Safety Assessment of Chamomile Ingredients as Used in Cosmetics Status: Scientific Literature Review for Public Comment Release Date: February 11, 2013 Panel Date: June 10-11, 2013 All interested persons are provided 60 days from the above date to comment on this Tentative Report and to identify additional published data that should be included or provide unpublished data which can be made public and included. Information may be submitted without identifying the source or the trade name of the cosmetic product containing the ingredient. All unpublished data submitted to CIR will be discussed in open meetings, will be available at the CIR office for review by any interested party and may be cited in a peer-reviewed scientific journal. Please submit data, comments, or requests to the CIR Director, Dr. F. Alan Andersen. The 2012 Cosmetic Ingredient Review Expert Panel members are: Chair, Wilma F. Bergfeld, M.D., F.A.C.P.; Donald V. Belsito, M.D.; Curtis D. Klaassen, Ph.D.; Daniel C. Liebler, Ph.D.; Ronald A Hill, 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 F. Alan Andersen, Ph.D. This report was prepared by Wilbur Johnson, Jr., M.S., Manager/Lead Specialist and Bart Heldreth, Ph.D., Chemist. © Cosmetic Ingredient Review 1101 17TH STREET, NW, SUITE 412 ◊ WASHINGTON, DC 20036-4702 ◊ PH 202.331.0651 ◊ FAX 202.331.0088 ◊ [email protected] ii Table of Contents INTRODUCTION .............................................................................................................................................................. 1 CHEMISTRY ..................................................................................................................................................................... 1 PHYSICAL AND CHEMICAL PROPERTIES ................................................................................................................................... 1 METHOD OF MANUFACTURE.................................................................................................................................................... 1 COMPOSITION/IMPURITIES ....................................................................................................................................................... 1 USE ..................................................................................................................................................................................... 3 COSMETIC ................................................................................................................................................................................ 3 NON-COSMETIC ....................................................................................................................................................................... 4 TOXICOKINETICS .......................................................................................................................................................... 4 TOXICOLOGY .................................................................................................................................................................. 4 ACUTE TOXICITY ..................................................................................................................................................................... 4 Oral .................................................................................................................................................................................... 4 Dermal ............................................................................................................................................................................... 5 REPEATED DOSE TOXICITY ...................................................................................................................................................... 5 ANTIMICROBIAL ACTIVITY ...................................................................................................................................................... 6 EFFECT ON NERVOUS SYSTEM ................................................................................................................................................. 7 OCULAR IRRITATION ............................................................................................................................................................... 8 SKIN IRRITATION ..................................................................................................................................................................... 8 SKIN IRRITATION AND SENSITIZATION ..................................................................................................................................... 8 Animal ................................................................................................................................................................................ 8 Human ................................................................................................................................................................................ 9 CASE REPORTS ...................................................................................................................................................................... 13 PHOTOTOXICITY .................................................................................................................................................................... 15 SENSORY IRRITATION ............................................................................................................................................................ 15 REPRODUCTIVE AND DEVELOPMENTAL TOXICITY .......................................................................................... 15 GENOTOXICITY ............................................................................................................................................................ 16 CARCINOGENICITY ..................................................................................................................................................... 17 ANTICARCINOGENICITY ......................................................................................................................................................... 17 BIOLOGICAL ACTIVITY ............................................................................................................................................. 18 NEUTROPHIL ACTIVATION ..................................................................................................................................................... 18 ANTI-INFLAMMATORY ACTIVITY ........................................................................................................................................... 18 IMMUNOMODULATORY ACTIVITY .......................................................................................................................................... 18 ANTISPASMODIC ACTIVITY .................................................................................................................................................... 19 EFFECT ON SMOOTH MUSCLE CONTRACTION ........................................................................................................................ 19 ENZYME INHIBITION .............................................................................................................................................................. 20 ANTIOXIDANT ACTIVITY ....................................................................................................................................................... 20 HYPNOTIC/SEDATIVE ACTIVITY ............................................................................................................................................ 21 ANTIDIURETIC EFFECT ........................................................................................................................................................... 21 WOUND HEALING ACTIVITY .................................................................................................................................................. 22 SUMMARY ...................................................................................................................................................................... 22 iii INTRODUCTION This is a review of the available scientific literature relevant to evaluating the safety of chamomile (German chamomile [Chamomilla recutita (matricaria) and Roman chamomile [Anthemis nobilis]) ingredients as used in cosmetics. These function mostly as fragrance ingredients and skin conditioning agents in cosmetic products. In addition to being a skin conditioning agent, chamomilla recutita (matricaria) flower/leaf/stem extract, also functions as a flavoring agent and an oral care agent. It should be noted that chamomilla recutita (matricaria) flower oil and anthemis nobilis flower oil are also known as German chamomile oil and Roman chamomile oil, respectively.1 These names are used frequently in the published literature. CHEMISTRY The definitions of the chamomile ingredients presented in this scientific literature review are included in Table 1. Physical and Chemical Properties Chemical and physical properties of chamomilla recutita (matricaria) flower oil and anthemis nobilis flower oil are included in Table 2. Method of Manufacture Chamomilla Recutita (Matricaria)