Veterans and agent orange : update 2002

EXECUTIVE SUMMARY 1 The Charge to the Committee, 2 The Committee’s Approach to Its Charge, 2 The Committee’s Evaluation, 3 Research Recommendations, 10 1 INTRODUCTION 12 Charge to the Committee, 13 Conclusions of Previous Veterans and Agent Orange Reports, 13 Organization of this Report, 18 References, 19 2 CONSIDERATIONS IN EVALUATING THE EVIDENCE 20 Choice of Health Outcomes, 20 Identification of Relevant Literature, 20 Committee’s Approach to Its Charge, 22 Issues in Evaluating the Evidence, 24 References, 28 3 TOXICOLOGY 30 Highlights of Previous Reports, 31 Toxicity Profile Update of 2,4-D, 31 Toxicity Profile Update of 2,4,5-T, 37 xiii Toxicity Profile Update of Cacodylic Acid, 38 Toxicity Profile Update of Picloram, 40 Toxicity Profile Update of TCDD, 40 Summary of Toxicity Profiles, 76 Relevance to Human Health, 81 References, 82 4 OVERVIEW OF EPIDEMIOLOGIC STUDIES 103 Occupational Studies, 104 Environmental Studies, 115 Vietnam-Veteran Studies, 118 References, 194 5 EXPOSURE ASSESSMENT 215 Exposure Assessment for Epidemiology, 215 Occupational Exposure to Herbicides and TCDD, 217 Environmental Exposure to Herbicides and TCDD, 226 Military Use of Herbicides in Vietnam, 229 Exposure Assessment in Studies of Vietnam Veterans, 232 References, 235 6 CANCER 242 Gastrointestinal Tract Tumors, 243 Hepatobiliary Cancers, 259 Nasopharyngeal Cancer, 264 Laryngeal Cancer, 268 Lung Cancer, 272 Bone and Joint Cancer, 278 Soft-Tissue Sarcomas, 282 Skin Cancer—Melanoma, 287 Skin Cancer—Basal-cell and Squamous-cell (Nonmelanoma), 295 Breast Cancer, 300 Cancers of the Female Reproductive System, 309 Prostate Cancer, 316 Testicular Cancer, 324 Urinary Bladder Cancer, 328 Renal Cancer, 333 Brain Tumors, 338 Non-Hodgkin’s Lymphoma, 343 Hodgkin’s Disease, 355 Multiple Myeloma, 361 Leukemia, 366 Chronic Lymphocytic Leukemia, 372 xiv CONTENTS Summary, 376 References, 381 7 REPRODUCTIVE AND DEVELOPMENTAL EFFECTS 393 Birth Defects, 393 Fertility, 405 Spontaneous Abortion, 409 Stillbirth, Neonatal Death, and Infant Death, 421 Low Birthweight and Preterm Delivery, 422 Childhood Cancer, 425 Sex Ratio, 432 Summary, 438 References, 441 8 NEUROBEHAVIORAL DISORDERS 447 Cognitive and Neuropsychiatric Effects, 448 Motor or Coordination Dysfunction, 452 Chronic Persistent Peripheral Neuropathy, 465 Acute and Subacute Transient Peripheral Neuropathy, 469 Summary, 470 References, 472 9 OTHER HEALTH EFFECTS 477 Chloracne, 477 Porphyria Cutanea Tarda, 479 Respiratory Disorders, 480 Immune System Disorders, 483 Diabetes, 485 Lipid and Lipoprotein Disorders, 493 Gastrointestinal and Digestive Disease, Including Liver Toxicity, 498 Circulatory Disorders, 502 AL Amyloidosis, 506 Endometriosis, 508 Thyroid Homeostasis, 510 Summary, 514 References, 519 10 RESEARCH RECOMMENDATIONS 523 Vietnam-Veteran Studies, 523 Studies of the Vietnamese, 526 Other Research, 526 References, 527 CONTENTS xv APPENDIXES A AGENDAS OF PUBLIC MEETINGS 529 B ICD-9 CODES FOR HEALTH OUTCOMES OF INTEREST 531 C COMMITTEE AND STAFF BIOGRAPHIES 534 INDEX 539