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 ForewordPrefaceAcknowledgementsList of contributorsPART I Introduction1 Cutaneous anatomy and functionRobert P. Chilcott1.1 Introduction and scope1.2 Surface features1.3 Functional histology of the epidermis and associated structures1.4 Species differencesSummaryReferences2 Biochemistry of the skinSimon C. Wilkinson2.1 Introduction and scope2.2 Protein synthesis and organisation during epidermal differentiation2.3 Lipid synthesis and organisation during epidermal differentiation2.4 Lipid classes in the stratum corneum2.5 Stratum corneum turnover2.6 Biotransformations in skinSummaryReferences3 Skin photobiologyMark A. Birch-Machin and Simon C. Wilkinson3.1 Introduction and scope3.2 Photoprotection and melanogenesis3.3 Increased environmental ultraviolet radiation exposure and its link with photoageing and skin cancer3.4 Mitochondrial DNA as a biomarker of sun exposure in human skin3.5 Apoptosis3.6 Sun protectionSummaryReferencesPART II Skin Absorption4 Skin as a route of entrySimon C. Wilkinson4.1 Salient anatomical features of the stratum corneum – the ‘brick and mortar model’4.2 Species and regional variation in skin structure4.3 Species and regional variation in skin permeability4.4 Intra- and inter-individual variation in percutaneous absorption4.5 Effect of age on skin barrier function4.6 Role of skin appendages4.7 The in vitro skin sandwich model4.8 Penetration of particles through appendagesSummaryReferences5 Physicochemical Factors Affecting Skin AbsorptionKeith R. Brain and Robert P. Chilcott5.1 Introduction5.2 Physicochemical properties5.3 Exposure considerationsSummaryReferences  6 Principles of Diffusion and ThermodynamicsW. John Pugh and Robert P. Chilcott6.1 Introduction and scope6.2 Some definitions pertaining to skin absorption kinetics 6.3 Basic concepts of diffusion6.4 Fick’s Laws of diffusion6.5 Thermodynamic activity6.6 Skin absorption of a substance from two different vehicles6.7 Partitioning6.8 Diffusivity6.9 Skin absorption data and risk assessmentsSummaryReferences7 In vivo measurements of skin absorptionJames C. Wakefield and Robert P. Chilcott7.1 Introduction and scope7.2 Why conduct in vivo studies?7.3 Ethics and legislation7.4 Standard methodology: OECD Guideline 4277.5 Alternative in vivo methodsSummaryReferences8 In vitro percutaneous absorption measurementsRuth U. Pendlington8.1 Introduction and scope8.2 Regulatory guidelines8.3 Why assess percutaneous absorption in vitro?8.4 Basic principle of in vitro percutaneous absorption measurements8.5 Choice of diffusion cell8.6 Skin membrane considerations8.7 Integrity measurements8.8 Choice of receptor fluid and sampling considerations8.9 Test material considerations8.10 Application of test preparation to the skin8.11 Examples of results from in vitro skin absorption studies8.12 What is considered to be absorbed?8.13 Micro-autoradiographySummaryReferences   PART III Toxicological Assessment9 Skin immunology and sensitisationDavid A. Basketter9.1 Introduction9.2 Definitions9.3 Skin sensitisation9.4 Identification of skin sensitisers9.5 Risk assessment9.6 Other types of allergic skin reaction9.7 Future prospectsSummaryReferences10 In vitro phototoxicity assaysPenny Jones10.1 Introduction and scope 10.2 In vitro strategies for phototoxicity testing10.3 The UV/visible absorption spectrum as a pre-screen for phototoxicity10.4 In vitro assays for phototoxicity using monolayer cultures10.5 In vitro assays for photoallergenicity10.6 In vitro assays for phototoxicity using human 3-D skin models SummaryReferences11 In vitro alternatives for irritation and corrosion assessmentPenny Jones11.1 Introduction and scope11.2 Acute dermal irritation/corrosion11.3 Validation/regulatory status of in vitro assays for skin corrosion 11.4 In vitro tests for skin corrosion11.5 Validation/regulatory status of in vitro assays for skin irritation11.6 In vitro tests for skin irritationSummaryReferences12 Instruments for measuring skin toxicity Helen Taylor12.1 Introduction and scope12.2 Skin surface pH12.3 Biomechanical properties12.4 Sebum12.5 Skin surface contours12.6 Thickness12.7 Desquamation12.8 Applications and measurement of transepidermal water loss12.9 Guidance for TEWL measurements 12.10 Hydration measurement12.11 Guidance for hydration measurements12.12 Relationship between hydration and dermal toxicity12.13 Colour measurement12.14 Measurement of vascular perfusion12.15 A final word of cautionSummaryReferencesPART IV Clinical Aspects 13 Introduction to dermatologyManjunatha Kalavala and Alex Anstey13.1 Introduction and scope13.2 Clinical assessment of patient with skin disease13.3 Cutaneous manifestations of disease following exposure to chemicals and pharmaceutical formulations13.4 Overview of standard treatmentsSummary14 Clinical aspects of phototoxicityAnthony D. Pearse and Alex Anstey14.1 Introduction and scope 14.2 UV-induced skin reactions14.3 Phototoxicity (photoirritancy) reactions14.4 Photosensitive reactionsSummaryReferences15 Occupational skin diseasesJon Spiro15.1 Introduction and scope15.2 Dermatitis 15.3 Development of occupational dermatitis 15.4 Patterns of occupational dermatitis 15.5 Incidence of occupational dermatitis15.6 Effects of dermatitis on work15.7 The outlook in occupational dermatitis15.8 Identification of occupational dermatitis15.9 Other occupational skin disorders15.10 Investigation of a case of dermatitis at workSummaryReferences16 Prevention of occupational skin diseaseChris Packham16.1 Prevention of occupational skin disease16.2 Defining the problem16.3 Material safety data sheets16.4 Chain of responsibility16.5 Managing dermal exposure16.6 Selection and use of personal protective equipment16.7 Protective or ‘barrier’ creams: do they have a role? 16.8 The role of education and training16.9 ConclusionsSummaryReferencesPART V Regulatory17 Occupational skin exposures: legal aspectsChris Packham17.1 Introduction and scope17.2 Brief overview of current United Kingdom legislation17.3 The employer’s perspective17.4 Hazard identification17.5 Risk assessment17.6 Gloves: a note of cautionSummaryReferences18 Safety assessment of cosmetics: an EU perspectiveJo Larner18.1 Introduction and scope18.2 Overview and scope of Cosmetics Directive 76/768/EC18.3 Overview of the requirements of the EU Cosmetics Directive18.4 Scientific advice18.5 Influence of other legislation18.6 Adverse effects from cosmetics18.7 Toxicity of cosmetic ingredients18.8 The safety assessment18.9 A final considerationSummaryReferencesAppendix 18.1 Additional obligations for cosmetic suppliers19 Regulatory dermatotoxicology and international guidelinesAdam Woolley19.1 Introduction19.2 Regulatory context19.3 Product groups and the human context19.4 Dermal toxicology with the different product groups19.5 Factors in dermal toxicity19.6 Repeat dose dermal toxicology19.7 Classic short-term dermal toxicity studies19.8 Pragmatic considerationsSummaryReferences20 Glossary of main terms and abbreviationsJames C. WakefieldIndex

"This is a very useful book for students or toxicologists who want to familiarize themselves with the specific subdiscipline of ermatoxicology, and with the currently validated methods of the trade. The fact that the book is easy to read with a logical story line makes it suitable for students." (BTS Newsletter, Summer 2009)