Allergic Contact Dermatitis assesses the potential effects of xenobiotic metabolism and protein reactivity on toxicity. It reviews current knowledge of percutaneous absorption and skin metabolism and includes discussion of the xenobiotics themselves. It answers questions such as: How does sensitisation relate to protein reactivity and levels of metabolism? How we can identify potential hazards in food, cosmetics and pharmaceuticals etc?
In a world where people are becoming increasingly aware of their allergies, this up to date one-stop reference will prove an invaluable addition to the shelves of any researcher in academia, government, regulatory bodies, public health officials and, of course, the food, cosmetics and pharmaceuticals industries will find the book to be of particular relevance.
Author(s): Camilla K. Smith, Camilla K. Smith
Publisher: CRC Press
Year: 2021
Language: English
Pages: 336
City: Boca Raton
Cover
Half Title
Acknowledgement
Title Page
Copyright Page
Table of Contents
List of Figures
List of Schemes
List of Tables
Acknowledgements
Preface
Chapter 1: Allergic Contact Dermatitis to Small Molecule Xenobiotics
1.1 Definition of Allergic Contact Dermatitis
1.2 Sensitisation and Elicitation Phases of ACD
1.2.1 Sensitisation
1.2.2 Elicitation
1.2.3 The Roles of Keratinocytes in the Immune System
1.3 ACD vs Irritant Contact Dermatitis (ICD)
1.4 Diagnosis and Treatment of ACD
1.4.1 Patch Testing
1.4.2 Treatment of ACD
1.5 Epidemiology of ACD
1.5.1 Incidence and Prevalence Statistics for ACD in the General Population
1.5.2 Individuals at Risk From Chemical Allergens in the Home
1.5.3 Individuals at Risk From Chemical Allergens at Work
1.5.4 Frequency of Sensitisation to Common Allergens
1.6 Factors Contributing to Xenobiotic-Derived ACD
Chapter 2: Skin Absorption of Chemical Allergens
2.1 Significance of Skin Absorption in Allergic Contact Dermatitis
2.2 Skin Barrier Function and The Stratum Corneum
2.3 Pathways of Allergen Absorption
2.4 Mechanisms of Allergen Absorption
2.5 The Skin Reservoir
2.6 Factors Influencing Allergen Absorption
2.6.1 Chemical Factors
2.6.2 Physiological Factors
2.7 Summary
Chapter 3: Enzymes and Mechanisms of Xenobiotic Metabolism
3.1 Activation and Detoxication of Xenobiotics
3.2 Factors Influencing the Metabolism of a Compound
3.3 The Three Phases of Metabolism
3.3.1 Phase I Metabolism
3.3.2 Phase II Metabolism
3.3.3 Phase III Metabolism
3.4 Protein Processing Enzymes
3.5 Summary
Chapter 4: Enzymes and Pathways of Xenobiotic Metabolism in Skin
4.1 Skin as a Metabolising Organ
4.2 Enzymology of the Skin
4.2.1 Overview of Enzymes Identified in Skin
4.2.2 Relative Activities of Hepatic and Cutaneous Enzymes
4.2.3 Inducibility of Cutaneous Enzyme Expression
4.3 Inter-Species and Inter-Individual Variability of Enzyme Expression
4.4 Summary
Chapter 5: Xenobiotics as Skin Sensitisers: Metabolic Activation and Detoxication, and Protein-Binding Mechanisms
5.1 Binding of Xenobiotics to Biological Macromolecules
5.1.1 Binding of Haptens to Protein/Peptide
5.2 Concepts of Prohapten Activation and Hapten Detoxication
5.2.1 Prohapten Activation and Hapten Detoxication by Skin Metabolising Enzymes
5.2.2 Non-Enzymatic Xenobiotic Oxidoreduction
5.3 Hypothetical Biotransformations of Small Molecules in Skin
5.3.1 Alcohols
5.3.2 Aldehydes
5.3.3 Ketones
5.3.4 Carboxylic Acids
5.3.5 Esters
5.3.6 Peroxides
5.3.7 Salicylates
5.3.8 Gallates
5.3.9 Coumarins and Anhydrides
5.3.10 Amines and Nitrobenzenes
5.3.11 N-rings
5.3.12 Dyes
5.3.13 Substituted 5 Atom Rings
5.3.14 Saturated 6 Atom Rings
5.3.15 Sulphonates and Sulphanilic Acids
5.3.16 Halogenated Compounds
5.3.17 Corticosteroids
5.3.18 Quaternary Ammonium Salts
5.4 Predicting Hapten Formation in Skin and Evaluating Sensitisation Potency de Novo
5.4.1 Predicting and Evaluating Chemical Properties
5.4.2 Predicting Metabolism
5.4.3 Evaluating Sensitisation Potency
5.5 Summary
Chapter 6: Protein-Hapten Binding and Immunorecognition Events During the Sensitisation and Elicitation Stages of ACD
6.1 Peptide-Hapten Antigen Formation and Immune Recognition Mechanisms
6.1.1 Possible Mechanisms of Peptide-Hapten Antigen Formation
6.1.2 Major Histocompatibility Complexes
6.1.3 The Roles of T-Cell Receptors
6.2 Potential Differential Immunorecognition Mechanisms in the Sensitisation and Elicitation Stages of ACD
6.2.1 Immune Mechanisms of Sensitisation
6.2.2 Immune Mechanisms of Elicitation
6.3 Summary
Chapter 7: Conclusion: The Future of in Vitro Models and De Novo Prediction of Xenobiotic Skin Sensitisation, and An MHC-Peptide-Hapten Hypothesis
7.1 Absorption, Chemical Reactivity, Metabolism and Immunocompetency All Contribute to ACD
7.2 Incorporation of Immunorecognition Mechanisms Into an MHC-Peptide-Hapten Hypothesis
7.3 Developing in Vitro Alternatives for the Hazard Identification of Skin Sensitisers
Appendix I: In Vivo Sensitisation Data and Physico-Chemical Properties of Xenobiotics (Discussed in Chapter 5)
Appendix II: Useful Web Addresses
Appendix III: Models and Approaches for Studying Cutaneous Metabolism
References
Index
