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