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بسمه تعالی
شتی –دکتر منوچهر دادگرنژاد یی و آرایشی و بهدا معاون اداره برنامه ریزی و ارزیابی مواد غذا
1395شهریور
Safety in Cosmetic
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Commission Decision of 7 August 2015 C(2015)53831 (hereinafter "the Decision") reorganizes the structure of the Commission Scientific Committees and establishes two Scientific Committees:
o the Scientific Committee on Consumer Safety - SCCS
o Scientific Committee on Health, Environmental and Emerging Risks - SCHEER
SCCS-SCHEER
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The Cosmetics Regulation Limitation of Certain Substances
• CMR substances
• Traces of prohibited substances
• Regulatory arrangements for nanomaterials
• Safety assessment for nanomaterials
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• Annex II - list of 1328 prohibited substances
• Annex III – list of 256 restricted substances
• Also prohibited are:
• certain colorants (other than those in Annex IV), preservatives (other than those in Annex V) and UV-filters (other than those in Annex VI);
• substances recognised as Carcinogenic, Mutagenic or toxic for Reproduction (CMR), apart from exceptional cases;
• nanomaterials – subject to a high level of protection of human health.
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CMR classification [Regulation N° 1272/2008]
o Carcinogenic
• Cat. 1A: Known to have carcinogenic potential for humans
• Cat. 1B: Presumed to have carcinogenic potential for humans
• Cat. 2: Suspected human carcinogen
o Mutagenic
• Cat. 1A: Substance known to induce heritable mutations in the germ cells of humans
• Cat. 1B: Substance to be regarded as if it induces heritable mutations in the germ cells of humans
• Cat. 2: Substance which causes concern for humans owing to the possibility that it may induce heritable mutations in the germ cells of humans
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o Reproductive toxicants
• Cat. 1A: Known human reproductive toxicant
• Cat. 1B: Presumed human reproductive toxicant
• Cat. 2: Suspected human reproductive toxicant
o Possibility to allow where, in view of exposure and concentration, they have been found safe for use in cosmetic products by the SCCS, and are regulated by the EC in the Annexes to the Regulation.
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Derogation to the Ban on CMR Substances
• CMR2 substances
o Possibility to allow where, in view of exposure and concentration, they have been found safe for use in cosmetic products by the SCCS, and are regulated by the EC in the Annexes to the Regulation
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Derogation to the Ban on CMR Substances
• CMR 1A or 1B substances
o Possibility, in the exceptional case that these substances comply with food safety requirements, intar alia as a result of their naturally occurring in food, and that no suitable alternative substances exist, to use such substances in cosmetic products on the condition that such use has been found safe by the SCCS.
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Trace impurities/ contaminants
• Presence of small quantities of a non-intended prohibited substance, that is technically unavoidable in good manufacturing practice, is allowed, provided that it does not cause harm to human health during the product use.
• Annex I requires the following information concerning the impurities and traces in the cosmetic product safety report:
• The purity of the substance and mixtures.
• In the case of traces of prohibited substances, evidence for their technical unavoidability.
• The relevant characteristics of packaging material, in particular purity and stability.
• There are currently not regulatory limits for most non-intended traces
• Safety is the responsibility of the manufacturer or the person under whose responsibility the product is placed on the market.
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Nanomaterials
• In Europe nano cosmetic ingredients will be regulated under the Cosmetics Regulation (EC) No 1223/2009.
• The Regulation provides the first regulatory definition of a nanomaterial*
• Requires:
• cosmetic products containing nanomaterials to be notified to the Commission 6 months prior to being placed on the market;
• nanoscale ingredients to be labelled (name of the ingredient, followed by ‘nano’ in brackets);
• if there are concerns over safety of a nanomaterial, the EC will refer it to the Scientific Committee on Consumer Safety (SCCS) for opinion.
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Nano-sized Cosmetic Ingredients
• Colorants, antioxidants, antimicrobials, UV filters, supplements (vitamins, minerals);
• Materials include:
• inorganic, organic
• uncoated, coated, doped
• manufactured particles, micelles, liposomes
• R&D on functional nanomaterials
• Used for better dispersibility, antimicrobial or antioxidant properties, effective UV protection, visual clarity of sunscreen formulations, etc;
• A growing range of products worldwide. Only a few products currently in Europe – mainly sunscreens containing nano UV filters.
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New applications in
consumer products
Increased surface area
Greater functionality per equivalent mass
Better control of material properties
Potential new properties
Improved dispersions
Stable formulations
Less use of chemical
substances
Enhanced uptake
of nutrients & supplements
Effective UV protection
Nanomaterials
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Nanomaterials Safety Concerns
N a n o p a r t i c l e s
Skin Gut Lung
Inhalation Skin application Ingestion
Other cells and tissues
?
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• Scientific evidence indicates that:
– Nanoparticles may cross membrane barriers, and reach new targets in the body;
– Nanoparticles may interact with biological entities close to the molecular level;
– Exposure to insoluble/ biopersistent nanoparticles may cause concerns over adverse health effects.
Nanomaterials Safety Concerns
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Hazard Identification/ Characterisation
• All toxicological endpoints needed for safety evaluation of a (non-nano) cosmetic ingredient should be addressed:
• Dermal/ percutaneous absorption; Toxicokinetics; Acute toxicity; Irritation and corrosivity; Skin sensitisation; Mutagenicity/genotoxicity; Repeated dose toxicity;
• Where appropriate, further studies on Carcinogenicity; Reproductive toxicity; Photo-induced toxicity;
• Additional human data (where available) .
• In vivo and in vitro methods may be used for toxicological evaluation. However, none of the in vitro methods has so far been validated against nanomaterials.
• Only a few elementary in silico models are currently available.
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Safety Assessment
• Any route-to-route extrapolation should be performed on a case-by-case, based on expert judgment of the available scientific information;
• Where data from valid/validated tests are available and uncertainties are not large, there may not be a reason for applying higher margins of safety than those used for a conventional substance;
• Where data are either insufficient or from inadequate tests, a Risk Assessor may consider applying additional uncertainty factors for a nanomaterial;
• Potential persistence and accumulation of nanoparticles should also be considered.
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Nanomaterials Current Challenges
• Lack of validated methods for detection/ characterisation of nanomaterials – especially in cosmetic products and in biological tissues;
• Uncertainties and knowledge gaps in relation to properties, behaviour and toxicological effects of nanomaterials;
• Lack of validated methods for assessment of exposure via dermal, inhalation, ingestion routes;
• Imminent ban on animal testing of cosmetic ingredients in Europe, and the lack of validated alternative testing methods for nanomaterials;
• Difficulties in the use of a category approach to safety assessment of nanomaterials;
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Summary
• The use of CMR substances in cosmetics is prohibited – subject to certain derogations;
• Presence of non-intended trace impurities/ contaminants is only allowed subject to certain provisions;
• The use of nanomaterials will require a thorough assessment of safety, with consideration of nano-aspects.
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Summary
• Guidance on safety assessment is available. First scientific opinions on nano cosmetic ingredients are available.
• Ban on animal testing will pose a major challenge to safety evaluation of new cosmetic ingredients - especially nanomaterials.
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Preclinical Safety Assessment
Cosmetic & Toiletry Products
Safety Review of Cosmetic Ingredients
Safety Review of Active Ingredients and Products
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Sources of Safety Information for Cosmetic Ingredients
Cosmetic Ingredient Review (CIR) - CTFA
o Prohibited Ingredients and other Hazardous Substance
– FDA
o California Proposition 65 List - California EPA
o List of Suspected Carcinogens - NTP
o Federal Insecticide, Fungicide and Rodenticide Act - EPA
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Sources of Safety Information for Cosmetic Ingredients
o Industry Guidelines to Restrict Ingredient Usage - IFRA
o Approved Colorant list (limited) - FDA
o Endocrine Disruptor Screening Program - EPA
o Voluntary Children’s Health Chemical Evaluation
Program – EPA
o COLIPA - EU
o Pubmed - Toxnet
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Toxicity/Preclinical Safety Review
o Single Dose Study: IV, IP, Dermal, Oral
o Multiple Dose Study: Subacute, Subchronic, Chronic
»Organ toxicity – structural and functional
o Carcinogenicity Study: Dermal, Oral
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Special Toxicity Studies
o Ocular Irritation
o Dermal Irritation/Sensitization
o Photo-Irritation/Sensitization
o Reproductive Tests, Embryo toxicity, teratology tests
o Mutagenicity Tests
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Other information required to access safe
• Skin Absorption Data
• Toxicokinetics/Pharmacokinetics Data
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Safety testing of ingredients and formulations
o Is there a need to test formulations if ingredients are safe
– Interactions during processing – pH, temperature
– Interaction within formulation – impurities
– Interaction within the body
– Interaction with other products used
o Misuse, overuse, unintended use
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Safety Evaluation for External Color Additives
[From 21 CFR Ch.1 Subpart C, 70.40 (4-1-99)]
• Safety factor should be 100 to 1 (based on NOEAL in most sensitive species)
• Safety of external color additives will be determined
o by: Acute Oral Toxicity
o Primary Irritation /Contact Sensitization
o Subacute Dermal Toxicity on intact/abraded skin
o Dermal Carcinogenicity
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SINGLE DOSE TOXICITY :
IV IP
Dermal Oral
MULTIPLE DOSE TOXICITY :
Subacute Subchronic
Chronic
ARCINOGENICITY Dermal Oral
S PECIAL T OXICITY :
Primary Skin Irritation
Cumulative Skin Irritation
Genital/Mucus Mem. Irritation
Contact Sensitization Eye Irritation
Comedogenicity
S OLAR S PECTRUM : ( )
Phototoxicity
Photo - mutagenicity Photosensitization
Photocar cinogenicity
R EPRODUCTIVE T OXICITY :
Segment II (Rat, Rabbit)
Segment I (Rat) Segment III (Rat)
M UTAGENICITY : Ames Test Mouse Micronucleus
Mammalian Chromosomal Aberration
O THERS : Skin Absorption
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Non animal test methods
o In vitro testing
o Human testing
– On satisfactory data being available only
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Safety Review of Naturals-Containing Products
o Most naturals have established long safe use history via oral route
o Not enough safety information with ocular and dermal exposure
o Safety issues are mostly related to irritation /sensitization and photo-irritation /sensitization
o Batch to batch variation
o FIFRA and California Prop 65
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Safety Review of Enzyme-Containing Products
o Dependent on the intended use of the enzyme (cosmetic, food, laundry detergent)
o Potential exposure route under normal or accidental contact (oral, eye, skin, inhalation)
o Major health effects associated with enzymes are related to irritation and sensitization
