Table of contents for Toxicologic biomarkers / edited by Anthony P. DeCaprio.


Bibliographic record and links to related information available from the Library of Congress catalog
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Counter
Challeng s in the Statistical Analysis of Biomarker Data ... 17
Stephen W. Looney and Joseph L. Hagan
Introduction . ... 17
The Importance of Distributional Assumptions .  .  21
Examining the Association Between Predictor
and  outcome .. .   24
Challenges in the Analysis of Cross-Classified
Categorical Data .... 27
Challenges in Comparing Mean Levels of Biomarkers
Acros; Groups .... 29
Challen es in Using Correlation Coefficients to Analyze
Biom rker Data .   .  31
Challenges in the Statistical Comparison
of Biomarkers . . .. 33
Concluding Remarks . ... 35
References . . . . 35
Biomarkers of Toxicant Exposure .................. 39
Ken Sexton
Introduction . . .. 39
Basics of Exposure Estimation . . . . 40
Biologic Markers (Biomarkers) of Human Exposure . . . . 42
Uses of Exposure Biomarkers . . . . 53
Conclusions . . .. 58
References . . .. 58
Biomarkers in Environmental Epidemiology  ........... 63
Christopher P. Wild
Introduction . . .. 63
Disease Mechanisms . . .. 64
The Promises of Molecular Cancer Epidemiology---Exposure,
Susceptibility, and Disease . . .. 65
Exposure Assessment . . .. 66
What to Measure . . . . 67
Where to Measure . . . . 69
When to Measure . . . .70
Exposure Biomarkers and Appropriate Study Design  . . .  71
Tests and Questions . . .. 73
Genetic Susceptibility ..  74
Biological Plausibility . . . . 76
Biomarker-Based Classification of Disease .... 77
Whither Molecular Epidemiology? .... .78
References . . . . 79
Use of Biomarkers in Health Risk Assessment ......... 85
Annette Santamaria, Laura Ferriby, Mark Harris, and
Dennis Paustenbach
Introduction . . . 85
Biomarkers and the Risk-Assessment Process .... 87
Limitations of Biomarkers . . .. 98
Conclusions . .    104
References . . .. 105
Bioma-kers of Toxicant Susceptibility .............. 111
Sofia  avanello
Introduction . .   111
Genetic Polymorphism . . .  Ill
Influence of Metabolic and DNA Repair Geno(Pheno)-
Types on Biological Indicators of
Ge otoxic Risk . . .. 130
Influence of Metabolic Geno(Pheno)-Types on Adverse
Drug Side Effects ...   133
References . . .. 138
Identification and Use of Biomarkers in Preclinical
Toxicologic Safety Assessment ................... 143
Donna M. Dambach and Jean-Charles Gautier
Introduction . . . . 143
Target Identification and Validation: Identification
of Potential Pharmacology-Related
Toxicity Biomarkers . . .. 144
Discovery Lead Optimization: Biomarker
Assessment of Pharmacology-Related
and Chemical-Related Toxicity . . .. 146
Preclinical Development: Application and
Refinement of Biomarkers .... 153
Conclusions: Use of Biomarker Data for Hazard and
Safety Risk Assessment . . . . 158
References .... 160
Use of Biomarkers in Clinical Toxicology and
Clinical Trials: A Critical Assessment of QTc Interval
Prolongation as a Biomarker  .................... 165
Daniel Bloomfield and John A. Wagner
Introduction .... 165
Conceptual Framework for the Use and
Development of Biomarkers .... 166
QT/QTc Interval as a Toxicologic Biomarker .... 168
Biological Issues with QTc as a Biomarker . . . . 170
Regulatory Guidance on the Use of QTc Interval
Prolongation as a Biomarker . . . . 179
Conclusions . . .. 183
References . . .. 184
Regulatory Guidance and Validation of
Toxicologic Biomarkers  ........................    187
Federico M. Goodsaid and Felix W. Frueh
Introduction . . .. 187
The Critical Path and Guidance Documents . . .. 189
Reviewer Training and Standardization in
Pharmacogenomics and Toxicogenomics . . . . 192
Validation of Genomic Biomarkers of Toxicity .... 194
Selection of Genomic Biomarkers of Toxicity
for Validation . . .. 196
Similarities and Differences in Biomarker Validation
Processes Between Regulatory Agencies . . .. 196
References .... 199
Use of Biomarkers in Occupational Safety and Health . . . 201
Edward V. Sargent
Introduction . . .. 201
Biomarkers of Exposure . . .. 202
Biomarkers of Biological Effect . . .. 203
Biomarkers of Susceptibility . . .. 204
Practical Issues in the Application of Biomarkers in
Occupational Health Programs . . .. 205
Specific Examples of Biomarker Application in
Occupational Health . . . . 208
Summary . . . . 215
References . . . . 215
Toxicogenomic and Toxicoproteomic Approaches
for Biomarkers  ..............................      221
Joshua W. Hamilton
Introduction . . .  221
Genomics and Proteomics . . . . 225
Development of Genomics Tools in Toxicology . . . . 227
Statistical and Bioinformatics-Based Analyses of
Toxicogenomics Results .. 237
Development of Toxicoproteomics as a
Biomarkers Tool . . .. 249
Summary . . .. 253
References . . . . 253
Biomarkers of Chemical Warfare Agents ............    259
William J. Smith and Harry Salem
Introductin . . . . 259
CWA: Definitions and Classification . . . . 260
Use of Biomarker Determinations in
CWA Research ....     262
Biomarkers of Specific CWA Exposure .... 263
Summary    . . . 269
References . . . . 269
Application of Biomarkers in Toxic Tort and
Forensic Litigation  .. . . . . . . . . . . . . . . . . . . . . . . 273
Gary E. Marchant
Introductin . . . . 273
Potential Applications of Biomarkers in Litigation . . . .274
Potential (bstacles and Complications . . . . 282
Conclusion . . . . 287
References . . . . 287



Library of Congress subject headings for this publication: Biochemical markers, Toxicology, Biological Markers, Drug Evaluation methods, Environmental Exposure, Hazardous Substances toxicity, Occupational Exposure