Handbook of
`Cosmetic Science
`@ and Technology
`
`edited by
`
`_ 9
`
`Petitioner Dr. Squatch
` Ex. 1037
`
`

`

`Handbook of
`Cosmetic Science
`and Technology
`
`edited by
`
`André O. Barel
`Free University of Brussels
`Brussels, Belgium
`
`Marc Paye
`Colgate-Palmolive Research and Development, Inc.
`Milmort, Belgium
`
`Howard I. Maibach
`University of California at San Francisco School of Medicine
`San Francisco, California
`
`Marcel Dekker, Inc.
`
`New York • Basel
`
`TM
`
`Copyright © 2001 by Marcel Dekker, Inc. All Rights Reserved.
`
`

`

`ISBN: 0-8247-0292-1
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`This book is printed on acid-free paper.
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`Copyright  2001 by Marcel Dekker, Inc. All Rights Reserved.
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`tion storage and retrieval system, without permission in writing from the publisher.
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`Current printing (last digit):
`10 9 8 7 6 5 4 3 2 1
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`PRINTED IN THE UNITED STATES OF AMERICA
`
`

`

`Preface
`
`Cosmetic composition and formulation are becoming increasingly complex, and cosmetic
`ingredients more sophisticated and functional, while laws and regulations impose more
`constraints on the cosmetic scientist and manufacturer. The Handbook of Cosmetic Science
`and Technology reviews in a single volume the multiple facets of the cosmetic field and
`provides the reader with an easy-to-access information source.
`This handbook covers topics as varied as the physiology of the potential targets
`of cosmetics, safety, legal and regulatory considerations throughout the world, cosmetic
`ingredients, vehicles and finished products, and new delivery systems, as well as microbi-
`ology and safety and efficacy testing.
`To achieve our goal, we, the editors, requested the contributions of expert scientists
`from academic dermatology and dermato-cosmetics, the cosmetics industry, ingredients
`and raw materials producers, and regulatory agencies. Because cosmetology is universal,
`while having some regional specificity, those authors were selected on a broad geographi-
`cal basis, with some coming from the United States, Europe, Japan, and Australia. They
`share in their chapters not only their experience and knowledge but also new information
`and their expert views regarding the future. We thank the authors for their high dedication,
`which permitted us to make this handbook a review of the state of the art in cosmetology
`in the new millennium. The staff of Marcel Dekker, Inc., played a great role in the produc-
`tion of the handbook, ensuring on a day-to-day basis the contact between the editors and
`the authors. Our thanks especially go to Sandra Beberman, Jane Roh, and Moraima Suarez
`for their constant and excellent help.
`Finally, we encourage our readership to send us their comments and suggestions on
`what should be modified or considered in future editions.
`
`Andre´ O. Barel
`Marc Paye
`Howard I. Maibach
`
`iii
`
`

`

`
`
`Copyright©MarcelDekker,Inc.Allrightsreserved.
`
`
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`
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`270 Madison Avenue, New York, New York 10016
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`MarcetDexxer,INc. i
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`le
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`

`

`Preface
`Contributors
`
`Part 1
`
`INTRODUCTION
`
`1.
`
`Introduction
`Andre´ O. Barel, Marc Paye, and Howard I. Maibach
`
`2. Definition of Cosmetics
`Stanley R. Milstein, John E. Bailey, and Allen R. Halper
`
`Part 2
`
`TARGET ORGANS FOR COSMETIC PRODUCTS
`
`3. The Microscopic Structure of the Epidermis and Its Derivatives
`Joel J. Elias
`
`4. The Normal Nail
`Josette Andre´
`
`5. Hair
`Ghassan Shaker and Dominique Van Neste
`
`Part 3
`
`SAFETY CONSIDERATIONS
`
`6. Safety Terminology
`Ai-Lean Chew and Howard I. Maibach
`
`7. Principles and Practice of Percutaneous Absorption
`Ronald C. Wester and Howard I. Maibach
`
`8. Principles and Mechanisms of Skin Irritation
`Sibylle Schliemann-Willers and Peter Elsner
`
`9. Allergy and Hypoallergenic Products
`An E. Goossens
`
`Contents
`
`iii
`xi
`
`1
`
`5
`
`19
`
`29
`
`35
`
`47
`
`53
`
`67
`
`77
`
`v
`
`

`

`vi
`
`Contents
`
`10. Dermatological Problems Linked to Perfumes
`Anton C. de Groot
`
`11.
`
`12.
`
`In Vitro Tests for Skin Irritation
`Michael K. Robinson, Rosemarie Osborne, and Mary A. Perkins
`
`In Vivo Irritation
`Saqib J. Bashir and Howard I. Maibach
`
`13. Eye Irritation Testing
`Leon H. Bruner, Rodger D. Curren, John W. Harbell, Rosemarie
`Osborne, and James K. Maurer
`
`Part 4
`
`VEHICLES OF COSMETIC PRODUCTS
`
`14. Main Cosmetic Vehicles
`Stephan Buchmann
`
`15. Encapsulation to Deliver Topical Actives
`Joce´lia Jansen and Howard I. Maibach
`
`16. Encapsulation Using Porous Microspheres
`Jorge Heller, Subhash J. Saxena, and John Barr
`
`17. Liposomes
`Hans Lautenschla¨ger
`
`18. Topical Delivery by Iontophoresis
`Ve´ronique Pre´at and Rita Vanbever
`
`19. Mousses
`Albert Zorko Abram and Roderick Peter John Tomlinson
`
`20. Cosmetic Patches
`Spiros A. Fotinos
`
`Part 5
`
`COSMETIC INGREDIENTS
`
`21. Antibacterial Agents and Preservatives
`Franc¸oise Siquet and Michel J. Devleeschouwer
`
`22. General Concepts of Skin Irritancy and Anti-irritant Products
`Andre´ O. Barel
`
`23. Anti-irritants for Surfactant-Based Products
`Marc Paye
`
`24. The Case of Alpha-Bisabolol
`Klaus Stanzl and Ju¨rgen Vollhardt
`
`25. Anti-irritants for Sensory Irritation
`Gary S. Hahn
`
`26. Antioxidants
`Stefan Udo Weber, John K. Lodge, Claude Saliou, and Lester Packer
`
`89
`
`95
`
`107
`
`119
`
`145
`
`171
`
`191
`
`201
`
`211
`
`221
`
`233
`
`245
`
`253
`
`271
`
`277
`
`285
`
`299
`
`

`

`Contents
`
`27. Alpha Hydroxy Acids
`Enzo Berardesca
`
`28. Colorants
`Gisbert Ottersta¨tter
`
`29. Hair Conditioners
`Charles Reich and Dean T. Su
`
`30. Hydrating Substances
`Marie Lode´n
`
`31. Ceramides and Lipids
`Bozena B. Michniak and Philip W. Wertz
`
`32. Natural Extracts
`Ju¨rgen Vollhardt
`
`33. Rheological Additives and Stabilizers
`Ekong A. Ekong, Mohand Melbouci, Kate Lusvardi, and
`Paquita E. Erazo-Majewicz
`
`34. Silicones: A Key Ingredient in Cosmetic and Toiletry Formulations
`Janet M. Blakely
`
`35. Skin-Feel Agents
`Germaine Zocchi
`
`36. Surfactants
`Takamitsu Tamura and Mitsuteru Masuda
`
`37. Classification of Surfactants
`Louis Oldenhove de Guertechin
`
`38. UV Filters
`Stanley B. Levy
`
`39. Vitamins
`Alois Kretz and Ulrich Moser
`
`40. Ellagic Acid: A New Skin-Whitening Active Ingredient
`Yoshimasa Tanaka
`
`Part 6
`
`COSMETIC PRODUCTS
`
`Skincare Products
`
`41. Cosmetics and Interactions with Superficial Epidermis
`Jørgen Serup
`
`42. Skin Cleansing Bars
`Joshua B. Ghaim and Elizabeth D. Volz
`
`43. Skin Cleansing Liquids
`Daisuke Kaneko and Kazutami Sakamoto
`
`vii
`
`311
`
`317
`
`331
`
`347
`
`361
`
`369
`
`377
`
`389
`
`399
`
`417
`
`431
`
`451
`
`463
`
`473
`
`479
`
`485
`
`499
`
`

`

`viii
`
`Contents
`
`44. Emulsion-Based Skincare Products: Formulating and Measuring Their
`Moisturizing Benefits
`Howard Epstein and F. Anthony Simion
`
`45. Anticellulite Products and Treatments
`Andre´ O. Barel
`
`46. Antiwrinkle Products
`William J. Cunningham
`
`47. Artificial Tanning Products
`Stanley B. Levy
`
`48. Barrier Creams
`Cees Korstanje
`
`49. Skin-Whitening Products
`Hongbo Zhai and Howard I. Maibach
`
`Haircare Products
`
`50.
`
`Interactions with Hair and Scalp
`Dominique Van Neste and Ghassan Shaker
`
`51. Hair Cosmetics
`Leszek J. Wolfram
`
`52. Ethnic Differences in Haircare Products
`Joerg Kahre
`
`Other Cosmetic Products
`
`53. Oral-Care Products
`Abdul Gaffar
`
`54. Decorative Products
`Mitchell L. Schlossman
`
`55. Cosmetics for Nails
`Douglas Schoon and Robert Baran
`
`56. Antiperspirants
`Jo¨rg Schreiber
`
`57. Deodorants
`Jo¨rg Schreiber
`
`58. Baby Care
`Uwe Scho¨nrock
`
`59. Cosmetics for the Elderly
`Uwe Scho¨nrock
`
`511
`
`531
`
`543
`
`551
`
`557
`
`567
`
`575
`
`581
`
`605
`
`619
`
`645
`
`685
`
`689
`
`703
`
`715
`
`723
`
`

`

`Contents
`
`Part 7
`
`LEGISLATION AND REGULATIONS WORLDWIDE
`
`60. EEC Cosmetic Directive and Legislation in Europe
`Rene´ Van Essche
`
`61. Regulatory Requirements for the Marketing of Cosmetics in the United
`States
`Stanley R. Milstein, John E. Bailey, and Allen R. Halper
`
`62. Legislation in Japan
`Mitsuteru Masuda
`
`Part 8
`
`TESTING COSMETIC PRODUCTS
`
`63. Stability Testing of Cosmetic Products
`Perry Romanowski and Randy Schueller
`
`64. Stability Control: Microbiological Tests
`Michel J. Devleeschouwer and Franc¸oise Siquet
`
`Part 9
`
`COSMETIC CLAIMS
`
`65.
`
`Introduction to the Proof of Claims
`Marc Paye and A. O. Barel
`
`66. Tests for Sensitive Skin
`Alessandra Pelosi, Sabrina Lazzerini, Enzo Berardesca, and
`Howard I. Maibach
`
`67. Tests for Skin Hydration
`Bernard Gabard
`
`68. Tests for Skin Protection: Barrier Effect
`Hongbo Zhai and Howard I. Maibach
`
`69. Objective Methods for Assessment of Human Facial Wrinkles
`Gary Grove and Mary Jo Grove
`
`70. Acnegenicity and Comedogenicity Testing for Cosmetics
`F. Anthony Simion
`
`71. Sensory Testing
`Linda P. Oddo and Kathy Shannon
`
`Index
`
`ix
`
`729
`
`737
`
`761
`
`769
`
`781
`
`797
`
`807
`
`815
`
`823
`
`829
`
`837
`
`845
`
`859
`
`

`

`
`
`Copyright©MarcelDekker,Inc.Allrightsreserved.
`
`
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`
`270 Madison Avenue, New York, New York 10016
`
`MarcetDexxer,INc. i
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`le
`
`

`

`Contributors
`
`Albert Zorko Abram, B.Sc. Soltec Research Pty Ltd., Rowville, Victoria, Australia
`
`Josette Andre´, M.D. Faculty of Medicine, Free University of Brussels, and Department
`of Dermatology, Hoˆpital Saint-Pierre, Brussels, Belgium
`
`John E. Bailey, Ph.D. Office of Cosmetics and Colors, Center for Food Safety and
`Applied Nutrition (CFSAN), U.S. Food and Drug Administration, Washington, D.C.
`
`Robert Baran, M.D. Nail Disease Center, Cannes, France
`
`Andre´ O. Barel, Ph.D. Faculty of Physical Education and Physiotherapy, Free Univer-
`sity of Brussels, Brussels, Belgium
`
`John Barr, Ph.D. Pharmaceutical Sciences, Advanced Polymer Systems, Redwood
`City, California
`
`Saqib J. Bashir, B.Sc.(Hons), M.B., Ch.B. Department of Dermatology, University of
`California at San Francisco School of Medicine, San Francisco, California
`
`Enzo Berardesca, M.D. Department of Dermatology, University of Pavia, Pavia, Italy
`
`Janet M. Blakely, B.Sc.(Hons) Life Sciences Group, Science and Technology, Dow
`Corning S.A., Brussels, Belgium
`
`Leon H. Bruner, D.V.M., Ph.D. Gillette Medical Evaluation Laboratory, The Gillette
`Company, Needham, Massachusetts
`
`Stephan Buchmann, Ph.D. Department of Pharmaceutical Technology, Spirig Pharma
`AG, Egerkingen, Switzerland
`
`xi
`
`

`

`xii
`
`Contributors
`
`Ai-Lean Chew, M.B.Ch.B. Department of Dermatology, University of California at
`San Francisco School of Medicine, San Francisco, California
`
`William J. Cunningham, M.D. CU-TECH, Mountain Lakes, New Jersey
`
`Rodger D. Curren, Ph.D.
`
`Institute for In Vitro Sciences, Inc., Gaithersburg, Maryland
`
`Anton C. de Groot, M.D., Ph.D. Department of Dermatology, Carolus Hospital,
`‘s-Hertogenbosch, The Netherlands
`
`Michel J. Devleeschouwer, Ph.D. Laboratory of Microbiology and Hygiene, Institute of
`Pharmacy and Biocontaminants Unit, School of Public Health, Free University of Brussels,
`Brussels, Belgium
`
`Ekong A. Ekong, Ph.D. Technology Division, Hercules Incorporated, Wilmington,
`Delaware
`
`Joel J. Elias, Ph.D. Department of Anatomy, University of California at San Francisco
`School of Medicine, San Francisco, California
`
`Peter Elsner, M.D. Department of Dermatology and Allergology, University of Jena,
`Jena, Germany
`
`Howard Epstein, M.S. Product Development, The Andrew Jergens Company, Cincin-
`nati, Ohio
`
`Paquita E. Erazo-Majewicz, Ph.D. Aqualon Division, Hercules Incorporated, Wil-
`mington, Delaware
`
`Spiros A. Fotinos, B.Sc.(Pharm), B.Sc.(Chem) Corporate Research and Innovation,
`Lavipharm, Peania Attica, Greece
`
`Bernard Gabard, Ph.D. Department of Biopharmacy, Spirig Pharma Ltd., Egerkingen,
`Switzerland
`
`Abdul Gaffar, Ph.D. Advanced Technology, Corporate Technology, Department of
`Oral Care, Colgate-Palmolive Company, Piscataway, New Jersey
`
`Joshua B. Ghaim, Ph.D. Product Development, Skin Care Global Technology, Colgate-
`Palmolive Company, Piscataway, New Jersey
`
`An E. Goossens, B.Pharm., Ph.D. Department of Dermatology, University Hospital,
`Katholieke Universiteit Leuven, Leuven, Belgium
`
`Gary Grove, Ph.D. Research and Development, KGL’s Skin Study Center, Broomall,
`and cyberDERM, inc., Media, Pennsylvania
`
`

`

`Contributors
`
`xiii
`
`Mary Jo Grove, M.S. KGL’s Skin Study Center, Broomall, and cyberDERM, inc.,
`Media, Pennsylvania
`
`Gary S. Hahn, M.D. Department of Pediatrics, University of California at San Diego
`School of Medicine, San Diego, and Board of Scientific Advisors, Cosmederm Technolo-
`gies, LLC, La Jolla, California
`
`Allen R. Halper Office of Cosmetics and Colors, Center for Food Safety and Applied
`Nutrition (CFSAN), U.S. Food and Drug Administration, Washington, D.C.
`
`John W. Harbell, Ph.D.
`
`Institute for In Vitro Sciences, Inc., Gaithersburg, Maryland
`
`Jorge Heller, Ph.D. Advanced Polymer Systems, Redwood City, California
`
`Joce´lia Jansen, Ph.D. Department of Pharmaceutical Sciences, State University of
`Ponta Grossa, Ponta Grossa, Parana´, Brazil
`
`Joerg Kahre, Ph.D. VTP Department, Henkel KGaA, Du¨sseldorf, Germany
`
`Daisuke Kaneko, Ph.D. Department of Product Development, AminoScience Labora-
`tories, Ajinomoto Co., Inc., Kanagawa, Japan
`
`Cees Korstanje, R.Ph., Ph.D. Biological Research Department, Yamanouchi Europe
`B.V., Leiderdorp, The Netherlands
`
`Alois Kretz, M.D. Cosmetics, Roche Vitamins Europe Ltd., Basel, Switzerland
`
`Hans Lautenschla¨ger, Ph.D. Development & Consulting, Pulheim, Germany
`
`Sabrina Lazzerini, M.D. Department of Dermatology, University of Pavia, Pavia, Italy
`
`Stanley B. Levy, M.D. Department of Dermatology, University of North Carolina
`School of Medicine at Chapel Hill, Chapel Hill, North Carolina, and Medical Affairs,
`Revlon Research Center, Edison, New Jersey
`
`Marie Lode´n, Pharm.Sc., Dr.Med.Sc. Department of Dermatology, ACO HUD AB,
`Upplands Va¨sby, Sweden
`
`John K. Lodge, Ph.D. School of Biological Sciences, University of Surrey, Guildford,
`Surrey, England
`
`Kate Lusvardi, Ph.D. Aqualon Division, Hercules Incorporated, Wilmington, Delaware
`
`Howard I. Maibach, M.D. Department of Dermatology, University of California at San
`Francisco School of Medicine, San Francisco, California
`
`Mitsuteru Masuda, Ph.D. Life Science Research Center, Research and Development
`Headquarters, Lion Corporation, Tokyo, Japan
`
`

`

`xiv
`
`Contributors
`
`James K. Maurer, D.V.M., Ph.D. Human and Environmental Safety Division, The
`Procter & Gamble Company, Cincinnati, Ohio
`
`Mohand Melbouci, Ph.D. Personal Care Department, Aqualon Division, Hercules In-
`corporated, Wilmington, Delaware
`
`Bozena B. Michniak, Ph.D. College of Pharmacy, University of South Carolina, Co-
`lumbia, South Carolina
`
`Stanley R. Milstein, Ph.D. Office of Cosmetics and Colors, Center for Food Safety and
`Applied Nutrition (CFSAN), U.S. Food and Drug Administration, Washington, D.C.
`
`Ulrich Moser, Ph.D. Roche Vitamins Europe Ltd., Basel, Switzerland
`
`Linda P. Oddo, B.S. Hill Top Research, Inc., Scottsdale, Arizona
`
`Louis Oldenhove de Guertechin, Ph.D. Department of Advanced Technology, Col-
`gate-Palmolive Research and Development, Inc., Milmort, Belgium
`
`Rosemarie Osborne, Ph.D. Human and Environmental Safety Division, The Procter &
`Gamble Company, Cincinnati, Ohio
`
`Gisbert Ottersta¨tter Color Department, DRAGOCO Gerberding & Co. AG, Holzmin-
`den, Germany
`
`Lester Packer, Ph.D. Department of Molecular and Cellular Biology, University of
`California at Berkeley, Berkeley, California
`
`Marc Paye, Ph.D. Skin Research Division, Department of Advanced Technology,
`Colgate-Palmolive Research and Development, Inc., Milmort, Belgium
`
`Alessandra Pelosi, M.D. Department of Dermatology, University of Pavia, Pavia, Italy
`
`Mary A. Perkins, A.Sc. Human and Environmental Safety Division, The Procter &
`Gamble Company, Cincinnati, Ohio
`
`Ve´ronique Pre´at, Ph.D. Unite´ de Pharmacie Gale´nique, Universite´ Catholique de Lou-
`vain, Brussels, Belgium
`
`Charles Reich, Ph.D. Advanced Technology, Hair Care, Colgate-Palmolive Technol-
`ogy Center, Piscataway, New Jersey
`
`Michael K. Robinson, Ph.D. Department of Human and Environmental Safety Divi-
`sion, The Procter & Gamble Company, Cincinnati, Ohio
`
`Perry Romanowski, B.S., M.S. Research and Development, Alberto Culver Company,
`Melrose Park, Illinois
`
`

`

`Contributors
`
`xv
`
`Kazutami Sakamoto, Ph.D. Applied Research Department, AminoScience Labora-
`tories, Ajinomoto Co., Inc., Kanagawa, Japan
`
`Claude Saliou, Pharm.D., Ph.D. Department of Molecular and Cell Biology, Univer-
`sity of California at Berkeley, Berkeley, California
`
`Subhash J. Saxena, Ph.D. Research and Development, Advanced Polymer Systems,
`Redwood City, California
`
`Sibylle Schliemann-Willers, M.D. Department of Dermatology and Allergology, Uni-
`versity of Jena, Jena, Germany
`
`Mitchell L. Schlossman, B.A., F.A.I.C., F.S.C.C. Kobo Products,
`Plainfield, New Jersey
`
`Inc., South
`
`Uwe Scho¨nrock, Ph.D. Active Ingredient Research, Beiersdorf AG, Hamburg, Ger-
`many
`
`Douglas Schoon, M.S. Research and Development, Creative Nail Design Inc., Vista,
`California
`
`Jo¨rg Schreiber, Ph.D. Research New Delivery Systems, Beiersdorf AG, Hamburg, Ger-
`many
`
`Randy Schueller, B.S. Consumer Products Research and Development, Alberto Culver
`Company, Melrose Park, Illinois
`
`Jørgen Serup, M.D., D.M.Sc. Department of Dermatological Research, Leo Pharma-
`ceutical Products, Copenhagen, Denmark
`
`Ghassan Shaker, M.B.Ch.B., D.Sc. Skinterface sprl, Tournai, Belgium
`
`Kathy Shannon, B.S. Hill Top Research, Inc., Scottsdale, Arizona
`
`F. Anthony Simion, Ph.D. Product Development, The Andrew Jergens Company, Cin-
`cinnati, Ohio
`
`Franc¸oise Siquet, Ph.D. Department of Microbiology, Colgate-Palmolive Technology
`Center, Milmort, Belgium
`
`Klaus Stanzl, Ph.D. DRAGOCO Gerberding & Co. AG, Holzminden, Germany
`
`Dean T. Su, Ph.D. Personal Care, Colgate-Palmolive Technology Center, Piscataway,
`New Jersey
`
`Takamitsu Tamura, Ph.D. Material Science Research Center, Lion Corporation,
`Tokyo, Japan
`
`

`

`xvi
`
`Contributors
`
`Yoshimasa Tanaka, Ph.D. Life Science Research Center, Lion Corporation, Tokyo,
`Japan
`
`Roderick Peter John Tomlinson Soltec Research Pty Ltd., Rowville, Victoria, Aus-
`tralia
`
`Rita Vanbever, Ph.D. Unite´ de Pharmacie Gale´nique, Universite´ Catholique de Lou-
`vain, Brussels, Belgium
`
`Rene´ Van Essche, D.V.M., M.B.A.
`Brussels, Belgium
`
`Institute of Pharmacy, Free University of Brussels,
`
`Dominique Van Neste, M.D., Ph.D. Skinterface sprl, Tournai, Belgium
`
`Ju¨ rgen Vollhardt, Ph.D. Research and Development, Cosmetic Division, DRAGOCO
`Inc., Totowa, New Jersey
`
`Elizabeth D. Volz, M.ChE. Research and Development, Colgate-Palmolive Company,
`Piscataway, New Jersey
`
`Stefan Udo Weber, M.D. Department of Molecular and Cell Biology, University of
`California at Berkeley, Berkeley, California
`
`Philip W. Wertz, Ph.D. Dows Institute, University of Iowa, Iowa City, Iowa
`
`Ronald C. Wester, Ph.D. Department of Dermatology, University of California at San
`Francisco School of Medicine, San Francisco, California
`
`Leszek J. Wolfram, Ph.D.
`
`Independent Consultant, Stamford, Connecticut
`
`Hongbo Zhai, M.D. Department of Dermatology, University of California at San Fran-
`cisco School of Medicine, San Francisco, California
`
`Germaine Zocchi, Ph.D. Department of Advanced Technology, Colgate-Palmolive Re-
`search and Development, Inc., Milmort, Belgium
`
`

`

`Antibacterial Agents and Preservatives
`
`21
`
`Franc¸oise Siquet
`Colgate-Palmolive Technology Center, Milmort, Belgium
`
`Michel J. Devleeschouwer
`Free University of Brussels, Brussels, Belgium
`
`INTRODUCTION
`
`The term ‘‘antibacterial agent’’ is largely used to qualify chemical agents that are included
`in cosmetics or household products to provide them either with a specific bactericidal or
`bacteriostatic activity during usage. The second function of antibacterial chemicals is to
`protect the product during its life by providing a preservative efficacy against microbial
`insults. A particular chemical agent can be used as an active ingredient in antibacterial
`product or as a preservative to protect the formula from microbial contamination. Taking
`into account that not only bacteria but also fungi or yeast can be concerned, to cover all
`germs simultaneously the word ‘‘antimicrobial’’ will be used.
`Historically, the first antibacterial products developed were skinwash products such
`as soap bars, derived from deodorant soap bars. The purpose was not only to clean the
`skin but also to reduce its microbial flora [1]. During the last 20 years, many different
`antibacterial or antimicrobial products were marketed. They include toothpastes and
`mouthwashes, liquid antibacterial soaps, deodorants, and even antibacterial products for
`dishwashing.
`The first part of this chapter will review the different kinds of antibacterial products
`and the methods to show their efficacy.
`The purpose of preservation is to protect all aspects of a product against microbial
`attack before and during consumer use. Integrity of products in terms of efficacy, fra-
`grance, appearance, and stability must be maintained. The second part of this chapter will
`review the preservative systems and how to build a well-preserved formula. The test meth-
`ods for preservative efficacy can be found in Chapter 64 of this book.
`
`ANTIBACTERIAL PRODUCTS
`Topical Antimicrobial Products
`
`Most antibacterial soap bars contain triclocarban (TCC) as the active ingredient. In the
`past, antibacterial soap bars were also formulated with formaldehyde. These were very
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`effective for hospital use, but skin toxicity and irritation were very high. Currently, liquid
`soaps are formulated with triclosan up to 1% maximum. Safety of the regular use of
`triclocarban and triclosan in hand-washing products was extensively discussed by the Food
`and Drug Administration (FDA) [1]. The agency prepared a tentative final monograph in
`1994 in which topical antimicrobial products were classified in the following categories:
`1) antiseptic handwash or healthcare personnel handwash, 2) patient presurgical skin prep-
`aration, and 3) surgical hand scrub. But this meant that products intended to be used in
`homecare would have to meet the requirements of products for healthcare. In response,
`two industrial associations, The Cosmetics, Toiletry, and Fragrance Association (CTFA)
`and the Soap and Detergent Association (SDA), proposed another classification, based on
`a healthcare continuum model (HCCM) in which the antimicrobial products were related
`to six categories; two to be used by the general population (antimicrobial handwashes and
`bodywashes), three for use by healthcare professionals (presurgical preparation, surgical
`scrubs, and healthcare personnel handwashes), and one category for food handlers. Since
`then, industry has submitted data to the FDA showing the efficacy of active ingredients
`used in the six categories; among these ingredients are triclosan, triclocarban, chloroxy-
`lenol (PCMX), povidone-iodine, surfactant iodophor, alcohol, and quaternary ammonium
`compounds [2].
`Extensive studies have also been carried out with essential oils as antibacterial agents
`in soaps. Unfortunately, the data showed that the minimal inhibitory concentration (MIC)
`for antimicrobial soaps formulated with different essential oils were more than 100 times
`higher that the MIC obtained on TCC-based soaps when tested against Staphylococcus
`aureus [3].
`Deodorants and Antiperspirants
`
`The first antiperspirants appeared on the market at the beginning of the 20th century. They
`were based on aluminium chloride, which induced skin irritation and fabric damage be-
`cause of the low pH of the solutions [4]. Several years later, Shelley and colleagues showed
`that underarm odor was provoked by the growth of the axillae bacterial flora which de-
`graded the apocrine secretions [5]. These bacteria are mainly staphylococci (S. epider-
`midis) and diphteroids from the Corynebacteriaceae family. Antiperspirants can prevent
`the growth of these degrading bacteria by reducing the available moisture of the axillaries
`among other mechanisms (see Chap. 56). Some products used the hexaclorophene as an
`active but its use was discontinued because of its neurotoxic properties [6]. Currently,
`many contain aluminium salts, or zirconium-aluminium combinations such as Al-Zi-Tri-/
`tetra-chlorydrex glycinate as active ingredients. Their low pH (4.0) also helps the antibac-
`terial activity. Antiperspirants are deodorants because they suppress the odor source by
`reducing perspiration and bacterial growth. Deodorants may or may not have an antimicro-
`bial action; either they are masking products—in this case they contain perfumes or essen-
`tial oils that hide the odor—or they can contain antibacterial agents which are mainly
`alcohols and triclosan [6].
`Oral Care Products
`
`These are mainly toothpastes and mouthrinses. In general, dental creams serve to clean
`the teeth, to remove dental stains, and most recently to reduce and/or to prevent gingivitis
`and to kill the germs responsible for bad mouth odor. Mouthrinses, whether their recom-
`mended use is before or after brushing, are also claimed to sanitize the mouth.
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`Active ingredients used in dental cream are mainly triclosan and chlorexhidine.
`Other ingredients such as the natural sanguinarine extract also claim a sanitizing effect
`on the oral flora. The same ingredients can be used in mouthrinses, but most also contain
`alcohol to ensure a good antiseptic effect of the product. It is interesting to observe that
`fluorinated dental creams without any specific active ingredient also exhibit antimicrobial
`activity [7]. This could be related to their fluoride content which, in association with the
`surfactant system in the formula, release antibacterial active cationic systems.
`
`Dishwashing Products
`
`Among the antibacterial household products that have recently appeared on the market,
`antibacterial hand dishwashing liquids have become increasingly popular. Even if these
`products are not true cosmetics, during the dishwashing, they are in direct contact with
`the skin for a certain time. From a safety point of view, they can be considered as rinse-
`off cosmetics.
`Furthermore, some products on the market have a double claim: ‘‘dishwashing liquid
`and antibacterial liquid soap.’’ They are classical dish liquids based on anionic and non-
`ionic surfactants, to which one or more antibacterial agents have been introduced. Some
`of these formula have been optimized to maintain their cleaning/degreasing performance
`on dishes and to fight bacteria on the hands, in the washing solution, and on washing
`implements. Ingredients used can be Triclosan, essential oils, or others. The use levels
`are chosen to ensure a good balance between a maximum efficacy, a low skin toxicity,
`and keeping good cleaning performances.
`
`Methods to Show Antimicrobial Product Efficacy
`
`In vitro and in vivo tests can be used to show the efficacy of antimicrobial products. Only
`the in vitro tests will be considered here because they are applicable to all antibacterial
`products. A detailed review of the in vivo tests, useful for topical antibacterials, can be
`found in Ref. 1.
`—The minimal inhibitory concentration (MIC) test principle is to determine the
`MIC of the test product by performing serial dilutions of the latter in growth medium and
`inoculating each dilution with the test strain. Products are generally tested at twofold serial
`dilutions. After suitable incubation, the first tube not exhibiting bacterial growth gives the
`MIC level, generally expressed in ppm (part per million) of product. The test can be
`carried out using either 2 mL of broth in tubes or 0.5 to 0.1 mL, in microtiter plates [8]
`or on agar plates. Control samples without any antimicrobials must be included in the
`test. This test is very useful to compare activities of different products, products from the
`same category (e.g., soaps) with different actives, or the active ingredients themselves.
`However, MIC data obtained on formulated products are very subjective and should be
`interpreted carefully. Usually, test organisms are Staphylococcus aureus, Staphylococcus
`epidermidis, and Escherichia coli, for topical antimicrobial. Pseudomonas aeruginosa and
`Salmonella typhimurium are added for the dishwashing products; for specific claims in
`the kitchen, Aspergillus niger and Candida albicans can be used as test strains. To test
`oral care products, the chosen organisms are Actynomyces viscosus, Streptococcus mutans,
`and Streptococcus sanguis, representatives of the oral flora [7].
`—The zone inhibition test method is largely used to test the resistance of bacteria
`to antibiotics [9]. Antibacterial agents or products at different concentrations are applied
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`to a substrate, a paper disk, or directly to the surface of an agar plate previously seeded
`with the test bacteria. During the incubation, the test product will diffuse into the agar
`layer and produce a zone of growth inhibition of the micro-organism. The larger the inhibi-
`tion zone, the higher the efficacy of the product. However, the data are influenced by the
`diffusion capacity of the product or the active into the agar; oily products will not diffuse
`at the same rate as aqueous-based products. It is thus very important to use negative and
`positive controls. The data will be expressed in millimeters of inhibition zone around the
`disk. The strains used for this test are usually the same that those used for the MIC test.
`These two methods give a good idea of the bacteriostatic concentrations of the tested
`product or ingredient.
`The requirements from the FDA monograph of 1994 [10] are the MIC test on the
`active ingredient, the vehicle, and the final formula, associated with a time-kill test method-
`ology to be carried out at several time points over a period of 30 minutes.
`—The time-kill test determines both the killing kinetics and the activity spectrum
`of antibacterial formulations. This test is generally performed in suspension. The principle
`is to place in contact a dilution of the product or the antibacterial agent and a specified
`bacterial inoculum during a defined period of time. At the end of the contact time, the
`antibacterial in the mixture is inactivated by dilution into neutralizing broth. Serial dilu-
`tions in appropriate broth are performed and the number of survival bacteria enumerated
`on solid culture media. This method can use different concentrations of test agents and
`bacterial inocula, and different contact times. In general, the concentrations are chosen
`so that the final organism/test solution concentration is representative of the use concentra-
`tion of the product.
`In the United States, there is no detailed standardized time-kill test, even if the U.S.
`Food and Drug Administration (FDA) requested a standard procedure [10]. In response,
`the American Society For Testing and Materials (ASTM) subcommittee of antimicrobial
`agents has prepared a draft to standardize the organism inocula, media, neutralizers, and
`contact times [11].
`In Europe, the situation is different: to test the antimicrobial efficacy of products
`and/or agents, standards exist since more than 20 years in France [12], Holland, Germany,
`and the United Kingdom. Recently, the Council of Europe has installed a Commission
`for the Normalization of European Norms [13], which is writing and publishing the Euro-
`pean Norms (EN) for testing disinfectants and antiseptics. The requirements for disinfec-
`tion are 99.99% to 99.999% of killing (4 to 5 log reductions) of the initial inoculum,
`depending on the test.
`These norms are also used by the industry to prove the efficacy of their antibacterial
`products, but the requirements are less strict: 99 to 99.9% killing (2–3 log reduction).
`Detailed review of the ENs can be found in Ref. 14.
`
`PRESERVATION AND PRESERVATIVE SYSTEMS
`Concept of Active Preservation and Self-Preserving Formula
`
`To ensure effective preservation, the method of choice is to add one or more active antimi-
`crobial ingredients to the product. These ingredients must be compatible with the other
`ingredients of the formula and must retain efficacy for an extended period of time. They
`also have to be nontoxic for the consumer.
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`To choose an active antimicrobial molecule as preservative is not so easy; this mole-
`cule must have a good oil-water partition coefficient because the contaminating microbes
`are living in the aqueous phase of the formula. It must not be inactivated by external
`factors such as the pH and the manufacturing process [15]. Other factors also have to be
`considered; such as the packaging, which could affect the preservative activity, the adsorp-
`tion rate on some components of the formul