Principles and Practice of Skin Toxicology

by Editor: Robert Chilcott (Health Protection Agency, Oxford ); Co-Editor: Shirley Price (University of Surrey)

• ISBN13: 9780470773086
• ISBN10: 0470773081
• Format: eBook
• Copyright: 2008-11-01
• Publisher: Wiley

Summary

Written by authorities in the field, this book provides a "bottom up" approach to studying skin toxicology. Principles and Practice of Skin Toxicology clearly outlines basic concepts, cites historical and modern references and contains a dictionary for easy reference. The inclusion of global legislation and regulatory aspects on the topic makes this a comprehensive review for every practitioner, clinical researcher in industry and academia, and MSc and PhD student of toxicology. Different sections cover skin structure and function, principles and measurement of skin absorption, clinical aspects of dermal toxicity and in vitro alternatives. A section on regulatory and legislative aspects includes case studies from the UK that fulfill European Union and US FDA requirements. A glossary provides definitions of technical terms, and the chapters contain an introduction, learning boxes and summary section for ease of use. Includes a chapter on drug delivery through the skin. Addresses risk assessment: a key area for the interpretation of skin absorption data that is rarely covered.

Table of Contents

Contents

Foreword

Preface

Acknowledgements

List of contributors

Introduction

Cutaneous anatomy and function

Introduction and scope

Surface features

Functional histology of the epidermis and associated structures

Species differences

Summary

References

Biochemistry of the skin

Introduction and scope

Protein synthesis and organisation during epidermal differentiation

Lipid synthesis and organisation during epidermal differentiation

Lipid classes in the stratum corneum

Stratum corneum turnover

Biotransformations in skin

Summary

References

Skin photobiology

Introduction and scope

Photoprotection and melanogenesis

Increased environmental ultraviolet radiation exposure and its link with photoageing and skin cancer

Mitochondrial DNA as a biomarker of sun exposure in human skin

Apoptosis

Sun protection

Summary

References

Skin Absorption

Skin as a route of entry

Salient anatomical features of the stratum corneum û the æbrick and mortar modelÆ

Species and regional variation in skin structure

Species and regional variation in skin permeability

Intra- and inter-individual variation in percutaneous absorption

Effect of age on skin barrier function

Role of skin appendages

The in vitro skin sandwich model

Penetration of particles through appendages

Summary

References

Physicochemical Factors Affecting Skin Absorption

Introduction

Physicochemical properties

Exposure considerations

Summary

References

Principles of Diffusion and Thermodynamics

Introduction and scope

Some definitions pertaining to skin absorption kinetics

Basic concepts of diffusion

FickÆs Laws of diffusion

Thermodynamic activity

Skin absorption of a substance from two different vehicles

Partitioning

Diffusivity

Skin absorption data and risk assessments

Summary

References

In vivo measurements of skin absorption

Introduction and scope

Why conduct in vivo studies?

Ethics and legislation

Standard methodology: OECD Guideline 427

Alternative in vivo methods

Summary

References

In vitro percutaneous absorption measurements

Introduction and scope

Regulatory guidelines

Why assess percutaneous absorption in vitro?

Basic principle of in vitro percutaneous absorption measurements

Choice of diffusion cell

Skin membrane considerations

Integrity measurements

Choice of receptor fluid and sampling considerations

Test material considerations

Application of test preparation to the skin

Examples of results from in vitro skin absorption studies

What is considered to be absorbed?

Micro-autoradiography

Summary

References

Toxicological Assessment

Skin immunology and sensitisation

Introduction

Definitions

Skin sensitisation

Identification of skin sensitisers

Risk assessment

Other types of allergic skin reaction

Future prospects

Summary

References

In vitro phototoxicity assays

Introduction and scope

In vitro strategies for phototoxicity testing

The UV/visible absorption spectrum as a pre-screen for phototoxicity

In vitro assays for phototoxicity using monolayer cultures

In vitro assays for photoallergenicity

In vitro assays for phototoxicity using human 3-D skin models

Summary

References

In vitro alternatives for irritation and corrosion assessment

Introduction and scope

Acute dermal irritation/corrosion

Validation/regulatory status of in vitro assays for skin corrosion

In vitro tests for skin corrosion

Validation/regulatory status of in vitro assays for skin irritation

In vitro tests for skin irritation

Summary

References

Instruments for measuring skin toxicity

Introduction and scope

Skin surface pH

Biomechanical properties

Sebum

Skin surface contours

Thickness

Desquamation

Applications and measurement of transepidermal water loss

Guidance for TEWL measurements

Hydration measurement

Guidance for hydration measurements

Relationship between hydration and dermal toxicity

Colour measurement

Measurement of vascular perfusion

A final word of caution

Summary

References

Clinical Aspects

Introduction to dermatology

Introduction and scope

Clinical assessment of patient with skin disease

Cutaneous manifestations of disease following exposure to chemicals and pharmaceutical formulations

Overview of standard treatments

Summary

Clinical aspects of phototoxicity

Introduction and scope

UV-induced skin reactions

Phototoxicity (photoirritancy) reactions

Photosensitive reactions

Summary

References

Occupational skin diseases

Introduction and scope

Dermatitis

Development of occupational dermatitis

Patterns of occupational dermatitis

Incidence of occupational dermatitis

Effects of dermatitis on work

The outlook in occupational dermatitis

Identification of occupational dermatitis

Other occupational skin disorders

Investigation of a case of dermatitis at work

Summary

References

Prevention of occupational skin disease

Prevention of occupational skin disease

Defining the problem

Material safety data sheets

Chain of responsibility

Managing dermal exposure

Selection and use of personal protective equipment

Protective or æbarrierÆ creams: do they have a role?

The role of education and training

Conclusions

Summary

References

Regulatory

Occupational skin exposures: legal aspects

Introduction and scope

Brief overview of current United Kingdom legislation

The employerÆs perspective

Hazard identification

Risk assessment

Gloves: a note of caution

Summary

References

Safety assessment of cosmetics: an EU perspective

Introduction and scope

Overview and scope of Cosmetics Directive 76/768/EC

Overview of the requirements of the EU Cosmetics Directive

Scientific advice

Influence of other legislation

Adverse effects from cosmetics

Toxicity of cosmetic ingredients

The safety assessment

A final consideration

Summary

References

Appendix 18.1 Additional obligations for cosmetic suppliers

Regulatory dermatotoxicology and international guidelines

Introduction

Regulatory context

Product groups and the human context

Dermal toxicology with the different product groups

Factors in dermal toxicity

Repeat dose dermal toxicology

Classic short-term dermal toxicity studies

Pragmatic considerations

Summary

References

Glossary of main terms and abbreviations

Index

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