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:

silvia.casati@jrc.it

For further information on Sens-it-iv please access:

http://www.sens-it-iv.eu/