Handbook of cosmetic science and technology second edition

Công nghệ sản xuất mỹ phẩm

edited by

Marc Paye

Colgate–Palmolive R & D Milmort, Belgium

André O Barel

Vrije Universiteit Brussels, Belgium

Howard I Maibach

University of California Hospital San Francisco, California, U.S.A.

Cover Illustration: Marianne Mahieu

Published in 2006 by

CRC Press

Taylor & Francis Group

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In 2001, we published the first edition of the Handbook of Cosmetic Science andTechnology with 71 chapters written by leading experts in their field of cosmetology,who have largely contributed to the international success of the Handbook.Since publication, comments were collected from readers and reviewers todetect improvements that could be added to this edition Most feedback was highlypositive as illustrated by some of the following: ‘‘ excellent overall coverage ofmost aspect of cosmetology ;’’ ‘‘ contains a lot of scientific information aboutthe physical properties of cosmetic ingredients ;’’ ‘‘ an excellent balance ofauthors from major cosmetic houses and with many academic leaders coming from ahuge range of countries provides an international view of cosmetics ;’’ ‘‘ an exten-sive and comprehensive index can be considered as a measure of the book’s value ’’This feedback was highly appreciated and motivated us in continuing the adventureand in initiating a second edition that, we hope, will receive the same success as thefirst one

Like in all first editions, a few improvements were suggested and were takeninto account; it was mainly to develop a more systematic chapter organization aswell as making some chapters more accessible and readable for nonexpert readers.Furthermore, cosmetology is, today, a fast moving science with new ingredients,new technologies, and changing regulations Thus, it was necessary to publish asecond edition to remain an up-to-date and practical Handbook of Cosmetic Scienceand Technology

The objectives pursued with the second edition are multiple Most chapters,recognized as essential for the cosmetologist, were kept but simplified, reviewedfor overlapping with others, made more readable, and mainly updated with newdevelopments or new anticipated trends Some chapters had to be largely revisitedsuch as in Part VI: Regulatory and Safety Considerations, that is probably the fastestchanging field Many chapters were added to cover new ingredients and technologiesidentified by the editors That is mainly evident in Part III: Cosmetic Ingredientswhere many new, active, and promising ingredients have emerged Testing the pro-ducts has also improved, in terms of physicochemistry as well as in cell culture mod-els or in skin measuring techniques Chapters were added or re-designed to reflectsuch an evolution Finally, some gaps in the first edition were filled with chapters

on additional product types, adding more emphasis on ethnic skin and its differences

in cosmetics requirements

iii

The editors are grateful to the authors, who contributed to the previous editionand updated their chapters, and to the new authors who agreed to share their experi-ences on emerging subjects, sometimes with unpublished information.

Finally, it is anticipated that future editions will benefit in the same way as thisedition, from readers’ suggested additions, deletions, and improvements

Marc PayeAndre´ O BarelHoward I Maibach

Preface iii Contributors xxiii

1 Introduction 1 Marc Paye, Andre´ O Barel, and Howard I Maibach

PART I TARGET ORGANS FOR COSMETIC PRODUCTS

2 The Microscopic Structure of the Epidermis and Its Derivatives 5 Joel J Elias

Wrinkles as an Aspect of Aged Skin 45

Local Differences in the Wrinkle Compared

to Surrounding Skin 46

v

Computer Model of the Periorbital Wrinkle 48

Origin of the Aligned Collagen Layer 50

Implications for Treatment of Wrinkles 51

References 51

5 Filaggrin and Dry Skin 53 Ian Scott

Introduction 53

Filaggrin Genotype as the Major Determinant

of Susceptibility to Dry Skin 54

The Life Cycle of Filaggrin 55

Filaggrin and the Natural Moisturizing Factor 56

Perspective on Profilaggrin and Filaggrin Functions 57

References 59

6 Hair 61 Dominique Van Neste

Introduction: What Is Hair? 61

Where Does Hair Come From? 67

Clinical Hair Growth Evaluation Methods 70

Basics About Psychosocial Aspects of Hair 83

PART II COSMETIC VEHICLES

8 Main Cosmetic Vehicles 99 Stephan Buchmann

Introduction 99

Function of Vehicles 99

Classification Systems of Vehicles 101

Description and Definition of Main Vehicles 104

Functional Design, Composition, and Resulting Effect 112 Preparation Methods 120

Characterization 120

References 122

9 Encapsulation to Deliver Topical Actives 125 Joce´lia Jansen and Howard I Maibach

Effect of Type Surfactants and Concentration 178

Non-Phospholipid-Based Elastic Vesicles 180

Mechanisms of Iontophoretic Transport 190

Parameters Affecting Iontophoretic Delivery 191

Effects of Iontophoresis on the Skin: Safety Issues 192

Topical Delivery of Drugs and Cosmetics by Iontophoresis 194 Conclusions 195

Influence of the Energy Source 203

Influence of the Formulation 204

Electrolytes in the Formulation 205

Examples of Cosmetic Iontophoresis 205

Iontophoresis Devices 207

Conclusion 208

References 208

16 Cosmetic Patches 211 Spiros A Fotinos

Introduction 211

History and Evolution 211

Borders Between Pharmaceutical and Cosmetic Patches 212 Applications of Cosmetic Patches 212

Differences Between Classical Cosmetic Forms

and Patches 213

Development of Cosmetic Patches 213

Types and Configuration 214

Structural Components of the Cosmetic Patches 216

Production Steps 219

Regulatory Issues 219

Future Trends 220

PART III COSMETIC INGREDIENTS

17 Antibacterial Agents and Preservatives 223 Franc¸oise Siquet and Michel J Devleeschouwer

21 Ceramides and Lipids 281

B B Michniak and P W Wertz

Historical Perspectives 281

Ceramides from Epidermis 282

Lipids from Other Keratinized Tissues 285

Commercially Available Ceramides 286

Pendant Organic Groups 290

Key Ingredients in the Cosmetics and Toiletries Industry 290 Skin Care, Sun Care, and Decorative Products 292

Hair Care Products 295

Longer Lasting Permanent Wave and Coloring Products 297 Antiperspirant and Deodorant Products 297

References 297

23 UV Filters 299 Stanley B Levy

Other Pigmentation Disorders 320

A New Prescription Combination Therapy—Triluma 322 Summary 323

References 324

26 Alpha Hydroxy Acids 327

M Carrera, G Primavera, and E Berardesca

References 331

27 Surfactants 333 Takamitsu Tamura

Solution Properties of Surfactants 333

Foaming Properties of Surfactants 337

Adsorption of Surfactants 340

References 343

28 Classification of Surfactants 347 Louis Oldenhove de Guertechin

Anti-Irritation by Using Only Mild Surfactants 370

Anti-Irritation by an Appropriate Combination

of Surfactants 370

Anti-Irritation by Polymers or Proteins/Peptides 371

Anti-Irritation by Refattening Agents 371

Vitamin E 386

Vitamin C 387

Thiol Antioxidants 388

Polyphenols 389

The Antioxidant Network 390

Regulation of Gene Transcription by Antioxidants 392

Perspectives 392

References 393

32 Dexpanthenol 399 Ehrhardt Proksch and Jens-Michael Jensen

Introduction 399

Biophysiology and Absorption 399

Modes of Administration 399

Indications and Clinical Applications 400

Side Effects, Contra-indications, and Product Safety 403 Conclusion 403

References 404

33 Hair Conditioners 407 Charles Reich, Dean Su, and Cheryl Kozubal

PART IV COSMETIC PRODUCTS

34 Skin Care Products 427 Howard Epstein

An Overview of Emulsion-Based Skincare Products 427

Formulating Hydrating Creams and Lotions 429

Oil-in-Water Emulsions 430

Other Ingredients 433

Skin Care Emulsions for the Aging Population 435

Formulating for Immediate Improvement in Appearance and

Texture of Skin 436

Future Formulation Challenges 439

References 439

35 Antiwrinkle Products 441 William J Cunningham

Introduction 441

Background 441

Prevention of Wrinkles of Photoaging 442

Substantiation of Antiwrinkle Claims 442

Representative Products for Wrinkles 443

Summary and Conclusions 445

Description and Validation of the Different Bioengineering

Measurements Used for Objective Evaluation of Cellulite 469 Treatments of Cellulite 471

Critical Review of Recent Clinical Anticellulite Studies 473 Conclusions 475

References 476

39 Skin Cleansing Bars 479 Joshua B Ghaim and Elizabeth D Volz

Soap Making/Manufacturing Process 485

Formulations: Regular and Translucent Soaps, Combars, Syndets, and Specialty Soaps 487

Bar Soap Performance Evaluations 489

References 492

40 Skin Cleansing Liquids 493 Daisuke Kaneko and Kazutami Sakamoto

Introduction 493

Surfactant-Type Skin Cleansers 495

Solvent-Type Skin Cleansers 499

Conclusion 501

References 502

41 Hair Cosmetics 505 Leszek J Wolfram

Introduction 505

The Structure and Properties of Hair 505

Shampoos: General Comments 507

The Teeth and Oral Environment 529

Dental Diseases Worldwide 533

Introduction 555

Color 555

Color Chemistry and Manufacture 558

Introduction 597

Biology of Sweat Glands in the Human Axilla 597

Antiperspirants 598

Drug-Delivery Systems and Application Forms

for Antiperspirant Actives 600

Future Trends 607

References 607

46 Deodorants 611 Jo¨rg Schreiber

Introduction 611

Biology of the Underarm Microflora 611

Deodorants 612

Drug-Delivery Systems and Application Forms

for Deodorant Actives 616

Introduction 641

The Development of Baby Skin 641

The Physiology of Baby Skin 642

Frequent Skin Problems in Newborns 643

The Care of Baby Skin 644

Quality Management in Baby Care 646

PART V TESTING OF COSMETIC PRODUCTS

50 Stability Testing of Cosmetic Products 655 Perry Romanowski and Randy Schueller

Introduction 655

Practical Definition of Stability Testing 655

Useful Information Provided by Stability Testing 656

Stability Test Design 657

Situations that Require Stability Testing 660

Formula-Related Reasons for Stability Testing 660

General Considerations Related to Formula Modification 664 Nonformula-Related Reasons 665

Conclusion 666

References 666

51 Stability Control: Microbiological Tests 667 Michel J Devleeschouwer and Franc¸oise Siquet

Microbiological Control of Raw Materials 667

Challenge Test for the Efficacy of Preservation 671

Determination of Water Availability or Aw 674

Culture Media, Neutralizing Solution, and Buffers 675

References 678

52 In Vitro Tests for Skin Irritation 683 Michael K Robinson and Mary A Perkins

Introduction 683

Skin Corrosion Testing 684

Skin Irritation Testing 687

54 In Vitro Reconstructed Human Skin and Skin Organ Culture Models Used

in Cosmetic Efficacy Testing 707 Alain Mavon

SQM and Skin Dryness 723

SQM and Skin Hydration 724

SQM and Skin Compatibility to Surfactant-Based

Solutions 725

Conclusion 729

References 730

56 Tests for Sensitive Skin 733

G Primavera, M Carrera, and E Berardesca

A Clinical Evaluation: The Regression Method 745

Incorporating Bioengineering Methods 746

59 Tribological Studies on Skin: Measurement of the Coefficient of Friction Raja K Sivamani, Gabriel Wu, Howard I Maibach, and Norm V Gitis Introduction 761

Skin Friction Coefficient Values 764

Introduction 781

Methods for Hair Removal 781

Experimental Testing of Hair Removal Efficacy 783

Computer Simulation of Hair Removal Efficacy 787

Concluding Remarks 789

References 789

62 Skin Lipid Structure Measured by Electron Paramagnetic

Resonance 793 Kouichi Nakagawa

Introduction 793

EPR Apparatus 794

EPR of Nitroxide Spin Probe 794

Spin Probe Lineshapes Owing to Molecular Motions 795 Spin Probes (or Spin Labels) 795

Conventional Order Parameter (S) 796

Order Parameter (S0) by the EPR Simulation 797

Conventional Order Parameter and Order Parameter by

Simulation Method 797

Other Applications of EPR Method 799

Summary and Future Prospects 799

PART VI REGULATORY AND SAFETY CONSIDERATIONS

64 Definition of Cosmetics 815 Stanley R Milstein, Allen R Halper, and Linda M Katz

Introduction 815

Cosmetics in History 815

Statutory Definition of Cosmetics 816

Cosmetics that Are Also Drugs: The Intended Use Doctrine 817 The Cosmetic/Drug Distinction: The Role of the Intended

Use Doctrine in FDA Assignment of Regulatory Category

(Trade Correspondence) 821

The Alpha Hydroxy Acid (AHA) Situation 826

Cosmeceuticals, Cosmetic Therapeutics, and Other Proposed

Definitions 827

References 828

65 Regulatory Requirements for the Marketing of Cosmetics in the

United States 833 Stanley R Milstein, Allen R Halper, and Linda M Katz

Scope 833

Basic U.S Legal Structure for Cosmetics 833

Basic U.S Regulatory Structure for Cosmetics 835

References 854

66 Legislation in Japan 861 Mitsuteru Masuda and Fusae Harada

Regulatory Environment 861

Cosmetics 862

Quasidrugs 864

Cosmetics in the Future 866

Quasidrugs in the Future 867

References 867

67 EEC Cosmetic Directive and Legislation

in Europe 869 Rene´ Van Essche

The Laws of the Member States Relating to Cosmetic Products

and the 6th Amendment 869

Implementation of the European Directive on Cosmetic Products

in the Different Member States of the European Union 874 References 877

68 Introduction to the ‘‘Proof of Claims’’ 879 Marc Paye and Andre´ O Barel

Regional Requirements 879

Categories of Claims 883

Type of Support 883

Conclusion 886

References 887

69 Safety Terminology 889 Ai-Lean Chew and Howard I Maibach

Introduction 889

Contact Dermatitis 889

Irritant Contact Dermatitis (Irritation) 889

Allergic Contact Dermatitis 890

Photoirritant Contact Dermatitis

(Photoirritation/Phototoxicity) 891

Photoallergic Contact Dermatitis 891

Contact Urticaria Syndrome 891

Molecular Mechanisms of Skin Irritancy 895

Factors Predisposing to Cutaneous Irritation 896

Epidemiology 897

Clinical Types of ICD 898

References 901

71 In Vivo Irritation 905 Saqib J Bashir and Howard I Maibach

Cosmetic and Occupational Irritants 923

Strategy of Making Anti-Irritant Cosmetics 925

In Vivo Studies of the Anti-Irritation Properties of

Some Cosmetic Ingredients 927

References 929

73 Ethnicity as a Possible Endogenous Factor in Irritant Contact

Dermatitis: Comparing the Irritant Response Among Caucasians,

Blacks, and Asians 933 Sara P Modjtahedi and Howard I Maibach

Introduction 933

Black vs Caucasian Irritation Response 934

Asian vs Caucasian Irritation Response 935

Steps to Percutaneous Absorption 943

Methods for Percutaneous Absorption 944

Individual and Regional Variation 947

Vehicle Influence on Percutaneous Absorption 947

Skin Cleansing and Decontamination 948

Cosmetic Percutaneous Absorption and Toxicity 951

Correlations with the Location of the Lesions 972

The Nature of Cosmetic Allergens 972

Diagnosing Cosmetic Allergy 977

Josette Andre´ Department of Dermatology, Saint-Pierre University Hospital, FreeUniversity of Brussels, Brussels, Belgium

Robert Baran Nail Disease Center, Cannes, France

Andre´ O Barel Algemenen en Biologische Scheikunde, Faculty of PhysicalEducation and Physiotherapy, Vrije Universiteit Brussel, Pleinlaan, Brussels,Belgium

John Barr Advanced Polymer Systems, Redwood City, California, U.S.A.Saqib J Bashir Department of Dermatology, University of California at SanFrancisco, School of Medicine, San Francisco, California, U.S.A

Leslie S Baumann Department of Dermatology and Cutaneous Surgery, Division

of Cosmetic Dermatology, University of Miami School of Medicine, Miami,Florida, U.S.A

E Berardesca San Gallicano Dermatological Institute, Via Chianesi, Rome, ItalyJanet Blakely Dow Corning S.A., Seneffe, Belgium

Stephan Buchmann Spirig Pharma AG, Egerkingen, Switzerland

M Carrera San Gallicano Dermatological Institute, Via Chianesi, Rome, ItalyVe´ranne Charbonnier Consulting, Colomars, France

Ai-Lean Chew Department of Dermatology, University of California at SanFrancisco, School of Medicine, San Francisco, California, U.S.A

Myeong Jun Choi Department of Dermatology, University of California, School ofMedicine, San Francisco, California, U.S.A

William J Cunningham CU-TECH, Parsippany, New Jersey, U.S.A

Louis Oldenhove de Guertechin Colgate-Palmolive R&D, Milmort, Belgium

xxiii

Michel J Devleeschouwer Free University of Brussels, Brussels, Belgium

Joel J Elias University of California at San Francisco, School of Medicine, SanFrancisco, California, U.S.A

Peter Elsner University of Jena, Jena, Germany

Howard Epstein Kao Brands, The Andrew Jergens Company, Cincinnati, Ohio, U.S.A.Spiros A Fotinos Lavipharm, Peania Attica, Greece

Bernard Gabard Scientific Consulting, Egerkingen, Switzerland

Abdul Gaffar Growth Technology Development, Research and Development,Colgate-Palmolive Company Technology Center, Piscataway, New Jersey, U.S.A.Joshua B Ghaim Colgate-Palmolive Company, Piscataway, New Jersey, U.S.A.Norm V Gitis Center for Tribology, Inc., Campbell, California, U.S.A

Nicholas Golda Keck School of Medicine of the University of Southern California,Los Angeles, California, U.S.A

An E Goossens University Hospital, Katholieke Universiteit Leuven, Leuven,Belgium

Martin Green Unilever R&D, Colworth, Sharnbrook, Bedford, U.K

Allen R Halper Office of Cosmetics and Colors, FDA/CFSAN, College Park,Maryland, U.S.A

Fusae Harada Research and Technology Headquarters, Lion Corporation,Edogawa-ku, Tokyo, Japan

Jorge Heller Advanced Polymer Systems, Redwood City, California, U.S.A.Joce´lia Jansen State University of Ponta Grossa, Ponta Grossa, Parana, BrazilJens-Michael Jensen Department of Dermatology, University Hospitals ofSchleswig-Holstein, Campus Kiel, Germany

Daisuke Kaneko AminoScience Laboratories, Ajinomoto Co., Inc., Kanagawa, JapanLinda M Katz Office of Cosmetics and Colors, FDA/CFSAN, College Park,Maryland, U.S.A

Brian C Keller Biozone Laboratories, Inc., Pittsburgh, California, U.S.A.John Koo Department of Dermatology, University of California, and UCSFPsoriasis and Skin Treatment Center and Phototherapy Unit, San Francisco,California, U.S.A.

Cheryl Kozubal Colgate-Palmolive Technology Center, Piscataway, New Jersey,U.S.A

Hans Lautenschla¨ger KOKO GmbH & Co., KG, Leichlingen, Germany

Ivy Lee Department of Dermatology, University of California at San Francisco,School of Medicine, San Francisco, California, U.S.A

Jackie Levin Department of Dermatology, University of California at SanFrancisco, School of Medicine, San Francisco, California, U.S.A

Stanley B Levy Department of Dermatology, University of North Carolina atChapel Hill and Revlon Research Center, Chapel Hill, North Carolina, U.S.A.Marie Lode´n Research & Development, ACO HUD AB, Upplands Va¨sby, SwedenJohn K Lodge University of Surrey, Guildford, Surrey, England

Howard I Maibach Department of Dermatology, University of California atSan Francisco, School of Medicine, San Francisco, California, U.S.A

Lucy K Martin Department of Dermatology and Cutaneous Surgery, Division ofCosmetic Dermatology, University of Miami School of Medicine, Miami, Florida, U.S.A.Mitsuteru Masuda Research and Technology Headquarters, Lion Corporation,Edogawa-ku, Tokyo, Japan

Peter Maurer Beiersdorf AG, Paul Gerson Unna Skin Research Center, ProductDevelopment Cosmed, Unnastr, Hamburg, Germany

Alain Mavon Lab of Skin Pharmacokinetics, Pierre Fabre Research Institute,Vigoulet-Auzil, France

B B Michniak School of Pharmacy, Rutgers University, Piscataway, New Jersey,U.S.A

Stanley R Milstein Office of Cosmetics and Colors, FDA/CFSAN, College Park,Maryland, U.S.A

Sara P Modjtahedi Department of Dermatology, University of California atSan Francisco, School of Medicine, San Francisco, California, U.S.A

Kouichi Nakagawa RI Research Center, Fukushima Medical University,

Fukushima, Japan

Gisbert Ottersta¨tter DRAGOCO Gerberding & Co., AG, Holzminden, GermanyLester Packer University of California at Berkeley, Berkeley, California, U.S.A.Marc Paye Colgate-Palmolive R&D, Milmort, Belgium

Mary A Perkins The Procter & Gamble Company, Miami Valley Laboratories,Cincinnati, Ohio, U.S.A

Ve´ronique Preat Universite´ Catholique de Louvain, Unite´ de Pharmacie

Gale´nique, Brussels, Belgium

G Primavera San Gallicano Dermatological Institute, Via Chianesi, Rome, ItalyEhrhardt Proksch Department of Dermatology, University Hospitals of Schleswig-Holstein, Campus Kiel, Germany

Charles Reich Colgate-Palmolive Technology Center, Piscataway, New Jersey, U.S.A.Michael K Robinson The Procter & Gamble Company, Miami Valley

Laboratories, Cincinnati, Ohio, U.S.A

Michiel E Roersma Philips Research, Care & Health Applications, Eindhoven,The Netherlands

Perry Romanowski Alberto Culver Company, Melrose Park, Illinois, U.S.A.Kazutami Sakamoto AminoScience Laboratories, Ajinomoto Co., Inc., Kanagawa,Japan

Claude Saliou University of California at Berkeley, Berkeley, California, U.S.A.Subhash J Saxena Advanced Polymer Systems, Redwood City, California, U.S.A.Sibylle Schliemann-Willers University of Jena, Jena, Germany

Mitchell L Schlossman KOBO Products Inc., South Plainfield, New Jersey, U.S.A.Uwe Scho¨nrock Beiersdorf AG, Hamburg, Germany

Douglas Schoon Creative Nail Design Inc., Vista, California

Jo¨rg Schreiber Beiersdorf AG, Hamburg, Germany

Klaus R Schro¨der Henkel KGaA, Du¨sseldorf, Germany

Randy Schueller Alberto Culver Company, Melrose Park, Illinois, U.S.A

Ian Scott Synergy Biosystems Ltd., Barclays Venture, Coventry, U.K

Franc¸oise Siquet Colgate-Palmolive Technology Center, Milmort, Belgium

Raja K Sivamani Department of Dermatology, University of California at SanFrancisco, School of Medicine, San Francisco, California, U.S.A.

Dean Su Colgate-Palmolive Technology Center, Piscataway, New Jersey, U.S.A.Dov Tamarkin Power Paper Ltd., Petah Tikvah, Israel

Takamitsu Tamura Material Science Research Center, Lion Corporation,

Edogawa-ku, Tokyo, Japan

Yoshimasa Tanaka Biological Science Research Center, Lion Corporation,Kanagawa, Japan

Jens Treu Beiersdorf AG, Paul Gerson Unna Skin Research Center, ProductDevelopment Cosmed, Unnastr, Hamburg, Germany

Rene´ Van Essche Free University of Brussels, Longueville, Belgium

Dominique Van Neste Skinterface Sprl, Tournai, Belgium

Isabelle Van Reeth Dow Corning S.A., Rue Jules Bordet, Parc Industriel—Zone C,Seneffe, Belgium

Elizabeth D Volz Colgate-Palmolive Company, Piscataway, New Jersey, U.S.A.Valentin Wascotte Universite´ Catholique de Louvain, Unite´ de PharmacieGale´nique, Brussels, Belgium

Stefan U Weber University of California at Berkeley, Berkeley, California, U.S.A

P W Wertz Dows Institute, University of Iowa, Iowa City, Iowa, U.S.A.Naissan O Wesley Department of Dermatology, University of California at SanFrancisco, School of Medicine, San Francisco, California, U.S.A

Ronald C Wester Department of Dermatology, University of California at SanFrancisco, School of Medicine, San Francisco, California, U.S.A

Joyce H D M Westerink Philips Research, Care & Health Applications,Eindhoven, The Netherlands

Leszek J Wolfram Stamford, Connecticut, U.S.A

Gabriel Wu Department of Dermatology, University of California at San

Francisco, School of Medicine, San Francisco, California, U.S.A

Hongbo Zhai Department of Dermatology, University of California at SanFrancisco, School of Medicine, San Francisco, California, U.S.A

Germaine Zocchi Colgate-Palmolive R&D, Inc., Milmort, Belgium

Algemenen en Biologische Scheikunde, Faculty of Physical Education and

Physiotherapy, Vrije Universiteit Brussel, Pleinlaan, Brussels, Belgium

Howard I Maibach

Department of Dermatology, University of California at San Francisco, School of

Medicine, San Francisco, California, U.S.A

Although cosmetics for the purpose of beautifying, perfuming, cleansing, or forrituals have existed since the origin of civilization, only in the 20th century great pro-gress has been made in the diversification of products and functions and in the safetyand protection of the consumer

Before 1938, cosmetics were not regulated as drugs, and cosmetology couldoften be considered as a way to sell dreams rather than objective efficacy; safetyfor consumers was also sometimes precarious Subsequently, the Food and DrugAssociation, through the Federal Food Drug and Cosmetic Act, regulated cosmeticswhich were required to be safe for the consumer

With industrialization, many new ingredients from several industries (oleo- andpetrochemical, food, etc.) were utilized in preparation of cosmetics offering a list ofnew functions and forms For a better control of these ingredients, U.S laws requiredingredient classification and product labeling since 1966

Finally, the latest innovation in the field of cosmetics is the development ofactive cosmetics (cosmeceuticals in the United States) Currently, cosmetics not onlyintend to improve the appearance or odor of the consumer but also intend to benefittheir target, whether it is the skin, the hair, the mucous membrane, or the tooth.With this functional approach, products became diversified and started to claim amultitude of biologic actions The cosmetic market then greatly extended with mil-lions of consumers worldwide The competitive environment pushed manufacturers

to promise more to the consumers and to develop cosmetic products of better qualityand higher efficacy Today, many cosmetic products aim at hydrating skin, reducing

or slowing the signs of aged skin, or protecting the skin against the multitude of dailyenvironmental aggressions In order for cosmetic products to support these activities,raw materials became more efficacious, safe, bioavailable, and innovative, whileremaining affordable With the continuous improvement of the basic sciences and

1

the development of new sciences (e.g., molecular biology), new sources for pure rawmaterials have been found Raw materials are not only produced from naturalsources and highly purified, but they can also be specifically synthesized or even pro-duced from genetically manipulated microorganisms However, the availability anduse of these sophisticated and active ingredients are not always sufficient for them to

be optimally delivered to their targets and to sustain their activity The cosmeticvehicle is also crucial to obtain this effect, and the role of the formulator is tocombine the right ingredient and the appropriate vehicle

Additional sciences also developed in parallel to active cosmetology andcontributed significantly to its rise; this is the case for biometric techniques, whichhave been developing for more than three decades and allow a progressive and non-invasive investigation of many skin properties Instruments and methods are nowavailable to objectively evaluate and measure cutaneous elasticity, topography, hydra-tion, turnover rate, or even to see directly in vivo inside the skin through microscopeevolution Major innovations in the field are reported by the International Society forBioengineering and the Skin Guidelines for the appropriate usage of instrumentaltechniques and for the accurate measurement of skin function and properties are reg-ularly published by expert groups such as the Standardization Group of the EuropeanSociety of Contact Dermatitis or the European Group for Efficacy Measurement ofCosmetics and Other Topical Products Today, any claimed effect of a cosmetic onthe skin should find appropriate techniques for a clear demonstration

For better protection of the consumer against misleading claims, National orFederal laws prohibit false advertisements on cosmetic products In Europe, theSixth Amendment of the European Directive on Cosmetic Products requires manu-facturers to have readily available a dossier with the proof of the claims made ontheir products The Seventh Amendment of the European Directive, published inMarch 2004, among several other requirements explained later in this book, alsomade information about the product more easily accessible to the public by anyappropriate means, including electronic means

Finally, the recent evolution of cosmetic products and the constraints imposed

on the cosmetic manufacturer lead cosmetology to largely increase its credibility

in front of scientists, physicians, and consumers Cosmetology has become ascience based on the combination of various expertise domains: chemistry, physics,biology, bioengineering, dermatology, microbiology, toxicology, statistics, andmany others

Because of such a complexity in cosmetic science, it was not possible to cover in

a useful manner all the aspects in one book Details of most of the above fields arecovered in the different volumes of the ‘‘Cosmetic Science and Technology’’ series Inthe first edition of the ‘‘Handbook of Cosmetic Sciences and Technologies,’’ we espe-cially aimed at producing a useful guide and a source of ideas for the formulation ofmodern cosmetics Four years later, new ingredients, more sophisticated products,more functional vehicles, and more sensitive testing methods have emerged About

20 chapters were added to those of the previous edition, while about 80% of theothers were updated The outstanding contributors reviewed the major ingredients,the major technologies, and the up-to-date regulations throughout the world that theformulator needs to know For more experienced scientists, recent innovations interms of ingredients and cosmetic vehicle forms are described, which should orientthe type of products of tomorrow Finally, the large overview of cosmetic formula-tions should serve the dermatologist who is daily faced with patients who requestrecommendation for the most appropriate product for their skin type or who have

specific intolerance to an ingredient This should help them to better understandcosmetics.

For easier access to the information contained within, the second edition of thehandbook has been reorganized and subdivided into six parts, including severalchapters written by different authors It could seem to some a large number of con-tributors, but it is intentionally that the editors chose that form, to guarantee thateach subject be described by a recognized expert in its field and well aware of thelatest development in that topic Also, authors were selected worldwide Indeed,cosmetology is universal, but there exists some regional specificity, which needs to

be addressed

The first part introduces the reader with a description of the anatomy andphysiology of the body targets for cosmetics: skin, hair, and nails

The second part covers cosmetic vehicles with a special emphasis on a few types

of recently introduced delivery systems, such as cosmetic patches, encapsulation

of actives, special liposomes, and iontophoresis The third part describes cosmeticingredients For some categories of ingredients, the most useful information is a list

of ingredients that exist with a critical analysis of the advantages and disadvantages.For others, however, a good understanding of the role of an ingredient in a product

is needed, of its limitations, mechanism of action, and regulatory constraints.Part four, the largest one, is the core of the handbook and provides guidance tothe formulation of skin cleansing products, skin care products, hair products, oralcare products, and decorative products Finally specific chapters cover the specialcosmetics for baby and elderly consumers or for men

In the fifth part, the stability control of cosmetic products is described, as well

as an overview on the in vitro and clinical tests used for proving the efficacy and erance of the products Finally, the last part compares the cosmetic legislation in theUnited States, Europe, and Japan, and provides useful information about safetyterminology and description of the principles and mechanism of unwanted interac-tions of cosmetics with their targets

tol-Given the number of contributions, it has been a challenge to edit this secondedition, only four years after the first; if it has been possible, this is due to thededication of the authors and to the continuous follow-up made with the authors

by Mrs S Beberman and A Tucker from Marcel Dekker Inc We thank all of themfor making this enormous task easy, enjoyable, and mainly feasible

The Microscopic Structure of the

Epidermis and Its Derivatives

The epithelial component of the skin, the epidermis, is classified histologically

as a stratified squamous keratinizing epithelium It is thickest on the palms and soles(Fig 1) and thinner elsewhere on the body (Fig 2) It lies on the connective tissuecomponent of the skin, the dermis, in which are located the blood vessels andlymphatic vessels Capillary loops in the dermis come to lie in close apposition tothe underside of the epidermis The epidermis, in common with other epithelia, isavascular The living cells of the epidermis receive their nutrients by diffusion ofsubstances from the underlying dermal capillaries through the basement membraneand then into the epithelium Metabolic products of the cells enter the circulation bydiffusion in the opposite direction

For other epithelia, the epidermis lies on a basement membrane (basal lamina).This extracellular membrane, interposed between the basal cells of the epidermis andthe connective tissue of the dermis, serves the important function of attaching thetwo tissues to each other The point of contact of the epidermis with this structure

is the basal cell membrane of the basal cells Along this surface the basal cellsshow many hemidesmosomes, which increase the adherence of the basal cells (andtherefore of the entire epidermis) to the basement membrane (and therefore to thedermis) In some locations, such as the renal glomerulus, the basal lamina also hasbeen shown to play a role as a diffusion barrier to certain molecules

This chapter is reproduced with permission from Bronaugh RL, Maibach HI, eds neous Absorption: Mechanisms—Methodology—Drug Delivery 2nd ed New York: MarcelDekker, Inc., 1989

Percuta-PART I TARGET ORGANS FOR COSMETIC PRODUCTS

5

The plane of contact between the epidermis and dermis is not straight, but is anundulating surface, more so in some locations than others Upward projections ofconnective tissue, the dermal papillae, alternate with complementary down growths

of the epidermis This serves to increase the surface area of contact between the twoand presumably, therefore, the attachment

Within the epidermis are found four different cell types with different functionsand embryologic origins, namely, keratinocytes, melanocytes, Langerhans cells, andMerkel cells These will be considered in turn

The keratinocytes are derived from the embryonic surface ectoderm and entiate into the stratified epithelium Dead cells are constantly sloughed from theupper surface of the epidermis and are replaced by new cells being generated fromthe deep layers It is generally considered that the basal layer is the major source

differ-of cell renewal in the epidermis Lavker and Sun (1) distinguish two types differ-of basalcells, a stem cell type and a type that helps anchor the epidermis to the dermis,and an actively dividing suprabasal cell population The basal cells have desmosomesconnecting them to the surrounding cells and, as mentioned earlier, hemidesmo-somes along the basal lamina surface They have tonofilaments coursing throughthe cytoplasm and coming into close apposition to the desmosomes These proteinfilaments are of the intermediate filament class and are made up principally of

Figure 2 Thin epidermis The strata spinosum, granulosum, and corneum are considerablythinner than in Figure 1 Hematoxylin and eosin,200

Figure 1 Thick epidermis from sole The spiral channel through the extremely thick stratumcorneum (sc) carries the secretion of a sweat gland to the surface The stratum granulosum (sg)stands out clearly because its cells are filled with keratohyalin granules that stain intensely with

keratin Basal cells have the usual cell organelles and free ribosomes, the site ofsynthesis of intracytoplasmic proteins.

As a result of the proliferation of cells from the deeper layers, the cells moveupward through the epidermis toward the surface As they do, they undergo differ-entiative changes which allowed microscopists to define various layers The cellsfrom the basal layer enter the stratum spinosum, a layer whose thickness variesaccording to the total thickness of the epidermis The layer derives its name because,with light microscopic methods, the surface of the cell is studded with many spinyprojections These contact similar projections from adjacent cells and the structurewas called an intercellular bridge by early light microscopists (Fig 3) Electronmicroscopy showed that the so-called ‘‘intercellular bridges’’ were really desmo-somes, and the light microscopic appearance is an indication of how tightly the cellsare held by each other at these points The number of tonofilaments increases in thespinous cells (prickle cells) and they aggregate into coarse bundles—the tonofibrils—which were recognizable to light microscopists using special stains

Electron microscopy reveals the formation within the spinous cells of a specificsecretory granule These small, membrane-bound granules form from the Golgi app-aratus and are the membrane-coating granules (MCG; lamellar bodies; Odlandbodies) They contain lipids of varying types, which have become increasingly char-acterized chemically (2,3)

As the cells of the stratum spinosum migrate into the next layer there appear intheir cytoplasm large numbers of granules that stain intensely with hematoxylin.These are the keratohyalin granules and their presence characterizes the stratum gran-ulosum Electron microscopy shows that the granules are not membrane-bound butare free in the cytoplasm Histidine-rich proteins (4,5) have been identified in the gran-ules The tonofilaments come to lie in close relationship to the keratohyalin granules.The membrane-coating granules are mainly in the upper part of the granular cell.When observed by either light or electron microscopy there is an abrupt trans-formation of the granular cell into the cornified cell with a loss of cell organelles Inthick epidermis, the first cornified cells stain more intensely with eosin and this layerhas been called the stratum lucidum The interior of the cornified cell consists of thekeratin filaments, which appear pale in the usual electron microscopic preparations,and interposed between them is a dark osmiophilic material The interfilamentous

Figure 3 High power view of upper part of stratum spinosum and lower part of stratumgranulosum Note that the many ‘‘intercellular bridges’’ (desmosomes) running between thecells, gives them a spiny appearance When the cells move up into the stratum granulosum,keratohyalin granules (k) appear in their cytoplasm Hematoxylin and eosin,l000

matrix material has been shown to have derivations from the keratohyalin granuleand is thought to serve the function of aggregation of the keratin filaments in thecornified cell (4,5).

In the uppermost cells of the granular layer the membrane-coating granulesmove toward the cell surface, their membrane fuses with the cell membrane, andtheir lipid contents are discharged into the intercellular space Thus, the intercellularspace in the cornified layer is filled with lipid material, which is generally thought to

be the principal water permeability barrier of the epidermis (2,3) The stratum neum has been compared to a brick wall, with the bricks representing the cornifiedcells, surrounded completely by mortar, representing the MCG material (6).The cornified cell is further strengthened by the addition of protein to the innersurface of the cell membrane Two proteins that have been identified in this processare involucrin (7,8) and keratolinin (9) A transglutaminase crosslinking of thesoluble proteins results in their fusion to the inner cell membrane to form the toughouter cell envelope of the cornified cell Desmosomes between the cells persist in thecornified layer

cor-It can be seen that formation of an outer structure (stratum corneum) whichcan resist abrasion from the outside world and serve as a water barrier for a land-dwelling animal has proven incompatible with the properties of living cells The liv-ing epidermal cells, therefore, die by an extremely specialized differentiative processthat results in their nonliving remains having the properties that made life on land asuccessful venture for vertebrates

Distributed among the keratinocytes of the basal layer are cells of a differentembryologic origin and function, the melanocytes In the embryo, cells of theneural crest migrate from their site of origin to the various parts of the skin andtake up a position in the basal layer of the epidermis They differentiate into mel-anocytes and extend long cytoplasmic processes between the keratinocytes in thedeep layers of the epidermis Because they contain the enzyme tyrosinase, theyare able to convert tyrosine to dihydroxyphenylalanine (dopa) and the latter todopaquinone with the subsequent formation of the pigmented polymer melanin.The tyrosinase is synthesized in the rough endoplasmic reticulum and transferred

to the Golgi body From the latter organelle, vesicles with an internal periodicstructure containing tyrosinase are formed These are the melanosomes, the mela-nin-synthesizing apparatus of the cell Melanin is formed within the melanosome,and as it accumulates the internal structure of the melanosome becomes obscured

In light microscope the pigmented melanosome appears as the small brown nin granule The melanin granules are then transferred from the melanocyte’s cyto-plasmic extensions to the keratinocytes, and become especially prominent in thebasal keratinocyte’s cytoplasm In this position their ability to absorb ultravioletradiation has a maximal effect in protecting the proliferating basal cell’s DNAfrom the mutagenic effects of this radiation Within the keratinocyte, varying numbers

mela-of melanosomes are mela-often contained within a single membrane-bound vesicle The sic method of demonstrating melanocytes is the dopa test Sections of skin are placed in

clas-a solution of dopclas-a clas-and only the melclas-anocytes turn into clas-a dclas-ark brown color (Fig 4).Within the epidermis is another population of cells which were first demon-strated by Langerhans in 1868 By placing skin in a solution of gold chloride, heshowed that a number of cells in the epidermis, particularly in the stratum spinosum,turned black The cytoplasmic extensions of the cell give them a dendritic appear-ance For many decades the nature of this cell type was unknown, including whether

it was a living, dead, or dying cell Electron microscopy showed that it was a viable

cell in appearance, lacked desmosomes, and possessed a very unusual cytoplasmicstructure—the Birbeck granule.

With the development of methods for identifying cell membrane receptors andmarkers in immune system cells, it was shown that Langerhans cells originate in thebone marrow They are now thought to be derived from circulating blood mono-cytes, with which they share common marker characteristics The monocytes migrateinto the epidermis and differentiate into Langerhans cells Considerable evidenceshows that these dendritic cells capture cutaneous antigens and present them to lym-phocytes in the initiation of an immune response Their population in the epidermis

is apparently constantly replenished by the blood-borne monocytes

Finally, a fourth cell type, the Merkel cell, can be found in the epidermis Theseappear to be epithelial cells and are found in the basal layer A characteristic feature

is the presence of many small, dense granules in their cytoplasm Sensory nerveendings form expanded terminations in close apposition to the surface of Merkelcells

Hair follicles begin their formation as a down growth of cells from the surfaceepidermis into the underlying connective tissue The growth extends into the deepdermis and subcutaneous tissue and forms in the deepest part of the structure a mass

of proliferative cells—the hair matrix The cells of the outermost part of the hair licle, the external root sheath, are continuous with the surface epidermis The deepestpart of the hair follicle is indented by a connective tissue structure, the hair papilla,which brings blood vessels close to the actively dividing hair matrix cells (Fig 5) Asthe cells in the matrix divide, the new cells are pushed upward toward the surface.Those moving up the center of the hair follicle will differentiate into the hair itself.The structure of the hair, from the center to the outer surface, consists of the medulla(when present), the cortex, and the cuticle The cortex forms the major part of thehair These cells accumulate keratin to a very high degree They do not die abruptly

fol-as in the cfol-ase of the surface epidermis Instead, the nucleus of the cell graduallybecomes denser and more pyknotic and eventually disappears Keratohyalin gran-ules are not seen with the light microscope Cells moving up from the matrix intothe region between the hair and the external root sheath form the internal rootsheath Here, the cells adjacent to the hair form the cuticle of the internal rootsheath Next is Huxley’s layer and, adjacent to the external root sheath, Henle’s

Figure 4 A thick section of the epidermis was made with the plane of section running allel to the surface of the skin and including the deep layers of the epidermis Dopa reactionshows whole melanocytes on surface view, illustrating their branching, dendritic nature(340)

layer These cells accumulate conspicuous trichohyalin granules in their cytoplasm inthe deeper part of the internal root sheath The cells of the internal root sheath dis-integrate higher up in the hair follicle and disappear at about the level of the sebac-eous gland Thereafter, the hair is found in the central space of the hair folliclewithout a surrounding internal root sheath.

When viewed with the light microscope, the hair follicle is surrounded by anexceedingly thick basement membrane called the glassy membrane Scattered amongthe keratinocytes in the hair matrix are melanocytes, which transfer pigment to theforming hair cells and give the hair color Hair growth is cyclic, with each folliclehaving alternating periods of growth and rest

About a third of the way down the hair follicle from the surface epidermis,the sebaceous glands connect to the hair follicle The sebaceous alveoli consist of

a rounded, solid mass of epithelial cells surrounded by a basement membrane.The outer cells proliferate and the newly formed cells are pushed into the interior

of the sebaceous alveolus As they move in this direction they accumulate a complex

of lipids and lipid-like substances As the lipids fill the cell it begins to die and thenucleus becomes often pyknotic The cells eventually disintegrate, releasing their oilycontents via a short duct into the space of the hair follicle (Fig 6) This is the classicexample of holocrine secretion where the entire gland cell becomes the secretion Insome scattered locations (e.g., nipple) sebaceous glands can be found independent

of the hair follicle In other areas their size relative to the hair follicle is very large(Fig 7) As the lipids are extracted in the usual histologic preparations, the cellstypically appear very pale

The major type of sweat gland in the human, the eccrine sweat gland, is uted over, practically, all parts of the body It produces a watery secretion which

distrib-is conveyed to the surface of the skin where its evaporation plays an important

Figure 5 The connective tissue hair papilla (p) indents into the base of the hair follicle Thefollicle cells in the hair matrix region (m) show many mitotic figures Iron hematoxylin andaniline blue,l50