Skin Decontamination: A Comprehensive Clinical Research Guide [1st ed. 2020] 978-3-030-24008-0, 978-3-030-24009-7

Table of contents :
Front Matter ....Pages i-xi
Isolated Human and Animal Stratum Corneum As a Partial Model for the 15 Steps of Percutaneous Absorption: Emphasizing Decontamination, Part I (Xiaoying Hui, Howard I. Maibach)....Pages 1-24
Isolated Human and Animal Stratum Corneum as a Partial Model for the 15 Steps of Percutaneous Absorption: Emphasizing Decontamination Part II (Xiaoying Hui, Howard I. Maibach)....Pages 25-44
Recent Knowledge: Human/Animal Skin Decontamination (Christina Phuong, Howard I. Maibach)....Pages 45-51
Decontamination of Chemically Contaminated Remains (Jill A. Harvilchuck, Dan Noort, Glenn Lawson, Kelly Kyburz, Miranda Verschraagen, Alison Director-Myska)....Pages 53-75
Effectiveness of Chemical, Biological, Radiological, and Nuclear (CBRN) Skin Decontaminants: Toward Tests Standardization (Denis Josse)....Pages 77-85
Effects of Soap-Water Wash on Human Epidermal Penetration (Hanjiang Zhu, Eui-Chang Jung, Christina Phuong, Xiaoying Hui, Howard I. Maibach)....Pages 87-99
Fuller’s Earth: Old and Faithful Skin Decontaminant Against Toxic Agents (Shlomit Dachir, Eliezer Fishbine, Yakov Meshulam, Hillel Buch, Nahum Allon, Tamar Kadar)....Pages 101-119
Comparison of Four Different Fuller’s Earth Formulations in Skin Decontamination (Annick Roul, Cong-Anh-Khanh Le, Marie-Paule Gustin, Emmanuel Clavaud, Bernard Verrier, Fabrice Pirot et al.)....Pages 121-139
The Mass Decontamination Paradigm: Response Relating to Gas Phase Exposures and Skin Decontamination (Christina Baxter, Sharyn Gaskin, Michael Logan, Dino Pisaniello)....Pages 141-162
Binding Affinity and Decontamination of Dermal Decontamination Gel (DDGel) to Model Chemical Warfare Agent (CWA) Simulants (Yachao Cao, Akram Elmahdy, Hanjiang Zhu, Xiaoying Hui, Howard I. Maibach)....Pages 163-181
Dermostyx (IB1): High Efficacy and Safe Topical Skin Protectant Against Percutaneous Toxic Agents (Shlomit Dachir, Izhak Barness, Eliezer Fishbine, Jacob Meshulam, Rita Sahar, Arik Eisenkraft et al.)....Pages 183-198
Understanding the Impact of Responder Management Strategies on Public Experiences and Behaviour During Mass Casualty Decontamination (Holly Carter, John Drury, Richard Amlôt)....Pages 199-210
Back Matter ....Pages 211-280

Citation preview

Skin Decontamination A Comprehensive Clinical Research Guide Hanjiang Zhu Howard I. Maibach  Editors

123

Skin Decontamination

Hanjiang Zhu  •  Howard I. Maibach Editors

Skin Decontamination A Comprehensive Clinical Research Guide

Editors Hanjiang Zhu, PhD Department of Dermatology University of California San Francisco, CA USA

Howard I. Maibach, MD Department of Dermatology University of California San Francisco School of Medicine San Francisco, CA USA

ISBN 978-3-030-24008-0    ISBN 978-3-030-24009-7 (eBook) https://doi.org/10.1007/978-3-030-24009-7 © Springer Nature Switzerland AG 2020 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

Preface

To general toxicologist and those involved in skin, hair and nail decontamination of chemical warfare and chemicals of mass destruction. The birth of this field occurred in Belgium – a century ago, when both government contenders utilized chemicals which produced marked lethality and/or incapacitation. This led to many countries being involved in research in the field of chemical decontamination  – mainly aimed at chemicals of mass destruction. Much of the experimental data remains buried in governmental archives such as the United States and the United Kingdom, and some remains classified until now. Today there is wide acceptance, by many governments, of various Fuller’s earth formulations (such as France) and the so-called RSDL – the United States. Combined with these highly specialized formulations, with deep research background, is another major approach to mass decontamination  – the water wash approach. In addition, worldwide, material safety data sheets (MSDS) recommend water wash for acute skin decontamination. Recent data suggests that water wash may, at various time points, increase skin penetration and the potential for increasing acute general toxicity from highly toxic chemicals. What appears to be a major paradigm shift is the apparent need to decontaminate millions of people from chemicals of nonacute lethality – such as the workers in the chemical industry who are exposed typically 5 days weekly for decades – to chemicals whose systemic toxicity (reproduction, carcinogenicity, and/or other internal organ toxicity) is often inadequately understood. This paradigm shift will require major new approaches to daily skin decontamination – not only for the acute event but for lifeline work, lifelong skin exposures. In addition, recently the American Food and Drug Administration (FDA) has suggested that maybe we have inadequate information on the chronic toxicity related to percutaneous penetration of sunscreens in man. Hence, even the cosmetic chemical ingredient domain may require a neo-evaluation of their long-term exposure and what can be done in daily skin decontamination.

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Preface

The editors wish to thank Ms. Gina Kahn for her indispensable support and assistance throughout the book production. The editors welcome your corrections and suggestions, which will be for the next edition. San Francisco, CA, USA  Hanjiang Zhu Howard I. Maibach

Contents

1 Isolated Human and Animal Stratum Corneum As a Partial Model for the 15 Steps of Percutaneous Absorption: Emphasizing Decontamination, Part I��������������������������������������������������    1 Xiaoying Hui and Howard I. Maibach 2 Isolated Human and Animal Stratum Corneum as a Partial Model for the 15 Steps of Percutaneous Absorption: Emphasizing Decontamination Part II��������������������������������������������������   25 Xiaoying Hui and Howard I. Maibach 3 Recent Knowledge: Human/Animal Skin Decontamination����������������   45 Christina Phuong and Howard I. Maibach 4 Decontamination of Chemically Contaminated Remains��������������������   53 Jill A. Harvilchuck, Dan Noort, Glenn Lawson, Kelly Kyburz, Miranda Verschraagen, and Alison Director-Myska 5 Effectiveness of Chemical, Biological, Radiological, and Nuclear (CBRN) Skin Decontaminants: Toward Tests Standardization����������   77 Denis Josse 6 Effects of Soap-Water Wash on Human Epidermal Penetration��������   87 Hanjiang Zhu, Eui-Chang Jung, Christina Phuong, Xiaoying Hui, and Howard I. Maibach 7 Fuller’s Earth: Old and Faithful Skin Decontaminant Against Toxic Agents��������������������������������������������������������������������������������  101 Shlomit Dachir, Eliezer Fishbine, Yakov Meshulam, Hillel Buch, Nahum Allon, and Tamar Kadar 8 Comparison of Four Different Fuller’s Earth Formulations in Skin Decontamination ������������������������������������������������������������������������  121 Annick Roul, Cong-Anh-Khanh Le, Marie-Paule Gustin, Emmanuel Clavaud, Bernard Verrier, Fabrice Pirot, and Françoise Falson vii

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9 The Mass Decontamination Paradigm: Response Relating to Gas Phase Exposures and Skin Decontamination����������������������������  141 Christina Baxter, Sharyn Gaskin, Michael Logan, and Dino Pisaniello 10 Binding Affinity and Decontamination of Dermal Decontamination Gel (DDGel) to Model Chemical Warfare Agent (CWA) Simulants��������������������������������������������������������������������������  163 Yachao Cao, Akram Elmahdy, Hanjiang Zhu, Xiaoying Hui, and Howard I. Maibach 11 Dermostyx (IB1): High Efficacy and Safe Topical Skin Protectant Against Percutaneous Toxic Agents ������������������������������������  183 Shlomit Dachir, Izhak Barness, Eliezer Fishbine, Jacob Meshulam, Rita Sahar, Arik Eisenkraft, Adina Amir, and Tamar Kadar 12 Understanding the Impact of Responder Management Strategies on Public Experiences and Behaviour During Mass Casualty Decontamination��������������������������������������������������������������������������������������  199 Holly Carter, John Drury, and Richard Amlôt  Appendix: Skin, Hair, and Nail – Abbreviated Decontamination Bibliography ����������������������������������������������������������������������������������������������������  211 Index������������������������������������������������������������������������������������������������������������������  275

Contributors

Nahum Allon, PhD  Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, Israel Adina  Amir, PhD  Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, Israel Richard Amlôt, BA (hons), MSc, PhD  Emergency Response Department Science and Technology, Public Health England, Salisbury, UK Izhak Barness, PhD  Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, Israel Christina Baxter, PhD  Department of Defense, Combating Terrorism Technical Support Office, Virginia, CA, USA Hillel Buch, BSc Agr.  Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, Israel Yachao  Cao, PhD  Department of Dermatology, University of California San Francisco, San Francisco, CA, USA Holly  Carter, BSc(hons), PhD  Emergency Response Department Science and Technology, Public Health England, Salisbury, UK Emmanuel Clavaud  Service départemental d’incendie et de secours de la Savoie, Saint Alban-Leysse, France Shlomit Dachir, PhD  Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, Israel Alison Director-Myska, PhD  Defense Threat Reduction Agency, Ft. Belvoir, VA, USA John Drury, BA(hons), MSc, PhD  School of Psychology, University of Sussex, Brighton, UK

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Contributors

Arik Eisenkraft, MD  Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, Israel Akram Elmahdy, MD  Department of Dermatology, University of California San Francisco, San Francisco, CA, USA Françoise  Falson, PhD, PharmD  Université de lyon 1, UMR 5305-CNRS/ UCBL1; LBTI Lyon and Direction générale de la Sécurité civile et de la gestion des crises Ministère de l’interieur, Paris, France Laboratoire de galénique industrielle ISPB UCBL1 Lyon, Lyon, France Eliezer Fishbine, BSc  Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, Israel Sharyn  Gaskin, BEH, BSc(Hons), PhD  Department of Occupational & Environmental Health, School of Public Health, University of Adelaide, Adelaide, SA, Australia Marie-Paule  Gustin  Université Lyon 1, CNRS UMR 5308,- Inserm U1111 / UCBL1, ENS Lyon, Lyon, France Jill A. Harvilchuck, Ph.D., D.A.B .T.  Battelle Memorial Institute, Columbus, OH, USA Xiaoying  Hui, MD  Department of Dermatology, University of California San Francisco, San Francisco, CA, USA Denis  Josse, PhD, PharmD  Colonel in the French Fire and Rescue Services, Alpes-Maritimes, Villeneuve-Loubet, France Eui-Chang Jung, PhD  Department of Dermatology, University of California San Francisco, San Francisco, CA, USA Department of Dermatology, Gyeongsang National University Changwon Hospital, Changwon, South Korea Tamar Kadar, DSc  Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, Israel Kelly Kyburz, PhD  Office of the Assistant Secretary of the Army for Manpower and Reserve Affairs, Pentagon, Washington, DC, USA Glenn Lawson, PhD  Defense Threat Reduction Agency, Ft. Belvoir, VA, USA Cong-Anh-Khanh Le, PhD, PharmD  Université de lyon 1, UMR 5305-CNRS/ UCBL1; LBTI Lyon and Direction générale de la Sécurité civile et de la gestion des crises Ministère de l’interieur, Paris, France Laboratoire de galénique industrielle ISPB UCBL1 Lyon, Lyon, France Michael  Logan, PhD  Research and Scientific Branch, Queensland Fire and Emergency Services, Brisbane, QLD, Australia

Contributors

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Howard I. Maibach, MD  Department of Dermatology, University of California San Francisco, San Francisco, CA, USA Jacob  Meshulam, MSc  Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, Israel Yakov  Meshulam, MSc  Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, Israel Dan Noort, PhD  TNO Defence, Security and Safety, Rijswijk, The Netherlands Reyna N. Parker  Bowdoin College, Brunswick, ME, USA Christina Phuong, BS, MD  Department of Dermatology, University of California San Francisco, San Francisco, CA, USA Fabrice Pirot, PhD, PharmD  Université de lyon 1, UMR 5305-CNRS/UCBL1; LBTI Lyon and Direction générale de la Sécurité civile et de la gestion des crises Ministère de l’interieur, Paris, France Laboratoire de galénique industrielle ISPB UCBL1 Lyon, Lyon, France Dino Pisaniello, BSc(Hons), MPH, PhD  Adelaide Exposure Science and Health Laboratory, School of Public Health, University of Adelaide, Adelaide, SA, Australia Annick  Roul, PhD, PharmD  Université de lyon 1, UMR 5305-CNRS/UCBL1; LBTI Lyon and Direction générale de la Sécurité civile et de la gestion des crises Ministère de l’interieur, Paris, France Laboratoire de galénique industrielle ISPB UCBL1 Lyon, Lyon, France Rita  Sahar, BSc  Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, Israel Bernard  Verrier, PhD  Université de lyon 1, UMR 5305-CNRS/UCBL1; LBTI Lyon and Direction générale de la Sécurité civile et de la gestion des crises Ministère de l’interieur, Paris, France Miranda Verschraagen, PhD, PharmD, Toxicologist-ERT  Netherlands Forensic Institute, The Hague, The Netherlands Hanjiang  Zhu, PhD  Department of Dermatology, University of California San Francisco, San Francisco, CA, USA

Chapter 1

Isolated Human and Animal Stratum Corneum As a Partial Model for the 15 Steps of Percutaneous Absorption: Emphasizing Decontamination, Part I Xiaoying Hui and Howard I. Maibach

Introduction: 15 Steps of Percutaneous Absorption The stratum corneum (SC) of humans and animals holds key insights to the development of an efficient protective barrier against contamination and to devising effective decontamination interventions. SC constitutes the main barrier to the absorption of molecules while participating in the homeostasis of the organism particularly by limiting outward movement of water. Current understanding no longer considers the SC of the skin barrier as dead “brick and mortar”, but rather a dynamic, living defense system. For instance, the acid mantle, a fine film with a slightly acidic pH on the surface of the skin, plays an integral role in making the skin less permeable to water and polar compounds and is formed in higher amounts with increased activity of enzyme phospholipase A2 [20, 57]. Additionally, acute perturbation of SC by organic solvents, detergents, or tape stripping resulting in lipid removal initiates a sequence of biological responses including epidermal lipid synthesis acceleration to rapidly restore the skin lipid content and barrier function [4]. Upon skin exposure, many chemical agents are locked into the SC within minutes [6]. For examples, many organic solvents including methyl chloroform, perchloroethylene and trichloroethylene can be found in expired air of humans subsequent hand exposures to contaminated water within as little as 6 min, proving rapid systemic absorption [32–34, 54]. The SC acts as a “reservoir” for topically applied molecules, and even rapid washing with water post-dermal exposure frequently fails to remove most chemicals [10]. Importantly, Rougier et al. [40, 41] discovered that SC sampling in vivo in humans and rats via tape stripping 30 minX. Hui (*) · H. I. Maibach Department of Dermatology, University of California San Francisco, San Francisco, CA, USA e-mail: [email protected]

© Springer Nature Switzerland AG 2020 H. Zhu, H. I. Maibach (eds.), Skin Decontamination, https://doi.org/10.1007/978-3-030-24009-7_1

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utes post exposure accurately predicts and quantifies chemical penetration for up to 4 days with linear-­type correlation. While percutaneous penetration is often considered a simplistic one-step diffusion process, it consists of at least 15 steps [51] related to absorption and excretion kinetics, extraction, vehicle characteristics, wash effects, etc. (Table 1.1). Examination of the chemical partitioning/diffusion of a wide array of compounds with differing physicochemical properties showed minimally differing lag times through the SC.  Therefore, different compounds have approximately the same diffusion coefficients with regard to their percutaneous absorption in vivo. Thus, for a given thickness of SC and a specific anatomical site, the penetration flux value of a substance depends mainly on its SC/vehicle partition coefficient [42, 43]. The abovementioned observations offer us new insights for improving decontamination techniques. The recommended emergency treatment of many chemical sprays and splashes to the skin consist of rinsing or washing with water and/or soap. However, many topically applied chemicals are not easily removed by water washing. Skin decontamination is the primary required intervention for chemical, biological, and radiological exposures and involves immediate removal of the contaminant via the most effective manner. Such removal techniques include physiTable 1.1  15 Steps related to the process of percutaneous absorptiona Number Factors determining percutaneous absorption 1 Release from vehicleb  Varies with solubility in vehicle, concentration, pH, etc. 2 Kinetics of skin penetrationb  Influenced by anatomical site, degree of occlusion, intrinsic skin condition, animal age, concentration of dosing solution, surface area dosed, frequency of dosing, post absorption, etc. 3 Excretion kineticsb 4 Tissue disposition 5 Substantivity to skinb 6 Wash effectsb  Wash resistance  Wash enhancement 7 Rub effectsb  Rub resistance  Rub enhancement 8 Transfer––skin, clothing + inanimate surfaceb 9 Exfoliationb 10 Volatilityb 11 Binding––all layersb 12 Anatomic pathways 13 Lateral spreadb 14 Vascular perfusionb 15 Cutaneous metabolismb a

Modified with permission from Wester and Maibach [51] Metric developed

b

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cal removal of the contaminant, solvating or emulsifying the contaminant in a liquid vehicle, transferring the contaminant to another medium through absorption/adsorption of the chemical, chemical alteration of the contaminant, and the use of friction to dislodge the contaminant. Ideally, a decontaminant effectively and rapidly removes the contaminant of interest, easily removes itself without undesirable residue, does not cause enhancement or wash-in effect, and does not damage the skin. Additionally, it is readily available, affordable, and easily disposed of [7]. In the first part of this review, we explore the many steps involved in percutaneous penetration, the laboratory techniques that provided the background for this knowledge, and the insights advancing our knowledge of chemical exposure risk assessment, exposure prevention and barrier methods, and postexposure decontamination.

Stratum Corneum Stratum Corneum and Barrier Function SC is the outermost layer of the five layers of the epidermis and is largely responsible for barrier function. The biological and chemical activity of SC is both intricate and complex. As SC is vital to maintain healthy skin, a comprehensive understanding of its structure and function is essential [9] (Table 1.2). The structure of SC is synonymous with that of “brick and mortar.” The bricks are corneocytes, protein complexes of tiny keratin threads in an organized matrix, and keratin is capable of holding large amounts of water between the fibers. SC contains approximately 12–16 layers of corneocytes, each with a mean thickness of 1 micrometer that varies with age, anatomical location, and UV radiation exposure [27]. Corneocytes are surrounded by crystalline lamellar lipid regions. Lamellar bodies are formed in the keratinocytes of the stratum spinosum and stratum granulosum layers, and as keratinocytes mature and ascend, enzymes degrade the lamellar body envelopes, releasing free fatty acids and ceramides that fuse to form a continuous lamellar lipid bilayer. This lipid bilayer is analogous to a “mortar” and is essential in maintaining the barrier properties of the skin [28, 36]. Each corneocyte is surrounded by an insoluble protein envelope primarily composed of two proteins, loricrin and involucrin, that have extensive structural links with one another. Cell envelopes are either “rigid” or “fragile” depending on the envelope’s interaction with the lamellar bilayer [28, 36]. Attached to the cell envelope is a layer of ceramide lipids that repel and trap water. This assembly prevents the absorption of water into the lower layers of the epidermis. The corneocytes are held together by corneodesmosomes that function as “rivets” and are the primary structures that must be degraded for desquamation [28, 36]. Natural moisturizing factor (NMF), a collection of water-soluble compounds specific to the SC, represents approximately 20–30% of the dry weight of the cor-

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Table 1.2  Stratum corneum structure and function Name Corneocyte

Extracellular matrix

Natural moisturizing factors pH and calcium gradients Specialized enzymes (lipases, glycosidase, proteases) Melanin granules and “dust”

Location—composition Cornified envelope: outer surface of the corneocyte Keratin filaments; γ-glutamyl isopeptide bonds Cytosol: filaggrin proteolytic product; glycerol Cytosol: cis-urocanic acid (histidase activity) Cytosol: cytokine activation; Proteolytic activation of pro IL-1α/β Lamellar bilayers: ceramides, cholesterol, nonessential fatty acids, proper ratio Corneodesmosomes Intercelluar DSG1/DSC1 homodimers Lamellar bilayers: antimicrobial peptides, FFA, sph Extracellular lacunae: hydrophilic products of corneodesmosomes Lamellar bilayers: cholesterol, FFA, secreted vit. E, redox gradient Lamellar bilayers: barrier lipids Within SC

Function Mechanical barrier (impact and shear resistance) Resiliency of stratum corneum Hydration Electromagnetic radiation barrier Initiation of inflammation Permeability

Cohesion (integrity)/ desquamation Antimicrobial barrier (innate immunity)a Toxic chemical/antigen exclusion Antioxidant Psychosensory interface Water holding capacity of SC

Within SC and all through epidermis Provides differentiation signals and lamellar granule secretion signals Within lamellar granules and all Processing and maturation of through epidermis SC lipids, desquamation Produced by melanocytes of basal layer, melanin “dust” in SC

UV protection of skin

This lipid bilayer is analogous to ‘mortar’ and is essential in maintaining the barrier properties of the skin [28, 36].

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neocyte. NMF components absorb water molecules from the atmosphere to maintain SC hydration, but their water solubility allows them to easily leach from the cells upon water contact. Repeated contact with water can dehydrate the skin; however, the lipid layer surrounding the corneocyte helps to form a seal to inhibit NMF loss [37]. The stratum basale consists of a single layer of columnar epidermal stem cells attached to the basal lamina via hemidesmosomes. The stratum spinosum just above is rich with progressively enlarging lamellar bodies with ongoing keratin synthesis and lipogenesis. The stratum granulosum is next with mature lamellar bodies capable of differentiating into corneocytes. Here, the intracellular organelles undergo

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self-destruction, and the packaged lipid in the lamellar granules (LG) is released to the intercellular space. SC forms the outermost seal with 18–21 cell layers of dead corneocytes and lipids that is 20–40 micrometers thick in humans. Filaggrin, a key protein in the hydration and formation of the SC barrier, acts as a source of hygroscopic amino acids and their derivatives including NMF [28, 36, 37].

Stratum Corneum Hydration Normal skin has a consistent water content of 5–15%, independent of variations in environmental humidity. The superficial SC plays a dual barrier role of minimizing transepidermal water loss (TEWL) and preventing the entrance of external molecules. Hydration fluctuations alter SC permeability, and percutaneous absorption may be enhanced with increasing SC water content. Water is an endogenous skin constituent with minimal irritants or toxic exposure effects that are quickly reversible. Skin hydration can be increased easily with an occlusive vehicle or more elegantly with vehicles containing specific NMFs or polymer patch delivery systems [61]. High SC water content is essential in sustaining its flexibility, and its water holding capacity correlates directly with its protein and lipid domains and water-soluble substances [18]. Table 1.3 shows the water holding capacities and lipid content of normal powdered versus delipidized powdered SC (the protein fraction) as determined by the amount of [3H]-water (μg equivalent) per milligram (mg) powdered SC after equilibration [17]. No statistical differences (p > 0.05) were observed in the capacities of normal powdered SC, delipidized powdered SC, or the combination of delipidized powdered SC plus its lipid content. Powdered SC can absorb up to 49% of its dry weight in water, a value consistent in the literature. Middleton [26] found that the Table 1.3  Lipid content and water holding capacity of powdered human stratum corneuma

Stratum corneum source 1 2 3 4 5 6 Mean SD

Lipid content (% dry wt) 2.38 2.21 2.39 2.69 2.08 2.01 2.29 0.25

Water uptake (μg/mg dry powdered SC) Delipidized SC Normal SC Lipid Protein Total 495.85 26.44 452.40 478.84 452.49 39.26 364.96 404.22 585.62 23.09 498.40 521.49 554.27 40.05 492.31 532.36 490.04 49.86 363.30 413.16 381.61 14.82 324.18 339.00 493.31 32.26 415.92 448.18 72.66 12.97 74.50 75.47

Modified with permission from Hui et al. [18]. The powdered SC absorbs up to 49% by weight of dry untreated, which is consistent with literature reports

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amount of water bound to guinea-pig footpad SC intact, in small pieces, or powdered was 40%, 40%, and 43% of dry corneum weight, respectively. Leveque and Rasseneur [21] demonstrated that human SC absorbs up to 50% of its dry weight in water. Powdered SC not in an intact sheet exhibits lower water retention capacity. Powdering ruptures the corneocyte walls, allowing water to extract the hydrophilic NMFs, a process normally requiring a solvent. The results obtained suggest the protein domain of the powdered SC plays an important role in water absorption. Furthermore, depletion of the powdered SC lipid content did not significantly affect water retention (p > 0.05, [17]). Additionally, if powdered SC is pretreated with water and ethanol or the dosing vehicle contains an ethanol concentration of 40% (v/v) or higher, the water retention capacity of the powdered SC can be reduced significantly (p