ECVAM - IHCP - JRC

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ECVAM Key Area Sensitisation Overview on
Activities Silvia Casati, Chantra Eskes
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ECVAM Key Area Sensitisation
Task Force input
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Sens-it-iv Novel Testing Strategies for In Vitro
Assessment of Allergens
Budget 11 M Partners 28 (including
universities, research institutes, industries,
SMEs, JRC) Coordinator Erwin Roggen (Novozymes)
Duration October 2005 November 2010
Deliverable In vitro tests and test strategies
ready to be validated, allowing the testing of
the sensitising potency of existing and new
chemical entities for classification and
labelling and for the purpose of risk assessment.

• Sens-it-iv aims to develop assay systems that
  model sensitisation, rather than irritation and
  toxicity of chemicals and proteins.
• The innovative aspect of the project is the
  coordinated and extensive characterisation of the
  impact of compounds on cell-cell interactions for
  the identification of the key mechanisms involved
  in sensitisation.

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Sens-it-iv Structure
Sens-it-iv Structure
Science module (Months 0-36)
(Months 0-60)
WP9 Technology transfer Dissemination
WP1 Compound Selection
WP2 EC- DC interactions and biology
WP3 DC T-cell Interactions and biology
WP7 Data Management
WP6 Metabonomics
WP10 Project management (Months 0-60)
WP8 In vitro assay development
WP5 Proteomics
WP4 Genomics
Technology module (Months 0-60)
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ECVAM Involvement in Sens-it-iv
Coordination Board E. Roggen (coordinator) H.
Weltzien (vice-coordinator IPR, Financial and
legal Officers
WP1 Chemicals Selection WP1 EC - DC
interactions WP3 DC - T-cell interactions
WP4 Genomics WP5 Proteomics WP6
Metabonomics WP7 Data Management WP8 In
vitro assays development WP9 Technology
transfer dissemination WP10 Project
management
European Commission
Advisory Committees
Steering Committee E. Roggen, S. Casati, O. De
Silva D. Basketter, I. Kimber, H. Weltzien
Management Team E. Roggen, S. Casati, C.
Borrebaeck F. Sallusto, H.J. Thierse, K. Park,
C. Helma, S. Gibbs, H. Hermans
WP10
WP1
WP2
WP9
WP3
WP8
WP4
WP7
WP5
WP6
General Assembly
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Sens-it-iv WP1 24 Months Achievements

• Selection of a tutorial set of compounds
• Repository established in ECVAM and chemicals
  distribution to other partners
• Procedures for chemicals handling
• Extended list of chemicals for subsequent project
  phases
• Database under development on physico-chemical
  properties of compounds and published in vitro
  and in vivo data (human and animal)

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Relevant Workshops
The relevance of epidermal disposition for
sensitisation hazard identification and risk
assessment (2006)
Chemical reactivity measurement and the
predictive identification of skin sensitisers
(2007)
Dendritic cells as a tool for a predictive
identification of skin sensitization hazard
(2004)
Others Chemical Respiratory Allergy
Opportunities for Hazard Identification and
Characterisation
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Collaboration with Industries
Definition of a set of reference chemicals for
methods development and evaluation
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The LLNA and REACH
Regulation (EC) N. 1907/2006 concerning the
Registration, Evaluation, Authorisation and
Restriction of Chemicals (REACH) Applies to new
and about 30,000 existing substances Annex
VII Standard information requirements for
substances manufactured or imported in quantities
of 1 tonne or more
The LLNA is the first-choice method for in vivo
testing Only in exceptional circumstances
should another test be used Justification for
the use of another test shall be provided

• Skin sensitisation
• An assessment of the available human, animal and
  alternative data
• In vivo testing

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• Under Peer Review
• Workshop on Alternative Endpoints for the LLNA
  Ispra, 25-27 September 2007
• Method under evaluation
• Peer-review panel being established
• ESAC statement - April 07
• Inclusion into RIP 3.3 TGD
• Draft TG submitted to CA

LLNA Related Activities

• LLNA Performance Standards
• Modifications to the standard LLNA incorporating
  non-radioactive endpoints
• Validation of the standard LLNA for the purposes
  of measuring relative potency using EC3 values
• Reduced LLNA

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Reduced-LLNA
Revised approach of the standard LLNA to reduce
animal use in skin sensitisation testing

• Reduced-LLNA
• top concencentration test chemical
• vehicle control
• 4-5 mice/group

• Standard LLNA
• 3 concencentrations test chemical
• vehicle control
• 4-5 mice/group

16-20 mice
8-10 mice
Does not provide information on potency For risk
assessment purposes a standard LLNA should be
conducted
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For further information on ECVAM activities
please contact silvia.casati_at_jrc.it For further
information on Sens-it-iv please
access http//www.sens-it-iv.eu/