BLUE BOOK 1 Pelargonic Acid CIR EXPERT PANEL MEETING JUNE 28-29, 2010 CIR Panel Book Page 1 CIR History of: Pelargonic Acid and its Esters A scientific literature review (SLR) on this group of ingredients was announced on September 25, 2009. During the 60-day comment period on the SLR, industry data on cetearyl isononanoate and isononyl nonanoate were received. Most of the data are on chemical and physical properties of these ingredients, and only the conclusions for the following studies were also received: acute oral toxicity (cetearyl isononanoate – Tegosoft CI), skin irritation (cetearyl isononanoate – Tegosoft CI), acute oral toxicity (isononyl isononanoate – Tegosoft INI), skin irritation (isononyl isononanoate – Tegosoft INI), and ocular irritation (isononyl isononanoate – Tegosoft INI). These data have been incorporated. The following data on pelargonic acid, a registered herbicide, have been requested from the Environmental Protection Agency (EPA) and will be incorporated: acute inhalation, oral, and dermal toxicity data; ocular irritation, skin irritation, and skin sensitization data; and genotoxicity, reproductive toxicity, and carcinogenicity data. 1st Review, Belsito and Marks Teams/Panel: December 7-8, 2009 An insufficient data announcement with the following data requests was issued: (1) potential for dermal sensitization and irritation at current use concentrations (a human repeated insult patch test protocol is recommended) for isodecyl isononanoate (used at 80%) as a representative ester (available irritation/sensitization data on other ingredients also would be useful), (2) UV absorption data for pelargonic acid and isodecyl isononanoate as a representative acid and ester, respectively (such data on other ingredients listed in the safety assessment also would be useful), and (3) metabolic fates of isononanoic acid and isodecanol as representative constituent fatty acid and alcohols that would be produced after ester linkage cleavage. 2nd Review, Belsito and Marks Teams/Panel: April 5-6, 2010 Data, on the following ingredients, RIPT and UV absorption data included, were received in response to the preceding announcement and have been incorporated into the report text: isodecyl isononanoate, cetearyl isononanoate, cetearyl nonanoate, cholesteryl nonanoate, isotridecyl isononanoate, isononyl isononanoate, neopentyl glycol, neopentyl glycol diisononanoate, PEG-5 isononanoate, and ethylhexyl pelargonate. A revised ingredient use concentration table, based on an industry survey, was also provided. In addition to the industry data included, the draft tentative report also contains the summary, discussion and conclusion from CIR published safety assessments on propylene glycol dipelargonate, isobutyl stearate, and isodecyl oleate, and data on the following ingredient moieties from the published literature: isononanoic acid, isononyl alcohol, isotridecyl alcohol, and neopentyl glycol. These data have been included for use in the safety evaluation of ingredients for which little or no data have been identified as well as to address concerns relating to safety of ingredient moieties that may result from ester metabolism. The Panel discussed the observation that INCI names for the esters in this safety assessment are not consistent with IUPAC nomenclature. However, it was noted that IUPAC nomenclature conditions are not suitable for ingredient labeling on cosmetic products, in that these ingredients are not pure substances. Therefore, the inclusion of sic by ingredient names in the safety assessment was considered a distraction. In table 1 of the safety assessment, the inclusion of [sic] after a technical name or CAS No. denotes those instances wherein the authors of the dictionary associated a specific branched chemical entity other than an omega-2 methyl substituted isomer with an “iso” INCI name. The removal of the following 4 ingredients from the safety assessment was discussed due to concern over metabolic products and their potential toxicity that was expressed: cholesteryl nonanoate, dihydrocholesteryl nonanoate, ethylhexyl isononanoate, and isotridecyl isononanoate . Both Teams did not agree with this proposal, and, thus, these ingredients were not deleted. The absence of method of manufacture and impurities data from the report text was also noted. CIR Panel Book Page 2 At the conclusion of the discussion, the Panel issued a tentative report with a safe as used conclusion on pelargonic acid and its esters. 3rd Review, Belsito and Marks Teams/Panel: June 28-29, 2010 The draft final safety assessment (Table 2) has been revised to include log P/molecular weight data on the following ingredients: butylene glycol diisononanoate, cetyl isononanoate, diethylene glycol diethylhexanoate/diisononanoate, diethylene glycol diisononanoate, dihydrocholesteryl nonanoate, dipentaerythrityl pentaisononanoate, ethylhexyl isononanoate, isodecyl isononanoate, isononyl isononanoate, isostearyl isononanoate, isotridecyl isononanoate, neopentyl glycol diisononanoate, pentaerythrityl tetraisononanoate, propylene glycol diisononanoate, tridecyl isononanoate, neopentyl glycol dicaprylate/dipelargonate/dicaprate, PEG-2 diisononanoate, and PEG-5 isononanoate. Industry data were received during the 60-day comment period for the tentative report that was issued. The report text now contains information relating to the production methodology for and impurities in pelargonic acid, cetearyl isononanoate, and isononyl isononanoate; neopentyl glycol impurities data; and the following industry data: short- term oral toxicity, short-term dermal toxicity, developmental toxicity, and genotoxicity data on isononyl isononanoate. Industry is also the source of methods of production data on cetearyl isononanoate and isononyl isononanoate that were received. CIR Panel Book Page 3 Literature Search on Pelargonic Acid and Nonanoate Esters* Ingre- Toxline ChemIDplus Multidatabase DART Household Beilstein Registry Kosmet Napralert RTECS CAplus dients &PubMed (See legend*) Products PA (207) (1) (1) (6) (1) 0 (1) (5) (60) (1) (216) BGD 0 0 0 0 0 0 0 0 0 0 0 CO 0 0 0 0 0 0 (1) 0 0 0 0 CYIN 0 0 0 0 (1) 0 0 0 0 0 0 CYN 0 0 0 0 0 0 0 0 0 0 0 CEI (1) (1) 0 0 0 0 (1) 0 0 0 0 CN 0 (1) 0 0 (1) 0 (1) 0 0 0 0 DGD 0 (1) 0 0 0 0 (2) 0 0 0 0 Dgdd 0 0 0 0 0 0 0 0 0 0 0 DN 0 0 0 0 0 0 0 0 0 0 0 DP 0 (1) 0 0 0 0 (1) 0 0 0 0 EI 0 (2) 0 0 (1) 0 (2) 0 0 0 0 G7D 0 0 0 0 0 0 (1) 0 0 0 0 IDI 0 (1) 0 0 0 0 (2) 0 0 0 0 INI 0 (1) 0 0 (1) 0 (2) 0 0 0 0(6) ISI 0 0 0 0 0 0 (1) 0 0 0 0 ITI 0 (2) 0 0 0 0 (2) 0 0 0 0 NPD 0 0 0 0 0 0 (1) 0 0 0 0 P2D 0 0 0 0 0 0 0 0 0 0 0 P5I 0 0 0 0 0 0 0 0(4) 0 0 0 PT 0 (1) 0 0 0 0 (1) 0 0 0 0 PN 0 0 0 0 0 0 0 0 0 0 0 P20O 0 0 0 0 0 0 0 0 0 0 0 PGD 0 0 0 0 0 0 (1) 0 0 0 0 TI 0 0 0 0 0 0 (1) 0 0 0 0 EHP 0 (1) 0 0 0 0 (1) 0 0 0 0 EP (7) (1) 0 0 0 0 (1) 0(2) (4) (1) (15) IP 0 (1) 0 0 0 0 (1) 0 0 0 0 MP (9) (1) 0 0 0 0 (1) 0 (5) (1) (28) NPD 0 0 0 0 0 0 0 0 0 0 0 PTT 0 (1) 0 0 0 0 (1) 0 0 0 0(2) Chemical Moieties of Concern IA 3(3) 0 0 0 0 0 1(19) INA 4(18) 0 1(1) 0 0 0 2(6) ITA 2(4) 0 0 0 0 0 4(8) NG 6(69) 7(7) 0 0 0 1 2(49) *Data in Table: Publications used (Total no. in search); Multidatabase = HSDB, CCRIS, ITER, IRIS, Gene-Tox, and LacMed; InitialSearch: 1-11-10 Search Updated (PubMed+Toxline) on 4-10-2010. No useful information was found. Ingredients PA - Pelargonic Acid OR Nonanoic Acid OR 112-05-0 BGD - Butylene Glycol Diisononanoate CO - Cellobiose Octanonanoate OR 172585-66-9 CYIN - Cetearyl Isononanoate CYN - Cetearyl Nonanoate CEI - Cetyl Isononanoate OR 84878-33-1 CN - Cholesteryl Nonanoate OR Cholesterin Pelargonate OR Cholesteryl Pelargonate OR 1182-66-7 DGD - Diethylene Glycol Diisononanoate OR PEG-2 Diisononanoate OR 106-01-4 OR 190282-37-2 Dgdd - Diethylene Glycol Diethylhexanoate/diisononanoate DN - Dihydrocholesteryl Nonanoate DP - Dipentaerythrityl Pentaisononanoate OR 84418-63-3 EI - Ethylhexyl Isononanoate OR 2-Ethylhexyl Isopelargonate OR 70969-70-9 OR 71566-49-9 G7D - Glycereth-7 Diisononanoate OR PEG-7 Glyceryl Ether Diisononanoate OR 125804-15-1 IDI - Isodecyl Isononanoate OR 41395-89-5 OR 59231-35-5 1 CIR Panel Book Page 4 Literature Search on Pelargonic Acid and Nonanoate Esters* INI - Isononyl Isononanoate OR 42131-25-9 OR 59219-71-5 ISI - Isostearyl Isononanoate OR 90967-66-1 ITI - Isotridecyl Isononanoate OR 42131-27-1 OR 59231-37-7 NPD - Neopentyl Glycol Diisononanoate OR 137636-04-5 P2D - PEG-2 Diisononanoate P5I - PEG-5 Isononanoate PT - Pentaerythrityl Tetraisononanoate OR 93803-89-5 PN - Phytosteryl Nonanoate P20O - Polyglyceryl-20 Octaisononanoate PGD - PropyleneGlycol Diisononanoate OR 125804-17-3 TI - Tridecyl Isononanoate OR 125804-18-4 EHP - Ethylhexyl Pelargonate OR 59587-44-9 EP - Ethyl Pelargonate OR Ethyl Nonanoate OR 123-29-5 IP - Isobutyl Pelargonate OR Isobutyl Nonanoate OR 30982-03-7 MP- Methyl Pelargonate OR Methyl Nonanoate OR 1731-84-6 NPD - Neopentyl Glycol Dicaprylate/Dipelargonate/Dicaprate PTT - Pentaerythrityl Tetrapelargonate OR 14450-05-6 Chemical Moieties of Concern IA - Isononanoic Acid OR 26896-18-4 OR 693-19-6 INA - Isononyl Alcohol OR Isononanol OR 27458-94-2 ITA - Isotridecyl Alcohol OR Isotridecanol OR 27458-92-0 NG - Neopentyl Glycol OR 126-30-7 Pelargonic Acid OR Nonanoic Acid OR 112-05-0 OR Butylene Glycol Diisononanoate OR Cellobiose Octanonanoate OR 172585-66-9 OR Cetearyl Isononanoate OR Cetearyl Nonanoate OR Cetyl Isononanoate OR 84878-33-1 OR Cholesteryl Nonanoate OR Cholesterin Pelargonate OR Cholesteryl Pelargonate OR 1182-66-7 OR Diethylene Glycol Diisononanoate OR PEG-2 Diisononanoate