Dermatotoxicology Methods: The Laboratory Worker's Ready Reference (target Organ Pathology Series) [paperback] [1998] 1 Ed. Francis N. Marzulli, Howard I. Maibach

This work presents and evaluates methods employed to identify the potential of certain types of chemicals to adversely affect the skin. A variety of test methods are included such as tests for skin penetration, metabolism, irritation, the skin immune system, photo effects, skin cancer, and topical effects of retinoids and depigmenting chemicals. Tests for chemicals that affect the reproductive and nervous system are also included. Both animal and human tests that have been standardised and tests that are under development and employ animal alternatives are addressed in this book. Besides different testing methods, a rationale for accepting non-animal models and a review of some regulatory agency discussions about animal alternative tests are included. The book contains black-and-white illustrations. Cover 1 Half Title 2 Title Page 4 Copyright Page 5 Table of Contents 6 Contributors 14 Preface 18 Preface to Dermatotoxicology, Fifth Edition 20 CHAPTER 1 Structure-Activity Relationships in Percutaneous Absorption 24 Introduction 24 Traditional Assessment of Skin Penetration 25 Structure-Activity Approach to Percutaneous Absorption 25 Limitations of QSAR 27 Conclusions 27 References 27 CHAPTER 2 Methods for in Vitro Percutaneous Absorption 30 Introduction 30 In Vitro Methodology 30 In Vivo and In Vitro Correlations 35 Barrier Properties of Skin Constructs 35 References 36 CHAPTER 3 Percutaneous Absorption in Humans 38 Introduction 38 Integrated Dermatopharmacokinetics in Man (Hydroquinone) 40 Discussion 50 References 50 CHAPTER 4 Percutaneous Absorption of Hazardous Substances from Soil and Water 52 Introduction 52 Discussion 61 Acknowledgment 62 References 62 CHAPTER 5 Isolated Perfused Porcine Skin Flap 64 Introduction 64 Overview of Method 64 Assessment of Viability 67 Percutaneous Absorption 68 Dermatopharmacokinetics 69 Other Applications 70 Discussion 71 References 71 CHAPTER 6 Methods in Physiologically Based Pharmacokinetic Modeling 74 Introduction 74 Why use PB-PK Models? 74 When can PB-PK Models be used? 75 How do you use PB-PK Models? 76 What are the Components of a PB-PK Model? 77 How do you develop PB-PK Models? 85 Conclusion 89 Nomenclature 89 References 89 CHAPTER 7 Methods for In Vitro Skin Metabolism Studies 92 Introduction 92 In Vitro Methodology 93 Skin Metabolism During Percutaneous Absorption 94 References 96 CHAPTER 8 Developing a Toxicology Evaluation Plan for Transdermal Delivery Systems 98 Assessment of Previous Experience 98 Transdermal Product Assessment: Issues in Test Selection 99 Summary 106 References 106 CHAPTER 9 Animal, Human, and In Vitro Test Methods for Predicting Skin Irritation 112 Animal Tests for Predicting Skin Irritation 113 Human Tests for Predicting Skin Irritation 118 In Vitro Skin Irritation Assays: Relevance to Human Skin 124 Summary 131 References 131 CHAPTER 10 Structure-Activity Relationships in Contact Sensitization: Classification and Ranking of Allergens 138 Introduction 138 Creating a QSAR Model 139 The Classification Model 139 The Rank Model 141 Conclusion 141 References 142 CHAPTER 11 Test Methods for Allergic Contact Dermatitis in Animals 144 Introduction 144 General Principles 146 Split Adjuvant Technique 148 Freund’s Complete Adjuvant Test 150 The Modified Draize Test 151 The Buehler Test 153 The Open Epicutaneous Test 154 Modified Guinea Pig Maximization Test 154 The Cumulative Contact Enhancement Test 155 The Epicutaneous Maximization Test 156 Single Injection Adjuvant Test 157 The Tierexperimenteller Nachweis (TINA) Test 158 The Footpad Test 159 The Guinea Pig Allergy Test Adapted to Cosmetic Ingredients 160 The Ear/Flank Test (Stevens Test) 161 Conclusions 162 References 162 CHAPTER 12 The Local Lymph Node Assay 168 Introduction 168 Methods 168 Application and Validation: Current Status 171 Conclusions 173 References 173 CHAPTER 13 Test Methods for Allergic Contact Dermatitis in Humans 176 Predictive Tests 177 Diagnostic Tests 177 Excited Skin Syndrome 181 References 181 CHAPTER 14 Contact Urticaria Syndrome 184 Introduction 184 Symptoms 184 Etiology and Mechanisms 184 Diagnostic Tests 192 References 194 CHAPTER 15 Diagnostic Tests in Dermatotoxicology 200 Introduction 200 Drug Eruptions 200 Contact Dermatitis 204 Contact Urticaria Syndrome: Immediate Contact Reactions 206 References 207 CHAPTER 16 Use of Cytokines in Dermatotoxicology 210 Introduction 210 Methods of Cytokine Analysis 212 Skin Model Systems for Examining Cytokines 216 Summary 223 References 223 CHAPTER 17 Characterization of Epidermal Langerhans Cells 230 Introduction 230 Epidermal Langerhans Cells and Cutaneous Immune Responses 230 Cytokine Products of Epidermal Langerhans Cells 231 Practical Application of Langerhans Cell Characterization 232 Methods 233 References 236 CHAPTER 18 Measuring and Quantifying Ultraviolet Radiation Exposures 240 Introduction 240 Optical Radiation Sources 244 UV Measurement 245 General Biophysical and Photobiological Factors 248 References 250 CHAPTER 19 Animal Models for Phototoxicity Testing 252 Introduction 252 Overview of Animal Models for Phototoxicity Testing 252 Specific Animal Models 257 Comparison of Species in Phototoxicity Testing 261 In Vivo Versus In Vitro Phototoxicity Testing 262 Summary 264 References 264 CHAPTER 20 Photoirritation (Phototoxicity) Testing in Humans 268 Definition 268 Screening 268 Spectral Measurements 268 Precautions 268 Exploratory Studies 269 Conclusions 271 References 271 CHAPTER 21 The Evaluation of Photoallergic Contact Sensitizers in Humans 274 Introduction 274 Photomaximization Test 275 Evaluation of Some Photocontact Sensitizers 275 Photopatch Testing 279 Action Spectrum 279 Conclusions 280 References 280 CHAPTER 22 Chemical Leukoderma (Depigmentation) 282 Introduction 282 Chemical Structure 282 Repigmentation 284 Animal Models 284 In Vitro Studies 289 Human Studies 289 Mechanism of Action 289 References 290 CHAPTER 23 New Models to Assess In Vitro Action of Retinoids 294 Introduction 294 Methods 295 Results 297 Conclusion 300 Acknowledgments 301 References 301 CHAPTER 24 Sample Protocols for Carcinogenesis and Photocarcinogenesis 304 Introduction 304 A Sample Protocol for Carcinogenesis Testing 305 Photocarcinogenesis Safety Testing 314 A Sample Protocol for Photocarcinogenesis Testing 316 References 324 CHAPTER 25 Testing for Reproductive Hazards from Dermal Exposure 326 Introduction 326 Testing and Methodology 326 Considerations and General Recommendations 327 Test Procedures for Developmental Toxicity Studies 327 Test Procedure for Reproduction Studies 330 References 334 CHAPTER 26 Quantitative Sensory Testing 336 Introduction 336 References 340 CHAPTER 27 Alternative Methods in Dermatotoxicology 342 Introduction 342 Materials and Methods 343 Results 347 Discussion and Summary 352 References 358 CHAPTER 28 Skin Equivalents to Measure Phototoxicity 360 Introduction 360 Cell Culture Conditions 361 Photoprotective Assessment of Sunscreens Using 3-D Cultures of Keratinocytes 362 Assessment of the Phototoxic Potential of Chemicals Using 3-D Cultures of Keratinocytes 363 Treatment of the Episkin Samples 364 Assessment of Lipoperoxidation Induced by UVA Using a 3-D Culture of Keratinocytes 367 General Conclusion 371 References 371 CHAPTER 29 A Practical Process for Assessing the Validity of Alternative Methods for Toxicity Testing 374 Introduction 374 The Definition of Validation 374 Reliability 375 Relevance 375 Initiating the Validation Process 375 Establishing the Relevance of the Alternative Method 375 Confirming the Establishment of Common Protocols and Standard Operating Procedures (SOP) 377 Confirming that Measures of Reliability to Be Tested in the Validation Study Have Been Adequately Defined 377 Defining the Reproducibility of the Test Results from an Assay 377 Defining the Reproducibility of Predictions from an Alternative Method Through the Use of Prediction Models 378 Completing the Initial Assessment of Alternative Method Readiness for the Validation Process 378 Confirming Alternative Method Reliability in a Validation Study 378 Assessing Alternative Method Relevance 390 Conclusion 396 Acknowledgments 397 References 397 CHAPTER 30 Update on Agency Initiatives in Alternative Methods 400 Introduction 400 Ocular Symposium 401 Dermal Irritation/Corrosivity 403 References 404 Index 406 Content: Cover Half Title Title Page Copyright Page Table of Contents Contributors Preface Preface to Dermatotoxicology, Fifth Edition CHAPTER 1 Structure-Activity Relationships in Percutaneous Absorption Introduction Traditional Assessment of Skin Penetration Structure-Activity Approach to Percutaneous Absorption Limitations of QSAR Conclusions References CHAPTER 2 Methods for in Vitro Percutaneous Absorption Introduction In Vitro Methodology In Vivo and In Vitro Correlations Barrier Properties of Skin Constructs References CHAPTER 3 Percutaneous Absorption in Humans IntroductionIntegrated Dermatopharmacokinetics in Man (Hydroquinone) Discussion References CHAPTER 4 Percutaneous Absorption of Hazardous Substances from Soil and Water Introduction Discussion Acknowledgment References CHAPTER 5 Isolated Perfused Porcine Skin Flap Introduction Overview of Method Assessment of Viability Percutaneous Absorption Dermatopharmacokinetics Other Applications Discussion References CHAPTER 6 Methods in Physiologically Based Pharmacokinetic Modeling Introduction Why use PB-PK Models? When can PB-PK Models be used? How do you use PB-PK Models? What are the Components of a PB-PK Model?How do you develop PB-PK Models? Conclusion Nomenclature References CHAPTER 7 Methods for In Vitro Skin Metabolism Studies Introduction In Vitro Methodology Skin Metabolism During Percutaneous Absorption References CHAPTER 8 Developing a Toxicology Evaluation Plan for Transdermal Delivery Systems Assessment of Previous Experience Transdermal Product Assessment: Issues in Test Selection Summary References CHAPTER 9 Animal, Human, and In Vitro Test Methods for Predicting Skin Irritation Animal Tests for Predicting Skin Irritation Human Tests for Predicting Skin IrritationIn Vitro Skin Irritation Assays: Relevance to Human Skin Summary References CHAPTER 10 Structure-Activity Relationships in Contact Sensitization: Classification and Ranking of Allergens Introduction Creating a QSAR Model The Classification Model The Rank Model Conclusion References CHAPTER 11 Test Methods for Allergic Contact Dermatitis in Animals Introduction General Principles Split Adjuvant Technique Freund's Complete Adjuvant Test The Modified Draize Test The Buehler Test The Open Epicutaneous Test Modified Guinea Pig Maximization TestThe Cumulative Contact Enhancement Test The Epicutaneous Maximization Test Single Injection Adjuvant Test The Tierexperimenteller Nachweis (TINA) Test The Footpad Test The Guinea Pig Allergy Test Adapted to Cosmetic Ingredients The Ear/Flank Test (Stevens Test) Conclusions References CHAPTER 12 The Local Lymph Node Assay Introduction Methods Application and Validation: Current Status Conclusions References CHAPTER 13 Test Methods for Allergic Contact Dermatitis in Humans Predictive Tests Diagnostic Tests Excited Skin Syndrome References Formerly, healthy and intact skin was considered to be an impermeable barrier designed to shield the living organism from all types of environmental injury and offered protection from all things chemical.