Safety Assessment of Citrus-Derived Ingredients as Used in Cosmetics Status: Draft Report for Panel Review Release Date: February 21, 2014 Panel Meeting Date: March 17-18, 2014 The 2014 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 report was prepared by Christina Burnett, Scientific Analyst/Writer and Monice Fiume, Senior 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] Commitment & Credibility since 1976 Memorandum To: CIR Expert Panel Members and Liaisons From: Christina L. Burnett, Scientific Writer/Analyst Monice M. Fiume , Senior Scientific Writer/Analyst Bart Heldreth, Ph.D., Chemist Date: February 21, 2014 Subject: Draft Safety Assessment on Citrus-Derived Ingredients In December 2013, CIR issued the Scientific Literature Review (SLR) for citrus-derived ingredients. These ingredients function primarily as skin conditioning agents-miscellaneous and fragrances. There are a total of 198 ingredients in this safety assessment. Unpublished data and concentration of use data that were provided by the Personal Care Products Council (Council) have been received and incorporated into the report. Comments received from the Council and the CIR Science and Support Committee have been considered. Many of the key issues from these comments need to be addressed by the Panel. Additionally, a letter with comments and suggestions from Dr. Ann Marie Api of the Research Institute for Fragrance Materials, Inc. (RIFM) has been received by CIR. The data and all comments can be found in this report’s package. All of the ingredients derived from citrus have been grouped into this report in accordance with the Panel’s preference for reviewing ingredient groups that are reasonably inclusive rather than limited without cause. We acknowledge that differences among species and plant parts can result in differences in cosmetic safety profiles. However, differences among species and/or plant parts may also be reasonably expected to result in no safety-relevant differences in the botanical cosmetic ingredients without evidence to the contrary. Sufficient data necessary to support changes to the grouping of these ingredients has not been submitted. To provide the Panel with a comprehensive report, CIR suggests that a complete component and property profile, in addition to all relevant toxicity data, be provided by the cosmetics industry to CIR for each of these ingredients, in accordance with the guidelines presented by the cosmetics industry for assessing botanical ingredients.1 According to the FDA’s VCRP database, citrus limon (lemon) peel oil has the most reported uses in cosmetic and personal care products, with a total of 510; more than half of the uses are in leave-on skin care preparations. Citrus limon (lemon) fruit extract has the second greatest number of overall uses reported, with a total of 448; more than half of those uses are in leave-on skin care preparations. In the Council’s survey of use concentrations, citrus limon (lemon) peel oil had a highest maximum use concentration range of 0.0001% to 0.5% with 0.5% reported in “other” skin care preparations. Citrus limon (lemon) fruit extract had a highest maximum use concentration range of 0.0001% to 1.2%, with 1.2% reported in night skin care products. Most of the other use concentrations that were reported had similar ranges. __________________________________________________________________________________________ 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 However, maximum use concentrations as high as 29% were reported for citrus aurantium dulcis (orange) peel oil in hair conditioners and as high as 19% for citrus aurantium dulcis (orange) fruit water in paste masks and mud packs. Usually, CIR does not review ingredients that only function as fragrance ingredients because, as fragrances, the safety of these ingredients is evaluated by the RIFM. Twenty-two of the citrus-derived ingredients may function only as fragrances. CIR staff is in the process of confirming with RIFM that these ingredients are fragrance ingredients; if confirmed, these ingredients will be deleted from this safety assessment. If no further data are needed, the Panel should issue a Tentative Report. __________________________________________________________________________________________ 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 Distributed for Comment Only -- Do Not Cite or Quote Citrus History December 2013 – Scientific Literature Review announced. Distributed for Comment Only -- Do Not Cite or Quote Citrus-Derived Ingredients Data Profile – March 2014 – Writers, Christina Burnett and Monice Fiume /Sensitization Use - Animal Clinical In Physical/Chemical Physical/Chemical Properties Method of Manufacturing Composition Acute Toxicity Carcinogenicity Irritation - Irritation/Sensitization - Ocular/Mucosal Phototoxicity Case Studies Citrus Limon (Lemon) Seed Oil X Citrus Paradisi (Grapefruit) X Seed Oil Citrus Aurantifolia (Lime) X Flower Extract Citrus Aurantifolia (Lime) Fruit X Extract Citrus Aurantifolia (Lime) Juice X Citrus Aurantifolia (Lime) Oil X X Citrus Aurantifolia (Lime) Peel X Citrus Aurantifolia (Lime) Peel X Extract Citrus Aurantifolia (Lime) Peel X Powder Citrus Aurantium Amara (Bitter X Orange) Flower Extract Citrus Aurantium Amara (Bitter X Orange) Flower Oil Citrus Aurantium Amara (Bitter X Orange) Flower Water Citrus Aurantium Amara (Bitter X X X X X X Orange) Flower Wax Citrus Aurantium Amara (Bitter X Orange) Fruit Extract Citrus Aurantium Amara (Bitter X Orange) Leaf/Twig Oil Citrus Aurantium Amara (Bitter X Orange) Peel Extract Citrus Aurantium Amara (Bitter X Orange) Peel Oil Citrus Aurantium Amara (Bitter X Orange) Peel Powder Citrus Aurantium Bergamia X (Bergamot) Fruit Extract Citrus Aurantium Bergamia (Bergamot) X Fruit Oil Citrus Aurantium Dulcis (Orange) X Flower Extract Citrus Aurantium Dulcis (Orange) X Flower Oil Citrus Aurantium Dulcis (Orange) X Flower Water Citrus Aurantium Dulcis (Orange) X Fruit Extract Citrus Aurantium Dulcis (Orange) X Fruit Water Citrus Aurantium Dulcis (Orange) X Juice Citrus Aurantium Dulcis (Orange) X Leaf Extract Distributed for Comment Only -- Do Not Cite or Quote Citrus-Derived Ingredients Data Profile – March 2014 – Writers, Christina Burnett and Monice Fiume /Sensitization Use - Animal Clinical In Physical/Chemical Physical/Chemical Properties Method of Manufacturing Composition Acute Toxicity Carcinogenicity Irritation - Irritation/Sensitization - Ocular/Mucosal Phototoxicity Case Studies Citrus Aurantium Dulcis (Orange) X X Oil Citrus Aurantium Dulcis (Orange) X Peel Extract Citrus Aurantium Dulcis (Orange) X Peel Oil Citrus Aurantium Dulcis (Orange) X Peel Powder Citrus Aurantium Dulcis (Orange) X X X X X X X Peel Wax Citrus Aurantium Tachibana X Peel Extract Citrus Depressa Peel Extract X Citrus Glauca Fruit Extract X Citrus Grandis (Grapefruit) X Citrus Grandis (Grapefruit) Extract X Citrus Grandis (Grapefruit) X Fruit Extract Citrus Grandis (Grapefruit) X Fruit Water Citrus Grandis (Grapefruit) Juice X Citrus Grandis (Grapefruit) X Peel Extract Citrus Grandis (Grapefruit) X Peel Oil Citrus Grandis (Grapefruit) X Seed Extract Citrus Japonica Fruit Extract X Citrus Junos Fruit Extract X Citrus Junos Peel Extract X Citrus Junos Peel Oil X Citrus Junos Seed Extract X Citrus Junos Seed Oil X Citrus Limon (Lemon) X Flower/Leaf/Stem Extract Citrus Limon (Lemon) Fruit Extract X Citrus Limon (Lemon) Fruit Water X X X X Citrus Limon (Lemon) Juice X Citrus Limon (Lemon) Juice X Extract Citrus Limon (Lemon) Peel Extract X Citrus Limon (Lemon) Peel Oil X Citrus Limon (Lemon) X Peel Powder Distributed for Comment Only -- Do Not Cite or Quote Citrus-Derived Ingredients Data Profile – March 2014 – Writers, Christina Burnett and Monice Fiume /Sensitization Use - Animal Clinical In Physical/Chemical Physical/Chemical Properties Method of Manufacturing Composition Acute Toxicity Carcinogenicity Irritation - Irritation/Sensitization - Ocular/Mucosal Phototoxicity Case Studies Citrus Madurensis Fruit Extract X Citrus Medica Limonum (Lemon) X Fruit Water Citrus Medica Limonum (Lemon) X Juice Extract Citrus Medica Limonum (Lemon) X Peel Wax Citrus Medica Vulgaris Fruit Extract X Citrus Nobilis (Mandarin Orange) X Fruit Extract Citrus Nobilis (Mandarin Orange) X Oil Citrus Nobilis (Mandarin Orange) X Peel Extract Citrus Nobilis (Mandarin Orange) X Peel Oil Citrus Nobilis (Mandarin Orange) X Water Citrus Paradisi (Grapefruit) Fruit X Extract Citrus Paradisi (Grapefruit) Fruit X X X Water Citrus Paradisi (Grapefruit) Peel X Extract Citrus Paradisi (Grapefruit) Peel Oil X Citrus Paradisi (Grapefruit) Seed X Extract Citrus Reticulata (Tangerine) Fruit X Extract Citrus Reticulata (Tangerine) Fruit X X X Water Citrus Reticulata (Tangerine) Leaf X Oil Citrus Reticulata (Tangerine) Peel X Extract Citrus Reticulata (Tangerine) Peel X Oil Citrus Sinensis (Sweet Orange) Fruit X Extract