Dermatotoxicology Methods: The Laboratory Worker's Ready Reference

Front Cover
Francis N. Marzulli
CRC Press, 2019 M05 7 - 390 pages
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.
 

Contents

StructureActivity Relationships in Percutaneous Absorption
1
Traditional Assessment of Skin Penetration
2
Limitations of QSAR
4
Methods for In Vitro Percutaneous Absorption
7
In Vivo and In Vitro Correlations
12
References
13
Percutaneous Absorption in Humans
15
Integrated Dematopharmacokinetics in Man Hydroquinone
17
Skin Model Systems for Examining Cytokines
193
Summary
200
Characterization of Epidermal Langerhans Cells
207
Cytokine Products of Epidermal Langerhans Cells
208
Practical Applications of Langerhans Cell Characterization
209
Methods
210
References
213
Measuring and Quantifying Ultraviolet Radiation Exposures
217

Discussion
27
Percutaneous Absorption of Hazardous Substances from Soil and Water
29
Discussion
38
Acknowledgment
39
Isolated Perfused Porcine Skin Flap
41
Assessment of Viability
44
Percutaneous Absorption
45
Dematopharmacokinetics
46
Other Applications
47
Discussion
48
Methods in Physiologically Based Pharmacokinetic Modeling
51
When can PBPK Models be used?
52
How do you use PBPK Models?
53
What are the components of a PBPK Model?
54
How do you develop PBPK Models?
62
Conclusion
66
Methods for In Vitro Skin Metabolism Studies
69
In Vitro Methodology
70
Skin Metabolism during Percutaneous Asorption
71
References
73
Developing a Toxicology Evaluation Plan for Transdermal Delivery Systems
75
Issues in Test Selections
76
Summary
83
Animal Human and in Vitro Test Methods for Prediction Skin Irritation
89
Animal Test for Predicting Skin Irritation
90
Human Test for Predicting Skin Irritation
95
Relevance to Human Skin
101
Summary
108
StructureActivity Relationships in Contact Sensitization Classification and Ranking of Allergens
115
Creating a QSAR Model
116
The Rank Model
118
References
119
Test Methods for Allergic Contact Dermatitis in Animals
121
General Principles
123
Split Adjuvant Technique
125
Freunds Complete Adjuvant Test
127
The Modified Draize Test
128
The Buehler Test
130
The Open Epicutaneous Test
131
The Cumulative Contact Enhancement Test
132
The Epicutaneous Maximization Test
133
Single Injection Adjuvant Test
134
The Tierexperimenteller Nachweis TINA Test
135
The Footpad Test
136
The Guinea Pig Allergy Test Adapted to Cosmetic Ingredients
137
The EarFlank Test Stevens Test
138
Conclusions
139
The Local Lymph Node Assay
145
Current Status
148
Conclusions
150
Test Methods for Allergic Contact Dermatitis in Humans
153
Predictive Test
154
Excited Skin Syndrome
158
Contact Urticaria Syndrome
161
Diagnostic Test
169
References
171
Diagnostic Test in Dermatotoxicology
177
Contact Dermatitis
181
Immediate Contact Reations
183
References
184
Use fo Cytokines in Dermatotoxicology
187
Methods of Cytokine Analysis
189
Optical Radiation Sources
221
UV Measurement
222
General Biophysical and Photobiological Factors
225
References
227
Animal Models for Phototoxicity Testing
229
Specific Animal Models
234
Comparison of Species in Phototoxicity Testing
238
In Vivo Versus In Vitro Phototoxicity Testing
239
Summary
241
Photoirritation Phototoxicity Testing in Humans
245
Exploratory Studies
246
Conclusions
248
The Evaluation of Photoallergic Contact Sensitizers in Humans
251
Photomaximization Test
252
Photopatch Testing
256
Conclusions
257
Chemical Leukoderma Depigmentation
259
Repigmentation
261
In Vitro Studies
266
References
267
New Models to Assess In Vitro Action of Retinoids
271
Methods
272
Results
274
Conclusion
277
Acknowledgments
278
Sample Protocols for Carcinogenesis and Photocarcinogenesis
281
A Sample Protocol for Carcinogenesis Testing
282
Photocarcinogenesis Safety Testing
291
A Sample Protocol for Photocarcinogenesis Testing
293
References
301
Testing for Reproductive Hazards from Dermal Exposure
303
Considerations and General Recommendations
304
Test Procedures for Reproductive Studies
307
References
311
Quantitative Sensory Testing
313
References
317
Alternative Methods in Dermatotoxicology
319
Materials and Methods
320
Results
324
Discussion and Summary
329
References
335
Skin Equivalents to Measure Phototoxicity
337
Cell Culture Conditions
338
Photoprotective Assessment of Sunscreens Using 3D Cultures of Keratinocytes
339
Assessment of the Phototoxic Potential of Chemicals Using 3D Cultures of Keratinocytes
340
Treatment of the Episkin Samples
341
Assessment of Lipoperoxidation Induces by UVA A 3D Cultures of Keratinocytes
344
General Conclusion
348
A Practical Process for Assessing the Validity of Alternative Methods for Toxicity Testing
351
Reliability
352
Confirming the Establishment of Common Protocols and Standard Operating Procedure SOP
354
Defining the Reproductivity of Predictions from an Alternative Method Through the Use of Prediction Models
355
Assessing Alternative Method Relevance
367
Conclusion
373
Acknowledgments
374
Update on Agency Initiatives in Alternative Methods
377
Ocular Symposium
378
Dermal IrritationCorrosivity
380
References
381
Index
383
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Francis N. Marzulli

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