9028ss271.ppt
- 1. 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 ROLE OF RESPONSIBLE PERSON RISK ASSESSMENT FOR COSMETIC PRODUCTS IN THE EU
- 3. 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
- 4. ACTUAL EU COSMETICS LEGISLATION COUNCIL DIRECTIVE 76/768/EEC COSMETICS REGULATION / RECAST N° 1223/2009 11/7/2013 SAME BASIC PRINCIPLES APPLY TESTING & 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 AUTHORITIES Notification (CPNP) (art. 13) CONSUMER Safe use (art. 19-21) RESPONSIBILITY OF COMPANY
- 5. TWO CHANNELS ARE FUNCTIONAL IN THE SAFETY ASSESSMENT PROCESS ACTUAL EU COSMETICS LEGISLATION 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. 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 ACTUAL EU COSMETICS LEGISLATION
- 7. 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 ACTUAL EU COSMETICS LEGISLATION
- 8. 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
- 9. 1) HAZARD IDENTIFICATION 2) DOSE-RESPONSE 3) EXPOSURE ASSESSMENT RISK CHARACTERISATION RISK MANAGEMENT RISK COMMUNICATION RISK ASSESSMENT : WHAT ?
- 10. 1) HAZARD IDENTIFICATION 2) DOSE-RESPONSE 3) EXPOSURE ASSESSMENT RISK CHARACTERISATION 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 PROPERTIES OF SUBSTANCES - PHYSICOCHEMISTRY, STABILITY - SCIENTIFIC LITERATURE
- 11. 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) RISK ASSESSMENT OF COSMETIC INGREDIENTS
- 12. 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 Reduction Refinement R R R Replacement Reduction Refinement R R R Replacement RISK ASSESSMENT OF COSMETIC INGREDIENTS HAZARD IDENTIFICATION
- 13. 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) RISK ASSESSMENT OF COSMETIC INGREDIENTS (in chemico tests)
- 14. 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 toxicity mostly : teratogenicity RISK ASSESSMENT OF COSMETIC INGREDIENTS HAZARD IDENTIFICATION TESTS IN TIF
- 15. - 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) 1) HAZARD IDENTIFICATION 2) DOSE-RESPONSE 3) EXPOSURE ASSESSMENT RISK CHARACTERISATION RISK ASSESSMENT OF COSMETIC INGREDIENTS
- 16. - WHAT IS AMOUNT AND TIME OF EXPOSURE ? 1) HAZARD IDENTIFICATION 2) DOSE-RESPONSE 3) EXPOSURE ASSESSMENT RISK CHARACTERISATION RISK ASSESSMENT OF COSMETIC INGREDIENTS - EXPOSURE DATA IN NoG SCCS/1501/12
- 17. - WHAT IS THE PROBABILITY THAT HARM WILL BE PRODUCED ? - WHAT IS THE NATURE OF IT ? - IMPORTANCE OF VARIABILITY, UNCERTAINTY → MOS 1) HAZARD IDENTIFICATION 2) DOSE-RESPONSE 3) EXPOSURE ASSESSMENT RISK CHARACTERISATION RISK ASSESSMENT OF COSMETIC INGREDIENTS
- 18. 1) HAZARD IDENTIFICATION 2) DOSE-RESPONSE 3) EXPOSURE ASSESSMENT RISK CHARACTERISATION MoS = NOAEL SED ≥ 100 Inter-species kinetics 4.0 Inter-species dynamics 2.5 Variability human kinetics 3.2 Variability human dynamics 3.2 10 10 Inter-species kinetics 4.0 Inter-species dynamics 2.5 Inter-species kinetics 4.0 Inter-species dynamics 2.5 Variability human kinetics 3.2 Variability human dynamics 3.2 10 10 FOR ACTIVE INGREDIENT MoS : Margin of Safety SED : Systemic Exposure Dosage NOAEL : No Observable Adverse Effect Level RISK ASSESSMENT OF COSMETIC INGREDIENTS
- 19. MoS = NOAEL S E D ≥ 100 SED = DAa x 10-3 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 90-day repeated dose toxicity study reproductive toxicity study ROUTE-TO-ROUTE EXTRAPOLATION = BIOAVAILABILITY = 50% (when oral absorption data are lacking) RISK ASSESSMENT OF COSMETIC INGREDIENTS NOAEL/2
- 20. 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
- 21. 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
- 22. RISK ASSESSMENT OF FINISHED COSMETIC PRODUCTS 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 1) HAZARD IDENTIFICATION→ toxicological profile of ingredients of cosmetic product 2) EXPOSURE ASSESSMENT FOR ALL COSMETIC PRODUCTS → specific exposure conditions of cosmetic product
- 23. 1) HAZARD IDENTIFICATION OF ALL INGREDIENTS → toxicological profile of all ingredients of the product RISK ASSESSMENT OF FINISHED COSMETIC PRODUCTS FOR ALL COSMETIC PRODUCTS 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. 1) HAZARD IDENTIFICATION OF ALL INGREDIENTS RISK ASSESSMENT OF FINISHED COSMETIC PRODUCTS FOR ALL COSMETIC PRODUCTS 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 WoE APPROACH
- 25. 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
- 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 = MANUFACTURER RP = IMPORTER 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