Alternative toxicological methods

Dedication......Page 6
Preface......Page 8
The Editors......Page 10
Contributors......Page 12
Contents......Page 20
Index......Page 606
PART I Progress in the Validation and Regulatory Acceptance of Alternatives......Page 26
1 Historical Developments in the Humane Care and Use of Research Animals: The First 4000 Years......Page 28
2 A History of Interagency Approaches to Alternatives and Establishment of the Interagency Regulatory Alternatives Group......Page 34
3 The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM): Recent Progress in the Evaluation of......Page 40
4 Validation and Regulatory Acceptance of Alternative Test Methods: Current Situation in the European Union......Page 56
5 Integrated In Vitro Approaches for Assessing Systemic Toxicity......Page 68
6 Summary of the OECD’s New Guidance Document on the Recognition, Assessment, and Use of Clinical Signs as Humane Endpoints for......Page 76
7 Pain and Distress Management in Animal Research and Testing: The Humane Society of the United States Pain and Distress Initiat......Page 86
PART II Development of Predictive Methods Based on Mechanisms of Eye Irritation at the Ocular Surface: Meeting Industry and Regu......Page 100
8 Meeting Industry and Regulatory Needs for Alternative Test Methods to the Draize Rabbit Eye Irritation Test......Page 102
9 The Ocular Surface: Barrier Function and Mechanisms of Injury and Repair......Page 114
10 Evaluation and Re.nement of the Bovine Cornea Opacity and Permeability Assay......Page 134
11 Corneal Organ Culture for Ocular Toxicity Test of Commercial Hair Care Products......Page 142
12 Human Corneal Equivalents for In Vitro Testing......Page 150
13 The EpiOcular Prediction Model: A Reproducible In Vitro Means of Assessing Ocular Irritancy......Page 156
14 Three-Dimensional Construct of the Human Corneal Epithelium for In Vitro Toxicology......Page 172
15 The Human Corneal Epithelial HCE-T TEP Assay for Eye Irritation: Scienti.c Relevance and Summary of Prevalidation Study Resul......Page 186
PART III Dermal Testing Alternatives......Page 212
16 Alternative Methods for Dermal Toxicity Testing......Page 214
17 Allergic Contact Hypersensitivity: Mechanisms and Methods*......Page 218
18 Validating In Vitro Dermal Absorption Studies: An Introductory Case Study......Page 232
19 A Molecular Diagnostic Approach to Irritant or Allergic Patch Testing Using the DermPatch......Page 246
20 In Vitro Skin Equivalent Models
for Toxicity Testing......Page 254
PART IV A Case Study in the Use of Alternatives to Determine the Mechanism of Sulfur Mustard Action......Page 273
21 Cellular Resistance of Tetrahymena to Sulfur Mustard......Page 276
22 Studies of Cellular Biochemical Changes Induced in Human Cells by Sulfur Mustard......Page 284
23 Human Keratinocyte In.ammatory Transcript Gene Activity Following Sulfur Mustard*......Page 294
24 Evaluation of Cytotoxicity Assays of Human Epidermal Keratinocytes Exposed In Vitro to Sulfur Mustard......Page 306
25 Comparison of Spectrophotometric and Fluorometric Assays of Proteolysis in Cultured Human Cells Exposed to Sulfur Mustard......Page 312
26 Effects of Low Dose Sulfur Mustard on Growth and DNA Damage in Human Cells in Culture......Page 320
27 Imaging Sulfur Mustard Lesions in Basal Cells and Human Epidermal Tissues by Confocal and Multiphoton Laser Scanning Microsco......Page 328
28 Suppression of Sulfur Mustard-Increased IL-8 in Human Keratinocyte Cell Cultures by Serine Protease Inhibitors: Implications......Page 338
29 Development of Medical Countermeasures to Sulfur Mustard Vesication......Page 348
PART V Neurotoxicology: Molecular Biomarkers, Transgenics, and Imaging Technologies......Page 354
30 Molecular Neurotoxicology of 6-Hydroxydopamine and Methamphetamine: Lessons Derived from Transgenic Models......Page 358
31 A Microassay Method Using a Neuroblastoma Cell Line to Examine Neurotoxicity of Organophosphate Mixtures......Page 366
32 Development of Integrin Expression as a Molecular Biomarker for Early, Sensitive Detection of Neurotoxicity......Page 372
33 Two-Photon Fluorescence Microscopy: A Review of Recent Advances in Deep-Tissue Imaging......Page 386
PART VI Role of Transgenics and Toxicogenomics in the Development of Alternative Toxicity Tests......Page 399
34 The Application of Genomics and Proteomics to Toxicological Sciences......Page 402
35 Use of Transgenic Animals in Regulatory Carcinogenicity Evaluations*......Page 416
36 Changes in Gene Expression after Exposure to Organophosphorus (OP) Agents......Page 438
PART VII Recent Innovations in Alternatives......Page 454
37 Archival Data in Toxicology: Minimizing Need for Animal Experiments......Page 456
38 Information Management at the Library of Congress: An Overview with Special Reference to Biomedicine*......Page 474
39 World Wide Web Biomedical, Chemical, and Toxicological Information Resources from the National Library of Medicine......Page 498
40 In Silico Approaches for Physiologically
Based Pharmacokinetic Modeling......Page 504
41 In Silico Application of Quantum Chemical
Methods for Relating Toxicity
to Chemical Reactivity......Page 558
42 In Silico Cardiac Toxicity: Increasing
the Discovery of Therapeutics through
High-Performance Computing......Page 568
43 Submillimeter-Wave Frequency Studies of the Vibrational Modes of Deoxyribonucleic Acid: A Metric for Mutagenicity?......Page 584
44 Trophoblast Toxicity Assay (TTA): A Gestational Toxicity Test Using Human Placental Trophoblasts......Page 592