Molecular Biological Markers for Toxicology and Risk Assessment

 
 
Academic Press
  • 1. Auflage
  • |
  • erschienen am 10. Juni 2016
  • |
  • 164 Seiten
 
E-Book | ePUB mit Adobe DRM | Systemvoraussetzungen
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978-0-12-801901-6 (ISBN)
 

Molecular Biological Markers for Toxicology and Risk Assessment provides an introduction to the exciting field of biomarkers and their use in toxicology and risk assessment. In recent years, new classes of molecular biomarkers capable of detecting early manifestations of ongoing chemical-induced cell injury and cell death have been developed as a result of advances in analytical chemistry, molecular biology, and computational modeling. The interplay between these emergent tools of science has resulted in new insights into initial mechanisms of chemical-induced toxicity and carcinogenicity.

Molecular Biological Markers for Toxicology and Risk Assessment guides the reader through a broad range of molecular biological markers, including the 'omic' biomarkers, and provides an examination of the various elements in the evolution of these modern tools. It then explores possible ways in which these markers may be applied to advance the field of chemical risk assessment. Since molecular biomarkers and related technologies are inherently complex, the book concludes with a section on risk communication in order that readers may appreciate both the strengths and limitations of molecular biological marker approaches to risk assessment practice.

  • Introduces the use of molecular biomarkers to detect toxic effects of chemicals as early as possible
  • Provides an accessible overview of this emerging, interdisciplinary field, to best inform decision making in chemical and pharmaceutical safety
  • Includes a section on risk communication of these complex concepts, essential for effective risk assessment
  • Provides new insights into the initial mechanisms of chemical-induced toxicity and carcinogenicity


Dr. Fowler began his scientific career at the National Institute of Environmental Health Sciences prior to becoming Director of the University of Maryland System-wide Program in Toxicology and Professor at the University of Maryland School of Medicine. He then served as Associate Director for Science in the Division of Toxicology and Environmental Medicine at Agency for Toxic Substances and Disease Registry (ATSDR). He is currently a private consultant and Co-owner of Toxicology Risk Assessment Consulting Services (TRACS), LLC. In addition, Dr. Fowler serves as an Adjunct Professor, Emory University Rollins School of Public Health and Presidents Professor of Biomedical Sciences, Center for Alaska Native Health Research (CANHR) at the University of Alaska- Fairbanks. Dr. Fowler, is an internationally recognized expert on the toxicology of metals and has served on a number of State, National and International Committees in his areas of expertise. These include the Maryland Governor's Council on Toxic Substances (Chair), various National Academy of Sciences / National Research Council Committees, including the 1993 landmark NAS/NRC Report on 'Measuring Lead Exposure in Infants Children and Other Sensitive Populations" for which he served as the Committee Chair. He has also served on a number of review committees of the National Institutes of Health, the USEPA Science Advisory Board and the Fulbright Scholarship review committee for Scandinavia (Chair, 2000-2001). In 2016, he became an Inaugural Member of the Fulbright 1946 Society and in 2018 became a member of the Fulbright Association Board of Directors. He has also served as a temporary advisor to the World Health Organization (WHO) and on working groups of the International Agency for Research Against Cancer (IARC) for a number of toxicology and risk assessment issues. He is presently appointed as a member of the Joint FAO/WHO Expert Committee on Food Additives (JECFA) for the period 2016-2020. Dr. Fowler has been honored as a Fellow of the Japanese Society for the Promotion of Science (JSPS), a Fulbright Scholar and Swedish Medical Research Council Visiting Professor at the Karolinska Institute, Stockholm, Sweden and elected as a Fellow of the Academy of Toxicological Sciences. His more recent awards include a CDC/ATSDR, Honor Award for Excellence in Leadership Award 2010, The US Pharmacopea (USP) Toxicology Committee 2010-2015 and the USP Elemental Impurities Panel which received the 2014 U.S. Pharmacopea Award for an Innovative Response to Public Health Challenges (Group Award). He is currently appointed to the USP Nanotechnology Subcommittee 2015-. Dr. Fowler was previously elected to the Council of the Society of Toxicology (2005-2007), the Board of Directors of the Academy of Toxicological Sciences (2006-2009), and more recently, to the Council of the Society for Risk Analysis (2014-2017). He is the Federal Legislative and National Active and Retired Federal Employees Association and (NARFE)-PAC Chair for the Rockville Maryland Chapter of NARFE and is currently Chair of the Federal Legislative Committee for the Maryland NARFE Federation. Dr. Fowler is the Past- President of the Rotary Club of North Bethesda, Maryland (2016-2017) and was selected as Rotarian of the Year in 2015 for his work in developing a taxi-based program to help persons with disabilities gain independence via reliable transportation to work. Dr. Fowler is the author of over 260 research papers and book chapters dealing with molecular mechanisms of metal toxicity, molecular biomarkers for early detection of metal-induced cell injury and application of computational toxicology for risk assessment. He has been the editor, co-editor or author of 10 books or monographs on metal toxicology and mechanisms of chemical - induced cell injury, molecular biomarkers and risk assessment and computational toxicology. Dr. Fowler is currently focused on the global problem of electronic waste (e-waste) in developing countries. He serves on the editorial boards of a number of scientific journals in toxicology and is an Associate Editor of the journal Toxicology and Applied Pharmacology and a past Associate Editor of Environmental Health Perspectives (2007-2016).
  • Englisch
  • San Diego
  • |
  • USA
Elsevier Science
  • 8,53 MB
978-0-12-801901-6 (9780128019016)
0128019018 (0128019018)
weitere Ausgaben werden ermittelt
  • Cover
  • Title Page
  • Copyright Page
  • Contents
  • Preface
  • Chapter 1 - Molecular Biological Markers for Toxicology and Risk Assessment
  • 1 - Introduction
  • 1.1 - Types of Biomarkers (Exposure, Effect Toxicity)
  • 2 - Enzyme Activity-Based Biomarkers
  • 2.1 - Tissue-Specific Isozymes
  • 3 - Currently Measured Biomarker Proteins
  • 3.1 - Glycosylated Hemoglobin
  • 3.2 - Prostate-Specific Antigen
  • 3.3 - Beta 2 Microglobulin
  • 3.4 - Retinol-Binding Protein
  • 3.5 - Alpha-1 Microglobulin
  • 3.6 - Stability Issues With B2M, RBP, and A-1MG
  • 3.7 - Cystatin c
  • 3.8 - Kidney Injury Molecule-1
  • 3.9 - Metallothionein
  • 3.10 - Lead-Binding Proteins
  • 4 - Omic Biomarkers
  • 4.1 - Genomics
  • 4.2 - Proteomics (2-D Gels, HPLC-MS, ICP-MS, Posttranslational Modifications, Epigenetics)
  • 4.3 - Metabolomics/Metabonomics (Porphyrins, Metabolites, Protein Fragments)
  • 5 - Computational Toxicology Approaches
  • 5.1 - Data Mining of Public Databases
  • 5.2 - Metaanalysis Approaches
  • 5.3 - Network and Pathway Analyses and Systems Biology Approaches Using Data From the Peer-Reviewed Published Literature
  • 6 - Application of Molecular Biomarkers for Risk Assessment
  • References
  • Chapter 2 - Historical Development of Biomarkers
  • 1 - Biomarkers of Exposure
  • 1.1 - Introduction
  • 2 - Exposome and Biomarkers of Exposure
  • 3 - Specific Biomonitoring Analytical Methodologies
  • 3.1 - High Performance Liquid Chromatography
  • 3.2 - Gas Chromatography
  • 3.3 - Mass Spectrometry
  • 3.4 - Atomic Absorption Spectroscopy
  • 3.5 - X-Ray Fluorescence (XRF), Electron (EDX), and Proton-Induced X-Ray Emmission Analysis (PIXEA)
  • 4 - Biomonitoring Studies
  • 4.1 - NHANES Studies
  • 4.2 - Other National/International Biomonitoring Programs
  • 5 - Biological Monitoring for Chemical Metabolites and Interconverted Chemical Species
  • 6 - Clinical Biomarkers-Current Usages and Prospects for the Future
  • 6.1 - Altered Metabolite Profiles
  • 6.2 - RIAs for Unique Proteins Resulting From Chemical or Pharmaceutical Exposures
  • 6.3 - Gene Expression Patterns
  • 6.4 - Genomic/Proteomic/Metabolomic Profiling
  • 7 - Biomarker Modifying Factors and Identification of Populations at Risk
  • 7.1 - Genetic Factors
  • 7.2 - Epigenetic Factors
  • 7.3 - Inducible Metabolic/Toxicant Regulation Systems
  • 7.3.1 - Cytochrome P-450 Family of Enzymes and Phase II Enzymes
  • 7.3.2 - Metallothionein Family of Metal-Binding Proteins
  • 7.3.3 - Antioxidant Systems
  • 8 - Technical Advances in Instrumentation
  • 8.1 - Automated and Robotic Analytical Systems
  • 8.2 - Mircrofluidics
  • 8.3 - Computer Management Systems
  • 9 - Basic Scientific Biomarker Validation Approaches
  • 9.1 - Correlations With Histopathology and Electron Microscopy
  • 9.2 - In Vivo/In Vitro Cell Biology Comparison Studies
  • References
  • Chapter 3 - Computational Toxicology
  • 1 - Introduction
  • 2 - Data Mining Approaches-Getting an Overview of the Current Molecular Biomarker Literature
  • 3 - Some Useful and Publically Available Data Resources
  • 3.1 - United States Agency Public Databases
  • 3.1.1 - NIH PubMed Database
  • 3.1.2 - NHANES
  • 3.1.3 - USFDA
  • 3.1.4 - USGS
  • 3.1.5 - ATSDR
  • 3.1.6 - USEPA IRIS
  • 3.1.7 - National Toxicology Program
  • 4 - International Public Health Databases
  • 4.1 - International Agency for Research Against Cancer
  • 4.2 - The Joint FAO/WHO Expert Committee on Food Additives and WHO Chemical Safety Programs
  • 4.3 - Food Safety and Quality Unit (AGND)
  • 4.4 - International Program on Chemical Safety
  • 5 - European Union
  • 5.1 - EFSA
  • 5.2 - European Chemicals Agency (ECHA)
  • 5.3 - Organization for Economic Co-Operation and Development (OECD)
  • 6 - Chemical Risk Assessment Resources in Selected Countries and States
  • 7 - WHO Chemical Risk Assessment Network
  • 8 - Computational Toxicology Approaches to Biomarker Development and Validation
  • 8.1 - US Environmental Protection Agency
  • 8.1.1 - EPA NEXGEN Initiative
  • 8.1.2 - Interagency Tox 21 Toxicology Testing Program
  • 9 - Toxicology Testing Resources in Europe
  • 10 - Computational Tools for Capturing the Biomarker Literature
  • 10.1 - National Library of Medicine Databases (www.nlm.nih.gov)
  • 11 - Computational Approaches for Assisting in Molecular Biomarker Development
  • 11.1 - Bioinformatic Algorithm Programs for Possible Biomarker Identification
  • 11.2 - Computational Approaches for Analysis of Complex Analytical Data Sets
  • 11.3 - PBPK/SAR/QSAR
  • 11.4 - PBPK
  • 11.5 - SAR/QSAR
  • 11.6 - Molecular Docking Approaches
  • 11.7 - Pathway Analysis
  • 11.8 - Systems Biology
  • 11.9 - High Throughput Screening
  • 12 - Applications of Computational Methods for Guiding Biological Marker Research-A Summary
  • References
  • Chapter 4 - Omic Biological Markers
  • 1 - Introduction
  • 1.1 - Genomics
  • 1.1.1 - GWAS Studies
  • 1.1.2 - mRNAs
  • 1.1.3 - SNPs
  • 2 - Statistical/Bayesian Approaches for Delineating Biomarkers
  • 2.1 - Applications of Genomic/Epigenomic Biomarkers for Risk Assessment
  • 2.2 - Genomic Risk Assessment Case Study
  • 2.2.1 - ALAD Polymorphisms and Risk of Lead-Induced Hypertension as an Example
  • 3 - Proteomics
  • 3.1 - Applications of Proteomics for Risk Assessment
  • 3.2 - Proteomic Risk Assessment Case Study
  • 3.2.1 - Differences in Proteomic Expression Patterns and Risk of Toxicity From Exposure to III-V Semiconductor Compounds
  • 3.2.2 - In Vivo Exposure Studies of Hamsters
  • 3.2.3 - In Vitro Exposure Studies in Both Hamster and Human Primary Cultures
  • 4 - Metabolomics/Metabonomics
  • 4.1 - Heme Biosynthetic Pathway
  • 4.2 - Applications of Metabolomics/Metabonomics for Risk Assessment-the Heme Biosynthetic Pathway as an Example
  • 4.3 - Microfluidics/Nanoproteomics
  • 5 - Current Applications of Omic Biomarkers for Risk Assessment Purposes
  • 5.1 - Next Steps Forward for Incorporating Omics Approaches into Risk Assessment Practice
  • References
  • Chapter 5 - Validation of Biological Markers for Epidemiological Studies
  • 1 - Introduction
  • 2 - Molecular Biomarker Validation Through Correlation With Other Biological Endpoints
  • 2.1 - Cellular Level
  • 2.1.1 - Morphological Methods
  • 2.1.1.1 - Histopathology
  • 2.1.1.2 - Ultrastructural Morphometry
  • 2.1.2 - Biochemical Methods
  • 2.1.2.1 - Serum/Urinary Enzyme Activities or Protein Patterns
  • 2.2 - Correlations With Chemical Measurements of Pharmaceutical or Toxic Agents
  • 2.3 - Correlation With Tissue Concentrations and Intracellular Binding Patterns of Chemicals
  • 2.4 - Impacts on Biomarker Responses in Mixture Exposure Conditions
  • 2.5 - Connectivity With Cell Death/Adverse Outcome Pathways
  • 2.6 - Molecular Biomarker Development via In Vitro or Alternative Animal Model Test Systems
  • 3 - Application of Computational Modeling Approaches for Extrapolating From In Vitro or Experimental Animal Model Systems f...
  • 4 - Ease of Application for Risk Assessment Practice
  • 5 - Correlations at the Population Level and Population-Based Risk Assessment Studies via NHANES
  • 5.1 - Data Mining
  • 6 - Applications to Risk Assessment Practice
  • References
  • Chapter 6 - Technical Translational Analysis of Molecular Biomarker Data
  • 1 - Introduction
  • 1.1 - Data Analysis
  • 1.2 - Types of Statistical Analyses
  • 1.3 - Evaluation of Statistical Analyses
  • 2 - Modeling and Interpretation of Data
  • 2.1 - Model Development
  • 2.1.1 - Evaluating the Model
  • 2.1.2 - Testing the Model
  • 3 - Integration of Diverse Data Sets
  • 4 - Validation of Biological Marker Data With Other Outcome Data
  • 4.1 - Other Potentially Useful Types of Correlative Health Outcome Data for Biological Marker Validation
  • 4.1.1 - NHANES Database
  • 4.1.2 - European Union Health Databases
  • 4.1.3 - Korean NHANES
  • 4.1.4 - Clinical Chemistry Analyzer Databases
  • 4.2 - Utilization of Molecular Biomarkers as Translational Bridges Between Epidemiological and Standard Clinical Chemistry ...
  • References
  • Chapter 7 - Quality Assurance/Quality Control (QA/QC) for Biomarker Data Sets
  • 1 - Introduction
  • 2 - General Definitions
  • 2.1 - Quality Assurance
  • 2.2 - Quality Control
  • 3 - Discussion of QA/QC Definition
  • 3.1 - Critical Role of QA/QC in Biomarker Development and Acceptance for Risk Assessment
  • 4 - Sample Handling for Biomarker Development
  • 5 - Intrinsic Variability of Measured Biomarker Endpoints
  • 6 - Equipment Maintenance, Internal Standards, and Chain of Custody for Assurance of Data Quality
  • 7 - Data Analysis and Archival Storage Needs
  • 7.1 - Specific Omic QA/QC Procedures
  • 7.1.1 - Genomics QA/QC
  • 7.1.2 - Proteomics QA/QC
  • 7.1.3 - Metabolomics/Metabonomics QA/QC
  • 8 - Summary and Conclusions
  • References
  • Chapter 8 - Translation of Biomarkers for Human Clinical and Epidemiological Studies
  • 1 - Introduction
  • 2 - Clear Definitions of Biomarker Terminology
  • 2.1 - Biomarkers of Exposure
  • 2.1.1 - Biomonitoring for Chemical/Drug Exposures
  • 2.1.2 - Biology-Based Biomarkers of Chemical/Drug Exposures
  • 2.2 - Biomarkers of Effects
  • 2.2.1 - Biomarkers of Toxicity
  • 2.2.2 - Biomarkers of Cell Injury/Cell Death
  • 2.2.3 - Adverse Outcome Pathways
  • 2.3 - Biomarkers of Cancer and Birth Defects
  • 3 - Biomarkers for Epidemiological Studies
  • 3.1 - Discussion of Strengths and Weaknesses of Biomarkers for Epidemiology Studies
  • 3.1.1 - Longitudinal Studies
  • 3.1.2 - Cluster Studies
  • 3.2 - Birth/Metabolic Defect Studies From In utero Exposures
  • 4 - Biomarkers for Chemical Mixture Risk Assessments
  • 5 - Merging Chemical Exposure Data and Genetic Inheritance Data for Risk Assessments
  • 6 - Summary and Conclusions
  • References
  • Chapter 9 - Risk Communication of Molecular Biomarker Information
  • 1 - Introduction
  • 1.1 - Translation of Biomarker Data Into "Plain English"
  • 1.2 - Biomarker Tutorials for Managers and Societal Decision Makers
  • 2 - Information Mapping Technology
  • 3 - Translation of Molecular Biomarker Data for Societal Decision Making
  • 3.1 - Communicating With the Professional Risk Assessment Community
  • 3.2 - Communicating With Societal Decision Makers
  • 3.3 - Communicating With the Lay Press and Lay Public
  • 3.3.1 - Importance of Informative Graphic Presentations in Communicating via the Media
  • 3.3.2 - Social Media Presentations
  • 4 - Summary and Conclusions
  • References
  • Chapter 10 - Future Research Directions
  • 1 - Further Validation of Biological Markers for Humans and Barriers to Acceptance Into Risk Acceptance Practice
  • 2 - Application of Artificial Intelligence Computer Programs for Integrating Diverse Data Sets and Facilitating Risk Assess...
  • 3 - Calculation of Acceptable Exposure Levels for Chemicals on an Individual or Mixture Basis
  • 4 - Incorporation of Individual Genotypes Into Biological Marker-Based Risk Assessments
  • 5 - Getting on the Rising Road-Some Suggestions
  • References
  • Index
  • Back Cover

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