ADMIN. Memo Agenda Minutes Format Report Strategies Citrus Hydrolyzed Proteins New Data Chamomile MI

Size: px
Start display at page:

Download "ADMIN. Memo Agenda Minutes Format Report Strategies Citrus Hydrolyzed Proteins New Data Chamomile MI"

Transcription

1 ADMIN Memo Agenda Minutes Format Report Strategies Citrus Hydrolyzed Proteins New Data Chamomile MI CIR EXPERT PANEL MEETING SEPTEMBER 21-22, 2015

2 Commitment & Credibility since 1976 MEMORANDUM To: CIR Expert Panel Members and Liaisons From: Director, CIR Subject: 136 th Meeting of the CIR Expert Panel Monday and Tuesday, September 21-22, 2015 Date: August 28, 2015 Enclosed are the agenda and accompanying materials for the 136 th CIR Expert Panel Meeting to be held on September 21-22, The meeting will be held at the Hilton-DoubleTree Hotel, 1515 Rhode Island Avenue, NW, Washington, DC Phone: (202) ; Fax: (202) The hotel is located within walking distance of our office building. The meeting agenda includes consideration of 13 ingredient groups advancing in the review process, one re-review, discussions on the latest SCCS opinion on MI, and the new data that may warrant the reopening of the 2013 Final Report on Chamomilla recutita-derived Ingredients. The Panel is also asked to provide guidance on the selection of ingredients for the next series of reports related to Citrus and Hydrolyzed Proteins. Strategy documents are included in this package. Finally, the CIR staff is seeking the Panel s review and comment on some proposed revisions to the format of CIR safety assessments. These proposed changes reflect CIR s review of the overall organization of the report as well as an examination of the content information included in each subsection, particularly the toxicology sections of the report. Schedule and hotel accommodations We have reserved rooms for the nights of Sunday September 20 and Monday September 21, at the Hilton-DoubleTree Hotel. If you encounter travel problems, please contact me on my cell phone at Team meetings New data 1. Methylisothiazolinone In June 2015, the European Scientific Committee on Consumer Safety (SCCS) issued their latest opinion on the preservative methylisothiazolinone (MI) based on a quantitative risk assessment (QRA) and data from their cosmetovigilance system. The Panel issued an amended safety assessment report for MI at the September 2014 Panel meeting. After reviewing the SCCS opinion, the question for the Panel is whether there is a need for further evaluation. 2. Chamomilla recutita-derived ingredients In December 2013, the Panel issued a final report with the conclusion that the flower-derived ingredients were safe when formulated to be nonsensitizing. The Panel further concluded that the data was insufficient for determining the safe use of ingredients derived from the whole plant and the leaves and stem. Industry has submitted additional information for the Panel to determine if the new data is sufficient to assess the safety of those ingredients considered insufficient in the 2013 final report L Street, NW, Suite 1200, Washington, DC (Main) (Fax) ( ) cirinfo@cir-safety.org (Website)

3 Re-review there is 1 report for re-review. 1. Monoglyceryl Monoesters (agenda and flash drive name monoglyceryl monoesters) Glyceryl stearate and glyceryl stearate SE were reviewed previously (published in 1982) with the conclusion that these ingredients are safe for topical application. Final reports (4) on 35 similar ingredients determined by the Panel to be safe as used, and 8 similar ingredients that have not been reviewed, are included in this report. Use frequencies and the concentrations of use have decreased for all ingredients except glyceryl rosinate and glyceryl hydrogenated rosinate, (glyceryl rosinate increased from 12% to 96%). New data have been added to the report. Since CIR is developing 2 reports from the family of glyceryl esters, the Panel should consider the need to reopen to revise the conclusion and, if reopened, whether new ingredients should be added. Draft reports - there are 5 draft reports for review. 1. Alkyl Taurate Amides and Taurate Salts (agenda and flash drive name taurate amides) This is the first time that the Panel is seeing this report on 20 ingredients. The Scientific Literature Review was announced for public comment on June 1, These 20 ingredients mostly function in cosmetics as surfactants cleansing agents. Some summary data from the ECHA database are included in the report. The highest rinse-off use concentration is up to 28% in bath products. Technical comments from the Council have been addressed. Are the data sufficient to proceed with issuing a tentative report, or should an insufficient data announcement be issued? 2. Hexamethylene Diisocyanate (HDI) Polymers (agenda and flash drive name HDI) This is the first time that the Panel is seeing this report on 19 ingredients. The Scientific Literature Review was announced for public comment on June 18, Although these copolymers are not diisocyanates, they are synthesized, in part, from the common diisocyanate monomer. Exposure to diisocyanates, such as HDI, has been shown to illicit the development of allergic responses. These ingredients are reported to function as viscosity increasing agents aqueous, anticaking agents, and film formers, and are reported to be used in 348 leave-on products at a maximum use concentration of 31%. Some acute toxicity, irritation and sensitization data are included on 3 ingredients. No data were available for the other ingredients in this report. Is the information sufficient to proceed with issuing a tentative report of safety, or should an insufficient data announcement be issued? 3. Inorganic Hydroxides (agenda and flash drive name inorganic hydroxides) This is the first time that the Panel is seeing this report on these 4 alkaline salts that are reported to function as ph adjusters in cosmetics. The Scientific Literature Review was issued on June 18, Although many of the inorganic hydroxides in this report are known caustic agents with acute exposures to skin, sodium hydroxide has been used in the manufacture of soap for millennia. Sodium hydroxide has the most reported uses (5147), half of which are in leave-on skin care products. The highest maximum concentration of use is 13.2% in rinse-off products; the lowest reported maximum use concentration is up to 0.5% in leave-on products. ECHA summary data and unpublished data have been added to the report. Technical comments have been considered. Are the data sufficient for issuing a tentative report, or should an insufficient data announcement be issued? 4. Polymerized Tetramethylcyclotetrasiloxanes (agenda and flash drive name cyclotetrasiloxanes) At the March 2015 meeting, the Panel agreed to table this report. Industry requested an additional 6 months to collect data and provide data for physical chemical properties, impurities and residual monomers, method of manufacture, dermal sensitization and irritation for polysilicone-2. The Panel requested these data, as well as additional data, for all ingredients in this report. To date, concentration of use data have been received and are incorporated into the report. Recent data submitted will be in Wave 2. Are the available data sufficient for issuing a tentative report with a safe as used, safe with qualifications conclusion, or should an insufficient conclusion on these ingredients, be issued? 5. Trimellitic Anhydride Copolymers (agenda and flash drive name trimellitic copolymers) This is the first time that the Panel is seeing this report on these 6 ingredients that are reported to function as film formers in cosmetics. The Scientific Literature Review was issued on June 1,

4 2015. Most of the information included in this report comes from ECHA summaries or OECD SIDS reports. Concentration of use data are included in the draft report. Technical comments have been considered. Are the data sufficient to issue a tentative report? If the data are insufficient, what are the data needs? Tentative reports there are 3 draft tentative reports. 1. Alkonium Clays (agenda and flash drive name alkonium clays) At the June 2015 meeting, the Panel issued an Insufficient Data Announcement for the 8 alkonium clays in this report. These ingredients are reported to function as dispersing agents - nonsurfactant, emulsion stabilizers, and viscosity increasing agents nonaqueous. The Panel requested data on particle size distribution, percent alkonium cation in the ingredient, percent of the cation releasable in solution, and inhalation and ocular irritation data at concentration of use. Some irritation and sensitization data were submitted and are included. Data on particle size are also included. No additional data have been submitted. Are there remaining unmet critical data needs (in which case a final report with an insufficient data conclusion would be issued)? Or, are the data sufficient to issue a final report with a safe or safe with qualifications conclusion? 2. Apple-derived ingredients (agenda and flash drive name apple) At the June 2015 meeting, the Panel issued an Insufficient Data Announcement for 9 of the 28 apple-derived ingredients in this report. The Panel agreed that the available data are sufficient for evaluating the safety of19 apple-derived ingredients when the source is either the fruit or the seed. Data needs included method of manufacture and impurities, a 28-day dermal-toxicity study and, if absorbed, genotoxicity and reproductive and developmental toxicity data and skin irritation and sensitization data. Recently-received information that may address the data needs will be provided in Wave 2. Additionally, at the Panel s request, the safety test data on apple polyphenol extract and procyanidin-b have been added to the report. Technical comments have been addressed. Are the data sufficient for issuing a final report with a safe or safe with qualifications conclusion for all of the ingredients, or should a final report with a split conclusion of safe or safe with qualification for some, and insufficient data for others, be issued? 3. Silk Proteins (agenda and flash drive name silk proteins) At the June 2015 meeting, the Panel issued an Insufficient Data Announcement and requested additional data on MEA-Hydrolyzed Silk and Silkworm Cocoon Extract. The data needed included method of manufacture and impurities, concentration of use, a 28-day dermal toxicity study and, if absorbed, genotoxicity and reproductive and developmental toxicity data and skin irritation and sensitization data. No additional data related to the identified needs have been submitted. The Panel agreed that the available data are sufficient for evaluating the safety of Fibroin, Hydrolyzed Fibroin, Hydrolyzed Sericin, Hydrolyzed Silk, Sericin, Silk, Silk Extract, and Silk Powder. Data relating to the allergenicity of silk proteins and a case report on the potential for silk to induce contact urticaria have been included. Are the available data sufficient for issuing a final report with a safe or safe with qualifications conclusion for all of the ingredients, or should a final report with a split conclusion of safe or safe with qualification for some, and insufficient data for others, be issued? Final reports - there are 5 draft final reports for consideration. After reviewing these drafts, especially the rationales provided in the Discussion sections, the Panel should issue them as final reports, as appropriate. 1. Citrus fruit-derived Ingredients (agenda and flash drive name Citrus fruit) At the June 2015 meeting, the Panel issued a tentative report with the conclusion that 80 Citrus fruit-derived ingredients are safe for use in cosmetic products when finished products, excluding rinse-off products, do not contain more than % (15 ppm) 5-methoxypsoralen (5-MOP), and when formulated to be non-sensitizing and non-irritating. No new unpublished data have been received. Technical comments have been addressed. A final report should be issued. 2. Nonoxynols (agenda and flash drive name nonoxynols). At the June 2015 meeting, the Panel issued a tentative amended report for public comment with the conclusion that 19 nonoxynols, -9, -11, -10, -12, -13, -14, -15, -18, -20, -23, -25, -30, -35, -40, -44, -50, -70, -100, and -120, are safe

5 in the present practices of use and concentration in cosmetics, and that 8 nonoxynols, -1, -2, -3, -4, -5, -6, -7, and -8, are safe as used in rinse-off products and safe at concentrations 5% in leave-on products. No new data have been received. Technical comments have been addressed. A final report should be issued. 3. Polysaccharide Gums (agenda and flash drive name polysaccharide gums). At the June 2015 meeting, the Panel issued a tentative report with the conclusion that 105 polysaccharide gums are safe in the present practices of use and concentration, and that the available data are insufficient for determining the safety of hydrolyzed carrageenan in cosmetic products. No new data have been received. Technical comments have been addressed. 4. Soy Peptides (agenda and flash drive name soy peptides) At the June 2015 meeting, the Panel issued a tentative report with the conclusion that 6 soy-based ingredients are safe in cosmetics in the present practices of use and concentration. Soy is a known food allergen. However, there was little concern that, as used, these ingredients would elicit type I immediate hypersensitivity because the ingredients are water soluble, would not penetrate the skin, and have molecular weights that are well below that which would cause IgE-binding. No new data or comments were received. 5. Trialkyl Trimellitates (agenda and flash drive name trimellitates) At the June 2015 meeting, the Panel issued a tentative report with the conclusion that 5 trialkyl trimellitates are safe in the present practices of use and concentration in cosmetics when formulated to be non-irritating. Unpublished data on a lipstick were submitted and are included in the report. Technical comments have been addressed. Full Panel Meeting Remember, the breakfast buffet will open at 8:00 am and the meeting starts at 8:30 am on day 1 and on day 2. The Panel will consider the 5 reports to be issued as final safety assessments, followed by the remaining reports advancing in the process and the re-review, and finish by providing comments on report format, the report strategies, and the new data. The majority of the agenda involves reviewing the draft and tentative reports. It is likely that the full Panel session will conclude before lunch on day 2, so plan your travel accordingly. Have a safe journey.

6 Agenda 136 th Cosmetic Ingredient Review Expert Panel Meeting September 21-22, 2015 The Hilton Double Tree Hotel 1515 Rhode Island Avenue, N.W. Washington, D.C Monday, September 21 8:00 am CONTINENTAL BREAKFAST 8:30 am WELCOME TO THE 136 th EXPERT PANEL TEAM MEETINGS Drs. Bergfeld/Gill 8:40 am TEAM MEETINGS Drs. Marks/Belsito Dr. Marks Team Dr. Belsito s Team* Admin (BH) report strategies (Citrus, HP) FR (WJ) polysaccharide gums Admin (LG/BH) new data (MI, Chamomille) FAR (WJ) nonoxynols TR (LB) alkonium clays TR (WJ) apple DR (LB) cyclotetrasiloxanes TR (WJ) silk proteins DR (LB) taurate amides FR (MF) trimellitates DR (LB) HDI DR (MF) trimellitic copolymers FR (CB) Citrus fruit RR (MF) monoglyceryl monoesters FR (CB) soy peptides Admin (MF) format DR (CB) inorganic hydroxides Admin (BH) report strategies (Citrus, HP) FR (WJ) polysaccharide gums Admin (LG/BH) new data (MI, Chamomille) FAR (WJ) nonoxynols TR (LB) alkonium clays TR (WJ) apple DR (LB) HDI TR (WJ) silk proteins DR (LB) cyclotetrasiloxanes FR (MF) trimellitates DR (LB) taurate amides DR (MF) trimellitic copolymers FR (CB) Citrus fruit RR (MF) monoglyceryl monoesters FR (CB) soy peptides Admin (MF) format DR (CB) inorganic hydroxides Noon 1:00pm Lunch for Panel, liaisons, and staff Team meetings - continue as needed 5:00 pm ADJOURN DAY 1 SESSION FR: Final report FAR: Final amended report TR: Tentative report DR: Draft report RR : Re-review NOTE: The order of presentation and discussion of each topic will be maintained. However, the scheduled times may be accelerated or delayed depending upon the time required for the Expert Panel to complete its review of each subject. *Team moves to breakout room.

7 Tuesday, September 22 8:00 am CONTINENTAL BREAKFAST 8:30 am WELCOME TO THE 136 th FULL CIR EXPERT PANEL MEETING 8:45 am Admin MINUTES OF THE June 2015 EXPERT PANEL MEETING Dr. Bergfeld 9:00 am DIRECTOR S REPORT Dr. Gill 9:10 am FINAL REPORTS, REPORTS ADVANCING TO THE NEXT LEVEL, RE-REVIEWS, and OTHER DISCUSSION ITEMS Final Reports FR (MF) FR (CB) FR (CB) FR (WJ) FAR (WJ) Trimellitates Dr. Belsito reports Citrus fruit Dr. Marks reports Soy peptides Dr. Belsito reports Polysaccharide gums Dr. Marks reports Nonoxynols Dr. Belsito reports Reports Advancing TR (WJ) TR (WJ) TR (LB) DR (LB) DR (LB) DR (LB) DR (CB) DR (MF) Apple Dr. Marks reports Silk proteins Dr. Belsito reports Alkonium clays Dr. Marks reports Taurate amides Dr. Belsito reports HDI Dr. Marks reports Cyclotetrasiloxanes Dr. Belsito reports Inorganic hydroxides Dr. Marks reports Trimellitic copolymers Dr. Belsito reports Re-review RR (MF) Monoglyceryl monoesters Dr. Marks reports Other Discussion Items Admin (MF) Admin (BH) Admin (LG/BH) Format Dr. Belsito reports Report strategies Dr. Marks reports New Data (MI, Chamomille) Dr. Belsito reports ADJOURN - Next meeting Monday and Tuesday, December 14-15, 2015 at The Hilton Double Tree Hotel, 1515 Rhode Island Avenue, NW, Washington, DC FR: Final report FAR: Final amended report TR: Tentative report DR: Draft report RR : Re-review

8 ONE HUNDRED THIRTY-FIFTH MEETING OF THE EXPERT PANEL June15-16, 2015 DoubleTree by Hilton Hotel Washington, D.C. Expert Panel Members Wilma F. Bergfeld, M.D., Chair Donald V. Belsito, M.D. Liaison Representatives Consumer Rachel Weintraub, Esq. Ronald A. Hill, Ph.D. Curtis D. Klaassen, Ph.D. Daniel C. Liebler, Ph.D. Industry Beth A. Lange, Ph.D. James G. Marks, Jr., M.D. Ronald C. Shank, Ph.D. Thomas J. Slaga, Ph.D. Paul W. Snyder, D.V.M., Ph.D. Government Linda Katz, MD., M.P.H. (Absent) Adopted (Date) Wilma F. Bergfeld, M.D.

9 Others Present at the Meeting Lillian Becker Enio Miranda-Bermudez Don Bjerke Ivan Boyer Christina Burnett Roberto Dal Toso Kapal Dewa Carol Eisenmann Monice Fiume Kevin Fries Lillian Gill Tracy Guerrero Bart Heldreth Carla Jackson Wilbur Johnson, Jr. Wendy Koch Dennis Laba Julia Linthicum Lauren Nardella Damani Parran Tom Re Noriko Shibuya David Steinberg Lorena Telofski Jeremy Wong CIR FDA Procter & Gamble CIR CIR Croda-Sederma FDA PCPC CIR CIR CIR SEHSC CIR CIR CIR SEHSC Presperse CIR The Rose Sheet Akzo L-Oreal Shiseido Steinberg & Associates JTJCCI Estee Lauder

10 CHAIRMAN S OPENING REMARKS MINUTES FROM THE 135 th CIR EXPERT PANEL MEETING The 135 th meeting of the Cosmetic Ingredient Review (CIR) Expert Panel was called to order by Dr. Wilma Bergfeld at 8:30 a.m. on June 16, 2015, and all attendees were welcomed. She noted that 14 ingredient reports were reviewed in Teams on the preceding day, and that Dr. Roberto Dal Toso, R&D Manager with Croda-Sederma had given a presentation on the development and use of plant cell cultures as sources of ingredients for cosmetics and other products. Dr. Dal Toso presented analytical data showing that the constituents of Centella asiatica meristem cells were comparable to that of a classical Centella asiatica extract identified as a cosmetic ingredient. Dr. Bergfeld recalled that this information was new to the Panel. Dr. Bergfeld complimented the CIR Staff on the overall appearance of the safety assessments reviewed, which continues to improve. APPROVAL OF MINUTES The minutes of the March 16-17, 2015 CIR Expert Panel meeting were unanimously approved. DIRECTOR S REPORT Dr. Gill discussed 2 projects that CIR is initiating this month. The first project focuses on the development of an electronic documentmanagement and tracking system with a goal of enhancing the project management and workflow efficiencies in CIR. It is the first step in building an information management framework that combines authoring capability, bibliography and document management, workflow of records, and the storage and retrieval of safety assessments and related files. The goal of the second initiative is to enhance the scientific and technical CIR capability of applying computational methods in the ingredient safety assessment process. Efforts this year will focus on evaluating the available computational methods for filling data gaps, including read-across of in vivo data or predictions such as QSAR results (e.g., chemical similarity, analog quality, in vivo data quality). Additionally, this project includes the development of a schema and ground floor electronic data system that CIR anticipates will lead to a full CIR toxicity and risk assessment database. Dr. Gill mentioned that a presentation from Industry is scheduled for the September 21-22, Panel meeting. The Silicones Environmental, Health and Safety Center have asked to provide a brief chemistry overview on polysilicones. Dr. Gill congratulated the Panel Chair, Dr. Wilma Bergfeld, for her recent honor. In early June, at the 23rd World Congress of Dermatology meeting in Vancouver, Galderma Pharma recognized Dr. Bergfeld as one of the top 4 women dermatologist leaders across the world. (Dr. Bergfeld is also the founding President of the Women s Dermatology Society, which is over 40 years old.) In recognition of this outstanding accomplishment, Galderma honored the 4 international women dermatologist in a bigger than life mural which was painted on-site during the meeting. The mural will hang in the lobby of Galderma Pharma s corporate office in New York. Final Safety Assessments Centella asiatica Derived Ingredients The Panel issued a final report with the conclusion that the following 9 ingredients are safe in the present practices of use and concentrations in cosmetic products when formulated to be non-sensitizing. centella asiatica extract centella asiatica callus culture centella asiatica leaf extract centella asiatica flower/leaf/stem extract centella asiatica leaf cell culture extract centella asiatica leaf water centella asiatica meristem cell culture centella asiatica meristem cell culture extract centella asiatica root extract In a briefing on plant cell cultures, an Industry expert stated that centella asiatica meristem cell culture consists of primary metabolites (lipids and glucides), amino acids, and secondary metabolites, and that 20% centella asiatica meristem cell culture was not toxic in a human repeated insult patch test or in in vitro ocular irritation, phototoxicity, and genotoxicity tests. Additional information suggested that the composition of centella asiatica meristem cell culture and centella asiatica callus culture are comparable, that the root, stem, and leaves are similar in terms of their composition, and that the greatest concentration of components (e.g., terpenoids and flavonoids) is found in the leaf. Centella asiatica extract was a reproductive toxicant in male rats at daily oral doses ranging from 100 to 300 mg/kg/day, as was centella asiatica leaf extract at a daily oral dose of 100 mg/kg/day. However, the Panel noted that these levels of exposure would not

11 be approached with ingredient use in a cosmetic product, and the Panel was not concerned about the toxicity risk at the levels reported in this safety assessment. PEGs Cocamine and Related Ingredients The Panel issued a final amended report with the conclusion that the following 47 PEGs cocamine and related ingredients are safe in cosmetics in the present practices of use and concentration when formulated to be non-irritating: PEG-2 cocamine PEG-3 cocamine* PEG-4 cocamine* PEG-5 cocamine PEG-8 cocamine* PEG-10 cocamine* PEG-12 cocamine* PEG-15 cocamine PEG-20 cocamine* PEG-2 hydrogenated tallow amine* PEG-5 hydrogenated tallow amine PEG-8 hydrogenated tallow amine PEG-10 hydrogenated tallow amine* PEG-15 hydrogenated tallow amine* PEG-20 hydrogenated tallow amine* PEG-30 hydrogenated tallow amine* PEG-40 hydrogenated tallow amine* PEG-50 hydrogenated tallow amine* PEG-2 lauramine* PEG-2 oleamine PEG-5 oleamine* PEG-6 oleamine* PEG-10 oleamine* PEG-15 oleamine* PEG-20 oleamine* PEG-25 oleamine* PEG-30 oleamine* PEG-12 palmitamine* PEG-2 rapseedamine PEG-2 soyamine PEG-5 soyamine PEG-8 soyamine* PEG-10 soyamine* PEG-15 soyamine* PEG-2 stearamine* PEG-5 stearamine* PEG-10 stearamine* PEG-15 stearamine* PEG-50 stearamine* PEG-2 tallow amine PEG-7 tallow amine* PEG-11 tallow amine* PEG-15 tallow amine* PEG-20 tallow amine* PEG-22 tallow amine* PEG-25 tallow amine* PEG-30 tallow amine* *Not reported to be in current use. Were ingredients in this group not in current use to be used in the future, the expectation is that they would be used in product categories and at concentrations comparable to others in this group. Although data gaps were noted, the data available for some of these ingredients and their analogs, together with the SAR-based readacross analysis presented, were used to support the safety of the PEGs cocamine and other related ingredients in this report. The Panel noted that exposure durations and frequencies for the smaller ingredients in this group (i.e., PEG-2, 3, 4, and 5 cocamine and related ingredients) would be relatively low, because these ingredients are used predominantly in rinse-off hair-coloring products. Polyenes The Panel issued a final safety assessment with the conclusion that the following 26 polyenes are safe in cosmetics in the present practices of use and concentration: butene/propylene copolymer* butylene/ethylene copolymer butylene/ethylene/propylene copolymer decene/butene copolymer ethylene/octene copolymer* ethylene/propylene copolymer hydrogenated poly(c6-12 olefin) hydrogenated poly(c6-14 olefin) hydrogenated poly(c6-20 olefin) hydrogenated polybutene* hydrogenated polydecene hydrogenated polydodecene* hydrogenated polyisobutene isobutylene/isoprene copolymer* isoprene/pentadiene copolymer* polybutene poly(c4-12 olefin)* poly(c6-14 olefin)* poly(c20-28 olefin)* poly(c30-45 olefin) polydecene polyethylene polyisobutene polyisoprene polypentene* polypropylene *Not reported to be in current use. Were ingredients in this group not in current use to be used in the future, the expectation is that they would be used in product categories and at concentrations comparable to others in this group.

12 These polyenes exhibited low systemic toxicity at high doses in single-dose and repeated-dose animal studies, no teratogenic or carcinogenic effects in animal studies, and no genotoxicity in in vitro and in vivo studies. The data indicated use concentrations as high as 95% in lipsticks, however minimal toxicity was observed in repeated dose studies and no irritation or sensitization was observed in multiple animal and human tests at concentrations as high as 100%. The Panel noted that, although molecular weights are in the range that could be dermally absorbed, the lack of heteroatom functional groups dramatically limits solubility and would prevent significant absorption. The lack of such functional groups also limits interactions with other biomolecules and probably accounts for the apparent biological inertness of these ingredients. Polysorbates The Panel issued a final amended report with the conclusion that the 80 polysorbates listed below are safe in cosmetics in the present practices of use and concentration when formulated to be non-irritating. polysorbate 20 polysorbate 21 polysorbate 40 polysorbate 60 polysorbate 61 polysorbate 65 polysorbate 80 polysorbate 81 polysorbate 85 PEG-30 sorbitan beeswax PEG-20 sorbitan cocoate PEG-40 sorbitan diisostearate PEG-2 sorbitan isostearate* PEG-5 sorbitan isostearate* PEG-20 sorbitan isostearate PEG-40 sorbitan lanolate PEG-75 sorbitan lanolate* PEG-10 sorbitan laurate PEG-40 sorbitan laurate PEG-44 sorbitan laurate PEG-75 sorbitan laurate PEG-80 sorbitan laurate PEG-3 sorbitan oleate PEG-6 sorbitan oleate PEG-20 sorbitan oleate* PEG-40 sorbitan oleate* PEG-80 sorbitan palmitate* PEG-40 sorbitan perisostearate* PEG-40 sorbitan peroleate PEG-3 sorbitan stearate PEG-4 sorbitan stearate* PEG-6 sorbitan stearate PEG-40 sorbitan stearate PEG-60 sorbitan stearate* PEG-30 sorbitan tetraoleate PEG-40 sorbitan tetraoleate PEG-60 sorbitan tetraoleate PEG-60 sorbitan tetrastearate* PEG-4 sorbitan triisostearate* PEG-20 sorbitan triisostearate* PEG-160 sorbitan triisostearate PEG-2 sorbitan trioleate* PEG-18 sorbitan trioleate PEG-3 sorbitan tristearate* sorbeth-2 beeswax* sorbeth-6 beeswax sorbeth-8 beeswax* sorbeth-20 beeswax sorbeth-2 cocoate* sorbeth-2 hexacaprylate/caprate* sorbeth-12 hexacocoate* sorbeth-2 hexaisostearate* sorbeth-2 hexalaurate* sorbeth-2 hexaoleate* sorbeth-40 hexaoleate (PEG-40 sorbitol hexaoleate)* sorbeth-50 hexaoleate (PEG-50 sorbitol hexaoleate)* sorbeth-6 hexastearate* sorbeth-150 hexastearate* sorbeth-3 isostearate* sorbeth-6 laurate* sorbeth-2/oleate/dimer dilinoleate crosspolymer* sorbeth-20 pentaisostearate* sorbeth-30 pentaisostearate* sorbeth-40 pentaisostearate* sorbeth-50 pentaisostearate* sorbeth-40 pentaoleate* sorbeth-20 tetraisostearate* sorbeth-30 tetraisostearate sorbeth-40 tetraisostearate* Sorbeth-50 tetraisostearate* sorbeth-4 tetraoleate sorbeth-6 tetraoleate sorbeth-30 tetraoleate sorbeth-40 tetraoleate sorbeth-60 tetraoleate sorbeth-30 tetraoleate laurate (PEG-30 sorbitol tetraoleate laurate)* sorbeth-60 tetrastearate (PEG-60 sorbitol tetrastearate)* sorbeth-3 tristearate* sorbeth-160 tristearate* sorbeth-450 tristearate* *Not reported to be in current use. Were ingredients in this group not in current use to be used in the future, the expectation is that they would be used in product categories and at concentrations comparable to others in this group. This report combines the polysorbate ingredients from reports published in 1984, 2000, and 2001 and reflects a change in the Panel s previous safe-as-used conclusion, with an additional restriction in the 2001 report. In the original safety assessment (2001) of sorbeth beeswax ingredients, the Panel recommended the qualification that cosmetic formulations containing the polyethylene glycol (PEG)

13 moiety not be used on damaged skin. Since then, new data available in the re-review of PEG ingredients showed that PEGs, when used in cosmetics, would not cause renal damage when applied to damaged skin. Therefore, the qualification is removed from the conclusion for these, and all other PEG-containing cosmetic ingredients. These ingredients mostly function as surfactants in cosmetics. Four of these ingredients have had name changes since their original safety assessments. Tentative Safety Assessments Citrus Fruit Derived Ingredients The Panel issued a tentative report for public comment with the conclusion that the 80 Citrus fruit-derived ingredients listed below are safe for use in cosmetic products when finished products, excluding rinse-off products, do not contain more than % (15 ppm) 5- methoxypsoralen (5-MOP), and when formulated to be non-sensitizing and non-irritating. citrus aurantifolia (lime)/citrus limon (lemon) fruit water* citrus aurantifolia (lime) fruit* citrus aurantifolia (lime) fruit extract citrus aurantifolia (lime) fruit water* citrus aurantifolia (lime) juice citrus aurantium amara (bitter orange) fruit extract citrus aurantium amara (bitter orange) fruit juice extract* citrus aurantium bergamia (bergamot) fruit extract citrus aurantium bergamia (bergamot) fruit water* citrus aurantium dulcis (orange) fruit extract citrus aurantium dulcis (orange) fruit powder* citrus aurantium dulcis (orange) fruit water citrus aurantium dulcis (orange) juice citrus aurantium sinensis (orange) fiber citrus clementina fruit extract* citrus clementina juice* citrus depressa fruit extract* citrus depressa fruit water* citrus glauca fruit extract citrus grandis (grapefruit) fruit extract citrus grandis (grapefruit) fruit/peel water citrus grandis (grapefruit) fruit water citrus grandis (grapefruit) juice citrus grandis/paradisi fruit water* citrus hassaku fruit extract* citrus hassaku/natsudaidai fruit juice* citrus hassaku/natsudaidai fruit powder* citrus iyo fruit extract* citrus iyo fruit water* citrus jabara juice* citrus japonica fruit extract citrus junos fruit extract citrus junos fruit juice* citrus junos fruit oil* citrus junos fruit powder* citrus junos fruit water* citrus limon (lemon) fruit extract citrus limon (lemon) fruit oil* citrus limon (lemon) fruit powder* citrus limon (lemon) fruit water citrus limon (lemon) juice citrus limon (lemon) juice extract citrus limon (lemon) juice powder* citrus madurensis fruit extract citrus madurensis fruit juice* citrus medica vulgaris fruit extract citrus nobilis (mandarin orange) fruit extract citrus nobilis (mandarin orange) fruit juice citrus paradisi (grapefruit) fruit extract citrus paradisi (grapefruit) fruit water* citrus paradisi (grapefruit) juice* citrus reticulata (tangerine) fruit* citrus reticulata (tangerine) fruit extract citrus reticulata (tangerine) fruit water* citrus shunkokan fruit extract* citrus sinensis (orange) fruit extract citrus sinensis (orange) fruit water citrus sphaerocarpa fruit juice* citrus sudachi fruit extract* citrus sudachi fruit juice* citrus tachibana/reticulata fruit juice* citrus tamurana fruit extract* citrus tangelo fruit juice* citrus tangelo fruit powder* citrus tangerina (tangerine) fruit* citrus tangerina (tangerine) fruit water* citrus tankan fruit extract* citrus tankan fruit water* citrus unshiu/citrus reticulata/citrus iyo fruit water* citrus unshiu fruit extract* citrus unshiu fruit juice* citrus unshiu fruit juice ferment extract filtrate citrus unshiu fruit oil* citrus unshiu fruit powder* citrus unshiu fruit water* citrus unshiu/sinensis/reticulata fruit extract* defatted citrus unshiu fruit* hydrolyzed citrus aurantium dulcis fruit extract microcitrus australasica fruit extract* microcitrus australis fruit extract* *Not reported to be in current use. Were ingredients in this group not in current use to be used in the future, the expectation is that they would be used in product categories and at concentrations comparable to others in this group. While the available dermal irritation and sensitization data supported the safety of these Citrus fruit-derived ingredients at current use concentrations, constituents of these ingredients, such as the furocoumarin 5-MOP, can potentially cause phototoxicity. The Panel stated that standards, set by Research Institute for Fragrance Materials (RIFM) for use of these ingredients in fragrances, adequately

14 protect against such adverse effects. The Panel also expressed concern that Citrus fruit-derived ingredients could be irritants and concluded that these botanicals must be formulated to be non-irritating. RIFM confirmed that citrus aurantium bergamia (bergamot) fruit oil, which only has fragrance listed as a function in the Dictionary, is under review as a fragrance ingredient and is thus excluded from CIR s purview for review. This ingredient was deleted from the report. Nonoxynols The Panel issued a tentative amended report for public comment with the conclusions that 19 nonoxynols, -9, -11, -10, -12, -13, -14, - 15, -18, -20, -23, -25, -30, -35, -40, -44, -50, -70, -100, and -120, are safe in the present practices of use and concentration in cosmetics, and that 8 nonoxynols, -1, -2, -3, -4, -5, -6, -7, and -8, are safe as used in rinse-off products and safe at concentrations 5% in leave-on products. The 27 nonoxynols are listed below. nonoxynol-1 nonoxynol-2 nonoxynol-3* nonoxynol-4 nonoxynol-5 nonoxynol-6 nonoxynol-7* nonoxynol-8* nonoxynol-9 nonoxynol-10 nonoxynol-11* nonoxynol-12 nonoxynol-13* nonoxynol-14 nonoxynol-15 nonoxynol-18* nonoxynol-20* nonoxynol-23 nonoxynol-25* nonoxynol-30 nonoxynol-35* nonoxynol-40* nonoxynol-44* nonoxynol-50* nonoxynol-70* nonoxynol-100* nonoxynol-120* *Not reported to be in current use. Were ingredients in this group not in current use to be used in the future, the expectation is that they would be used in product categories and at concentrations comparable to others in this group. The Panel previously evaluated the safety of nonoxynols-2, -4, -8, -9, -10, -12, -14, -15, -30, -40, and -50 in cosmetics and issued a final report (published in 1983) with the conclusion these nonoxynols are safe as cosmetic ingredients in the present practices of concentration and use. The Panel reevaluated the safety of nonoxynols-2,-4, and -8 and evaluated the safety of nonoxynols-1,-3, -5, -6, and -7 in cosmetics for the first time, and issued a final report (published in 1999) with the conclusion that nonoxynols-1, -2, -3, -4, -5, -6, -7, and -8 are safe as used in rinse-off products and safe at concentrations 5% in leave-on products. This conclusion modified a previous conclusion for nonoxynols-2, -4, and -8, which had been considered safe as used in both rinse-off and leave-on products. The Panel reopened the 1983 and 1999 final safety assessments to gain additional information on the basis for the European Union s (EU) 0.1% limitation on the concentrations of nonylphenol ethoxylates (another name for nonoxynols) and nonylphenol in cosmetic and other industrial products, in light of the Panel s previous conclusion that restricted the use of nonxynols in leave-on products to concentrations < 5%. Restrictions in the European Union on the concentrations of nonylphenol and nonylphenol ethoxylates in industrial products is based on the premise that European water bodies are at risk from the persistence of the nonoxynols and their degradation products in the environment, and their potential to cause endocrine disruption in ecological species. The Panel determined that this is not an issue that is relevant for assessing the consumer safety of nonoxynols as used in cosmetic products. Polysaccharide Gums The Panel issued a tentative report for public comment with the conclusion that the following 106 polysaccharide gums are safe in the present practices of use and concentration, and that the available data are insufficient for determining the safety of hydrolyzed carrageenan in cosmetic products. A total of 126 ingredients were reviewed in this report. Linear Polysaccharides and Salts Thereof agar agarose algin alginic acid ammonium alginate* amylose* Linear Modified astragalus gummifer gum calcium alginate calcium carrageenan* carrageenan magnesium alginate* mannan polianthes tuberosa polysaccharide potassium alginate potassium carrageenan* sodium carrageenan TEA-alginate* amylodextrin hydrolyzed furcellaran* maltodextrin potassium undecylenoyl carrageenan*

15 sodium algin sulfate* sodium/tea-undecylenoyl carrageenan* Branched Natural/Unmodified amylopectin* aphanothece sacrum polysaccharide* arabinoxylan* avena sativa (oat) starch cassia angustifolia seed polysaccharide cichorium intybus (chicory) root oligosaccharides Branched Modified calcium starch isododecenylsuccinate* calcium starch octenylsuccinate* corn starch modified dextrin dextrin behenate* dextrin isostearate* dextrin laurate* dextrin myristate dextrin palmitate dextrin palmitate/ethylhexanoate dextrin stearate glyceryl alginate glyceryl dimaltodextrin* glyceryl starch hydrolyzed pectin hydroxypropyltrimonium hydrolyzed corn starch Cyclic cyclodextrin cyclotetraglucose* Cyclic Modified galactoarabinan ghatti gum* glucomannan inulin pectin phaseolus angularis seed starch* phaseolus radiatus seed starch* pisum sativum (pea) starch* pueraria lobata starch hydroxypropyltrimonium hydrolyzed wheat starch hydroxypropyl oxidized starch* hydroxypropyl starch hydroxypropyltrimonium maltodextrin crosspolymer laurdimonium hydroxypropyl hydrolyzed wheat starch palmitoyl inulin* potassium dextrin octenylsuccinate potassium undecylenoyl alginate* potato starch modified propylene glycol alginate sodium carboxymethyl inulin* sodium carboxymethyl starch undecylenoyl inulin* sodium dextrin octenylsuccinate* solanum tuberosum (potato) starch starch acetate sterculia urens gum tamarindus indica seed gum tapioca starch triticum vulgare(wheat) starch xyloglucan* sodium hydrolyzed potato starch dodecenylsuccinate sodium hydroxypropyl oxidized starch succinate* sodium oxidized starch acetate/succinate sodium starch octenylsuccinate sodium/tea-undecylenoyl alginate* starch acetate/adipate* starch diethylaminoethyl ether starch hydroxypropyltrimonium chloride starch laurate* starch tallowate* stearoyl inulin tapioca starch crosspolymer* TEA-dextrin octenylsuccinate* hydroxyethyl cyclodextrin hydroxypropyl cyclodextrin cyclodextrin hydroxypropyltrimonium chloride* cyclodextrin laurate methyl cyclodextrin Unknown Structural Configuration algae exopolysaccharides* cassia angustifolia seed polysaccharide* prunus persica (peach) gum* Unknown Structural Configuration Modified hydrogenated potato starch* hydrogenated starch hydrolysate hydrolyzed corn starch hydroxyethyl ether* hydrolyzed corn starch octenylsuccinate hydrolyzed soy starch* hydrolyzed starch hydrolyzed triticum spelta starch* hydrolyzed wheat starch

16 *Not reported to be in current use. Were ingredients in this group not in current use to be used in the future, the expectation is that they would be used in product categories and at concentrations comparable to others in this group. The Panel was concerned about the absence of adequate information to distinguish between the cosmetic ingredient hydrolyzed carrageenan and degraded carrageenan (poligeenan). A study suggested the induction of colon tumors in rats that received degraded carrageenan (poligeenan) in the diet. Although composition data on hydrolyzed carrageenan and degraded carrageenan (poligeenan) were not available, the Panel noted that, given the no-observed-effect level (NOEL) for colon carcinogencity in the oral studies and the maximum use concentration of polysaccharide gums in lipstick products, the burden to the colon that would result from the incidental ingestion of lipstick would be well below the NOEL. Additional information was received on a previous report that indicated the inhalation of konjac flour induced respiratory sensitization in test animals. Additional research suggested that the purified antigen AG40D-2 (acidic protein) was responsible for the respiratory sensitization observed, and that this effect was not attributed to glucomannan. Thus, the Panel s concerns relating to the respiratory sensitization potential of glucomannan were addressed. The Panel expressed concern about pesticide residues and heavy metals that may be present in botanical ingredients. They stressed that the cosmetics industry should continue to use current good manufacturing practices (cgmps) to limit impurities. They agreed that the same concern and suggestion are applicable to alkylating and other agents (e.g., haloethylaminopropionic acid; 3-(dodecenyl)-2,5- furandione; and 2,3-epoxypropyltrimethylammonium chloride) that are used to modify polysaccharide gums. Soy Proteins and Peptides The Panel issued a tentative safety assessment with the conclusion that the 6 soy-based ingredients listed below are safe in cosmetics in the present practices of use and concentration: glycine max (soybean) polypeptide glycine soja (soybean) peptide* glycine soja (soybean) protein hydrolyzed soy protein hydrolyzed soy protein extract* hydrolyzed soymilk protein *Not reported to be in current use. Were ingredients in this group not in current use to be used in the future, the expectation is that they would be used in product categories and at concentrations comparable to others in this group. The Panel noted that soy proteins are known food allergens that can elicit Type I immediate hypersensitivity reactions when ingested by sensitized individuals. However, the Panel was not concerned that such reactions would be induced by dermal exposure, because these ingredients are water soluble, would not penetrate the skin, and have molecular weights that are well below that which would cause IgE-binding. The Panel determined that studies showing little-to-no irritation in ocular animal studies, no dermal irritation or sensitization in animals and human subjects, and no reported cases of Type I immediate hypersensitivity reactions from cosmetic use to support their conclusion for these ingredients. Trialkyl Trimellitates The Panel issued a tentative report for public comment with the conclusion that the following 5 trialkyl trimellitates are safe as used in cosmetics at the present practices of use and concentration when formulated to be non-irritating: tridecyl trimellitate tricaprylyl/capryl trimellitate* triethylhexyl trimellitate triisodecyl trimellitate triisotridecyl trimellitate *Not reported to be in current use. Were this ingredient to be used in the future, the expectation is that it would be used in product categories and at concentrations comparable to others in this group. The Panel discussed the observation that triethylhexyl trimellitate exhibited estrogenic activity in an in vitro test using human osteoblastic (US-O2) reporter gene cell lines for ERα and ERβ. However, trialkyl trimellitates are not expected to be absorbed through the skin, thus the Panel was not concerned with risks imposed by this observation. The Panel noted studies suggesting the induction of peroxisome proliferation by triethylhexyl trimellitate, however it appeared only to have a weak effect on peroxisome proliferation. They further stated that even if there was an effect, peroxisome proliferation is not believed to pose the risk of inducing hepatocarcinogenesis in humans because humans do not react to peroxisome proliferators in the same manner as rodents.

17 Although no carcinogenicity data were available, negative genotoxicity data on tricaprylyl/capryl trimellitate and triethylhexyl trimellitate, the lack of structural alerts for carcinogenicity, and expected low dermal penetration, led the Panel to conclude that carcinogenicity would not be a concern with cosmetic use of these ingredients. The Panel recognized that there were little toxicity data available for the branched ingredient triisodecyl trimellitate. They concluded that despite the absence of this information, there is little concern about the safety of this ingredient as used in cosmetics. However, if data are available on triisodecyl trimellitate, they could serve to strengthen the safety evaluation. Insufficient Data Announcement Alkonium Clays The Panel issued an Insufficient Data Announcement for the 8 alkonium clays listed below. These ingredients are the products of the reactions of an ammonium salt with a smectite clay. These ingredients are reported to function as dispersing agents-nonsurfactant, emulsion stabilizers, and viscosity increasing agents-nonaqueous. hydrogenated tallowalkonium bentonite quaternium-18/benzalkonium bentonite quaternium-90 bentonite stearalkonium bentonite benzalkonium montmorillonite quaternium-90 montmorillonite benzalkonium sepiolite quaternium-90 sepiolite The data requested by the Panel are: Particle size distributions relevant for assessing potential inhalation exposures Percent (by weight) alkonium cation in these ingredients and the percent (by weight) releasable/exchangeable in solution Inhalation data at concentration of use (2.2% in powders and 3.2% in sprays) Ocular irritation at concentration of use, if available Pyrus malus-derived Ingredients Pyrus malus and Malus domestica are two genus and species names for apple. The Panel agreed that the available data are sufficient for evaluating the safety of the following 19 apple-derived ingredients in cosmetics, the ingredient source being either the fruit or seed. pyrus malus (apple) carpel powder pyrus malus (apple) fiber pyrus malus (apple) fruit extract pyrus malus (apple) fruit pyrus malus (apple) fruit water pyrus malus (apple) juice pyrus malus (apple) pectin extract pyrus malus (apple) peel extract pyrus malus (apple) peel powder pyrus malus (apple) pulp extract pyrus malus (apple) seed extract pyrus malus (apple) seed oil malus domestica (apple) fiber malus domestica (apple) fruit extract malus domestica (apple) fruit water malus domestica (apple) fruit cell culture extract malus domestica (apple) juice malus domestica (apple) seed oil pyrus malus (apple) peel wax However, the Panel issued an insufficient data announcement on the following 9 apple-derived ingredients: pyrus malus (apple) bark extract pyrus malus (apple) flower extract pyrus malus (apple) leaf extract pyrus malus (apple) root bark powder pyrus malus (apple) root extract pyrus malus (apple) stem extract malus domestica (apple) oil malus domestica (apple) stem extract malus domestica (apple) callus extract The data that are needed to evaluate the safety of these 12 ingredients are: Method of manufacture and impurities 28-day dermal toxicity study; if absorbed, genotoxicity and reproductive and developmental toxicity data may be needed Skin irritation and sensitization data Silk Proteins The safety of 10 silk protein ingredients in cosmetics is reviewed in this safety assessment. The Panel agreed that the available data are sufficient for evaluating the safety of the following 8 silk protein ingredients.

18 fibroin hydrolyzed fibroin hydrolyzed sericin hydrolyzed silk sericin silk silk extract silk powder However, the Panel issued an insufficient data announcement on two silk protein ingredients, MEA-Hydrolyzed Silk and Silkworm Cocoon Extract: The data that are needed to evaluate the safety of these two ingredients are: Method of manufacture and impurities Concentration of use 28-day dermal toxicity study; if absorbed, genotoxicity and reproductive and developmental toxicity data may be needed Skin irritation and sensitization data Re-review Summaries The Panel approved the summaries of their actions at the March meeting to not reopen the safety assessments of bisabolol and isostearamidopropyl morpholine lactate. The Panel also reiterated the CIR Procedures, that call for a change in classification of this ingredient from insufficient to Use Not Supported by the Data and Information Submitted to the CIR, if after 2 years, the data requests are not fulfilled and this ingredient continues to have reported use in leave-on formulations according to the VCRP. Briefing on Plant Cell Cultures as a Source for Cosmetic ingredients Roberto Dal Toso, Ph.D., is the co-founder and R&D manager of the Instituto di Richerch Biotechnologiche (I.R.B.), SpA, currently known as Croda-Sederma. At the request of the Industry, Dr. Dal Toso delivered a presentation to the Panel on the development and use of plant cell cultures as sources of ingredients for cosmetics and foods, among other products. Dr. Dal Toso explained that meristematic tissues enable the growth of plants. These tissues are composed of rapidly dividing, undifferentiated and incompletely differentiated stem cells (i.e., meristem cells). Meristem cells are found predominantly in the apical shoot and root tips, as well as in cylinder-shaped cambial meristem tissues that are responsible for the lateral growth of plants and in seeds. Meristem cells can be harvested and grown as calluses on solid culture media. Each callus is a blend of numerous undifferentiated cells. Calluses can also be obtained from differentiated ( adult ) cells of a plant through dedifferentiation, which produces cells exhibiting the characteristics of meristem cells. The cultures developed in this manner have no contact with the environment outside of the laboratory, and therefore exhibit no variations in composition from differences in geographical, climatic, or seasonal conditions and harvesting methods, and need no protection from pesticides or other substances typically used in the cultivation of plants in the field. These highly controlled conditions also help to limit the variations in constituents that would be expected from the natural biological cycles of plants growing in the field, and ensures the absence of contamination from soil microorganisms, aflatoxins, heavy metals, and other pollutants in the ingredients derived from the cultures. Dr. Dal Toso presented analytical data showing that the constituents of Centella asiatica meristem cells were comparable to that of a classical Centella asiatica extract identified as a cosmetic ingredient. He also presented data from tests of a commercial Centella asiatica meristem cell culture product indicating the lack of irritation, mutagenicity, and phototoxicity in vitro, and the absence of irritation in a human repeat insult patch test. Draft 2016 Ingredient Review Priorities The following 2016 Priority list was approved by the CIR Expert Panel. There are 18 ingredient/ingredient groups on the list. However, it is likely that not all of those listed will be chosen for work in Ingredient Number of formulations containing ingredient propanediol 548 linoleic acid 532 hydroxyethyl acrylate/sodium acryloyldimethyl taurate copolymer 446 ammonium acryloyldimethyltaurate/

19 vp copolymer 421 hydrofluorocarbon 152a 426 triethoxycaprylylsilane 409 tetrahexyldecyl ascorbate 382 panthenyl ethyl ether 378 etidronic acid 370 dicaprylyl carbonate 366 trimethyl pentanyl diisobutyrate 351 humulus lupulus (hops) extract 336 melaleuca alternifolia (tea tree) leaf oil 336 PPG-2 hydroxyethyl cocamide 332 methylpropanediol 327 sucrose acetate isobutyrate 326 hydroxyethyl-3,4- methylenedioxyaniline HCl 58 (requested by the PCPC HCTC) tetrafluoropropene 0 (requested by the CIR SSC) These 2016 CIR priorities are based on those ingredients listed in the 2015 VCRP data that have not been reviewed by CIR and have the largest number of uses, or have been specifically requested by stakeholders. Some ingredients are excluded from review by the CIR, as discussed in the CIR Procedures. This list above only names the lead ingredients. Families of ingredients may be reviewed, as appropriate (proposed ingredient families are posted on the CIR website). Interested parties are encouraged to submit data pertinent to these ingredients to the CIR for use in the development of the Scientific Literature Review. Although the specific data needs vary for each safety assessment, the following are typical data that the Panel reviews for each safety assessment. chemistry, impurities, and method of manufacture toxicokinetics data, specifically dermal absorption and/or penetration repeated-dose toxicity data inhalation toxicity data, if the ingredient is used in a product that can be incidentally inhaled reproductive/developmental toxicity data genotoxicity data; and if positive, carcinogenicity data may be needed dermal irritation and sensitization data For the review of botanical ingredients, the additional data needed include: species, plant part, extraction method, solvent, and data on component chemical characterization. It is important that these data are specific to the cosmetic ingredient(s).

20 Commitment & Credibility since 1976 Memorandum To: From: CIR Expert Panel Members and Liaisons Monice M. Fiume MMF Assistant Director/Senior Scientific Analyst Date: August 27, 2015 Subject: Report Formatting In response to the Panel s comments about the consistency in report format, the CIR staff has developed two alternatives for your consideration. A representative current format and the two proposed formats are presented in an outline so that you can easily see the layout of the report. We are asking the Panel to review and comment on the proposed formats so that one outline can be developed for all staff to utilize in preparing safety assessments. Each major section of the report is represented by a row in the outline. You will note that there may be no change proposed for some sections, and major changes proposed for others. Some of those changes are the types of information included in each section, and in one instance, it is the title of the section. Because there are substantive changes proposed to the Toxicological Studies section through the end of the report, Dr. Boyer has prepared an accompanying memo that discusses the rationale for those proposed changes. That memo follows this one, and then the proposed outline is presented. Included here is a listing of the proposed changes. The entire outline follows.

21 PROPOSED CHANGES: Section Heading Change Proposed Format I Change Proposed Format II Toxicokinetics 1. Animal replaces non-human 2. Computational Studies has been added 1. same as Proposed Format I, except the order of presentation has changed from in vitro, non-human, human to human, animal, computational studies Toxicological Studies Reproductive and Developmental Toxicity Genotoxicity Carcinogenicity 1. Acute-Dose Toxicity replaces Single-Dose (Acute Toxicity 2. The word exposure is included in the sub-heading describing the route of administration (e.g. Dermal Exposure instead of Dermal as a subheading 3. the order of describing the route of exposure has been specified to be Dermal; Oral; Inhalation; Other (when applicable) 1. the section heading is renamed to Developmental and Reproductive Toxicity (DART) 2. the order of describing the route of exposure has been specified to be Dermal; Oral; Inhalation 1. the order of presentation of studies types has been reversed, i.e., instead of presenting in vitro studies and then in vivo studies, it is being proposed that in vivo studies be described first, then in vitro 2. Computational Analyses/Predictions (for genotoxicity) has been added 1. Co-carcinogenicity, tumor promotion, and anticarcinogenicity would no longer be separate sub-headings 2. the order of describing the route of exposure has been specified to be Dermal; Oral; Inhalation; Other (when applicable) same as Proposed Format I same as Proposed Format I same as Proposed Format I same as Proposed Format I

22 Section Heading Change Proposed Format I Change Proposed Format II Irritation and Sensitization 1. Dermal Exposure has been added as a sub-heading, and now includes several 3 rd level headings 2. instead of ocular toxicity and mucous membrane toxicity, the word exposure replaces toxicity (e.g., ocular exposure) 3. the sub-heading Clinical Reports has been added to address retrospective and multicenter studies, case reports, and adverse event reports. 4. the order of presentation of testing and test species has been changed to first describe in vivo testing, and then in vitro, a. and under in vivo, human testing would be described first, followed by animal 1. The section heading has changed from Irritation and Sensitization to Dermal Toxicity: 2. the order of presentation of testing and test species has been changed to first describe in vivo testing, and then in vitro, a. and under in vivo, human testing would be described first, followed by animal 3. Other Dermal Effects: has been added 4. In contrast to Proposed Format 1 Clinical Reports in not included here Other Toxicity Clinical Reports 1. this is a new Level 1 heading, serving as a place to describe other studies, examples being neurotoxicity, immunotoxicity, endocrine activity 2. the study types used as examples above would not always be included, just when appropriate 1. included under Irritation and Sensitization (and discussed above) Ocular Toxicity 1. Included under Irritation and Sensitization in current format and Proposed Format I; own major (level 1) heading in Proposed Format II 2. Named Ocular Toxicity instead of Ocular Irritation 3. Includes Sensitization and Other Effects, in addition to irritation Mucous Membrane Toxicity 1. Included under Irritation and Sensitization in current format and Proposed Format I; own major (level 1) heading in Proposed Format II 2. Named Mucous Membrane Toxicity instead of Mucous Membrane Irritation 3. Includes Sensitization and Other Effects, in addition to irritation same as Proposed Format I 1. allows incorporating clinical reports that address endpoints other than irritation and sensitization, when applicable 2. would include retrospective & multicenter studies, case reports, and adverse event reports

23 Section Heading Change Proposed Format I Change Proposed Format II Epidemiological Studies 1. Epidemiology is sometimes included in current format, especially in hair dye reports 2. in the proposed formats, cancer and non-cancer endpoints would be described, when applicable same as Proposed Format I Quantitative Risk Assessment (QRA) Application of the Framework For Identifying And Evaluating Analogs 1. would describe QRAs from other organizations, SCCS, OSHA, WHO, for example, when available 2. could include cancer and non-cancer endpoints 1. new and emerging - would be included when applicable, using a format similar to that included in the PEGs Cocamine report same as Proposed Format I same as Proposed Format I

24 Memorandum Commitment & Credibility since 1976 To: CIR Expert Panel Members and Liaisons From: Ivan J. Boyer, PhD, DABT Senior Toxicologist Date: August 27, 2015 Subject: Revision of the Toxicological Studies Section of CIR Safety Assessment Reports: Comparison and Explanation of the Alternate Proposals CIR staff reviewed the Toxicological Studies section of CIR safety assessments. Three outlines resulted, including one that represents the format of many of our current reports and two others proposed as alternatives to the current format. This memorandum asks for the Panel s evaluation of the rationale underlying the proposed alternatives, leading ultimately to one unified format outline to be used by all staff. The three-column table below provides a more detailed presentation of the alternative formats for the Toxicological Studies section of CIR safety assessment reports (compared to the more general three-column table that presents the alternatives for all of the reports sections). The table below presents the following outlines, for side-by-side comparison: Representative Current Format of CIR safety assessment reports, which was prepared based on an examination of the overall structures of recent reports Proposed Format-1, which includes several modifications to the Representative Current Format Proposed Format-2, which is a further departure from the Representative Current Format This memo is organized to address the main subsections of the Toxicological Studies section as follows: Acute-Dose Toxicity Studies through Carcinogenicity Studies Irritation and Sensitization Studies versus Dermal Toxicity Studies Other Toxicity Studies Observational Reports and Assessments CIR staff seeks Panel assistance to clarify and validate the rationale for the proposed alternatives, which is presented in this memorandum. Acute-Dose Toxicity Studies through Carcinogenicity Studies Proposed Format-1 and Proposed Format-2 differ from the Representative Current Format in the following ways: Acute-Dose Toxicity replaces Single-Dose (Acute) Toxicity. This is because acute-exposure studies are not necessarily single-dose studies (e.g., several doses may be administered over a 24-hour period in an acute-exposure study). The subsequent heading, Repeated-Dose Toxicity, covers subacute-, subchronic-, and chronic-exposure studies designed to characterize the overall toxicological profile of ingredients, in accord with the Representative Current Format. (Note that we are not proposing report headings that distinguish among subacute-, subchronic-, and chronic- repeated-dose toxicity studies; all such studies would be covered under the Repeated-Dose Toxicity heading.) The second-level headings appear, consistently, in the following order in the proposed formats: Dermal Exposure, Oral Exposure, and Inhalation Exposure. The Representative Current Format is inconsistent

25 about this, sometimes placing Oral first and Dermal last, for example (note that the word Exposure does not appear in the corresponding headings of the Representative Current Format). The rationale for placing Dermal Exposure first is that, of the three routes, the dermal route is generally the principal route by which consumers are exposed to cosmetic ingredients. With exceptions, the oral route is next in importance, followed by the inhalation route, because the magnitudes of exposures to ingredients via these routes can generally be expected to be incidental, by comparison with the dermal route. The second-level headings under Genotoxicity include In Vivo followed by In Vitro in the proposed formats, which is the reverse of the order in which these headings appear in the Representative Current Format. The reason for placing In Vivo first in the proposed formats is that data from well-conducted, well-reported in vivo genotoxicity studies generally carry more weight, in a weight-of-evidence assessment, than data from in vitro tests. Providing the results of in vivo tests first indicates up front that there are such data to be evaluated for an ingredient or ingredient group. When there are data from in vivo studies, the data from in vitro tests presented subsequently would generally play a subsidiary role in the weight-ofevidence assessment of potential genotoxicity. Developmental and Reproductive Toxicity (DART) in the proposed formats replaces Reproductive and Developmental Toxicity as a first-level heading of the Representative Current Format. This change is consistent with current common usage of the term (i.e., DART) in the Toxicological literature. Thus, the proposed formats are identical up to Irritation and Sensitization \ Dermal Toxicity. Up to the aforementioned headings, the first-level headings identify the types of toxicity studies to be summarized (i.e., Acute-Dose Toxicity studies, Repeated-Dose Toxicity studies, and so forth), and the second-level headings identify the route of exposure (i.e., Dermal Exposure, Oral Exposure, and Inhalation Exposure) used in the studies. The exception is that, under Genotoxicity: Second-level headings separate in vivo studies, in vitro studies, and computational analyses from each other Exposure routes used in the in vivo studies are identified in third-level headings, under In Vivo These topmost section headings (i.e., from Acute-Dose Toxicity through Carcinogenicity) of the proposed formats are similar to those of the Representative Current Format, in which the types of general-toxicity studies (acute-dose studies followed by repeated-dose studies) appear first, and are followed by studies addressing three major sets of toxicity endpoints, including Developmental and Reproductive Toxicity studies, Genotoxicity studies and Carcinogenicity studies. Irritation and Sensitization Studies versus Dermal Toxicity Studies The proposed formats differ substantially from each other beginning with Irritation and Sensitization (Proposed Format-1) versus Dermal Toxicity (Proposed Format-2). Irritation and Sensitization appears as a first-level heading in the Representative Current Format and in Proposed Format-1. Dermal Toxicity is the corresponding first-level heading in Proposed Format-2. The proposed modifications to the structure of CIR safety assessments, under these headings, are driven by the following issues: Importance of assessing the potential effects (especially irritation and sensitization endpoints) of direct contact with cosmetic ingredients Availability of data from both in vivo and in vitro studies (as for Genotoxicity) Availability of data from human subjects and test animals Availability of a Quantitative Risk Assessment (QRA) methodology (developed by RIFM) to assess the potential for inducing dermal sensitization Emergence of computational tools for predicting irritation and sensitization endpoints (as for Genotoxicity)

26 Starting with Irritation and Sensitization or Dermal Toxicity, the headings and subheadings differ from those of most of the preceding report sections (i.e., Acute-Dose Toxicity, Repeated-Dose Toxicity, etc.) in all three outlines (Representative Current Format, Proposed Format-1 and Proposed Format-2). The outlines under Irritation and Sensitization and Dermal Toxicity are, thus, presented down to fourth-level headings in the outlines below (only first- and second-level headings are presented in these outlines for the preceding report sections). Irritation and Sensitization appears as a first-level heading in Proposed Format-1 and in the Representative Current Format, primarily because of the importance of addressing these endpoints for dermal, ocular, and mucousmembrane exposure in every safety assessment. In Proposed Format-2, the single first-level Irritation and Sensitization heading is replaced with three first-level headings, namely Dermal Toxicity, Ocular Toxicity, and Mucous-Membrane Toxicity. One reason for the proposed change to Dermal Toxicity, Ocular Toxicity, and Mucous-Membrane Toxicity as first-level headings in Proposed Format-2 is to provide a report structure that is amenable to the inclusion of studies that address endpoints other than to irritation and sensitization (e.g., comedogenicity or pigmentary disturbances). The second-level headings of Proposed Format-2, including Irritation studies, Sensitization studies, Photosensitivity studies, and Other Dermal Toxicity studies, then stem logically from then first-level headings. Note that Clinical Reports appears as a second-level heading under Irritation and Sensitization in Proposed Format-1, but appears as a first-level heading (after Other Toxicity) in Proposed Format-2. Clinical Reports appears under Irritation and Sensitization in Proposed Format-1 in acknowledgement of the observation that most of the relevant clinical reports address irritation and sensitization endpoints. However, the placement of Clinical Reports in Proposed Format-1 appears to be incongruent with the other second-level headings at the second level in Proposed Format-1, which identify reports based on the target tissues\organs (endpoints) addressed, rather than based on the nature of the reports (e.g., experimental studies, clinical reports, or epidemiological reports). On the other hand, the placement of Clinical Reports under Other Toxicity in Proposed Fomat-2 allows incorporating clinical reports that address endpoints other than irritation and sensitization, when applicable. The proposed formats (i.e., both Proposed Fromat-1 and Proposed Format-2) differ from the Representative Current Format in three notable respects: In Vivo precedes In Vitro in the proposed formats, for essentially the same reasons discussed above for Genotoxicity. In vivo studies with human subjects precede in vivo studies using test animals in the proposed formats for similar reasons. Data from well-conducted studies with human subjects generally carry more weight in a weight-of-evidence assessment for the endpoints that the studies address; data from animal studies can play a subsidiary (but still important) role when human data are available. The fourth-level headings under In Vivo are Human and Animal (with Human preceding Animal) in the proposed formats, rather than Non-Human and Human (with Non-Human preceding Human) in the Representative Current Format. The use of the terms animal studies and human studies to distinguish studies conducted using test animals, in vivo, from those conducted with human subjects is consistent with long-standing convention in both the toxicology and the pharmacology literature. Other Toxicity Studies Other Toxicity is the last first-level heading that covers experimental studies (as opposed to observational reports and assessments), preceding Epidemiological Reports in Proposed Format-1 and preceding Clinical Reports in Proposed Format-2. Some examples of potentially relevant other endpoints include neurotoxicity, immunotoxicity (other than skin sensitization induced by topical exposures), and endocrine effects (other than those observed in reproductive toxicity tests). The Other Toxicity section enables the incorporation of experimental studies, when relevant, that address toxicity endpoints that are not covered under in the previous sections of safety assessment report.

27 Observational Reports and Assessments The final sections of Proposed Format-1 and Proposed Format-2 are identical, except that Clinical Reports appears as a first-level heading (after Other Toxicity) of Proposed Format-2, rather than as a second-level under Irritation and Sensitization as it is in Proposed Format-1, as discussed above. In Proposed Format-2, the first-level headings comprise Clinical Reports, Epidemiological Reports, Quantitative Risk Assessments, and Application of the Framework for Identifying and Evaluating Analogs. The information summarized under these headings is from observational reports (i.e., clinical reports and epidemiological reports) or from assessments (e.g., Quantitative Risk Assessments from SCCS and the application of the Framework). Thus, the studies summarized in these reports sections are sorted into groups by the investigational or assessment approaches used in the studies, which are distinct from the experimental approaches used in the studies summarized in the preceding sections of safety assessment reports. Note that Clinical Reports (i.e., Retrospective and Multicenter Studies, Case Reports, and Adverse Event Reports) are not always incorporated into CIR safety assessment reports, but are included when relevant and appropriate. Following are the three outlines referenced in this memorandum, including a Representative Current Format, Proposed Format-1, and Proposed Format-2. They are presented for the Panel s for reference, if warranted, during discussions of the Report Format topic at the September 2015 Panel meeting.

28 CURRENT FORMAT PROPOSED FORMAT I PROPOSED FORMAT II ABSTRACT no change no change INTRODUCTION no change no change CHEMISTRY Definition and Structure Physical and Chemical Properties Method of Manufacture Impurities/Constituents Other Sub-Sections as Appropriate; e.g.: no change no change o Natural Occurrence o UV Absorption o Nitrosation USE Cosmetic Non-Cosmetic no change no change TOXICOKINETICS Absorption, Distribution, Metabolism, and Excretion o o o In Vitro Non-Human Dermal Oral Human Dermal Oral Dermal Absorption Penetration Enhancement TOXICOKINETICS Absorption, Distribution, Metabolism, and Excretion (ADME) o o o o In Vitro Animal Studies Dermal Application Other Routes Human Studies Dermal Application Other Routes Computational Studies PBPK Modelling and/or IVIVE QSAR/QSPR Calculations Dermal Penetration Penetration Enhancement TOXICOKINETICS ADME o Human In Vivo Dermal Application Other Routes In Vitro Skin Samples Human cells/cell-free systems o Animal Studies In Vivo Dermal Application Other Routes In Vitro Skin samples Animal cells/cell-free systems o Computational Studies PBPK Modelling and/or IVIVE QSAR/QSPR Calculations Dermal Penetration Penetration Enhancement

29 CURRENT FORMAT PROPOSED FORMAT I PROPOSED FORMAT II TOXICOLOGICAL STUDIES TOXICOLOGICAL STUDIES same as Proposed Format - I Single-Dose (Acute) Toxicity Acute-Dose Toxicity o Oral o Dermal Exposure o Inhalation o Oral Exposure o Dermal o Inhalation Exposure Repeated-Dose Toxicity o Other (when applicable) o Oral Repeated-Dose Toxicity o Inhalation o Dermal Exposure o Dermal o Oral Exposure o Other (i.e., parenteral other than o Inhalation Exposure dermal or inhalation, e.g., intraperitoneal injections) o Other (when applicable) REPRODUCTIVE AND DEVELOPMENTAL TOXICITY Dermal Exposure Oral Exposure Inhalation Exposure In Vitro Test for Endocrine Activity GENOTOXICITY In Vitro In Vivo CARCINOGENICITY o Dermal Exposure o Oral Exposure o Inhalation Exposure Co-Carcinogenicity Tumor Promotion Anti-Carcinogenicity DEVELOPMENTAL AND REPRODUCTIVE TOXICITY (DART) Dermal Exposure Oral Exposure Inhalation Exposure GENOTOXICITY In Vivo In Vitro Computational Analyses/Predictions (for genotoxicity) CARCINOGENICITY Dermal Exposure Oral Exposure Inhalation Exposure same as Proposed Format - I same as Proposed Format - I same as Proposed Format - I

30 CURRENT FORMAT PROPOSED FORMAT I PROPOSED FORMAT II IRRITATION AND SENSITIZATION IRRITATION AND SENSITIZATION DERMAL TOXICITY Skin Irritation Dermal Exposure Irritation o Non-Human o In Vivo o In Vivo o Human Human Human Skin Sensitization Animal Animal o Non-Human o In Vitro o In Vitro o Human o Photosensitivity o Computational Analyses\Predictions Photosensitization/Phototoxicity Phototoxicity Sensitization Ocular Irritation Photoallergy o In Vivo Mucosal Irritation o Computational Analyses\Predictions (for Human Case Studies dermal irritation) Animal o Quantitative Risk Assessment (QRA) (for o In Vitro Dermal Sensitization; RIFM Method) o Computational Analyses\Predictions Ocular Exposure o Quantitative Risk Assessment (QRA) o In Vivo Human (for Dermal Sensitization; RIFM Method) Animal Photosensitivity o In Vitro o Phototoxicity Mucous Membrane Exposure o Photoallergy o In Vivo Other Dermal Effects (e.g., comedogenicity, Human pigmentary disturbances) Animal o In Vivo o In Vitro o In Vitro Clinical Reports (Relevant clinical reports addressing endpoints other than irritation and sensitization may be placed under Other Toxicity, below) o Retrospective and Multicenter Studies o Case Reports o Adverse Event Reports OCULAR TOXICITY Irritation o In Vivo o In Vitro Sensitization o Human o Animal Other Ocular Effects (e.g., corneal opacity, cataracts) o In Vivo o In Vitro

31 CURRENT FORMAT PROPOSED FORMAT I PROPOSED FORMAT II MUCOUS MEMBRANE TOXICITY Irritation o In Vivo o In Vitro Sensitization o Human o Animal Other Mucous Membrane Effects o In Vivo o In Vitro OTHER TOXICITY (when relevant; examples provided) same as Proposed Format - I Neurotoxicity Immunotoxicity Endocrine Effects CLINICAL REPORTS Retrospective & Multicenter Studies Case Reports Adverse Event Reports EPIDEMIOLOGICAL STUDIES same as Proposed Format I Cancer Endpoints (Epidemiological reports addressing potential carcinogenicity may be placed under Carcinogenicity, above) o Primary Studies Prospective Studies Retrospective Studies o Meta-Analyses Non-Cancer Endpoints o o Primary Studies Prospective Studies Retrospective Studies Meta-Analyses QUANTITATIVE RISK ASSESSMENT e.g., from U.S. EPA, OSHA, NIOSH, ACGIH, WHO, SCCS, etc.) Cancer Endpoints Non-Cancer Endpoints same as Proposed Format I APPLICATION OF THE FRAMEWORK FOR same as Proposed Format I IDENTIFYING AND EVALUATING ANALOGS SUMMARY no change no change DISCUSSION no change no change

32 CURRENT FORMAT PROPOSED FORMAT I PROPOSED FORMAT II CONCLUSION no change no change TABLES (or FIGURES AND TABLES) no change no change REFERENCES no change no change

33 Memorandum Commitment & Credibility since 1976 To: CIR Expert Panel Members and Liaisons CC: CIR SSC From: Bart Heldreth, PhD, Chemist Date: July 17, 2015 Subject: Request for Endorsement of Review Strategies for Un-reviewed Citrus Ingredients At the March 2014 CIR Expert Panel Meeting, the Panel recommended that CIR sort the Citrus ingredients by the plant parts from which they are derived, starting with the parts reported to have the greatest number of uses in the FDA s VCRP. For example, citrus limon (lemon) peel oil had the most reported uses, so the first assessment to be reviewed by the Panel focused on all Citrus-derived peel oils. At the September 2014 CIR Expert Panel Meeting, the Panel issued a final safety assessment with the conclusion that the fourteen Citrus-derived peel oils listed in the report are safe for use in cosmetic products when finished products, excluding rinse-off products, do not contain more than % (15 ppm) 5-methoxypsoralen (5-MOP), and when formulated to be non-sensitizing and non-irritating. Also at the March 2014 CIR Expert Panel Meeting, the Panel recommended that Citrus-derived fruit extracts be the next citrus ingredient group reviewed, because citrus limon (lemon) fruit extract had the second greatest number of overall reported uses (of all citrus-derived ingredients). At the June 2015 CIR Expert Panel Meeting, the Panel issued a tentative report for public comment with the conclusion that the eighty Citrus fruitderived ingredients listed therein are safe for use in cosmetic products when finished products, excluding rinseoff products, do not contain more than % (15 ppm) 5-methoxypsoralen (5-MOP), and when formulated to be non-sensitizing and non-irritating. Accordingly, CIR is requesting the Panel s guidance in identifying the next group of Citrus-derived ingredients to be included in a new Draft Report. The ninety-eight ingredients listed below constitute the Citrus-derived cosmetic ingredients that have not been reviewed. Those ingredients below with a line drawn through the name have been excluded from CIR review as meeting both of the fragrance only criteria: 1) fragrance as the only listed function in the INCI Dictionary and 2) the safety of which is being determined (or has been determined) by the Research Institute for Fragrance Materials (RIFM). Potential review strategies include assessing all of the following ingredients in one report (e.g., like the recent Pyrus malus report) or choosing only one plant part sub-grouping to assess next (e.g., like the ongoing Citrus-fruit report).

34 Flower-derived FOU (VCRP yr.2015) 1. Citrus Aurantifolia (Lime) Flower Extract 2 2. Citrus Aurantium Amara (Bitter Orange) Flower Extract Citrus Aurantium Amara (Bitter Orange) Flower Oil Citrus Aurantium Amara (Bitter Orange) Flower Water Citrus Aurantium Amara (Bitter Orange) Flower Wax 3 6. Citrus Aurantium Dulcis (Orange) Flower Extract Citrus Aurantium Dulcis (Orange) Flower Oil 0 Citrus Aurantium Dulcis (Orange) Flower Water fragrance & RIFM Citrus Aurantium Dulcis (Orange) Flower Wax 0 9. Citrus Aurantium Dulcis (Orange) Flower Citrus Natsudaidai Flower Water fragrance/not RIFM Citrus Tamurana Flower Extract Citrus Unshiu Flower Powder Citrus Unshiu Flower Water fragrance/not RIFM 0 Leaf-derived 14. Citrus Aurantifolia (Lime) Leaf Oil fragrance/not RIFM Citrus Aurantium Bergamia (Bergamot) Leaf Extract Citrus Aurantium Bergamia (Bergamot) Leaf Oil Citrus Aurantium Dulcis (Orange) Leaf Extract Citrus Grandis (Grapefruit) Leaf Extract Citrus Hystrix Leaf Extract Citrus Limon (Lemon) Leaf Extract 0 Citrus Limon (Lemon) Leaf Oil fragrance & RIFM Citrus Reticulata (Tangerine) Leaf Oil Citrus Reticulata (Tangerine) Leaf Water 0 Peel-derived 23. Citrus Aurantifolia (Lime) Peel Citrus Aurantifolia (Lime) Peel Extract Citrus Aurantifolia (Lime) Peel Powder Citrus Aurantifolia (Lime) Peel Water - fragrance/not RIFM Citrus Aurantium Amara (Bitter Orange) Peel Extract Citrus Aurantium Amara (Bitter Orange) Peel Powder Citrus Aurantium Amara (Bitter Orange) Peel Citrus Aurantium (Bitter Orange) Peel Wax VCRP/not INCI Dictionary Citrus Aurantium Bergamia (Bergamot) Peel Water 0 Citrus Aurantium Bergamia (Bergamot) Peel Oil - fragrance & RIFM Citrus Aurantium Dulcis (Orange) Peel Extract Citrus Aurantium Dulcis (Orange) Peel Powder Citrus Aurantium Dulcis (Orange) Peel Wax Citrus Aurantium Sinensis Peel Extract Citrus Aurantium Tachibana Peel Extract Citrus Depressa Peel Extract Citrus Depressa Peel Powder Citrus Grandis (Grapefruit) Peel Extract Citrus Grandis (Grapefruit) Peel Powder Citrus Grandis (Grapefruit) Peel Citrus Hassaku/Natsudaidai Peel Powder Citrus Iyo Peel Extract Citrus Iyo Peel Water Citrus Jabara Peel Extract Citrus Jabara Peel Powder fragrance/not RIFM Citrus Jabara Peel Water Citrus Junos Peel Extract 1

35 49. Citrus Junos Peel Powder fragrance/not RIFM Citrus Junos Peel Water Citrus Limon (Lemon) Peel Citrus Limon (Lemon) Peel Extract Citrus Limon (Lemon) Peel Powder Citrus Limon (Lemon) Peel Water Citrus Limon (Lemon) Peel Wax Citrus Natsudaidai Peel Extract Citrus Nobilis (Mandarin Orange) Peel Extract Citrus Nobilis (Mandarin Orange) Peel Powder Citrus Paradisi (Grapefruit) Peel Extract 14 Citrus Paradisi (Grapefruit) Peel Oil fragrance & RIFM Citrus Reticulata (Tangerine) Peel Extract Citrus Reticulata (Tangerine) Peel Powder Citrus Shunkokan Peel Extract Citrus Sunki Peel Extract Citrus Tachibana/Reticulata Peel Powder Citrus Tangelo Peel Powder Citrus Tangerina (Tangerine) Peel Extract Citrus Tangerina (Tangerine) Peel Citrus Unshiu Peel Extract Citrus Unshiu Peel Powder fragrance/not RIFM Citrus Unshiu Peel Water 0 Seed & Pericarp-derived 71. Citrus Aurantium Dulcis (Orange) Seed Extract Citrus Grandis (Grapefruit) Seed Extract Citrus Jabara Pericarp Extract Citrus Junos Seed Extract Citrus Junos Seed Oil Citrus Paradisi (Grapefruit) Seed Extract Citrus Unshiu Pericarp Extract 0 Whole plant and multi-part-derived 78. Citrus Aurantifolia (Lime) Oil Citrus Aurantium Amara (Bitter Orange) Leaf/Twig Extract Citrus Aurantium Amara (Bitter Orange) Leaf/Twig Oil Citrus Aurantium (Bitter Orange) Oil VCRP/not INCI Dictionary Citrus Aurantium Dulcis (Orange) Flower/Leaf/Stem Powder Citrus Aurantium Dulcis (Orange) Oil fragrance/not RIFM Citrus Aurantium Sinensis Powder Citrus Grandis (Grapefruit) Extract Citrus Grandis (Grapefruit) Citrus Grandis Peel/Seed Extract Citrus Iyo Oil Citrus Junos Extract Citrus Limon (Lemon) Flower/Leaf/Stem Extract Citrus Limon (Lemon) Flower/Leaf/Stem Oil fragrance/not RIFM Citrus Limon (Lemon) Leaf/Peel/Stem Oil Citrus Nobilis (Mandarin Orange) Oil fragrance/not RIFM Citrus Nobilis (Mandarin Orange) Water Citrus Nobilis (Mandarin Orange) Citrus Reticulata (Tangerine) Extract Citrus Tangerina (Tangerine) Extract Citrus Unshiu Extract 0

36

37 Memorandum Commitment & Credibility since 1976 To: CIR Expert Panel Members and Liaisons CC: CIR SSC From: Bart Heldreth, PhD, Chemist Date: July 17, 2015 Subject: Request for Endorsement of Review Strategies for Un-reviewed Hydrolyzed Protein Ingredients The CIR Expert Panel has reviewed a number of hydrolyzed protein ingredients, initially as individual ingredient reports, but more recently in multiple ingredient reports. In 1985, the CIR Expert Panel concluded that hydrolyzed collagen is safe as a cosmetic ingredient in the present practices of use and concentration (published re-review not re-opened in year 2006). In 2001, the CIR Expert Panel concluded that rice-derived hydrolyzed protein ingredients are safe as cosmetic ingredients in the present practices of use and concentration. At the March 2013 CIR Expert Panel Meeting, the Panel recommended that CIR sort the appropriate groupings of the hydrolyzed proteins (from an initial draft report which included all hydrolyzed protein ingredients, regardless of source), specifically reciting that those ingredients derived from soy, silk, and wheat should be done first. However, no specific instructions where recited for the scheduling of assessments for hydrolyzed protein ingredients from other sources. At the June 2014 CIR Expert Panel Meeting, the Panel concluded that hydrolyzed wheat gluten and hydrolyzed wheat protein are safe for use in cosmetics when formulated to restrict peptides to a weight-average MW of 3500 Da or less. At the December 2014 Expert Panel Meeting, the Panel concluded that hydrolyzed oat protein (as well as other oat-derived ingredients) is safe in cosmetics in the present practices of use and concentration when formulated to be non-sensitizing. At the June 2015 CIR Expert Panel Meeting, the Panel issued a tentative safety assessment with the conclusion that the three soy-based hydrolyzed protein ingredients (and other non-hydrolyzed proteins) are safe in cosmetics in the present practices of use and concentration. Also at the June meeting, the Panel issued a notice that the data were sufficient for three out of the four silk-derived hydrolyzed protein ingredients (and other non-hydrolyzed proteins), but insufficient for the fourth (MEA-hydrolyzed silk and one non-hydrolyzed protein ingredient). Keratin-derived hydrolyzed protein ingredients (as well as non-hydrolyzed keratin protein ingredients) are scheduled for assessment in 2015, and report preparation is currently in progress. Accordingly, the question being asked is, which of the remaining hydrolyzed protein ingredients should CIR prepare a Draft Report on next? Upon analysis of the original, all-hydrolyzed proteins report, the following ingredients had the next highest frequency of use values: hydrolyzed elastin (176 uses (year 2012; 222 uses year 2015), used at up to 2.5%), hydrolyzed vegetable protein (153 (year 2012; 149 year 2015), used at up to 0.2%), and hydrolyzed milk protein (123 uses (year 2012; 200 uses year 2015), used at up to 0.3%). (Gelatin was not in the original allhydrolyzed proteins report (FOU 232).) The forty-four ingredients listed below constitute the hydrolyzed protein cosmetic ingredients hereto un-reviewed.

38 Potential review strategies include assessing all of the following ingredients in one report or choosing only one protein source to assess at a time. If a source by source report strategy is the Panel consensus for a path forward, what are the priorities (i.e., what are the next five or so reports that should be done)? Collagen-derived FOU (VCRP yr.2015) ammonium hydrolyzed collagen 0 calcium hydrolyzed collagen 0 MEA hydrolyzed collagen 0 zinc hydrolyzed collagen 0 gelatin 232 hydrolyzed gelatin 0 hydrolyzed reticulin 0 (A report on hydrolyzed collagen and other collagen-derived ingredients is due for re-review in year 2021) Actin-derived hydrolyzed actin 13 (There are no other actin-derived cosmetic ingredients) Egg-derived hydrolyzed albumen 0 hydrolyzed conalbumin 0 hydrolyzed egg protein 0 (No egg protein ingredients have been assessed (only other egg protein ingredient is albumen with 18 FOU)) Bovine milk-derived hydrolyzed casein 11 hydrolyzed lactalbumin 0 hydrolyzed milk protein 200 sodium hydrolyzed casein 0 hydrolyzed whey protein 0 (No milk protein ingredients have been assessed (8 non-hydrolyzed protein ingredients; highest FOU is 52)) Elastin-derived hydrolyzed elastin 222 (Non-hydrolyzed elastin has not been assessed (35 FOU)) Fibronectin-derived hydrolyzed fibronectin 10 (Non-hydrolyzed fibronectin has not been assessed (0 FOU)) Lupine-derived hydrolyzed lupine protein 100 (Non-hydrolyzed lupine protein (lupinus albus protein) has not been assessed (0 FOU)) Blood plasma-derived hydrolyzed hemoglobin 0 hydrolyzed serum protein 0 (Non-hydrolyzed hemoglobin and serum protein have not been assessed (0 and 16 FOU respectively)) Zea mays-derived hydrolyzed zein 0 (Non-hydrolyzed zein has not been assessed (4 FOU))

39 Other source-derived with no straight-forward groupings (continued) FOU (VCRP yr.2015) hydrolyzed amaranth protein 2 hydrolyzed avocado protein 0 hydrolyzed barley protein 30 hydrolyzed brazil nut protein 11 hydrolyzed conchiolin protein 96 hydrolyzed cottonseed protein 35 hydrolyzed extension 0 hydrolyzed gadidae protein 2 hydrolyzed hazelnut protein 25 hydrolyzed hemp seed protein 0 hydrolyzed honey protein 0 hydrolyzed jojoba protein 21 hydrolyzed maple sycamore protein 0 hydrolyzed pea protein 5 hydrolyzed potato protein 17 hydrolyzed royal jelly protein 1 hydrolyzed sesame protein 0 hydrolyzed sponging 0 hydrolyzed sweet almond protein 84 hydrolyzed vegetable protein 149 hydrolyzed yeast protein 60 hydrolyzed yogurt protein 12

40

41

42

43

44

45

46

47

48

49

50

51

52

53

54

55

56

57

58

59

60

61

62

63

64

65

66

67

68

69

70

71

72

73

74

75

76

77

78

79

80

81

82

83

84

85

86

87

88

89

90

91

92

93

94

95

96

97

98

99

100

101

102

103

104

105

106

107

108

109

110

111

112

113

114 Chamomilla recutita derived ingredients SUMMARY The safety of German chamomile (Chamomilla recutita (matricaria))-derived ingredients is reviewed in this assessment. These ingredients function mostly as fragrance ingredients and skin conditioning agents in cosmetic products. The VCRP and Council survey data combined indicate that the following 8 chamomile ingredients have been used in cosmetic products: chamomilla recutita (matricaria) extract, chamomilla recutita (matricaria) flower, chamomilla recutita (matricaria) flower extract, chamomilla recutita (matricaria) flower/leaf extract, chamomilla recutita (matricaria) flower oil, chamomilla recutita (matricaria) flower powder, chamomilla recutita (matricaria) flower water, and chamomilla recutita (matricaria) oil. Of the ingredients reviewed in this safety assessment, the highest use concentration has been reported as 0.5% for chamomilla recutita (matricaria) flower. Chamomilla recutita (matricaria) flower oil is produced by the steam distillation of chamomile (Chamomilla recutita) flowers. One of the trade name mixtures associated with chamomilla recutita (matricaria) flower extract [INCI name: mineral oil (and) prunus armeniaca (apricot) kernel oil (and) chamomilla recutita (matricaria) extract] is manufactured by prolonged maceration in a mixture of mineral oil and apricot kernel oil. Another trade name mixture associated with chamomilla recutita (matricaria) flower extract [INCI name: propylene glycol (and) water (and) chamomilla recutita (matricaria) flower extract] is manufactured by hydroglycolic extraction. Sesquiterpenes, sesquiterpene alcohols (α-bisabolol, major component), and paraffin hydrocarbons are among the components of chamomilla recutita (matricaria) flower oil. A UV spectral analysis has indicated an absorption maximum of 285 nm for chamomilla recutita (matricaria) flower oil. Additionally, a logp value of 5.29 has been reported for this ingredient. In vivo data on the absorption, distribution, metabolism, and excretion of the Chamomilla recutita-derived cosmetic ingredients reviewed in this safety assessment were not found in the published literature. However, data relating to the absorption of and systemic exposure to bisabolol, a major component of chamomilla recutita (matricaria) flower oil, were considered. Using an in vitro membrane diffusion model, most of the components of chamomilla recutita (matricaria) oil, except for chamazulene, passed through the cellophane membrane. The following ingredients did not induce acute toxicity when administered orally to mice or rats: chamomilla recutita (matricaria) flower (1,440 mg/kg), chamomilla recutita (matricaria) flower oil (5,000 mg/kg), and chamomilla recutita (matricaria) flower oil (5,600 mg/kg). The same was true for chamomilla recutita (matricaria) oil (5,000 mg/kg) when administered dermally to rabbits. Chamomile recutita (matricaria) flowers (in the form of herbal tea) did not induce oral toxicity when consumed repeatedly by rats or humans. Chamomilla recutita (matricaria) flower extract also did not induce oral toxicity in rats when administered repeatedly. The antimicrobial activity of chamomilla recutita (matricaria) flower oil has been demonstrated using various bacterial and fungal strains. Seven hay fever patients experienced conjunctivitis after ocular rinsing with Chamomilla recutita (matricaria) tea (from flowers). The results of a provocation test involving the tea extract confirmed that the tea induced allergic conjunctivitis. Chamomilla recutita (matricaria) flower oil was not irritating to the hen s egg chorioallantoic membrane in the HET-CAM in vitro assay for assessing ocular irritation potential. The following trade name mixtures associated with chamomilla recutita (matricaria) flower extract were evaluated for ocular irritation in rabbits: mineral oil (and) prunus armeniaca (apricot) kernel oil (and) chamomilla recutita (matricaria) extract, propylene glycol (and) water (and) chamomilla recutita (matricaria) flower extract, and propylene glycol (and) water salvia officinalis (sage) leaf extract chamomilla recutita (matricaria flower extract). Each was classified as a non-irritant. Skin irritation was observed in an acute dermal toxicity study on chamomilla recutita (matricaria) flower oil involving rabbits. Undiluted Chamomilla recutita (matricaria) flower oil was classified as non-irritating to the skin of hairless mice, and moderately irritating to the skin of rabbits. The following trade name mixtures associated with chamomilla recutita (matricaria) flower extract were evaluated for skin irritation in rabbits: mineral oil (and) prunus armeniaca (apricot) kernel oil (and) chamomilla recutita (matricaria) extract, propylene glycol (and) water (and) chamomilla recutita (matricaria) flower extract, and propylene glycol (and) water salvia officinalis (sage) leaf extract chamomilla recutita (matricaria flower extract). Each was classified as a non-irritant.

115 Cross-reactivity of 10% chamomilla recutita (matricaria) extract with carabron (a sesquiterpene lactone) was not demonstrated in a guinea pig skin sensitization study. In a single application, epicutaeous patch test involving 29 normal subjects and 21 patients (17 with sensitive skin; 3 with eczema; 1 with allergy), results for a cuticle softener containing 0.3% chamomilla recutita (matricaria) flower extract were negative for skin irritation. In human predictive patch tests, chamomilla recutita (matricaria) flower oil (4%) was neither a skin irritant in subjects tested nor a skin sensitizer in a maximization test involving 25 subjects. Other predictive HRIPT results for a shave balm containing 0.2% chamomilla recutita (matricaria) flower extract (105 subjects), an eye lotion containing 0.4% chamomilla recutita (matricaria) flower extract (107 subjects), a facial cleansing and makeup remover towelettes containing 0.01% chamomilla recutita (matricaria) extract (50 subjects), and a hair gel styling mist containing % chamomilla recutita (matricaria) flower/leaf extract (103 subjects) were negative for skin irritation and sensitization. In provocative tests, skin sensitization was observed in 18 of 24 patients patch tested with 1% chamomilla recutita (matricaria) ether extract and in 4 of 5 patients and 48 of 85 patients patch tested with 2.5% chamomilla recutita (matricaria) ether extract in petrolatum. Five of 9 patients with positive patch test reactions to sesquiterpene lactone mix also had an allergic reaction to 2.5% Chamomilla recutita (matricaria) [plant part(s) not specified] in petrolatum. Skin sensitization was also observed in 19 gardeners and greenhouse workers with compositae-related symptoms who were patch tested with 2.5% Chamomilla recutita (matricaria) in petrolatum. Of 36 patients patch tested with ether extracts of Chamomilla recutita (matricaria), 30 had positive patch test reactions, most of which were ++ or +++. Similarly, of the 35 patients patch tested with 2.5% Chamomilla recutita (matricaria) in petrolatum, 22 had sensitization reactions (+ to +++). The number of patients (group of 35, sesquiterpene lactones mix sensitive) with positive reactions to chamomilla recutita (matricaria) flower aqueous extract decreased with decreasing test concentrations (100% [30 patients] to 1% [9 patients]). Of 129 patients (sensitive to compositae mix) patch-tested with 2.5% chamomilla recutita (matricaria) flower extract, 83 had sensitization reactions. In the prick test, chamomilla recutita (matricaria) extract (applied to forearm, 3.5 mg/ml) induced wheal formation in all 9 patients. Provocative testing also yielded patch test reactions to chamomilla recutita flower oil, a doubtful positive reaction in 1 of 14 patients (4% concentration) and a ++ reaction to 4% and 1% in a second patient. Patch testing also resulted in a low incidence of skin sensitization to chamomilla recutita (matricaria) flower oil in 3 of 74 patients (2% in yellow soft paraffin), 2 of 200 patients, and 2 of 86 patients. The 86 patients were also sensitive to a perfume mixture. Positive reactions to chamomilla recutita (matricaria) flower extract and Chamomilla recutita plant parts (petals, leaves, flowers, and stems) were also observed in case reports. Barely perceptible erythema was observed in hairless mice and miniature swine treated with chamomilla recutita (matricaria) flower oil in a photoxicity study, and these results were classified as negative. Photoaggravation was observed in 1 of 5 patients tested with 2.5% chamomilla recutita (matricaria) ether extract in a standard photopatch test. For 37 regular users of chamomile (herbal product, genus and species not stated), both the frequency of threatening miscarriages and the frequency preterm labors were 21.6% higher when compared to non-users (group of 283); many of the subjects also consumed licorice. The incidence of sister chromatid exchanges in bone marrow cells from mice dosed orally with chamomilla recutita (matricaria) flower extract was comparable to that observed in in bone marrow cells from control mice. The genotoxicity of one of the trade name mixtures associated with chamomilla recutita (matricaria) flower extract [mineral oil (and) prunus armeniaca (apricot) kernel oil (and) chamomilla recutita (matricaria) extract] was evaluated using the following bacterial strains: Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537, and Escherichia coli strain WP2 uvra pkm101. Results were negative both with and without metabolic activation. The antigenotoxic activity of chamomilla recutita (matricaria) flower oil and chamomilla recutita (matricaria) flower oil t was also demonstrated in vitro. Carcinogenicity data on chamomile ingredients were not found in the published literature. Chamomilla recutita (matricaria) flower extract and chamomilla recutita flower oil caused a significant decrease in cell viability in human cancer cell lines. Various biological effects of chamomile ingredients (Chamomilla recutita (matricaria), such as immunomodulatory activity and wound healing activity, have been identified in the published literature. DISCUSSION Botanical ingredients, derived from natural plant sources, are complex mixtures. The Panel expressed concern that multiple botanical ingredients may each contribute to the final concentration of a single constituent. Azulene has

116 been identified as a component of chamomilla recutita (matricaria) flower oil, and the Panel previously concluded that the available data are insufficient to support the safety of azulene for use in cosmetic products. The Panel also expressed concern over components of chamomilla recutita (matricaria) flower extract (i.e., quercetin, and quercetin-3-glucoside (isoquercitrin)) that may be genotoxic/carcinogenic, and components of chamomilla recutita (matricaria) flower oil (i.e., β- farnesene, linalool, and linalool acetate) that may be sensitizers (linalool and linalool acetate) and have insecticidal activity (β-farnesene). The Panel concluded that these components are not at levels of toxicologic concern in cosmetics, but also noted that, given the presence of Chamomilla recutita-derived ingredients in fragrances, plant constituents of toxicologic concern should not exceed any limitations that may have been established by the International Fragrance Association (IFRA). Thus, when formulating products, manufacturers should avoid reaching levels of plant constituents that may cause sensitization or other adverse effects. The Panel also expressed concern about pesticide residues and heavy metals that may be present in Chamomilla recutita-derived ingredients. They stressed that the cosmetics industry should continue to use current good manufacturing practices (cgmps) to limit impurities in the ingredient before blending into cosmetic formulations. The Panel was concerned that cosmetics containing these ingredients be formulated to be non-sensitizing because the levels of potentially sensitizing constituents in the ingredients (e.g., sesquiterpene lactones), can be quite variable (depending on plant growth conditions, extraction methods, and other factors), and the data available from sensitization tests may not represent the complete spectrum of concentrations of such constituents in the ingredients as used in cosmetic products. In addition, the Panel was concerned that the concentrations of potentially sensitizing constituents should not exceed levels of concern in formulations containing ingredients from multiple plant species that each can contribute such constituents to the overall formulations. In response to the Panel s request for skin irritation and sensitization data on chamomilla recutita (matricaria) flower extract, human repeated insult patch test (HRIPT) data on products containing 0.2%, 0.3%, and 0.4% chamomilla recutita (matricaria) flower extract were received. The 3 studies yielded negative results, and were considered sufficient, together with other skin sensitization data in the safety assessment, for evaluating the skin irritation and sensitization potential of all 5 Chamomilla recutita (matricaria) flower-derived ingredients in cosmetics. Current use concentration data received from the Personal Care Products Council indicate that Chamomilla recutita (matricaria) flower-derived ingredients are being used in leave-on products at concentrations up to 0.5% (chamomilla recutita (matricaria) flower extract), and the Panel agreed that the HRIPT data on products containing chamomilla recutita (matricaria) flower extract can be used to evaluate the safety of Chamomilla recutita (matricaria) flower-derived ingredients over the range of use concentrations reported. The Panel also considered that FDA has listed Chamomilla recutita flowers as generally recognized as safe (GRAS) for their intended use in food for human consumption. However, the Panel determined that the available data are insufficient for determining that ingredients derived from Chamomilla recutita leaf, and stem, or the whole plant are safe for use in cosmetics and that chemical composition data on these ingredients are needed. Provocative patch testing involves patients with diseased skin. The Panel discussed the relevance of positive provocative test results for chamomilla recutita (matricaria) extract (ether extracts) at concentrations up to 2.5%, considering that the method of preparation of these extracts is dissimilar to those used to produce commercial Chamomilla recutita-derived ingredients. The commercial ingredients are produced by steam distillation or using multiple extraction solvents, such as oils, propylene glycol, water, and carbon dioxide, whereas, the ether extracts of freshly cut plants would probably contain the maximally concentrated organic constituents. Therefore, the content of the ether extracts prepared specifically for the tests performed may deviate from the content of the commercially-supplied ingredients. Because chamomilla recutita (matricaria) flower oil may contain (-)-α-bisabolol at concentrations as high as 41.45%, safety test data from the CIR final report on bisabolol are included in Table 1 of this safety assessment. The Panel concluded that bisabolol is safe as used in cosmetic formulations; reported use concentrations ranged from 0.001% to 1%. The following data on bisabolol are included in this report to support the safety of chamomilla recutita (matricaria) flower oil in cosmetic products: skin penetration, skin penetration enhancement, acute inhalation toxicity, acute oral and intraperitoneal toxicity, repeated dose oral and dermal toxicity, ocular irritation, skin irritation and sensitization, photosensitization, genotoxicity, and reproductive and developmental toxicity data. The Panel discussed the issue of incidental inhalation exposure from propellant and pump hair sprays and face powders and sprays. Inhalation toxicity data were not available. However, the Panel considered pertinent data indicating that incidental inhalation exposures to these ingredients in such cosmetic products would not cause adverse health effects, including acute inhalation toxicity data on bisabolol and data characterizing the potential for these ingredients to cause acute and repeated dose oral toxicity, and ocular or dermal irritation or sensitization. The Panel noted that 95% 99% of droplets/particles produced in cosmetic aerosols would not be respirable to any appreciable amount. Coupled with the small actual exposure in the breathing zone and the concentrations at which the ingredients are used, the available information indicates that incidental inhalation would not be a significant route of exposure that might lead to

117 local respiratory or systemic effects. A detailed discussion and summary of the Panel s approach to evaluating incidental inhalation exposures to ingredients in cosmetic products is available at CONCLUSION The CIR Expert Panel concluded that chamomilla recutita (matricaria) flower, chamomilla recutita (matricaria) flower extract, chamomilla recutita (matricaria) flower powder, chamomilla recutita (matricaria) flower water, chamomilla recutita (matricaria) flower oil are safe in the present practices of use and concentration, described in this safety assessment, in cosmetics, when formulated to be non-sensitizing. The Panel also concluded that the available data are insufficient to make a determination that chamomilla recutita (matricaria) extract, chamomilla recutita (matricaria) flower/leaf extract, chamomilla recutita (matricaria) flower/leaf/stem extract, chamomilla recutita (matricaria) flower/leaf/stem water, chamomilla recutita (matricaria) leaf extract, and chamomilla recutita (matricaria) oil are safe under the intended conditions of use in cosmetics.

118

119

120

121

122 Memorandum Commitment & Credibility since 1976 To: CIR Expert Panel Members and Liaisons From: Christina Burnett, Senior Scientific Writer/Analyst Date: August 28, 2015 Subject: Update on Methylisothiazolinone Enclosed is the latest opinion (issued June 2015) from the European Scientific Committee on Consumer Safety (SCCS) for the preservative methylisothiazolinone (MI). (It is identified as methis092015data in the pdf document.) The latest opinion is based on quantitative risk assessment (QRA) and cosmetovigilance system data submitted by Cosmetics Europe and on the findings in peer-reviewed published literature of increased incidences of contact allergy from MI exposure in Europe. The SCCS has found that the data: does not support the safe use of MI as a preservative in rinse-off cosmetic products up to a concentration limit of 100 ppm from the view of induction of contact allergy. For rinse-off cosmetic products, a concentration of 15 ppm (0.0015%) MI is considered safe for the consumer from the point of view of induction of contact allergy. The information provided does not support the safe use of MI as a preservative in leave-on hair cosmetic products up to a concentration limit of 100 ppm from the point of view of induction of contact allergy. In their previous opinion in 2014, the SCCS stated that: in leave-on cosmetic products (including wet wipes ), no safe concentration has been adequately demonstrated for induction or elicitation of contact allergy. In rinse-off cosmetic products, the SCCS has recommended that concentrations up to % (15 ppm) MI are safe, in terms of the potential for induction of contact allergy, but stated that there is no information available to evaluate the potential for this ingredient to elicit contact allergy." In September 2014, the CIR Expert Panel issued a Final Amended Safety Assessment on methylisothiazolinone with the conclusion that MI is safe for use in rinse-off cosmetic products at concentrations up to 100 ppm and safe in leave-on cosmetic products when they are formulated to be non-sensitizing, which may be determined based on a QRA. The Panel should carefully review the latest SCCS opinion and determine if the Final Amended Safety Assessment on methylisothiazolinone should be reopened for further evaluation.

123 SCCS/1557/15 Scientific Committee on Consumer Safety SCCS OPINION ON Methylisothiazolinone (MI) (P94) Submission III (Sensitisation only) The SCCS adopted this opinion at its 10 th plenary meeting on 25 June 2015

Cosmetic Ingredient Review Expert Panel 136 th Meeting (September 21-22, 2015) - Findings

Cosmetic Ingredient Review Expert Panel 136 th Meeting (September 21-22, 2015) - Findings Announcement Cosmetic Ingredient Review Expert Panel 136 th Meeting (September 21-22, 2015) - Findings September 25, 2015 Final Safety Assessments Polysaccharide Gums 106 ingredients Soy Proteins and Peptides

More information

Safety Assessment of Polysorbates as Used in Cosmetics

Safety Assessment of Polysorbates as Used in Cosmetics Safety Assessment of Polysorbates as Used in Cosmetics Status: ReReview for Panel Review Release Date: February 2, 215 Panel Meeting Date: March 1617, 215 The 215 Cosmetic Ingredient Review Expert Panel

More information

Cosmetic Ingredient Review Expert Panel 133 rd Meeting (December 8-9, 2014) - Findings

Cosmetic Ingredient Review Expert Panel 133 rd Meeting (December 8-9, 2014) - Findings December 12, 2014 Announcement Cosmetic Ingredient Review Expert Panel 133 rd Meeting (December 8-9, 2014) - Findings Final Safety Assessments Avena sativa (Oat)-Derived Ingredients 21 ingredients Glycerin

More information

Safety Assessment of Polysorbates as Used in Cosmetics

Safety Assessment of Polysorbates as Used in Cosmetics Safety Assessment of Polysorbates as Used in Cosmetics Status: Draft Final Amended Report for Panel Review Release Date: May 22, 2015 Panel Meeting Date: June 15-16, 2015 The 2015 Cosmetic Ingredient Review

More information

Safety Assessment of Nonoxynols as Used in Cosmetics

Safety Assessment of Nonoxynols as Used in Cosmetics Safety Assessment of Nonoxynols as Used in Cosmetics Status: Re-review for Panel Review Release Date: February 20, 2015 Panel Date: March 16-17, 2015 The 2015 Cosmetic Ingredient Review Expert Panel members

More information

Amended Safety Assessment of Chamomilla Recutita-Derived Ingredients as Used in Cosmetics

Amended Safety Assessment of Chamomilla Recutita-Derived Ingredients as Used in Cosmetics Amended Safety Assessment of Chamomilla Recutita-Derived Ingredients as Used in Cosmetics Status: Draft Final Amended Report for Panel Review Release Date: May 13, 2016 Panel Date: June 6-7, 2016 The 2016

More information

Safety Assessment of Nonoxynols as Used in Cosmetics

Safety Assessment of Nonoxynols as Used in Cosmetics Safety Assessment of Nonoxynols as Used in Cosmetics Status: Draft Amended Report for Panel Review Release Date: May 22, 2015 Panel Date: June15-16, 2015 The 2015 Cosmetic Ingredient Review Expert Panel

More information

Safety Assessment of Polysorbates as Used in Cosmetics

Safety Assessment of Polysorbates as Used in Cosmetics Safety Assessment of Polysorbates as Used in Cosmetics Status: Final Amended Report Release Date: July 10, 2015 Panel Meeting Date: June 15-16, 2015 The 2015 Cosmetic Ingredient Review Expert Panel members

More information

Safety Assessment of Polymerized Tetramethylcyclotetrasiloxanes as Used in Cosmetics

Safety Assessment of Polymerized Tetramethylcyclotetrasiloxanes as Used in Cosmetics Safety Assessment of Polymerized Tetramethylcyclotetrasiloxanes as Used in Cosmetics Status: Tentative Report for Public Comment Release Date: January 6, 2016 Panel Meeting Date: March 31-April 1, 2016

More information

Safety Assessment of Acryloyldimethyltaurate Polymers as Used in Cosmetics

Safety Assessment of Acryloyldimethyltaurate Polymers as Used in Cosmetics Safety Assessment of Acryloyldimethyltaurate Polymers as Used in Cosmetics Status: Tentative Report for Public Comment Release Date: October 7, 2016 Panel Meeting Date: April 10-11, 2017 All interested

More information

Amended Safety Assessment of Butyl Polyoxyalkylene Ethers as Used in Cosmetics

Amended Safety Assessment of Butyl Polyoxyalkylene Ethers as Used in Cosmetics Amended Safety Assessment of Butyl Polyoxyalkylene Ethers as Used in Cosmetics Status: Re-Review for Panel Review Release Date: May 13, 2016 Panel Meeting Date: June 6-7, 2016 The 2016 Cosmetic Ingredient

More information

DevaCurl-B Leave In Miracle Curl Plumper 6.0 oz

DevaCurl-B Leave In Miracle Curl Plumper 6.0 oz DevaCurl-B Leave In Miracle Curl Plumper 6.0 oz Water, Glycerin, PEG-6 Caprylic/Capric Glycerides, Guar Hydroxypropyltrimonium Chloride, Hydrolyzed Wheat Protein, PEG-40 Hydrogenated Castor Oil, Propylene

More information

ADMIN. Memo Agenda Minutes Aerosols Precedents and Frameworks Hair Dye Findings

ADMIN. Memo Agenda Minutes Aerosols Precedents and Frameworks Hair Dye Findings ADMIN Memo Agenda Minutes Aerosols Precedents and Frameworks Hair Dye Findings CIR EXPERT PANEL MEETING APRIL 10 11, 2017 MEMORANDUM Commitment & Credibility since 1976 To: CIR Expert Panel Members and

More information

Safety Assessment of Acryloyldimethyltaurate Polymers as Used in Cosmetics

Safety Assessment of Acryloyldimethyltaurate Polymers as Used in Cosmetics Safety Assessment of Acryloyldimethyltaurate Polymers as Used in Cosmetics Status: Final Report Release Date: May 24, 201 Panel Meeting Date: April 10-11, 201 The 201 Cosmetic Ingredient Review Expert

More information

Safety Assessment of Ceramides as Used in Cosmetics

Safety Assessment of Ceramides as Used in Cosmetics Safety Assessment of Ceramides as Used in Cosmetics Status: Draft Report for Panel Review Release Date: May 16, 2014 Panel Meeting Date: June 9-10, 2014 The 2014 Cosmetic Ingredient Review Expert Panel

More information

Safety Assessment of Plant-Derived Proteins and Peptides as Used in Cosmetics

Safety Assessment of Plant-Derived Proteins and Peptides as Used in Cosmetics Safety Assessment of Plant-Derived Proteins and Peptides as Used in Cosmetics Status: Draft Report for Panel Review Release Date: November 11, 2016 Panel Meeting Date: December 5-6, 2016 The 2016 Cosmetic

More information

Amended Safety Assessment of Butyl Polyoxyalkylene Ethers as Used in Cosmetics

Amended Safety Assessment of Butyl Polyoxyalkylene Ethers as Used in Cosmetics Amended Safety Assessment of Butyl Polyoxyalkylene Ethers as Used in Cosmetics Status: Draft Tentative Amended Report for Panel Review Release Date: November 11, 216 Panel Meeting Date: December 5-6, 216

More information

ADMIN Agenda Memo Minutes Report Strategies Report Strategies Unified Memo Boric Acid Strategy Glyceryl Esters Strategy Botanical Ingredient

ADMIN Agenda Memo Minutes Report Strategies Report Strategies Unified Memo Boric Acid Strategy Glyceryl Esters Strategy Botanical Ingredient ADMIN Agenda Memo Minutes Report Strategies Report Strategies Unified Memo Boric Acid Strategy Glyceryl Esters Strategy Botanical Ingredient Strategy: Citrus Fruit-derived Ingredients PEGs Cocamine CIR

More information

Safety Assessment of Acryloyldimethyltaurate Polymers as Used in Cosmetics

Safety Assessment of Acryloyldimethyltaurate Polymers as Used in Cosmetics Safety Assessment of Acryloyldimethyltaurate Polymers as Used in Cosmetics Status: Draft Tentative Report for Panel Review Release Date: September 2, 206 Panel Meeting Date: September 26-27, 206 The 206

More information

Safety Assessment of Hexamethylene Diisocyanate (HDI) Polymers as Used in Cosmetics

Safety Assessment of Hexamethylene Diisocyanate (HDI) Polymers as Used in Cosmetics Safety Assessment of Hexamethylene Diisocyanate (HDI) Polymers as Used in Cosmetics Status: Scientific Literature Review for Public Comment Release Date: June 18, 2015 Panel Meeting Date: September 21-22,

More information

Amended Safety Assessment of Persulfates as Used in Cosmetics

Amended Safety Assessment of Persulfates as Used in Cosmetics Amended Safety Assessment of Persulfates as Used in Cosmetics Status: Draft Amended Report for Panel Review Release Date: November 11, 2016 Panel Date: December 5-6, 2016 The 2016 Cosmetic Ingredient Review

More information

Safety Assessment of Polyquaternium-22 and Polyquaternium-39 as Used in Cosmetics

Safety Assessment of Polyquaternium-22 and Polyquaternium-39 as Used in Cosmetics Safety Assessment of and as Used in Cosmetics Status: Final Report Release Date: October 4, 2013 Panel Meeting Date: September 9-10, 2013 The 2013 Cosmetic Ingredient Review Expert Panel members are: Chair,

More information

Safety Assessment of Organo-Titanium Ingredients as Used in Cosmetics

Safety Assessment of Organo-Titanium Ingredients as Used in Cosmetics Safety Assessment of Organo-Titanium Ingredients as Used in Cosmetics Status: Scientific Literature Review for Public Comment Release Date: March 13, 201 Panel Date: June 4-5, 201 All interested persons

More information

Safety Assessment of Polyene Group as Used in Cosmetics

Safety Assessment of Polyene Group as Used in Cosmetics Safety Assessment of Polyene Group as Used in Cosmetics Status: Draft Report for Panel Review Release Date: February 20, 2015 Panel Meeting Date: March 16-17, 2015 The 2015 Cosmetic Ingredient Review Expert

More information

Safety Assessment of Rosmarinus Officinalis (Rosemary)-Derived Ingredients as Used in Cosmetics

Safety Assessment of Rosmarinus Officinalis (Rosemary)-Derived Ingredients as Used in Cosmetics Safety Assessment of Rosmarinus Officinalis (Rosemary)-Derived Ingredients as Used in Cosmetics Status: Draft Final Report for Panel Review Release Date: May 16, 2014 Panel Meeting Date: June 9-10, 2014

More information

Memo Agenda Minutes. Strategy ADMIN

Memo Agenda Minutes. Strategy ADMIN Memo Agenda Minutes Strategy ADMIN CIR EXPERT PANEL MEETING DECEMBER 5 6, 2016 Commitment & Credibility since 1976 MEMORANDUM To: From: Subject: Date: CIR Expert Panel Members and Liaisons Director, CIR

More information

ACB Pisum Sativum Peptide Sample Formulations

ACB Pisum Sativum Peptide Sample Formulations ACB Pisum Sativum Peptide Sample Formulations Code: 16810 INCI Name: Pisum Sativum (Pea) Peptide CAS #: 90082-41-0 EINECS #: 290-130-6 Sample Finished Formulation Guidelines Anti-Aging Shampoo FNFHB02-19

More information

Distributed for Comment Only -- Do Not Cite or Quote MEMORANDUM

Distributed for Comment Only -- Do Not Cite or Quote MEMORANDUM Memo Agenda Minutes/Meeting Summary Boilerplate Documents Memo Table Formaldehyde Releasers Hair dye epidemiology Memo Minutes Report Infant Skin Memo Transcripts Report Makri 2004 ADMIN CIR EXPERT PANEL

More information

Memo/Agenda Minutes Re-Review Summaries Alpha Hydroxy Acids Sodium Alpha-Olefin Sulfonates Polyvinyl Alcohol ADMIN

Memo/Agenda Minutes Re-Review Summaries Alpha Hydroxy Acids Sodium Alpha-Olefin Sulfonates Polyvinyl Alcohol ADMIN Memo/Agenda Minutes Re-Review Summaries Alpha Hydroxy Acids Sodium Alpha-Olefin Sulfonates Polyvinyl Alcohol ADMIN CIR EXPERT PANEL MEETING MARCH 17-18, 2014 Commitment & Credibility since 1976 MEMORANDUM

More information

Safety Assessment of Anthemis Nobilis-Derived Ingredients as Used in Cosmetics

Safety Assessment of Anthemis Nobilis-Derived Ingredients as Used in Cosmetics Safety Assessment of Anthemis Nobilis-Derived Ingredients as Used in Cosmetics Status: Draft Final Report for Panel Review Release Date: November15, 2013 Panel Date: December 9-10, 2013 The 2013 Cosmetic

More information

Safety Assessment of Nonoxynols as Used in Cosmetics

Safety Assessment of Nonoxynols as Used in Cosmetics Safety Assessment of Nonoxynols as Used in Cosmetics Status: Draft Final Amended Report for Panel Review Release Date: November 20, 2015 Panel Date: December 14-15, 2015 The 2015 Cosmetic Ingredient Review

More information

Safety Assessment of Soy Proteins and Peptides as Used in Cosmetics

Safety Assessment of Soy Proteins and Peptides as Used in Cosmetics Safety Assessment of Soy Proteins and Peptides as Used in Cosmetics Status: Draft Final Report for Panel Review Release Date: August 28, 2015 Panel Meeting Date: September 21-22, 2015 The 2015 Cosmetic

More information

Safety Assessment of Amino Acid Alkyl Amides as Used in Cosmetics

Safety Assessment of Amino Acid Alkyl Amides as Used in Cosmetics Safety Assessment of Amino Acid Alkyl Amides as Used in Cosmetics Status: Draft Final Report for Panel Review Release Date: November 5, 203 Panel Meeting Date: December 9-0, 203 The 203 Cosmetic Ingredient

More information

Safety Assessment of Plant-Derived Proteins and Peptides as Used in Cosmetics

Safety Assessment of Plant-Derived Proteins and Peptides as Used in Cosmetics Safety Assessment of Plant-Derived s and Peptides as Used in Cosmetics Status: Tentative Report for Public Comment Release Date: June 21, 2017 Panel Meeting Date: September 11-12, 2017 All interested persons

More information

Prof. Marina Heinonen University of Helsinki Member of the NDA Panel and EFSA s WG on Novel Foods

Prof. Marina Heinonen University of Helsinki Member of the NDA Panel and EFSA s WG on Novel Foods Guidance on Novel Foods Composition, production process and specification Prof. Marina Heinonen University of Helsinki Member of the NDA Panel and EFSA s WG on Novel Foods Info-Session 06 March 2017 Parma

More information

Safety Assessment of Eucalyptus globulus (Eucalyptus)-Derived Ingredients as Used in Cosmetics

Safety Assessment of Eucalyptus globulus (Eucalyptus)-Derived Ingredients as Used in Cosmetics Safety Assessment of Eucalyptus globulus (Eucalyptus)-Derived Ingredients as Used in Cosmetics Status: Draft Final Report for Panel Review Release Date: May 11, 2018 Panel Meeting Date: June 4-5, 2018

More information

Safety Assessment of Rosmarinus Officinalis (Rosemary)-Derived Ingredients as Used in Cosmetics

Safety Assessment of Rosmarinus Officinalis (Rosemary)-Derived Ingredients as Used in Cosmetics Safety Assessment of Rosmarinus Officinalis (Rosemary)-Derived Ingredients as Used in Cosmetics Status: Draft Final Report for Panel Review Release Date: February 21, 2014 Panel Meeting Date: March 17-18,

More information

Safety Assessment of Ginkgo biloba-derived Ingredients as Used in Cosmetics

Safety Assessment of Ginkgo biloba-derived Ingredients as Used in Cosmetics Safety Assessment of Ginkgo biloba-derived Ingredients as Used in Cosmetics Status: Draft Final Report for Panel Review Release Date: August 29, 2018 Panel Meeting Date: September 24-25, 2018 The 2018

More information

Decision tree for the safety assessment of botanical cosmetic ingredients. Personal Care Products Council CIR Science and Support Committee

Decision tree for the safety assessment of botanical cosmetic ingredients. Personal Care Products Council CIR Science and Support Committee Decision tree for the safety assessment of botanical cosmetic ingredients Personal Care Products Council CIR Science and Support Committee Using the Decision Tree Provided as a guidance tool for finished

More information

Safety Assessment of Alkoxylated Fatty Amides as Used in Cosmetics

Safety Assessment of Alkoxylated Fatty Amides as Used in Cosmetics Safety Assessment of Alkoxylated Fatty Amides as Used in Cosmetics Status: Draft Tentative Report for Panel Review Release Date: November 9, 2018 Panel Meeting Date: December 3-4, 2018 The 2018 Cosmetic

More information

SAFETY ASSESSMENT. Product Name: Soap Range (by Ancient Wisdom Marketing, Sheffield)

SAFETY ASSESSMENT. Product Name: Soap Range (by Ancient Wisdom Marketing, Sheffield) The Elms Oxford Rd Chieveley Newbury RG20 8RT United Kingdom Telephone: +44 1635 248830 Fax: +44 1635 247206 Email: innova@zoom.co.uk SAFETY ASSESSMENT Product Name: Soap Range (by Ancient Wisdom Marketing,

More information

Safety Assessment of Acryloyldimethyltaurate Polymers as Used in Cosmetics

Safety Assessment of Acryloyldimethyltaurate Polymers as Used in Cosmetics Safety Assessment of Acryloyldimethyltaurate Polymers as Used in Cosmetics Status: Draft Final Report for Panel Review Release Date: March 7, 207 Panel Meeting Date: April 0-, 207 The 207 Cosmetic Ingredient

More information

GREEN TEA CIR EXPERT PANEL MEETING JUNE 27-28, 2011

GREEN TEA CIR EXPERT PANEL MEETING JUNE 27-28, 2011 GREEN TEA CIR EXPERT PANEL MEETING JUNE 27-28, 2011 Administrative Memorandum To: From: CIR Expert Panel Members and Liaisons Monice M. Fiume MMF Senior Scientific Analyst/Writer Date: June 3, 2011 Subject:

More information

Safety Assessment of Anthemis Nobilis-Derived Ingredients as Used in Cosmetics

Safety Assessment of Anthemis Nobilis-Derived Ingredients as Used in Cosmetics PINK Safety Assessment of Anthemis Nobilis-Derived Ingredients as Used in Cosmetics Status: Draft Tentative Report for Panel Review Release Date: August 16, 2013 Panel Date: September 9-10, 2013 The 2013

More information

BLUE TEA CIR EXPERT PANEL MEETING SEPTEMBER 26-27, 2011

BLUE TEA CIR EXPERT PANEL MEETING SEPTEMBER 26-27, 2011 BLUE TEA CIR EXPERT PANEL MEETING SEPTEMBER 26-27, 2011 Memorandum To: CIR Expert Panel Members and Liaisons From: Monice M. Fiume MMF Senior Scientific Analyst/Writer Date: September 1, 2011 Subject:

More information

Safety Assessment of PCA (2-Pyrrolidone-5-Carboxylic Acid) and Its Salts as Used in Cosmetics

Safety Assessment of PCA (2-Pyrrolidone-5-Carboxylic Acid) and Its Salts as Used in Cosmetics Safety Assessment of PCA (2-Pyrrolidone-5-Carboxylic Acid) and Its Salts as Used in Cosmetics Status: Tentative Amended Report for Public Comment Release Date: September 17, 2014 Panel Meeting Date: December

More information

Safety Assessment of Polysilsesquioxanes as Used in Cosmetics

Safety Assessment of Polysilsesquioxanes as Used in Cosmetics Safety Assessment of Polysilsesquioxanes as Used in Cosmetics Status: Scientific Literature Review for Public Comment Release Date: April 13, 2017 Panel Meeting Date: June 12-13, 2017 All interested persons

More information

Safety Assessment of Chamomilla Recutita-Derived Ingredients as Used in Cosmetics

Safety Assessment of Chamomilla Recutita-Derived Ingredients as Used in Cosmetics PINK Safety Assessment of Chamomilla Recutita-Derived Ingredients as Used in Cosmetics Status: Draft Tentative Report for Panel Review Release Date: August 16, 2013 Panel Date: September 9-10, 2013 The

More information

Safety Assessment of Propylene Glycol Esters as Used in Cosmetics

Safety Assessment of Propylene Glycol Esters as Used in Cosmetics Safety Assessment of Propylene Glycol Esters as Used in Cosmetics Status: Tentative Amended Report for Public Comment Release Date: September 20, 2014 Panel Meeting Date: December 8-9, 2014 All interested

More information

Safety Assessment of Propylene Glycol Esters as Used in Cosmetics

Safety Assessment of Propylene Glycol Esters as Used in Cosmetics Safety Assessment of Propylene Glycol Esters as Used in Cosmetics Status: Final Amended Report Release Date: January 15, 2015 Panel Meeting Date: December 8-9, 2014 The 2014 Cosmetic Ingredient Review

More information

Safety Assessment of Barium Sulfate as Used in Cosmetics

Safety Assessment of Barium Sulfate as Used in Cosmetics Safety Assessment of Barium Sulfate as Used in Cosmetics Status: Draft Final Report for Panel Review Release Date: May16, 2014 Panel Date: June 9-10, 2014 The 2014 Cosmetic Ingredient Review Expert Panel

More information

SAFETY ASSESSMENT. Product: Bath Potions Range (Ancient Wisdom) Product variants:

SAFETY ASSESSMENT. Product: Bath Potions Range (Ancient Wisdom) Product variants: The Elms Oxford Rd Chieveley Newbury RG20 8RT United Kingdom Telephone: +44 1635 248830 Fax: +44 1635 247206 Email: innova47@aol.com SAFETY ASSESSMENT Product: Bath Potions Range (Ancient Wisdom) Product

More information

ACB FRUIT MIX Natural + Efficacious + Multi-Functional + Great for Problem Skin. Tomorrow s Vision Today!

ACB FRUIT MIX Natural + Efficacious + Multi-Functional + Great for Problem Skin. Tomorrow s Vision Today! ACB FRUIT MIX Natural + Efficacious + Multi-Functional + Great for Problem Skin Tomorrow s Vision Today! PRODUCT REFERENCES ACB FRUIT MIX: Product Code: 20343 INCI Name: Water & Saccharum Officinarum (Sugar

More information

Safety Assessment of Polyene Group as Used in Cosmetics

Safety Assessment of Polyene Group as Used in Cosmetics Safety Assessment of Polyene Group as Used in Cosmetics Status: Scientific Literature Review for Public Comment Release Date: December 2, 2014 Panel Meeting Date: March 16-17, 2015 The 2014 Cosmetic Ingredient

More information

Safety Assessment of Bovine Milk Proteins and Protein Derivatives as Used in Cosmetics

Safety Assessment of Bovine Milk Proteins and Protein Derivatives as Used in Cosmetics Safety Assessment of Bovine Milk Proteins and Protein Derivatives as Used in Cosmetics Status: Draft Final Report for Panel Review Release Date: August 18, 2017 Panel Meeting Date: September 11-12, 2017

More information

Amended Safety Assessment of Acid Violet 43 as Used in Cosmetics

Amended Safety Assessment of Acid Violet 43 as Used in Cosmetics Amended Safety Assessment of Acid Violet 43 as Used in Cosmetics Status: Draft Final Amended Report for Panel Review Release Date: November 11, 2016 Panel Meeting Date: December 5-6, 2016 The 2016 Cosmetic

More information

is the global expert in innovation for Health & Personal Care market

is the global expert in innovation for Health & Personal Care market is the global expert in innovation for Health & Personal Care market Performance-tested specialties to help formulator by offering ready-to-use solutions. Innovation-driven experience in formulation to

More information

TRI-K Skin Care Portfolio

TRI-K Skin Care Portfolio TRI-K Skin Care Portfolio NATURAL PEPTIDES NatuePep NaturePep Pea Pisum Sativum Extract NaturePep Sacha Inchi Hydrolyzed Plukenetia Volubilis Seed Extract 2 PROTEINS & AMINO ACIDS BAOBAB Baobab Tein NPNF

More information

Clean Conscience. DESN 410 F001: 2D Core Studio Cindy Lee

Clean Conscience. DESN 410 F001: 2D Core Studio Cindy Lee Clean Conscience DESN 410 F001: 2D Core Studio Cindy Lee Topic Introduction Research & Development Result The Prompt Research Not Just a Pretty Face Stacy Malkan No More Dirty Looks Siobhan O Conner &

More information

A Structure Activity Relationship (SAR) Based Case Study for a Cosmetic Ingredient

A Structure Activity Relationship (SAR) Based Case Study for a Cosmetic Ingredient A Structure Activity Relationship (SAR) Based Case Study for a Cosmetic Ingredient Karen Blackburn, Ph.D. Shengde Wu, Ph.D. The Procter and Gamble Co. March, 2012 Presentation utline Background to P&G

More information

Amended Safety Assessment of Butyl Polyoxyalkylene Ethers as Used in Cosmetics

Amended Safety Assessment of Butyl Polyoxyalkylene Ethers as Used in Cosmetics Amended Safety Assessment of Butyl Polyoxyalkylene Ethers as Used in Cosmetics Status: Draft Final Amended Report for Panel Review Release Date: March 17, 2017 Panel Meeting Date: April 10-11, 2017 The

More information

PINK. Safety Assessment of Isethionate Salts as Used in Cosmetics

PINK. Safety Assessment of Isethionate Salts as Used in Cosmetics PINK Safety Assessment of Isethionate Salts as Used in Cosmetics CIR EXPERT PANEL MEETING JUNE 10-11, 2013 Commitment & Credibility since 1976 Memorandum To: From: CIR Expert Panel Members and Liaisons

More information

PINK Citric Acid CIR EXPERT PANEL MEETING DECEMBER 12-13, 2011

PINK Citric Acid CIR EXPERT PANEL MEETING DECEMBER 12-13, 2011 PINK Citric Acid CIR EXPERT PANEL MEETING DECEMBER 12-1, 2011 Memorandum To: CIR Expert Panel Members and Liaisons From: Monice M. Fiume MMF Senior Scientific Analyst/Writer Date: November 21, 2011 Subject:

More information

Safety Assessment of Ammonia and Ammonium Hydroxide as Used in Cosmetics

Safety Assessment of Ammonia and Ammonium Hydroxide as Used in Cosmetics Safety Assessment of Ammonia and Ammonium Hydroxide as Used in Cosmetics Status: Draft Final Report for Panel Review Release Date: November 10, 2017 Panel Date: December 4-5, 2017. The 2017 Cosmetic Ingredient

More information

TRI-K Hair Care Portfolio

TRI-K Hair Care Portfolio TRI-K Hair Care Portfolio PROTEINS & AMINO ACIDS BAOBAB Baobab Tein NPNF Barla Q Pro NPNF BARLEY Hydrolyzed Adansonia Digitata Seed Extract Laurdimonium Hydroxypropyl Hydrolyzed Barley Protein Barla Tein

More information

Safety Assessment of Isostearamidopropyl Morpholine Lactate as Used in Cosmetics

Safety Assessment of Isostearamidopropyl Morpholine Lactate as Used in Cosmetics Safety Assessment of Isostearamidopropyl Morpholine Lactate as Used in Cosmetics Status: Re-Review for Panel Review Release Date: February 20, 2015 Panel Meeting Date: March 17-18, 2015 The 2015 Cosmetic

More information

Safety Assessment of Polyurethanes as Used in Cosmetics

Safety Assessment of Polyurethanes as Used in Cosmetics Safety Assessment of Polyurethanes as Used in Cosmetics Status: Draft Report for Panel Review Release Date: March 17, 2017 Panel Meeting Date: April 10-11, 2017 The 2017 Cosmetic Ingredient Review Expert

More information

Glycyrrhizin is a foaming agent also acts as sweetener and nutrient.

Glycyrrhizin is a foaming agent also acts as sweetener and nutrient. Paper No.: 13 Paper Title: Food Additives Module 13: Foaming and Anti-foaming agents 13.1 Introduction Foaming and Anti-foaming agents are important part of food industry not only for manufacturing of

More information

Safety Assessment of Ethers and Esters of Ascorbic Acid as Used in Cosmetics

Safety Assessment of Ethers and Esters of Ascorbic Acid as Used in Cosmetics Safety Assessment of Ethers and Esters of Ascorbic Acid as Used in Cosmetics Status: Draft Final Report for Panel Review Release Date: May 19, 2017 Panel Date: June 12-13, 2017 The 2017 Cosmetic Ingredient

More information

There are no supported uses of propylene oxide in consumer products.

There are no supported uses of propylene oxide in consumer products. Global Product Strategy (GPS) Safety Summary Propylene Oxide This GPS Safety Summary is a high-level summary intended to provide the general public with an overview of product safety information on this

More information

Memo Agenda Minutes Priorities Read-across Re-review Summary of Lard ADMIN

Memo Agenda Minutes Priorities Read-across Re-review Summary of Lard ADMIN Memo Agenda Minutes Priorities Read-across Re-review Summary of Lard ADMIN CIR EXPERT PANEL MEETING JUNE 12 13, 2017 Commitment & Credibility since 1976 MEMORANDM To: From: Subject: Date: CIR Expert Panel

More information

Safety Assessment of Hamamelis virginiana (Witch Hazel)-Derived Ingredients as Used in Cosmetics

Safety Assessment of Hamamelis virginiana (Witch Hazel)-Derived Ingredients as Used in Cosmetics Safety Assessment of Hamamelis virginiana (Witch Hazel)-Derived Ingredients as Used in Cosmetics Status: Draft Final Report for Panel Review Release Date: February 9, 208 Panel Meeting Date: March 5-6,

More information

Safety Assessment of Alkyl Phosphates as Used in Cosmetics

Safety Assessment of Alkyl Phosphates as Used in Cosmetics Safety Assessment of Alkyl Phosphates as Used in Cosmetics Status: Draft Report for Panel Review Release Date: May 16, 2014 Panel Meeting Date: June 9-10, 2014 The 2014 Cosmetic Ingredient Review Expert

More information

NOP s Final Guidance on Materials Classification. What s new? March 29, 2017

NOP s Final Guidance on Materials Classification. What s new? March 29, 2017 March 29, 2017 Ms. Michelle Arsenault National Organic Standards Board USDA-AMS-NOP 1400 Independence Ave., SW Room 2648-S, Mail Stop 0268 Washington, DC 20250-0268 Re. MS: Materials Classification Guidance

More information

Safety Assessment of PEG Diesters as Used in Cosmetics

Safety Assessment of PEG Diesters as Used in Cosmetics Safety Assessment of PEG Diesters as Used in Cosmetics Status: Final Amended Report Release Date: April 7, 2015 Panel Meeting Date: March 16-17, 2015 The 2015 Cosmetic Ingredient Review Expert Panel members

More information

Biocidal Products Committee (BPC)

Biocidal Products Committee (BPC) Biocidal Products Committee (BPC) Opinion on the application for approval of the active substance: Hydrated lime Product type: 2 ECHA/BPC/100/2016 Adopted 14 April 2016 Annankatu 18, P.O. Box 400, FI-00121

More information

Safety Assessment of Sorbitan Esters as Used in Cosmetics

Safety Assessment of Sorbitan Esters as Used in Cosmetics Safety Assessment of Sorbitan Esters as Used in Cosmetics Status: Draft Final Amended Report for Panel Review Release Date: November 4, 04 Panel Meeting Date: December 89, 04 The 04 Cosmetic Ingredient

More information

Safety Assessment of Hexamethylene Diisocyanate (HDI) Polymers as Used in Cosmetics

Safety Assessment of Hexamethylene Diisocyanate (HDI) Polymers as Used in Cosmetics Safety Assessment of Hexamethylene Diisocyanate (HDI) Polymers as Used in Cosmetics Status: Final Report Release Date: July 7, 2016 Panel Meeting Date: June 6-7, 2016 The 2016 Cosmetic Ingredient Review

More information

Ingredients. on the spot! instant stain remover pen Natural enzymes (protein) and plant derived non-ionic glucopon surfactants (alkyl glucoside).

Ingredients. on the spot! instant stain remover pen Natural enzymes (protein) and plant derived non-ionic glucopon surfactants (alkyl glucoside). Sometimes even the safe, natural ingredients found in our cleaning products look scary or unfamiliar when called by their official names. Orange oil goes by Citrus Aurantium Dulcis sometimes, but it s

More information

Vitacyclix Product List

Vitacyclix Product List Vitacyclix Product List Bioflavonoids Grapefruit Bioflavonoid Complex Extract of grapefruit containing naringin, hesperidin, neohesperidin and poncrin 20% Grapefruit Bioflavonoid Complex Extract of grapefruit

More information

The Elms Oxford Rd Chieveley Newbury RG20 8RT United Kingdom Telephone: Fax:

The Elms Oxford Rd Chieveley Newbury RG20 8RT United Kingdom Telephone: Fax: The Elms Oxford Rd Chieveley Newbury RG20 8RT United Kingdom Telephone: +44 1635 248830 Fax: +44 1635 247206 Email: innova47@aol.com SAFETY ASSESSMENT Product: AW Soaps (Ancient Wisdom) The following Safety

More information

peg-150 distearate, tocopheryl acetate, polyquaternium-7, glyceryl acrylate acrylic acid copolymer,

peg-150 distearate, tocopheryl acetate, polyquaternium-7, glyceryl acrylate acrylic acid copolymer, Orange Cocoa And Cream Shampoo, Shower Gel & Bubble Bath: Aqua/Water/Eau, Sodium Laureth Sulfate, Lauryl Betaine, Parfum/Fragrance, Acrylates Copolymer, Glycerin, Glycol Distearate, Disodium Laureth Sulfosuccinate,

More information

Ingredients. biodegradable; derived from corn sugars biodegradable; derived from plants

Ingredients. biodegradable; derived from corn sugars biodegradable; derived from plants Ingredients Sometimes even the safe, natural ingredients found in our cleaning products look scary or unfamiliar when called by their official names. Orange oil goes by Citrus Aurantium Dulcis sometimes,

More information

Safety Assessment of Alkyl Taurate Amides and Taurate Salts as Used in Cosmetics

Safety Assessment of Alkyl Taurate Amides and Taurate Salts as Used in Cosmetics Safety Assessment of Alkyl Amides and Salts as Used in Cosmetics Status: Final Report Release Date: February 8, 2016 Panel Meeting Date: December 14-15, 2015 The 2015 Cosmetic Ingredient Review Expert

More information

Import Health Standard

Import Health Standard Import Health Standard F Fresh Citrus spp. for Human Consumption MPI.IHS.FP.CITRUS Issued under the TITLE Import Health Standard: Fresh Citrus spp. for Human Consumption COMMENCEMENT This Import Health

More information

The Good, The Bad & The Ugly: Formulation Tips for Traditional Preservatives. Personal Care Products Council Microbiology Seminar

The Good, The Bad & The Ugly: Formulation Tips for Traditional Preservatives. Personal Care Products Council Microbiology Seminar The Good, The Bad & The Ugly: Formulation Tips for Traditional Preservatives Personal Care Products Council Microbiology Seminar October 24, 2013 Chuck Jones The Dow Chemical Company Lest You Think Preservative

More information

To: Member Associations (FOR ACTION) Members of the Scientific Committee. Cc: RIFM Customer Associations Members of the JAG.

To: Member Associations (FOR ACTION) Members of the Scientific Committee. Cc: RIFM Customer Associations Members of the JAG. To: Member Associations (FOR ACTION) Members of the Scientific Committee Cc: RIFM Customer Associations Members of the JAG June 10, 2015 NOTIFICATION OF IFRA STANDARDS No. 13 48 th Amendment to the IFRA

More information

U.S. Environmental Protection Agency Office of Pesticide Programs List of Inert Pesticide Ingredients List 4A - Minimal Risk Inert Ingredients - By

U.S. Environmental Protection Agency Office of Pesticide Programs List of Inert Pesticide Ingredients List 4A - Minimal Risk Inert Ingredients - By U.S. Environmental Protection Agency Office of Pesticide Programs List of Inert Pesticide Ingredients List - Minimal Risk Inert Ingredients - By Chemical Name Inert Ingredients Ordered Alphabetically by

More information

Amended Safety Assessment of Butyl Polyoxyalkylene Ethers as Used in Cosmetics

Amended Safety Assessment of Butyl Polyoxyalkylene Ethers as Used in Cosmetics Amended Safety Assessment of Butyl Polyoxyalkylene Ethers as Used in Cosmetics Status: Final Amended Report Release Date: May 22, 2017 Panel Meeting Date: April -11, 2017 The 2017 Cosmetic Ingredient Review

More information

CHEMICAL IDENTITY. INCI NAME: propylene glycol IUPAC: propane-1,2-diol CAS: EC NUMBER: EMPIRICAL FORMULA: C3H8O2 STRUCTURAL FORMULA:

CHEMICAL IDENTITY. INCI NAME: propylene glycol IUPAC: propane-1,2-diol CAS: EC NUMBER: EMPIRICAL FORMULA: C3H8O2 STRUCTURAL FORMULA: PROPYLENE GLYCOL CHEMICAL IDENTITY INCI NAME: propylene glycol IUPAC: propane-1,2-diol CAS: 57-55-6 EC NUMBER: 200-338-0 EMPIRICAL FORMULA: C3H8O2 STRUCTURAL FORMULA: PHYSICAL FORM: Colourless Transparent

More information

Safety Assessment of Silicates as Used in Cosmetics

Safety Assessment of Silicates as Used in Cosmetics Safety Assessment of Silicates as Used in Cosmetics Status: Re-Review for Panel Review Release Date: May 23, 2018 Panel Meeting Date: June 4-5, 2018 The 2018 Cosmetic Ingredient Review Expert Panel members

More information

EUROPEAN FOOD SAFETY AUTHORITY

EUROPEAN FOOD SAFETY AUTHORITY EUROPEAN FOOD SAFETY AUTHORITY Call for scientific data on food additives permitted in the EU and belonging to the functional classes of emulsifiers, stabilisers and gelling agents Published: 23 November

More information

Variations (A16619) Ingredients:

Variations (A16619) Ingredients: Variations (A16619) Ingredients: Amazing Grace Shower Gel: Aqua/Water/Eau, Sodium Laureth Sulfate, Lauryl Betaine, Polysorbate 20, Parfum/Fragrance, Ppg-2 Hydroxyethyl Cocamide, Peg-18 Glyceryl Oleate/Cocoate,

More information

Agenda Item 4(c) CX/MMP 08/8/6 October 2007

Agenda Item 4(c) CX/MMP 08/8/6 October 2007 E Agenda Item 4(c) CX/MMP 08/8/6 October 2007 JOINT FAO/WHO FOOD STANDARDS PROGRAMME CODEX COMMITTEE ON MILK AND MILK PRODUCTS Eighth Session Queenstown, New Zealand, 4-8 February 2008 PROPOSED DRAFT AMENDMENT

More information

Safety Assessment of Pyrus malus (Apple)-derived Ingredients as Used in Cosmetics

Safety Assessment of Pyrus malus (Apple)-derived Ingredients as Used in Cosmetics Safety Assessment of Pyrus malus (Apple)-derived Ingredients as Used in Cosmetics Status: Draft Report for Panel Review Release Date: May 22, 2015 Panel Date: June 15-16, 2015 The 2015 Cosmetic Ingredient

More information

Safety Assessment of Alkonium Clays as Used in Cosmetics

Safety Assessment of Alkonium Clays as Used in Cosmetics Safety Assessment of Alkonium Clays as Used in Cosmetics Status: Draft Report for Panel Review Release Date: May 22, 2015 Panel Meeting Date: June 15-16, 2015 The 2015 Cosmetic Ingredient Review Expert

More information

Soil Composition. Air

Soil Composition. Air Soil Composition Air Soil Included Air Approximately 40 to 60% of the volume of a soil is actually empty space between the solid particles (voids). These voids are filled with air and/or water. The air

More information