QUANTITATIVE RISK ASSESSMENT (QRA) IMPLEMENTATION CONTINUES: IMPACT OF IFRA S S 42 ND AMENDMENT

Transcription

1 QUANTITATIVE RISK ASSESSMENT (QRA) IMPLEMENTATION CONTINUES: IMPACT OF IFRA S S 42 ND AMENDMENT Anne Marie Api, PhD Research Institute for Fragrance Materials, Inc. Vice President, Human Health Sciences QRA Implementation Workshop 2 June 4, 2007

2 Contact Dermatitis, 2001, 45, Dermal Sensitization Quantitative Risk Assessment (QRA) For Fragrance Ingredients Technical Dossier March 15, 2006 Revised May 26, 2006 The group recommended an exposure-based QRA methodology for fragrance ingredients now implemented Api QRA Worksop 2 June 2007 Revised June 22,2006 QRA Expert Group Anne Marie Api (RIFM), David A. Basketter (SEAC, Unilever), Peter A. Cadby (Firmenich), Marie-France Cano (LVMH), Graham Ellis (Givaudan), G. Frank Gerberick (Procter & Gamble), Peter Griem (Clariant Produkte GmbH), Pauline M. McNamee (Procter & Gamble), Cindy A. Ryan (Procter & Gamble) and Bob Safford (SEAC, Unilever)

3 QRA FOR DERMAL SENSITIZATION Determine potential (hazard) to induce sensitization Pre-clinical studies Human data (historical) Structure based predictive approach Dose-response assessment Determine WoE NESIL Calculate SAF Exposure assessment Dose metrics: expressed in Dose/Area Understand consumer exposure per product type Risk characterization Api QRA Worksop 2 June 2007

4 QRA FOR DERMAL SENSITIZATION FRAGRANCE INGREDIENTS: WHAT S S NEW NESIL - No Expected Sensitization Induction Level Establishment of scientifically sound NESILs is key Weight of evidence approach to use of data Identifies studies inappropriate for consideration Can be derived from animal and human data SAF Sensitization Assessment Factor Greater understanding of different elements comprising overall SAF Extrapolation from controlled experimental situation to real life exposure scenarios Detailed scientific rationale for SAF determination Exposure Consistent use of the same dose metric (μg/cm 2 ) Sources of exposure data in calculation of exposure to fragrance ingredients in consumer products Api QRA Worksop 2 June 2007

5 SAF SUMMARY 10 Inter-individual Variability (Age, gender, ethnicity, inherent dermal barrier and genetic effects) Vehicle or Product Matrix Effects (e.g. presence of irritants, penetration enhancer) Use Considerations (Site of contact, barrier function, occlusion) Api QRA Worksop 2 June 2007

6 EXPOSURE DATA (DOSE/AREA) Product Type Source Exposure mg/cm 2 /day Deo/AP Solid RIFM 9.1 Hydroalcoholic, Unshaved Women s Facial Cream Cano & Rich* Colipa Shaving Cream SCCP 0.07 Eye Product Body Cream Lip Products Hair Sprays Toothpaste CTFA Colipa Colipa CTFA Colipa Mouthwash Colipa 1.4 Shampoo Body Wash/Gels CTFA SCCP Api QRA Worksop 2 June 2007 *Cano & Rich, 2001; Tozer et al., 2004

7 CONSUMER EXPOSURE LEVEL Exposure assessment for shampoos: Calculated exposure = 23,630 mg/day (CTFA) Area = 1430 cm 2 (EPA, 1997; area hands + ½ head) Retention Factor = 1% or 0.01 (SCCNFP, 2003) Exposure = 23,630 mg/day * cm 2 = 0.2 mg/cm 2 /day Api QRA Worksop 2 June 2007

8 RISK CHARACTERIZATION FOR FRAGRANCE INGREDIENTS Acceptable Exposure Levels (AELs) to fragrance ingredients that are dermal sensitizers can be determined in specific real life consumer product types Acceptable Exposure Level (AEL) Sensitization Assessment Factor (SAF) Comparison of Acceptable Exposure Levels (AEL) to calculated Consumer Exposure Level (CEL) Api QRA Worksop 2 June 2007 = WoE NESIL AEL CEL to be Acceptable

9 IFRA 42 nd AMENDMENT 14 revised Standards based on QRA (25 materials) 14 new Standards based on QRA (26 materials) Addition of 4 materials to the list of prohibited materials with insufficient data ("list of other materials") Reformatted Standard on crude Peru Balsam Revised version of the QRA Booklet (Version 2.1 May 10, 2007) Revised Annex 1 - provides guidance on contributions from other sources Api QRA Worksop 2 June 2007

10 IFRA 42 nd AMENDMENT REVISED STANDARDS p-t-butyldihydrocinnamaldehyde p-t-butyl-α-methylhydrocinnamic aldehyde Cinnamyl alcohol Cinnamaldehyde Eugenol Hexen-2-al Hydroxycitronellal Isoeugenol Methoxydicyclopentadiene carboxaldehyde 2-Methoxy-4-methylphenol 1-Octen-3-yl acetate Peru balsam (3) Balsam oil, Peru Peru balsam absolute Peru balsam anhydrol Rose ketones includes 12 isomers 2,4,6-Trimethyl-3- cyclohexene-1-methanol (isocyclogeraniol) Api QRA Worksop 2 June 2007

11 IFRA 42 nd AMENDMENT NEW STANDARDS α-amylcinnamyl alcohol α-amylcinnamyl aldehyde Anisyl alcohol Benzyl Alcohol Benzyl Benzoate Benzyl Cinnamate Benzyl Salicylate Citronellol Includes 7 isomers α-hexyl-cinnamaldehyde Hexyl salicylate Isocyclocitral Includes 3 isomers α-methyl cinnamic aldehyde Methyl ionone Includes 5 isomers Api QRA Worksop 2 June 2007

12 42 nd AMENDMENT REVISED STANDARDS PROHIBITED INSUFFICIENT DATA Allyl 2-octynoate (Allyl heptine carbonate ) Amylcyclopentenone 3-Methyl-2(3)-nonenenitrile p-methylhydrocinnamic aldehyde Api QRA Worksop 2 June 2007

13 TIMING 42 ND AMENDMENT ONLY Letter of notification 4 weeks Amendment enters into force for new creations* 60 days 24 months Inform customers about status of (active) formulations Amendment enters into force for existing fragrance compounds* *The timing refers to the mixture of fragrance ingredients, the so-called fragrance compound or fragrance oil, not the finished consumer product. Api QRA Worksop 2 June 2007

14 IFRA/RIFM INFORMATIONAL BOOKLET VERSION 2.1 (MAY 10, 2007) How new and existing IFRA Standards will be set Definition of the IFRA product categories Changes in product categorization Product types not previously included Category 10: toilet seat wipes Category 11: tights with moisturizers; floor waxes; deodorizers for textiles or fabrics Re-categorization (new/updated exposure) Category 5: Wipes or Refreshing Tissues for Face, Neck, Hands, Body Category 7: Insect Repellent (intended to be applied to the skin) Api QRA Worksop 2 June 2007

15 IFRA/RIFM INFORMATIONAL BOOKLET VERSION 2.1 (MAY 10, 2007) 2 New tables added Table 1 Defines the SAF and product type consumer exposure levels that drive the IFRA QRA categories Consumer exposure that drives IFRA QRA Category 2 has been changed to 9.1 mg/cm 2 /day (from 8.5 mg/cm 2 /day) as a result of new exposure data on axilla surface area Table 3 Defines IFRA product categories by an alphabetical list of product types Api QRA Worksop 2 June 2007

16 DATA NEEDED FOR PRODUCT (RE-)CATEGORIZATION New form developed Product Type Name of Product Type Description of the Product Type Description of how the Product Type is Used What, if any, instructions are given to the Consumer on the product label Api QRA Worksop 2 June 2007

17 DATA NEEDED FOR PRODUCT (RE-)CATEGORIZATION Exposure Data Amount of fragrance in the product type? How much is used/use? How many uses/day? What is the surface area exposed? Will the fragrance come into direct contact with the skin? If not, please explain. Is the product rinsed off? If yes, should a retention factor be applied? Please explain. Is the product type an article? If yes, Amount of fragrance applied to the product? Amount of fragrance transferred from the product to the exposed area? Api QRA Worksop 2 June 2007

18 QRA DERMAL SENSITIZATION CINNAMIC ALDEHYDE Weight of Evidence NESIL Guinea-pig data moderate sensitizer [30] Local Lymph Node Assay EC 3 = 280 µg/cm 2 [23] Human data HRIPT NOEL = 591 µg/cm 2 Weight of Evidence NESIL = 590 µg/cm 2 SAF Considerations Inter-individual variability Product matrix differences Variations in use patterns Deo/AP SAF is 300 Conditioners SAF is 100 Exposure Calculation for Daily Exposure to 0.05% CA (IFRA Standard): = [Amount of CA in product x Amount product applied (mg)]/surface area exposed (cm 2 ) Consumer exposure Deo/AP=0.05% x 9.1 mg/cm 2 = 4.5 µg/cm 2 Conditioners = 0.05 % x 0.2 mg/cm 2 = 0.1 µg/cm 2 Api QRA Worksop 2 June 2007

19 QRA DERMAL SENSITIZATION CINNAMIC ALDEHYDE IN SOLID AP - INDUCTION 2.0 μg/cm 2 AEL 0.02% 1.7 μg/cm 2 CEL 0.05% 4.5 μg/cm 2 CEL 590 μg/cm 2 WoE NESIL AEL/CEL Acceptable SAF = 300 AEL/CEL Unacceptable Cinnamic Aldehyde Level - log μg/cm 2 Api QRA Worksop 2 June 2007

20 QRA DERMAL SENSITIZATION CINNAMIC ALDEHYDE IN CONDITIONERS - INDUCTION 0.05% 0.1 μg/cm 2 CEL 3.0% = 5.8 μg/cm 2 Potential Consumer exposure 5.9 μg/cm 2 AEL 590 μg/cm 2 WoE NESIL AEL/CEL Acceptable SAF = Cinnamic Aldehyde Level - log μg/cm 2 Api QRA Worksop 2 June 2007

21 IFRA STANDARD FOR CINNAMIC ALDEHYDE BASED ON QRA IFRA CA Examples of Product Type Cat. QRA 1 Lip Products 0.02% 2 Deodorant/Antiperspirant 0.02% 3 Hydroalc., Shaved Skin 0.09% 4 Hydroalc., Unshaved Skin 0.3% 5 Women Facial Cream 0.1% 6 Mouthwash 0.4% 7 Intimate Wipes 0.04% 8 Hair Styling Aids Non-Spray 0.6% 9 Conditioners, Rinse-off 3.0% 10 Hard Surface Cleaners 2.5% 11 Candle (Non-Skin/Incidental Skin) Limited Api QRA Worksop 2 June 2007

22 42 nd AMENDMENT: REVISED IFRA STANDARDS BASED ON QRA IFRA Cat. 1 p-t-butyldi- hydrocinnald (Bourgenol) 0.03% BMHCA 0.1% Cinn alcohol Eugenol 0.09% 0.2% t-2-hexenal 0.001% % 0.2% 0.1% 0.2% 0.001% 3 0.2% 0.6% 0.5% 0.9% 0.004% 4 0.5% 1.9% 1.4% 2.7% 0.01% 5 0.3% 1.0% 0.7% 1.4% 0.01% 6 0.8% 3.0% 2.2% 4.3% 0.02% 7 0.1% 0.3% 0.2% 0.4% 0.002% 8 1.1% 2.0% 2.0% 2.0% 0.02% 9 5.0% % 11 Limited Api QRA Worksop 2 June % 2.5% Limited 5.0% 2.5% Limited 5.0% 2.5% Limited 0.1% 0.2% Limited

23 42 nd AMENDMENT: EXISTING IFRA STANDARDS BASED ON QRA IFRA Cat. Hydroxy- citronellal Isocyclo- geraniol Isoeugenol Methoxydicyclo pentadiene carboxaldehyde 1 0.1% 0.1% 0.01% 0.1% 2 0.2% 0.1% 0.01% 0.2% 3 0.8% 0.6% 0.04% 0.8% 4 2.3% 1.8% 0.1% 2.3% 5 1.2% 0.9% 0.1% 1.2% 6 3.6% 2.8% 0.2% 3.6% 7 0.4% 0.3% 0.02% 0.4% 8 2.0% 2.0% 0.3% 2.0% 9 5.0% % 11 Limited Api QRA Worksop 2 June % 2.5% Limited 1.3% 2.1% Limited 5.0% 2.5% Limited

24 42 nd AMENDMENT: EXISTING IFRA STANDARDS BASED ON QRA IFRA Cat. 1 2-Methoxy- 4-methyl phenol 0.003% 1-Octen-3-yl acetate 0.1% Peru Balsam Rose ketones 0.03% 0.003% % 0.1% 0.04% 0.004% % 0.5% 0.1% 0.02% % 1.6% 0.4% 0.05% % 0.8% 0.2% 0.02% % 2.5% 0.7% 0.07% % 0.3% 0.07% 0.008% 8 0.1% 2.0% 1.0% 0.1% 9 0.6% % 11 Limited Api QRA Worksop 2 June % 2.5% Limited 4.8% 2.5% Limited 0.5% 0.8% Limited

25 42 nd AMENDMENT: NEW IFRA STANDARDS BASED ON QRA IFRA Cat. 1 α-amyl cinn alc 0.1% α-amyl cinn ald 0.7% Anisyl alcohol 0.04% Benzyl alcohol Benzyl benzoate Benzyl cinnamate 0.2% 1.7% 0.1% 2 0.1% 0.9% 0.1% 0.2% 2.2% 0.2% 3 0.5% 3.6% 0.2% 0.9% 8.9% 0.7% 4 1.6% 10.7% 0.7% 2.7% 26.7% 2.1% 5 0.8% 5.6% 0.4% 1.4% 14.0% 1.1% 6 2.5% 17.1% 1.1% 4.3% 42.8% 3.4% 7 0.3% 1.8% 0.1% 0.4% 4.5% 0.4% 8 2.0% 2.0% 1.5% 2.0% 2.0% 2.0% 9 5.0% % 11 Limited 5.0% 2.5% Limited 5.0% 2.5% Limited 5.0% 2.5% Limited 5.0% 2.5% Limited 5.0% 2.5% Limited

26 42 nd AMENDMENT: NEW IFRA STANDARDS BASED ON QRA IFRA Cat. 1 Benzyl salicylate 0.5% 2 0.7% 3 2.7% 4 8.0% 5 4.2% % 7 1.3% 8 2.0% 9 5.0% % 11 Limited Citronellol 0.8% 1.1% 4.4% 13.3% 7.0% 21.4% 2.2% 2.0% 5.0% 2.5% Limited Geraniol α-hexyl cinn ald 0.3% 1.0% 0.4% 1.8% 5.3% 2.8% 8.6% 0.9% 2.0% 5.0% 2.5% Limited 1.3% 5.3% 16.0% 8.4% 25.7% 2.7% 2.0% 5.0% 2.5% Limited

27 42 nd AMENDMENT: NEW IFRA STANDARDS BASED ON QRA IFRA Cat. Hexyl salicylate 1 0.7% Isocyclo- citral 0.2% α-methyl cinn ald Methyl ionone 0.1% 2.0% 2 0.9% 0.3% 0.1% 2.6% 3 3.6% 1.1% 0.5% 10.7% % 3.2% 1.6% 32.1% 5 5.6% 1.7% 0.8% 16.9% % 5.1% 2.5% 51.4% 7 1.8% 0.5% 0.3% 5.4% 8 2.0% 2.0% 2.0% 2.0% 9 5.0% % 11 Limited Api QRA Worksop 2 June % 2.5% Limited 5.0% 2.5% Limited 5.0% 2.5% Limited

28 REFINEMENT RISK ASSESSMENT- SKIN SENSITIZATION RA Risk Mgmt Clinical Reports Api QRA Worksop 2 June 2007

29 PATCH TEST DATABASE Fragrance Ingredient U. HOSPITAL LEUVEN Product Type Positive Patch Test Reactions Cinnamic Deodorant 2 Aldehyde Aftershave 1 Isoeugenol Deodorant 1 Hair Dye 1 Hydroalcoholic 5 Citral Hydroalcoholic 6 303/3323 (9.1%) Positive to Fragrance Mix; 133/303 Positive to Own Cosmetic; 66/133 fragrance-related contact allergic reactions Api QRA Worksop 2 June 2007

30 IFRA PRODUCT CATEGORIES IFRA Category Category 1 Category 2 Category 3 Category 4 Category 5 Category 6 Category 7 Category 8 Category 9 Category 10 Category 11 BASED ON QRA Examples of Products Lip Products, Toys, Insect Repellents Deodorants/Antiperspirants Hydroalcoholic Products for Shaved Skin, Eye Products, Men s Facial Cream & Balms, Tampons Hydroalcoholic Products for Unshaved Skin, Hair Styling Aids & Sprays, Body Creams Women s Facial Cream/Facial Make-up, Hand Cream, Facial Masks, Wipes/Refreshing Tissue for Hands, Face, Neck, Body Mouthwash, Toothpaste Intimate Wipes, Baby Wipes, Insect Repellent (intended to be applied to the skin) Make-up Remover, Hair Styling Aids Non-Spray, Nail Care Shampoo, Rinse-Off Conditioners, Bar Soap, Feminine Hygiene Pads & Liners Detergents, Hard Surface Cleaners, Diapers, Toilet Seat Wipes All Non-Skin or incidental skin contact products

31 IFRA QRA PRODUCT CATEGORY 11 All non-skin contact or incidental skin contact. Including: Candles Air Fresheners and Fragrancing of all types (plug-ins, solid substrate, membrane delivery, ambient, electrical, pot pourri, powders, fragrancing sachets, incense, etc.) Deodorizers/Maskers Not Intended For Skin Contact (e.g. fabric drying machine deodorizers, carpet powders) Insecticides (e.g. mosquito coil, paper, electrical, etc.) Toilet Blocks; Joss Sticks; Shoe Polishes Machine Dishwash Detergent and Deodorizers Machine Only Laundry Detergent (e.g. liquitabs) Plastic articles (excluding toys) Fuels; Paints; Cat litter; Animal Sprays Treated Textiles (e.g. starch sprays, fabric treated with fragrances after wash, deodorizers for textiles or fabrics, tights with moisturizers) Odored Distilled Water (that can be added to steam irons) Floor wax Pragmatic Level These products result in negligible skin contact. The approach for a pragmatic concentration of fragrance ingredient in this category is explained in IFRA RIFM Booklet

32 IFRA PRODUCT CATEGORY 5 SAF Product Type Consumer Exposure Level mg/cm 2 /day 100 Facial Cream/Make-up Hand Cream 4.2 IFRA Category 5 Consumer Exposure 4.2 Api QRA Worksop 2 June 2007

33 IFRA PRODUCT CATEGORIES BASED ON QRA IFRA Category SAF Category Consumer Exposure mg/cm 2 /day Product Type Designating IFRA Category Category 1 Category 2 Category 3 Category 4 Category Lipstick Solid Antiperspirant Aftershave Perfume Hand Cream Category 6 Category 7 Category 8 Category 9 Category 10 Category Toothpaste Intimate Wipes Hair Styling Aids Conditioners, Rinse-Off Hard Surface Cleaners Candles Api QRA Worksop 2 June 2007

34 QRA IMPLEMENTATION STATUS Technical dossier & Informational booklet published on RIFM (& IFRA) websites Publications - in preparation Perfumer & Flavorist article online (Api & Vey) Peer-reviewed scientific papers to be submitted Trade press in preparation Api QRA Worksop 2 June 2007

35 QRA IMPLEMENTATION STATUS Scientific Meetings SOT Annual Meeting Symposium (March 28, 2007) only positive feedback 9 th Contact Dermatitis Meeting, Hershey PA July 13, 2007 Australasian College Derm./ISCD/Asia-Pacific Environ Occup. Dermatitis Symposium Sept. 27, 2007 Implementation guidance - users & customers on going QRA Implementation Workshop 2 More needed? Api QRA Worksop 2 June 2007

36 QRA IMPLEMENTATION FUTURE FOCUS 40 th Amendment May fragrance ingredients 42 nd Amendment May Standards on 51 fragrance ingredients (new and existing) 43 rd Amendment (Spring 2008) - about 10 fragrance ingredients (new and existing) Key goal (2011): review all chemically defined fragrance ingredients with structural alerts for dermal sensitization that are used > 1 metric ton per year on a worldwide basis. REXPAN: Compliance with IFRA Standards Api QRA Worksop 2 June 2007

37 IFRA Certificates Changes and Impact due to 42nd Amendment Dr. Matthias Vey Scientific Director International Fragrance Association (IFRA) RIFM / IFRA QRA Implementation Workshop Marriott Saddle Brook June 4,

38 QRA DERMAL SENSITIZATION PROPOSED PRODUCT CATEGORIES From the 40 th Amendment on, IFRA Standards for sensitizing fragrance ingredients are based on the QRA (Quantitative Risk Assessment) concept. In practice this means an increased number of product categories with individual limitations (restrictions). Grouping product types according to similar SAFs (Safety Assessment Factors) and exposure, which lead to similar acceptable use levels (restriction) of a fragrance ingredient, resulted in 11 product categories in the IFRA Standards based on the QRA. 2

39 QRA based IFRA STANDARD Limits for 11 different product categories 3

40 QRA impact on the IFRA Certificate In order for the users of fragrance compounds to be adequately informed about the compliance of the fragrance compound with the requirements of the Code of Practice and the most recent Amendment for the intended application(s), the fragrance supplier industry provides the customer(s) with an IFRA Certificate The format of the Certificate became more complex with the introduction of the QRA Standards and the 11 product categories. Guidance was developed to ensure broadest harmonisation of content while allowing some freedom for the format 4

41 QRA impact on the IFRA Certificate Categories of product use as contained in different types of IFRA Standards, might be different for each type of critical endpoint (sensitization, systemic toxicity, phototoxicity), some overlapping, others not. For fragrance compounds containing one (or more) ingredients restricted via a QRA Standard the new QRA rules superimpose different categories than those already existing. For fragrances used in children s toys, lip products as well as oral care, IFRA asks that only materials assessed and approved for use in flavor be used. 5

42 QRA impact on the IFRA Certificate Categories of applications can be different: Phototoxicity: Leave-on, rinse-off and non-skin Systemic toxicity: Fine Fragrance, EdT, Fragrancing cream, other leave-on, rinse-off, non-skin, other non-cosmetic products not covered above (those categories were not developed by IFRA but required by European regulations addressing methyl eugenol only) Sensitization up to IFRA 39 skin contact and non-skin contact Sensitization via QRA - 11 categories 6

43 QRA impact on the IFRA Certificate Guidance introducing the system of classes for reporting compliance in the IFRA Certificate was first distributed with IFRA IL 768 (January 15, 2007) Since the 40 th Amendment a number of changes were introduced (due to new data received on exposure, surface area, etc) with regard to new product types included or re-categorised in the 11 IFRA QRA categories, which were published as part of the 42 nd Amendment. The changes introduced via the 42 nd Amendment are described in the QRA Information booklet, a revised version of which was distributed as part of the 42 nd Amendment. 7

44 Code of Practice - Standards 42 nd Amendment, notified May 16, revised Standards, for materials already restricted, based on the QRA, covering about 27 materials (including isomers) 14 new Standards based on the QRA, covering about 20 materials (including isomers) Addition of 4 materials, formerly restricted, to the list of other materials as there are insufficient data to apply QRA and there is no reported use, therefore no interest in producing data Reformatted Standard prohibiting the use of crude Peru balsam (the restriction part of the former Standard is part of the revised Standards based on QRA) 8

45 Code of Practice Standards Currently (42 nd Amendment): 151 Standards for fragrance ingredients 75 Standards prohibiting the use of certain fragrance ingredients* 65 ingredients are limited for their use in fragrance compounds 11 raw materials: special purity criteria Including 26 other materials, banned due to insufficient data 9

46 QRA impact on the IFRA Certificate The changes in the categories introduced via the 42 nd Amendment (new entries in categories or re-categorization of product types) do also have an impact on the classes for the IFRA Certificate. Comprehensive information about the changes in the system of classes was distributed with IFRA IL 773 of May 30, 2007 Some exemplary cases will be presented in on the following slides. 10

47 Changes in Classes Insect repellents were moved from category 1 to 7. With IL 764 IFRA recommended to its membership to follow the same rules for lip products (and oral care, category 6) as for toys. This will be reflected in the next revision of the Code of Practice No further need to split classes for category 1 QRA Product Type Old IFRA Category Systemic toxicity (Methyleugenol level) Phototoxicity Food use approval IFRA Certificate Class Category 1 Lip products of all types Leave-on Other Leave-on (4 ppm) Yes Yes* Class 1.A* Insect repellent Leave--on Other Leave--on Yes No Class 1.B Toys Leave-on Other Leave-on Yes Yes* Class 1.A 11

48 Changes in classes QRA Product Type Category 4 Old IFRA category Systemic toxicity (Methyleugenol level) Phototoxicity IFRA Certificate Class Hydroalc. Products, applied to unshaved skin Leave-on Leave on EdT (80 ppm) Fine Fragrance Yes Yes Class 4.A Class 4.B (200 ppm) Scent strips for hydroalcoholic products, scratch and sniff samples, other paper products not mentioned elsewhere for which skin exposure is only incidental (e.g. spectacle cleaning tissues Leave-on EdT (80 ppm) Yes Class 4.A Hair deodorant Leave-on Leave-on (4 ppm) Yes Class 4.C 12

49 Changes in classes QRA Product Type Old IFRA category Systemic toxicity (Methyl-eugenol level) Phototoxicity IFRA Certificate Class Category 5 Women s Facial Creams/Facial Make-up Leave-on Leave-on (4 ppm) Yes Class 5.A Hand cream Leave-on Leave-on (4 ppm) Yes Class 5.A Facial Masks Leave-on Leave-on (4 ppm) Yes Class 5.A** Wipes or Refreshing tissues for face, neck, hands, body Leave-on Leave-on (4 ppm) Yes Class 5.A ** There are several types of masks: peel off (similar to rinse-off), rinse off and leave-on (only removing excess with a tissue). To facilitate the table the most restrictive, i.e. leave-on is applied for all 13

50 Changes in classes QRA Product Type Category 7 Old IFRA category Systemic toxicity (Methyl-eugenol level) Phototoxicity IFRA Certificate Class Intimate wipes, toilet paper Leave-on Leave-on (4 ppm) No Class 7.A Baby wipes Leave-on Leave-on (4 ppm) No Class 7.A Insect repellent Leave-on Leave-on (4 ppm) Yes Class 7.B QRA Product Type Old IFRA category Systemic toxicity (Methyl-eugenol level) Phototoxicity IFRA Certificate Class Category 10 Addition Toilet seat wipes Leave-on Other leave-on (4 ppm) No Class 10.B 14

51 Changes in classes QRA Product Type Old IFRA category Systemic toxicity (Methyl-eugenol level Phototoxicity IFRA Certificate Class Category 11 Additions and changes Pot pourri, fragrancing sachets, liquid refills for air fresheners (noncartridge systems) Leave-on Other non-cosmetic (10 ppm) No Class 11.B Liquid refills for air fresheners (cartridge systems) Non-skin Non-skin (200 ppm in fragrance compound) No Class 11.A 15

52 Definition of Classes QRA Product Type Old IFRA category Systemic toxicity (Methyl-eugenol level Phototoxicity IFRA Certificate Class Category 11 Additions and changes Treated textiles (e.g. starch sprays, fabric treated with fragrances after wash, deodorizers for textiles or fabrics, tights with moisturizers) Leave-on Other non-cosmetic (10 ppm) No Class 11.B Floor wax Non-skin Non-skin (200 ppm in fragrance compound) No Class 11.A 16

53 Aerosols Pressurized aerosols: When calculating fragrance ingredient concentration in pressurized aerosols, to determine compliance with an IFRA Standard (determining the concentration reaching the skin), the propellant should be discounted because it flashes off very rapidly. The basis for the calculation should be the active solution or the mixture of the fragrance compound (fragrance mixture or fragrance oil) and other excipients (e.g. water, ethanol, active components). 17

54 Aerosols Aerosol skin contact: Skin contact from aerosol products (e.g. aerosol air freshener) as defined in Category 9 relates to those aerosol products that are not intended for skin contact, but their use may result in skin contact. This excludes deodorant/antiperspirants, hair styling aids and sprays, which are part of other categories. 18

55 IFRA Certificates General Suggestions to keep workload of customers and suppliers manageable (1/2): The notification of new Standards asks fragrance suppliers to inform their clients about the conformity of existing compounds within 60 days. Suggestions: Provide the information with priority for active formulas Customers to share information about the actual use of the compound and only ask the confirmation of the actual use(s), not across all potential uses (classes) 19

56 IFRA Certificates General Suggestions to keep workload of customers and suppliers manageable (2/2): Abstain from asking for calculation of a theoretical maximum use level wherever possible and instead focus on the confirmation of the current or foreseen use level Practical reason often, due to the nature of the base in which the compound will be used, oils can only be used in a limited number of finished products. Further, for modifications of existing products due to new Standards, it is best for the perfumers to have the actual use level so they can create the best modification possible. 20

57 Thank you very much for your attention Avenue des Arts 6, B 1210 Bruxelles, Phone: , mvey@ifraorg.org 21

58 I F R A Timetable for 42 nd Amendment QRA Implementation Workshop June 4, 2007 William Troy, Ph.D. Chairman IFRA Scientific Com.

59 I F R A Standard IFRA Time Lines Historically, IFRA established an effective date for new Amendments that was Immediate, for new creations 12 months for existing fragrances Based on the date of issuance of the Amendment 2

60 I F R A As various elements of the process were changed (e.g., customer consultation, publication on website), the effective dates became one month and 13 months, following the announcement, for new and existing fragrances With the advent of the 40 th Amendment it was clear that this timing would not be practical, due to the complexity of the new approach 3

61 I F R A Timing for 40th Product categories expanded from 2 to more than 20 (with sub-categories) Company computer systems had to be modified Reporting formats had to be modified Personnel training needs 4

62 I F R A Scientific Committee decided that an exceptional period of - 13 months for new creations, and - 25 months for existing fragrances would be adopted for this Amendment Therefore, the 4 materials with new IFRA restrictions would continue to be used in new creations for 13 months, and in existing fragrances for 25 mo. 5

63 I F R A Some Definitions New creation : : fragrance for which a new brief, or other fragrance creation direction, is issued subsequent to the official date of issuance of a new Amendment Existing fragrance : A fragrance that is already sold in the marketplace 6

64 I F R A Some Definitions (cont d) A fragrance for which development (whether new or reformulation) had already begun prior to the official date of issuance of a new Amendment 7

65 I F R A 42 nd Amendment 14 materials, or groups of materials, which already have IFRA use restrictions have been converted to QRA-format Standards 14 materials, or groups of materials, are newly restricted 8

66 I F R A 42 nd Amendment (cont d) For the 14 currently restricted materials, and taking into account 10 skin contact product categories, there are a total of 140 potential restrictions. Of the 140, 47 of the new levels are more restrictive than the current levels of restriction 9

67 I F R A 42 nd Amendment Compliance Timing For Standards applying to new creations: one month after issuance (June 16, 2007) For Standards applying to existing creations: 25 months after issuance (June 16, 2009) For fragrance materials added to the list of other materials: one month for new, and 13 months for existing, fragrances 10

68 I F R A The Future The increased complexity of the IFRA process, resulting from the QRA, and the sharply increased numbers of materials being restricted, have prompted the question: Shouldn t t we make a permanent change in the implementation time for new Amendments? 11

69 I F R A A task force of the IFRA JAG studied this question, and the IFRA Board was also consulted It was recognized that, until all currently restricted materials are subjected to the QRA, Amendments will contain more materials than usual Once these are dealt with, however, the situation should return to normal 12

70 I F R A From a public credibility point of view, the Board felt strongly that we cannot afford to permanently lengthen the amount of time allotted for product reformulations, following the publication of a new Amendment They did approve, however, the extraordinary use of an extended time period, when necessary 13

71 I F R A Therefore, the use of the 1/13 month implementation periods will be retained for most IFRA Amendments, with exceptions being allowed on a case by case basis (as it has been for the 42 nd ) 14