Monitoring Human Tissues for Toxic Substances -- Copyright -- Preface -- Contents -- Executive Summary -- THE NATIONAL HUMAN MONITORING PROGRAM -- CHARGE TO THE COMMITTEE -- RELATIONSHIP OF TISSUE MONITORING TO EPA PROGRAM PRIORITIES -- GOALS AND POTENTIAL USES OF A NATIONAL PROGRAM TO MONITOR HUMAN TISSUES -- CONCLUSIONS AND RECOMMENDATIONS -- Toxicologic Issues -- Relevance of Human Tissue Monitoring to Risk Assessment -- Choice of Tissues to Monitor -- Sampling Methods -- Collection, Short-Term Storage, and Archiving of Tissues -- Chemical Assay of Specimens -- Program Design and Management Issues -- Administrative and Agency Issues -- Funding -- Science Review -- Other Administrative Issues -- Analysis and Reporting of Data -- Cooperation and Information Transfer with Other Organizations -- Monitoring Human Tissues for Toxic Substances -- 1 Introduction -- BACKGROUND -- CHARGE TO THE COMMITTEE -- ENVIRONMENTAL AND PUBLIC HEALTH RATIONALE FOR MONITORING CHEMICALS IN HUMAN TISSUES -- RELATIONSHIP OF TISSUE MONITORING TO EPA PROGRAM PRIORITIES -- GOALS AND POTENTIAL USES OF A NATIONAL PROGRAM TO MONITOR HUMAN TISSUES -- 2 Review of the National Human Adipose Tissue Survey and Selected Program Alternatives -- DEVELOPMENT OF THE PROGRAM -- Program Deficiencies -- Toxicologic Issues (see Chapter 3) -- Sampling Strategy (See Chapter 4) -- Collection, Storage, and Archiving of Tissues (see Chapter 5) -- Chemical Assay Issues (see Chapter 6) -- Programmatic Issues (see Chapter 7) -- EXISTING PROGRAMS AS POSSIBLE ALTERNATIVES TO THE NATIONAL HUMAN ADIPOSE TISSUE SURVEY -- National Center for Health Statistics: National Health and Nutrition Examination Surveys (NHANES) -- Agency for Toxic Substances and Disease Registry: National Exposure and Disease Registries -- National Institute of Standards and Technology: Environmental Specimen Banking Program.

Environmental Protection Agency: Total Exposure Assessment Methodology Study -- Food and Drug Administration: Total-Diet Study -- National Oceanographic and Atmospheric Administration: National Status and Trends Mussel Watch Program -- Foreign Programs -- Conclusions -- SUMMARY AND RECOMMENDATIONS -- 3 Toxicologic Issues -- INTRODUCTION -- RELATION BETWEEN ENVIRONMENTAL MONITORING AND TISSUE MONITORING -- RELEVANCE OF HUMAN TISSUE MONITORING TO RISK ASSESSMENT -- Biologic Markers -- Markers of Exposure or Dose -- Markers of Effect -- Markers of Biologically Effective Dose -- Markers of Early Biologic Effect -- Markers of Susceptibility -- Summary -- CHOICE OF TISSUES TO MONITOR -- Background -- Blood -- Adipose Tissue -- Lean Tissues -- Biologic Fluids -- Hair -- SUMMARY AND RECOMMENDATIONS -- 4 Sampling Methods -- INTRODUCTION -- SOME FEATURES FOR SAMPLING IN A CONTINUING POPULATION SURVEY -- COMMONLY REQUIRED COMPROMISES IN SAMPLING METHODS -- Shrinking of Target Population -- Revision of Goals to Fit Sample of Affordable Size -- Acceptance of Nonresponse -- Substitution for Sample Units -- Analyses of Effects of Compromises -- THE NATIONAL HUMAN ADIPOSE TISSUE SURVEY SAMPLE -- Goals of Study and Target Population -- First Stage: Metropolitan Sampling Area -- Second Stage: Medical Examiner or Pathologist -- Third Stage: Specimen Donor -- Fourth Stage: Body Source of Specimen -- Sampling Errors -- IMPROVEMENTS THAT ARE POSSIBLE WITHOUT CHANGING BASIC DATA COLLECTION METHODS -- Sample Size -- Cooperation of Medical Examiners and Hospital Pathologists -- Adherence to Quotas -- Replacement of MSAs -- Nonrandom Selection of Counties, Medical Examiners, and Hospitals -- Composite Specimens -- COMPUTATION OF SAMPLING ERRORS -- CRITICISMS OF NHATS STATISTICAL SAMPLING METHODS -- The Benefits of Blood Collection for Probability Sampling.

Use of Composite Specimens -- NHATS Sample Design -- SUMMARY AND RECOMMENDATIONS -- 5 Collection, Short-Term Storage, and Archiving of Tissues -- INTRODUCTION -- COLLECTION -- SHORT- AND LONG-TERM STORAGE -- Quality Control -- Specimen Size -- ADDITIONAL ISSUES FOR CONSIDERATION -- Specimens for Tissue Banking -- Tissue Storage Conditions -- Temperature -- Storage Containers and Specimen Size -- Archival Information -- Access to Archived Specimens -- STATUS OF THE NHATS ARCHIVE -- History -- Current Status -- SUMMARY AND RECOMMENDATION -- 6 Chemical Assay of Specimens -- INTRODUCTION -- MAJOR FEATURES OF A PROGRAM FOR CHEMICAL ANALYSIS OF TISSUES FOR POPULATION-BASED SURVEILLANCE OF EXPOSURES -- Monitoring-Program Development -- Selection Based on Analytic Expediency and Constraints -- Selection Based on Regulatory Interest -- Selection Based on Prior Detection in Human Tissues -- Selection Based on Indications of Health Relevance -- Selection Based on Indications of Environmental Contamination -- Summary -- Design of Chemical Assay Programs -- Determination of Requirements for Analytic Performance -- Development and Validation of Method -- Design of Quality Assurance -- Identification of Additional Resources Needed -- Implementation of Method Development and Validation Studies -- Pilot-Scale Monitoring -- Continuing Monitoring: Review of Analytic Program and Goals -- Exploratory Analyses -- "Volunteer" Chemicals in Monitoring Assays -- Alternative Detection Methods -- Alternative Sample-Preparation Schemes -- Establishing Goals for New Assay Technology -- PRACTICAL LIMITATIONS AND COMPROMISES -- Methods to Reduce the Number of Analyses -- Compositing of Samples -- Subsampling or Stratified Assays -- Less-Frequent Analysis or Staggered Assays -- Special Studies -- CURRENT AND PREVIOUS ANALYTIC PRACTICES OF THE NHATS PROGRAM.

SUMMARY AND RECOMMENDATIONS -- Definition of Goals -- Formalization of the Planning Process -- Critical Evaluation of Program Results -- Links to Analytic-Methods Research -- Regular Schedule of Analyses -- 7 Program Design and Management Issues -- INTRODUCTION -- ADMINISTRATIVE AND AGENCY ISSUES -- Administrative Location -- Environmental Protection Agency -- Agency for Toxic Substances and Disease Registry -- Centers for Disease Control -- Summary -- Funding -- Science Advisory Committee -- Other Administrative Issues -- IMPLEMENTATION AND OPERATIONAL ISSUES -- Flexibility -- Legal and Ethical Issues -- ANALYSIS AND REPORTING OF DATA -- Types of Data Analysis and Reporting -- Integration of Data Sets with Data from Other Sources -- Reporting Frequency -- Review Process for Reports -- Production and Dissemination of Reports -- COOPERATION AND INFORMATION TRANSFER WITH OTHER ORGANIZATIONS -- TRANSITION -- SUMMARY AND RECOMMENDATIONS -- Administrative Location -- Funding -- Scientific Advisory Committee -- Other Issues -- Analysis and Reporting of Data -- References -- Appendix A Workshop Agenda January 24-25, 1989 -- SESSION I: NHMP AND ITS USE/NON-USE -- SESSION II: MONITORING OBJECTIVES -- SESSION III: PROGRAM DESIGN -- SESSION IV: ALTERNATIVE MONITORING PROGRAMS -- SESSION V: COMMITTEE PANEL DISCUSSION -- Appendix B Workshop Participants January 24-25, 1989 -- Appendix C Summary of Workshop -- MAJOR THEMES -- General Themes -- Specific Themes -- SUMMARY -- Appendix D The National Health and Nutrition Examination Survey -- HISTORY -- PURPOSES -- DESIGN -- General Features -- Statistical Design -- METHODOLOGY IN NHANES I, II, AND HHANES -- DATA COLLECTION METHODS -- QUALITY ASSURANCE -- DATA PROCESSING -- DATA REPORTING -- RESEARCH INITIATIVES -- NHANES III -- MAJOR FACTORS AFFECTING THE DESIGN FOR NHANES III.

PRECISION SPECIFICATIONS AND DOMAINS FOR ANALYSIS -- Appendix E Foreign Environmental Monitoring Programs Using Human Tissues or Tissue Specimen Banking -- GERMANY -- History -- Current Program -- SWEDEN -- CANADA -- JAPAN.