SAFETY ASSESSMENT

OF COSMETIC PRODUCTS IN
THE EU
Vera ROGIERS

Head of Dept. of Toxicology

Vrije Universiteit Brussel
Belgium

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

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

ACTUAL EU COSMETICS LEGISLATION

COUNCIL
DIRECTIVE
76/768/EEC

11/7/20
13

SAME BASIC PRINCIPLES

APPLY

COSMETICS REGULATION /
RECAST
N 1223/2009
TESTING & MARKETING BANS
ARTICLES & ANNEXES

RESPONSIBILITY OF
SAFE COMPANY
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. 19-21)

ACTUAL EU COSMETICS LEGISLATION

TWO CHANNELS ARE FUNCTIONAL IN THE SAFETY
ASSESSMENT PROCESS
COMMISSION
SUBSTANCES ON
ANNEXES
II, III, IV, V, VI

SCCS
IN DG SANCO
WRITTEN SAFETY
EVALUATION (opinion)

INDUSTRY

SUBSTANCES / MIXTURES IN
FINISHED PRODUCT
AND PRODUCT
TIF
:
COSMETIC SAFETY
REPORT A
&B

SAFETY ASSESSOR

WRITTEN SAFETY
EVALUATION (cosmetic product
safety assessme

DG SANCO

RESPONSIBLE
PERSON

RISK MANAGEMENT

RISK MANAGEMENT

BY COMMISSION
FOR CONSUMER
PROTECTION

INDUSTRIAL MEASURES
FOR
CONSUMER PROTECTION

ACTUAL EU COSMETICS LEGISLATION

SCCS OPINIONS
RISK ASSESSMENTS
ADVICE ON
ON COSMETIC
SCIENTIFIC ISSUES
SUBSTANCES PRESENT
RELATED TO SAFETY
ON ANNEXES
OF COSMETICS AND
(II, III, IV, V, VI,
THEIR INGREDIENTS
(-) ANNEX II
: FORBIDDEN SUBSTANCES
Reg.1223/2009)

(-) ANNEX III

: RESTRICTED SUBSTANCES WITH CONCERN
FOR HUMAN HEALTH
(+) ANNEX IV
: COLORANTS
(+) ANNEX V
: PRESERVATIVES
(+) ANNEX VI
: UV-FILTERS

ADVICE TO
COMMISSION
ACCORDING TO TRANSPARANT RULES

NOTES OF GUIDANCE (NoG)

SCCS : Scientific Committee on Consumer Saf

ACTUAL EU COSMETICS LEGISLATION

THE SCCSs NOTES OF GUIDANCE FOR THE

TESTING OF COSMETIC SUBSTANCES AND
THEIR SAFETY EVALUATION
8th REVISION (SCCS/1501/12)

Notes of Guidance available on website :

http://ec.europa.eu/health/scientific_committees/consu
mer_safety/statements/index_en.htm
Opinions available on website :
http://ec.europa.eu/health/scientific_committees/consu
mer_safety/index_en.htm

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

RISK ASSESSMENT : WHAT ?

1) HAZARD
IDENTIFICATION

2) DOSERESPONSE
RISK CHARACTERISATION
RISK
MANAGEMENT
RISK
COMMUNICATION

3) EXPOSURE
ASSESSMENT

RISK ASSESSMENT OF COSMETIC

INGREDIENTS
1) HAZARD
IDENTIFICATION

2) DOSERESPONSE

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

RISK ASSESSMENT OF COSMETIC

INGREDIENTS
1) HAZARD
IDENTIFICATION

2) DOSERESPONSE

3) EXPOSURE
ASSESSMENT

RISK CHARACTERISATION

HAZARD TESTS PRESENT IN NOTES OF GUIDANCE (SCCS/1501/12)

- acute toxicity
- skin and eye irritation
- skin sensibilisation
- dermal absorption
- repeated dose toxicity
- mutagenicity/genotoxicity

- carcinogenicity
- reproductive toxicity
- toxicokinetics
- photo-induced toxicity (if relevan
- human data (if available)

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 STRA

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

RISK ASSESSMENT OF COSMETIC

INGREDIENTS
HAZARD IDENTIFICATION TESTS
IN TIF

PHYSICO-CHEMICAL CHARACTERISATION :

emphasis on :
purity
solubility
partition coefficient (log Pow)
(in chemico tests)
stability in solution
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
- Skin sensitisation :
(in vitro
screening tests ; in
Sensitisation not excluded
;
vivo)
preferably non-sensitising
(LLNA : 3R- in vivo test in vitro

RISK ASSESSMENT OF COSMETIC

INGREDIENTS
HAZARD IDENTIFICATION TESTS
IN TIF
SYSTEMIC TOXICITY
Dermal absorption (in vitro test)
Dermatomed pig or human skin
(400-600 )
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 in vivo test
Carcinogenicity (in vivo test) : if available
Reproductive toxicity (in
vivo test)
maternal toxicity
mostly : teratogenicity

RISK ASSESSMENT OF COSMETIC

INGREDIENTS
1) HAZARD
IDENTIFICATION

2) DOSERESPONSE

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

RISK ASSESSMENT OF COSMETIC

INGREDIENTS
1) HAZARD
IDENTIFICATION

2) DOSERESPONSE

3) EXPOSURE
ASSESSMENT

RISK CHARACTERISATION

- WHAT IS AMOUNT AND TIME OF

EXPOSURE ?
- EXPOSURE DATA IN NoG
SCCS/1501/12

RISK ASSESSMENT OF COSMETIC

INGREDIENTS
1) HAZARD
IDENTIFICATION

2) DOSERESPONSE

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

RISK ASSESSMENT OF COSMETIC

INGREDIENTS
1) HAZARD
IDENTIFICATION

2) DOSERESPONSE

3) EXPOSURE
ASSESSMENT

RISK CHARACTERISATION

MoS

FOR ACTIVE
=INGREDIENT
NOAEL 100
SED

MoS :
SED :
Dosage
NOAEL :
Effect

Margin of Safety
Systemic Exposure
No Observable Adverse
Level

RISK ASSESSMENT OF COSMETIC

INGREDIENTS
NOAEL

MoS =
S E D 100
DAa x 10-3 x SSA x F
SED =
bw
SED
DAa
10-3 =
F =
SSA=

= systemic exposure dosage (mg/kg bw/day)

= dermal absorption amount (g/cm2)
factor g mg
frequency of application (F = 1)
skin surface area ( 580 cm2 )

=NOAEL
No observable adverse effect level derived from
SYSTEMIC TOXICITY
90-day repeated dose toxicity
reproductive toxicity study
ROUTE-TO-ROUTE
EXTRAPOLATION

= BIOAVAILABILITY = 50%

(when oral absorption data are lackin

NOAEL/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

RISK ASSESSMENT OF FINISHED

COSMETIC PRODUCTS
FOR ALL COSMETIC PRODUCTS
HAZARD IDENTIFICATION OF ALL INGREDIENTS

YSICO-CHEMICAL AND QSAR DATA ON INGREDIENTS (AND ANALOGUES)

LABLE TOX DATA ON INGREDIENTS (AND ANALOGUES)

AINED IN VIVO (EARLIER OR FOR OTHER PURPOSES preambule 50, Reg.

AVAILABLE TOX DATA ON INGREDIENTS (AND ANALOGUES)

OBTAINED USING ALTERNATIVE METHODS
(validated methods)

RISK ASSESSMENT OF FINISHED

COSMETIC PRODUCTS
FOR ALL COSMETIC PRODUCTS

AZARD IDENTIFICATION toxicological profile of ingredients of cosmetic

2) EXPOSURE ASSESSMENT
Percutaneous
Duration of
absorption Interferences
contact
within product
Excessive
use pattern
Frequency
of use
Quantity
applied
EXPOSURE
Body surface
ASSESSMENT
location
Concentration
in product
Route of
exposure
Rinse-off
leave-on
Stage of
Type and sizedevelopment
Type of
of exposed
product
population

specific exposure conditions of cosmetic product

RISK ASSESSMENT OF FINISHED

COSMETIC PRODUCTS
FOR ALL COSMETIC PRODUCTS

HAZARD IDENTIFICATION OF ALL INGREDIENTS toxicological profile of a

ingredients of the product

EXPOSURE ASSESSMENT specific exposure conditions of the product

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

RISK ASSESSMENT OF FINISHED

COSMETIC PRODUCTS
FOR ALL COSMETIC PRODUCTS

1) HAZARD IDENTIFICATION OF ALL INGREDIENTS

2)
3)

EXPOSURE ASSESSMENT
DOSE-RESPONSE ASSESSMENT

4) 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 noninvasive bioengeneering methods ETHICS !

incorporation, if necessary, of extra safety factor

WoE
APPROACH

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

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 Communit
Art. 4
WHO IS THE RP ?
legal or natural person
responsible for compliance with Reg. 1223/2009
Cosmetic produced
in EU

Cosmetic is imported
in EU

(no export/no back

import)

Manufacturer in EU
RP =
MANUFACTURER

Manufacturer
outside EU
RP = IMPORTER

APPOINTED EU PERSON (accepting written

mandate)
DISTRIBUTOR (his name/trademark or
modification

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 complian

inform immediately competent national authorities (CNA) of MS and provide

details/corrective measures when risk exists for human health

cooperate with CNA of MS providing information/documentation demonstrat

conformity (language !) also identification of distributors on demand
MORE SPECIFIC :

ensure compliance in particular with all safety requirements in connection w

- presentation
- labelling
- use / disposal
- safety assessment before marketing according to Annex I and keep it
updated

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 marketin

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 conform

THANK YOU FOR

YOUR ATTENTION !