ADMIN Memo Agenda Minutes RRsum Glyoxal RRsum Quaternium-26 RRsum Biotin Aerosols Endocrine Activity Hair Dyes CIR EXPERT PANEL MEETING SEPTEMBER 11 – 12, 2017 Distributed for Comment Only -- Do Not Cite or Quote Commitment & Credibility since 1976 MEMORANDM To: CIR Expert Panel Members and Liaisons From: Bart Heldreth, PhD, Interim Director, CIR Subject: 144th Meeting of the CIR Expert Panel — Monday and Tuesday, September 11-12, 2017 Date: August 18, 2017 Welcome to our September 2017 Panel meeting. CIR is still in an interim leadership phase, but we are all set and ready for our third meeting of the year. Enclosed are the agenda and accompanying materials for the 144th CIR Expert Panel Meeting to be held on September 11-12, 2017. The location again is the Loews Madison Hotel, 1177 Fifteenth Street, NW, Washington, DC 20005. Phone: (202) 862-1600. Fax: (202) 785-1255. The meeting agenda includes the consideration of 15 ingredient groups advancing in the review process and 3 re-review summaries. Following up on the Panel’s continuing standardization of guidance language documents, the agenda also includes 3 items for discussion. These 3 very cogent documents include the topics of Endocrine Activity, Hair Dyes, and Incidentally Respirable Particles. Through Ivan’s efforts, the culmination of input from the Panel, stakeholders, and Dr. Mihaich, has resulted in a new draft of the Endocrine Activity Guidance document for the Panel’s review. Additionally, a synopsis of the current state of the CIR guidance documentation for dealing with hair dyes is available for review. We are expecting a presentation on this topic in December, and this review presents an opportunity for the Panel to prefigure what they expect to see and hear in that presentation. And, with regard to how we handle aerosols, or otherwise incidentally inhalable particles, we have two great speakers to present on this topic, and to help inform a redrafting of the CIR Aerosols guidance document. The first speaker, Dr. Yevgen Nazarenko, is a Fellow at McGill University and is the first author of the two papers of which there was much discussion at the last Panel meeting, specifically, those titled: • Potential for Inhalation Exposure to Engineered Nanoparticles from Nanotechnology-Based Cosmetic Powders and • Nanomaterial Inhalation Exposure from Nanotechnology-Based Cosmetic Powders: a Quantitative Assessment The second speaker, Dr. Madhuri Singal, is currently a Senior Consumer Safety Associate Inhalation Toxicologist at Reckitt-Benckiser, and a Clinical Instructor at Rutgers University. Those here who have worked closely with RIFM over the years may remember Dr. Singal from her tenure there as Respiratory Science Program Manager from 2007-2013. Schedule and hotel accommodations We have reserved rooms for the nights of Sunday, September 10 and Monday September 11, at the Loews Madison Hotel. If you encounter travel problems, please contact Monice on her cell phone at 703-801-8156. 1620 L Street, NW Suite 1200, Washington, DC 20036 (Main) 202-331-0651 (Fax) 202-331-0088 (Email) [email protected] (Website) www.cir-safety.org Distributed for Comment Only -- Do Not Cite or Quote Team Meetings Draft Reports - there are 3 draft reports for review. 1. Ammonia and Ammonium Hydroxide (agenda and flash drive name – Ammonia and Ammonium Hydroxide) – This is the first time that the Panel is seeing this report on these 2 nitrogenous ingredients. In July 2017, an SLR was issued with an invitation for submission of data on these ingredients. Concentration of use data and comments were received from the Council. The CIR final report on Phosphoric Acid and Its Salts is included, as the Panel may find the data on ammonium phosphate supportive to the safety of Ammonia and/or Ammonium Hydroxide, as a surrogate. In addition, data from the European Chemicals Agency (ECHA) registration dossier on Ammonia on potential surrogate chemicals have been included in this report. The Panel should determine whether data on these surrogate chemicals are relevant to this safety assessment. One of the comments received from the Council suggests that two of these proposed surrogate chemicals, which are also cosmetic ingredients, should be added to this ingredient family. Ammonia and Ammonium Hydroxide, however, were proposed as a grouping during the priorities-setting process last year, and these additional ingredients were not recommended for inclusion until now. Ammonia and Ammonium Hydroxide constitute a perfect grouping because these ingredients are exactly the same thing in cosmetic products, existing with each other in equilibrium. The Panel should determine whether or not this change is warranted. After reviewing these documents, if the available data are deemed sufficient to make a determination of safety, the Panel should issue a Tentative Report with a safe as used, safe with qualifications, or unsafe Conclusion. If the available data are insufficient, the Panel should issue an Insufficient Data Announcement (IDA), specifying the data needs therein. 2. Alkyl Sultaines (agenda and flash drive name – Sultaines). This is the first time that the Panel is seeing this report on 13 alkyl sultaine ingredients. The sultaines/alkyl sultaines are structurally related to betaines/alkyl betaines (which the Panel has assessed the safety of), and are sometimes referred to as sulfobetaines. Each of the ingredients named in this report is a sulfopropyl quaternary ammonium salt. The structures of these ingredients are so similar that certain toxicological data, on a given endpoint, for one ingredient may be informative about the toxicity of one or more of the other ingredients in this report. Indeed, in the ECHA assessment, data on Cocamidopropyl Hydroxysultaine was used to read-across data to Lauramidopropyl Hydroxysultaine. The Council has provided concentration of use survey data and comments on the SLR that was issued on June 30th. The concentration of use survey conducted in 2017 reported the highest reported maximum concentrations of use of 11.5% in rinse-off products and up to 2.5% in leave-ons. 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 those needs and issue an IDA. 3. Hamamelis virginiana (Witch Hazel) (agenda and flash drive name – Witch Hazel). This is the first time that the Panel is seeing these 8 ingredients derived from part(s) of the Hamamelis virginiana (Witch Hazel) plant. In July 2017, an SLR was issued with an invitation for data on these ingredients. Data regarding concentration of use, method of manufacture, impurities, in vitro dermal and ocular irritation, and human dermal sensitization were submitted. “Witch hazel” is a ubiquitous term and is used generically, along with other terms (e.g., “hamamelis water,” “witch hazel extract,” “witch hazel oil,” and other variations) in the literature. Much of the information in the literature does not clarify the source plant part(s), the solvent(s), and/or the extraction method(s). If no further data are needed to formulate a Conclusion of safety, the Panel should develop the basis for the 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 IDA. Page 2 – 144th Meeting of the CIR Expert Panel — Monday and Tuesday, September 11-12, 2017 Distributed for Comment Only -- Do Not Cite or Quote Tentative Reports – there are 4 draft tentative reports. 1. Panthenol, Pantothenic Acid, and Derivatives (agenda and flash drive name – Panthenol and Derivatives). At the April 2017 meeting, the Panel issued an Insufficient Data Announcement with requested data needs as follows: • Method of Manufacturing for Panthenyl Ethyl Ether, Panthenyl Ethyl Ether Acetate, and Panthenyl Triacetate • Impurities of 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 was for chronic toxicity data on Panthenyl Ethyl Ether. Council comments and Industry data have been submitted and have been incorporated into the report as appropriate. Panel edits from the April 2017 Meeting were addressed; the Abstract and Discussion were added to the report. The Panel should consider whether or not the data are now sufficient for making a determination of safety for all of the ingredients, and whether the N-nitrosation boilerplate language should be included in the Discussion in regards to the presence of possible residual amines as impurities for Panthenol. The Panel should be prepared to formulate a tentative Conclusion, provide the rationale to be described in the Discussion, and issue a Tentative Report for public comment. If the data are sufficient for all, then a safe (or safe with qualifications) Conclusion should be issued. If the data are not sufficient for some or all of the ingredients, then that decision should be reflected in the Conclusion. 2. Polyaminopropyl Biguanide (agenda and flash drive name – Polyaminopropyl Biguanide). Given the inclusion of two chemical names in the title of this safety assessment, the report introduction contains a fair amount of detail relating to the use of the INCI name Polyaminopropyl Biguanide to represent the chemical polyhexamethylene biguanide hydrochloride throughout the report text. An Insufficient Data Announcement with the following data requests was issued at the June 2017 Expert Panel meeting (this was the second IDA issued for this ingredient): a) Calculation of a margin of safety (MoS) for Polyaminopropyl Biguanide inhalation exposure, using toxicity data from a short-term (28-day) rat inhalation-exposure study and use concentration data on Polyaminopropyl Biguanide in hair sprays, both of which were included in the CIR safety assessment. b) Further clarification of urticarial reactions reported in SCCS assessment of Polyaminopropyl Biguanide. c) Raw data sheets (i.e., individual scores obtained during the induction and challenge phases) on subjects evaluated in the HRIPT on a product containing 0.2% Polyaminopropyl Biguanide submitted (HRIPT with raw data sheets) by the Council on May 2, 2017. d) A dermal sensitization quantitative risk assessment (QRA) for Polyaminopropyl Biguanide. Additionally, industry was encouraged to provide any available HRIPT data that could yield a more refined no-expected-sensitization-induction-level (NESIL); the current NESIL of 25µg/cm2 was considered likely to be overly conservative for use in the QRA. Furthermore, at the meeting, the Council informed the Panel that they would provide CIR with a corrected HRIPT summary and a corrected concentration of use table. In response to this IDA: a) MoSs for Polyaminopropyl Biguanide inhalation were calculated by the CIR staff. The Panel should determine whether the safety assessment report presents the modelling effort adequately. Page 3 – 144th Meeting of the CIR Expert Panel — Monday and Tuesday, September 11-12, 2017 Distributed for Comment Only -- Do Not Cite or Quote b) Given the Panel’s concern about contact urticaria, the 3 case reports in the published literature that were identified as relevant are summarized under the Contact Urticaria subheading in the section on Case Reports. The Panel should also determine whether case reports relating to anaphylaxis should be added to the Case Reports, Contact Urticaria section of the safety assessment report. c) The updated use data corrected the previously reported highest maximum use concentration of 0.5% in suntan products; the highest maximum use concentration in a leave-on product is now 0.2% in eye lotions. A corrected summary of the HRIPT on a leave-on product containing 0.5% Polyaminopropyl Biguanide (provided by the Council on 6-15-2017) was also received. d) To date, a dermal sensitization QRA has not been received from the Council, and the same is true for any additional available HRIPT data that might yield a more refined NESIL. The Panel should decide if all of the needs defined in the IDA have been met, or are otherwise deemed moot. Other comments from Council were received and addressed. In addition, comments relating to the inhalation toxicity of polyhexamethylene guanidine phosphate (PHMG) were received from Women’s Voices for the Earth. In these comments, the “discrepancy of professional opinion” with respect to how similar PHMG and Polyaminopropyl Biguanide are to each other was noted and publications were provided. The papers cited by WVE applied a no observed adverse effect concentration (NOAEC) from a 28-day inhalation-exposure study of Polyaminopropyl Biguanide (0.024 mg/m3) to read-across to the risks associated with inhalation exposure to PHMG. The Panel should consider this issue and determine whether or not the publications relating to PHMG-induced lung injury that are summarized in the Other Clinical Reports section of the Draft Tentative Report are relevant to this safety assessment. The Panel expressed concern about the irritation and sensitization potential of Polyaminopropyl Biguanide and discussed the likely recommendation that products containing Polyaminopropyl Biguanide be formulated to be non-irritating and non-sensitizing using the QRA or a similar risk assessment method. 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. With respect specifically to the potential for incidental inhalation exposure, the Panel should determine whether a safe Conclusion with inhalation-specific qualifications is warranted. 3. Mentha piperita (Peppermint) (agenda and flash drive name – Peppermint). At the April 2017 meeting, the Panel agreed that the safety assessment published in 2001 should be reopened to add 6 additional Mentha piperita (peppermint)-derived ingredients. At that meeting, the Panel issued an IDA with the following data requests for all ten ingredients: • Skin irritation and sensitization data • Composition, method of manufacture, and impurities data The following data were received in response to the Panel’s IDA: 1) use concentration data on the 6 ingredients that are being added; 2) method of manufacture, composition, and impurities data on Peppermint Leaf Extract (butylene glycol/water), Peppermint Leaf Extract (water/ethanol), peppermint leaf extract powder (not an INCI ingredient), and Peppermint Leaf Water; and 3) in vitro skin irritation data on Peppermint Leaf Extract (water/ethanol) (at concentrations of 10% and 100%) and an HRIPT on Peppermint Leaf Extract (water/ethanol) (at a concentration of 100%). Regarding the statement in the prior final report Conclusion that the concentration of pulegone in these ingredients should not exceed 1%, the Panel considered whether, in hindsight, their concern should have been addressed using a non-sensitizing-qualification approach (which may be based on a QRA). Furthermore, it was noted that the 1% concentration limit on pulegone was based, in part, on maximum leave-on product concentrations of 0.2% - 2% Mentha Piperita (Peppermint) Oil, but that the oil is now being used at concentrations up to 5% in leave-on Page 4 – 144th Meeting of the CIR Expert Panel — Monday and Tuesday, September 11-12, 2017 Distributed for Comment Only -- Do Not Cite or Quote products. Taking into consideration that skin irritation was observed in subjects after application of a cleansing gel containing 50% Mentha Piperita (Peppermint) Leaf Water (diluted to 5% concentration of the leaf water) and that Mentha Piperita (Peppermint) Leaf Water is being used at concentrations up to 40% in leave-on products, the Panel considered the possibility of issuing a Conclusion stating that products containing Mentha piperita (peppermint)-derived ingredients should be formulated to be non-irritating. Furthermore, given the terpene content of these ingredients, addition of the safe when formulated to be non-sensitizing qualification to the Conclusion that will be developed was further considered. The unpublished data, and received comments, have been incorporated into the report, as appropriate, and a draft Discussion has been added. The Panel should determine whether the data provided satisfy all of the data needs, and, if not, be prepared to state the additional needs that are needed to make a determination of safety, and issue a Tentative Amended Report with an insufficient data Conclusion. However, if the data that were received address all concerns, or those concerns are otherwise deemed moot, the Panel should determine whether a safe as used, safe with qualifications, or unsafe Conclusion should be issued. 4. Triglycerides (agenda and flash drive name – Triglycerides). This re-review was considered at the April 2017 meeting, and the Panel determined that it was appropriate to consolidate three previous reports on 25 triglyceride ingredients, and to include 26 triglycerides that had not yet been reviewed by the Panel. However, a question was raised about removing one of the ingredients, Glyceryl Tribehenate/Isostearate/Eicosandioate. The Panel should determine whether this ingredient should be removed from the report. Also at the April meeting, the Panel requested the following information in an IDA: • sensitization data for Tribehenin at the reported maximum concentration of use (i.e., 15.6% in mascara); • sensitization data for Caprylic/Capric Triglyceride at the reported maximum concentration of use (i.e., 95.6% in face and neck products); • sensitization data for Triethylhexanoin at the reported maximum concentration of use (i.e., 100% in face and neck products); • irritation and sensitization testing of C10-40 Isoalkyl Acid Triglyceride at the expected maximum concentration of use (no concentrations of use were reported); • clarification of the skin bleaching potential of Docosahexenoic/Docosapentenoic/Oleic/ Palmitic Triglyceride, including a dose-response for this action The following were received in response to the IDA: • TKL Research. (2000) Human repeated insult patch test: Moisturizer with 6% Tribehenin; • Consumer Product Testing Co. (2000) Repeated insult patch test protocol of a material containing 20% Tribehenin; • Anonymous. (2015) Clinical evaluation report: Human patch test (facial oil containing 95.51% Caprylic/Capric Triglyceride); • Product Investigations, Inc. (2015) Determination of the sensitizing propensities of facial oil (containing 95.51% Caprylic/Capric Triglyceride) on human skin; • KGL. Inc. (2015) Photocontact allergenicity potential of a facial oil containing 95.51% Caprylic/Capric Triglyceride. Also received were concentration of use data for the additional (add-on) triglycerides, and concentration of use information that was an update to that which was reported in the re-review document that the Panel reviewed in April. The most significant change that was reported in the update is that the maximum concentration of use of Tribehenin in deodorants is 5.1%, not 50.6%. Therefore, the maximum concentration of use reported for Tribehenin is 15% in mascara. After reviewing the available data, the Panel should determine whether a Tentative Amended Report with a safe as used, safe with qualifications, insufficient data, or mixed Conclusion should be issued at this meeting. Page 5 – 144th Meeting of the CIR Expert Panel — Monday and Tuesday, September 11-12, 2017 Distributed for Comment Only -- Do Not Cite or Quote Final Reports - there are 8 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. Bovine Milk Proteins (agenda and flash drive name – Milk Proteins). In April 2017, the Panel issued a Tentative Report with the Conclusion that the 16 bovine milk proteins and protein- derived ingredients are safe in the present practices of use and concentration. Data received since the April meeting include the results of the concentration of use survey on Lactoglobulin: no uses were reported. The 2017 FDA VCRP data indicate this ingredient has 1 reported use in a face and neck skin care preparation. Comments received from the Council prior to the April meeting, and on the tentative report, have been considered. The Panel should carefully review the Abstract, Discussion, and Conclusion of this report. If these are satisfactory, the Panel should issue a Final Report. 2. Plant Derived Proteins (agenda and flash drive name – Plant Proteins). In June 2017, the Panel issued a Tentative Report with the Conclusion that 18 of the 19 plant-derived protein and peptide ingredients are safe in cosmetics in the present practices of use and concentration. The Panel also concluded that the data on Hydrolyzed Maple Sycamore are insufficient to determine safety. No new unpublished data were received since the June meeting. The Council suggested expanding information regarding tree nut allergies with information from a review article. This, and all other comments received from the Council have been considered and incorporated in the report, as appropriate. The Panel should carefully review the Abstract, Discussion, and Conclusion of this report. If these are satisfactory, the Panel should issue a Final Report. 3. Ectodermal Derived Ingredients (agenda and flash drive name – Tissue Proteins). At the June 2017 meeting, the Panel issued a tentative report with the Conclusion that these 19 ingredients are safe in cosmetics in the present practices of use and concentration described in this safety assessment. Since the June meeting, CIR staff have received updated concentration of use data on Soluble Collagen and the results of the concentration of use survey on Atelocollagen. The maximum leave-on concentration for Atelocollagen is 0.005% in skin care products. The Council provided comments on the tentative report. Included in those comments was a recommendation to change the name of the report to the “Safety Assessment of Skin and Connective Tissue- Derived Proteins and Peptides.” Also, inclusion of information from the Hydrolyzed Wheat Protein (HWP) report regarding molecular weight size and Type 1 sensitivity reactions was suggested. The CIR Science and Support committee have also suggested incorporating this information in the Discussion section of the report. Included in the report are limited relevant information and supporting discussion language from the HWP report for the Panel’s review, but significant changes have been held in ambience until the Panel has had the opportunity to confer at the meeting on whether the limitations applied in the HWP report are relevant to the ingredients in this report. The Panel will need to determine if these additions are appropriate for the ingredients in this report and if further language is needed. All other Council comments have been incorporated, as appropriate. The Panel should carefully review the Abstract, Discussion, and Conclusion of this report. If these are satisfactory, the Panel should issue a Final Report. 4. Butyrospermum parkii (Shea) (agenda and flash drive name – Shea). At the April 2017 meeting, the Panel issued a revised tentative report for the 13 Butyrospermum parkii (shea)-derived ingredients with the Conclusion that these are safe in cosmetics in the present practices of use and concentration described in this safety assessment when formulated to be non-sensitizing. Previously, the Panel had concluded that 9 of the ingredients were safe as used in the present practices of use and concentration and that the data were insufficient for Butyrospermum Parkii (Shea) Nut Extract, Butyrospermum Parkii (Shea) Nut Shell Powder, Butyrospermum Parkii (Shea) Seedcake Extract, and Hydrolyzed Shea Seedcake Extract. However, the data needs for these 4 ingredients were fulfilled. The Panel should review the minutes from the Full Panel meeting of April 2017 to see if the discussion in the report adequately captures the rationale for the revised Conclusion with the sensitization caveat. Since the April meeting, an HRIPT on Butyrospermum Parkii (Shea) Seedcake Extract at 0.42% was received. These data have been incorporated into the report, as have comments received from the Council, as appropriate. Page 6 – 144th Meeting of the CIR Expert Panel — Monday and Tuesday, September 11-12, 2017 Distributed for Comment Only -- Do Not Cite or Quote The Panel should carefully review the Abstract, Discussion, and Conclusion of this report. If these are satisfactory, the Panel should issue a Final Report. 5. Humulus lupulus (Hops) (agenda and flash drive name – Hops). In April 2017, the Panel issued a Tentative Report with the Conclusion that Humulus Lupulus (Hops) Extract and Humulus Lupulus (Hops) Oil are safe as used when formulated to be non-sensitizing. The Panel changed the name of the report to reflect the revision of the names of the ingredients being reviewed. Specifically, five INCI ingredient names were consolidated under the name Humulus Lupulus (Hops) Extract, and humulus lupulus (hops) cone oil is now named Humulus Lupulus (Hops) Oil. No new data have been submitted. Council comments have been addressed. The Panel should review the Discussion to ensure that it captures the rationale for the report Conclusion and review the Abstract and Conclusion to ensure that they capture the Panel’s thinking. The Panel should be prepared to issue a Final Report. 6. Monoalkylglycol Dialkyl Acid Esters (agenda and flash drive name – Monoalkylglycol Dialkyl Acid Esters). In June 2017, the Panel concluded that 25 of the 28 monoalkylglycol dialkyl acid ester ingredients are safe as used in cosmetics. The Panel also concluded that the data on 3 of the 28 ingredients are insufficient to come to a Conclusion of safety. The data needs, as described in the December 2016 Insufficient Data Announcement, were: • Dermal penetration for Diethylpentanediol Dineopentanoate, Dioctadecanyl Didecyltetradecanoate, and Dioctadecanyl Ditetradecyloctadecanoate • If there is dermal absorption for any of the three ingredients specified in the previous bullet, then: 28-day dermal toxicity, genotoxicity, and irritation and sensitization at maximum concentration of use or greater (≥ 57%) • Because these ingredients can potentially form ester hydrolysis products, toxicity data on the hydrolysis products of these three ingredients including: Diethylpentanediol Dineopentanoate o 2,4-diethyl-1,5-pentanediol o neopentanoic acid o Dioctadecanyl Didecyltetradecanoate o 9,10-dinonyl-1,18-octadecanediol o decyltetradecanoic acid o Dioctadecanyl Ditetradecyloctadecanoate o 9,10-dinonyl-1,18-octadecanediol (repeat from above) o tetradecyloctadecanoic acid o Of the requested data, acute oral, genotoxicity, irritation, and sensitization for Diethylpentanediol Dineopentanoate were submitted; dermal penetration and 28-day dermal toxicity data were not submitted. Council comments have been addressed. Additionally, since the last time the Panel examined this report, data were discovered for one of the two hydrolysis products of Diethylpentanediol Dineopentanoate, neopentanoic acid, but not the other, 2,4-diethyl-1,5- pentanediol. These data include: acute oral, dermal, and inhalation toxicity; oral and dermal repeated dose toxicity; genotoxicity; dermal (100%) and eye irritation (100%); and sensitization (guinea pig maximization study (intradermal induction at 0.05%, topical induction at 25%, challenge 10%). No other data have been submitted to address the IDA. The Panel should consider whether the data that were received, in conjunction with the data on Diethylpentanediol Dineopentanoate already in the report, warrant a change in the Conclusion for this ingredient. If the new data warrant a change to the Conclusion of this report, the Panel should provide the rationale to be included in the Discussion, and issue a Final Report. If the data does not warrant a change to the Conclusion, the Panel should review the Abstract, Conclusion, and Discussion, ensuring that it captures the rationale for the current report Conclusion, and issue a Final Report. 7. Polyurethanes (agenda and flash drive name – Polyurethanes). In April 2017, the Panel issued a Tentative Report with the Conclusion that these ingredients are safe as used when formulated to be non-sensitizing. The Council has reported that the definitions of Polyurethane-60 and -61 were erroneously stated in the Web-Based Ingredient Dictionary (wINCI), but that the monographs have since been updated. Therein, dimethyl aminopropylamine (DMAPA) was erroneously stated instead of Page 7 – 144th Meeting of the CIR Expert Panel — Monday and Tuesday, September 11-12, 2017 Distributed for Comment Only -- Do Not Cite or Quote dimethylolpropionic acid (DMPA). With these changes, there are now no ingredients in this report for which DMAPA was used as a monomer. Council comments have been addressed. No new toxicity data were submitted. The Panel should review the Discussion to ensure that it captures the rationale for the report Conclusion. The Panel should also review the Abstract and Conclusion to ensure that they capture the Panel’s thinking, and issue a Final Report. 8. Alkane Diols (agenda and flash drive name – Alkane Diols). At the April 2017 Meeting, the Panel issued a Tentative Report with a safe Conclusion for 9 (out of 10) of the alkane diols and an insufficient data Conclusion for concentration of use for 1,4-Butanediol. A neurotoxicity study referring to 2,5-hexanedione has been added, Panel edits from the April 2017 Meeting were addressed, the Abstract and Discussion were updated, and the Conclusion was added to the report. For the Panel’s consideration with regard to 2,3-butanedione (aka diacetyl; a potential metabolite of the ingredient, 2,3-Butanediol), the Council has submitted a comment and accompanying article that refer to the toxicity of this metabolite; and, a draft report on 2,3-butanedione is now available from NTP with a Conclusion that indicates there is evidence of carcinogenicity in 2-year inhalation studies in rats exposed to 2,3-butanedione. The Panel should be prepared to provide any additional rationale to be described in the Discussion; to verify the Abstract, Discussion, and Conclusion; and to issue a Final Report. Other Items – there are 6 other items of business for consideration, comprising 3 re-review summaries, and 3 guidance document updates. Re-Review Summaries - After reviewing these drafts the Panel should issue them as final summaries, as appropriate. 1. Glyoxal (agenda and flash drive name – Glyoxal). The Panel has reviewed information that has become available since the year 2000 assessment, along with updated information regarding product types, and frequency and concentrations of use. The Panel determined to not reopen this safety assessment and reaffirmed the Conclusion published in 2000 that Glyoxal is safe for use in products intended to be applied to the nail at concentrations ≤ 1.25% and that the available data are insufficient to support the safety for other uses. 2. Quaternium-26 (agenda and flash drive name – Quaternium-26). New safety test data, since the final report was issued on Quaternium-26, were neither found in the published literature nor provided by the Council; however, the Panel reviewed updated information regarding product types and ingredient use frequencies provided by the FDA and use concentrations provided by the Council. The Panel determined to not reopen this safety assessment and reaffirmed the original Conclusion that Quaternium-26 is safe as used in cosmetic products. 3. Biotin – (agenda and flash drive name – Biotin). Some new safety test data were identified in the published literature; these data were similar to data that were included in the original assessment. The Panel reviewed updated information regarding product types and ingredient use frequencies provided by the FDA and maximum use concentrations provided by the Council. The Panel determined to not reopen this safety assessment and reaffirmed the original Conclusion that Biotin is safe as used in cosmetic products. Guidance Document Updates 4. Aerosols and the CIR Particle Size Document (agenda and flash drive name – Aerosols). The Aerosols document has been updated to address some of the comments received to date. At the April 2017 meeting, the Panel noted that a few sentences could be added to this document to address the topic of incidental inhalation exposures to nano-size ingredients that may be added to cosmetic formulations and may be present in the droplets/particulates released to the air in the breathing zone during the use of cosmetic sprays and powders. The document has not yet been revised to address this topic. Page 8 – 144th Meeting of the CIR Expert Panel — Monday and Tuesday, September 11-12, 2017 Distributed for Comment Only -- Do Not Cite or Quote The Panel should use the material presented by the speakers to inform such revision and issue an update guidance document. 5. Endocrine Activity (agenda and flash drive name – Endocrine Activity). This is the second draft of the CIR Expert Panel Endocrine Activity and Endocrine Disruption Background and Framework document. The first draft was reviewed by the Panel at the April 2017 meeting. Comments on the first draft received from the CIR Science and Support Committee and from Dr. Mihaich have been addressed in this draft. The Panel should review the document for the adequacy of the content, scope, and detail, including the draft Framework for Discussion Sections that appears at the end of the Document and the adequacy of the revisions implemented in response to the comments received. 6. Hair Dyes (agenda and flash drive name – Hair Dyes). This is the latest draft of the CIR Expert Panel Hair Dye Epidemiology document. The previous draft was reviewed by the Panel at the April 2017 meeting. Comments on the previous draft received from the Council’s Hair Coloring Technical Committee (HCTC) and from the Panel been addressed in the current draft. The Panel should review this draft of the document and determine whether it is suitable for posting on the CIR website, to replace the version currently posted. Please note that the Document may be revised again at the next few meetings, after the Panel receives the expected presentations on hair-dye chemistry and the recently completed European hair-dye self-testing study. Indeed, the Panel should consider review of these documents as an opportunity to prefigure any questions or concerns to be answered in those presentations. 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 8 reports to be issued as final safety assessments, followed by the remaining reports advancing in the process, including the tentative reports, draft reports, re-review summaries, and guidance documents. The agenda is split fairly evenly between reviewing the draft and tentative reports, and the final 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! Page 9 – 144th Meeting of the CIR Expert Panel — Monday and Tuesday, September 11-12, 2017