Alternative Methods to Animal Testing A Cosmetic Industry Perspective

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Alternative Methods to Animal Testing A
Cosmetic Industry Perspective

• Conference on Alternative Approaches to Animal
  Testing
• EUROPE GOES ALTERNATIVE
• Brussels, 7 November 2005
• Odile de Silva
• LOréal

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LOREAL contribution to Validation Studies and
International Programmes on Alternative Methods

• 1989 LOréal ends tests on cosmetic finished
  products
• 1992 EC/HO Validation study on eye irritation
  (3 methods)
• 1993 MEIC Programme and acute toxicity
• IRAG Alternatives to eye irritation (8
  methods).
• 1994 Ring study on the BCOP test
• 1995 ECVAM/COLIPA Validation study on
  Phototoxicity
• 1996 Colipa Validation study on eye irritation
  (2 methods)
• 1997 4th FWP Langerhans cells in reconstructed
  skin
• - Human skin models
• 1999 Colipa Guidelines on in vitro percutaneous
  absorption
• 2000 ECVAM pre validation study on skin
  irritation
• 2001 BIOMED II
• 2002 Dendritic cells and the Colipa Research
  Programme
• 2004 ECVAM validation study on skin irritation
• 2005 6th FWP - Sensitiv

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PCOP for liquid and water-soluble materials
Prediction of MAS
Statistical analysis on 41 substances predicted
MAS 8.08 26.16 X DO30 5.47 X DO30²

Concordance 90 Kappa
0.83 (plt0.01). R2 0.84
95 confidence intervals too wide
? overpredicted ? underpredicted.
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Reconstructed skin and LOréal
RESEARCH
 Tanned epidermis 
 Epidermis mimicking an allergenic response 
The full reconstructed human skin ( E. Bell, D.
Asselineau)
The 1rst living reconstructed human epidermis
(M. Pruniéras, M. Régnier)
1994
1986
1983
1997
2002
2001
2005
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Replacement of the skin irritancy test
The EpiSkin Model
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Replacement of the skin irritancy test
Viability endpoint -Predictive model
Set of 48 chemicals -20- Irritants -28- Non
Irritants
Performance
Recommended ECVAM limits
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Episkin ranking compounds according their
transcutaneous diffusion potential
Stratum corneum
Viable epidermis
Collagen Matrix
Used in wells
RF receptor fluid
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Comet assay on Episkin Detection of
photogenotoxic compounds
UV-A 15 min
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Epidermis and Langerhans cells
Physiology of Langerhans cells
Langerin positive cells
Epidermal sheet
Histology
Sensitisation
Photoimmunosuppression and UV
Control
Irritant
Sensitiser
SSR UV filters
Control
SSR
M. Régnier et al., J.Invest.Dermatol., 1997 V.
Facy et al. , J. Invest. Dermatol. , 2004
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In vitro identification of contact sensitizers
with human cell lines one component of the
battery ?
U937 cell line Read out system 48h
U937 / CD86 test LOréal internal validation 67
references tested including 52
sensitizers Accuracy with human clinic
95 Kappa 0.91
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The use of the Reconstructed Human Epidermis
Model EPISKIN as a predictive in vitro
irritation model for cosmetic ingredients. Compar
ison of 2 cationic surfactants differing only by
their carbon chain length (C-22 and
C-16).Similarity between human clinical
irritation scores and in vitro results
C-16 carbons
C-22 carbons
In vitro strong decrease of epidermis viability
(50 reduction). Poor tolerance, dose-effect. In
vivo(clinical data) Significant increase of
irritation values since 0.125. Irritant, with
dose-effect
In vitro no change in epidermis viability. Good
tolerance In vivo(clinical data) no significant
increase of irritation values. Well tolerated
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The COLIPA research and development programme
(since 1992)

• To develop novel approaches in the cosmetics
  fields of expertise for product safety assessment
  that do not involve any new animal testing.

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THE COSMETIC CONTEXT

• RISK ASSESSMENT and NOT HAZARD Article 2 of the
  Cosmetics Directive
• NOT ONLY TOLERANCE BUT SYSTEMIC AND SUB-CHRONIC
  TOXICITY

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COLIPA-SCAAT ACTIVITIES

• The Steering Committee for Alternatives to Animal
  Testing (SCAAT) has provided a focal point for
  the cosmetics industrys efforts in the EU to
  develop alternative approaches for over 10 years
• The COLIPA RD programme is directed towards
  identifying novel cellular and molecular
  endpoints for incorporation into new / improved
  alternative methods
• It is the intention that these alternative
  methods and strategies will be developed and
  evaluated to the stage that they are ready for
  prevalidation

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Not applicable
Toxicity
2009
Genotoxicity
Photomutagenicity
Eye irritation
Subacute Subchronic
Skin sensitisation
Skin irritation
Photosensitisation
Acute toxicity
Toxicokinetics
2013
Phototoxicity
Teratogenicity
Percutaneous absorption
Reprotoxicity
Finished Products
Skin corrosion
Carcinogenicity
Done
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THE COLIPA STRATEGY FOR THE DEVELOPMENT OF IN
VITRO ALTERNATIVES TO SKIN SENSITISATION

• COLLABORATION
• With ECVAM in their respective COLIPA ECVAM
  TFs ECVAM Workshops
• With other industry sectors chemical
  pharmaceutical companies
• With academia through COLIPA EU sponsored
  projects

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THE COLIPA STRATEGY FOR THE DEVELOPMENT OF IN
VITRO ALTERNATIVES TO SKIN IRRITATION
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THE COLIPA STRATEGY FOR THE DEVELOPMENT OF IN
VITRO ALTERNATIVES IN EYE IRRITATION
DEVELOP NEW OR IMPROVED METHOD READY FOR
PREVALIDATION
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THE COLIPA STRATEGY FOR THE DEVELOPMENT OF IN
VITRO ALTERNATIVES IN GENOTOXICITY
DEVELOPMENT OF THE COLIPA STRATEGY
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OTHER ENDPOINTS RD NEEDS

• COLIPA current focus/priorities cover the fields
  where we have expertise eye and skin
  irritation, skin sensitisation, and genotoxicity.
• There is a clear need to develop alternative
  approaches that cover all toxicological endpoints
• The cosmetic industry scientists have no specific
  expertise for developing systemic and chronic
  toxicity alternative approaches.
• Other partners national government labs, ECVAM,
  and other industry sectors are very active in
  some of these areas (e.g. reproductive toxicity,
  acute toxicity)

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THE CHALLENGES

• Good science the cutting edge
• To attract the best scientists from academia
• To start now integrated projects for systemic and
  sub-chronic toxicity
• To combine all these data
• Systems Biology
• New and pragmatic thinking
• Thresholds of Toxicological Concern (TTC)

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FACING UP TO THE CHALLENGES

• The cosmetics industry has taken a leading role
  in its areas of expertise
• The cosmetics industry is ready to work in
  partnership with other stakeholders for the
  remaining challenges and to respond in a positive
  way to the EU political agenda in relation to
  developing alternative approaches to animal
  testing for assessing safety
• For the cosmetics industry , the SAFETY of its
  products is, and must always remain, the number
  one priority