Veterans and Agent Orange -- Copyright -- Foreword -- Preface -- CONDUCT OF THE STUDY -- Contents -- 1 Executive Summary -- ORGANIZATION AND FRAMEWORK -- CONCLUSIONS ABOUT HEALTH OUTCOMES -- Health Outcomes with Sufficient Evidence of an Association -- Health Outcomes with Limited/Suggestive Evidence of an Association -- Health Outcomes with Limited/Suggestive Evidence of No Association -- Health Outcomes with Inadequate/Insufficient Evidence to Determine Whether an Association Exists -- Increased Risk in Vietnam Veterans -- RESEARCH RECOMMENDATIONS -- Epidemiologic Studies of Vietnam Veterans -- Mandated Research Efforts -- REFERENCES -- 2 History of the Controversy Over the Use of Herbicides -- MILITARY USE OF HERBICIDES IN VIETNAM -- Herbicide Development and Testing -- Use of Herbicides in Vietnam -- EARLY CONCERNS ABOUT THE USE OF HERBICIDES IN VIETNAM -- Early Accounts of Dioxin (TCDD) -- Concerns Over the Long-Term Use of Herbicides -- CONCERNS ABOUT EXPOSURE TO AGENT ORANGE -- Vietnam Veterans Return Home -- The Beginning of the Controversy -- AGENT ORANGE PRODUCT LIABILITY LITIGATION -- Class Action Suit -- CONCERNS ABOUT OTHER EXPOSURES TO 2,4,5-T AND TCDD -- Occupational Exposure -- Production Workers -- Agricultural and Forestry Workers -- Pulp and Paper Mill Workers -- Major Event Associated with Occupational Exposure to Dioxin (TCDD) -- Environmental Exposures -- Domestic Use of Herbicides -- Major Events Associated with Environmental Exposure to Dioxin (TCDD) -- THE FEDERAL GOVERNMENT'S RESPONSE TO PUBLIC CONCERNS -- White House -- U.S. Congress -- Hearings -- Legislation on Agent Orange -- Office of Technology Assessment -- General Accounting Office -- Department of the Air Force -- Department of Veterans Affairs -- Health Care -- Research Efforts -- Compensation and Benefits -- Outreach Activities.

Department of Health and Human Services -- Centers for Disease Control -- Environmental Protection Agency -- RESPONSE BY OTHERS TO PUBLIC CONCERNS -- State Governments -- Veterans' Advocates -- Australia and South Korea -- National Research Council and Institute of Medicine -- REFERENCES -- 3 The U.S. Military and the Herbicide Program in Vietnam -- MILITARY AND DEMOGRAPHIC CHARACTERISTICS OF VIETNAM VETERANS -- Estimates of the Number of Military Personnel Serving in Vietnam -- Federal Estimates -- Other Survey Estimates -- Military and Demographic Characteristics -- Studies of Women Veterans -- THE MILITARY USE OF HERBICIDES IN VIETNAM -- Operation Ranch Hand -- Herbicide Formulations -- Military Herbicides -- Level of Toxic Contaminants -- Termination of the Program -- Disposal of Surplus Herbicides -- Ground Spraying of Herbicides -- The HERBS and Services HERBS Tapes -- Geographical Distribution of Herbicide Sprays -- SUMMARY -- REFERENCES -- 4 Toxicology -- OVERVIEW -- Chemistry -- Exposure and Metabolism -- Carcinogenicity: TCDD -- Mechanism of Action -- Carcinogenicity: Herbicides -- Mechanism of Action -- Immunotoxicity: TCDD -- Mechanism of Action -- Immunotoxicity: Herbicides -- Reproductive and Developmental Toxicity: TCDD -- Mechanism of Action -- Reproductive and Developmental Toxicity: Herbicides -- Other Toxicity: TCDD -- Other Toxicity: Herbicides -- TOXICITY PROFILE OF TETRACHLORODIBENZO-P-DIOXIN -- Introduction -- Exposure and Pharmacokinetics -- Bioavailability Following Various Routes of Exposure -- Distribution -- Metabolism -- Excretion -- Mechanism of Action -- Introduction -- Ah Receptor -- Non-Ah-Mediated Toxicity -- Health Outcomes in Animal Studies -- Carcinogenicity -- Immunotoxicity -- Hepatotoxicity -- Reproductive and Developmental Toxicity -- Reproductive Toxicity -- Neurotoxicity -- Metabolic Toxicity.

Gastrointestinal Toxicity -- Respiratory Tract Associated Toxicity -- Cardiovascular Toxicity -- Corticosteroids -- Dermal Toxicity -- TOXICITY PROFILE OF 2,4-DICHLOROPHENOXYACETIC ACID -- Introduction -- Pharmacokinetics -- Carcinogenicity -- Genotoxicity -- Acute Toxicity -- Chronic Systemic Toxicity -- Reproductive and Developmental Toxicity -- Immunotoxicity -- TOXICITY PROFILE OF 2,4,5-TRICHLOROPHENOXYACETIC ACID -- Introduction -- Pharmacokinetics -- Carcinogenicity -- Genotoxicity -- Acute Toxicity -- Chronic Systemic Toxicity -- Reproductive and Developmental Toxicity -- Immunotoxicity -- TOXICITY PROFILE OF CACODYLIC ACID -- Introduction -- Pharmacokinetics -- Carcinogenicity -- Genotoxicity -- Acute Toxicity -- Chronic Systemic Toxicity -- Reproductive and Developmental Toxicity -- Immunotoxicity -- TOXICITY PROFILE OF PICLORAM -- Introduction -- Pharmacokinetics -- Carcinogenicity -- Genotoxicity -- Acute Toxicity -- Chronic Systemic Toxicity -- Reproductive and Developmental Toxicity -- Immunotoxicity -- REFERENCES -- 5 Methodologic Considerations in Evaluating the Evidence -- QUESTIONS TO BE ADDRESSED -- Are Herbicides Statistically Associated with the Health Outcome? -- What Is the Increased Risk of the Disease in Question Among Those Exposed to Herbicides in Vietnam? -- BURDEN OF PROOF -- CATEGORIES OF EVIDENCE -- Experiments in Humans: Randomized Controlled Trials -- Experiments in Animals: Animal Models -- Controlled Epidemiologic Studies (Observational) -- Cohort Studies -- Proportionate Mortality Studies -- Case-Control Studies -- Case Reports and Case Series -- Information from Death Certificates -- Integration of Collective Results -- Meta-Analysis -- Considerations in Assessing the Strength of Scientific Evidence -- Strength of Association -- Dose-Response Relation -- Temporally Correct Association -- Consistency of Association.

Specificity of Association -- Biologic Plausibility -- Other Considerations -- The Role of Studies of Occupational and Environmental Exposures -- NATURE OF THE CONCLUSIONS -- Quantification -- Resolution -- Uncertainty and Confidence -- Qualitative Aspects of the Review Process -- Comprehensiveness -- Neutrality -- Judgment -- SUMMARY OF THE EVIDENCE -- Categories of Association -- Increased Risk in Vietnam Veterans -- REFERENCES -- 6 Exposure Assessment -- AN OVERVIEW OF EXPOSURE ASSESSMENT FOR EPIDEMIOLOGY -- Hierarchy of Exposure Assessment Strategies -- Exposure Assessment for Cohort Studies -- Exposure Assessment for Case-Control Studies -- Exposure Misclassification -- Biomarkers -- Biomarkers for TCDD -- Chloracne as a Biomarker -- EXPOSURE ASSESSMENT IN OCCUPATIONAL AND ENVIRONMENTAL STUDIES -- Occupational Studies -- Production Workers -- Agricultural/Forestry Workers -- Herbicide/Pesticide Applicators -- Paper and Pulp Mill Workers -- Environmental Studies -- Vietnamese Studies -- Conclusions on Exposure Assessment in Occupational and Environmental Studies -- EXPOSURE ASSESSMENT IN STUDIES OF VIETNAM VETERANS -- Self-Reports -- Records-Based Measures -- Vietnam Service -- Branch of Service -- Combat Experience -- Military Occupation -- Reconstructing Estimated Exposure from Troop Location and Herbicide Spray Data -- The CDC Exposure Opportunity Index -- The CDC Agent Orange Study -- The Stellmans' Study -- Ranch Hand Exposure Index -- Biomarkers of Exposure in Vietnam -- CDC Agent Orange Validation Study (AOVS) -- ESTIMATES OF EXPOSURE TO HERBICIDES AND TCDD DURING VIETNAM SERVICE -- EXPOSURE RECONSTRUCTION -- Development of the Exposure Reconstruction Model -- Evaluation of the Exposure Reconstruction Model -- SUMMARY -- REFERENCES -- 7 Epidemiologic Studies -- OCCUPATIONAL STUDIES -- Production Workers.

National Institute for Occupational Safety and Health -- Monsanto -- Dow -- BASF -- Other Chemical Plants -- Agricultural/Forestry Workers -- Cohort Studies -- Case-Control Studies -- Paper/Pulp Workers -- Other Occupational Studies -- ENVIRONMENTAL STUDIES -- Seveso -- Times Beach and Quail Run -- Vietnam -- Other Environmental Studies -- VIETNAM VETERAN STUDIES -- United States -- Ranch Hands -- Centers for Disease Control -- Department of Veterans Affairs -- American Legion -- State Studies -- Other U.S. Vietnam Veteran Studies -- Australia -- REFERENCES -- 8 Cancer -- CANCER EPIDEMIOLOGY -- SPECIFIC ISSUES WITH REGARD TO HERBICIDE EXPOSURE IN VIETNAM -- EXPOSURE -- PLAUSIBILITY DATA -- EXPECTED NUMBER OF CANCER CASES AMONG VIETNAM VETERANS -- OVERALL CANCER -- Background -- Epidemiologic Studies -- Occupational Studies -- Environmental Studies -- Vietnam Veterans Studies -- Summary -- GASTROINTESTINAL TRACT TUMORS -- Background -- Epidemiologic Studies -- Summary -- Conclusions -- Strength of Evidence in Epidemiologic Studies -- Biologic Plausibility -- Increased Risk of Disease Among Vietnam Veterans -- HEPATOBILIARY CANCERS -- Background -- Epidemiologic Studies -- Occupational Studies -- Environmental Studies -- Vietnam Veterans Studies -- Summary -- Conclusions -- Strength of Evidence in Epidemiologic Studies -- Biologic Plausibility -- Increased Risk of Disease Among Vietnam Veterans -- NASAL/NASOPHARYNGEAL CANCER -- Background -- Epidemiologic Studies -- Conclusions -- Strength of Evidence in Epidemiologic Studies -- Biologic Plausibility -- Increased Risk of Disease Among Vietnam Veterans -- RESPIRATORY CANCERS -- Background -- Epidemiologic Studies -- Occupational Studies -- Environmental Studies -- Vietnam Veterans Studies -- Epidemiologic Studies of Laryngeal Cancer -- Summary -- Conclusions.

Strength of Evidence in Epidemiologic Studies.