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E-raamat: Applications of Toxicogenomic Technologies to Predictive Toxicology and Risk Assessment

  • Formaat: 300 pages
  • Ilmumisaeg: 19-Nov-2007
  • Kirjastus: National Academies Press
  • Keel: eng
  • ISBN-13: 9780309178891
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  • Formaat: 300 pages
  • Ilmumisaeg: 19-Nov-2007
  • Kirjastus: National Academies Press
  • Keel: eng
  • ISBN-13: 9780309178891
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The new field of toxicogenomics presents a potentially powerful set of tools to better understand the health effects of exposures to toxicants in the environment. At the request of the National Institute of Environmental Health Sciences, the National Research Council assembled a committee to identify the benefits of toxicogenomics, the challenges to achieving them, and potential approaches to overcoming such challenges. The report concludes that realizing the potential of toxicogenomics to improve public health decisions will require a concerted effort to generate data, make use of existing data, and study data in new waysan effort requiring funding, interagency coordination, and data management strategies.

Table of Contents



Front Matter Summary 1 Introduction 2 Toxicogenomic Technologies 3 Experimental Design and Data Analysis 4 Application to Exposure Assessment 5 Application to Hazard Screening 6 Application to Analyzing Variation in Human Susceptibility 7 Application to the Study of Mechanisms of Action 8 Other Potential Applications of Toxicogenomic Technologies to Risk Assessment 9 Validation 10 Sample and Data Collection and Analysis 11 Ethical, Legal, and Social Issues 12 Conclusions and Recommendations References Appendix A: Biographic Information on the Committee on Applications of Toxicogenomic Technologies to Predictive Toxicology Appendix B: Minimum Information About a Microarray Experiment for Toxicogenomics Appendix C: Overview of Risk Assessment
SUMMARY 1
1 INTRODUCTION
11
Background,
11
Committee Charge and Response,
17
2 TOXICOGENOMIC TECHNOLOGIES
22
Genomic Technologies,
24
Transcriptomic Technologies,
27
Proteomic Technologies,
34
Metabolomic Technologies,
41
Technology Advancement and Economy of Scale,
43
3 EXPERIMENTAL DESIGN AND DATA ANALYSIS
45
Experimental Design,
45
Types of Experiments,
47
Toxicogenomics and Biomarker Discovery,
54
Conclusions,
56
Recommendations,
57
4 APPLICATION TO EXPOSURE ASSESSMENT
59
Conventional Biomarkers of Exposure and Response,
60
State of the Art: Toxicogenomic Approaches to the Development of Exposure Biomarkers,
61
Evaluation of Exposure in Risk Assessment,
67
Scientific Challenges,
68
Conclusions,
71
Recommendations,
72
5 APPLICATION TO HAZARD SCREENING
73
Description and Properties of Current Hazard Screening Methods,
73
In Vitro Versus In Vivo Testing,
76
Development of Predicitve Algorithms for Screening Purposes,
77
State of the Art,
77
Potential Applications,
83
Challenges and Limitations,
86
Conclusions,
89
Recommendations,
90
6 APPLICATION TO ANALYZING VARIATION IN HUMAN SUSCEPTIBILITY
92
State of the Art in Assessment of Individual Variation,
93
Risk Assessment,
100
Challenges,
102
Conclusions,
103
Recommendations,
105
7 APPLICATION TO THE STUDY OF MECHANISMS OF ACTION
107
State of the Art in Transcriptomics Analyses,
108
Conclusions,
118
Recommendations,
119
8 OTHER POTENTIAL APPLICATIONS OF TOXICOGENOMIC TECHNOLOGIES TO RISK ASSESSMENT
121
Potential Applications to Risk Assessment,
121
Implications for Better Use and Potential Reduction in the Use of Experimental Animals,
131
Implications of Toxicogenomics for Risk Assessment Infrastructure Needs,
132
Conclusions,
133
Recommendations,
133
9 VALIDATION
135
Levels of Validation,
135
Conclusions,
149
Recommendations,
151
10 SAMPLE AND DATA COLLECTION AND ANALYSIS 152
Leveraging Samples and Information in Population-Based Studies and Clinical Trials for Toxicogenomic Studies,
152
Existing Toxicogenomic Data Repositories: Standardization, Availability and Transparency,
161
Conclusions,
166
Recommendations,
169
11 ETHICAL, LEGAL, AND SOCIAL ISSUES 172
Research Issues,
172
Ethical and Social Issues,
178
Regulatory Implications,
186
Litigation,
191
Communication and Education,
195
Conclusions and Recommendations,
197
12 CONCLUSIONS AND RECOMMENDATIONS 201
A New Human Toxicogenomics Initiative,
202
Data Analysis Tools,
203
Exposure Assessment,
204
Hazard Screening,
205
Variability in Susceptibility,
206
Mechanistic Information,
207
Dose-response Relationships,
208
Cross-species Extrapolation,
209
Developmental Exposures,
209
Mixtures,
209
Validation,
210
Ethical, Legal, and Social Issues,
210
Education and Training in Toxicogenomics,
212
REFERENCES 213
APPENDIXES
A BIOGRAPHIC INFORMATION ON THE COMMITTEE ON APPLICATIONS OF TOXICOGENOMIC TECHNOLOGIES TO PREDICTIVE TOXICOLOGY
255
B MINIMUM INFORMATION ABOUT A MICROARRAY EXPERIMENT FOR TOXICOGENOMICS
262
C OVERVIEW OF RISK ASSESSMENT
270


Committee on Applications of Toxicogenomic Technologies to Predictive Toxicology and Risk Assessment, National Research Council