Cover Image

Not for Sale



View/Hide Left Panel
Click for next page ( R12


The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement



Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.

OCR for page R11
Contents EXECUTIVE SUMMARY Organization and Framework, 2 Toxicology Summary, 3 Exposure Assessment, 4 Conclusions about Health Outcomes, 5 Health Outcomes with Sufficient Evidence of an Association, 5 Health Outcomes with Limited/Suggestive Evidence of Association, 8 Health Outcomes with Inadequate/Insufficient Evidence to Determine Whether an Association Exists, 11 Health Outcomes with Limited/Suggestive Evidence of No Association, 12 The Relationship Between the Length of Time Since Exposure and the Possible Risk of Cancer Development, 13 Increased Risk of Disease in Vietnam Veterans, 14 2 RESEARCH HIGHLIGHTS Birth Defects, 15 Introduction, 15 Background, 15 Epidemiologic Studies of Birth Defects, 16 Summary, 25 Conclusions, 26 Peripheral Neuropathy, 28 Introduction, 28 x~ 15

OCR for page R11
xt! REFERENCES CONTENTS Review of the Scientific Literature on Acute and Subacute Transient Peripheral Neuropathy, 29 Summary of Acute and Subacute Transient Peripheral Neuropathy, 30 Conclusions, 31 The contents of the entire report, from which this Summary and Research Highlights is extracted are listed below. EXECUTIVE SUMMARY 33 VETERANS AND AGENT ORANGE: THE INITIAL IOM REPORT 17 Background, 17 Conclusions About Health Outcomes, 19 Research Recommendations, 23 Impact of the Report, 24 DVA Task Force, 24 Military Use of Herbicides in Vietnam, 26 Federal Government's Response to Concerns Over the Military Use of Herbicides in Vietnam, 27 U.S. Congress, 27 Department of Veterans Affairs, 29 Department of the Air Force, 31 Environmental Protection Agency, 32 TOXICOLOGY Summary, 35 Introduction, 35 Summary of VAO, 37 Chemistry, 38 Toxicokinetics, 38 Disease Outcomes and Mechanisms of Toxicity, 39 Literature Update, 43 Overview, 43 Update of Toxicity Profiles, 45 Toxicity Profile Update of 2,4-D, 46 Toxicity Profile Update of 2,4,5-T, 49 Toxicity Profile Update of Cacodylic Acid, 50 Toxicity Profile Update of Picloram, 51 Toxicity Profile Update of TCDD, 51 35

OCR for page R11
CONTENTS 4 METHODOLOGIC CONSIDERATIONS IN EVALUATING THE EVIDENCE Questions to Be Addressed, 88 Are Herbicides Statistically Associated with the Health Outcome?, 90 What Is the Increased Risk of the Disease in Question Among Those Exposed to Herbicides in Vietnam?, 91 Is There a Plausible Biologic Mechanism?, 92 Issues in Evaluating the Evidence, 92 Experimental Studies, 92 Epidemiologic Studies, 93 The Role of Case Studies and Other Studies with No Comparison Groups, 94 Publication Bias, 95 The Role of Judgment, 96 Integration of New Evidence, 96 Summary of the Evidence, 97 Categories of Association, 97 EXPOSURE ASSESSMENT Exposure Assessment in the Evaluation of Epidemiologic Studies, 99 Estimates of Exposure to Herbicides and TCDD During Vietnam Service, 101 Review of the Recent Literature, 104 TCDD Half-Life Investigations, 104 TCDD Exposure Levels for Selected Epidemiologic Studies, 105 Other Dioxin Congeners, 106 Development of Exposure Indices, 107 6 EPIDEMIOLOGIC STUDIES Occupational Studies, 113 Production Workers, 128 Agricultural Workers, 135 Environmental Studies, 140 Seveso, 141 Vietnam, 148 Other Environmental Studies, 148 Vietnam Veterans, 149 United States, 150 CANCER Introduction, 175 Plausibility Data, 176 . . . x~ 88 99 112 175

OCR for page R11
xlv CONTENTS Expected Number of Cancer Cases Among Vietnam Veterans in the Absence of Any Increase in Risk Due to Herbicide Exposure, 176 Gastrointestinal Tract Tumors, 177 Background, 177 Summary of VAO, 177 Update of the Scientific Literature, 178 Summary, 180 Conclusions, 181 Hepatobiliary Cancers, 181 Background, 181 Epidemiologic Studies, 182 Summary, 185 Conclusions, 185 Nasal/Nasopharyngeal Cancer, 187 Background, 187 Epidemiological Studies, 188 Summary, 189 Conclusions, 189 Respiratory Cancers, 189 Background, 189 Epidemiologic Studies, 191 Epidemiologic Studies of Laryngeal Cancer, 202 Summary, 203 Conclusions, 203 Bone Cancer, 204 Background, 204 Summary of VAO, 204 Update of the Scientific Literature, 204 Summary, 205 Conclusions, 205 Soft-Tissue Sarcomas, 205 Background, 205 Summary of VAO, 205 Update of the Scientific Literature, 206 Summary, 208 Conclusions, 208 Skin Cancers, 209 Background, 209 Epidemiologic Studies, 209 Summary, 210 Conclusions, 210 Cancers of the Female Reproductive System, 211

OCR for page R11
CONTENTS XV Background, 211 Summary of VAO, 211 Update of the Scientific Literature, 212 Summary, 213 Conclusions, 213 Breast Cancer, 213 Background, 213 Epidemiologic Studies, 214 Summary, 217 Conclusions, 217 Prostate Cancer, 217 Background, 217 Epidemiologic Studies, 219 Summary, 221 Conclusions, 223 Renal, Bladder, and Testicular Cancers, 223 Background, 223 Renal Cancer, 224 Summary of VAO, 224 Update of the Scientific Literature, 224 Summary, 225 Conclusions, 225 Bladder Cancer, 225 Summary of VAO, 225 Update of the Scientific Literature, 226 Summary, 227 Conclusions, 227 Testicular Cancer, 227 Summary of VAO, 227 Update of the Scientific Literature, 227 Summary, 228 Conclusions, 228 Brain Tumors, 228 Background, 228 Summary of VAO, 229 Update of the Scientific Literature, 229 Summary, 230 Conclusions, 230 Malignant Lymphomas and Myeloma, 231 Background, 231 Non-Hodgkin's Lymphoma, 231 Summary of VAO, 231 Update of the Scientific Literature, 232

OCR for page R11
xv! CONTENTS Summary, 234 Conclusions, 234 Hodgkin's Disease, 235 Summary of VAO, 235 Update of the Scientific Literature, 235 Summary, 236 Conclusions, 236 Multiple Myeloma, 236 Background, 236 Epidemiologic Studies, 237 Summary, 244 Conclusions, 244 Leukemia, 245 Background, 245 Summary of VAO, 245 Update of Scientific Literature, 245 Summary, 246 Conclusions, 247 Overall Summary for Cancer, 247 Health Outcomes with Sufficient Evidence of an Association, 247 Health Outcomes with Limited/Suggestive Evidence of Association, 247 Health Outcomes with Inadequate/Insufficient Evidence to Determine Whether an Association Exists, 249 Health Outcomes with Limited/Suggestive Evidence of No Association, 250 Increased Risk in Vietnam Veterans, 251 8 LATENCY AND CANCER RISK Analysis of Latency in Epidemiologic Studies, 261 Questions Addressed by the Committee, 264 Results of the Literature Review of Herbicide Exposure and Cancer, 266 Limitations of the Literature Review Approach, 266 Overview of the Findings, 267 Respiratory Cancer, 268 Background, 268 Conclusions, 271 Prostate Cancer, 273 Background, 273 Conclusions, 274 Relevance of the Latency Issue in Assessing the Effect of Herbicides on Cancer Risk in Vietnam Veterans, 276 9 REPRODUCTIVE EFFECTS 260 278

OCR for page R11
CONTENTS Introduction, 278 Fertility, 279 Background, 279 Summary of VA 0, 280 Update of the Scientific Literature, 280 Conclusions, 282 Spontaneous Abortion, 282 Background, 282 Summary of VA 0, 283 Update of the Scientific Literature, 283 Conclusions, 284 Stillbirth, 284 Background, 284 Summary of VA 0, 285 Update of the Scientific Literature, 285 Conclusions, 285 Birth Defects, 286 Background, 286 Epidemiologic Studies of Birth Defects, 286 Summary, 295 Conclusions, 298 Childhood Cancer, 298 Background, 298 Summary of VA 0, 299 Update of Scientific Literature, 299 Conclusions, 300 Conclusions for Reproductive Effects, 300 10 NEUROBEHAVIORAL DISORDERS Introduction, 304 Cognitive and Neuropsychiatric Effects, 307 Summary of VA 0, 307 Update of the Scientific Literature, 307 Conclusions, 308 Motor/Coordination Dysfunction, 309 Summary of VA 0, 309 Update of the Scientific Literature, 309 Conclusions, 310 Chronic Persistent Peripheral Neuropathy, 310 Summary of VA 0, 310 Update of the Scientific Literature, 310 Conclusions, 311 Acute and Subacute Transient Peripheral Neuropathy, 311 . . xv 304

OCR for page R11
. . . xvit! CONTENTS Review of the Scientific Literature, 312 Summary of Acute and Subacute Transient Peripheral Neuropathy, 313 Conclusions, 314 Conclusions for Neurobehavioral Disorders, 314 11 OTHER HEALTH EFFECTS Introduction, 317 Chloracne, 317 Summary of VAO, 318 Update of the Scientific Literature, 318 Conclusions, 320 Porphyria Cutanea Tarda, 321 Summary of VAO, 321 Update of the Scientific Literature, 322 Conclusions, 323 Respiratory Disorders, 324 Summary of VAO, 324 Update of the Scientific Literature, 325 Conclusions, 325 Immune System Disorders, 326 Immune Suppression, 326 Allergy and Autoimmunity, 327 Summary of VAO, 327 Update of the Scientific Literature, 328 Conclusions, 329 Other Metabolic and Digestive Disorders, 330 Diabetes Mellitus, 330 Liver Toxicity, 331 Lipid Abnormalities, 333 Gastrointestinal Ulcers, 334 Conclusions, 334 Circulatory Disorders, 335 Summary of VAO, 335 Update of the Scientific Literature, 336 Conclusions, 337 APPENDIXES A Information Gathering B Risk of Disease in Vietnam Veterans by Bryan Langholz and Malcolm Pike C Committee and Staff Biographies 317 343 349 360

OCR for page R11
SUMMARY AND RESEARCH HIGHLIGHTS Vtercus Qn~ Agent Range Update 1996

OCR for page R11