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Robert Peter Chilcott, Senior Toxicologist, Chemical Hazards and Poisons Division HQ, Health Protection Agency, Chilton, UK.
Shirley Price, Senior Lecturer in Toxicopathology, School of Biomedical and Molecular Sciences, University of Surrey, Guildford, UK.
Foreword
Preface
Acknowledgements
List of contributors
PART I Introduction
1 Cutaneous anatomy and function
Robert P. Chilcott
1.1 Introduction and scope
1.2 Surface features
1.3 Functional histology of the epidermis and associated structures
1.4 Species differences
Summary
References
2 Biochemistry of the skin
Simon C. Wilkinson
2.1 Introduction and scope
2.2 Protein synthesis and organisation during epidermal differentiation
2.3 Lipid synthesis and organisation during epidermal differentiation
2.4 Lipid classes in the stratum corneum
2.5 Stratum corneum turnover
2.6 Biotransformations in skin
3 Skin photobiology
Mark A. Birch-Machin and Simon C. Wilkinson
3.1 Introduction and scope
3.2 Photoprotection and melanogenesis
3.3 Increased environmental ultraviolet radiation exposure and its link with photoageing and skin cancer
3.4 Mitochondrial DNA as a biomarker of sun exposure in human skin
3.5 Apoptosis
3.6 Sun protection
PART II Skin Absorption
4 Skin as a route of entry
4.1 Salient anatomical features of the stratum corneum - the 'brick and mortar model'
4.2 Species and regional variation in skin structure
4.3 Species and regional variation in skin permeability
4.4 Intra- and inter-individual variation in percutaneous absorption
4.5 Effect of age on skin barrier function
4.6 Role of skin appendages
4.7 The in vitro skin sandwich model
4.8 Penetration of particles through appendages
5 Physicochemical Factors Affecting Skin Absorption
Keith R. Brain and Robert P. Chilcott
5.1 Introduction
5.2 Physicochemical properties
5.3 Exposure considerations
6 Principles of Diffusion and Thermodynamics
W. John Pugh and Robert P. Chilcott
6.1 Introduction and scope
6.2 Some definitions pertaining to skin absorption kinetics
6.3 Basic concepts of diffusion
6.4 Fick's Laws of diffusion
6.5 Thermodynamic activity
6.6 Skin absorption of a substance from two different vehicles
6.7 Partitioning
6.8 Diffusivity
6.9 Skin absorption data and risk assessments
7 In vivo measurements of skin absorption
James C. Wakefield and Robert P. Chilcott
7.1 Introduction and scope
7.2 Why conduct in vivo studies?
7.3 Ethics and legislation
7.4 Standard methodology: OECD Guideline 427
7.5 Alternative in vivo methods
8 In vitro percutaneous absorption measurements
Ruth U. Pendlington
8.1 Introduction and scope
8.2 Regulatory guidelines
8.3 Why assess percutaneous absorption in vitro?
8.4 Basic principle of in vitro percutaneous absorption measurements
8.5 Choice of diffusion cell
8.6 Skin membrane considerations
8.7 Integrity measurements
8.8 Choice of receptor fluid and sampling considerations
8.9 Test material considerations
8.10 Application of test preparation to the skin
8.11 Examples of results from in vitro skin absorption studies
8.12 What is considered to be absorbed?
8.13 Micro-autoradiography
PART III Toxicological Assessment
9 Skin immunology and sensitisation
David A. Basketter
9.1 Introduction
9.2 Definitions
9.3 Skin sensitisation
9.4 Identification of skin sensitisers
9.5 Risk assessment
9.6 Other types of allergic skin reaction
9.7 Future prospects
10 In vitro phototoxicity assays
Penny Jones
10.1 Introduction and scope
10.2 In vitro strategies for phototoxicity testing
10.3 The UV/visible absorption spectrum as a pre-screen for phototoxicity
10.4 In vitro assays for phototoxicity using monolayer cultures
10.5 In vitro assays for photoallergenicity
10.6 In vitro assays for phototoxicity using human 3-D skin models
11 In vitro alternatives for irritation and corrosion assessment
11.1 Introduction and scope
11.2 Acute dermal irritation/corrosion
11.3 Validation/regulatory status of in vitro assays for skin corrosion
11.4 In vitro tests for skin corrosion
11.5 Validation/regulatory status of in vitro assays for skin irritation
11.6 In vitro tests for skin irritation
12 Instruments for measuring skin toxicity
Helen Taylor
12.1 Introduction and scope
12.2 Skin surface pH
12.3 Biomechanical properties
12.4 Sebum
12.5 Skin surface contours
12.6 Thickness
12.7 Desquamation
12.8 Applications and measurement of transepidermal water loss
12.9 Guidance for TEWL measurements
12.10 Hydration measurement
12.11 Guidance for hydration measurements
12.12 Relationship between hydration and dermal toxicity
12.13 Colour measurement
12.14 Measurement of vascular perfusion
12.15 A final word of caution
PART IV Clinical Aspects
13 Introduction to dermatology
Manjunatha Kalavala and Alex Anstey
13.1 Introduction and scope
13.2 Clinical assessment of patient with skin disease
13.3 Cutaneous manifestations of disease following exposure to chemicals and pharmaceutical formulations
13.4 Overview of standard treatments
14 Clinical aspects of phototoxicity
Anthony D. Pearse and Alex Anstey
14.1 Introduction and scope
14.2 UV-induced skin reactions
14.3 Phototoxicity (photoirritancy) reactions
14.4 Photosensitive reactions
15 Occupational skin diseases
Jon Spiro
15.1 Introduction and scope
15.2 Dermatitis
15.3 Development of occupational dermatitis
15.4 Patterns of occupational dermatitis
15.5 Incidence of occupational dermatitis
15.6 Effects of dermatitis on work
15.7 The outlook in occupational dermatitis
15.8 Identification of occupational dermatitis
15.9 Other occupational skin disorders
15.10 Investigation of a case of dermatitis at work
16 Prevention of occupational skin disease
Chris Packham
16.1 Prevention of occupational skin disease
16.2 Defining the problem
16.3 Material safety data sheets
16.4 Chain of responsibility
16.5 Managing dermal exposure
16.6 Selection and use of personal protective equipment
16.7 Protective or 'barrier' creams: do they have a role?
16.8 The role of education and training
16.9 Conclusions
PART V Regulatory
17 Occupational skin exposures: legal aspects
17.1 Introduction and scope
17.2 Brief overview of current United Kingdom legislation
17.3 The employer's perspective
17.4 Hazard identification
17.5 Risk assessment
17.6 Gloves: a note of caution
18 Safety assessment of cosmetics: an EU perspective
Jo Larner
18.1 Introduction and scope
18.2 Overview and scope of Cosmetics Directive 76/768/EC
18.3 Overview of the requirements of the EU Cosmetics Directive
18.4 Scientific advice
18.5 Influence of other legislation
18.6 Adverse effects from cosmetics
18.7 Toxicity of cosmetic ingredients
18.8 The safety assessment
18.9 A final consideration
Appendix 18.1 Additional obligations for cosmetic suppliers
19 Regulatory dermatotoxicology and international guidelines
Adam Woolley
19.1 Introduction
19.2 Regulatory context
19.3 Product groups and the human context
19.4 Dermal toxicology with the different product groups
19.5 Factors in dermal toxicity
19.6 Repeat dose dermal toxicology
19.7 Classic short-term dermal toxicity studies
19.8 Pragmatic considerations
20 Glossary of main terms and abbreviations
James C. Wakefield
Index
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