ECVAM Key Area Sensitisation: Overview on Activities Silvia Casati, Chantra Eskes.
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Transcript of ECVAM Key Area Sensitisation: Overview on Activities Silvia Casati, Chantra Eskes.
ECVAM Key Area Sensitisation:
Overview on Activities
Silvia Casati, Chantra Eskes
ECVAM Key Area Sensitisation
Refine
Reduce
Replace
Collaboration with industries
Support to policies:• Cosmetics Directive• REACH
Task Forceinput
Research Activities
Test development
Prevalidation/Validation
LLNA related activities
Budget: 11 M€Partners: 28 (including universities, research institutes, industries, SMEs, JRC)Coordinator: Erwin Roggen (Novozymes) Duration: October 2005 – November 2010
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.
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-ivNovel Testing Strategies for In Vitro Assessment of Allergens
WP8: In vitro assaydevelopment
WP7: Data Management
WP9:Technology transfer
&Dissemination
Technology module (Months 0-60)
(Months 0-60)
WP1: Compound Selection
WP3: DC – T-cell Interactions and biology
WP2: EC- DC
interactionsand biology
WP4: Genomics
WP5: Proteomics
WP6: Metabonomics
Science module (Months 0-36)
WP
10:
Pro
ject
man
agem
ent
(Mo
nth
s 0-
60)
Sens-it-iv StructureSens-it-iv Structure
Coordination BoardE. Roggen (coordinator)
H. Weltzien (vice-coordinatorIPR, Financial and legal Officers
Steering CommitteeE. Roggen, S. Casati, O. De Silva
D. Basketter, I. Kimber, H. Weltzien
Management TeamE. Roggen, S. Casati, C. BorrebaeckF. Sallusto, H.J. Thierse, K. Park, C. Helma, S. Gibbs, H. Hermans
EuropeanCommission
WP10
WP9
WP8
WP7WP6WP5
WP4
WP3
WP2
WP1
Adv
isor
yC
omm
ittee
s
General Assembly
WP1: Chemicals SelectionWP1: EC - DC interactions WP3: DC - T-cell interactions WP4: GenomicsWP5: ProteomicsWP6: MetabonomicsWP7: Data ManagementWP8: In vitro assays development WP9: Technology transfer &
disseminationWP10: Project management
ECVAM Involvement in Sens-it-iv
• 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)
Sens-it-iv WP1: 24 Months Achievements
“Dendritic cells as a tool for a predictive identification of skin sensitization hazard” (2004)
“The relevance of epidermal disposition for sensitisation hazard identification and risk assessment” (2006)
“Chemical reactivity measurement and the predictive identification of skin sensitisers” (2007)
Skin penetration
Protein binding
DC activation
DC migration
DC TCELL DC- T cell
interactions
Memory T cells
EC
EC
Others
Chemical Respiratory Allergy: Opportunities for
Hazard Identification and Characterisation
Relevant Workshops
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:
• An assessment of the available human, animal and alternative data
• In vivo testing
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
• 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
• 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
Revised approach of the standard LLNA
to reduce animal use in skin sensitisation testing
Standard LLNA
• 3 concencentrations test chemical
• + vehicle control
• 4-5 mice/group
Reduced-LLNA
• top concencentration 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
Reduced-LLNA
For further information on ECVAM activities please contact:
For further information on Sens-it-iv please access:
http://www.sens-it-iv.eu/