1. OF COSMETIC PRODUCTS IN THE EU
SAFETY ASSESSMENT
OF COSMETIC PRODUCTS IN THE EU
Vera ROGIERS
Head of Dept. of Toxicology Vrije Universiteit Brussel Belgium

2. CONTENTS  ACTUAL EU COSMETICS LEGISLATION
 RISK ASSESSMENT OF COSMETIC INGREDIENTS ACCORDING TO THE NOTES OF GUIDANCE OF SCCS
 RISK ASSESSMENT FOR COSMETIC PRODUCTS IN THE EU
 ROLE OF RESPONSIBLE PERSON

3. CONTENTS  ACTUAL EU COSMETICS LEGISLATION
 RISK ASSESSMENT OF COSMETIC INGREDIENTS ACCORDING TO THE NOTES OF GUIDANCE OF SCCS
 RISK ASSESSMENT FOR COSMETIC PRODUCTS IN THE EU
 ROLE OF RESPONSIBLE PERSON

4. ACTUAL EU COSMETICS LEGISLATION
11/7/2013
COUNCIL DIRECTIVE
76/768/EEC
COSMETICS REGULATION / RECAST
N° 1223/2009
TESTING & MARKETING BANS
SAME BASIC PRINCIPLES APPLY
ARTICLES & ANNEXES
RESPONSIBILITY OF COMPANY
SAFE PRODUCT FOR CONSUMER (art. 3)
SAFETY IS BASED UPON SAFE INGREDIENTS (toxicological profile, chemical structure, exposure, art.10)
DEMONSTRATION OF SAFETY (art. 10 – 11)
PROVIDING ADEQUATE INFORMATION
AUTHORITIES
Notification (CPNP)
(art. 13)
CONSUMER
Safe use
(art )

5. ACTUAL EU COSMETICS LEGISLATION
TWO CHANNELS ARE FUNCTIONAL IN THE SAFETY ASSESSMENT PROCESS
SUBSTANCES ON ANNEXES
SCCS IN DG SANCO
DG SANCO
II, III, IV, V, VI
WRITTEN SAFETY EVALUATION (opinion)
RISK MANAGEMENT
BY COMMISSION
FOR CONSUMER
PROTECTION
COMMISSION
SUBSTANCES / MIXTURES IN FINISHED PRODUCT AND PRODUCT
SAFETY ASSESSOR
RESPONSIBLE
PERSON
COSMETIC SAFETY REPORT A & B
WRITTEN SAFETY EVALUATION (cosmetic product safety assessment)
RISK MANAGEMENT
INDUSTRIAL MEASURES
FOR
CONSUMER PROTECTION
INDUSTRY
TIF :

6. ACTUAL EU COSMETICS LEGISLATION
SCCS OPINIONS
RISK ASSESSMENTS ON COSMETIC SUBSTANCES PRESENT ON ANNEXES (II, III, IV, V, VI, Reg.1223/2009)
ADVICE ON SCIENTIFIC ISSUES RELATED TO SAFETY OF COSMETICS AND THEIR INGREDIENTS
ADVICE TO COMMISSION
(-) ANNEX II : FORBIDDEN SUBSTANCES
(-) ANNEX III : RESTRICTED SUBSTANCES WITH CONCERN FOR HUMAN HEALTH
(+) ANNEX IV : COLORANTS
(+) ANNEX V : PRESERVATIVES
(+) ANNEX VI : UV-FILTERS
ACCORDING TO TRANSPARANT RULES
NOTES OF GUIDANCE (NoG)
SCCS : Scientific Committee on Consumer Safety

7. ACTUAL EU COSMETICS LEGISLATION
THE SCCS’s NOTES OF GUIDANCE FOR THE TESTING OF COSMETIC SUBSTANCES AND THEIR SAFETY EVALUATION
8th REVISION (SCCS/1501/12)
Notes of Guidance available on website :
Opinions available on website :

8. CONTENTS  ACTUAL EU COSMETICS LEGISLATION
 RISK ASSESSMENT OF COSMETIC INGREDIENTS ACCORDING TO THE NOTES OF GUIDANCE OF SCCS
 RISK ASSESSMENT FOR COSMETIC PRODUCTS IN THE EU
 ROLE OF RESPONSIBLE PERSON

9. 1) HAZARD IDENTIFICATION RISK CHARACTERISATION
RISK ASSESSMENT : WHAT ?
1) HAZARD IDENTIFICATION
2) DOSE-RESPONSE
3) EXPOSURE ASSESSMENT
RISK CHARACTERISATION
RISK MANAGEMENT
RISK COMMUNICATION

10. RISK ASSESSMENT OF COSMETIC INGREDIENTS
1) HAZARD IDENTIFICATION
2) DOSE-RESPONSE
3) EXPOSURE ASSESSMENT
RISK CHARACTERISATION
- CAN X CAUSE ADVERSE HEALTH EFFECT ?
- BASED ON : - EPIDEMIOLOGICAL STUDIES
- CLINICAL STUDIES
- IN VIVO STUDIES
- IN VITRO STUDIES
- QSAR
HAZARD :
INTRINSIC
PROPERTIES
OF SUBSTANCES
- PHYSICOCHEMISTRY, STABILITY
- SCIENTIFIC LITERATURE

11. RISK ASSESSMENT OF COSMETIC INGREDIENTS
1) HAZARD IDENTIFICATION
2) DOSE-RESPONSE
3) EXPOSURE ASSESSMENT
RISK CHARACTERISATION
HAZARD TESTS PRESENT IN NOTES OF GUIDANCE (SCCS/1501/12)
- skin and eye irritation
- skin sensibilisation
- dermal absorption
- mutagenicity/genotoxicity
acute toxicity
- repeated dose toxicity
- reproductive toxicity
- carcinogenicity
- toxicokinetics
- photo-induced toxicity (if relevant)
- human data (if available)

12. RISK ASSESSMENT OF COSMETIC INGREDIENTS HAZARD IDENTIFICATION
TRADITIONALLY, HAZARD TESTS ARE BASED ON USE OF ANIMALS
IN EU, CLEAR WISH OF ALL STAKEHOLDERS TO IMPLEMENT 3Rs STRATEGY, CONSISTING OF REFINEMENT, REDUCTION AND REPLACEMENT
WHENEVER POSSIBLE RESULTS OF IN VITRO REPLACEMENT TESTS ARE GIVEN TO GUARANTEE SAFETY OF COSMETICS IN EUROPE. THESE MUST BE VALIDATED

13. RISK ASSESSMENT OF COSMETIC INGREDIENTS
HAZARD IDENTIFICATION TESTS IN TIF
PHYSICO-CHEMICAL CHARACTERISATION :
emphasis on :
purity
solubility
partition coefficient (log Pow)
stability in solution
(in chemico tests)
ACUTE TOXICITY : oral rat (3R- in vivo test); if available (mostly for classification)
LOCAL TOXICITY :
- Irritation and corrosivity
Skin irritation : non-irritative at maximal use concentration (in vitro tests)
Eye/mucosa irritation : non-irritative at maximal use concentration
(in vitro screening tests ; in vivo)
Skin sensitisation : Sensitisation not excluded ; preferably non-sensitising (LLNA : 3R- in vivo test → in vitro tests)

14. RISK ASSESSMENT OF COSMETIC INGREDIENTS
HAZARD IDENTIFICATION TESTS IN TIF
SYSTEMIC TOXICITY
Dermal absorption (in vitro test)
Dermatomed pig or human skin ( µ)
Repeated dose toxicity (in vivo test)
90- day oral study in rat
Mutagenicity/genotoxicity tests (in vitro tests)
3 endpoints of genotoxicity
gene mutation
structural aberrations (clastogens)
aneuploidy (aneugens)
when → overruled by Θ in vivo test
Carcinogenicity (in vivo test) : if available
Reproductive toxicity (in vivo test)
maternal toxicity
mostly : teratogenicity

15. RISK ASSESSMENT OF COSMETIC INGREDIENTS
1) HAZARD IDENTIFICATION
2) DOSE-RESPONSE
3) EXPOSURE ASSESSMENT
RISK CHARACTERISATION
- WHAT IS RELATIONSHIP BETWEEN DOSE AND INCIDENCE / SEVERITY OF ADVERSE HEALTH EFFECT ?
- WHAT IS DOSE NECESSARY TO CAUSE HARM ?
NOAEL ! (= No Observable Adverse Effect Level = the highest dose or exposure level within a specific system where no adverse treatment- related findings are observed)
NOAEL taken from : 90-DAY ORAL REPEATED DOSE TOXICITY STUDY
REPRODUCTIVE TOXICITY STUDY (MATERNAL TOXICITY, MOSTLY TERATOGENICITY)

16. RISK ASSESSMENT OF COSMETIC INGREDIENTS
1) HAZARD IDENTIFICATION
2) DOSE-RESPONSE
3) EXPOSURE ASSESSMENT
RISK CHARACTERISATION
- WHAT IS AMOUNT AND TIME OF EXPOSURE ?
- EXPOSURE DATA IN NoG SCCS/1501/12

17. RISK ASSESSMENT OF COSMETIC INGREDIENTS
1) HAZARD IDENTIFICATION
2) DOSE-RESPONSE
3) EXPOSURE ASSESSMENT
RISK CHARACTERISATION
- WHAT IS THE PROBABILITY THAT HARM WILL BE PRODUCED ?
- WHAT IS THE NATURE OF IT ?
- IMPORTANCE OF VARIABILITY, UNCERTAINTY → MOS

18. RISK ASSESSMENT OF COSMETIC INGREDIENTS
1) HAZARD IDENTIFICATION
2) DOSE-RESPONSE
3) EXPOSURE ASSESSMENT
RISK CHARACTERISATION
FOR ACTIVE INGREDIENT
MoS : Margin of Safety
SED : Systemic Exposure Dosage
NOAEL : No Observable Adverse Effect Level
MoS = NOAEL
SED
≥ 100

19. RISK ASSESSMENT OF COSMETIC INGREDIENTS
MoS =
NOAEL
S E D
≥ 100
SED =
DAa x x SSA x F bw
SED = systemic exposure dosage (mg/kg bw/day)
DAa = dermal absorption amount (µg/cm2)
10-3 = factor µg → mg
F = frequency of application (F = 1)
SSA = skin surface area ( 580 cm2 )
NOAEL
= No observable adverse effect level derived from SYSTEMIC TOXICITY day repeated dose toxicity study
reproductive toxicity study
ROUTE-TO-ROUTE EXTRAPOLATION
= BIOAVAILABILITY = 50%
(when oral absorption data are lacking)
NOAEL/2

20. CONTENTS  ACTUAL EU COSMETICS LEGISLATION
 RISK ASSESSMENT OF COSMETIC INGREDIENTS ACCORDING TO THE NOTES OF GUIDANCE OF SCCS
 RISK ASSESSMENT FOR COSMETIC PRODUCTS IN THE EU
 ROLE OF RESPONSIBLE PERSON

21. RISK ASSESSMENT OF FINISHED COSMETIC PRODUCTS
FOR ALL COSMETIC PRODUCTS
1) HAZARD IDENTIFICATION OF ALL INGREDIENTS
→ PHYSICO-CHEMICAL AND QSAR DATA ON INGREDIENTS (AND ANALOGUES)
→ AVAILABLE TOX DATA ON INGREDIENTS (AND ANALOGUES)
OBTAINED IN VIVO (EARLIER OR FOR OTHER PURPOSES preambule 50, Reg. 1223/2009)
→ AVAILABLE TOX DATA ON INGREDIENTS (AND ANALOGUES)
OBTAINED USING ALTERNATIVE METHODS
(validated methods)

22. RISK ASSESSMENT OF FINISHED COSMETIC PRODUCTS
FOR ALL COSMETIC PRODUCTS
1) HAZARD IDENTIFICATION→ toxicological profile of ingredients of cosmetic product
2) EXPOSURE ASSESSMENT
EXPOSURE
ASSESSMENT
Type and size of exposed
population
Stage of
development
Route of
exposure
Body surface location
Frequency of use
Interferences within product
Percutaneous absorption
Duration of
contact
Excessive use pattern
Concentration in product
Quantity applied
Rinse-off leave-on
Type of product
→ specific exposure conditions of cosmetic product

23. RISK ASSESSMENT OF FINISHED COSMETIC PRODUCTS
FOR ALL COSMETIC PRODUCTS
HAZARD IDENTIFICATION OF ALL INGREDIENTS → toxicological profile of all
ingredients of the product
2) EXPOSURE ASSESSMENT → specific exposure conditions of the product
3) DOSE-RESPONSE ASSESSMENT → NOAELs of at least active ingredients of the product
Use existing in vivo data, determined before the animal testing bans
(also of analogues, read accross)
Use data generated for other legislative purposes (e.g. REACH)
for new cosmetic ingredients → lacking of in vivo data

24. RISK ASSESSMENT OF FINISHED COSMETIC PRODUCTS
FOR ALL COSMETIC PRODUCTS
HAZARD IDENTIFICATION OF ALL INGREDIENTS
2) EXPOSURE ASSESSMENT
3) DOSE-RESPONSE ASSESSMENT
RISK-CHARACTERIZATION
MOS calculation of (active) ingredients for systemic toxicity whenever possible
evaluation of local toxicity of finished product
in chimico, in silico and in vitro tests (validated or not) on finished product compared to benchmarks
when SAFE, in vivo skin compatibility testing of finished product on human volunteers using non-invasive bioengeneering methods ETHICS !
incorporation, if necessary, of extra safety factor
WoE
APPROACH

25. CONTENTS  ACTUAL EU COSMETICS LEGISLATION
 RISK ASSESSMENT OF COSMETIC INGREDIENTS ACCORDING TO THE NOTES OF GUIDANCE OF SCCS
 RISK ASSESSMENT FOR COSMETIC PRODUCTS IN THE EU
 ROLE OF RESPONSIBLE PERSON

26. ROLE OF RESPONSIBLE PERSON (RP)
BASIS INDUSTRY IS RESPONSIBLE FOR SAFETY OF COSMETIC PRODUCTS PLACED ON EU MARKET
In preambule 11, Reg. 1223/2009 :
“each cosmetic product should be linked to a RP established within th Community”
Art. 4
WHO IS THE RP ?
legal or natural person
responsible for compliance with Reg. 1223/2009
Cosmetic produced in EU (no export/no back import)
Cosmetic is imported in EU
Manufacturer in EU
Manufacturer outside EU
RP = IMPORTER
RP = MANUFACTURER
APPOINTED EU PERSON (accepting written mandate)
DISTRIBUTOR (his name/trademark or modification affecting compliance)

27. ROLE OF RESPONSIBLE PERSON (RP)
WHAT ARE OBLIGATIONS OF RP ?
IN GENERAL :
ensure full compliance with Reg. 1223/2009
take immediate corrective measures when cosmetic product is not compliant
inform immediately competent national authorities (CNA) of MS and provide all
details/corrective measures when risk exists for human health
cooperate with CNA of MS providing information/documentation demonstrating
conformity (language !) – also identification of distributors on demand
MORE SPECIFIC :
ensure compliance in particular with all safety requirements in connection with :
- presentation
- labelling
- use / disposal
- safety assessment before marketing according to Annex I and keep it
updated

28. ROLE OF RESPONSIBLE PERSON (RP)
WHAT ARE OBLIGATIONS OF RP ?
MORE SPECIFIC :
keep a PIF for each product (different formats possible, language ! )
at address indicated on label
notify each product via CPNP (art.13) before marketing (exception original labelling and packaging photograph)
notify cosmetic product containing nanomaterials : 6 months prior marketing
make easily accessible for public information :
- qualitative and quantitative composition (hazardous substances)
- perfume / aroma (name, code nr, supplier)
- undesirable and serious undesirable effects (SUE)
- communication on SUE !
take all appropriate measures to bring non-compliant products into conformity

29. THANK YOU FOR
YOUR ATTENTION !