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

Transcription

1 Memo Agenda Minutes Priorities Read-across Re-review Summary of Lard ADMIN CIR EXPERT PANEL MEETING JUNE 12 13, 2017

2 Commitment & Credibility since 1976 MEMORANDM To: From: Subject: Date: CIR Expert Panel Members and Liaisons Director, CIR rd 143 Meeting of the CIR Expert Panel Monday and Tuesday, June 12-13, 2017 May 19, 2017 Welcome to our June 2017 Panel meeting. CIR is in a leadership transition phase, but we are all set and ready for our second meeting of the year. rd Enclosed are the agenda and accompanying materials for the 143 CIR Expert Panel Meeting to be held on June 12-13, The location again is the Loews Madison Hotel, 1177 Fifteenth Street, NW, Washington, DC Phone: (202) Fax: (202) The meeting agenda includes the consideration of 8 ingredient groups advancing in the review process, 5 re-reviews, and one re-review summary. Following up on the Panel s continuing standardization of the use of read-across in reports, the agenda also includes a read-across and inference guidance document for discussion. Lastly, the agenda includes a review of the final draft of the 2018 CIR Priority List of ingredients, which will be finalized at this meeting. Schedule and hotel accommodations We have reserved rooms for the nights of Sunday, June 11 and Monday June 12, at the Loews Madison Hotel. If you encounter travel problems, please contact Monice on her cell phone at Team Meetings Re-Review Reports there are 4 safety assessments to re-review and decide either to reaffirm or to reth open to revise the conclusion or add ingredients. The Panel has already agreed to reopen the 5 rereview, Parabens, which should progress towards a Tentative Report or Insufficient Data Announcement. 1. Biotin (agenda and flash drive name Biotin). In 2001, the Panel published a Final Report on the Safety Assessment of Biotin. Based on the available data, the Panel concluded that Biotin is safe as used in cosmetics. No additional ingredients are proposed for inclusion. The frequency of use of this ingredient has increased since 2001, but the maximum concentration of use has decreased. The Panel should review the document and determine whether the original conclusion should be reaffirmed or the report re-opened for reconsideration. If there is a reason to re-open the safety assessment, please identify any data needs and discussion points. 2. Glyoxal (agenda and flash drive name Glyoxal). After the original report in 1995 was published with an insufficient data conclusion, the Panel reassessed the safety of Glyoxal and published an amended report in 2000 with the conclusion of safe for use in products intended to be applied to the nail at concentrations 1.25%. The available data were determined to be insufficient to support the safety for other uses. New data have been added to the report and the Panel should consider whether there is a reason to re-open the review, or if the conclusion published in 2000 should be reaffirmed.

3 3. Fatty Amidopropyl N,N-Dimethyl-2-Hydroxyethylammonium Chlorides (agenda and flash drive name - Quaternium-26) In 2000, the Panel published a final report on the safety of Quaternium-26 (a quaternary ammonium salt) and, based on the available animal and clinical data in the report, concluded that this ingredient is safe in the present practices of use. The conclusion also stated that Quaternium-26 should not be used in products in which N-nitroso compounds may be formed. Because no new data were available, the Panel needs to first determine whether or not there is any reason to reopen the safety assessment of Quaternium-26 for cause. However, in 2015 the Panel agreed to add two ingredients, Hydroxyethyl Cetearamidopropyl Dimonium Chloride and Hydroxyethyl Erucamidopropyl Dimonium Chloride, to this re-review. If the Panel determines that their original conclusion is still valid and should be reaffirmed, then the Panel should still reopen the report to add the 2 additional quaternary ammonium salts. 4. Malic Acid and Sodium Malate (agenda and flash drive name Malic Acid). In 2001, the Panel published the Final Report on the Safety Assessment of Malic Acid and Sodium Malate. Based on the available animal and clinical data available at that time, the Panel concluded that Malic Acid and Sodium Malate are safe for use as ph adjusters in cosmetic formulations; however, the Panel determined that the data were insufficient to determine the safety of these ingredients for any other functions. The data needs, based on the reported function for Sodium Malate (skin conditioning agent humectant), were concentration of use data, dermal irritation and sensitization data, and ocular irritation data. The frequency of use and concentrations have increased. After reviewing the available data, the Panel should determine whether the published final report on Malic Acid and Sodium Malate should be re-opened to amend the original conclusion, or if the original conclusion should be reaffirmed. If the decision to re-open is made, the Panel should consider whether the available data on fumaric acid and/or succinic acid should be included in the amended safety assessment to be used as read-across where there are notable data gaps, specifically with regards to carcinogenicity. 5. Parabens (agenda and flash drive name Parabens). This report includes the combination of 7 ingredients that were reviewed previously (4 total reports, last published in 2008) and 13 ingredients for which safety has not yet been assessed. In 2016, Sodium Methylparaben was included on the CIR 2017 Priority List due to the number of uses reported in the FDA s VCRP database. Although it has not been 15 years, the Panel agreed it was appropriate to look again at the paraben ingredients that were previously reviewed together with additional paraben and paraben salt ingredients, which have not yet been reviewed. The Panel should review the available data to either affirm or to change the conclusion of the 2008 report for the original seven paraben ingredients. The Panel should also determine whether this conclusion can be applied to the newly added ingredients or a split conclusion is warranted. Whether the conclusion remains the same (and extends to all of the new ingredients) or is changed and/or split, the Panel should form a conclusion of safety and explain the basis of the conclusion for the Discussion. The Panel should issue a Tentative Amended Report if appropriate. However, if the new data information (and/or added ingredients) raise new questions that are not answered by the available data, then an Insufficient Data Announcement should be issued, including a list of data needs. Draft Reports - there are 2 draft reports for review. 1. Polysilsesquioxanes (agenda and flash drive name Polysilsesquioxanes) This is the first time that the Panel is seeing this report on 18 polysilicone ingredients. In April 2017, an SLR was issued with an invitation for submission of data on these ingredients. Concentration of use data were submitted. Data for Polymethylsilsesquioxane and Polymethylsilsesquioxane/ Trimethylsiloxysilicate were also submitted, including data on chemical and physical properties, a reverse mutation assay, HRIPTs, and a phototoxicity test. If no further data are needed, the Panel should develop a Discussion and issue a Tentative Report. If more data are required, the Panel should list the data that are needed for a conclusion of safety, and issue an Insufficient Data Announcement. 2. Tissue-Derived Proteins and Peptides (agenda and flash drive name Tissue-Derived Proteins). This is the first time that the Panel is seeing this report on 19 tissue-derived ingredients. In April 2017, CIR issued the SLR for these ingredients, which mainly function as skin and hair conditioning agents in personal care products. However, the majority of the ingredients in this report were originally included in a larger hydrolyzed source proteins safety assessment from At the time, the Panel decided to divide the ingredients in that larger report into smaller, Page rd Meeting of the CIR Expert Panel Monday and Tuesday, June 12-13, 2017

4 more manageable safety assessments, with Hydrolyzed Wheat Protein and Hydrolyzed Wheat Gluten being the first ingredients reviewed. The Panel agreed upon this grouping of the 19 ingredients at the September 2015 meeting. If no further data are needed, the Panel should formulate a Discussion and issue a Tentative Report. However, if additional data are required, the Panel should be prepared to identify the data needs and issue an Insufficient Data Announcement. Tentative Reports there are 4 draft tentative reports. 1. Monoalkylglycol Dialkyl Acid Esters (agenda and flash drive name Glycol Esters). At the December 2016 meeting, the Panel issued an Insufficient Data Announcement. The requests were for dermal penetration data for Diethylpentanediol Dineopentanoate, Dioctadecanyl Didecyltetradecanoate, and Dioctadecanyl Ditetradecyloctadecanoate; if there is dermal absorption for any of the three ingredients, then: 28-day dermal toxicity and genotoxicity test data, and irritation and sensitization tests at maximum concentration of use or greater ( 57%) are needed; because these ingredients can potentially form ester hydrolysis products, toxicity data on the potential hydrolysis products, including Diethylpentanediol Dineopentanoate, Ethylpentanediol, Neopentanoic Acid, Dioctadecanyl Didecyltetradecanoate, Octadecanol, Decyltetradecanoic Acid, and Tetradecyloctadecanoic Acid are needed. Summaries of the data presented in an MSDS of Diethylpentanediol Dineopentanoate were provided. No other data have been submitted to address the IDA. VCRP data have been updated. The Panel should come to a conclusion of safety for these ingredients (which may include an insufficient data conclusion), develop the Discussion, and issue a Tentative Report 2. Persulfates (agenda and flash drive name Persulfates) In 2001, the Panel published a Final Report with the conclusion that Ammonium Persulfate, Potassium Persulfate, and Sodium Persulfate are safe as used as oxidizing agents in hair colorants and lighteners designed for brief discontinuous use followed by thorough rinsing from the hair and skin. In 2016, the Panel reopened the report and issued a Draft Amended Report that was reviewed at the December 2016 Panel meeting. Review of the Draft Amended Report resulted in the Panel s issuance of an Insufficient Data Announcement with the following 2 data requests on the 3 persulfates: 1) No-Observed-Effect-Level (NOEL) for sensitization and urticaria 2) Concentrations of use in leave-on products and dentifrices To date, responses to the data request have not been received. VCRP data have been updated. The Panel should determine whether or not a Tentative Amended Report with the original conclusion for the use of persulfates in hair coloring preparations (rinse-off products), and an insufficient data conclusion for the use of these ingredients in leave-on products and dentifrices, should be issued at this Panel meeting. 3. Plant-Derived Proteins and Peptides (agenda and flash drive name Plant-Derived Proteins). At the December 2016 meeting, the Panel determined that the data were sufficient for 18 of the 19 plant-derived proteins and peptides and concluded that these ingredients are safe for use in the present practices of use and concentration. However, the Panel issued an insufficient data announcement for Hydrolyzed Maple Sycamore Protein, with the remaining data needed to evaluate the safety of this ingredient including: 1) Method of manufacturing 2) Chemical composition and impurities 3) Clarification on food safety status, specifically whether this ingredient is generally recognized as safe (GRAS). If this ingredient is not GRAS, then studies of systemic endpoints such as a 28-day dermal toxicity, reproductive and developmental toxicity, and genotoxicity are needed, as well as UV absorption spectra No data have been received. VCRP data have been updated. The Panel should carefully review the draft Abstract, Discussion, and Conclusion of this report, and issue a tentative report (possibly with a split conclusion). Page rd Meeting of the CIR Expert Panel Monday and Tuesday, June 12-13, 2017

5 4. Polyaminopropyl Biguanide (polyhexamethylene biguanide hydrochloride) (agenda and flash drive name - Polyaminopropyl Biguanide). An Insufficient Data Announcement with the following data requests was issued at the April 10-11, 2017 Expert Panel meeting: (1) Skin sensitization data to determine a no-effect-level for Polyaminopropyl Biguanide (polyhexamethylene biguanide hydrochloride)-induced sensitization (2) Data needed to evaluate anaphylactic reactions to Polyaminopropyl Biguanide (polyhexamethylene biguanide hydrochloride) in case studies (3) Data from Korean studies on lung injury/mortalities attributable to exposure to a structurallyrelated disinfectant (polyhexamethylene guanidine (PHMG) phosphate) used in humidifiers. Data have been received and incorporated into the report. Because of copyright restrictions, some of the requested information is not included with the report package. After reviewing the available data, the Panel should determine whether a Tentative Report with a safe as used, safe with qualifications, insufficient data, or unsafe conclusion should be issued at this meeting. Final Reports - there are 2 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. Ethers and Esters of Ascorbic Acid (agenda and flash drive name - Ethers Esters of Ascorbate). At the December 2016 meeting, the Panel issued a tentative report for public comment with the conclusion that 7 ethers and esters of Ascorbic Acid are safe in the present practices of use and concentration described in the safety assessment. Updated frequency of use data have been added. Technical comments have been addressed. 2. Hydroxyethyl-3,4-Methylenedioxyaniline HCl (agenda and flash drive name Hair Dye - HMA). At the December 2016 meeting, the Panel issued a tentative report for public comment with the conclusion of safe for use as a hair dye ingredient in the present practices of use and concentrations described in this safety assessment; the Panel noted that this ingredient should not be used in cosmetic products in which N-nitroso compounds can be formed. Requested edits were made to the document, and technical comments have been addressed. VCRP data were updated; the number of reported uses did not change. Other Items there are 3 other items of business for consideration, comprising a re-review summary, a read-across report usage document and finalization of the 2018 Priorities. 1. Lard and Lard-Derived ingredients (agenda and flash drive name Lard). At the April 2017 meeting the Panel determined to not reopen this safety assessment and reaffirmed the original conclusion that Lard, Hydrogenated Lard, Lard Glyceride, Hydrogenated Lard Glyceride, Lard Glycerides, and Hydrogenated Lard Glycerides are safe as cosmetic ingredients in the practices of use and concentration. 2. Read-Across Report Usage (agenda and flash drive name Read-Across Report Usage). This is the first draft of a guidance document for standardizing the reporting of read-across in CIR safety assessment reports. The Panel should have a full discussion of what they would like to see in such a document and how they would like to see read-across reported in the safety assessments. 3. Priorities (agenda and flash drive name Priorities). At the April 2017 meeting, the Panel assessed the Draft 2018 Priorities List. Comments have been incorporated into the current draft and input has been provided by the CIR Science and Support Committee. The Panel should finalize the 2018 Priorities. Page rd Meeting of the CIR Expert Panel Monday and Tuesday, June 12-13, 2017

6 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 2 reports to be issued as final safety assessments, followed by the remaining reports advancing in the process, including the re-reviews, the re-review summary, the read-across guidance document, and the 2018 Priorities. The majority of the agenda involves reviewing the tentative reports and re-reviews. It is likely that the full Panel session will conclude before lunch on day 2, so plan your travel accordingly. Have a safe journey! Page rd Meeting of the CIR Expert Panel Monday and Tuesday, June 12-13, 2017

7 Agenda 143 rd Cosmetic Ingredient Review Expert Panel Meeting June 12-13, 2017 The Loews Madison Hotel th Street, N.W. Washington, D.C Monday, June 12 8:00 am CONTINENTAL BREAKFAST 8:30 am WELCOME TO THE 143 rd EXPERT PANEL TEAM MEETINGS Drs. Bergfeld/Heldreth 8:40 am TEAM MEETINGS Drs. Marks/Belsito Dr. Marks Team* Dr. Belsito s Team RR (MF) Biotin Admin (BH) Read-Across Report Usage TR (CB) Plant-Derived Proteins Admin (BH) Priorities DR (CB) Tissue-Derived Proteins FR (LS) Hair Dye - HMA RR (CB) Malic Acid FR (WJ) Ethers Esters of Ascorbate RRsum (LB) Lard RR (WJ) Quaternium-26 RR (IB/LB) Parabens TAR (WJ) Persulfates RR (LB) Glyoxal TR (WJ) Polyaminopropyl Biguanide DR (LB) Polysilsesquioxanes TR (CB) Plant-Derived Proteins TR (LB) Glycol Esters DR (CB) Tissue-Derived Proteins FR (WJ) Ethers Esters of Ascorbate RR (CB) Malic Acid RR (WJ) Quaternium-26 RRsum (LB) Lard TAR (WJ) Persulfates RR (LB) Glyoxal TR (WJ) Polyaminopropyl Biguanide DR (LB) Polysilsesquioxanes FR (LS) Hair Dye - HMA TR (LB) Glycol Esters Admin (BH) Read-Across Report Usage RR (IB/LB) Parabens Admin (BH) Priorities RR (MF) Biotin Noon 1:00pm 5:00 pm Lunch for Panel, liaisons, and staff FR: Final Report TR: Tentative Report TAR: Tentative Amended Report DR: Draft Report RR: Re-review RRsum: Re-review summary 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.

8 Tuesday, June 13 8:00 am CONTINENTAL BREAKFAST 8:30 am WELCOME TO THE 143 rd FULL CIR EXPERT PANEL MEETING Dr. Bergfeld 8:45 am Admin MINUTES OF THE APRIL 2017 EXPERT PANEL MEETING Dr. Bergfeld 9:00 am DIRECTOR S REPORT Dr. Heldreth 9:10 am FINAL REPORTS, REPORTS ADVANCING TO THE NEXT LEVEL, OTHER ITEMS Final Reports FR (LS) FR (WJ) Hair Dye - HMA Dr. Marks reports Ethers Esters of Ascorbate Dr. Belsito reports Reports Advancing RR (WJ) TAR (WJ) TR (WJ) TR (CB) DR (CB) RR (CB) RR (MF) RR (IB/LB) RR (LB) DR (LB) TR (LB) Quaternium-26 Dr. Marks reports Persulfates Dr. Belsito reports Polyaminopropyl Biguanide Dr. Marks reports Plant-Derived Proteins Dr. Belsito reports Tissue-Derived Proteins Dr. Marks reports Malic Acid Dr. Belsito reports Biotin Dr. Marks reports Parabens Dr. Belsito reports Glyoxal - Dr. Marks reports Polysilsesquioxanes Dr. Belsito reports Glycol Esters Dr. Marks reports Other Items RRsum (LB) Admin (BH) Admin (BH) Lard Dr. Belsito reports Read-Across Report Usage Dr. Marks reports Priorities Dr. Belsito reports ADJOURN - Next meeting Monday and Tuesday, September 11-12, 2017 at The Loews Madison Hotel th Street, N.W., Washington, DC FR: Final Report TR: Tentative Report TAR: Tentative Amended Report DR: Draft Report RR: Re-review RRsum Re-review summary

9 ONE HUNDRED FORTY-SECOND MEETING OF THE EXPERT PANEL April 10-11, 2017 Loews Madison Hotel Washington, D.C. Expert Panel Members Wilma F. Bergfeld, M.D., Chair Donald V. Belsito, M.D. Liaison Representatives Consumer Absent Ronald A. Hill, Ph.D. Curtis D. Klaassen, Ph.D. Daniel C. Liebler, Ph.D. Industry Beth A. Jonas, 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, M.D., M.P.H. (Absent) Adopted (Date) Wilma F. Bergfeld, M.D.

10 Others Present at the Meeting Jay Ansell Robena Aziz Lillian Becker Don Bjerke Ivan Boyer Roshil Budhram Kristen Buono Christina Burnett Pete Colombo Kapal Dewa Monice Fiume Kevin Fries Lillian Gill Dave Gossai Jaspreet Gujral Bart Heldreth Carla Jackson Wilbur Johnson, Jr. Julia Linthicum Damani Parran Goran Periz Laura Scott Louise Walter PCPC FDA CIR P & G CIR L-Brands Presperse CIR DTL FDA CIR CIR CIR L Oreal Avon CIR CIR CIR CIR Akzo FDA CIR GULC

11 CHAIRMAN S OPENING REMARKS MINUTES FROM THE 142 nd CIR EXPERT PANEL MEETING The 142 nd meeting of the Cosmetic Ingredient Review (CIR) Expert Panel was called to order at 8:30 a.m by Dr. Wilma Bergfeld, and all attendees were welcomed. She noted that 15 ingredient reports, 6 of which are final reports, and the 2018 CIR Priority List were reviewed in Teams on the preceding day. Other Team discussion topics, for which position papers had been prepared for review, included the hair dye epidemiology boilerplate update, endocrine activity and endocrine disruption, aerosols, and information sources for CIR safety assessments. Comments relating to these topics were made by Panel members and additional comments are anticipated. Dr. Bergfeld stated that the document on endocrine activity and endocrine disruption will be available for Panel review at the June 2017 meeting, and, at some point, will be subjected to a public comment period. Additionally, the CIR Precedents Aerosols document (Aerosols Document) will be available for review at the June meeting, and a review of read-across criteria will be included on the meeting agenda. Dr. Bergfeld mentioned the Panel s awareness of an increase in the number of botanical ingredients entering the CIR review process, and noted that difficulties are associated with reviewing ingredients in this category. Dr. Bergfeld thanked the CIR staff for the excellent preparation of documents for review, and noted that document quality continues to improve. APPROVAL OF MINUTES The minutes of the December 5-6, 2016 CIR Expert Panel meeting were unanimously approved. DIRECTOR S REPORT Dr. Gill congratulated Dr. Paul Snyder on his election to a 3-year term as President-elect, President and Past- President of the Society of Toxicologic Pathology. This organization is the world leader in preclinical safety testing. This past February, Dr. Bergfeld, Dr. Heldreth, and Ms. Fiume were invited to Beijing by the China Association of Flavor and Fragrance Cosmetics Industry (CAFFCI) to present on the scientific integrity and rigor of the CIR process before regulatory officials and scientists of the China Food and Drug Administration (CFDA). This is the second time in as many years that CIR has been asked to address CFDA. This year, the participants were particularly interested in learning about the CIR Expert Panel s experiences assessing the safety of botanical ingredients, which was the focus of Ms. Fiume s presentation. CFDA expressed an interest in gaining a more refined understanding of the CIR process. Dr. Gill extended an invitation to members of CAFFCI and the CFDA to attend a future Panel meeting and to meet with the CIR staff. Dr. Heldreth was an invited speaker at the regional meeting of the Society of Cosmetic Chemists in March. He presented on the process and value of CIR. Finally, Dr. Gill announced that she is stepping down as the Director of CIR in early June. She acknowledged the CIR staff for the incredible work that they produce; the CIR Expert Panel for their renowned scientific expertise and contributions to the safety assessment process; and all of the others who partner with CIR and participate in the CIR process to help ensure the safety of personal care products. Final Safety Assessments Acryloyldimethyltaurate Polymers The Expert Panel issued a final report with the conclusion that the following 21 acryloyldimethyltaurate polymers are safe in cosmetics in the present practices of use and concentration described in the safety assessment:

12 Acrylamide/Sodium Acryloyldimethyltaurate Copolymer Acrylamide/Sodium Acryloyldimethyltaurate/Acrylic Acid Copolymer* Ammonium Acryloyldimethyltaurate/Beheneth-25 Methacrylate Crosspolymer Ammonium Acryloyldimethyltaurate/Carboxyethyl Acrylate Crosspolymer Ammonium Acryloyldimethyltaurate/Laureth-7 Methacrylate Copolymer Ammonium Acryloyldimethyltaurate/Steareth-25 Methacrylate Crosspolymer* Ammonium Acryloyldimethyltaurate/Steareth-8 Methacrylate Copolymer Ammonium Acryloyldimethyltaurate/Vinyl Formamide Copolymer* Ammonium Acryloyldimethyltaurate/VP Copolymer Ammonium Polyacryloyldimethyl Taurate Dimethylacrylamide/Sodium Acryloyldimethyltaurate Crosspolymer HEA/Sodium Acryloyldimethyltaurate/Steareth-20 Methacrylate Copolymer Hydroxyethyl Acrylate/Sodium Acryloyldimethyl Taurate Copolymer Sodium Acrylate/Acryloyldimethyltaurate/Dimethylacrylamide Crosspolymer Sodium Acrylate/Sodium Acryloyldimethyl Taurate Copolymer Sodium Acrylate/Sodium Acryloyldimethyl Taurate/Acrylamide Copolymer Sodium Acryloyl Dimethyl Taurate/PEG-8 Diacrylate Crosspolymer* Sodium Acryloyldimethyl Taurate/Acrylamide/VP Copolymer Sodium Acryloyldimethyltaurate/Methacrylamidolauric Acid Copolymer Sodium Acryloyldimethyltaurate/VP Crosspolymer Sodium Polyacryloyldimethyl Taurate * 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 the group. The Panel noted that these are large molecules and that dermal penetration would be unlikely to occur. The Panel advised that formulators should use current good manufacturing practices (cgmps) to ensure that residual monomers (e.g., vinyl formamide and methacrylamidolauric acid) are minimized in these ingredients and the final products. The Panel noted that the presence of acrylamide is restricted to < 5 ppm in cosmetic formulations containing Polyacrylamide, and that this limit was also appropriate for the acryloyldimethyltaurate polymers. In 2017, Ammonium Acryloyldimethyltaurate/VP Copolymer was reported to be used in 584 formulations, including 524 leave-on products and 60 rinse-off products. Hydroxyethyl Acrylate/Sodium Acryloyldimethyl Taurate Copolymer has the highest reported maximum concentration of use; it is reported to be used at < 4.3% in depilatories (rinse-off products) and < 3.6% in eyeliner and eye shadow (leave-on products). Butyl Polyoxyalkylene Ethers The Expert Panel issued a final amended report with the conclusion that the following 46 butyl polyoxyalkylene ethers are safe in cosmetics in the present practices of use and concentration described in the safety assessment when formulated to be non-irritating: Buteth-3 PPG-2-Buteth-1* PPG-2-Buteth-2* PPG-2-Buteth-3* PPG-3-Buteth-5* PPG-4-Buteth-4* PPG-5-Buteth-5 PPG-5-Buteth-7* PPG-7-Buteth-4 PPG-7-Buteth-10 PPG-9-Buteth-12 PPG-10-Buteth-9* PPG-12-Buteth-12* PPG-12-Buteth-16 PPG-15-Buteth-20 PPG-17-Buteth-17 PPG-19-Buteth-19* PPG-20-Buteth-30 PPG-24-Buteth-27* PPG-26-Buteth-26 PPG-28-Buteth-35 PPG-30-Buteth-30* PPG-33-Buteth-45 PPG-36-Buteth-36* PPG-38-Buteth-37 PPG-2 Butyl Ether PPG-3 Butyl Ether* PPG-4 Butyl Ether* PPG-5 Butyl Ether* PPG-9 Butyl Ether* PPG-12 Butyl Ether* PPG-14 Butyl Ether PPG-15 Butyl Ether* PPG-16 Butyl Ether* PPG-17 Butyl Ether* PPG-18 Butyl Ether* PPG-20 Butyl Ether* PPG-22 Butyl Ether* PPG-24 Butyl Ether* PPG-26 Butyl Ether* PPG-30 Butyl Ether* PPG-33 Butyl Ether PPG-40 Butyl Ether PPG-52 Butyl Ether PPG-53 Butyl Ether* Propylene Glycol Butyl Ether*

13 *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. Twenty-three of these ingredients were reviewed previously; 4 were reviewed in 2000 and found to be safe as used and 19 were reviewed in 2001 and found to be safe when formulated to avoid irritation. The Panel s conclusion at this meeting supersedes the conclusion from in 2000 for PPG-12-Buteth-16, PPG-9-Buteth-12, PPG-26-Buteth-26, and PPG-28-Buteth-35. Because of the potential for dermal irritation, the Panel specified that products containing these ingredients must be formulated to be non-irritating. Also, some of the ingredients in this group are ethoxylated; therefore, the Panel specified that industry should use current good manufacturing practices (cgmp) to minimize the presence of ethylene glycol and dioxanes in finished products. The Panel noted that, although the smaller ingredients are more rapidly absorbed, the weight of the evidence clearly indicates low systemic toxicity across the group. The Panel determined that information reported for poly[oxy(methyl-1,2-ethanediyl)]-α-butyl-ω-hydroxy- [(butoxymethylethoxy)methylethoxy]propan-1- ol, and 1-(2-butoxy-1-methylethoxy)-propan-2-ol is appropriate for read-across in this report. The ingredients and endpoints for which this information is applied are identified in the report. Etidronic Acid and its Salts The Expert Panel issued a final report with the conclusion that the following 4 ingredients are safe in cosmetics in the present practices of use and concentration described in the safety assessment. Etidronic Acid Disodium Etidronate Tetrapotassium Etidronate Tetrasodium Etidronate The Panel acknowledged the moderately widespread clinical use of these ingredients to treat bone diseases and determined that there are no systemic concerns about their use in cosmetics based on the data presented. Although there were no available phototoxicity or photosensitization data, the Panel agreed that these ingredients are not expected to absorb UV light, based on the chemical structures. Inhalation toxicity data on sodium etidronate and genotoxicity data on sodium etidronate and trisodium etidronate were used to address concerns about the lack of inhalation toxicity data and the minimal genotoxicity data available for the other ingredients in this safety assessment. In 2017, Etidronic Acid was reported to have the greatest number of uses (362) in cosmetic formulations. Etidronic Acid also had the highest reported maximum concentration of use in rinse-off products (0.9% in other hair coloring preparations) and in leave-on products (0.12% in the category of other fragrance preparations). Hydrofluorocarbon 152a The Expert Panel issued a final report with the conclusion that Hydrofluorocarbon 152a is safe in cosmetics in the present practices of use and concentration described in the safety assessment. This ingredient is a gas (at standard temperature and pressure) that functions as a propellant and is used at concentrations < 80% in hair sprays and 35% in underarm deodorants. Hydrofluorocarbon 152a is largely inert, is rapidly volatilized and dispersed upon application, and is quickly cleared from the body by exhalation. The Panel found the overall safety profile of this ingredient to be favorable, and concluded that it is safe for use in cosmetics. The Panel noted that the European Union has issued regulations restricting the use of fluorinated gases in personal care and household products. The regulations are directed toward protection of the global environment, which falls outside of the Panel s purview of personal use safety.

14 Rosa canina-derived Ingredients The Expert Panel issued a final report with the conclusion that the following 12 Rosa canina-derived ingredients are safe in cosmetics in the present practices of use and concentration described in the safety assessment when formulated to be non-irritating and non-sensitizing: Rosa Canina Fruit Extract Rosa Canina Bud Extract* Rosa Canina Flower Rosa Canina Flower Extract Rosa Canina Flower Powder* Rosa Canina Flower Oil* Rosa Canina Fruit Rosa Canina Fruit Juice* Rosa Canina Leaf Extract Rosa Canina Seed* Rosa Canina Seed Extract Rosa Canina Seed Powder *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. Rosa canina (also known as dog rose) is an herb that belongs to the Rosaceae family. The highest use frequency is reported for Rosa Canina Fruit Extract (342 uses). The Council survey data indicate that Rosa canina-derived ingredients are being used in cosmetics at maximum ingredient use concentrations up to 1.5% (i.e., Rosa Canina Seed Extract in leave-on products (lipstick)). Tentative Safety Assessments Alkane Diols The Expert Panel issued a tentative report for public comment, with a split conclusion. The data for 1,4-Butanediol are insufficient to evaluate safety, and the following 9 alkane diols are safe in cosmetics in the present practices of use and concentration as described in the safety assessment: Propanediol 1,5-Pentanediol* Hexanediol Octanediol 1,10-Decanediol Methylpropanediol 2,3-Butanediol* Butyl Ethyl Propanediol Isopentyldiol *Not reported to be in current use. Were the ingredients in this group not currently in 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. Data received after the September 2016 CIR Expert Panel Meeting met many of the data needs identified therein. One outstanding need, however, is concentration of use of 1,4-Butanediol in cosmetics. Therefore, the Panel issued a conclusion of insufficient data for 1,4-Butanediol. Although no neurotoxicity data were found in the literature or submitted for Isopentyldiol, the Panel determined that acute oral toxicity data in mice showed no adverse clinical or histopathological changes and, therefore, specific neurotoxicity data was not needed. The Panel also concluded that there was no safety concern for the known neurotoxin, 2,5-hexanediol, being present as a possible impurity of Hexanediol. This conclusion was based on the low maximum concentration of Hexanediol reported to be used (0.5%) in leave-on products, the > 96% purity reported for Hexanediol, and research showing no adverse behavioral effects in rats subcutaneously exposed to 20 mg/kg/day 2,5-hexanedione for up to 50 days. Butyrospermum parkii (Shea)-Derived Ingredients The Expert Panel issued a revised tentative report for public comment with the amended conclusion that the following 13 ingredients are safe in cosmetics in the present practices of use and concentration described in the safety assessment when formulated to be non-sensitizing.

15 Butyrospermum Parkii (Shea) Butter Buyrospemum Parkii (Shea) Oil Butyrospermum Parkii (Shea) Butter Extract Butyrospermum Parkii (Shea) Butter Unsaponifiables Butyrospermum Parkii (Shea) Nut Extract Butyrospermum Parkii (Shea) Nut Shell Powder Butyrospermum Parkii (Shea) Seedcake Extract Hydrogenated Shea Butter Hydrogenated Shea Oil* Hydrolyzed Shea Seedcake Extract* Shea Butter Glyceride Shea Butter Glycerides Shea Oleine *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, because botanical ingredients are complex mixtures, there is concern that multiple botanical ingredients in one formulation may each contribute to the final concentration of a single shared constituent. Therefore, when formulating products, manufacturers should avoid reaching levels, in final formulations, of botanical constituents that may cause sensitization or other adverse effects. There are no safety test data for Butyrospermum Parkii (Shea) Nut Extract and Butyrospermum Parkii (Shea) Nut Shell Powder, and no safety test data for Butyrospermum Parkii (Shea) Seedcake Extract and Butyrospermum Parkii (Shea) Butter at maximum use concentrations (5.5% and 100% in leave-on products, respectively). However, human repeated insult patch tests (HRIPT) for Butyrospermum Parkii (Shea) Seedcake Extract and Butyrospermum Parkii (Shea) Butter were negative when tested at lower concentrations. Moreover, based on the Panel s clinical experience, absence of adverse event reports, and the negative safety test data on other ingredients, the Panel was not concerned about dermal irritation or sensitization potential following exposure to these ingredients. Humulus lupulus (Hops) Extract and Oil The Panel issued a tentative report with the conclusion that the following two ingredients are safe in cosmetics in the present practices of use and concentration as described in the safety assessment when formulated to be nonsensitizing: Humulus Lupulus (Hops) Extract Humulus Lupulus (Hops) Oil* *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. Since the September 2016 Panel meeting, the International Nomenclature of Cosmetic Ingredients (INCI) Committee issued new monographs for Humulus lupulus (hops)-derived ingredients. Humulus Lupulus (Hops) Extract is now defined as the extract of the inflorescence (hops cone) of Humulus lupulus (hops) and not the extract of the whole plant. The following names are no longer cosmetic ingredient names and have been revised so that they are now listed as technical names for Humulus Lupulus (Hops) Extract: Humulus Lupulus (Hops) Cone Extract, Humulus Lupulus (Hops) Flower Extract, Humulus Lupulus (Hops) Stem Extract, and Humulus Lupulus (Hops) Strobile. The INCI name Humulus Lupulus (Hops) Cone Oil has been revised to Humulus Lupulus (Hops) Oil, and is now defined as the volatile oil obtained from the inflorescence (hops cone) of Humulus lupulus. The Panel noted that, because botanical ingredients are complex mixtures, there is concern that multiple botanical ingredients in one formulation may each contribute to the final concentration of a single shared constituent. Therefore, when formulating products, manufacturers should avoid reaching levels, in final formulations, of botanical constituents that may cause sensitization or other adverse effects. Humulus Lupulus (Hops) Extract was reported to be used in 375 formulations, including 317 leave-on formulations and 54 rinse-off formulations, and used at concentrations < 0.2% in hair conditioners. The highest reported maximum concentration of use in products intended for dermal contact is 0.13% in eye lotions, deodorants, and other skin care preparations.

16 Bovine Milk Proteins and Protein Derivatives The Panel issued a tentative report for public comment with the conclusion that the 16 bovine milk proteins and protein derivatives listed below are safe in cosmetics in the present practices of use and concentration described in the safety assessment. Ammonium Caseinate* Calcium Caseinate* Casein Casein Extract Hydrolyzed Casein Hydrolyzed Lactalbumin* Hydrolyzed Milk Protein Hydrolyzed Whey Protein Hydrolyzed Yogurt Protein Lactoglobulin Milk Protein Milk Protein Extract Potassium Caseinate* Sodium Caseinate Sodium Hydrolyzed Casein* Whey 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. While the maximum reported use concentration of Sodium Caseinate is 96.9%, this concentration is in bath oils, tablets, and salts, which are diluted in water prior to use. The maximum concentration of use reported in the caseinderived ingredients is 2% in leave-on products. Safety test data of Hydrolyzed Casein were negative at concentrations up to 30%. These observations supported the Panel s safe as used conclusion for Sodium Caseinate at the concentrations in diluted bath products. The Panel noted that bovine milk proteins are known food allergens that can elicit Type I immediate hypersensitivity reactions when ingested by sensitized individuals. The Panel reviewed studies showing no relevant ocular irritation and no dermal irritation or sensitization in animals and human subjects. Additionally, no reported cases of Type I immediate hypersensitivity reactions from cosmetic use were reported in the literature, and the Panel has not found such reactions to bovine milk products in their clinical experience. Thus, the Panel concluded that the induction of Type I sensitivity to bovine milk proteins in cosmetics is not likely. Polyurethanes The Panel issued a tentative report on the following 66 polyurethanes with the conclusion that these ingredients are safe in cosmetics in the present practices of use and concentration described in the safety assessment when formulated to be non-sensitizing. Polyurethane-1 Polyurethane-2 Polyurethane-4* Polyurethane-5* Polyurethane-6 Polyurethane-7 Polyurethane-8 Polyurethane-9 Polyurethane-10 Polyurethane-11 Polyurethane-12* Polyurethane-13* Polyurethane-14 Polyurethane-15 Polyurethane-16 Polyurethane-17* Polyurethane-18 Polyurethane-19* Polyurethane-20* Polyurethane-21* Polyurethane-23* Polyurethane-24 Polyurethane-25* Polyurethane-26* Polyurethane-27* Polyurethane-28* Polyurethane-29* Polyurethane-32* Polyurethane-33 Polyurethane-34 Polyurethane-35 Polyurethane-36* Polyurethane-39 Polyurethane-40 Polyurethane-41* Polyurethane-42* Polyurethane-43* Polyurethane-44* Polyurethane-45* Polyurethane-46 Polyurethane-47* Polyurethane-48* Polyurethane-49* Polyurethane-50* Polyurethane-51* Polyurethane-52* Polyurethane-53* Polyurethane-54* Polyurethane-55* Polyurethane-56* Polyurethane-57* Polyurethane-58* Polyurethane-59* Polyurethane-60* Polyurethane-61* Polyurethane-62* Polyurethane-63* Polyurethane-64* Polyurethane-65* Polyurethane-66* Polyurethane-67* Polyurethane-68* Polyurethane-69* Polyurethane-70* Polyurethane-71* Polyurethane-72*

17 *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. Residual monomers would be expected to be either consumed in reaction or washed away in manufacturing and purification processes. Producers and formulators should use cgmp to prevent conditions wherein monomers could be released from these polymeric ingredients. Many of these polyurethanes are reported to be supplied as emulsions or solutions with multiple components, which may include sensitizers such as methylisothiazolinone (MI; e.g., Polyurethane-60 and -61). Suppliers and formulators should be aware of how these polymers ingredients are supplied, and should avoid reaching levels of components that may cause sensitization or other adverse health effects. Because some of these polyurethanes are supplied as emulsions or in solution, there is some confusion about the concentrations of the polyurethanes in the safety evaluation data. While these ingredients are reported to be supplied in emulsions or solutions at concentrations ranging from 20% to 66%, it is not always clear from the submitted data whether the concentrations reported are the concentrations of the polyurethane ingredients or of the emulsions or solutions tested. The Panel asked for clarification of the concentrations reported in these studies. Polyurethane-11 was reported to be used in 315 formulations, including 303 leave-on formulations and 12 rinse-off formulations. The other ingredients were reported to have uses in 33 or fewer formulations. Polyurethane-1 has the highest reported maximum concentration of use, < 15% in nail products. The highest maximum concentration of use reported for products resulting in leave-on dermal exposure is 7.5% for Polyurethane-33 in the other skin care preparations category. The other reported maximum concentrations of use were < 9% (in nail, hair, or rinse-off dermal preparations). Re-review Lard and Lard-Derived Ingredients The Expert Panel reaffirmed their prior conclusion that the following six lard-derived ingredients are safe as used in cosmetic products, provided that established limitations imposed on heavy metal and pesticide concentrations are not exceeded. Lard Hydrogenated Lard* Lard Glyceride Hydrogenated Lard Glyceride Lard Glycerides* Hydrogenated Lard Glycerides* *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 number of product formulations containing these ingredients did not increase significantly since the initial safety assessment, according to Voluntary Cosmetic Registration Program (VCRP) data received from the Food and Drug Administration (FDA). The maximum reported use concentration for Lard Glyceride decreased from 10% in 1984 to 1.6% in 2016, according to Council surveys. The established heavy metal and pesticide concentration limits for these ingredients are: lead 0.1 ppm; arsenic 3 ppm; mercury 1 ppm; and total PCB/pesticide contamination 40 ppm, with 10 ppm for any specific residue. Insufficient Data Announcements Mentha piperita (Peppermint)-Derived Ingredients The Panel agreed that the 2001 final report (published in 2001) on Mentha Piperita (Peppermint) Oil, Mentha Piperita (Peppermint) Leaf Extract, Mentha Piperita (Peppermint) Leaf, and Mentha Piperita (Peppermint) Leaf Water should be reopened to add 6 Mentha piperita (peppermint)-derived ingredients:

18 Mentha Piperita (Peppermint) Extract Mentha Piperita (Peppermint) Flower/Leaf/Stem Extract Mentha Piperita (Peppermint) Flower/Leaf/Stem Water Mentha Piperita (Peppermint) Leaf Cell Extract Mentha Piperita (Peppermint) Leaf Juice Mentha Piperita (Peppermint) Meristem Cell Culture The Panel issued an Insufficient Data Announcement with the following data requests for all ten ingredients: Skin irritation and sensitization data Composition, method of manufacture, and impurities data A CIR final report on Mentha piperita (peppermint)-derived ingredients was published in 2001 with a conclusion stating that the following ingredients are safe as used in cosmetic formulations: Mentha Piperita (Peppermint) Oil, Mentha Piperita (Peppermint) Leaf Extract, Mentha Piperita (Peppermint) Leaf, and Mentha Piperita (Peppermint) Leaf Water. The conclusion includes a statement indicating that the concentration of pulegone in these ingredients should not exceed 1%. Most of the data in the 2001 report are on Mentha Piperita (Peppermint) Oil. The Panel noted that this ingredient is included in the data requests particularly because the maximum use concentration of this ingredient in leave-on products has increased from 2% in 1997 (published in 2001 report) to 5% in Mentha Piperita (Peppermint) Leaf, Mentha Piperita (Peppermint) Leaf Extract, and Mentha Piperita (Peppermint) Leaf Water are included in the data requests because the prior published final report does not contain data on these ingredients. Panthenol, Pantothenic Acid, and Derivatives The Panel issued an Insufficient Data Announcement for this safety assessment, containing the following ingredients: Panthenol Pantothenic Acid Panthenyl Ethyl Ether Panthenyl Ethyl Ether Acetate Panthenyl Triacetate Calcium Pantothenate Sodium Pantothenate Additional data are needed to address the following insufficiencies: Method of manufacturing for Panthenyl Ethyl Ether, Panthenyl Ethyl Ether Acetate, and Panthenyl Triacetate Impurities data for Panthenyl Ethyl Ether, Panthenyl Ethyl Ether Acetate, and Panthenyl Triacetate Sensitization data, specifically an HRIPT or a guinea pig maximization test for Panthenol at a concentration > 5% A supplementary request from the Panel is for chronic toxicity data on Panthenyl Ethyl Ether. Panthenol and Pantothenic Acid (vitamin B5) were originally reviewed by the CIR Expert Panel in 1987 and determined to be safe for use in cosmetics as described in that safety assessment. These two ingredients were rereviewed in 2006, wherein the Panel decided not to reopen the report and issued a re-review summary. Panthenol and Pantothenic Acid are included in the present safety assessment because they are structurally similar to the 5 new ingredients listed above. Polyaminopropyl Biguanide (polyhexamethylene biguanide hydrochloride) The Panel found the data are insufficient to determine the safety of Polyaminopropyl Biguanide (polyhexamethylene biguanide hydrochloride). The data needs are: Skin sensitization data to determine the no-effect-level (i.e., threshold) for Polyaminopropyl Biguanide (polyhexamethylene biguanide hydrochloride)-induced sensitization

19 Data needed to evaluate anaphylactic reactions to Polyaminopropyl Biguanide (polyhexamethylene biguanide hydrochloride) in case studies Data from Korean studies on lung injury/mortalities attributable to exposure to a disinfectant (polyhexamethylene guanidine phosphate) used in humidifiers It was also noted that a positive local lymph node assay (LLNA) on Polyaminopropyl Biguanide (polyhexamethylene biguanide hydrochloride) was mentioned in a publication by Gerberick et al. (2000); however, details relating to the LLNA results are not included. The Council liaison informed the Panel that efforts are underway to obtain the complete primary report, given the need for additional information about this observation. The Panel accelerated the priority for review of this ingredient, prompted by the European Scientific Committee on Consumer Safety s (SCCS s) announced plan to issue a revised concentration limit (0.1%) for this ingredient in cosmetic products (which has since been issued). Upon review, the Panel was also concerned about reports of the elicitation of sensitization reactions to this ingredient at a concentration of 0.1% in a select group of individuals, and reports of anaphylaxis when this ingredient was used in wound dressings. Given the confusing nomenclature of this ingredient (e.g., the ingredient name Polyaminopropyl Biguanide refers exclusively to the chemical polyhexamethylene biguanide hydrochloride) a supplementary request was made to confirm, for the sake of relevance, the identity of the chemical that is the subject of the Korean reports noted above. Triglycerides The Panel reviewed the safety of the following 51 triglycerides, and found the data are insufficient to determine safety of several of the ingredients: Acetic/Linoleic/Palmitic Triglyceride C12-18 Acid Triglyceride C18-36 Acid Triglyceride C8-12 Acid Triglyceride Capric/Lauric/Myristic/Oleic Triglyceride Caprylic/Capric Triglyceride Caprylic/Capric/Lauric Triglyceride Caprylic/Capric/Linoleic Triglyceride Caprylic/Capric/Myristic/Stearic Triglyceride Caprylic/Capric/Palmitic/Stearic Triglyceride Caprylic/Capric/Stearic Triglyceride C10-40 Isoalkyl Acid Triglyceride Cod Liver/Mink/Tallow Triglyceride C10-18 Triglycerides Docosahexenoic/Docosapentenoic/Oleic/Palmitic Triglyceride Glyceryl Stearate Diacetate Glyceryl Triacetyl Hydroxystearate Glyceryl Triacetyl Ricinoleate Glyceryl Tribehenate/Isostearate/Eicosandioate Glyceryl Tri-Hydrogenated Rosinate Glyceryl Tripalmate/Palm Kernelate/Olivate/Macadamiate/Rapeseedate Hydrogenated C12-18 Triglycerides Isomerized Safflower Glycerides Jojoba Oil/Caprylic/Capric Triglyceride Esters Lauric/Palmitic/Oleic Triglyceride Oleic/Linoleic Triglyceride Oleic/Palmitic/Lauric/Myristic/Linoleic Triglyceride Palmitic/Stearic Triglyceride Ricinoleic/Caproic/Caprylic/Capric Triglyceride Triarachidin Tribehenin Tricaprin Tricaprylin Tierucin Triethylhexanoin Triheptanoin Triheptylundecanoin Trihydroxystearin Triisononanoin Triisopalmitin Triisostearin Trilaurin Trilinolein Trilinolenin Trimyristin Triolein Tripalmitin Tripalmitolein Triricinolein Tristearin Triundecanoin This re-review was initiated in accordance with CIRs Procedures to reassess previously-reviewed ingredients every 15 years. In 2000, the Panel published a safety assessment of Trihydroxystearin. Twenty-four additional ingredients, also reviewed previously, have been incorporated into this re-review: a report on Trilaurin and 22 other glyceryl

20 triesters, published in 2001, and in 2003, the Panel reaffirmed their original conclusion for Caprylic/Capric Triglyceride (which was first published in 1980). (Ingredients that were previously reviewed are indicated above in blue.) All 25 previously-reviewed ingredients were found to be safe as used. The 26 remaining ingredients that have not been reviewed previously, were incorporated into the current safety assessment because they are also triglycerides (i.e., closely related structural analogs of the other ingredients in this group). The Panel reviewed the new data included in the re-review, and noted that the frequency and concentration of use of a number of the ingredients have increased markedly. The Panel also noted that the report does not include irritation and sensitization data at the new, higher reported use concentrations. Additionally, the Panel had a question about the irritation and sensitization potential of one of the new ingredients, because of its chemical structure. According to the International Cosmetic Ingredient Dictionary and Handbook, a possible reported function of one of the ingredients is skin bleaching agent; skin bleaching agent is not a cosmetic function (but is a drug function in the US) and, therefore, the Panel would not be evaluating safety of the ingredient for that use; however, the Panel requested clarification about the skin-bleaching potential of this ingredient. The Panel requested the following data to address the data gaps: sensitization data for Tribehenin at the reported maximum concentration of use; sensitization data for Caprylic/Capric Triglyceride at the reported maximum concentration of use; sensitization data for Triethylhexanoin at the reported maximum concentration of use; irritation and sensitization testing of C10-40 Isoalkyl Acid Triglyceride at the expected maximum concentration of use; clarification of the skin bleaching potential of Docosahexenoic/Docosapentenoic/Oleic/Palmitic Triglyceride, including a dose-response for this action; and clarification of the structure of the eicosandioic acid residue of Glyceryl Tribehenate/Isostearate/Eicosandioate. Other Items: Boilerplates, Guidance, and Priorities Information Sources At its December 2016 meeting, the CIR Expert Panel requested that a statement informing readers about the search engines and information sources that are used in typical searches for information is included in each CIR safety assessment. The Panel approved the following statement to be included in the Introduction of all reports: This safety assessment includes relevant published and unpublished data that are available for each endpoint that is evaluated. Published data are identified by conducting an exhaustive search of the world s literature. A listing of the search engines that are used and the sources that are typically explored, as well as the endpoints that CIR typically evaluates, is provided on the CIR website ( Unpublished data are provided by the cosmetics and chemical industries, as well as by other interested parties. However, this language will not be used and the supporting documents will not be posted until the CIR Science and Support Committee (SSC) and all interested parties have the opportunity for review. The SSC is scheduled to meet in May Endocrine Activity and Endocrine Disruption The Panel reviewed a preliminary draft Endocrine Activity and Endocrine Disruption Background and Framework document (EA&ED Document), which was prepared in response to their request. The EA&ED Document is based partially on Dr. Mihaich s presentation at the December 2016 Panel meeting and several key references addressing the critical issues and criteria for identifying and characterizing endocrine- disrupting chemicals (EDCs). The Panel found the EA&ED Document to be well written, and requested that it be reviewed by Dr. Mihaich, the CIR SSC, and all other interested stakeholders.

21 Hair Dye Epidemiology The Panel reviewed an updated draft of the CIR Hair Dye Epidemiology document (HDE Document), which was last revised in July of Several epidemiological studies have appeared in the published scientific literature since 2014, and these studies were summarized and added to the HDE Document for the Panel s review. The added studies include two meta-analyses and two case-control studies addressing lymphoma and leukemia, one case control study addressing breast cancer, and one case-control study addressing polymorphisms in DNA repairenzyme genes. In addition, an older metaanalysis addressing breast cancer, among other cancers, was included; the practice of including meta-analyses in the HDE Document began with the 2014 edition. The Panel generally approved the HDE Document. However, the HDE Document should be revised to indicate, briefly, the extent and the manner in which, the studies summarized in the HDE Document addressed potential confounding factors. Additionally, the HDE Document should briefly elaborate the nature of the associations reported between hair dye use and carcinogenicity in each epidemiological study. The Panel requested that the HDE Document be reviewed by the Council s Hair Color Technical Committee (HCTC) and all other interested stakeholders. Aerosols The Panel reviewed a revised draft of the CIR Precedents Aerosols document (Aerosols Document). The version currently posted on the CIR Website was revised in 2012, and additional revisions were made in 2016 to incorporate new information and analysis submitted by the CIR SCC. The analysis addresses incidental inhalation exposures to ingredients in loose powder cosmetic products. The Panel also reviewed extensive comments received from Women s Voices for the Earth (WVE). The Panel found that the comments were thoughtful and raised valid issues. In particular, the methods and data used to characterize the particle-size distributions released to the breathing zone during the use of cosmetic sprays and powders are not well characterized in the Aerosols Document. The Panel requested more information on the nature of these distributions, especially for representative deodorant spray products, which appear to deliver aerosols with the largest respirable fractions based on the limited data available to CIR to date. CIR will extend invitations to experts in the field to present information and their perspectives on these issues to the Panel. The topics to be addressed include current analytical methods for characterizing particulates released from cosmetic products and the significance of results obtained from the application of such methods for assessing the safety of cosmetic ingredients CIR Priorities Interested parties are invited to comment on the inclusion of the ingredients listed below as 2018 CIR Draft Priorities. The selection of these ingredients was based on the list of ingredients that have not yet been reviewed by the CIR Expert Panel and have the greatest number of uses reported by the VCRP in While the number of proposed new reports below is fewer than usual, a number of previously prioritized report projects are being carried forward into Comments are also being sought on the additional ingredients that might be included in each ingredient family. Proposed ingredient families may be found (for both newly proposed and previously prioritized report projects), starting at page 17 in the document available at the following url: It is likely that not all of the ingredients listed will be chosen for work in CIR plans to finalize the proposed 2018 priority list at the June 2017 Panel meeting. Ingredient Number of formulations containing ingredient Sorbitol Tetrasodium Glutamate Diacetate 470 Isopropyl Titanium Triisostearate 457 Adenosine 447 Ascorbyl Glucoside 432 Magnesium Chloride 426 Polysilicone VP/Eicosene Copolymer 356 Tris(Tetramethylhydroxypiperidinol) Citrate 320

22 Cocos Nucifera (Coconut) Fruit Extract 305 Hordeum Vulgare Extract 291 Punica Granatum Extract Hair Dye N/A (annual election) Triclosan N/A (for cause)

23 Date: May 19, 2017 From: Bart Heldreth, Ph.D., CIR To: CIR Expert Panel Members and Liaisons Re: Draft Final 2018 Priority List The CIR Procedures require that we prepare the Draft 2018 Priority List for public comment by June 1, The Draft 2018 Priority List was prepared and issued for public comment in April, to allow more time for the acquisition of data and comments. The list was based on frequency of use data (FOU) from FDA s Voluntary Cosmetic Registration Program (VCRP), received from FDA on February 15, 2017, and CIR staff workflow. While this list included only the lead ingredients, potential groupings for each selected lead were provided in an attachment. The Expert Panel has reviewed the draft and now has the opportunity to review any further revisions to this list, the groupings recited in Attachment 1, and any public comments, and issue a Final 2018 Priority List. CIR will select a number of ingredients/ingredient groups from this list for review in 2018; CIR is not committing to begin all of these reports by year-end *** Nine of these reports were established as 2016 or 2017 Priorities, or by strategy memos, but will not be addressed in These reports (shaded in blue in the following table) are: Fatty Acids and Soaps (94 ingredients), Brown Algae (84 ingredients), Alkylamide MIPA Ingredients (13 ingredients), Alkoxylated Amides (39 ingredients), Vanilla-Derived Ingredients (11 ingredients), Palm Tree-Derived Ingredients (8 ingredients), Papaya-Derived Ingredients (5 ingredients), Chinese Skullcap Derived-Ingredients (3 ingredients), and the Wheat-Derived Ingredients (23 ingredients). CIR is already committed to prioritizing these reports as 2018 work products; therefore, no action from the Panel is currently required for these 9 reports. The remaining cosmetic ingredients listed in the table are 1) those with the highest frequencies of use and 2) are neither excluded for being previously reviewed nor for purview by another safety assessment body (e.g., RIFM for fragrance only ingredients, or FDA for certain color ingredients). Highlighted (in yellow) are those new priorities suggested by the CIR staff, the Expert Panel, or the Hair Color Technical Committee (Attachment 2), for the 2018 Final Annual Priority List. While some ingredients with high FOUs were not selected for the 2018 Priority List, these ingredients are not being excluded from review, but will be tracked for future prioritization. The rationales for selecting some of these high frequency of use ingredients and not others include: current review elsewhere (e.g., NICNAS is known to be preparing a dossier), exposure by non-cosmetic use (e.g., OTC drug) is significantly greater than possible cosmetic use (reducing potential risk), the INC is working to change the cosmetic nomenclature (e.g., Yeast Extract is to be renamed by various genus/species names), or to enhance the efficiency for CIR staff and/or the Panel.

24 Draft Final CIR 2018 Priority List (5/19/2017) LEAD INGREDIENT FOU (2017) ***Brown Algae Ingredients -added by strategy memo / 84 ingredients ***Fatty Acids and Soaps -LINOLEIC ACID -group of 94 ingredients ***Alkylamide MIPA Ingredients -LAURAMIDE MIPA -group of 13 alkylamide MIPA ingredients ***Alkoxylated Amides -PPG-2 HYDROXYETHYL COCAMIDE -added by strategy memo / 39 ingredients ***Vanilla-Derived Ingredients -VANILLA PLANIFOLIA FRUIT EXTRACT -group of 11 ingredients ***Palm Tree-Derived Ingredients Euterpe Oleracea Fruit Extract -group of 8 ingredients ****Papaya-Derived Ingredients CARICA PAPAYA (PAPAYA) FRUIT EXTRACT -5 ingredients ****Chinese Skullcap-Derived Ingredients SCUTELLARIA BAICALENSIS (CHINESE SKULLCAP) ROOT EXTRACT -3 ingredients ***Wheat-Derived Ingredients TRITICUM VULGARE (WHEAT) GERM EXTRACT -23 non-protein ingredients SORBITOL 3 Hexa/Penta-hydric Alcohols 1950 TETRASODIUM GLUTAMATE DIACETATE 2 Amino Acid Diacetates 470 ISOPROPYL TITANIUM TRIISOSTEARATE 5 Organo-Titanium Ingredients 457 ADENOSINE -5 Adenosine Ingredients 447 ASCORBYL GLUCOSIDE -1 ingredient 432 MAGNESIUM CHLORIDE-14 Alkaline Metal Halides (incl. KCl (which has a FOU of 399)) 426 POLYSILICONE-11-1 ingredient 358 VP/EICOSENE COPOLYMER 30 VP Polymer Ingredients 356 TRIS(TETRAMETHYLHYDROXYPIPERIDINOL) CITRATE -1 light stabilizer ingredient 320 COCOS NUCIFERA (COCONUT) FRUIT EXTRACT -10 Coconut Ingredients 305 HORDEUM VULGARE EXTRACT -14 Barley Ingredients 291 PUNICA GRANATUM EXTRACT -20 Pomegranate Ingredients 273 BASIC RED Hair Dye 45 (hair dye) TRICLOSAN per request (for cause) 426 N/A

25 Draft Final 2018 CIR Priority List, with Ingredient Groupings (CIR will choose from these groupings to create a feasible number of reports. Not all of these groupings will be acted upon in 2018) Group/INGREDIENT NAME Brown Algae ***(This grouping carried over from 2016) Fatty Acids and Soaps (Fatty Acid Salts) ***(This grouping carried over from 2016) LINOLEIC ACID FOU Yr.2017 Structure/Formula/Description/Rationale N/A added by strategy memo 604 All of the ingredients in this report are structurally related as simply fatty acids and their simple inorganic salts (soaps). Related Prior Reports (color coded when included): Fatty Acids and Sodium/Potassium Soaps from plant oils Final Plant Oils Report 03/04/2011 Hydroxystearic Acid - IJT 18(S1):1-10, 1999 Isostearic Acid - IJT 24(Suppl. 1):1-102, 2005 (Not reopened; JACT 2(7):61-74, 1983) Oleic Acid,Lauric Acid, Palmitic Acid, Myristic Acid, and Stearic Acid - IJT 25(Suppl. 2) :1-89,2006 (Not reopened; JACT 6(3): , 1987) 1 Ingredient Group Potential Add-ons (reported FOU) (Total # in Ingredient Group) (84) 1. Aluminum Distearate (26) 2. Aluminum Isostearate 3. Aluminum Isostearates/ Palmitates 4. Aluminum Isostearates/ Stearates 5. Aluminum Isostearates/ Laurates/Palmitates 6. Aluminum Isostearates/ Laurates/Stearates 7. Aluminum Lanolate 8. Aluminum Stearate (48) 9. Aluminum Stearates (4) 10. Aluminum Tristearate (7) 11. Ammonium Isostearate

26 2 Group/INGREDIENT NAME FOU Yr.2017 Structure/Formula/Description/Rationale Pelargonic Acid - IJT-30(SUPPL. 3)2011 Ricinoleic Acid - IJT 26(Suppl. 3):31-77, 2007 Lithium Stearate, Aluminum Distearate, Aluminum Stearate, Aluminum Tristearate, Ammonium Stearate,, Magnesium Stearate, Potassium Stearate, Sodium Stearate, and Zinc Stearate - IJT 22(Suppl. 1):1-35, 2003 (Not reopened; JACT 1(2): , 1982) Aluminum dimyristate, Aluminum Isostearates/ Myristates, aluminum myristate, aluminum myristates/palmitates, calcium myristate, cetyl myristate, and magnesium myristate (and myristate esters) - IJT 29(Suppl. 3) : ,2010 DEA-Isostearate, DEA-Linoleate, DEA-Myristate, and DEA Stearate (and other DEA salts) Final Report 2011 MEA-Undecylenate and MEA-Tallowate Final Report 2012 TEA-Fatty Acid Salts - IJT 32(Suppl. 1):59-83, 2013 Ingredient Group Potential Add-ons (reported FOU) (Total # in Ingredient Group) 12. Ammonium Oleate 13. Ammonium Stearate (4) 14. Arachidic Acid (3) 15. Beeswax Acid 16. Behenic Acid (130) 17. C14-28 Alkyl Acid (18)* 18. C10-40 Isoalkyl Acid 19. C14-28 Isoalkyl Acid (18)* 20. C32-36 Isoalkyl Acid 21. Calcium Behenate (2) 22. Calcium Laurate 23. Calcium Stearate (370) 24. Calcium Undecylenate 25. Capric Acid (3) 26. Caproic Acid 27. Caprylic Acid (5) 28. Erucic Acid 29. Isomerized Linoleic Acid (19) 30. Isomerized Safflower Acid 31. Isostearic Acid (237) 32. Lauric Acid (454) 33. Linolenic Acid (176) 34. Lithium Stearate (91) 35. Magnesium Lanolate 36. Magnesium Laurate (9) 37. Magnesium Palmitate 38. Magnesium Stearate (569) 39. Magnesium Tallowate 40. Myristic Acid (323) 41. Oleic Acid (1075) 42. Ozonized Oleic Acid

27 3 Group/INGREDIENT NAME FOU Yr.2017 Structure/Formula/Description/Rationale Ingredient Group Potential Add-ons (reported FOU) (Total # in Ingredient Group) 43. Palmitic Acid (1141) 44. Potassium Behenate (5) 45. Potassium Borageate 46. Potassium Camelliate 47. Potassium Caprate 48. Potassium Caprylate 49. Potassium Caprylate/ Caprate 50. Potassium Castorate (2) 51. Potassium Hydrogenated Tallowate (1) 52. Potassium Isostearate (5) 53. Potassium Lanolate 54. Potassium Laurate (25) 55. Potassium Linoleate 56. Potassium Linseedate 57. Potassium Oleate (53) 58. Potassium Olivate/ Sunflowerseedate 59. Potassium Palm Kernelate (17) 60. Potassium Palmitate 61. Potassium Stearate (123) 62. Potassium Sunflowerseedate 63. Potassium Tallate 64. Potassium Tallowate 65. Potassium Undecylenate 66. Sodium Arganate 67. Sodium Beeswax 68. Sodium Behenate (14) 69. Sodium Camellia Japonica Seedate

28 Group/INGREDIENT NAME FOU Yr.2017 Structure/Formula/Description/Rationale Ingredient Group Potential Add-ons (reported FOU) (Total # in Ingredient Group) 70. Sodium Caprate 71. Sodium Caprylate 72. Sodium Castorate (2) 73. Sodium Dilinoleate 74. Sodium Hydrogenated Tallowate 75. Sodium Isostearate (10) 76. Sodium Lanolate 77. Sodium Lardate 78. Sodium Laurate (76) 79. Sodium Laurate/ Linoleate/Oleate/ Palmitate 80. Sodium Linoleate 81. Sodium Oleate (21) 82. Sodium Palmitate (83) 83. Sodium Stearate (557) 84. Sodium Tallowate (136) 85. Sodium Tamanuseedate 86. Sodium Undecylenate 87. Stearic Acid (5200) 88. Undecanoic Acid 89. Undecylenic Acid 90. Zinc Laurate (78) 91. Zinc Palmitate 92. Zinc Stearate (2119) 93. Zinc Undecylenate (1) 4 (94)

29 Group/INGREDIENT NAME Alkylamide MIPA Ingredients ****(This grouping carried over from 2017) LAURAMIDE MIPA FOU Yr Structure/Formula/Description/Rationale The ingredients in this group are each an MIPA (mixture of isopropanol amides) of a simple carboxylic acid. (one example of an iso ) wherein R is fatty chain Alkoxylated Amides ****(This grouping carried over from 2017) PPG-2 HYDROXYETHYL COCAMIDE The ingredients in this report are each structurally related as alkoxylated (PEG, PPG, etc.) simple amides. Ingredient Group Potential Add-ons (reported FOU) (Total # in Ingredient Group) 1. Cocamide MIPA 2. Coconut Oil MIPA Amides 3. Hydroxyethyl Stearamide-MIPA 4. Isostearamide MIPA 5. Linoleamide MIPA 6. Myristamide MIPA 7. Oleamide MIPA 8. Palmamide MIPA 9. Palm Kernelamide MIPA 10. Ricinoleamide MIPA 11. Stearamide MIPA 12. MIPA- Myristate (13) 1. PEG-2 Cocamide (8) 2. PEG-3 Cocamide 3. PEG-4 Cocamide 4. PEG-5 Cocamide (25) 5. PEG-6 Cocamide (20) 6. PEG-7 Cocamide 7. PEG-11 Cocamide 8. PEG-20 Cocamide 9. PEG-3 Cocamide DEA 10. PEG-6 Hydrogenated Palmamide 11. PEG-50 Hydrogenated Palmamide (13) 12. PEG-13 Hydrogenated Tallow Amide 13. PEG-5 Lanolinamide 14. PEG-3 Lauramide 15. PEG-5 Lauramide 16. PEG-6 Lauramide

30 Group/INGREDIENT NAME FOU Yr.2017 Structure/Formula/Description/Rationale Ingredient Group Potential Add-ons (reported FOU) (Total # in Ingredient Group) 17. PEG-11 Lauramide 18. PEG-3 Oleamide 19. PEG-4 Oleamide 20. PEG-5 Oleamide 21. PEG-6 Oleamide 22. PEG-7 Oleamide 23. PEG-9 Oleamide 24. PEG-5 Oleamide Dioleate 25. PEG-4 Rapeseedamide (257) 26. PEG-4 Stearamide 27. PEG-10 Stearamide 28. PEG-15 Stearamide 29. PEG-50 Stearamide 30. PEG-5 Tallow Amide 31. PEG-8 Tallow Amide 32. PEG-50 Tallow Amide (27) 33. PEG-2 Tallowamide DEA 34. Polyglyceryl-4-PEG-2 Cocamide 35. PPG-2 Cocamide (2) 36. PPG-1 Hydroxyethyl Caprylamide 37. PPG-2 Hydroxyethyl Coco/Isostearamide (44) 38. PPG-3 Hydroxyethyl Soyamide 6 (39)

31 Group/INGREDIENT NAME Vanilla-Derived Ingredients ****(This grouping carried over from 2017) VANILLA PLANIFOLIA FRUIT EXTRACT Palm Tree-Derived Ingredients ****(This grouping carried over from 2017) EUTERPE OLERACEA FRUIT EXTRACT FOU Yr.2017 Structure/Formula/Description/Rationale 332 The ingredients inthis group are each derived from Vanilla. 323 The ingredients in this group are each derived from the species Euterpe (palm trees). Ingredient Group Potential Add-ons (reported FOU) (Total # in Ingredient Group) 1. Vanilla Planifolia Flower Extract 2. Vanilla Planifolia Fruit Extract 3. Vanilla Planifolia Fruit Oil 4. Vanilla Planifolia Fruit Water 5. Vanilla Planifolia Leaf Cell Extract 6. Vanilla Planifolia Seed 7. Vanilla Planifolia Seed Powder 8. Vanilla Tahitensis Fruit 9. Vanilla Tahitensis Fruit Extract 10. Vanilla Tahitensis Seed (11) 1. Euterpe Edulis Fruit Extract 2. Euterpe Edulis Juice Extract 3. Euterpe Oleracea Juice 4. Euterpe Oleracea Palm Heart Extract 5. Euterpe Oleracea Pulp Powder 6. Euterpe Oleracea Seed Powder 7. Hydrolyzed Euterpe Oleracea Fruit (8) 7

32 Group/INGREDIENT NAME Papaya-Derived Ingredients ****(This grouping carried over from 2017) CARICA PAPAYA (PAPAYA) FRUIT EXTRACT FOU Yr Structure/Formula/Description/Rationale The ingredients in this group are each derived from Carica papaya. Ingredient Group Potential Add-ons (reported FOU) (Total # in Ingredient Group) 1. Carica Papaya (Papaya) Fruit 2. Carica Papaya (Papaya) Juice 3. Carica Papaya (Papaya) Fruit Water 4. Carica Papaya (Papaya) Leaf Extract (5) Scutellaria baicalensis (Chinese Skullcap)Derived Ingredients ****(This grouping carried over from 2017) SCUTELLARIA BAICALENSIS (CHINESE SKULLCAP) ROOT EXTRACT Wheat-Derived Ingredients ****(This grouping carried over from 2017) TRITICUM VULGARE (WHEAT) GERM EXTRACT The ingredients in this group are each derived from Scutellaria baicalensis. 1. Scutellaria Baicalensis Extract 2. Scutellaria Baicalensis Root Powder (3) The ingredients in this report are derived from wheat, but exclude those recently reviewed such as the hydrolyzed proteins and oils. 1. Triticum Aestivum (Wheat) Flour Lipids 2. Triticum Aestivum (Wheat) Germ Extract 3. Triticum Aestivum (Wheat) Leaf Extract 4. Triticum Aestivum (Wheat) Peptide 5. Triticum Aestivum (Wheat) Seed Extract 6. Triticum Monococcum (Wheat) Seed Extract 7. Triticum Monococcum (Wheat) Stem Water

33 9 Group/INGREDIENT NAME FOU Yr.2017 Structure/Formula/Description/Rationale Ingredient Group Potential Add-ons (reported FOU) (Total # in Ingredient Group) 8. Triticum Turgidum Durum (Wheat) Seed Extract 9. Triticum Vulgare/ Aestivum (Wheat) Grain Extract 10. Triticum Vulgare (Wheat) Bran 11. Triticum Vulgare (Wheat) Bran Extract 12. Triticum Vulgare (Wheat) Flour Extract 13. Triticum Vulgare (Wheat) Flour Lipids 14. Triticum Vulgare (Wheat) Germ 15. Triticum Vulgare (Wheat) Germ Extract 16. Triticum Vulgare (Wheat) Germ Powder 17. Triticum Vulgare (Wheat) Germ Protein 18. Triticum Vulgare (Wheat) Protein 19. Triticum Vulgare (Wheat) Seed Extract 20. Triticum Vulgare (Wheat) Sprout Extract 21. Triticum Vulgare (Wheat) Starch 22. Triticum Vulgare (Wheat) Straw Water (23)

34 Group/INGREDIENT NAME Hexa/Penta-hydric Alcohols SORBITOL Amino Acid Diacetates TETRASODIUM GLUTAMATE DIACETATE FOU Yr Structure/Formula/Description/Rationale The ingredients in this group share in common similar, acyclic polyol structures. Sorbitol Mannitol Xylitol The ingredients in this group are disubsituted amino 1. Beta-Alanine Diacetic acid chelating agents. Acid (2) Tetrasodium Glutamate Diacetate Organo-Titanium Ingredients ISOPROPYL TITANIUM TRIISOSTEARATE 457 Ingredient Group Potential Add-ons (reported FOU) (Total # in Ingredient Group) 1. Mannitol (316) 2. Xylitol (347) (3) (2) β-alanine Diacetic Acid The ingredients in this group are organometallic derivatives of titanium Titanium Citrate Titanium Ethoxide Titanium Isostearates Titanium Salicylate (5) 10

35 Group/INGREDIENT NAME Adenosine Ingredients ADENOSINE FOU Yr Structure/Formula/Description/Rationale The ingredients in this report share a common adenosine core structure. Ingredient Group Potential Add-ons (reported FOU) (Total # in Ingredient Group) 1. Adenosine Phosphate (90) 2. Adenosine Triphosphate (30) 3. Disodium Adenosine Phosphate 4. Disodium Adenosine Triphosphate (36) (5) Adenosine ASCORBYL GLUCOSIDE Alkaline Metal Halides MAGNESIUM CHLORIDE POTASSIUM CHLORIDE N/A single ingredient report (1) Ascorbyl Glucoside The ingredients in this group are salts, each 1. Magnesium Bromide (2) comprising an alkaline earth metal and a halogen. 2. Magnesium Fluoride (maybe OTC Drug only) 3. Potassium Bromide (7) 4. Potassium Fluoride (maybe OTC Drug only) 5. Potassium Iodide (36)

36 Group/INGREDIENT NAME Vinylpyrrolidone Polymers VP/HEXADECENE COPOLYMER VP/EICOSENE COPOLYMER 12 FOU Yr Structure/Formula/Description/Rationale Ingredient Group Potential Add-ons (reported FOU) (Total # in Ingredient Group) 6. Calcium Chloride (239) 7. Calcium Fluoride (maybe OTC Drug only) 8. Lithium Chloride 9. Lithium Fluoride 10. Sodium Chloride (6551) 11. Sodium Fluoride (27) (maybe OTC Drug only) 12. Sodium Iodide (1) (14) The ingredients in this group are polymers prepared, 1. Acrylates/Stearyl inter alia, from the monomer, vinylpyrrolidone. Methacrylate/VP Copolymer 2. Acrylates/VP Copolymer (10) 3. Acrylic Acid/VP Crosspolymer (18) 4. Ammonium Acryloyldimethyltaurate/ Acrylates/VP Copolymer: CIR [SQ] IJT-21(SUPPL. VP Copolymer 3)2002 Ammonium Acryloyldimethyltaurate/VP Copolymer: 5. Butylated PVP (1) CIR Tentative Report [S] 6. Ethylhexyl Methacrylic Acid/Styrene/VP Copolymer: CIR [S] 2014 Acrylate/VP/Dimethicone PVP: CIR [S] IJT-17(Suppl. 4)1998 (2013 not remethacrylate Copolymer opened) 7. Ethylhexyl Sodium Acryloyldimethyltaurate/VP Crosspolymer: Methacrylate/Methyl CIR Tentative Report [S] Methacrylate/VP Styrene/VP Copolymer: CIR [S] 2014 Copolymer Vinyl Caprolactam/VP/Dimethylaminoethyl Methacrylate Copolymer: CIR [SQ] IJT-21(SUPPL. 8. Hydrolyzed Wheat 3)2002 Protein/PVP Crosspolymer VP/Dimethylaminoethylmethacrylate Copolymer: CIR (49)

37 Group/INGREDIENT NAME 13 FOU Yr.2017 Structure/Formula/Description/Rationale [SQ] IJT-21(SUPPL. 3)2002 VP/VA Copolymer: CIR [S] IJT-25(SUPPL. 2)2006 Ingredient Group Potential Add-ons (reported FOU) (Total # in Ingredient Group) 9. Maltodextrin/VP Copolymer (3) 10. Methacrylic Acid/Styrene/VP Copolymer 11. PVP (939) 12. PVP/Decene Copolymer 13. PVP/VA/Itaconic Acid Copolymer 14. PVP/VA/Vinyl Propionate Copolymer 15. Sodium Acryloyldimethyltaurate/ VP Crosspolymer (8) 16. Styrene/VP Copolymer (77) 17. Triacontanyl PVP (63) 18. Triacontene/VP Copolymer 19. Vinyl Caprolactam/VP/ Dimethylaminoethyl Methacrylate Copolymer (69) 20. VP/Acrylates/Lauryl Methacrylate Copolymer (15) 21. VP/Dimethiconylacrylate/ Polycarbamyl/Polyglycol Ester (8) 22. VP/Dimethylaminoethylmethacrylate Copolymer

38 Group/INGREDIENT NAME FOU Yr.2017 Structure/Formula/Description/Rationale POLYSILICONE Polysilicone-11 is a crosslinked dimethyl siloxane formed by the reaction of Bis-Vinyldimethicone and Hydrogen Dimethicone. Ingredient Group Potential Add-ons (reported FOU) (Total # in Ingredient Group) (79) 23. VP/Dimethylaminoethylm ethacrylate/polycarbamyl Polyglycol Ester 24. VP/DMAPA Acrylates Copolymer (30) 25. VP/Polycarbamyl Polyglycol Ester (13) 26. VP/VA Copolymer (497) 27. VP/Vinyl Alcohol Copolymer 28. VP/Vinyl Caprolactam/DMAPA Acrylates Copolymer (15) (30) N/A single ingredient report Bis-Vinyldimethicone 14 Hydrogen Dimethicone, wherein R can be either hydrogen or a methyl group. (1)

39 Group/INGREDIENT NAME TRIS(TETRAMETHYLHYDROXYPIPERIDINOL) CITRATE Coconut Ingredients COCOS NUCIFERA (COCONUT) FRUIT EXTRACT FOU Yr.2017 Structure/Formula/Description/Rationale Ingredient Group Potential Add-ons (reported FOU) (Total # in Ingredient Group) N/A single ingredient report Tris(Tetramethylhydroxypiperidinol) Citrate (1) The ingredients in this group are derived from Cocus 1. Cocos Nucifera (Coconut) nucifera, commonly known as coconut. Flower Extract 2. Cocos Nucifera (Coconut) Fruit (13) 3. Cocos Nucifera (Coconut) Fruit/Fruit Juice Extract 4. Cocos Nucifera (Coconut) Fruit Juice (17) 5. Cocos Nucifera (Coconut) Fruit Powder (11) Cocos Nucifera (Coconut) Oil: CIR [S] IJT-30(SUPPL. 6. Cocos Nucifera (Coconut) 1)2011 Oil (2573) Cocos Nucifera (Coconut) Seed Butter: CIR: [S] Final 7. Cocos Nucifera (Coconut) Report 2011 Seed Butter 8. Cocos Nucifera (Coconut) Shell Powder (25) 9. Cocos Nucifera (Coconut) Water (43) (maybe fragrance only) (10) 15

40 Group/INGREDIENT NAME Barley Ingredients HORDEUM VULGARE EXTRACT FOU Yr Structure/Formula/Description/Rationale The ingredients in this group are derived from Hordeum vulgare, commonly known as barley. Ingredient Group Potential Add-ons (reported FOU) (Total # in Ingredient Group) 1. Hordeum Vulgare Flower/Leaf/Stem Juice 2. Hordeum Vulgare Juice 3. Hordeum Vulgare Leaf Extract 4. Hordeum Vulgare Leaf Juice 5. Hordeum Vulgare Leaf Powder 6. Hordeum Vulgare Leaf/Stem Powder 7. Hordeum Vulgare Powder 8. Hordeum Vulgare Root Extract 9. Hordeum Vulgare Seed Extract 10. Hordeum Vulgare Seed Flour 11. Hordeum Vulgare Seed Water 12. Hordeum Vulgare Sprout Extract 13. Hordeum Vulgare Stem Water (14) 16

41 Group/INGREDIENT NAME Pomegranate Ingredients PUNICA GRANATUM EXTRACT 17 FOU Yr Structure/Formula/Description/Rationale Ingredient Group Potential Add-ons (reported FOU) (Total # in Ingredient Group) The ingredients in this group are derived from Punica 1. Punica Granatum Bark granatum, commonly known as pomegranate. Extract (6) 2. Punica Granatum Bark/Fruit Extract 3. Punica Granatum Callus Culture Extract 4. Punica Granatum Flower Extract 5. Punica Granatum Fruit Extract (99) 6. Punica Granatum Fruit Juice (78) 7. Punica Granatum Hydrogenated Punica Granatum Seed Oil: CIR[S] 2011 Fruit/Root/Stem Powder Punica Granatum Seed Oil: CIR [S] Punica Granatum Fruit/Sucrose Ferment Filtrate 9. Punica Granatum Fruit Water 10. Punica Granatum Juice Extract (2) 11. Punica Granatum Leaf Cell Extract 12. Punica Granatum Peel Extract 13. Punica Granatum Pericarp Extract (12) 14. Punica Granatum Seed 15. Punica Granatum Seed