Safety Assessment of Alkyl Esters As Used in Cosmetics
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PINK Safety Assessment of Alkyl Esters as Used in Cosmetics CIR EXPERT PANEL MEETING DECEMBER 10-11, 2012 Memorandum To: CIR Expert Panel Members and Liaisons From: Monice M. Fiume MMF Senior Scientific Analyst/Writer Date: November 16, 2012 Subject: Amended Safety Assessment of Alkyl Esters as Used in Cosmetics Enclosed in the Amended Safety Assessment of Alkyl Esters as Used in Cosmetics. The status of this document is draft tentative amended report for CIR Expert Panel Review. This report was tabled at the September meeting so that historical use data from reports on ingredients previously reviewed by CIR could be added to the safety assessment. You will find these data incor- porated into Table 8. Incorporation of the historical data into the table allows the Panel a side-by-side comparison of the concentration reported when determining safety in the original safety assessments compared to the use data submitted with the current re-review. Increases in reported concentrations are highlighted. Also at the September meeting, the Panel deleted 16 alkyl ethylhexanoates from the report. Concern about the possible fetotoxicity of 2-ethylhexanoic acid, a possible metabolite of the ethylhexanoates, led to a determination that these ingredients are not “no brainers” and therefore, the ethylhexanoates should not be included in this review. The following unpublished data have been received since the last review. These data, which are included under the data tab of this submission, have been incorporated. 1. Personal Care Products Council. 2012. Updated concentration of use by FDA product category: alkyl esters and ethylhexanoates; 2. Personal Care Products Council. 2012. Updated concentration of use by FDA product category: cetyl esters; 3. Product Investigations, Inc. 2008. Determination of the irritating and sensitizing propensities of a product on human skin (body oil containing 77.9% Ethylhexyl Palmitate); 4. Clinical Research Laboratories. 2009. Repeated insult patch test of eyebrow pencil containing 38.8% Ethylhexyl Stearate; 5. Product Investigations, Inc. 2008. Determination of the irritating and sensitizing propensities of a product on human skin (lip gloss containing 25.9% Ethylhexyl Stearate); 6. Consumer Product Testing Co. 2005. Repeated insult patch test of a concealer containing 29.5% Isocetyl Myristate; 7. Clinical Research Laboratories. 2011. Repeated insult patch test of lipstick containing 15.2% Cetyl Ricinoleate. Again, the data profile is being provided in order by chain length and chemical structure and by alphabetical order. The data profile on the component alcohol and acids is included between the two. As a final note, please be aware that the Supplemental books from the March meeting that provided the original CIR safety assessments will be available on the CIR website. It is expected the Panel will issue a Tentative Amended Report at this meeting. Distributed for Comment Only -- Do Not Cite or Quote CIR Panel Book Page 1 Distributed for Comment Only -- Do Not Cite or Quote Alkyl Esters Re-Review History March 5-6, 2012: original consideration of re-review The re-review of Cetyl Esters was presented for consideration to re-open. An additional 200 alkyl esters were presented as potential add-on ingredients. The Panel stated that 52 ingredients (that were included for supporting data but not included for review in the safety assessment) that have been reviewed or re-reviewed previously should also be included in the safety assessment. The Panel considered an additional 6 ingredients that might have been included, but determined that it was not appropriate. The ingredients that will not be included (for the following reasons) are: decyl hempseedate (hempseedate has not been reviewed); hexyldecyl ester of hydrolyzed collagen (lack of chemical similarity); lauryl Carpotroche brasiliensis seedate; lauryl Theobroma grandiflorum seedate; myristyl Carpotroche brasiliensis seedate; and myristyl Theobroma grandiflorum seedate (these four ingredients have reported function as skin bleaching agents). A concern was expressed regarding the lack of data on biotransformation of branched fatty acids and branched alcohols in the skin. September 10-11, 2012: Tentative Amended Report The safety assessment was revised since the March meeting to include the additional 52 ingredients. Additionally, another unreviewed alkyl ester (Cetyl Myristoleate) was identified and added. The additions resulted in a family of 254 ingredients being evaluated in this safety assessment. Concentration of use data were received from industry and incorporated. Frequency of use data were updated using the May 2012 VCRP submission. The Panel deleted the 16 ethylhexanoates from the report; a discussion of the fact that cetearyl ethylhexanoate is now used at higher concentrations than previously reported and the fetotoxicity of 2-ethylhexanoic acid, a possible metabolite, led to the determination that these ingredients are not “no brainers.” These ingredients will be reviewed separately. The report was tabled for a more direct comparison of historic vs. current use for some of the previously reviewed ingredients, and to determine whether existing data support that higher concentration. December 10-11, 2012: Tentative Amended Report The ethylhexanoates have been removed and the historic use data have been added to the report. The following unpublished data have been received and added to the report: 1. Personal Care Products Council. 2012. Updated concentration of use by FDA product category: alkyl esters and ethylhexanoates; 2. Personal Care Products Council. 2012. Updated concentration of use by FDA product category: cetyl esters; 3. Product Investigations, Inc. 2008. Determination of the irritating and sensitizing propensities of a product on human skin (body oil containing 77.9% Ethylhexyl Palmitate); 4. Clinical Research Laboratories. 2009. Repeated insult patch test of eyebrow pencil containing 38.8% Ethylhexyl Stearate; 5. Product Investigations, Inc. 2008. Determination of the irritating and sensitizing propensities of a product on human skin (lip gloss containing 25.9% Ethylhexyl Stearate); 6. Consumer Product Testing Co. 2005. Repeated insult patch test of a concealer containing 29.5% Isocetyl Myristate; 7. Clinical Research Laboratories. 2011. Repeated insult patch test of lipstick containing 15.2% Cetyl Ricinoleate. CIR Panel Book Page 2 Distributed for Comment Only -- Do Not Cite or Quote Alkyl Esters Data Profile –presented by chain length and structure – Dec 2012 – Writer, Monice Fiume on-Human on-Human on-Human on_Animal Year Reviewed Composition/Con- stituents/Impurities Mfg of Methods Toxicokinetics Penetration Dermal Acute Tox-Derm Acute Tox-Oral Acute Tox-Inhal Rptd Dose-Derm Rpted Dose-Oral Rptd Dose-Inhal Tox Repro/Dev Genotoxicity Carcinogenicity Derm Irritation- N Derm Sensitization N N Derm Irritation- Human Derm Sensitization Human Human Phototox - Irritation Ocular Phototox- Phototox- Straight chain alkyl ingredients by total length Cetyl Esters 1997 X X X X Caprylyl Butyrate Caprylyl Caprylate Hexyl Laurate Butyl Myristate 2010 X X X X X X X X Decyl Laurate Butyl Stearate 1985* X X X X X X X X X X Arachidyl Propionate 1990* X X X X X X X X X X Stearyl Caprylate 2010 Decyl Myristate 2010 Lauryl Laurate Cetyl Caprylate Tridecyl Laurate Cetyl Caprate Decyl Palmitate Lauryl Myristate 2010 Myristyl Laurate X Tridecyl Myristate 2010 Myristyl Myristate 2010 X X X X X X Cetyl Laurate Lauryl Palmitate X Lauryl Stearate Cetyl Myristate 2010 Tridecyl Stearate Myristyl Stearate 1985* X X X X Cetyl Palmitate 1982* X X X X X X X X X X X Stearyl Palmitate 2010 Cetyl Stearate 1985* X X Lauryl Behenate X Stearyl Heptanoate 2010 X X X X X X X Tridecyl Behenate Stearyl Stearate 2010 Cetyl Behenate X Stearyl Behenate 2010 Arachidyl Behenate Behenyl Behenate Unsaturated, straight chain Heptyl Undecylenate Butyl Oleate X X X X Caprylyl Eicosenoate Decyl Oleate 1982* X X X X X X X Cetyl Myristoleate Lauryl Oleate X Oleyl Myristate 2010 Cetyl Oleate X X Tridecyl Erucate Oleyl Stearate X Stearyl Linoleate Oleyl Oleate X Oleyl Arachidate X Stearyl Erucate Erucyl Oleate Oleyl Erucate Arachidyl Erucate Behenyl Erucate Erucyl Arachidate Erucyl Erucate Lignoceryl Erucate Branched, by longest length Isohexyl Neopentanoate Isopropyl Sorbate Ethylhexyl Neopentanoate Isobutyl Pelargonate 2010 Isodecyl Neopentanoate Ethylhexyl Isononanoate 2010 X X CIR Panel Book Page 3 Distributed for Comment Only -- Do Not Cite or Quote Alkyl Esters Data Profile –presented by chain length and structure – Dec 2012 – Writer, Monice Fiume on-Human on-Human on-Human on_Animal Year Reviewed Composition/Con- stituents/Impurities Mfg of Methods Toxicokinetics Penetration Dermal Acute Tox-Derm Acute Tox-Oral Acute Tox-Inhal Rptd Dose-Derm Rpted Dose-Oral Rptd Dose-Inhal Tox Repro/Dev Genotoxicity Carcinogenicity Derm Irritation- N Derm Sensitization N N Derm Irritation- Human Derm Sensitization Human Human Phototox - Irritation Ocular Phototox- Phototox- Isohexyl Caprate Isopropyl Laurate X Tridecyl Neopentanoate Octyldodecyl Neopentanoate Isononyl Isononanoate 2010 X X X X X X X X Ethylhexyl Pelargonate 2010 X X X Propylheptyl Caprylate X X X X X X X X Isopropyl Myristate 2010 X X X X X X X X X X X X X Myristyl Neopentanoate Isobutyl Myristate 2010 Isohexyl Laurate Isoamyl Laurate Isodecyl Isononanoate 2010 X X Isopropyl Palmitate 1982* X X X X X X X X X X Ethylhexyl Laurate X X X X X X X X X X Isostearyl Neopentanoate 1985* X X X X X X X X X X Isotridecyl Isononanoate 2010