Veterans and Agent Orange Health Effects of Herbicides Used in Vietnam (1994) / Chapter Skim
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From page 790... ...
510511 hepatobiliary cancer, 454 Hod,? kin's disease, 550-553 kidney cancer, 515 leukemia, 332-335, 566-568 multiple myelomas, 11-12, 558-561 non-Hodgkin's lymphoma, 9, 256-257, 530540 prostate cancer, 11, 518, 519, 575
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INDEX reproductive outcomes, 510-511, 598 respiratory cancer, 11, 466 soft-tissue sarcomas, 37, 326-328, 479-481, 486-488 sperm dysfunction, 632 suicide, 650 See also Professional pesticide/herbicide applicators Agricultural herbicides, 24, 35, 39, 174-175, 181 Ah receptor in animal studies, 114, 123 in nervous system, 161 in TCDD biologic plausibility, 3, 133-138, 452-453 in TCDD carcinogenicity, 118, 439 in TCDD hepatotoxicity, 151, 152, 457 in TCDD immunotoxicity, 122, 150 in TCDD reproductive toxicity, 123 in TCDD teratogenicity, 159-160 AIDS, 338, 527, 541, 695 Air Force, 81 Vietnam casualties, 83 See also Operation Ranch Hand; Ranch Hand study Alcohol consumption, 507 American Association for the Advancement of Science, 29, 92 Herbicide Assessment Commission, 30-31 American Cancer Society, 334 American Legion, 60, 278-279, 399, 601-602, 626, 633 6-Aminolevulinic acid synthetase, 153-154 Amitrole, 323 Angina, 708 Animal studies Ah receptor, 3, 123, 134 blood abnormalities, 125 cacodylic acid acute toxicity, 188 cacodylic acid carcinogenicity, 118, 119, 187 cacodylic acid chronic exposure, 188-189 cacodylic acid developmental toxicity, 189 cacodylic acid genotoxicity, 187-188 cacodylic acid pharmacokinetics, 186-187 cacodylic acid reproductive toxicity, 189 characteristics of, 111-114 2,4-D carcinogenicity, 118-119, 176-178 2,4-D chronic exposure, 179-180 2,4-D developmental toxicity, 124, 180-181 2,4-D genotoxicity, 178-179 791 2,4-D immunotoxicity' 122-123, 181 2,4-D pharmacokinetics, 175 2,4-D reproductive toxicity, 124, 180, 181 evidentiary role, 228 generalizability, 112, 113, 114, 118, 122 123, 160 hepatic abnormalities, 124-125, 688 male-meLliated disorders, 593-594 nonhuman primates, 151 picloram in, 118, 119, 125, 190-192 2,4,5-T acute toxicity, 184 2,4,5-T carcinogenicity, 118, 119, 182-184 2,4,5-T chronic exposure, 184 2,4,5-T developmental/reproductive toxicity, 124, 185 2,4,5-T genotoxicity, 184 2,4,5-T immunotoxicity, 123 2,4,5-T pharmacokinetics, 182 TCDD carcinogenicity, 3, 116, 138-142 TCDD cardiovascular toxicity, 171 TCDD dermal toxicity, 173-174 TCDD developmental toxicity, 123-124, 156-157, 159-160 TCDD gastrointestinal toxicity, 169-170 TCDD hepatotoxicity, 124-125, 151-156 TCDD immunotoxicity, 119-122, 146-151 TCDD-induced wasting syndrome, 162-166 TCDD metabolic toxicity, 166-169 TCDD neurotoxicity, 160-166 TCDD pharmacokinetics, 127-133 TCDD reproductive toxicity, 123-124, 156 159 TCDD respiratory tract toxicity, 170 Arkansas, 373-374, 663 Armed Forces Institute of Pathology, 494 Army, U.S., 81, 280, 281, 702 Chemical Corps, 13, 15, 16-17, 94-95, 272, 273, 286, 394, 470, 571, 703-704, 705, 711, 722-725 Vietnam casualties, 83 Aryl hydrocarbon hydroxylase, 135, 153, 155 156, 170 Assembly of Life Sciences (ALS) , 62, 63 Asthma, 708, 711, 713 Ataxia' 658 Atlanta Congenital Defects Program, 387 Australia, 61, 91, 340, 406, 418, 444, 470, 488-489, 537, 546, 614-615, 633, 702, 710 Autoimmune disease, 697-699 Autoimmunity, 693
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792 B B cell function, 147, 148 BASE, 312-313, 444, 530, 550, 558 Beck's Depression Inventory, 650, 651 Bias, methodological. See Methodological bias Biochemical warfare, 29, 45 Biologic plausibility Ah receptor-TCDD interaction, 3, 133-137, 439, 452-453 altered sperm parameters, 634 animal studies, 228 bone cancer, 474 brain tumors, 525 carcinogenicity, 116-118, 119, 146, 176 178, 182-184, 187, 190-191, 439, 451 childhood cancer, 630 chloracne, 678 circulatory disorders, 708 diabetes mellitus, 692 evidentiary role of, 111, 114, 223-224, 240 241, 434 female reproductive system cancers, 512 fetal/ir~fant death, 624 genitourinary tract cancers, 521-522 genotoxicity, 178-179, 184, 187-188, 191 hepatobiliary cancer, 453-453, 457 Hodgkin's disease, 557 hyperlipidemia, 692 immunotoxicity, 122, 146-151, 181, 192, 699 infertility, 634 leukemia, 571 liver disorders, 691-692 low birthweight outcomes, 628 male-mediated reproductive outcomes, 593 595 motor/coordination dysfunction, 661 multiple myeloma, 12, 563 nasal/nasopharyngeal cancer, 460 neuropsychological disorders, 658 non-Hodgkin's lymphoma, 549 peripheral nervous system disorders, 666 porphyria cutanea tarda, 679, 682 renal toxicity, 179-180 reproductive outcomes, 123-124, 180-181, 185, 189, 192, 605, 618, 628 respiratory cancers, 472 respiratory disorders, 713 skin cancer, 503 soft-tissue sarcoma, 500 See also TCDD biologic plausibility INDEX Biological samples, 20-21, 729-730 Biomarkers chloracne as, 4, 10, 172-173, 262, 401, 672 674 in exposure assessment, 259-262, 280-284 research recommendations, 17, 725 sperm parameters as, 631 Bionetics Research Laboratory, 30 Birth defects definition, 605-606 environmental exposure studies, 608-609 epidemiology, 606 evaluation of epidemiologic data, 615-618 first reports of herbicide association, 1 herbicide association in, 13-14, 618 occupational exposure studies, 607-608 risk factors, 606-607 TCDD biologic plausibility in, 618 in Vietnam veterans' children, 609-615, 618 See also Reproductive disorders; Teratogenicity Bladder cancer epidemiologic studies, 515-517 herbicide association in, 12, 521, 576 histopathology, 513 incidence, 513 risk factors, 513-514 Vietnam veterans' risk, 513, 517, 522 Boehringer, 313 Bone cancer in children, 628 epidemiology, 472-473 herbicide association in, 13, 473-474, 577 Vietnam veterans' risk, 473, 474 Brain tumors, 339 in agricultural workers, 320 clinical features, 522 2,4-D exposure and, 119, 176-177 epidemiology, 522-523 herbicide association in, 12, 525, 576 Vietnam veterans' risk, 525 Breast cancer in agricultural workers, 510 environmental exposure studies, 511, 512 epidemiology, 505, 506-507 herbicide association in, 13 histopathology, 505-506 risk factors, 507 Vietnam veterans' risk, 505, 511 Bronchitis, 708, 711, 713 Bureau of Labor Statistics, 79, 80 n-Butyl esters, 27
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cacodylic acid as, 118, 119, 187 2,4-D as, 118-119, 176-178 herbicides as, 3 mechanism of action, 434 picloram as, 118, 119, 190-191 2,4,5-T as, 118, 119, 182-184 TCDD as, 3, 116-118, 434, 439 See also Cancer Cardiovascular system cardiomegaly, 703 circulatory disorders, 699-709 lipid abnormalities in, 688 TCDD in, 171 Case-control studies agriculture/forestry workers, 326-341 evidentiary role of, 234-235, 727 exposure assessment for, 256-257, 727 Causality, statistical association vs., 7, 227, 239, 246 Centers for Disease Control, 19, 40-41, 51 Agent Orange action/research, 57-62, 63-64 Agent Orange Study, 276-278 birth defects research, 387-389, 609-612 exposure opportunity index, 274-276, 611612 research methodology, 728 validation study, 59, 260-261, 281-284, 285, 387, 742-743 See also Selected Cancers Study; Vietnam Experience Study Central nervous system. See Neurolo~ic disorders Cerebrospinal Malformation Study, 610 Cerebrovascular disease, 702 stroke, 658, 659, 660
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See P450 Czechoslovakia, 317, 649, 675, 688 D 2,4-D. See 2,4-Dichlorophenoxyacetic acid Data sources Agent Orange Registry, 20, 53, 56, 729 agricultural/forestry worker studies, 265266, 318-341 animal studies, 111-114, 228 case reports, 235-236 CDC studies, 387-391 chemical production workers, 303-318 computerized data bases, 735-736 controlled epidemiologic studies, 228-237 death certificates, 236-237 Department of Veterans Affairs epidemiologic studies, 393-399 environmental exposure studies, 267-269, 372-375, 383-384 epidemiologic studies as, 737-738 exposure reconstruction model, 725-726 herbicide/pesticide applicators, 266-267, 323-326 HERBS tapes, 20, 62, 85, 96-98, 273-279, 287, 291, 602, 725 International Register of Workers Exposed to Phenoxy Herbicides and Their Contaminants, 313-314 mandated efforts, 20-21 military herbicide use in Vietnam, 84-85 non-military herbicide exposures, 4-5, 222223, 241-242 organization of, 737 paper/pulp mill workers, 341, 364
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INDEX presentations/reports to committee, 739-756 randomized controlled trials, 227-228 recommendations for future research, 287289, 291, 722-725, 729-730 reproductive outcomes, 593-595 review of, 244-245 self-reports, 270-271 state government, 60 state-sponsored Vietnam veteran studies, 400-405, 495-496 stored biological samples as, 20-21, 729-730 TCDD production workers, 264-265 troop location, 273-279, 287 Vietnam casualties, 82-83 Vietnam veteran demographics, 79, 80-84 in Vietnam veteran exposure assessment, 270-287 Vietnam veteran reproductive outcomes, 601 Vietnamese civilian health outcomes, 371372 women veterans, 83-84 See also Epidemiologic studies; Military records DDT, 87, 91 Death certificates, 236-237 Defoliants Agent Orange as, 90 military applications, 25, 26 tactical role of, in Vietnam, 85 Vietnam herbicide mission maps, 99-100 Demographic data, Vietnam veterans, 79, 8084 Denmark, 317, 443, 444, 454, 463, 477, 480, 509, 510, 537, 553, 565, 567 Department of Agriculture, U.S., 35, 39, 443 Department of Defense, U.S., 17, 27, 29, 31, 78 herbicide spray mission records, 84-85 herbicide use precautions, 95 military records, 78, 724-725 Department of Veterans Affairs, U.S., 2, 8, 17, 18, 20, 50-51, 284 in Agent Orange controversy, 33, 53-54 Agent Orange Registry, 729 health care in, 54 military records, 78-79, 724-725 outreach activities, 56 recommendations for, 724-725, 726-730 research efforts, 5~55 veterans' advocacy groups and, 61 Vietnam veteran epidemiologic studies, 50, 393-399, 445, 469-470, 493-495, 543547, 562 795 Depressive disorders, 650, 651 Desiccant herbicides, 88-89 Developmental disorders cacodylic acid in, 189 2,4-D in, 180-181 neurological, 660 picloram in, 192 2,4,5-T in, 185 TCDD in, 123-124, 149, 156-157, 159-160, 185 See also Low birthweight Diabetes mellitus, 683-685, 691, 692, 698 Diamond Shamrock Corporation, 34, 35 Diazinon, 91 Dibenzofurans, 126 2,4-Dichlorophenoxyacetic acid (2,4-D) acute toxicity, 179 in Agent Orange, 27 in Agent White, 90 altered sperm parameters, 632 animal studies, 174-181 carcinogenicity, 118-119, 176-178, 439 chemical properties, 114, 175 chemical structure, 111, 114 chronic exposure, 179-180 development of, 24, 26, 35 developmental toxicity, 124, 180-181 domestic use, 174-175, 177-178 formulations, 175 genotoxicity, 119, 178-179 immunotoxicity, 122, 181 ingestion of, 653 kidney toxicity, 125 liver toxicity, 125 metabolism, 115, 116 military field tests, 26 in neuropsychiatric outcomes, 649, 650, 653 in non-Hodgkin's lymphoma, 256-257, 574 occupational exposure, 36, 37, 310-311, 321 pharmacokinetics, 175 reproductive toxicity, 124, 180-181, 597 598 role of, 88 teratogenic potential, 30, 92 therapeutic application, 659 See also Herbicides Diet breast cancer and, 507 in cancer risk, 442 chloracne and, 174 gastrointestinal cancers and, 446 Dinoxol, 91
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See Department of Veterans Affairs Dystonia, 658 E Electrical transformers, 364-365, 444, 626, 675 Emphysema, 708, 713 Encephalopathy, 649 Endocrine system, 150-151 Environmental exposures accidental exposures. 364-365, 368-370 in agricultural areas, 372-375 Alsea, Oregon, 39, 42-43, 372-373, 598 birth defects and, 608-609 bladder cancer and, 516-517 brain tumors and, 523 as cancer risk factor, 442 cancer studies, 442, 444, 454 155, 469 chloracne and, 676-677 circulatory disorders and, 701-702 epidemiologic studies, 3, 301, 365-384, 469 evidentiary role of research on, 4-5, 222223, 241-242 INDEX exposure assessment strategies, 262-263, 267-270 female reproductive system cancers and, 511 hepatobiliary cancers and, 454 l-55 immune modulation and, 693-694 leukemia and, 568-570 motor/coordination dysfunction and, 658659 multiple myeloma and, 562 neonatal death and, 621 neuropsychiatric outcomes and, 651-653 non-Hodgkin's lymphoma and, 540-541 peripheral nervous system disorders and, 663-665 porphyria cutanea tarda and, 680-681 respiratory cancers and, 469 soft-tissue sarcomas and, 491-492 spontaneous abortion and, 598-599 stillbirth and, 620 See also Missouri, Times Beach; Seveso, Italy Environmental Protection Agency, 39, 59-60, 93 in Alsea, Oregon, 42-43 TCDD cancer potency estimate, 138 in Times Beach, Missouri, 41 Enzyme induction liver, 155-156 lung, 170 porphyria, 153-154 Epidemiologic studies agricultural/forestry workers, 318-323, 326341 altered sperm parameters, 632 autoimmunity, 697-698 birth defects, 607-618 bladder cancer, 515-517 bone cancer, 472-473 brain tumors, 523 cancer, 45, 59, 317, 320-323, 367, 383-384, 391-393, 401, 402-403, 435~445, 574 case-control studies, 326-341 chemical industry production workers, 303318 childhood cancer, 628-630 chloracne, 674-678 circulatory disorders, 700-707 cleft lip/palate, 373-374, 375 cohort studies, 229-232 colon cancer, 12, 328-329, 576-577 congressionally mandated, 50 controlled observational, 228
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384, 391, 393, 395-396, 401, 403, 476, 477-500, 572-573, 574 spontaneous abortion, 42, 336-337, 372 373, 405-406, 596-605 state-sponsored, 399-405, 495-496, 546 strength of evidence in assessment of, 238 241 TCDD biomarkers, 259-262 testicular cancer, 405, 519 in Times Beach, 368-370 Vietnam veterans in, 50, 57-59, 62-63, 384 418 Vietnamese in, 370-372, 599-601 See also Exposure assessment Epidermal growth factor, 145, 154 Epstein-Barr virus, 528 Erbon, 309 Erythrocyte sedimentation, 696 Estrogen hepatic binding, 154 receptor mediated responses, 145 Ethoxyresorufin O-deethylase (EROD) , 153, 155 Exposure assessment biomarkers for, 17, 259-262, 280-284 for cancer studies, 436-439 for case-control studies, 256-257 CDC Agent Orange Study, 58 CDC exposure opportunity index, 274-276, 611-612 CDC validation study, 59, 260-261, 281 284, 387 for cohort studies, 254-256 current estimates, 284-287 difficulties in, 14-15, 222, 247-248, 284, 286-287 for environmental studies, 262-263, 267 270 evidentiary role of, 4, 15, 250-253 exposure-dose relationship, 252-253 ground spraying, 288-289 historic exposure reconstruction, 17-18, 19 20, 254, 255-256, 725-726, 728
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798 individual differences, 261, 286 job exposure matrix, 259-262 limitations in existing data sources, 14-15, 290-291 misclassification bias in, 17, 257-259, 724 in non-military settings, 4-5, 15, 222-223, 241-242 for occupational studies, 262-267, 269-270 paper/pulp mill workers, 266-267 process perspective, 252-253 for Ranch Hand study, 386 research recommendations, 16-18, 287-290, 291, 721-722, 724-725 for risk assessment, 14-15, 247-248, 250, 578 self-reports, 270-271 serum TCDD in, 19, 20-21, 261, 282-285, 289, 290, 725, 742-743 Seveso accident, 267-268, 285, 598-599 state-sponsored studies, 400, 401-402, 403 404 Stellmans' study, 278-279, 284 strategies for, 253-254 Times Beach case, 268, 368-369 Vietnam military records in, 271-280 Vietnam service as element of, 271, 284 287 Vietnam spray data, 273-279 Vietnam troop movement data in, 95-96, 273-279, 287 Vietnamese population, 269, 731 workshop on, 746-747 Exposure reconstruction model data sources, 725-726 epidemiologic research and, 726-728 evaluation of, 18, 289-290, 726 recommendations, 15-16, 17-20, 287-290, 291, 721-722, 725-728 F Federal government, in herbicide management/ research, 45-60 Federation of American Scientists, 29 Finland, 324, 364, 383-384, 443, 444, 467, 492, 541, 561 Florida, 324, 467 Food crops, 89 Agent Orange in destruction of, 62, 90 as military target, 27, 31, 87, 97, 98-100, 106 INDEX Forest Service, U.S., 42 Forestry workers See Agricultural/forestry workers Forests early defoliant field tests in, 26 2,4,5-T spraying, 42-43 in Vietnam, 31-32, 62, 90, 104 Fort Detrick, Maryland, 25 Fungicides, 91 G Gastrointestinal disorders cacodylic acid in, 188 TCDD in, 169-170 ulcers, 690-692 Gastrointestinal tract cancers biologic plausibility, 451 epidemiology, 445-447 herbicide association in, 12, 447-451, 576577 in Vietnam veterans, 446, 452 General Accounting Office, 52-53, 96 General Birth Defects Study, 610, 626 General Services Administration, 77 Genetic alteration cacodylic acid in, 119, 187-188 cancer mechanism, 433-434 2,4-D in, 119, 178-179 male-mediated reproductive outcomes, 593594 picloram in, 191 2,4,5-Tin, 119, 184 TCDD in, 118, 142, 143-144, 439 Genetic factors in Ah receptor-mediated events, 134 in cancer risk, 10 in porphyria cutanea tarda, 10, 679 Geneva Protocol, 45 Germany, 312-313, 326, 443, 477, 508-509, 530, 565, 675-676 Givaudan Company, 43 Glucocorticoid receptor, 154 Great Britain. See United Kingdom Ground/perimeter spraying, 20, 24, 74, 85, 90, 91, 94-96, 100, 272, 286, 287, 288 289 Growth factors epidermal, 145, 154 TCDD induction of, 136-137 transforming, 145
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INDEX H Halogenated aromatic hydrocarbons, 125, 126, 151 in hepatic enzyme induction, 155 Hawaii, 60, 400, 603 Headaches, 650, 660 Health and Human Services, U.S., Department of, 57-59 Health outcomes categories of evidence in assessing, 227-237 categories of herbicide association in, 5-8, 221, 223-225, 246-247 early herbicide research, 29-32, 35-36 early TCDD research, 28-29 in evaluating exposure reconstruction model, 289-290 evidence of no association of herbicides in, 12-13,224,247,447-451,503,521,525, 576-577 insufficient evidence for determining herbicide association in, 13-14, 19, 247, 457,460,473-474,512,521,571,577578, 605, 618, 624, 627, 630, 634, 657, 666, 691, 699, 708, 713, 727 limited/suggestive evidence of herbicide association in, 10-12, 19, 247, 472, 519521, 563, 574-576, 727 research priorities, 19, 726-727 sufficient evidence of herbicide association in, 8-10, 246-247, 500, 548, 556-557, 572-574, 678, 682 See also Epidemiologic studies; specific disease Healthy worker effect, 230 Hearing loss, 659-660 Helicopters, in herbicide delivery, 26, 86, 87, 93, 94 Hepatitis B infection, 453 Hepatitis C infection, 453 Hepatobiliary cancers epidemiology, 452-455 evidence for herbicide association, 13, 577 Herbicides action of, 88 agricultural role of, 24, 35, 39, 174-175, 181 banned from U.S. military use, 32, 45 carcinogenicity, 118-119 developmental toxicity, 124 early concerns about, 29-32, 35-36 evidence of no association in health 799 outcomes, 12-13, 224, 247, 447-451, 503, 521, 525, 576-577 immunotoxicity, 122-123 insufficient evidence for determining association in health outcomes, 13-14, 19, 247, 457, 460, 473-474, 512, 521, 571, 577-578, 605, 618, 624, 627, 630, 634, 657, 666, 691, 699, 708, 713, 727 limited/suggestive evidence of association in health outcomes, 10-12, 19, 247, 472, 519-521, 563, 574-576, 727 military application in Vietnam, 1, 3, 24, 27, 74, 84-96, 98-107, 286 military research and development, 25-26 reproductive toxicity, 124 selective, 24, 88 settings for occupational exposure, 36-38 sufficient evidence of association in health outcomes, 8-10, 246-247, 500, 548, 556557, 572-574, 678, 682 TCDD contamination of, 2, 3, 27, 91-92, 114, 126-127 types of, 88 See also Agent Orange; 2,4-Dichlorophenoxyacetic acid; 2,4,5-Trichlorophenoxyacetic acid; 2,3,7,8-Tetrachlorodibenzo-p-dioxin HERBS tapes, 20, 602, 725 contents, 96-97, 273 deficiencies, 97, 104-105 in exposure assessment, 273-279, 287, 291 source of, 62, 85, 96 Hercules, Inc., 35 Hexachlorophene, 40 Highway workers, 326 Historic exposure reconstruction, 17-18, 19-20, 254, 255-256, 725-726, 728 Hodgkin's disease in agricultural/forestry workers, 328, 329, 331, 335-336, 341, 550-553 biologic plausibility of TCDD in, 557 in chemical industry workers, 549-550 in environmental exposure studies, 384 epidemiology, 526, 527-528 herbicide association in, 8, 9-10, 556-557, 574 histopathology, 526-527 research recommendations, 19, 727 in Vietnam veterans, 258, 526, 554-556 Hoffman-Taff, 40 Hormonal system estrogen-mediated responses, 145, 154
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. association in altered sperm parameters, 14, 634 basis for finding of, 13, 247, 577 in birth defects, 14, 605 in bone cancer, 13, 473-474, 577 cancer in children of Vietnam veterans, 14, 630 INDEX in circulatory disorders, 14, 708 in cognitive and neuropsychiatric clisorders, 14, 657-658 in diabetes mellitus, 14, 691 in female reproductive system/breast cancers, 13, 14, 512, 577 in gastrointestinal tract ulcers, 14, 691 in genitourinary tract cancers, 13, 521, 577 in hepatic enzyme abnormalities, 14, 691 in hepatobiliary cancers, 13, 577 in immune system disorders, 14, 699 in infertility, 14, 634 in leukemia, 13, 571, 577-578 in lipid abnormalities, 14, 691 in liver cancer, 13, 457, 577 in low birthweight, 14, 627 in motor/coordination dysfunction, 14, 661 in nasal/nasopharyngeal cancer, 13, 460, 577 in neuropsychiatric outcomes, 14, 657, 666 in perinatal death, 14, 624 in peripheral nervous system disorders, 14, 666 in renal cancer, 13, 521, 577 research recommendations, 19, 727 in respiratory disorders, 14, 713 in spontaneous abortions, 14, 605 in testicular cancer, 13, 521, 577 Interagency Working Group on the Long-Term Health Effects of Phenoxyherbicides and Contaminants, 46 Interleukin-1, 148 International Agency for Research on Cancer (IARC)
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521. 576 Lipid abnormalities, 688-690, 692 epidemiologic studies, 45 TCDD in, 152-153, 259-260 Liver cancer in children, 628 epidemiologic studies, 453-455 herbicide association in, 13, 457, 577 picloram in, 190 research recommendations, 19, 727 risk factors, 453 in Seveso, Italy, studies, 454 155 TCDD in, 116, 138-139, 142, 143 in Vietnam veterans, 391, 393, 455, 457 See also Hepatobiliary cancers Liver disorders 2,4-D in, 179 enzyme activity, 155-156, 685-687, 691692 epidemiologic studies, 45 herbicides in, 125 lipid abnormalities, 688 picloram chronic toxicity, 191-192 in Seveso, Italy, studies, 367 TCDD in, 115, 124, 129-130, 151-156, 155, 165-166 Low birthwei$ht definition, 625
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802 epidemiology, 625-626 herbicide association in, 14, 627-628 risk factors, 625-626 Low-density lipoprotein receptors, 154-155 Lung cancer in a:,ricultural/forestry workers, 466 cacodylic acid and, 187 2,4-D in, 177 herbicide association in, 472 in herbicide/pesticide applicators, 326, 466468 in paper/pulp mill workers, 364, 468 in production workers, 461-466 in Seveso, Italy, studies, 469 in Vietnam veterans, 469-470, 472 See also Respiratory cancers M Maine, 60, 400, 603 Malathion, 87, 88, 91 Malignant lymphomas 2,4-D exposure and, 119, 177-178 See also Hodgkin's disease; Multiple myeloma; Non-Hodgkin's lymphoma Mangrove forests, 31, 62, 90, 104 Marine Corps, 81, 96, 280, 545, 702, 710 non-Hodgkin's lymphoma in, 542, 545, 546 547 Vietnam casualties, 83 Massachusetts, 60, 400-401, 405-406, 445, 470, 496, 602-603, 613, 620, 621, 622 Mast cells, 693 MC-1 spray system, 25 Medical Literature Analysis and Retrieval System, 735 Melanomas. See Skin cancer Melatonin, in TCDD-induced wasting syndrome, 165 Meta-analysis, 243, 244 Methodological bias analyzing stored biological samples, 20-21, 729-730 cancer studies, 436 controlling for, 33, 226-227, 234-235, 242 246 exposure assessment, 17, 257-259, 286-287, 291, 724 healthy worker effect, 230 proportionate mortality studies, 233 recall bias, 256, 601 INDEX reproductive outcome studies, 591-592, 601 self-reports, 270-271 Methodology Agent Orange Study, 58-59, 63-64 Agent Orange Working Group, 19, 728 Alsea investigation, 372-373, 598 American Legion Agent Orange study, 602 assessment of strength of evidence, 238-241 BASE study, 312-313 burden of proof approach, 226-227, 245 cancer studies, 435-440, 442-443, 445 case-control studies, 234-235, 256-257, 326-341 case reports, 235-236 categories of evidence, 227-237 categories of health outcome association, 5 8, 223-225, 246-247 CDC Birth Defects Study, 611-612 CDC epidemiologic studies, 19, 387-393, 498, 728 circulatory disease studies, 699-700, 705 706, 707 cohort studies, 229-232, 254-256, 318-323 confidence intervals, 244 controlled observational studies, 228 Department of Veterans Affairs studies, 393-399, 494-495 disease latency effects, 231-232, 434, 436 438, 494, 495, 727 dose-response relationship, 239-230, 252 Dow studies, 307-312 environmental exposure assessment, 262 263, 269-270 evaluation of epidemiologic studies, 300-301 evaluation of exposure reconstruction model, 18, 289-290, 726 expected cancer incidence, 439-440 exposure assessment strategies, 251-259, 270-287 immune system research, 692 indirect adjustment, 229 information management, 735-738 judgment in, 245-246 meta-analysis, 225, 237-238, 242-243 neurological assessment, 14, 641~42, 649 neuropsychiatric studies, 657 NIOSH studies, 303-305 Nitro, West Virginia, industrial accident studies, 305-307 NRC Commission on Life Sciences, 63 occupational exposure assessment, 262-264, 269-270
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See Spontaneous abortion Missouri, 621, 626, 664-665, 681 Times Beach, 40-42, 268, 368-370, 693694 Mixed-function oxidase activity, 131, 155, 156 Monsanto Company, 34, 35, 38, 305-307, 444, 674, 700 Montagnards, 31, 371, 599 Mortality studies cancer, 442-445 death certificate data, 236-237 methodology, 229-233, 435 standardized mortality ratio, 229-230 Motor coordination dysfunction environmental studies, 658-659 herbicide association in, 661-662 occupational studies, 658 Vietnam veterans' risk, 662 Motor/sensory/coordination problems, 14, 658662 MPTP, 661 Multiple myeloma, 331, 334, 335, 336, 341 in agricultural/forestry workers, 558-561 biologic plausibility of TODD in, 563 epidemiologic studies, 331, 334, 335, 336, 341, 557-563 epidemiology, 526, 528 herbicide association in, 10, 11-12, 563, 574, 576 histopathology, 527 Vietnam veterans' risk, 563 Myocardial infarction, 708 N Nasal/nasopharyngeal cancer clinical description, 457-458 epidemiology, 458-459 herbicide association in, 13, 19, 460, 577
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From page 804... ...
385, 724 National Research Council, 20, 62-64 National Toxicology Program, 139-141 National Veterans Legal Services Project, 60 National Vietnam Veterans Birth Defects/ Learning Disabilities Registry and Data Base, 741-742 National Vietnam Veterans Readjustment Study, 79, 83, 655 Navy, 81, 280-281, 286 herbicide use in, 95 non-Hodgkin's lymphoma odds ratio in, 542 Vietnam casualties, 83 Nebraska, 9, 37, 332, 333-334, 535 Neonatal death. See Perinatal death Netherlands, 316-317, 323, 325-326, 443, 464, 468, 477, 558 Neurasthenia, 649 Neurobehavioral toxicity, 2,4-D, 180 Neuroblastoma, 594 in children, 628 Neurologic disorders assessment issues, 14, 641-642 childhood cancer, 628 classification of, 640 cognitive and neuropsychiatric effects, 649658 compensation for Vietnam veterans, 55 2,4-D in, 179 epidemiologic studies, 44 45, 643-648 herbicide association in, 14, 657, 661, 666 motor/coordination dysfunction, 14, 658-662 in occupational studies, 649-651, 658, 662663 peripheral nervous system disorders, 662-666 in Seveso, Italy, studies, 365-366, 523 TCDD in, 160-166 in Vietnam veterans' offspring, 609, 660 Vietnam veterans' risk, 658, 662, 666 INDEX New Hampshire, 341, 364 New Jersey, 656, 695 Agent Orange Commission, 60, 280-281, 401~02, 741 New Mexico, 60, 402 New York, 60, 364-365, 402-403, 444, 470, 495, 626 New Zealand, 329-331, 373, 486, 490, 535536, 552, 560-561 Non-Hodgkin's lymphoma age of onset, 436 in agricultural/forestry workers, 530-540 compensation for Vietnam veterans, 51, 5556 2,4-D in, 256-257 environmental studies, 540-541 epidemiologic studies, 328, 329, 330, 331, 333-334, 335-338, 383, 384, 391-393, 401, 528-540, 573-574 epidemiology, 526, 527 herbicide association in, 8-10, 548, 573-574 histopathology, 526 in paper/pulp workers, 540 in production workers, 9, 529-530, 548 research recommendations, 19, 727 in Selected Cancers Study, 234-235 in Vietnam veterans, 9, 401, 526, 541-548, 549 Northeast Pharmaceutical and Chemical Corporation, 40 Null hypothesis, 225 o Occupational exposure, 5, 303 cancer mortality, 443-444 as cancer risk factor, 442 epidemiologic studies, 303-365 exposure assessment strategies, 253-256, 258-259, 262-267, 269-270 pulp/paper workers, 37-38, 267, 341, 364, 443, 447, 454, 468, 516, 523, 540, 561562, 568 research recommendations, 15-16, 731 vs.
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From page 805... ...
See Porphyria cutanea tarda Pennsylvania, 60, 403, 562 Perimeter spraying. See Ground/perimeter spraying Perinatal death definitions, 618-619 descriptive epidemiology, 619-620 epidemiological studies, 620-624 herbicide association in, 14, 624 risk factors, 619-620 TODD biologic plausibility in, 624 Peripheral nervous system disorders, 55, 662666 environmental studies, 663-665 herbicide association with, 666 occupational studies, 662-663 Vietnam veterans' risk, 666 Pharmacokinetics cacodylic acid, 186-187 2,4-D, 175 picloram, 190 2,4,5-T, 182 805 TCDD, 127-133, 260-261, 284 TCDD-induced wasting syndrome, 162-166 Phenoxy herbicides, 8, 9, 10, 11, 27 action of, 27 See also Herbicides Phenoxyenolpyruvate carboxykinase, 172 Phenoxypropionic acids, 327 Phytar 560-G, 89 Picloram, 88, 90, 91 acute toxicity, 191 animal studies, 189-192 carcinogenicity, 118, 119, 190-191 chemical properties, 189 chemical structure, 111, 114-115 chronic exposure, 191-192 developmental/reproductive toxicity, 192 domestic use, 189 genotoxicity, 191 immunotoxicity, 122-123, 192 liver toxicity, 125 metabolism, 115, 116 pharmacokinetics, 190 Pleurisy, 711, 713 Pneumoconiosis, 713 Pneumonia, 710, 713 Pointman Project, 60, 280, 401-402, 656 Polychlorinated dibenzodioxins, 126, 327 Polymorphonuclear neutrophils, 148 Porphyria, 153-154 Porphyria cutanea tarda clinical features, 679 compensation for Vietnam veterans, 50, 55 epidemiologic studies, 680-682 herbicide association in, 10, 682 Vietnam veterans' risk, 682-683 Posttraumatic stress disorder, 397-398, 653 656, 658 Production workers bladder cancer, 513-517 brain cancer, 523 cancer mortality, 443-444 chloracne, 674-676 circulatory disorders, 700-701 diabetes mellitus, 684 epidemiologic studies, 36-37, 303-318 exposure assessment, 264-265 female reproductive/breast cancer, 508-510 gastrointestinal tract cancers, 447 gastrointestinal ulcers, 691 hepatic enzyme dysfunction, 686, 687 hepatobiliary cancers, 453-454, 455 Hodgkin's disease, 9
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From page 806... ...
665, 681, 687, 694 R Race/ethnicity, Vietnam veterans, 81, 82, 83, 84 Radiation exposure, 564, 595 Railroad workers, 323-324, 467, 486, 649-650. 658 Ranch Hand study, 62-63, 260, 272, 622 appropriation For, 51 autoimmune disease in, 698 circulatory disease in, 703-705, 706 data sources, 385-386 diabetes mellitus in, 684 exposure assessment in, 279-280, 281, 386 gastrointestinal ulcers in, 691 immune system disorders in, 696 lipid abnormalities in, 689 low birthweight in, 626, 627 methodology, 230-231, 385-386, 445, 757762 multiple myelomas in, 562 neurological disorders in, 659 non-Hodgkin's lymphoma in, 541 participants, 722-723 peripheral nervous system disorders in, 665 porphyria cutanea tarda in, 681-682 recommendations for, 16-17, 722-724 reproductive outcomes in, 601, 612-613, 632, 633, 727 respiratory cancers in, 469 respiratory disorders in, 711-712 role of, 53 serum TCDD levels in, 656 skin disorders in, 678 soft tissue sarcoma in, 492~93 status of, 53 TCDD half-life estimates, 260-261 TCDD serum levels, 273, 281, 285 See also Operation Ranch Hand Rectal cancer.
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From page 807... ...
INDEX Relative risk, 224, 229, 230, 239, 258 Reproductive disorders altered sperm parameters, 631, 632, 633-634 animal studies, 123-124 cacodylic acid in, 189 2,4-D in, 180-181 female reproductive system cancers, 13, 14, 505-512, 577 herbicide association in, 13-14, 605, 634 infertility, 631, 632-634 male-mediated, 593-595 methodological approach to study of, 591 592 occupational risk factors, 594-595 picloram in, 192 in Ranch Hand study, 758-762 research recommendations, 727 2,4,5-T in, 185 TCDD in, 123-124, 156-159 See also Birth defects; Low birthweight; Perinatal death; Spontaneous abortion Reproductive system cancers, women epidemiologic studies, 508-512 epidemiology, 505, 506-508 herbicide association in, 13, 14, 512, 577 histopathology, 506 Vietnam veterans' risk, 512 Research needs biomarkers, 17, 725 cost of, 727 exposure assessment, 4, 15, 16-17, 287-290, 291, 721-722, 724-728 health outcome priorities, 19, 726-727 Hodgkin's disease, 19, 727 mandated serum testing, 21, 730 military records, 17, 724-725 motor/coordination dysfunction, 660-661 neurobehavioral functioning, 657 occupational exposure data, 731 recommendations, 15-21, 721-731 research management, 16, 17-18, 723-724, 726 risk assessment, 731 Vietnamese population studies, 731 Respiratory cancers in agricultural/forestry workers, 466 compensation for Vietnam veterans, 55 epidemiologic studies, 461-472 epidemiology, 460-461 herbicide association in, 10-11, 19, 574-575 in paper/pulp workers, 468-469 in production workers, 461-466 807 risk factors, 461 in Seveso outcomes, 469 Vietnam veterans' risk, 460~61, 469-470, 472 Respiratory disorders herbicide association in, 14, 713 in paper/pulp mill workers, 341, 364 in production workers, 709-710 research methodology, 708-709, 712-713 TCDD in, 170, 472, 709-710, 712, 713-714 Vietnam veterans' risk, 713-714 Risk assessment for Vietnam veterans, 5, 221, 246 birth defects, 618 bone cancer, 474 475 cancer, 440, 442-443, 578 cancer in offspring, 630-631 chloracne, 678-679 circulatory disorders, 708 diabetes mellitus, 692 female reproductive system cancers, 512 fetal/infant death, 625 gastrointestinal cancers, 452 genitourinary tract cancers, 522 hepatic enzyme disorders, 692 hepatobiliary cancers, 457 Hodgkin's disease, 557 immune system disorders, 699 leukemia, 571-572 lipid abnormalities, 692 low birthweight outcomes, 628 motor/coordination dysfunction, 662 multiple myeloma, 563 nasal/nasopharyngeal, 460 neuropsychiatric outcomes, 658 non-Hodgkin's lymphoma, 549 peripheral nervous system disorders, 666 porphyria cutanea tarda, 682-683 reproductive outcomes, 634 respiratory cancer, 472 respiratory disorders, 713-714 skin cancer, 505 soft-tissue sarcoma, 500 spontaneous abortion, 605 Risk assessment methodology, 5, 221, 246 EPA dioxin research, 59-60 predisposing, factors, 731 relative risk determination, 224, 229, 258 standardized mortality ratio in, 229-230 strength of association in, 239 terminology, 224 Rung Sat Special Zone, 100, 104, 105, 106
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From page 808... ...
808 S Seasonal factors in herbicide distribution, 26, 87 Selected Cancers Study goals, 59, 387, 391 Hodgkin's disease in, 554-556 liver cancer in, 455 methodology, 57, 234-235, 243, 258, 391393, 440, 527 nasal/nasopharyngeal cancer, 459 non-Hodgkin's lymphoma in, 9, 541-543, 573 soft-tissue sarcoma in, 493, 498 Selective herbicides, 24, 88 Self-Report Symptom Inventory, 641 Serotonergic system, 166 Serum levels, TCDD in CDC validation study, 281-284 mandated testing, 728, 729 measurement technique, 260 pharmacokinetics, 259-261 recommendations, 20-21 significance of, 4, 19, 261, 284-285, 289, 290, 725, 742-743 Services HERBS tapes, 97-98 Seveso, Italy accidental contamination in, 43 bladder cancer, 517 brain tumors, 523 cancer mortality, 444 chloracne, 267, 676-677 circulatory disorders, 701-702 epidemiologic studies, 44-45, 63, 365-368 exposure assessment, 267-268, 285, 598599 female reproductive cancers, 511 gastrointestinal ulcers, 691 hepatic enzyme disorders, 686-687 immune modulation, 695 leukemia, 13, 569-570, 571 lipid abnormalities, 689 liver cancer, 454 455 liver disorders, 367 lung cancer, 469 mortality studies, 652 multiple myeloma, 562 neuropsychiatric outcomes, 651-652 non-Hodgkin's lymphoma, 540-541 peripheral nervous system disorders, 663664 porphyria cutanea tarda, 680-681 INDEX prostate cancer, 11 reproductive outcomes, 598-599 respiratory outcomes, 710 response to accident, 43-44 skin cancer, 503 soft-tissue sarcoma, 491-492 Silvex, 309, 324 Skin cancer animal studies, 141, 142-143 biologic plausibility for TCDD, 503 clinical features, 501, 502 epidemiologic studies, 502-503 epidemiology, 501-502 herbicide association in, 12, 576 TCDD in, 141, 142-143, 502-503 Skin sensitivity to 2,4-D, 181 to picloram, 192 to TCDD, 172-174 See also Chloracne; Porphyria cutanea tarda Sleep disorders, 650 Soft-tissue sarcoma, 311, 314 age of onset, 436 in agricultural/forestry workers, 322, 326 328, 329-330, 335-336, 337, 339-340 biologic plausibility of TCDD in, 500 case-control studies, 481-491 in children, 628 clinical features, 475, 476 in cohort studies, 231, 243 compensation for Vietnam veterans, 51, 55, 56 environmental exposure studies, 375, 383, 384 epidemiologic studies, 231, 476, 477-500 epidemiology, 475 herbicide association in, 8, 9-10, 500, 572 573 in pesticide applicators, 491 in production workers, 8, 477-479, 499 research recommendations, 19, 727 risk factors, 10, 477 in Vietnam veterans, 395-396, 401, 475, 492-498, 500 Somatostatin, 168, 169 South Korea, 61-62 Special Forces, 286 Sperm parameter disorders, 631, 632, 633-634 Spina bifida, 609, 611, 612 Spontaneous abortion, 592 in agricultural/forestry workers, 336-337 in Alsea, Oregon, case, 42-43, 372-373, 598
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From page 809... ...
. dloxm TCDD biologic plausibility Ah receptor in, 133-138 animal carcinogenicity studies, 138-146, 439 in brain tumors, 525 carcinogenesis, 116-118, 434, 439 cardiovascular toxicity, 171 in childhood cancer, 630 in chloracne, 172-174, 678 in fetal/infant death, 624 gastrointestinal toxicity, 169-170, 451 in genitourinary tract cancers, 521-522 in hepatobiliary cancers, 457 in Hodgkin's disease, 557 in immune system disorders, 122, 146-151, 699 in leukemia, 571 in motor dysfunction, 661 in multiple myeloma, 563 in nasal/nasopharyngeal cancer, 460 in neurological disorders, 160-166 in non-Hodgkin's lymphoma, 549 in porphyria cutanea tarda, 682 in reproductive disorders, 123-124, 156159, 605, 618, 634 respiratory toxicity, 170 in skin cancer, 503 in soft-tissue sarcoma, 500 Teratogenicity, 57, 62, 606-607 cacodylic acid, 189 2,4-D, 180-181 picloram, 192 2,4,5-T, 185, 373-374 TCDD, 28, 30, 123, 159-160, 185, 368, 370, 372 viral potential, 607 See also Birth defects Testicular cancer, 405 epidemiologic studies, 519 epidemiology, 515 herbicide association in, 13, 521 histopathology, 513 Vietnam veterans' risk, 519, 522 Testosterone, 123, 157-158 Tetrachlorobenzene, 28 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)
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From page 810... ...
acute toxicity' 184 in A,,ent Orange, 27 animal studies, 181-185 carcino$enicity, 37, 118, 119, 182-184 chemical properties, 114, 182
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From page 811... ...
military herbicide use in, 1, 3, 24, 27, 84-85, 89-93, 94-96, 98-107, 286 Vietnam Experience Study cancer mortality in, 444" 445 childhood cancer in, 629 chloracne in, 677 circulatory disorders in, 702 Hodgkin's disease in, 556 immune system disorders in, 696 liver cancer in, 455 low birthweight outcomes in, 626 lung cancer in, 469 methodology, 57-58, 281, 284, 389-391 neonatal death in, 622 neurologic/neuropsychiatric outcomes in, 656 non-Hodgkin's lymphoma in, 542-543 origins, 50 reproductive outcomes in, 601, 609, 610611, 626, 632 respiratory disorders in, 710-711 Vietnam Veteran Agent Orange Health Study, 741 Vietnam veterans, 1 advocacy groups, 60-61 altered sperm parameters in, 632, 634 Australian, 61, 91, 406, 418, 444, 470, 496497, 546, 614-615, 633, 702, 710 autoimmune disease in, 698, 699 birth defects in children of, 609-615, 618 bladder cancer in? 517 bone cancer in, 473, 474 475 brain tumors in, 522, 523, 525 cancer in children of, 629, 630-631 cancer mortality, 444 145 cancer studies, 391-393, 401, 402-403, 405, 436-438 chloracne in, 677-679 circulatory disorders in, 702-705 class action suit, 34-35 compensation for, 34-35, 47, 50-51, 55-56 congressional responses to concerns of, 4652 defining, 78 demographics, 79, 80-84 diabetes mellitus in' 684-685, 698 discharges for disabilities, 32
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From page 812... ...
812 distribution by branch of service, 81 epidemiologic studies, 50, 57-59, 62-63, 384 418 expected cancer incidence, 439-440, 442, 446,452,461,501,505,513,522,526, 564 exposure assessment strategies for, 270-284 female reproductive system cancers in, 505, 511-512, 577 gastrointestinal tract cancers in, 446 gastrointestinal ulcers in, 691, 692 genitourinary tract cancers in, 513, 518, 522 health concerns of, 1, 32-34, 46-47 hepatic enzyme disorders in, 687 hepatobiliary cancers in, 455, 457 Hodgkin's disease in, 526, 554-556, 557 immune modulation in, 695-696, 699 infertility, 632, 633, 634 leukemia in, 13, 564, 570, 571-572 lipid abnormalities in, 689, 692 low birthweight outcomes for, 626, 628 military experiences, 75, 82, 272, 286, 399 motor/coordination dysfunction in, 659-660, 662 multiple myeloma in, 526' 562, 563 nasal/nasopharyngeal cancer in, 459, 460 in National Personnel Records Center, 17 neuropsychiatric outcomes, 653-656, 658 non-Hodgkin's lymphoma in, 526, 541-548, 549 number of, 3, 4, 74, 75-80 peripheral nervous system disorders in, 665, 666 porphyria cutanea tarda in, 681, 682-683 prostate cancer in, 513, 518, 519, 522 records-based exposure assessment, 271-280 reproductive outcomes, 405-406, 418, 601 603, 609-615, 618, 620-622, 625 respiratory cancers in, 469-470, 472 respiratory disorders in, 710-712, 713-714 risk assessment for, 14-15, 221, 225-226, 247-248, 578 serum testing, 20-21 skin cancer in, 501, 505 soft-tissue sarcoma in, 475, 492-498, 500 INDEX South Korean, 61-62 spontaneous abortions in, 601-603, 605 suicide incidence, 655-656 twin studies, 398-399, 406, 703, 711 women, 50, 83-84 Vietnam Veterans of America, 60 Vietnamese epidemiologic studies, 599-601 exposure assessment, 269, 370-372 reproductive outcomes, 599-601, 608-609 research recommendations, 731 Viral infection immune system response, 692-693 TCDD-enhanced susceptibility, 149 teratogenic potential, 607 Vitamin A, 174 W War Research Service, 25 Washington state, 336-338, 341, 487~88, 535 Wasting syndrome, TCDD-induced, 162-166 Wechsler Adult Intelligence Scales, 641 West Virginia, 60, 404, 470, 496, 546, 621, 662-663, 686, 689, 700 Nitro accident, 38-39, 305-307, 597, 607, 686, 700 Wilm's tumor, 594 Wisconsin, 37, 60, 336, 404 1-05, 445, 455, 470, 496, 517, 523, 534, 546, 556, 560, 702, 710 Women veterans, 79 circulatory disease in, 702 epidemiologic studies, 50, 81 expected cancer incidence, 440, 461, 501, 505,513,522,526,564 mortality studies, 394-395, 470, 545 research recommendations, 728 statistics, 83-84 See also Reproductive system cancers, women World Health Organization Mortality Data Bank, 314 World War II, 25, 32, 82
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