BLUE BOOK 1 Methyl Acetate CIR EXPERT PANEL MEETING AUGUST 30-31, 2010 Memorandum To: CIR Expert Panel Members and Liaisons From: Bart Heldreth Ph.D., Chemist Date: July 30, 2010 Subject: Draft Final Report of Methyl Acetate, Simple Alkyl Acetate Esters, Acetic Acid and its Salts as used in Cosmetics . This review includes Methyl Acetate and the following acetate esters, relevant metabolites and acetate salts: Propyl Acetate, Isopropyl Acetate, t-Butyl Acetate, Isobutyl Acetate, Butoxyethyl Acetate, Nonyl Acetate, Myristyl Acetate, Cetyl Acetate, Stearyl Acetate, Isostearyl Acetate, Acetic Acid, Sodium Acetate, Potassium Acetate, Magnesium Acetate, Calcium Acetate, Zinc Acetate, Propyl Alcohol, and Isopropyl Alcohol. At the June 2010 meeting, the Panel reviewed information submitted in response to an insufficient data announcement for HRIPT data for Cetyl Acetate at the highest concentration of use (lipstick). On reviewing the data in the report, evaluating the newly available unpublished studies and assessing the newly added ingredients, the Panel determined that the data are now sufficient, and issued a Tentative Report, with a safe as used conclusion. Included in this report are Research Institute for Fragrance Materials (RIFM) sponsored toxicity studies on Methyl Acetate and Propyl Acetate, which were provided in “wave 2” at the June Panel Meeting but are now incorporated in full. The Tentative Report was issued for a 60 day comment period (60 days as of the August panel meeting start date). The Panel should now review the Draft Final Report, confirm the conclusion of safe, and issue a Final Report. All of the materials are in the Panel book as well as in the URL for this meeting's web page http://www.cir- safety.org/aug10.shtml. CIR Panel Book Page 1 CIR Panel Book Page 2 CIR Expert Panel History with Methyl Acetate 2009 – Methyl Acetate was selected for review. December 2009 - CIR issued a Scientific Literature Review. Draft Report April 2010 - The draft report was brought before the Expert Panel, with the addition of Acetic Acid and the metal salt ingredients. The Panel decided to request a draft tentative report. The Panel stated that additional data are needed, specifically an HRIPT of Cetyl Acetate at the highest concentration of use (reportedly 17% at the time of the panel meeting) to address the issue of sensitization. Draft Tentative Report June 2010 – The draft tentative report was brought before the Expert Panel, with the addition of an unpublished maximization study of Cetyl Acetate at 12.6% in a lipstick formulation (which, according to industry, is the actual highest use concentration in a lipstick for Cetyl Acetate, not 17%). The Expert Panel determined that all data needs had been met and requested that a Tentative Report be issued, with a safe as used conclusion. Tentative Report July 1, 2010 – The tentative report was prepared and made available for a 60 day public comment period. CIR Panel Book Page 3 Ingredient Managers: Angela Howard & Bart Heldreth Dates: 9/1/2009-2/28/2010 Ingredient Name(s): CAS RN Ingredient Name(s): CAS RN Ingredient Name(s): CAS RN Ingredient Name(s): CAS RN Ingredient Name(s): CAS RN Methyl Acetate 79-20-9 Isobutyl Acetate 110-19-0 Stearyl Acetate 822-23-1 Isopropyl Alcohol 67-63-0 Potassium Acetate 127-08-2 Butoxyethyl Acetate 112-07-2 Isopropyl Acetate 108-21-4 Myristyl Acetate 638-59-5 Magenesium Acetate 142-72-3 t -Butyl Acetate 540-88-5 Isostearyl Acetate NL Nonyl Acetate 143-13-5 Acetic Acid 64-19-7 Calcium Acetate 62-54-4 Cetyl Acetate 629-70-9 Propyl Acetate 109-60-4 Propyl Alcohol 71-23-8 Sodium Acetate 127-09-3 Zinc Acetate 557-34-6 Checklist Database Search Terms Date Hits Notes Free PubMed A, B 8/18/2009 D 11/3/2009 E 11/4/2009 F 2/5/2010 Free HPDB A HSDB; Chem Idplus, Toxline, CCRIS, CPDB, DART, 100- GENETOX, IRIS, ITER, LactMed, 200/ch Multi-Database, TRI, Haz-Map, Free TOXNET A, F em Household Products, TOXMAP Free NTP A Free search/ Pay retrieval NTIS Yr license Merck A FDA A Federal Register Notices SCCP A, B, F Opinions and EU Directives IPCS A 11/20/2009 Password Required RIFM F Pay Service STN A, F RTECS, Beilstein OECD A 9/3/2009 SIDS Reports HPVIS A 12/17/2009 High Production Volume Iinformation System FOIA Submitted FOIA Results Search Terms Key A CAS No(s) B INCI Names C Methanol D isopropyl alcohol AND toxicity E propyl alcohol AND toxicity F Acetic Acid and the metal acetate salts via name and CAS Nos. (and CAS files where available) CIR Panel Book Page 4 Transcripts/ Minutes 115th COSMETIC INGREDIENT REVIEW EXPERT PANEL MEETING Washington, D.C. Monday, June 28, 2010 CIR Panel Book Page 5 2 11 DR. BELSITO: Okay. In April we went 12 insufficient asking for an HRIPT for cetyl acetate 13 at the highest use concentration of lipstick. And 14 we got those data from the Council. It was for 24 15 subjects -- 27 subjects and essentially was 16 negative. And so the question now is is the data 17 adequate and do we -- are we comfortable with the 18 discussion? And this morning we got some updated 19 concentration of use on the acetic acid and 20 acetates. 21 Is this yours, also, Lillian? Oh, okay. 22 So is there anything different from what we had CIR Panel Book Page 6 81 1 before on the concentrations? 2 DR. HELDRETH: Well, for the acid and 3 the salts I had added them to this grouping after 4 the cycle of requesting the data. So this is new. 5 We didn't have on the acid and the salts, we 6 didn't have concentration of use yet. 7 DR. BELSITO: Oh. 8 DR. HELDRETH: These are -- for the acid 9 and the salts. 10 DR. BELSITO: Okay. 11 DR. LIEBLER: Right. I think previously 12 we didn't have anything, right, with these? 13 DR. BELSITO: So this is all new data. 14 Okay. So all quite low. 15 DR. HELDRETH: The high uses were in the 16 -- the higher uses I should say were in the 17 esters. And we had that data. 18 DR. BELSITO: Right. 19 DR. HELDRETH: So this is only related 20 to the acids and the salts that were added in 21 April. 22 DR. BELSITO: Okay. So are we CIR Panel Book Page 7 82 1 comfortable with the information that we have on 2 manufacturing and impurities? 3 DR. LIEBLER: I think it's brief, but 4 reasonable. 5 DR. BELSITO: Okay. So in the 6 irritation and sensitization studies, at the last 7 meeting we looked at a study with 11.7 percent 8 cetyl acetate and I don't see that here. I see 9 12.6 percent. And unfortunately, I didn't save 10 the whole report. I just saved the conclusion in 11 my old report. But I had noted that it was 11.7 12 percent. These were studies that were handed out 13 at the last meeting. So did I just copy the 14 concentration down wrong? 15 DR. BRESLAWEC: You had what percentage? 16 DR. BELSITO: My note was 11.7 percent 17 cetyl acetate. 18 DR. BRESLAWEC: Could it have been 17 19 percent? 20 DR. BELSITO: I mean, it could have been 21 anything because it's not in this document and I 22 didn't save -- this was CIR supplement page 250. CIR Panel Book Page 8 83 1 You know, I didn't save all 250 pages in my 2 document. I just stuck this in my old document, 3 so I don't -- 4 DR. HELDRETH: No, you're correct. It's 5 not in the back of the book here. We had the 11.7 6 percent and we asked that we would get an HRIPT 7 study at the maximum dose and Industry did come 8 back with a maximization. 9 DR. BELSITO: Right. And that's the 10 only one you included. But why throw out an 11 existing study? 12 DR. HELDRETH: It was an accident on my 13 part. 14 DR. BELSITO: Okay. 15 DR. HELDRETH: It will be in there. 16 DR. BELSITO: And then we also had one 17 on isopropyl alcohol at at 80.74 percent that's 18 not in this current document either that we 19 reviewed last time. 20 DR. BRESLAWEC: It was isopropyl alcohol 21 at what percentage? 22 DR. BELSITO: It was isopropyl alcohol CIR Panel Book Page 9 84 1 at 80.74 percent. 2 DR. BRESLAWEC: Okay. We will find it 3 and include it. 4 DR. BELSITO: Yeah. The derm signing 5 off on it was Norm Cainoff. Again, I just have 6 the last conclusion pages, but I'll keep them in 7 my book. 8 Okay. In the discussion on page 26, the 9 third line, what is ASDFHQE? 10 DR. BRESLAWEC: That is a special coding 11 system. 12 (Laughter) 13 DR. BELSITO: Just for the heck of it I 14 typed it in to search the web. It didn't come up 15 with anything either. 16 DR. HELDRETH: I think what happened is 17 I inserted a citation there and somehow when the 18 citations were updated it left the gibberish there 19 and I didn't catch it before it got in 20 publication. 21 DR. BELSITO: Okay. So we need to add 22 to this report or the summary the two missing CIR Panel Book Page 10 85 1 studies that I just found out.