From 1962 to 1971, the US military sprayed herbicides over Vietnam to strip the thick jungle canopy that could conceal opposition forces, to destroy crops that those forces might depend on, and to clear tall grasses and bushes from the perimeters of US base camps and outlying fire-support bases. Mixtures of 2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), picloram, and cacodylic acid made up the bulk of the herbicides sprayed. The main chemical mixture sprayed was Agent Orange, a 50:50 mixture of 2,4-D and 2,4,5-T. At the time of the spraying, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic form of dioxin, was an unintended contaminant generated during the production of 2,4,5-T and so was present in Agent Orange and some other formulations sprayed in Vietnam.

Because of complaints from returning Vietnam veterans about their own health and that of their children combined with emerging toxicologic evidence of adverse effects of phenoxy herbicides and TCDD, the National Academy of Sciences (NAS) was asked to perform a comprehensive evaluation of scientific and medical information regarding the health effects of exposure to Agent Orange, other herbicides used in Vietnam, and the various components of those herbicides, including TCDD. Updated evaluations are conducted every two years to review newly available literature and draw conclusions from the overall evidence.Veterans and Agent Orange: Update 2012 reviews peer-reviewed scientific reports concerning associations between health outcomes and exposure to TCDD and other chemicals in the herbicides used in Vietnam that were published in October 2010--September 2012 and integrates this information with the previously established evidence database. This report considers whether a statistical association with herbicide exposure exists, taking into account the strength of the scientific evidence and the appropriateness of the statistical and epidemiological methods used to detect the association; the increased risk of disease among those exposed to herbicides during service in the Republic of Vietnam during the Vietnam era; and whether there exists a plausible biological mechanism or other evidence of a causal relationship between herbicide exposure and the disease.

Contents

• THE NATIONAL ACADEMIES
• COMMITTEE TO REVIEW THE HEALTH EFFECTS IN VIETNAM VETERANS OF EXPOSURE TO HERBICIDES (NINTH BIENNIAL UPDATE)
• Reviewers
• Preface
• Summary
  • CHARGE TO THE COMMITTEE
  • COMMITTEE'S APPROACH TO ITS CHARGE
  • EVIDENCE REVIEWED BY THE COMMITTEE
  • THE COMMITTEE'S CONCLUSIONS
  • COMMITTEE RECOMMENDATIONS
• 1. Introduction
  • CHARGE TO THE COMMITTEE
  • CONCLUSIONS OF PREVIOUS VETERANS AND AGENT ORANGE REPORTS
  • ORGANIZATION OF THIS REPORT
  • REFERENCES
• 2. Evaluating the Evidence
  • CHOICE OF HEALTH OUTCOMES
  • IDENTIFICATION OF RELEVANT LITERATURE
  • COMMITTEE'S APPROACH
  • EVALUATION OF THE EVIDENCE
  • REFERENCES
• 3. Exposure to the Herbicides Used in Vietnam
  • MILITARY USE OF HERBICIDES IN VIETNAM
  • TCDD IN HERBICIDES USED IN VIETNAM
  • EXPOSURE OF VIETNAM VETERANS
  • EXPOSURE OF THE VIETNAMESE POPULATION
  • MODELS FOR CHARACTERIZING HERBICIDE EXPOSURE
  • METHODOLOGIC ISSUES IN EXPOSURE ASSESSMENT
  • REFERENCES
• 4. Information Related to Biologic Plausibility
  • PICLORAM
  • CACODYLIC ACID
  • PHENOXY HERBICIDES 2,4-DICHLOROPHENOXY ACID AND 2,4,5-TRICHLOROPHENOXYACETIC ACID
  • 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN
  • LIMITATIONS OF EXTRAPOLATING RESULTS OF LABORATORY STUDIES TO HUMAN RESPONSES
  • EPIGENETICS
  • DEVELOPMENTAL IMMUNOTOXICITY
  • REFERENCES
• 5. Epidemiologic Studies: Compendium of New Publications
  • NEW EPIDEMIOLOGIC PUBLICATIONS
  • REFERENCES
• 6. Epidemiologic Studies: Background on Multiply Referenced Populations
  • VIETNAM-VETERAN STUDIES
  • OCCUPATIONAL STUDIES
  • ENVIRONMENTAL STUDIES
  • CASE-CONTROL STUDIES
  • REFERENCES
• 7. Immune-System Disorders
  • CATEGORIES OF IMMUNE DYSFUNCTION
  • CONCLUSIONS FROM VAO AND PREVIOUS UPDATES
  • UPDATE OF THE EPIDEMIOLOGIC LITERATURE AND HUMAN STUDIES
  • BIOLOGIC PLAUSIBILITY
  • SYNTHESIS
  • CONCLUSIONS
  • TRANSLATION BETWEEN ANIMAL AND HUMAN STUDIES
  • REFERENCES
• 8. Cancer
  • ORGANIZATION OF CANCER GROUPS
  • BIOLOGIC PLAUSIBILITY
  • THE COMMITTEE'S VIEW OF “GENERAL” HUMAN CARCINOGENS
  • ORAL, NASAL, AND PHARYNGEAL CANCER
  • CANCERS OF THE DIGESTIVE ORGANS
  • LARYNGEAL CANCER
  • LUNG CANCER
  • BONE AND JOINT CANCER
  • SOFT-TISSUE SARCOMA
  • SKIN CANCERS
  • BREAST CANCER
  • CANCERS OF THE FEMALE REPRODUCTIVE SYSTEM
  • PROSTATE CANCER
  • TESTICULAR CANCER
  • BLADDER CANCER
  • RENAL CANCER
  • BRAIN CANCER
  • ENDOCRINE CANCERS
  • LYMPHOHEMATOPOIETIC CANCERS
  • REFERENCES
• 9. Fertility and Gestational Outcomes
  • BIOLOGIC PLAUSIBILITY OF EFFECTS ON FERTILITY AND REPRODUCTION
  • ENDOMETRIOSIS
  • FERTILITY
  • SPONTANEOUS ABORTION, STILLBIRTH, NEONATAL DEATH, AND INFANT DEATH
  • BIRTH WEIGHT AND PRETERM DELIVERY
  • REFERENCES
• 10. Effects on Future Generations
  • BIOLOGIC PLAUSIBILITY OF EFFECTS IN FUTURE GENERATIONS
  • BIRTH DEFECTS
  • CANCERS IN OFFSPRING
  • EFFECTS OCCURRING LATER IN OFFSPRING'S LIFE OR IN LATER GENERATIONS
  • REFERENCES
• 11. Neurologic Disorders
  • BIOLOGIC PLAUSIBILITY
  • NEUROBEHAVIORAL (COGNITIVE OR NEUROPSYCHIATRIC) DISORDERS
  • NEURODEGENERATIVE DISEASES
  • CHRONIC PERIPHERAL SYSTEM DISORDERS
  • HEARING LOSS
  • REFERENCES
• 12. Cardiovascular and Metabolic Outcomes
  • TYPE 2 DIABETES
  • CIRCULATORY DISORDERS
  • REFERENCES
• 13. Other Chronic Health Outcomes
  • RESPIRATORY DISORDERS
  • GASTROINTESTINAL AND DIGESTIVE DISEASES, INCLUDING LIVER TOXICITY
  • THYROID HOMEOSTASIS
  • EYE PROBLEMS
  • BONE CONDITIONS
  • REFERENCES
• 14. Conclusions and Recommendations
  • SYNOPSIS OF COMMITTEE CONCLUSIONS
  • COMMITTEE RECOMMENDATIONS
  • REFERENCES
• APPENDIXES
  • Appendix A. Issues Raised by the Public and Agendas of Public Meetings Held by the Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides (Ninth Biennial Update) and Other Written Submissions to the Committee
  • Appendix B. Short-Term Adverse Health Responses
  • Appendix C. Clarification of Cancer Groupings Used in Reporting Results, with Correspondence to National Institute for Occupational Safety and Health Cause-of-Death Codes and International Classification of Diseases Codes for Cancers
  • Appendix D. Biographies of Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides (Ninth Biennial Update) and Staff

Suggested citation:

IOM (Institute of Medicine). 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press.

NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.