Principles and Practice of Skin Toxicology

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Principles and Practice of Skin Toxicology, 2008, 0470511729.pdf......Page 2
Principles and Practice of Skin Toxicology......Page 4
Contents......Page 10
Foreword......Page 18
Preface......Page 20
Acknowledgements......Page 22
List of contributors......Page 24
PART I Introduction......Page 26
1.2 Surface features......Page 28
1.3 Functional histology of the epidermis and associated structures......Page 33
1.4 Species differences......Page 38
References......Page 40
2.1 Introduction and scope......Page 42
2.2 Protein synthesis and organisation during epidermal differentiation......Page 43
2.3 Lipid synthesis and organisation during epidermal differentiation......Page 44
2.4 Lipid classes in the stratum corneum......Page 45
2.5 Stratum corneum turnover......Page 48
2.6 Biotransformations in skin......Page 49
References......Page 67
3.2 Photoprotection and melanogenesis......Page 76
3.3 Increased environmental ultraviolet radiation exposure and its link with photoageing and skin cancer......Page 80
3.4 Mitochondrial DNA as a biomarker of sun exposure in human skin......Page 85
3.5 Apoptosis......Page 86
3.6 Sun protection......Page 88
References......Page 90
PART II Skin Absorption......Page 94
4.1 Salient anatomical features of the stratum corneum – the ‘brick and mortar model’......Page 96
4.2 Species and regional variation in skin structure......Page 97
4.3 Species and regional variation in skin permeability......Page 99
4.4 Intra- and inter-individual variation in percutaneous absorption......Page 100
4.5 Effect of age on skin barrier function......Page 101
4.6 Role of skin appendages......Page 102
4.7 The in vitro skin sandwich model......Page 103
4.8 Penetration of particles through appendages......Page 104
References......Page 105
5.1 Introduction......Page 108
5.2 Physicochemical properties......Page 109
5.3 Exposure considerations......Page 114
References......Page 116
6.1 Introduction and scope......Page 118
6.2 Some definitions pertaining to skin absorption kinetics......Page 119
6.4 Fick’s Laws of diffusion......Page 122
6.5 Thermodynamic activity......Page 123
6.6 Skin absorption of a substance from two different vehicles......Page 124
6.7 Partitioning......Page 126
6.8 Diffusivity......Page 127
6.9 Skin absorption data and risk assessments......Page 130
References......Page 131
7.1 Introduction and scope......Page 134
7.3 Ethics and legislation......Page 135
7.4 Standard methodology: OECD Guideline 427......Page 140
7.5 Alternative in vivo methods......Page 144
References......Page 151
8.2 Regulatory guidelines......Page 154
8.3 Why assess percutaneous absorption in vitro?......Page 155
8.5 Choice of diffusion cell......Page 156
8.6 Skin membrane considerations......Page 161
8.7 Integrity measurements......Page 162
8.8 Choice of receptor fluid and sampling considerations......Page 163
8.9 Test material considerations......Page 164
8.10 Application of test preparation to the skin......Page 165
8.11 Examples of results from in vitro skin absorption studies......Page 167
8.12 What is considered to be absorbed?......Page 171
References......Page 172
PART III Toxicological Assessment......Page 174
9.2 Definitions......Page 176
9.3 Skin sensitisation......Page 177
9.4 Identification of skin sensitisers......Page 180
9.5 Risk assessment......Page 185
9.6 Other types of allergic skin reaction......Page 188
Summary......Page 189
References......Page 190
10.2 In vitro strategies for phototoxicity testing......Page 194
10.3 The UV/visible absorption spectrum as a pre-screen for phototoxicity......Page 196
10.4 In vitro assays for phototoxicity using monolayer cultures......Page 197
10.5 In vitro assays for photoallergenicity......Page 199
10.6 In vitro assays for phototoxicity using human 3-D skin models......Page 202
References......Page 206
11.2 Acute dermal irritation/corrosion......Page 210
11.3 Validation/regulatory status of in vitro assays for skin corrosion......Page 211
11.4 In vitro tests for skin corrosion......Page 213
11.5 Validation/regulatory status of in vitro assays for skin irritation......Page 219
11.6 In vitro tests for skin irritation......Page 220
Summary......Page 222
References......Page 223
12.1 Introduction and scope......Page 226
12.2 Skin surface pH......Page 227
12.3 Biomechanical properties......Page 229
12.7 Desquamation......Page 230
12.8 Applications and measurement of transepidermal water loss......Page 231
12.9 Guidance for TEWL measurements......Page 233
12.10 Hydration measurement......Page 234
12.11 Guidance for hydration measurements......Page 237
12.13 Colour measurement......Page 238
12.14 Measurement of vascular perfusion......Page 240
12.15 A final word of caution......Page 241
References......Page 242
PART IV Clinical Aspects......Page 246
13.1 Introduction and scope......Page 248
13.2 Clinical assessment of patient with skin disease......Page 249
13.3 Cutaneous manifestations of disease following exposure to chemicals and pharmaceutical formulations......Page 259
13.4 Overview of standard treatments......Page 266
Summary......Page 268
14.1 Introduction and scope......Page 270
14.3 Phototoxicity (photoirritancy) reactions......Page 272
14.4 Photosensitive reactions......Page 276
References......Page 281
15.1 Introduction and scope......Page 284
15.2 Dermatitis......Page 285
15.3 Development of occupational dermatitis......Page 288
15.4 Patterns of occupational dermatitis......Page 289
15.6 Effects of dermatitis on work......Page 290
15.8 Identification of occupational dermatitis......Page 291
15.9 Other occupational skin disorders......Page 292
15.10 Investigation of a case of dermatitis at work......Page 295
References......Page 301
16.1 Prevention of occupational skin disease......Page 304
16.2 Defining the problem......Page 305
16.3 Material safety data sheets......Page 307
16.4 Chain of responsibility......Page 308
16.5 Managing dermal exposure......Page 309
16.6 Selection and use of personal protective equipment......Page 314
References......Page 319
PART V Regulatory......Page 322
17.1 Introduction and scope......Page 324
17.2 Brief overview of current United Kingdom legislation......Page 325
17.3 The employer’s perspective......Page 328
17.4 Hazard identification......Page 329
17.5 Risk assessment......Page 331
17.6 Gloves: a note of caution......Page 334
References......Page 335
18.1 Introduction and scope......Page 336
18.2 Overview and scope of Cosmetics Directive 76/768/EC......Page 337
18.3 Overview of the requirements of the EU Cosmetics Directive......Page 340
18.4 Scientific advice......Page 341
18.5 Influence of other legislation......Page 342
18.6 Adverse effects from cosmetics......Page 343
18.7 Toxicity of cosmetic ingredients......Page 345
18.8 The safety assessment......Page 351
18.9 A final consideration......Page 353
References......Page 354
Appendix 18.1 Additional obligations for cosmetic suppliers......Page 355
19.1 Introduction......Page 358
19.2 Regulatory context......Page 359
19.3 Product groups and the human context......Page 360
19.4 Dermal toxicology with the different product groups......Page 361
19.5 Factors in dermal toxicity......Page 363
19.6 Repeat dose dermal toxicology......Page 364
19.7 Classic short-term dermal toxicity studies......Page 366
19.8 Pragmatic considerations......Page 369
References......Page 370
20 Glossary of main terms and abbreviations......Page 372
Index......Page 383
Colour Plates......Page 396