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

SAFETY ASSESSMENT OF COSMETIC PRODUCTS IN THE EU

Vera ROGIERSHead of Dept. of Toxicology

Vrije Universiteit BrusselBelgium

CONTENTS

ACTUAL EU COSMETICS LEGISLATION

RISK ASSESSMENT OF COSMETIC INGREDIENTS ACCORDING TO THE NOTES OF GUIDANCE OF SCCS

ROLE OF RESPONSIBLE PERSON

RISK ASSESSMENT FOR COSMETIC PRODUCTS IN THE EU


COUNCIL DIRECTIVE76/768/EEC

COSMETICS REGULATION / RECAST N° 1223/2009

11/7/2013

SAME BASIC PRINCIPLES APPLYTESTING & MARKETING BANS

ARTICLES & ANNEXES

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

AUTHORITIESNotification (CPNP)

(art. 13)

CONSUMERSafe use

(art. 19-21)

RESPONSIBILITY OF COMPANY

TWO CHANNELS ARE FUNCTIONAL IN THE SAFETY ASSESSMENT PROCESS


SUBSTANCES ONANNEXES

SCCSIN DG SANCO

DG SANCO

II, III, IV, V, VI

WRITTEN SAFETYEVALUATION (opinion)

RISK MANAGEMENT

BY COMMISSION FOR CONSUMER

PROTECTION

COMMISSION

SUBSTANCES / MIXTURES INFINISHED PRODUCT

AND PRODUCT

SAFETY ASSESSOR

RESPONSIBLE PERSON

COSMETIC SAFETY REPORT A & B

WRITTEN SAFETYEVALUATION (cosmetic product safety assessment)

RISK MANAGEMENT

INDUSTRIAL MEASURESFOR

CONSUMER PROTECTION

INDUSTRY

TIF :

ACCORDING TO TRANSPARANT RULES

NOTES OF GUIDANCE (NoG)

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

SCCS : Scientific Committee on Consumer Safety


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


CONTENTS





1) HAZARD IDENTIFICATION 2) DOSE-RESPONSE 3) EXPOSURE ASSESSMENT

RISK CHARACTERISATION

RISK MANAGEMENT

RISK COMMUNICATION

RISK ASSESSMENT : WHAT ?



RISK ASSESSMENT OF COSMETIC INGREDIENTS

- CAN X CAUSE ADVERSE HEALTH EFFECT ?

- BASED ON : - EPIDEMIOLOGICAL STUDIES- CLINICAL STUDIES- IN VIVO STUDIES- IN VITRO STUDIES- QSAR

HAZARD :INTRINSIC

PROPERTIESOF SUBSTANCES

- PHYSICOCHEMISTRY, STABILITY

- SCIENTIFIC LITERATURE



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)


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

ReductionRefinement

R

RR

Replacement

ReductionRefinement

R

RR

Replacement


HAZARD IDENTIFICATION

HAZARD IDENTIFICATION TESTS IN TIF

PHYSICO-CHEMICAL CHARACTERISATION : emphasis on :

purity solubility partition coefficient (log Pow) 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 (in vitro screening tests ; in vivo)

- Skin sensitisation : Sensitisation not excluded ; preferably non-sensitising (LLNA : 3R- in vivo test → in vitro tests)


(in chemico tests)

Dermal absorption (in vitro test)Dermatomed pig or human skin (400-600 µ)

Repeated dose toxicity (in vivo test)90- day oral study in rat

SYSTEMIC TOXICITY

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 toxicitymostly : teratogenicity


HAZARD IDENTIFICATION TESTS IN TIF

- 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)




- WHAT IS AMOUNT AND TIME OF EXPOSURE ?




- EXPOSURE DATA IN NoG SCCS/1501/12

- WHAT IS THE PROBABILITY THAT HARM WILL BE PRODUCED ?

- WHAT IS THE NATURE OF IT ?

- IMPORTANCE OF VARIABILITY, UNCERTAINTY → MOS






MoS = NOAEL SED

≥ 100

Inter-specieskinetics4.0

Inter-speciesdynamics

2.5

Variabilityhuman kinetics

3.2

Variabilityhuman dynamics

3.2

10 10



2.5



2.5

Variabilityhuman kinetics

3.2

Variabilityhuman dynamics

3.2

10 10

FOR ACTIVE INGREDIENT MoS : Margin of SafetySED : Systemic Exposure DosageNOAEL : No Observable Adverse Effect

Level


MoS = NOAEL

S E D≥ 100

SED = DAa x 10-3 x SSA x Fbw

SED = systemic exposure dosage (mg/kg bw/day)DAa = dermal absorption amount (µg/cm2) 10-3 = factor µg → mgF = frequency of application (F = 1)SSA = skin surface area ( 580 cm2 )

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

reproductive toxicity study

ROUTE-TO-ROUTE EXTRAPOLATION = BIOAVAILABILITY = 50%(when oral absorption data are lacking)


NOAEL/2

CONTENTS





1) HAZARD IDENTIFICATION OF ALL INGREDIENTS

→ 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)

→ PHYSICO-CHEMICAL AND QSAR DATA ON INGREDIENTS (AND ANALOGUES)

RISK ASSESSMENT OF FINISHED COSMETIC PRODUCTS

FOR ALL COSMETIC PRODUCTS


EXPOSUREASSESSMENT

Type and sizeof exposedpopulation

Stage ofdevelopment

Route ofexposure

Body surfacelocation

Frequencyof use

Interferenceswithin product

PercutaneousabsorptionDuration of

contactExcessive

use pattern

Concentrationin product

Quantityapplied

Rinse-offleave-on

Type ofproduct

1) HAZARD IDENTIFICATION→ toxicological profile of ingredients of cosmetic product

2) EXPOSURE ASSESSMENT


→ specific exposure conditions of cosmetic product

1) 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

1) HAZARD IDENTIFICATION OF ALL INGREDIENTS



2) EXPOSURE ASSESSMENT

3) 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 non-invasive bioengeneering methods ETHICS !

incorporation, if necessary, of extra safety factor

WoEAPPROACH

CONTENTS





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 = MANUFACTURER RP = IMPORTER

APPOINTED EU PERSON (accepting written mandate) DISTRIBUTOR (his name/trademark or modification

affecting compliance)


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


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

THANK YOU FOR YOUR ATTENTION !

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

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