ECVAM Key Area Sensitisation:
Overview on Activities
Silvia Casati, Chantra Eskes
ECVAM Key Area Sensitisation
Research Activities
Refine
Test development
Reduce
Prevalidation/Validation
Collaboration with
industries
Support to policies:
• Cosmetics Directive
• REACH
Replace
LLNA related
activities
Task Force
input
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.
Sens-it-iv
Sens-it-iv Structure
Structure
Science module (Months 0-36)
(Months 0-60)
WP9:
Technology transfer
&
Dissemination
WP10: Project management (Months 0-60)
WP1:
Compound Selection
WP2:
EC- DC
interactions
and biology
WP3:
DC – T-cell
Interactions
and biology
WP6:
Metabonomics
WP7:
Data Management
WP8:
In vitro assay
development
WP4:
Genomics
WP5:
Proteomics
Technology module (Months 0-60)
ECVAM Involvement in Sens-it-iv
Coordination Board
European
Commission
E. Roggen (coordinator)
H. Weltzien (vice-coordinator
IPR, Financial and legal Officers
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
WP1
WP2
WP10
WP9
WP3
WP8
WP4
WP5
WP7
WP6
General Assembly
WP1:
WP1:
WP3:
WP4:
WP5:
WP6:
WP7:
WP8:
WP9:
Chemicals Selection
EC - DC interactions
DC - T-cell interactions
Genomics
Proteomics
Metabonomics
Data Management
In vitro assays development
Technology transfer &
dissemination
WP10: Project management
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)
Relevant Workshops
Skin
penetration
Protein
binding
EC
EC
DC activation
DC migration
DC
TCELL
DC- T cell
interactions
Memory T
cells
“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
Collaboration with Industries
Definition of a set of reference chemicals for methods
development and evaluation
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
Skin sensitisation:
The LLNA is the first-choice method
for in vivo testing
• An assessment of the
available human, animal and
alternative data
Only in exceptional circumstances
should another test be used
• In vivo testing
Justification for the use of another
test shall be provided
LLNA Related Activities
• LLNA Performance Standards
• Under Peer Review
• Modifications to the standard
LLNA incorporating nonradioactive endpoints
• Workshop on: “Alternative Endpoints for
the LLNA” Ispra, 25-27 September 2007
• Validation of the standard
LLNA for the purposes of
measuring relative potency
using EC3 values
• Peer-review panel being
established
• Reduced LLNA
• Method under evaluation
• ESAC statement - April ’07
• Inclusion into RIP 3.3 TGD
• Draft TG submitted to CA
Reduced-LLNA
Revised approach of the standard LLNA
to reduce animal use in skin sensitisation testing
Standard LLNA
Reduced-LLNA
•
3 concencentrations
test chemical
• top concencentration test
chemical
•
+ vehicle control
• + vehicle control
•
4-5 mice/group
• 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
For further information on ECVAM activities please contact:
[email protected]
For further information on Sens-it-iv please access:
http://www.sens-it-iv.eu/