2012: NANOTEST (30954), ENPRA (20579), PREDICT-IV (30603), NHECD (31045), COPHES (31637), COSMOS (31875), DETECTIVE (31877), SCR&TOX (31878), COACH (31879), ESNATS (30590), DIXA (…).
 
  1
To develop novel ways of categorising chemicals according to their toxicological mode-of-actions to facilitate read-across between chemical compounds to enable a more efficient and reliable hazard assessment, using hepatotoxicity and neurotoxicity as case studies (TA4 Str. Obj. 3, Gen. Obj. 3.3)
Deliverable  1.1
Description of the modes-of-action and related biochemical/biological key event effects associated with repeat-dose systemic toxicity
31/12/2012
Scientific Publications
The single market
JRC KB - JRC Knowledge Base
Deliverable  1.2
Datasets from in vitro High Throughput Screening (HTS), High Content Imaging (HCI), metabonomics and in vitro electrophysiology measurements to support mode-of-action identification and category formation
31/12/2012
Scientific Publications
The single market
JRC KB - JRC Knowledge Base
RTD - Research and Innovation
Deliverable  1.3
Datasets from in silico (QSAR) modelling to support mode-of-action identification and category formation
31/12/2012
Scientific Publications
The single market
JRC KB - JRC Knowledge Base
RTD - Research and Innovation
Cosmetics Europe - European Cosmetics Association
Deliverable  1.4
Establishment of data/knowledge basis (e.g. Key Events Catalogue Mode-of-Action Wiki, Effectopedia) to facilitate scientific community participation in the definition of modes-of-action together with SEURAT-1 and other external collaboration partners, as listed
31/12/2012
JRC Scientific Support - Scientific information systems and databases
The single market
RTD - Research and Innovation
Cosmetics Europe - European Cosmetics Association
OECD - Organisation for Economic Co-operation and Development (OECD)
WHO - World Health Organization
Deliverable  1.5
Training courses and workshops on mode-of-action and chemical categorisation in the context of collaborations within International Programme of Chemical Safety (IPCS), SEURAT-1 and other external partners.
30/11/2012
JRC Scientific Support - Training
The single market
RTD - Research and Innovation
Cosmetics Europe - European Cosmetics Association
WHO - World Health Organization
  2
To support the EU legislation on chemicals and develop tools to perform chemical risk assessment based on animal-free testing methods, and to devise a general testing strategy for assessing combination effects of chemicals (mixtures) for realistic exposure scenarios with emphasis on neurotoxicity and endocrine disruption (TA4 Str. Obj. 3, Gen. Obj. 3.3)
Deliverable  2.1
Physiological-based pharmaco-kinetic (PBPK) based computer models relating exposure data to internal dose for establishing in vivo activity thresholds (e.g. no-effect levels) from in vitro dose-response data
31/12/2012
Scientific Publications
The single market
JRC KB - JRC Knowledge Base
RTD - Research and Innovation
Cosmetics Europe - European Cosmetics Association
Deliverable  2.2
A method for expressing the uncertainty in risk assessment, resulting from the use of non-animal data, and predicting extrapolation factors for application to in vitro and in silico data
31/12/2012
Scientific Publications
The single market
JRC KB - JRC Knowledge Base
Deliverable  2.3
A method to establish TTCs (Thresholds of Toxicological Concern) based on non-animal data to be used in risk assessment
31/12/2012
Scientific Publications
The single market
JRC KB - JRC Knowledge Base
RTD - Research and Innovation
SANCO - Health and Consumers
Cosmetics Europe - European Cosmetics Association
ILSI  - Europe - International Life Science Institute Europe
Deliverable  2.4
Report on different approaches for the risk assessment of chemical mixtures combining computational predictions and in vitro cell-based measurements focusing on neurotoxicity and endocrine disruption
31/12/2012
Scientific Publications
The single market
TypeYearNumberTitle
C 200917820 Combination effects of chemicals - Council conclusions
ENV - Environment
JRC KB - JRC Knowledge Base
Deliverable  2.5
Report illustrating the possibilities of profiling REACH data sources as the basis of policy action, including practical limitations, and a report providing the results of database profiling exercises on properties or effects of policy interest, including recommendations on substances that may require further assessment and/or policy action.
28/09/2012
JRC contributions to policy documents
The single market
TypeYearNumberTitle
REG 20061907 Regulation concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) Reg. 1907/2006
SectionTopic
1: Forthcoming initiatives 2012Review of REACH
ENV - Environment
Deliverable  2.6
Content update and maintenance of databasis supporting implementation of chemicals legislation and related activites, such as EDEXIM (European Database Export Import of Dangerous Chemicals), JRC (Q)SAR Model Database (including information on QSAR models in the form of standardised reporting formats in support to regulatory (e.g. REACH) submissions that include the use of non-testing data), CLASSLAB (searchable format of Annex VI to the CLP Regulation), ESIS (European chemical Substances Information System), EU Wine Databank and CHELIST (Chemical Lists Information System).
31/12/2012
JRC Scientific Support - Scientific information systems and databases
The single market
TypeYearNumberTitle
REG 20061907 Regulation concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) Reg. 1907/2006
REG 2008555 Regulation (EC) No 555/2008 laying down detailed rules for implementing Council Regulation (EC) No 479/2008 on the common organisation of the market in wine as regards support programmes, trade with third countries, production potential and on controls in the wine sector
REG 2008689 Regulation (EC) 689/2008 concerning the export/import management process of dangerous chemicals
REG 20081272 Regulation (EC) 1272/2008 on classification, labelling and packaging of substances and mixtures
SectionTopic
1: Forthcoming initiatives 2012Review of REACH
AGRI - Agriculture and Rural Development
ENTR - Enterprise and Industry
ENV - Environment
ECHA - European Chemicals Agency (ECHA)
  3
To support the implementation of the EU Community strategy on Endocrine Disrupting Chemicals (EDCs), by participating in the definition of a scientific criteria to identify EDCs, creating the EAS (Endocrine Active Substances) web portal, and identifying substances of potential ED concern (TA4 Str. Obj. 3, Gen. Obj. 3.2)
Deliverable  3.1
Establishment of a web portal database for managing Endocrine Active Substances information, based on OECD Harmonised Templates (OHT).
28/09/2012
JRC Scientific Support - Scientific information systems and databases
The single market
TypeYearNumberTitle
SEC 20111001 4th Report on the implementation of the ''Community Strategy for Endocrine Disrupters'' a range of substances suspected of interfering with the hormone systems of humans and wildlife (COM (1999) 706).
SectionTopic
1: Forthcoming initiatives 2012Strategy on endocrine disruptors
ENV - Environment
Deliverable  3.2
A revised OECD Harmonised Template (OHT) for capturing data focusing in particular on "intermediate effects" (observed via in vitro and/or in silico methods)
31/05/2012
JRC Scientific Support - Scientific information systems and databases
The single market
TypeYearNumberTitle
SEC 20111001 4th Report on the implementation of the ''Community Strategy for Endocrine Disrupters'' a range of substances suspected of interfering with the hormone systems of humans and wildlife (COM (1999) 706).
SectionTopic
1: Forthcoming initiatives 2012Strategy on endocrine disruptors
ECHA - European Chemicals Agency (ECHA)
OECD - Organisation for Economic Co-operation and Development (OECD)
Deliverable  3.3
Policy support documents on endocrine-disrupting (ED) criteria to support DG ENV in their process to propose amendments to EU chemicals legislation for inclusion of ED criteria, based on a review of expert reports, MS proposals and discussions in an expert group co-ordinated and chaired by the ST Action
31/12/2012
JRC contributions to policy documents
The single market
TypeYearNumberTitle
SEC 20111001 4th Report on the implementation of the ''Community Strategy for Endocrine Disrupters'' a range of substances suspected of interfering with the hormone systems of humans and wildlife (COM (1999) 706).
ENV - Environment
Deliverable  3.4
Policy support documents providing advice on test strategy development, method validation, and performance-based test guideline definitions in the OECD EDTA TF (Endocrine Disrupter Testing and Assessment Task Force) and the OECD VMG NA (Validation Management Group for Non-Animal Testing)
31/12/2012
JRC contributions to policy documents
The single market
TypeYearNumberTitle
SEC 20111001 4th Report on the implementation of the ''Community Strategy for Endocrine Disrupters'' a range of substances suspected of interfering with the hormone systems of humans and wildlife (COM (1999) 706).
SectionTopic
1: Forthcoming initiatives 2012Strategy on endocrine disruptors
ENV - Environment
OECD - Organisation for Economic Co-operation and Development (OECD)
Deliverable  3.5
Datasets from high throughput screening (HTS) measurements of estrogen receptor/androgen receptor (ER/AR) assays, contributing to performance evaluation and standardisation of such assays for inclusion in the OECD testing framework (also contributing to Gen. Obj. 3.1)
31/12/2012
Scientific Publications
The single market
TypeYearNumberTitle
SEC 20111001 4th Report on the implementation of the ''Community Strategy for Endocrine Disrupters'' a range of substances suspected of interfering with the hormone systems of humans and wildlife (COM (1999) 706).
JRC KB - JRC Knowledge Base
OECD - Organisation for Economic Co-operation and Development (OECD)
  4
To identify nanomaterial specific hazard categories based on the toxicological mode-of-actions as predicted for selected nanomaterials available in the JRC repository; and to further develop the Nanohub database in collaboration with the NBS action (15024) (TA4 Str. Obj. 3, Gen. Obj. 3.2)
Deliverable  4.1
Datasets from in vitro High Throughput Screening (HTS) measurements of the approximately 25 nanomaterials stored in the JRC repository to support mode-of-action identification and category formation
31/07/2012
Scientific Publications
The single market
TypeYearNumberTitle
SEC 20082036 REGULATORY ASPECTS OF NANOMATERIALS
JRC KB - JRC Knowledge Base
RTD - Research and Innovation
Deliverable  4.2
Results of applying a mode-of-action toxicity prediction framework to selected nanomaterials
31/07/2012
Scientific Publications
The single market
TypeYearNumberTitle
SEC 20082036 REGULATORY ASPECTS OF NANOMATERIALS
ENV - Environment
JRC KB - JRC Knowledge Base
RTD - Research and Innovation
Deliverable  4.3
Enhanced Nanohub database incorporating the revised OECD Harmonised Templates for physico-chemical properties and intermediate biological effects
31/07/2012
JRC Scientific Support - Scientific information systems and databases
The single market
TypeYearNumberTitle
SEC 20082036 REGULATORY ASPECTS OF NANOMATERIALS
ENV - Environment
RTD - Research and Innovation
  5
To provide quality-controlled in vitro models, including the characterisation of their phenotype, definition of cell culture protocols, and evaluation of their suitability for safety assessment (including the validation of the Cytochrome P450 Induction Test and the validation of transcriptional assays for detection of (anti)-estrogenic compounds) in support to the innovation pillar of ECVAM (European Centre for the Validation of Alternative Methods) (TA4 Str. Obj.3, Gen. Obj. 3.1)
Deliverable  5.1
Report on the amplification of quality-controlled undifferentiated stem cells, and definition of standardised quality controls for stem cells to be used in toxicological tests
31/12/2012
JRC Scientific Support - Validated methods, Reference methods and measurements
The single market
RTD - Research and Innovation
Cosmetics Europe - European Cosmetics Association
Deliverable  5.2
Standard Operation Procedure (SOP) for the automated video analysis of beating cardiomyocyte cultures in vitro and demonstration application to cardiomyocyte testing with a small set of reference compounds
31/12/2012
JRC Scientific Support - Validated methods, Reference methods and measurements
The single market
Deliverable  5.3
Test reports as a participant trial laboratory in the validation study for the Cytochrome P450 Induction Test using human cryo-HepaRG and cryopreserved human hepatocytes, in collaboration with IVM (15015).
31/07/2012
JRC Scientific Support - Validated methods, Reference methods and measurements
The single market
TypeYearNumberTitle
DIR 201063 Directive on the protection of animals used for scientific purposes
ENTR - Enterprise and Industry
ENV - Environment
OECD - Organisation for Economic Co-operation and Development (OECD)
Deliverable  5.4
Test reports on toxicogenomic analysis derived from stem cell based toxicity test in the context of pre/postnatal development
31/12/2012
Scientific Publications
The single market
JRC KB - JRC Knowledge Base
RTD - Research and Innovation
Cosmetics Europe - European Cosmetics Association
Deliverable  5.5
Guidance for test developers of in vitro tests together with descriptions of how to document test protocols, carry out data analysis and undertake in-house performance assessment, for publication on the Institute's web site
31/12/2012
JRC Scientific Support - Validated methods, Reference methods and measurements
The single market
RTD - Research and Innovation
  • Search by Keyword icon.help