Safety Assessment of Hydrogen Peroxide as Used in Cosmetics Status: Draft Report for Panel Review Release Date: May 11, 2018 Panel Meeting Date: June 4-5, 2018 The 2018 Cosmetic Ingredient Review Expert Panel members are: Chair, 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 Executive Director is Bart Heldreth Ph.D. This report was prepared by Lillian C. Becker, Scientific Analyst/Writer. © Cosmetic Ingredient Review 1620 L Street, NW, Suite 1200 ♢ Washington, DC 20036-4702 ♢ ph 202.331.0651 ♢ fax 202.331.0088 [email protected] Distributed for Comment Only -- Do Not Cite or Quote Commitment & Credibility since 1976 MEMORANDUM To: CIR Expert Panel and Liaisons From: Lillian C. Becker, M.S. Scientific Analyst and Writer Date: May 11, 2018 Subject: Safety Assessment of Hydrogen Peroxide as Used in Cosmetics Enclosed is the Draft Report of the Safety Assessment of Hydrogen Peroxide as used in Cosmetics. [hydper062018rep] In June 2016, Hydrogen Peroxide was chosen as the hair dye ingredient to be reviewed for 2017. On April 13, 2018, CIR issued the Scientific Literature Review (SLR) for this ingredient with a request for any pertinent data. The Council has submitted concentration of use data. [hydper062018data] No other data have been submitted for this ingredient. Council comments have been addressed. [hydper062018pcpc] According to FDA’s VCRP [hydper062018FDA] and the Council survey, Hydrogen Peroxide is reported to be used in hair dyes up to 15% in a professional product (that is diluted for use) and at up to 12.4% in consumer hair dyes and colors formulations; Hydrogen Peroxide is reported to be used in a total of 250 hair-coloring formulations. Hydrogen Peroxide is also used in other categories of ingredients, including formulations that result in dermal leave-on exposure at up to 3% in the category of other shaving preparations. There are reported to be 93 formulations that come in contact with mucous membranes and may result in incidental ingestion, including at up to 4.6% in dentifrices. Also included in this packet are the flow chart [hydper062018flow], history [hydper062018hist], data profile [hydper062018prof], and search strategy [hydper062018strat]. 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 Insufficient Data Announcement (IDA). __________________________________________________________________________________________ 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 SAFETY ASSESSMENT FLOW CHART INGREDIENT/FAMILY _____ Hydrogen Peroxide ___________________________________________ MEETING ___June 2018________________________________________________________________ Public Comment CIR Expert Panel Report Status Priority List INGREDIENT PRIORITY LIST SLR Apr 13, 2018 DRAFT REPORT June 2018 Draft Report 60 day public comment period Table Table IDA TR IDA Notice IDA DRAFT TENTATIVE REPORT Draft TR Table Table Tentative Report Issue TR Draft FR DRAFT FINAL REPORT 60 day Public comment period Table Table Different Conclusion Issue PUBLISH Final Report FR Distributed for Comment Only -- Do Not Cite or Quote History – Hydrogen Peroxide June, 2016 – Hydrogen Peroxide added to the Priority List as the hair dye ingredient for the year. April 13, 2018 – SLR posted. June, 2018 – Panel examines Draft Report. Distributed for Comment Only -- Do Not Cite or Quote Hydrogen Peroxide Data Profile for June, 2018. Writer – Lillian Becker Acute Repeated ADME toxicity dose toxicity Irritation Sensitization Use Log K Penetration Dermal Oral Dermal Inhale Oral Dermal Ocular Carcinogenicity Phototoxicity Ocular In Vitro Dermal DermalHuman Dermal In Vitro Animal Human VitroIn Repro/Devel Genotoxicity Inhale ow Animal Animal Hydrogen Peroxide X X X X X X X X X X X X X X X X X X Distributed for Comment Only -- Do Not Cite or Quote Hydrogen Peroxide Ingredient CAS # InfoB SciFin PubMed TOXNET FDA EU ECHA IUCLID SIDS ECETOC HPVIS NICNAS NTIS NTP WHO FAO NIOSH FEMA Web Hydrogen 7722-84-1 √ √ √ √ √ √ √ N √ √ N √ N N √ √ √ N √ Peroxide Search Strategy Search terms: Hydrogen Peroxide and 7722-84-1 SciFinder Hydrogen Peroxide and 7722-84-1 – 15,307 hits. Refined for dermal, oral, inhalation toxicity; toxicokinetic; impurities; irritation; sensitization; ocular irritation; developmental and reproductive; genotoxicity; carcinogenicity; acute toxicity PubMed “Hydrogen Peroxide” OR “7722-84-1” - 72,899 hits ("Hydrogen Peroxide" OR "7722-84-1") AND tox* - 12033 hits ("Hydrogen Peroxide" OR "7722-84-1") AND derm* - 264 hits, 6 possibly useful ("Hydrogen Peroxide" OR "7722-84-1") AND inhal* - 313 hits, 6 possibly useful ("Hydrogen Peroxide" OR "7722-84-1") AND tox* AND repro* - 292 hits, 2 possibly useful ("Hydrogen Peroxide" OR "7722-84-1") AND genotoxicity - 405 hits, 10 possibly useful ("Hydrogen Peroxide" OR "7722-84-1") AND carcinogenicity 146 hits, 5 possibly useful ("Hydrogen Peroxide" OR "7722-84-1") AND sensitizat* - 189 hits, 0 possibly useful “hair dye” AND “Hydrogen Peroxide” OR “7722-84-1” - 0 hits. Distributed for Comment Only -- Do Not Cite or Quote Safety Assessment of Hydrogen Peroxide as Used in Cosmetics Status: Draft Report for Panel Review Release Date: May 11, 2018 Panel Meeting Date: June 4-5, 2018 The 2018 Cosmetic Ingredient Review Expert Panel members are: Chair, 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 Executive Director is Bart Heldreth Ph.D. This report was prepared by Lillian C. Becker, Scientific Analyst/Writer. © Cosmetic Ingredient Review 1620 L Street, NW, Suite 1200 ♢ Washington, DC 20036-4702 ♢ ph 202.331.0651 ♢ fax 202.331.0088 [email protected] Distributed for Comment Only -- Do Not Cite or Quote INTRODUCTION This is a review of the safety of Hydrogen Peroxide as used in cosmetics. According to the web-based International Cosmetic Ingredient Dictionary and Handbook (wINCI Dictionary), this ingredient is reported to function in cosmetics as an antimicrobial agent, cosmetic biocide, oral health care agent, and oxidizing agent.1 The wINCI Dictionary also lists oral health care drug as a function of Hydrogen Peroxide. However, in the United States (U.S.), this is not considered a cosmetic function, and therefore the Cosmetic Ingredient Review (CIR) Expert Panel (Panel) will not evaluate safety in relation to that function. This safety assessment includes relevant published and unpublished data that are available for each endpoint that is evaluated. Published data are identified by conducting an exhaustive search of the world’s literature. A listing of the search engines and websites that are used and the sources that are typically explored, as well as the endpoints that CIR typically evaluates, is provided on the CIR website (http://www.cir-safety.org/supplementaldoc/preliminary-search-engines-and- websites; http://www.cir-safety.org/supplementaldoc/cir-report-format-outline). Unpublished data are provided by the cosmetics industry, as well as by other interested parties. There are several studies in this report that evaluate the safety of Hydrogen Peroxide mixed with an oxidative hair dye or hair dye ingredient in a 1:1 mixture. The resulting mixture is not a mixture containing the ingredients in proportional amounts but a reaction product of the two substances with little to no expected residual Hydrogen Peroxide. These studies are included in this safety assessment to acknowledge that Hydrogen Peroxide is an ingredient in hair dyes as an oxidizer. Some of the data included in this safety assessment were found on the European Chemicals Agency (ECHA)2 website. In this safety assessment, ECHA is cited as the references for summaries of information obtained from this website. Also referenced in this safety assessment are summary data found in reports made publically available by the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC),3,4 European Chemicals Bureau,5 Human & Environmental Risk Assessment (HERA),6 International Agency for Research on Cancer (IARC),7-11 International Programme on Chemical Safety (IPCS) INCHEM,12 Joint Food and Agriculture Organization (FAO)/World Health Organization (WHO) Expert Committee on Food Additives (JECFA),13 U.S. National Institutes of Health National Center for Biotechnology,14 Australia’s National Industrial Chemicals Notification and Assessment Scheme (NICNAS),15 European Commission’s (EC) Scientific Committee on Cosmetic Products, Non-Food Products Intended for Consumers (SCCNFP),16 EC Scientific Committee on Consumer Products (SCCP),17 and Biocidal Products Committee of Finland.18 Reports by these organizations are cited in this assessment to identify the source of the summary data obtained. CHEMISTRY Definition and Structure Hydrogen Peroxide is the inorganic oxide that conforms to the structure in Figure 1.1 Figure 1. Hydrogen Peroxide Physical and Chemical Properties Physical and chemical properties of Hydrogen Peroxide are