Index
A
Adipose tissue, TCDD distribution, 130, 131, 168-169, 259, 269, 280
early military research, 25-26
Aflatoxin, 453
Agent Blue, 27, 89-90, 93, 97, 100
Agent Orange
amount used in Vietnam, 1, 27, 74, 90, 97-98, 106
chemical composition, 27
disposal of Vietnam surplus, 93-94
effectiveness as defoliant, 90
federal government action/research, 45-60
legislation, 47-52
military application in Vietnam, 1, 3, 27, 74, 84-85, 90, 92-93, 97-107, 543-545
Orange II formulation, 90
product liability litigation, 34-35
suspension of use, 92-93
TCDD as contaminant of, 91, 114, 126-127
Vietnam veterans' concerns, 32-34
See also Herbicides
Agent Orange, the Deadly Fog, 33
Agent Orange Act of 1991, 2, 7, 20, 21, 51, 572, 721, 728-730
Agent Orange Briefs, 56
Agent Orange Registry, 20, 53, 56, 729
Agent Orange Review, 56
Agent Orange Scientific Task Force, 60-61
Agent Orange Study, 19, 57, 58-59, 63-64, 276-278
Agent Orange Victims International, 34
Agent Orange Working Group, 19, 46, 58, 277, 743
research methodology, 728
TCDD in, 126
Agent White, 27, 90, 92-93, 97, 115, 189
Agricultural/forestry workers
cancers, 13, 37, 320-323, 443, 447, 454
case-control studies, 326-341, 486-488
cohort studies, 318-323
epidemiologic studies, 37, 318-323
exposure assessment, 265-266
female reproductive and breast cancers, 510-511
hepatobiliary cancer, 454
Hodgkin's disease, 550-553
kidney cancer, 515
multiple myelomas, 11-12, 558-561
reproductive outcomes, 510-511, 598
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 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
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
δ-Aminolevulinic acid synthetase, 153-154
Amitrole, 323
Angina, 708
Animal studies
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
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-mediated 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
Armed Forces Institute of Pathology, 494
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
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
B
BASF, 312-313, 444, 530, 550, 558
Beck's Depression Inventory, 650, 651
Bias, methodological. See Methodological bias
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/infant 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
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
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
herbicide association in, 13
histopathology, 505-506
risk factors, 507
Vietnam veterans' risk, 505, 511
Bureau of Labor Statistics, 79, 80
n-Butyl esters, 27
C
Cacodylic acid, 88-89
acute toxicity, 188
animal studies, 185-189
carcinogenicity, 118, 119, 187
chemical properties, 186
chronic exposure, 188-189
developmental toxicity, 124, 189
domestic use, 185-186
formulations in Vietnam, 186
kidney toxicity, 125
pharmacokinetics, 186-187
reproductive toxicity, 124, 189
California, 341
Camp Drum, New York, 25-26, 89
Canada, 11, 319-320, 323, 374-375, 443, 467-468, 537-539, 620, 650
Cancer
age-specific incidence, 436-438
in agriculture workers, 320-323, 443
biologic plausibility, 116-118, 119, 434
categories of herbicide association in, 572
in children, 14, 594-595, 628-631
clinical features, 433-436
environmental exposure epidemiologic studies, 444, 469
epidemiologic studies, 45, 317, 320-323, 325-326, 367, 383-384, 391-393, 443-445
epidemiology, 433, 435-438, 442, 525
evidence of no herbicide association in, 12-13, 576-577
expected incidence in Vietnam veterans, 439-440, 442, 452, 460-461, 473, 475, 501, 505, 513, 522, 526, 564
in herbicide/pesticide applicators, 320-321, 323, 325-326, 443, 447 , 466-468, 488, 491
insufficient evidence for determining herbicide association in, 13 -14, 577-578
latency effects in studies, 231-232, 434, 435, 436-438, 494, 495, 727
limited/suggestive evidence of herbicide association in, 10-12, 574-576
mortality studies, 442-445
multistage model, 142-143, 434, 439
occupational studies, 443-444
P450 induction to, 144-145, 170
phenoxy herbicide association in, 483
research recommendations, 19, 727
sufficient evidence of herbicide association, 8-10, 572-574
TCDD animal studies, 138-142
TCDD genotoxicity, 143-144
TCDD in initiation/promotion, 116, 142-143, 434, 439
TCDD in P450 induction to, 144-145
Vietnam veterans' risk, 391-393, 401, 402-403, 405, 436-438, 444-445, 578
See also Carcinogen(s);
specific cancer;
specific cancer site
Carcinogen(s)
cacodylic acid as, 118, 119, 187
herbicides as, 3
mechanism of action, 434
picloram as, 118, 119, 190-191
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, 611-612
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 Neurologic disorders
Cerebrospinal Malformation Study, 610
Cerebrovascular disease, 702
Cervical cancer, 13, 505, 509, 510, 512
Chemical production
Agent Orange product liability litigation, 34-35
hexachlorophene, 40
TCDD contamination in, 91, 126
See also Industrial accidents;
Production workers
Chemoreception
characteristics of, 133-134
dioxin-responsive enhancers in, 135-136
estrogen-mediated, 145
TCDD dose-response linearity, 137-138
in TCDD hepatotoxicity, 154-155
in TCDD-induced wasting syndrome, 164
See also Ah receptor
Children, cancer in, 14, 594-595, 628-631
China, 458
Chloracne, 39
animal studies, 173-174
in chemical production workers, 308, 310, 316
clinical features, 672-673
compensation for Vietnam veterans, 50, 51, 55, 56
diet and, 174
epidemiologic studies, 674-678
herbicide association in, 10, 678
in Seveso accident, 366-367
skin cancer and, 502
as TCDD biomarker, 4, 10, 28, 172-173, 262, 401, 672-674
Chlordane, 91
Chlorodibenzodioxins, 28
Chlorophenols, 9
Circulatory disorders
epidemiologic studies, 700-707
herbicide association in, 14, 708
research methodology, 699-700
Cleanup efforts
after Nitro accident, 38
Agent Orange disposal, 93-94
Cleft lip/palate, 373-374, 375, 611, 612
Coast Guard, 81
Cognitive neuropsychiatric disorders
environmental studies, 651-653
herbicide association in, 657-658
occupational studies, 649-651
Vietnam veterans' risk, 653-656
Cohort studies
agriculture/forestry workers, 318-323
definition, 229
exposure assessment for, 254-256
methodology, 229-232
Colon cancer.
See also Gastrointestinal tract cancers
in agricultural workers, 328-329
herbicide association in, 12-13, 576-577
Colorectal cancer, 446
Vietnam veterans' risk, 447, 450, 451, 452
Compensation for veterans, 227
congressional legislation, 47, 50-51
Department of Veterans Affairs, 55-56
product liability litigation, 34-35
Confidence intervals, 244
Corticosterone, TCDD and, 168, 171-172
Cytochrome P450. 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 workers studies, 265-266, 318-341
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, 222-223, 241-242
organization of, 737
presentations/reports to committee, 739-756
randomized controlled trials, 227-228
recommendations for future research, 287-289, 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
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, 371-372
women veterans, 83-84
See also Epidemiologic studies;
Military records
Death certificates, 236-237
Defoliants
Agent Orange as, 90
tactical role of, in Vietnam, 85
Vietnam herbicide mission maps, 99-100
Demographic data, Vietnam veterans, 79, 80-84
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
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, 54-55
veterans' advocacy groups and, 61
Vietnam veteran epidemiologic studies, 50, 393-399, 445, 469-470, 493-495, 543-547, 562
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
chronic exposure, 179-180
developmental toxicity, 124, 180-181
domestic use, 174-175, 177-178
formulations, 175
ingestion of, 653
kidney toxicity, 125
liver toxicity, 125
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
therapeutic application, 659
See also Herbicides
Diet
breast cancer and, 507
in cancer risk, 442
chloracne and, 174
gastrointestinal cancers and, 446
Dinoxol, 91
Dioxin. See 2,3,7,8-Tetrachlorodibenzo-p-dioxin
Dioxin Registry, 36-37
Dioxin-responsive enhancers, 135-136
Diquat, 91
Domestic herbicide use
agricultural use, 24, 35, 39, 174-175, 181
2,4,-D, 174-175
picloram, 189
2,4,5-T, 181-182
TCDD contamination in, 91
See also Agricultural/forestry workers
Dopaminergic system, 163-164, 165
Dose-response relationship
2,4-D pharmacokinetics, 175
dermal application of TCDD, 128-129
evidentiary role of, 239-230, 252
fetal mortality in animals, 159
research recommendations, 19, 727
TCDD-chloracne, 673
in TCDD-exposed workers, 445
TCDD-immune system processes, 696
TCDD immunotoxicity, 122
TCDD threshold, 137-138
TCDD tissue distribution, 130
Dow Chemical Company, 34, 35, 307-312, 461-462, 529, 558, 598, 607, 620, 674
DVA. See Department of Veterans Affairs
Dystonia, 658
E
Electrical transformers, 364-365, 444, 626, 675
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, 454-455, 469
chloracne and, 676-677
circulatory disorders and, 701-702
epidemiologic studies, 3, 301, 365-384, 469
evidentiary role of research on, 4-5, 222-223, 241-242
exposure assessment strategies, 262-263, 267-270
female reproductive system cancers and, 511
hepatobiliary cancers and, 454-455
immune modulation and, 693-694
leukemia and, 568-570
motor/coordination dysfunction and, 658-659
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, 326-341
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, 303-318
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
cost of, 727
diabetes mellitus, 684-685
environmental exposures, 365-384
evaluation of, 300-301, 591-592, 737-738
evidentiary role of, 224-225, 228-237, 300, 305
exposure assessment for, 251-259
exposure reconstruction model and, 725, 726-728
female reproductive system/breast cancers, 508-511
gastrointestinal tract cancers, 446-447
gastrointestinal ulcers, 691
hepatic enzyme disorders, 686-688
hepatobiliary cancers, 453-455
herbicide/pesticide applicators, 323-326
Hodgkin's disease, 9, 329, 331, 335-336, 341, 384, 391, 393, 549-553, 549-556, 574
immune modulation, 693-696
infertility, 632-633
kidney cancer, 515
leukemia, 13, 332-333, 334-335, 564-571, 577-578
lipid abnormalities, 688-690
liver cancer, 13, 329, 391, 393
low birthweight, 626-627
meta-analysis, 225, 237-238, 242-243, 243, 244
motor/coordination dysfunction, 658-661
multiple myeloma, 11-12, 331, 334, 335, 336, 341, 557-563, 576
nasal/nasopharyngeal cancer, 459
neurological disorders, 365-366, 642-648
neuropsychiatric disorders, 649-657
non-Hodgkin's lymphoma, 9, 328, 329, 330, 331, 333-334, 335-338, 383, 384, 391-393, 401, 528-548, 573-574
NRC Commission on Life Sciences, 63
perinatal death, 620-624
peripheral nervous system disorders, 662-666
porphyria cutanea tarda, 680-682
proportionate mortality studies, 232-233
prostate cancer, 11, 518-519, 575-576
recommendations, 15-20, 721-725, 731
reproductive outcomes, 41-42, 311-312, 321, 364-365, 368, 370, 371-375, 387-388, 389-390, 591-592
resolution in, 242-243
respiratory cancers, 10-11, 364, 461-472, 575
respiratory disease, 709-713
of Seveso population, 44-45, 365-368, 444, 454-455, 469, 491-492, 503, 511, 517, 523, 540, 568-570, 571, 598-599
skin cancer, 502-503
soft tissue sarcoma, 8, 311, 326-328, 329-330, 335-336, 337, 339-340, 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
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
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
Stellman's 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
Food crops, 89
Agent Orange in destruction of, 62, 90
as military target, 27, 31, 87, 97, 98-100, 106
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, 576-577
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
male-mediated reproductive outcomes, 593-594
picloram in, 191
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
TCDD induction of, 136-137
transforming, 145
H
Halogenated aromatic hydrocarbons, 125, 126, 151
in hepatic enzyme induction, 155
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, 577-578, 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, 519-521, 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 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
settings for occupational exposure, 36-38
sufficient evidence of association in health outcomes, 8-10, 246-247, 500, 548, 556-557, 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
in exposure assessment, 273-279, 287, 291
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
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
in TCDD carcinogenesis, 116, 145
TCDD in, 156-159
in TCDD-induced wasting syndrome, 165
Hourglass spray system, 25
Hydatidiform mole, 30, 600-601
Hypercholesterolemia, 690
Hyperlipidemia, 152-153, 688, 692
Hypertension, 705, 706, 707, 708
Hyperthyroidism, TCDD-induced, 168
Hypoglycemia, TCDD-induced, 166-168
I
I Corps, 52, 96, 98, 394, 493-494, 542, 543, 546
mortality study, 233
II Corps, 542
III Corps, 59, 104, 276, 281-282, 542, 543
Immune system
autoimmunity, 697-699
cellular immunity, 147
2,4-D toxicity, 181
endocrine system and, 150-151
herbicide toxicity, 122-123
humoral immunity, 147-148
immune modulation in, 692-696, 698-699
macrophage function, 148
picloram toxicity, 192
research methodology, 692
suppression in, 693
TCDD toxicity, 119-122, 146-151, 338
Immunoglobulin antibodies, 693, 696, 697
Incineration, of Agent Orange, 93-94
Industrial accidents, 316-317
BASF, 312-313, 444, 530, 550, 558
Nitro, West Virginia, 38-39, 305-307, 597, 607, 686, 700
Industrie Chimiche Meda Societa Anonima, 43
Infertility, 631-634
Influenza, 713
Institute of Medicine, 2, 20, 57, 62-64, 742, 743-744
Insufficient evidence for determining herbicide association
in altered sperm parameters, 14, 634
basis for finding of, 13, 247, 577
in bone cancer, 13, 473-474, 577
cancer in children of Vietnam veterans, 14, 630
in circulatory disorders, 14, 708
in cognitive and neuropsychiatric disorders, 14, 657-658
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 lipid abnormalities, 14, 691
in motor/coordination dysfunction, 14, 661
in nasal/nasopharyngeal cancer, 13, 460, 577
in neuropsychiatric outcomes, 14, 657, 666
in peripheral nervous system disorders, 14, 666
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), 8, 12-13, 246, 264-265, 270, 313-314, 478, 479, 499, 565, 573, 577, 731
International Register of Workers Exposed to Phenoxy Herbicides and Their Contaminants, 313-314
Intrauterine growth retardation, 625, 626
Iowa, 11, 37, 60, 318-319, 332, 333, 334-335, 374, 400, 447, 495, 534, 550, 560, 567, 603, 660, 677
Italy, 320-321, 338-340, 340-341, 384, 486-487, 492, 523, 537, 552 , 553, 561, 566, 632
See also Seveso, Italy
J
Job exposure matrix, 256
Johnston Island, 93
K
Kansas, 9, 37, 335-336, 487, 490, 550
Kaposi's sarcoma, 338, 487, 695
Kidney cancer
in children, 628
epidemiologic studies, 515
herbicide association in, 13, 521, 577
histopathology, 513
risk factors, 514
Vietnam veterans' risk, 522
Kidneys, 2,4-D toxicity in, 125, 179-180
L
Laos, 106
Laryngeal cancer, 461, 470-471
See also Respiratory cancers
Latency effects in cancer studies, 231-232, 434, 435, 436-438, 494 , 495, 727
Lawn care products, 119, 177-178
Legal issues
Agent Orange manufacturers' liability, 34-35
federal government liability, 34
South Korean Vietnam veterans, 62
in Times Beach, Missouri, 41
Legislation
Agent Orange Act of 1991, 2, 7, 20, 21, 51, 572, 721, 728-730
federal, 45-60
Public Law 102-4, 2, 7, 20, 21, 51, 572, 721, 728-730
Vietnam veterans' compensation, 47, 50-51, 55-56
Leiomyosarcomas, 475
Leukemia
in agricultural workers, 13, 332-333, 334-335, 566-568
in children, 628
epidemiologic studies, 564-572
epidemiology, 564
herbicide association in, 13, 571, 577-578
in production workers, 564-566
in pulp/paper workers, 568
risk factors, 564
in Seveso, Italy, 13, 568-570, 571, 577
TCDD biologic plausibility in, 571
Vietnam veterans' risk, 564, 570, 571-572
Limited/suggestive evidence of herbicide association
basis for finding of, 10-12, 247, 574-575
in cancer, 10-12, 519-521, 574-576
in multiple myeloma, 10, 11-12, 563, 574, 576
in prostate cancer, 11, 519-521, 575-576
research recommendations, 19, 727
in respiratory cancers, 10-11, 472, 574, 575
Limited/suggestive evidence of no herbicide association
basis for finding of, 12-13, 224, 247, 576-577
in gastrointestinal tract cancers, 12-13, 447-451, 576-577
in urinary bladder cancer, 12, 521, 576
Lindane, 91
Lipid abnormalities, 688-690, 692
epidemiologic studies, 45
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, 454-455
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, 691-692
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 birthweight
definition, 625
epidemiology, 625-626
herbicide association in, 14, 627-628
risk factors, 625-626
Low-density lipoprotein receptors, 154-155
Lung cancer
in agricultural/forestry workers, 466
cacodylic acid and, 187
2,4-D in, 177
herbicide association in, 472
in herbicide/pesticide applicators, 326, 466-468
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
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
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
reproductive outcomes 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
BASF 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, 641-642, 649
neuropsychiatric studies, 657
NIOSH studies, 303-305
Nitro, West Virginia, industrial accident studies, 305-307
NRC Commission on Life Sciences, 63
odds ratio determination, 234, 239
Office of Technology Assessment, 19, 728
paper/pulp mill worker studies, 341, 364
Ranch Hand study, 230-231, 385-386, 498, 757-762
relative risk assessment, 229, 239, 258
reproductive outcome studies, 591-592
respiratory disease studies, 708-709, 712-713
risk assessment, 225-226
sample size and disease frequency, 231, 242-243, 440, 499
Selected Cancers Study, 234-235, 498
self-reports, 270-271
soft tissue sarcoma studies, 482-490, 497-500
standardized mortality ratio, 229-230
statistical significance/power, 226-227, 243
TCDD biomarkers, 259-262
Times Beach studies, 368-370
type I error, 243
type II error, 243
See also Data sources;
Methodological bias;
Research needs;
Risk assessment methodology
Methods of herbicide application
early military research, 25-26
in Operation Ranch Hand, 85-87
in Vietnam, 1, 3, 24, 27, 74, 85-87, 94-96
2-Methyl-4-chlorophenoxyacetic acid, 700
6-Methyl-1,3,8-trichlorodibenzofuran, 153
Midwest Research Institute, 29-30
Military operations
aerial spraying of herbicides in Vietnam, 27, 85-91
banning of strategic herbicide use, 32, 45
disposal of surplus Agent Orange, 93-94
distribution of personnel in Vietnam, 81, 82
early herbicide research, 25-26
early objections to herbicide use in Vietnam, 29, 31-32
ground spraying of herbicides in Vietnam, 94-96
herbicide applications in Vietnam, 1, 3, 24, 27, 74, 84-96, 98-107, 286
precautions in herbicide use, 95
South Vietnam tactical zones, 98
U.S. involvement in Vietnam, 75-76, 84
Vietnam troop movements, 52-53, 96, 273-279, 287
See also Military records;
Operation Ranch Hand
Military records, 742-743
for exposure assessment, 271-280, 287-288
ground spraying of herbicides in Vietnam, 94, 95
of herbicide spray missions, 27, 62, 84-85, 104-106
recommendations for research, 17, 724-725
Vietnam casualties, 82-83
Vietnam veterans in, 75-80, 106
Minnesota, 37, 326, 332, 333, 468
Minnesota Multiphasic Personality Inventory, 641
Miscarriages. See Spontaneous abortion
Missouri, 621, 626, 664-665, 681
Times Beach, 40-42, 268, 368-370, 693-694
Mixed-function oxidase activity, 131, 155, 156
Monsanto Company, 34, 35, 38, 305-307, 444, 674, 700
Mortality studies
cancer, 442-445
death certificate data, 236-237
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, 658-662
MPTP, 661
Multiple myeloma, 331, 334, 335, 336, 341
in agricultural/forestry workers, 558-561
biologic plausibility of TCDD in, 563
epidemiologic studies, 331, 334, 335, 336, 341, 557-563
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
treatment, 458
Vietnam veterans' risk, 460
Nasal olfactory mucosa, 130
National Academy of Sciences (NAS), 2, 28-29, 31, 43, 47, 51, 55, 57
National Cancer Institute (NCI), 9, 30, 37, 439
National Institute for Occupational Safety and Health (NIOSH), 8, 12, 36-37, 260, 264, 270, 285, 303-305, 443, 478, 479, 499, 564, 573, 577, 650-651, 686, 731
National Institutes of Health, 92
National Library of Medicine, 735
National Personnel Records Center, 17, 77, 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
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, 649-658
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, 662-663
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
Agent Orange Commission, 60, 280-281, 401-402, 741
New York, 60, 364-365, 402-403, 444, 470, 495, 626
New Zealand, 329-331, 373, 486, 490, 535-536, 552, 560-561
Non-Hodgkin's lymphoma
age of onset, 436
in agricultural/forestry workers, 530-540
compensation for Vietnam veterans, 51, 55-56
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
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
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, 561-562, 568
research recommendations, 15-16, 731
vs. Vietnam veteran exposure, 4, 285, 290
See also Agricultural/forestry workers;
Production workers;
Professional
pesticide/herbicide applicators
Operation Ranch Hand, 3, 4, 15, 16-17, 24, 74
application techniques, 25, 85-86, 87-88
disposal of surplus herbicide, 93-94
herbicide formulations, 88-91
number of military personnel in, 94, 273
objectives, 85
operations data, 86, 87, 92, 106-107
suspension of, 27, 31, 32, 92-93
targeting procedures, 86
See also Ranch Hand study
Ovarian cancer, 338-339, 506, 510-511
herbicide association in, 13, 512
See also Reproductive system cancers, women
P
PACER HO, 93
Pancreatic cancer. See Gastrointestinal tract cancers
Paper/pulp industry workers
cancers in, 443, 454, 468, 516, 523, 540, 568
chemical exposures in, 37-38, 267
epidemiologic studies, 38, 341, 364
Parkinsonism, 661
PCT. See Porphyria cutanea tarda
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
TCDD biologic plausibility in, 624
Peripheral nervous system disorders, 55, 662-666
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
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
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
liver toxicity, 125
pharmacokinetics, 190
Pneumoconiosis, 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
immune system disorders, 697-698
lipid abnormalities, 688-689
multiple myeloma, 557-578
nasal/nasopharyngeal cancers, 458, 459
neurologic/neuropsychiatric disorders, 649, 650-651, 662-663
non-Hodgkin's lymphoma, 9, 529-530, 548
porphyria cutanea tarda, 680
prostate cancer, 518
renal cancer, 515
reproductive outcomes, 596-598, 607, 620, 621
respiratory cancer, 10, 461-466, 471
respiratory disorders, 709-710
skin cancer, 502
soft tissue sarcoma, 8, 477-479, 499
testicular cancer, 519
See also Industrial accidents
Professional pesticide/herbicide applicators
cancer in, 320-321, 323, 325-326, 443, 447, 466-468, 488, 491
epidemiologic studies, 323-326, 447, 466-468
exposure assessment, 266-267
reproductive outcomes, 324-325
Prolactin, 165
Proportionate mortality ratio, 232-233
Prostate cancer
epidemiologic studies, 518-519
herbicide association in, 10, 11, 519-521, 575-576
histopathology, 513
research recommendations, 19, 727
Vietnam veterans' risk, 11, 518, 519, 522
Psychiatric disorders
assessment for, 641
epidemiological studies, 649-657
herbicide association in, 14, 657
posttraumatic stress disorder, 397-398, 653-656, 658
Public concern, 1, 2, 23-24, 29-32, 35-36, 39
federal government response to, 45-60
Public Law 102-4, 2, 7, 20, 21, 51, 572, 721, 728-730
Pulmonary system
disorders in Vietnam veterans, 402
TCDD absorption, 129
See also Respiratory cancers;
Respiratory disorders
Q
Quail Run mobile home park, 268, 369-370, 455, 665, 681, 687, 694
R
Race/ethnicity, Vietnam veterans, 81, 82, 83, 84
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
methodology, 230-231, 385-386, 445, 757-762
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, 492-493
status of, 53
TCDD half-life estimates, 260-261
TCDD serum levels, 273, 281, 285
See also Operation Ranch Hand
Rectal cancer. See Gastrointestinal tract cancers
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
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
See also Birth defects;
Low birthweight;
Perinatal death;
Spontaneous
abortion
Reproductive system cancers, women
epidemiologic studies, 508-512
herbicide association in, 13, 14, 512, 577
histopathology, 506
Vietnam veterans' risk, 512
Research needs
cost of, 727
exposure assessment, 4, 15, 16-17, 287-290, 291, 721-722, 724-728
health outcome priorities, 19, 726-727
mandated serum testing, 21, 730
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
risk factors, 461
in Seveso outcomes, 469
Vietnam veterans' risk, 460-461, 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 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
S
Seasonal factors
in herbicide distribution, 26, 87
Selected Cancers Study
Hodgkin's disease in, 554-556
liver cancer in, 455
methodology, 57, 234-235, 243, 258, 391-393, 440, 527
nasal/nasopharyngeal cancer, 459
non-Hodgkin's lymphoma in, 9, 541-543, 573
soft tissue sarcoma in, 493, 498
Self-Report Symptom Inventory, 641
Serotonergic system, 166
Serum levels, TCDD
in CDC validation study, 281-284
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
circulatory disorders, 701-702
epidemiologic studies, 44-45, 63, 365-368
exposure assessment, 267-268, 285, 598-599
female reproductive cancers, 511
gastrointestinal ulcers, 691
hepatic enzyme disorders, 686-687
immune modulation, 695
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, 663-664
porphyria cutanea tarda, 680-681
prostate cancer, 11
reproductive outcomes, 598-599
respiratory outcomes, 710
response to accident, 43-44
skin cancer, 503
soft tissue sarcoma, 491-492
Skin cancer
biologic plausibility for TCDD, 503
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
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
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
in Vietnam veterans, 395-396, 401, 475, 492-498, 500
South Korea, 61-62
Special Forces, 286
Sperm parameter disorders, 631, 632, 633-634
Spontaneous abortion, 592
in agricultural/forestry workers, 336-337
definition, 595-596
environmental exposure and, 598-599
epidemiologic data, quality of, 603-605
herbicide association in, 14, 605
maternal risk factors, 596
occupational exposure and, 596-598
risk factors, 594
in Vietnam veterans' wives, 405-406, 601-603
in Vietnamese civilians, 599-601
Standardized mortality ratio, role of, 229-230
State governments, 60
Vietnam veteran epidemiologic studies by, 399-405, 495-496
See also specific state
Stillbirth. See Perinatal death
Stomach
TCDD effects in, 169
See also Gastrointestinal tract cancers
Stroke risk, in herbicide exposure, 658, 659, 660
Substance use, 655
Sufficient evidence of herbicide association
basis for finding of, 8-10, 246-247, 572
in Hodgkin's disease, 8, 9-10, 556-557, 573-574
in non-Hodgkin's lymphoma, 8-9, 10, 548, 573-574
in porphyria cutanea tarda, 10, 682
in soft tissue sarcoma, 8, 9-10, 500
Surveillance, Epidemiology, and End Result program, 336, 439-440, 506
Sweden, 8, 9, 13, 37, 322-323, 326-329, 375, 443, 444, 447, 467, 479, 480, 481, 482-486, 490, 510, 528-529, 530-533, 539, 548, 551-553, 561, 572-573
Systemic autoimmune disease, 697-699
Systemic lupus erythematosus, 697
T
2,4,5-T. See 2,4,5-Trichlorophenoxyacetic acid
in autoimmunity, 697
in immune modulation, 694, 695
in Vietnam veterans, 698
T-H Agricultural & Nutrition Company, 35
TCDD. See 2,3,7,8-Tetrachlorodibenzo-p-dioxin
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 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, 156-159, 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
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
Tetrachlorobenzene, 28
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)
Ah receptor interaction, 3, 114, 118, 122, 123, 133-138, 150, 151, 152, 159-160, 439, 452-453, 457
animal studies, 111-114, 138-142, 477
as antiestrogen, 512
autoimmunity and, 697-699
bioavailability, 128-129
biomarkers, 4, 17, 259-262, 725
in body temperature regulation, 169
carcinogenicity, 28-29, 116-118, 138-146, 439, 451
cardiovascular toxicity, 171
categorization as dioxin, 23n, 125
cell proliferation capability of, 145
chemical properties, 28, 114, 127
chemical structure, 125-126
chloracne and, 4, 10, 28, 172-173, 262
circulatory disorders and, 701-708
concerns about, 1, 2, 23-24, 28-32, 35-36
corticosteroids and, 168, 171-172
cytochrome P4501A2 and, 130, 144-145, 170, 709
developmental toxicity, 123-124, 149, 156-157, 159-160, 185
diabetes mellitus and, 683
distribution in brain, 160-161
dose-response relationships, 111-114, 122, 128-129, 130, 137-138, 445, 673, 696
environmental exposure assessment, 262-263, 267-270
environmental persistence, 288
estrogen-mediation of carcinogenesis, 144-145
excretion, 132-133
in fatty acid biosynthesis, 168-169
in female reproductive system/breast cancers, 512
gastrointestinal toxicity, 169-170, 447-452, 690-692
hepatic enzyme disorders and, 155-156, 685-688, 691-692
in hepatobiliary cancers, 457
as herbicide contaminant, 2, 3, 27, 91-92, 114, 126-127
in hexachlorophene manufacture, 40
in hypoglycemia, 166-168
in immune modulation, 694-696
immunotoxicity, 119-122, 146-151, 338, 477
in inflammatory responses, 148
in lipid abnormalities, 688-690
liver toxicity, 115-116, 124, 138-139, 142, 143, 151-156, 165-166
metabolism, 115-116, 131-133, 155
in nasal/nasopharyngeal cancer, 460
in neuropsychiatric outcomes, 649-650, 651-652, 656, 657-658, 658
non-Ah-mediated toxicity, 138
in non-Hodgkin's lymphoma, 8, 9, 528-529, 574
occupational exposure, 36-39, 262-267, 269-270, 303
as opioid antagonist, 164
oral administration, 128
pharmacokinetics, 127-133, 160, 259-261, 284
as promoter of carcinogenesis, 116, 142-143, 434, 439
reproductive toxicity, 123-124, 156-159, 368, 371-372, 597, 599, 605
in respiratory disorders, 170, 472, 709-710, 712-714
serum levels, 4, 19, 21, 261, 281-285, 289, 290, 725, 728, 729, 742-743
skin cancer and, 141, 142-143, 502-503
in soft tissue sarcoma, 477, 478, 490, 498-500
sources of exposure, 127
teratogenicity, 28-29, 30, 31, 123, 159-160, 185, 368, 370, 372
wasting syndrome, 160-161, 162-166
See also Herbicides
Thompson Chemicals Corporation, 35
Thyroid
TCDD effects, 168-169
Times Beach. See Missouri, Times Beach
Tissue distribution, TCDD, 129-131, 259
Tobacco exposure, 11, 223, 442, 461, 463
in perinatal mortality, 619-620
Topography, 25
Tordon101, 90
Transforming growth factor-α 145
2,4,5-Trichlorophenol, 28
2,4,5-Trichlorophenoxyacetic acid (2,4,5-T)
acute toxicity, 184
in Agent Orange, 27
animal studies, 181-185
chloracne and, 36
chronic exposure, 184
circulatory disorders and, 700-701
development of, 24, 26, 35, 181
developmental toxicity, 185
domestic use, 181
environmental exposure events, 42-43
liver toxicity, 125
pharmacokinetics, 182
reproductive toxicity, 185
respiratory disorders and, 709
suspension of, 1, 39, 42-43, 92, 181-182
TCDD contamination of, 2, 3, 27, 91, 114, 126, 182
teratogenicity, 30, 92, 373-374
See also Herbicides;
2,3,7,8-Tetrachlorodibenzo-p-dioxin
Triglyceride levels, 688-689
Trinoxol, 91
Tuberculosis, 711
Tumor necrosis factor, 148
Twin studies, 398-399, 406, 703, 711
U
Ulcers, gastrointestinal, 690-692
Uniroyal Inc., 35
United Kingdom, 315-316, 340, 382, 444, 462-463, 464, 477, 479, 537 , 565, 595, 689
United Nations, 45
USSR, 317
Utah, 560
Uterine cancer, 506
evidence for herbicide association, 13
See also Reproductive system cancers, women
V
Veterans Administration. See Department of Veterans Affairs
Veterans' Dioxin and Radiation Exposure Compensation Standards Act , 50
Vietnam
Con Thieu province, 96
concerns about herbicide use in, 29-32, 45
herbicide targeting in, 99-106
Khe Sanh-Thonh Son Lam area, 96
research in, 30-31
troop movements in, 52-53, 96, 287
U.S. casualties in, 82-83
U.S. 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, 610-611, 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, 496-497, 546, 614-615, 633 , 702, 710
autoimmune disease in, 698, 699
birth defects in children of, 609-615, 618
bladder cancer in, 517
brain tumors in, 522, 523, 525
cancer in children of, 629, 630-631
cancer mortality, 444-445
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, 46-52
defining, 78
diabetes mellitus in, 684-685, 698
discharges for disabilities, 32
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
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
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
soft tissue sarcoma in, 475, 492-498, 500
South Korean, 61-62
spontaneous abortions in, 601-603, 605
suicide incidence, 655-656
twin studies, 398-399, 406, 703, 711
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, 487-488, 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, 404-405, 445, 455, 470, 496, 517, 523, 534 , 546, 556, 560, 702, 710
Women veterans, 79
circulatory disease in, 702
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