Safety Assessment of Trimellitic Anhydride Copolymers as Used in Cosmetics Status: Draft Report for Panel Review Release Date: August 28, 2015 Panel Meeting Date: September 21-22, 2015 The 2015 Cosmetic Ingredient Review Expert Panel members are: Chairman, Wilma F. Bergfeld, M.D., F.A.C.P.; Donald V. Belsito, M.D.; Ronald A. Hill, Ph.D.; Curtis D. Klaassen, Ph.D.; Daniel C. Liebler, Ph.D.; James G. Marks, Jr., M.D., Ronald C. Shank, Ph.D.; Thomas J. Slaga, Ph.D.; and Paul W. Snyder, D.V.M., Ph.D. The CIR Director is Lillian J. Gill, D.P.A. This safety assessment was prepared by Monice M. Fiume, Assistant Director/Senior Scientific Analyst/Writer and Bart Heldreth, Ph.D., Chemist. © Cosmetic Ingredient Review 1620 L Street, NW, Suite 1200 ♢ Washington, DC 20036-4702 ♢ ph 202.331.0651 ♢ fax 202.331.0088 ♢ [email protected] Commitment & Credibility since 1976 Memorandum To: CIR Expert Panel Members and Liaisons From: Monice M. Fiume MMF Assistant Director/Senior Scientific Analyst Date: August 28, 2015 Subject: Safety Assessment of Trimellitic Anhydride Copolymers as Used in Cosmetics Enclosed is the Draft Report on the Safety Assessment of Trimellitic Anhydride Copolymers as Used in Cosmetics. (It is identified as melply092015rep in the pdf document.) This is the first time the Panel is seeing a safety assessment on this family of six ingredients. The Scientific Literature Review was issued on June 1, 2015. The trimellitic anhydride copolymers included in this report form a family of cosmetic ingredients because that they all share in common trimellitic anhydride (aka 1,2,4-benzenetricarboxylic acid anhydride) as a monomer. Each copolymer is also composed of 1 to 4 of the following additional monomers: adipic acid, cyclohexanedimethanol (CHDM), ethylene glycol, isophthalic acid, maleic anhydride, neopentyl glycol, phthalic anhydride, propylene glycol, sebacic acid, trimethylpentanediol, or trimethylolpropane (chain-terminated by isostearic acid). Most of these ingredients are reported to function in cosmetics as film formers. No information has been submitted regarding the amount of each residual monomer present in these copolymer ingredients, and therefore it should be assumed that it is possible that residual amounts of the monomer(s) could be present in each copolymer. Accordingly, relevant information on the toxicity of these monomers is presented in Table 2 of the report. Much of this information came from ECHA or OECD SIDS reports, and some from previous CIR reports (melply092015prev_1 through melply092015prev_5.) This information is not intended to be exhaustive or complete, but purely summary information intended to provide insight as to any possible toxicity concerns for these monomers. Concentration of use data (melply092015data) were submitted by the Council. Comments on the SLR (melply092015pcpc) also were received from the Council and have been addressed. If the data included in this report adequately addresses the safety of the trimellitic anhydride copolymers, 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 not sufficient for making a determination of safety, then an Insufficient Data Announcement should be issued that provides a listing of the additional data that are needed. SAFETY ASSESSMENT FLOW CHART INGREDIENT/FAMILY _____Trimellitic Anhydride Copolymers______________________________________________ MEETING ________Sept 2015______________________________________________________________________________________ Public Comment CIR Expert Panel Report Status Priority List INGREDIENT PRIORITY LIST SLR June 1, 2015 DRAFT REPORT Draft Report Sept 2015 60 day public comment period Table Table IDA TR IDA Notice IDA DRAFT TENTATIVE 60 day public comment period Draft TR REPORT Table Table Tentative Report Issue TR Draft FR DRAFT FINAL REPORT 60 day Public comment period Table Table Different Conclusion PUBLISH Final Report Issue FR Distributed for comment only -- do not cite or quote Trimellitic Anhydride Copolymers – Sept 2015 – Monice Fiume icity Acute, Acute, Rptd Rptd – – – – al ation icity ation Use Reported Mfg of Method Impurities Toxicokinetics Dermal Penetration Animal Tox Dermal Animal Tox Oral Animal Tox, Acute, Inhal Animal Tox Derm Dose, Animal Tox, Rptd Dose, Oral Animal Tox Dose, Inhal Tox Repro/Dev Genotox Ocular Irritation Irr Membrane Mucous Dermal Irr/Sens Reports Case Carcinogenicity General Trimellitic Anhydride X X Copolymers Adipic Acid/CHDM/MA/ Neopentyl Glycol/Trimellitic Anhydride Copolymer Adipic Acid/Neopentyl Glycol/ X Trimellitic Anhydride Copolymer Isostearoyl Trimellitic Anhydride/ Trimethylolpropane Copolymer Phthalic Anhydride/Trimellitic X X X Anhydride/Glycols Copolymer Propylene Glycol/Sebacic Acid/ Trimellitic Anhydride Copolymer Trimethylpentanediol/Isophthalic Acid/Trimellitic Anhydride Copolymer Distributed for comment only -- do not cite or quote INFORMATION ON MONOMERS - Dose, icity Acute, Rptd Acute, Rptd Rptd – – – – icity . CIR by Reviewed Toxicokinetics Dermal Absorption Animal Tox Dermal Animal Tox, Rptd Oral Animal Tox Dose, Inhal Tox Repro/Dev Genotox Ocular Irritation Irr Membrane Mucous Animal Tox Oral Animal Tox, Acute, Inhal Respiratory Effects Human Recommended Limits Exposure Carcinogenicity Dermal Irr/Sens Animal Tox Derm Dose, trimellitic anhydride X X X X X X X X X X X X adipic acid X X X X X X X X X X cyclohexanedimethanol X X X X X X X ethylene glycol X X isophthalic acid X X X X X X X X X X maleic anhydride X X X X X X X X X X X X X neopentyl glycol X X X X X X X X X phthalic anhydride X X X X X X X X X X X propylene glycol X X X X X X X X X X sebacic acid X X X X trimethylpentanediol X X X X X X X X trimethylolpropane X X X X X X X X Distributed for comment only -- do not cite or quote Trimellitic Anhydride Copolymers Ingredient VCRP InfoBase PubMed SciFinder ChemPortal NTIS FDA ECHA HPV IUCLID/SIDS EU NICNAS Web Adipic Acid/CHDM/MA/Neopentyl Glycol/ 0 --- 0 0 0 0 0 0 no 0 Google Trimellitic Anhydride Copolymer restriction ChemID No hits: PubChem HSDB ChemSpdr Adipic Acid/Neopentyl Glycol/Trimellitic 411 CAS#: there/nothing 0 0 0 0 0 no not assessed Google; Anhydride Copolymer supplier useful restriction PubChem; (CAS # 28407-73-0) ChemID Technical Names: Adipic Acid, Polyester with 1,2,4-Benzenetricarboxylic Acid Cyclic 1,2- No hits Anhydride and 2,2-Dimethyl-1,3-Propanediol; HSDB by CAS # - Hexanedioic Acid, Polymer with 1,3-Dihydro- ChemSpdr refined by 1,3-Dioxo-5-Isobenzofurancarboxylic Acid and document type – 2,2-Dimethyl-1,3-Propanediol; 6 hits/0 useful 1,2,4-Benzenetricarboxylic acid, cyclic 1,2- anhydride, polyester with adipic acid and 2,2- trimellitic dimethyl-1,3-propanediol; anhydride 1,3-Propanediol, 2,2-dimethyl-, polyester with copolymer – 286 adipic acid and 1,2,4-benzenetricarboxylic acid hits/4 useful cyclic 1,2-anhydride ; 5 hits/5 used 1,3-Propanediol, 2,2-dimethyl-, polymer with 1,2,4-Benzenetri- 1,3-dihydro-1,3-dioxo-5-isobenzofuran- carboxylic carboxylic acid and hexanedioic acid; anhydride – 68 5-Isobenzofurancarboxylic acid, 1,3-dihydro- hits/4 useful 1,3-dioxo-, polymer with 2,2-dimethyl-1,3- propanediol and hexanedioic acid; nothing new Adipic acid-1,2,4-benzenetricarboxylic searching by anhydride-neopentyl glycol copolymer; individual names Adipic acid-1,2,4-benzenetricarboxylic anhydride-neopentyl glycol polymer; Adipic acid-neopentyl glycol-trimellitic anhydride copolymer; Adipic acid-neopentyl glycol-trimellitic anhydride polymer Supplier/Trade Names: Uniplex 670-P (Unitex Chemical Corporation) Isostearoyl Trimellitic Anhydride/ 0 CAS#: 0 0 0 0 0 0 no 0 No hits: Trimethylolpropane Copolymer supplier restriction PubChem (CAS # 1190965-82-2) ChemID Supplier/Trade Names: Schercemol ISTC Ester HSDB (Lubrizol Advanced Materials, Inc.) ChemSpdr; Google Distributed for comment only -- do not cite or quote Ingredient VCRP InfoBase PubMed SciFinder ChemPortal NTIS FDA ECHA HPV IUCLID/SIDS EU NICNAS Web Phthalic Anhydride/ Trimellitic Anhydride/ 74 CAS#: 0 0 0 0 0 0 no 0 No hits: Glycols Copolymer supplier; restriction PubChem (CAS # 186688-25-5) TRN 20 (7) ChemIDHS Technical Names: Phthalic 2006 DB Anhydride/Trimellitic ChemSpdr; Anhydride/Glycol/Neopentyl Glycol Google Copolymer; Phthalic/Trimelitic/Glycols Copolymer; 5-Isobenzofurancarboxylic acid, 1,3-dihydro-1, 3-dioxo-, polymer with 2,2-dimethyl-1,3-pro- panediol, 1,2-ethanediol and 1,3-isobenzo- furandione; 1,2-Ethanediol, polymer with 1,3-dihydro-1,3- dioxo-5-isobenzofurancarboxylic acid, 2,2- dimethyl-1,3-propanediol and 1,3-isobenzo- furandione; 1,3-Isobenzofurandione, polymer with 1,3- dihydro-1,3-dioxo-5-isobenzofurancarboxylic acid, 2,2-dimethyl-1,3-propanediol and 1,2- ethanediol; 1,3-Propanediol, 2,2-dimethyl-, polymer with 1,3-dihydro-1,3-dioxo-5-isobenzofuran- carboxylic acid, 1,2-ethanediol and 1,3- isobenzofurandione; Ethylene glycol-neopentyl glycol-phthalic anhydride-trimellitic anhydride copolymer Supplier/Trade Names: Polynex Resin (Estron Chemical, Inc.) Propylene Glycol/Sebacic Acid/Trimellitic 0 --- 0 0 0 0 0 0 no 0 No hits: Anhydride Copolymer restriction PubChem ChemID HSDB ChemSpdr Trimethylpentanediol/Isophthalic 0 --- 0 0 0 0 0 0 no 0 No hits: Acid/Trimellitic Anhydride Copolymer restriction PubChem ChemID HSDB ChemSpdr Distributed for comment only -- do not cite or quote SciFinder – Feb 24 2015: trimellitic anhydride copolymer (refined by document type) – 286 hits/4 useful Search by CAS # (28407-73-0;