Principles and Practice of Skin Toxicology

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.

Contents 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 Summary References 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 Summary References PART II Skin Absorption 4 Skin as a route of entry Simon C. Wilkinson 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 Summary References 5 Physicochemical Factors Affecting Skin Absorption Keith R. Brain and Robert P. Chilcott 5.1 Introduction 5.2 Physicochemical properties 5.3 Exposure considerations Summary References 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 Summary References 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 Summary References 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 Summary References 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 Summary References 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 Summary References 11 In vitro alternatives for irritation and corrosion assessment Penny Jones 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 Summary References 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 Summary References 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 Summary 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 Summary References 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 Summary References 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 Summary References PART V Regulatory 17 Occupational skin exposures: legal aspects Chris Packham 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 Summary References 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 Summary References 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 Summary References 20 Glossary of main terms and abbreviations James C. Wakefield Index