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Gulf War and Health: Updated Literature Review of Depleted Uranium
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Index
A
Abrams tanks, 15, 93–94, 96–97
ventilation in, 16, 95
Absorption, 25–27
increased by skin excoriation, 27
skin, 27
via deep wounds, 27
Accuracy impairment (A-IIac), 209
Acute lymphocytic leukemia, 107
Acute myeloid leukemia, 107
Aerosols, inhalable, 93–94
Afghanistan. See Operation Enduring Freedom in Afghanistan
A-IIac. See Accuracy impairment
Alpha particles, 17
Amyotrophic lateral sclerosis, 114
Animal studies. See Nonhuman studies
Association
defining, 75
tests of, 81–82
Asthma, 113–114
Atomic Weapons Establishment workers, 142
Automated Neuropsychological Assessment Metrics Test Library, 148
B
Background, 13–22
dose-response modeling and risk assessment, 20–21
exposure of military personnel to depleted uranium, 14–16
radiologic and chemical effects of exposure to depleted uranium, 17–20
uses of depleted uranium, 14
Balkans studies, 151–153
Baltimore Veterans Affairs Medical Center (BVAMC), 15, 97, 143–151, 204, 209–210, 212
Beck Depression Inventory (BDI), 145, 147, 209
Becquerel (Bq), 17
Beta particles, 18
Bias
control of, 82–83
studies vulnerable to, 86
Biokinetic models of exposure, 25
Biologic plausibility, 80
of neurologic effects, 36
Biomarkers, 80, 160
Biotransformation, 27
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Birth defects, and other adverse reproductive outcomes, 114–115
Bladder cancer, 109–110, 199
Blood-brain barrier, 31
BNFL. See British Nuclear Fuels PLC
Bone, a primary reservoir of uranium, 28–29
Bone cancer, 108–109, 153, 198
Bosnia-Herzegovina war, 14, 16, 153
Bq. See Becquerel
Bradley fighting vehicles, 15, 93, 95, 97
Brain and other central nervous system cancers, 110, 200
Brain lipid oxidation, 35
Brain regions, accumulation in, 28
Breast cancer, 106
British Nuclear Fuels PLC (BNFL), 136–137, 204
Bronchial cancer, 123
BVAMC. See Baltimore Veterans Affairs Medical Center
C
Camp Doha fire, 15, 94–95
Cancer
biological latency of, 80
causes of, 105
incidence of, 193
Cancer outcomes, 105–111, 193–203
bladder cancer, 109–110, 199
bone cancer, 108–109, 153, 198
brain and other central nervous system cancers, 110, 200
in depleted-uranium–exposed animals, 29–30
leukemias, 107, 196
lung cancer, 88–89, 106–107, 123, 126–135, 138, 194–196
lymphomas, 107–108, 197–198
male genital cancers, 111, 201–202
other cancers, 203
renal cancer, 109, 132, 198–199
stomach cancer, 110, 134, 200–201
Capstone report, 16, 24, 93–96, 98, 208
Carcinogenic effects, 29–30
Cardiovascular effects, 39, 126, 212
Case-control studies, 75, 85–86
nested, 86, 130, 161, 163
retrospective, 133
Case reports and case series, 87
Categories of strength of association, 90–91
inadequate/insufficient evidence to determine whether an association exists, 4, 91, 195–202, 207, 209–211, 214–215
limited/suggestive evidence of an association, 4, 91
limited/suggestive evidence of no association, 4, 91
origin of, 90
sufficient evidence of a causal relationship, 4, 90
sufficient evidence of an association, 4, 91
Causation
defining, 75
true cause-effect association, 80
CEDR. See Comprehensive Epidemiology Data Resource
Cell toxicity, evaluating, 80
Central nervous system cancers, 110, 200
Chemical effects, of exposure to depleted uranium, 17–20
Chemical toxicity, 19–20
Chest X-ray testing, 114
Chondrosarcoma, 109
Chordoma, 109
Chromosomal aberrations, 30–31
Chronic bronchitis, 113
Chronic kidney disease (CKD), 111
Chronic lymphocytic leukemia, 107
Chronic myeloid leukemia, 107
Chronic nephritis, 132, 203–204
Chronic obstructive pulmonary disease (COPD), 113–114
CKD. See Chronic kidney disease
Cleft lip and palate, 114
Clinical end points of interest, 105–116
cancer outcomes, 105–111
noncancer outcomes, 111–115
Clinical outcomes, adverse, 81
Coexposures, 83–84
to other agents, 89
synergism, 83–84
Cohort descriptions, 117–192
depleted-uranium studies, 143–153
environmental-exposure studies, 153–163
summary, 163–190
uranium-processing cohorts, 118–143
Cohort studies, 75, 84–85
prospective, 85
retrospective, 83, 85, 135, 140, 151
Colon cancer, 156
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Colorado Plateau uranium-mill workers, 119–123, 203, 208, 212
Committee
approach to its charge, 3–4
charge to, 3
task of, 10
Comparison-group issues, in study populations, 77
Comprehensive Epidemiology Data Resource (CEDR), 124–125
Computerized Occupational Referent Population System (CORPS), 126
Conclusions, 193–262
cancer outcomes, 193–203
noncancer outcomes, 203–214
summary, 214–215
Conditional logistic regression, 130
Confidence interval, 204
Control of bias, 82–83
information bias, 83
selection bias, 77, 83
COPD. See Chronic obstructive pulmonary disease
CORPS. See Computerized Occupational Referent Population System
Cox proportional-hazard models, 140
Cox regression analyses, 141
Cross-sectional studies, 75, 86–87
D
Danish Cancer Society, 152
Death-certificate data, 113, 119–121, 127–128, 132, 137
Depleted Uranium Follow-up Program, 15, 143–144, 148, 209–210, 212
Depleted-uranium studies
Balkans studies, 151–153
Baltimore Veterans Affairs Medical Center, 15, 143–151
cohort descriptions, 143–153
UK Gulf War studies, 151
Deposition pattern in the human body, especially airways, 89
Dermal effects, 40
Developmental studies. See Reproductive and developmental studies
Direct measurement, in individual workers, 78, 95
Disease occurrence, 86–87
Distribution issues, 27–28
DOD. See US Department of Defense
DOE. See US Department of Energy
Dose reconstruction, 89
Dose-response modeling and risk assessment, 20–21, 79, 128, 131–132, 139, 159, 195
Dosimeter, thermoluminescent, 100
Down syndrome, 114
Drinking water and residential exposure, 206
Dupree-Ellis et al., 2000, 198, 200, 203
Dusts, uranium-particle-containing, 25
E
Ecologic studies, 87
Effective dose equivalent, 19
Egyptian processors, 142–143, 207
Electromagnetic separation, 127
Emphysema, 113, 123, 126
End Stage Renal Disease Program Management and Medical Information System (ESRD), 122–123
Environmental-exposure studies
cohort descriptions, 153–163
Finnish well-water studies, 157–163
residential studies, 153–157
Environmental monitoring, 80
Epidemiologic studies
controlling for risk factors, 75
principal objectives of, 75–76
Epidemiologic-study designs, 84–87
case-control studies, 85–86
case reports and case series, 87
cohort studies, 84–85
cross-sectional studies, 86–87
ecologic studies, 87
ESRD. See End Stage Renal Disease Program Management and Medical Information System
EUROCAT Protocol, 153
Ewing tumor, 109
Excretion and retention, 28–29
Exposure assessment, 77–80, 93–103.
See Levels I, II, III
classifying workers by maximum exposure, 78–79
direct measurement in individual workers, 78
estimation of exposure to depleted uranium during the Gulf War, 93–100
exposure-monitoring methods, 100–102
exposure of military personnel to depleted uranium, 14–16
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other methods of estimating exposures, 79–80
self-reporting in, 79
using work history to model cumulative exposure, 78
F
False-negative results, 79
Fernald Feed Materials Production Center (FFMPC) workers, 97, 123–126, 133, 156, 206, 208, 212
Fernald Resident Medical Monitoring Program (FMMP), 156–157
FFMPC. See Fernald Feed Materials Production Center
Fibrosarcoma, 109
Finnish well-water studies, 157–163
FMMP. See Fernald Resident Medical Monitoring Program
Friendly-fire incidents, 94
G
Gamma rays, 18
Gastric cancer, 110
Gastrointestinal effects, 36
absorption of uranium, 26
Genitourinary diseases, 204
Genotoxic effects, 26, 30–31, 147, 212
tests for, 148
Geographic proximity modeling, 80
German peacekeeping personnel, 16
Glomerular filtration rate (GFR), 111–112
Greenham Common US Air Force base, 153
Gulf War and Health, Volume 1: Depleted Uranium, Pyridostigmine Bromide, Sarin, Vaccines, 2–5, 9–10, 24, 27, 29–32, 36–41, 73, 88–89, 117–118, 144, 193, 195, 203, 207–208
summary of findings in the section on depleted uranium in, 9
Gulf War veterans, 3, 7–8, 14, 20–21, 30, 76, 81, 93, 97–98, 106, 114, 117–118, 143–144, 146, 148–151, 193, 201–203, 209–210, 212–213
depleted-uranium surveillance study of, 204–206
H
Half-life, radioactive, 17
Hazard ratios (HRs), 161–163
Healthy-warrior effect, 77, 85
Healthy-worker effect, 77, 204
Heavy-armor tanks, 14.
See also individual vehicle listings
Hematologic effects, 41, 213
Hematopoietic cancer, 123, 134
Hepatotoxicity, 36–37
Hodgkin lymphoma, 107, 121, 123, 152, 197
HPRT mutation frequency, 148–150
HRs. See Hazard ratios
Human Respiratory Tract Model, 101
I
IARC. See International Agency for Research on Cancer
ICP-MS. See Inductively coupled plasma-mass spectrometry
Immune system effects, 38–39, 213
In vitro models, 24
to assess neurologic effects, 33–34
In vivo models, to assess neurologic effects, 34–36
Inadequate/insufficient evidence to determine whether an association exists, 4, 91, 195–202, 207, 209–211, 214–215
Inclusion criteria, 88
Inductively coupled plasma-mass spectrometry (ICP-MS), 26, 28, 31, 33–35
Information bias, 83
Information-gathering strategy, 73–74
Inhalation studies, 26
Interaction. See Synergism
Internal comparison groups, 77
Internal dose, of radiation, 78
International Agency for Research on Cancer (IARC), 75, 90
International Classification of Diseases
ICD-6, 120
ICD-8, 127–128
ICD-9, 122, 151, 156–157
ICD-10, 107–108
International Classification of Diseases Adapted for Use in the United States, ICDA-8, 130
International Commission on Radiological Protection, 13, 25, 102, 140, 162
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International Red Cross and Red Crescent Movement, 16
Intervention strategies, 20
Italian Ministry of Defense, 152
K
Kidneys, a primary reservoir of uranium, 28–29
Kinetic-energy cartridges and ammunition rounds, 2, 14
Kosovo war, 2, 14, 16
Kuwait, invasion of, 7
L
Leukemias, 107, 196
Level I exposure, 15, 94
Level II exposure, 15, 94, 98–100
Level III exposure, 15–16, 94–95, 117
Life Table Analysis System (LTAS)
modified, 120–122
Monson’s, 125
Limited/suggestive evidence of an association, 4, 91
Limited/suggestive evidence of no association, 4, 91
Linear no-threshold model, validity of, 21
Linear regression, 143, 160
Longitudinal studies, 84
LTAS. See Life Table Analysis System
Lung cancer, 88–89, 106–107, 123, 126–135, 138, 194–196
Lymphatic cancer, 123, 134
Lymphomas, 107–108, 197–198.
See also Hodgkin lymphoma;
Non-Hodgkin lymphoma
Lymphosarcoma, 123
M
Male genital cancers, 111, 201–202
Malignant fibrous histiocytoma, 109
Malignant neoplasms, 126
Mallinckrodt Chemical Workers (MCW), 131–133, 203, 212
MCW. See Mallinckrodt Chemical Workers
Mechanism-of-action studies, 23
Mechanisms of toxicity, radiologic vs chemical, 89
Medical Subject Heading (MeSH), 73
Metallotoxic effects, 31
Metastasis, from other primary cancers, 131
Methodology, 73–92
categories of strength of association, 90–91
considerations in statistical inference, 81–84
epidemiologic-study designs, 84–87
exposure assessment, 77–80
factors influencing the relevance and quality of studies, 76–84
inclusion criteria, 88
information-gathering strategy, 73–74
outcome assessment, 80–81
principal objectives of epidemiologic studies, 75
rationale for not including studies of uranium miners, 88–90
study populations, 76–77
Monson’s life-table analysis, 125
Morbidity, 204–207
drinking water and residential exposure, 206
Gulf War veterans depleted-uranium surveillance study, 204–206
occupational uranium exposure, 206–207
Mortality, 113, 119, 123, 129–131, 133, 135, 138–139, 141, 203–204
all-cause, 81, 126–127
cause-specific, 120, 128
patterns of, 118
Motor vehicle department records (state), 128, 134
Musculoskeletal effects, 40–41
Mutations, 105.
See also HPRT mutation frequency
N
National Center for Health Statistics, 154
National Council on Radiation Protection and Measurements, 98
National Death Index (NDI), 122, 125, 130, 132, 139
National Health and Nutrition Examination Survey, 111
National Health Interview Survey, 209
National Health Services Central Register (NHSCR), 136–138, 151
National Institute for Occupational Safety and Health (NIOSH), 121–122, 124, 126, 134
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National Report on Human Exposure to Environmental Chemicals, 101
National Research Council, 16, 20, 24, 96, 162, 208
National Technical Information Service, 73
NDI. See National Death Index
Nephrotoxic effects, 208
Nested case-control studies, 86, 130, 161, 163
Neurobehavioral and neurocognitive effects, 114
Neurocognitive tests, 147
Neurologic effects, 32–36, 114, 209–210
biologic plausibility, 36
in vitro models to assess, 33–34
in vivo models to assess, 34–36
Neuronal lethality, 33
Neuropsychologic tests, 146
NHANES III. See Third National Health and Nutrition Examination Survey
NHIS. See US National Health Interview Study
NHL. See Non-Hodgkin lymphoma
NHSCR. See National Health Services Central Register
NIOSH. See National Institute for Occupational Safety and Health
Noncancer outcomes, 111–115, 203–214
birth defects and other adverse reproductive outcomes, 114–115
neurobehavioral and neurocognitive effects, 114
neurologic effects, 114, 209–210
nonmalignant renal disease, 111–112, 203–208
nonmalignant respiratory disease, 113–114, 208–209
other health outcomes, 211–214
reproductive and developmental effects, 210–211
Non-Hodgkin lymphoma (NHL), 107–108, 197
Nonhuman studies, 23–24, 29–30
Nonmalignant renal disease, 111–112, 203–208
conclusion, 207–208
morbidity, 204–207
mortality, 203–204
Nonmalignant respiratory disease, 113–114, 122–123, 208–209
North Atlantic Treaty Organization, 14
No-threshold model, linear, 21
Nuclear-fuels fabrication workers, 135–136
Nuclear Regulatory Commission, 140
Null hypotheses, 81–82
O
Oak Ridge nuclear facilities workers, 126–131, 194, 204
Occupational studies, 84
of uranium exposure, 206–207
Ocular effects, 40
Office for National Statistics (ONS), 136–138
Office of the Special Assistant for Gulf War Illnesses, 15
OIF. See Operation Iraqi Freedom
ONS. See Office for National Statistics
Operation Enduring Freedom in Afghanistan, 9
Operation Iraqi Freedom (OIF), 2, 9, 14, 76, 117, 144
Osteosarcoma, 109
Outcome assessment, 80–81
adequate followup period, 80–81
adverse clinical outcomes, 81
biological plausibility, 80
biomarkers, 80
Outcomes, 105–116, 193–262
cancer outcomes, 105–111, 193–203
noncancer outcomes, 111–115, 203–214
specificity of, 81
summary, 214–215
P
p values, 82
Pension Benefit Information, 132
Persian Gulf War. See Gulf War veterans
Persian Gulf War Veterans Act, 1, 7
Person-years at risk (PYARs), 134–135, 142
Peyer’s patches, 26, 29
Pharmacokinetics, of uranium, 28
Phosphate-fertilizer production workers, 134–135
Physicochemical properties, differences in, 89
Pleura, cancer of, 138
Pneumoconiosis, 113, 123
Pneumonia, 113
Poisson regression analysis, 128–129
Portsmouth Uranium Enrichment facility workers, 133–134
Prevalence odds ratios, 86–87
Prospective cohort studies, 85
Prostatic cancer, 106, 111, 142, 201–202
PubMed, 73
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Pulmonary fibrosis, uranium’s ability to induce, 30–31
PYARs. See Person-years at risk
R
Radiation
estimates of risk, 19
film badges measuring, 78, 100, 132
internal dose of, 78
Radioactive decay, 17
Radioactivity, 17
Radiogenic-cancer risk estimation, 20
Radiologic considerations, 17–19
Radiologic effects, of exposure to depleted uranium, 17–20
Radiologic vs chemical mechanisms of toxicity, 89
RAI. See Rocketdyne/Atomics International workers
RCCs. See Renal-cell carcinomas
Rectal cancer, 156
Regression analyses, 146
Cox, 141
REM sleep, 35–36
Renal cancer, 109, 132, 198–199
Renal-cell carcinomas (RCCs), 109
Renal disease, 157
Renal dysfunction, evaluating, 80
Renal effects, 31–32
Renal toxicants, 19–20
Reproductive and developmental studies, 37–38, 145, 210–211
multigenerational, 39
Residential studies, 100, 153–157
Respiratory effects, 31
neoplasms, 129
Reticulosarcoma, 123
Retrospective case-control studies, 133
Retrospective cohort studies, 83, 85, 135, 140, 151
Review of Toxicologic and Radiologic Risks to Military Personnel from Exposure to Depleted Uranium During and After Combat, 16, 24, 208
Risk estimates, 20–21
of radiation, 19
Risk ratios (RRs), 84, 131, 136–138, 141, 155, 198
Risk transfer, 89
Rocketdyne/Atomics International (RAI) workers, 139–141, 212
Royal Society report, 16, 93–96, 98, 100
RRs. See Risk ratios
S
Sandia report, 93–96, 98, 100
Savannah River Plant workers, 141–142, 204
SCEs. See Sister-chromatid exchanges
Selection bias, 77, 83
Self-reporting, 79
Sievert, 19
SIRs. See Standardized incidence ratios
Sister-chromatid exchanges (SCEs), 212
Skeletal effects, 213
Sleep-wake cycle disturbances, 35
Smoking, a confounding variable, 89
SMRs. See Standardized mortality ratios
Springfields processing plant, 201
Standardized incidence ratios (SIRs), 135, 152, 155, 198, 202
Standardized mortality ratios (SMRs), 77, 81, 85, 120–122, 128–142, 154–155, 194–196, 198
cause-specific, 135
Statistical inference, 81–84
coexposures, 83–84
control of bias, 82–83
the p value, 82
tests of association, 81–82
type I and type II, 82
Stomach cancer, 110, 134, 200–201
Structure-activity relationships, 23
Study populations, 76–77
comparison-group issues, 77
relevance to veteran populations, 76
Sufficient evidence of a causal relationship, 4, 90
Sufficient evidence of an association, 4, 91
Summary, 1–5, 214–215
of findings in the section on depleted uranium in Gulf War and Health, Volume 1, 9
Swedish Armed Forces, 151
Swedish Cancer Registry, 152
Swedish Rescue Services Agency, 151–152
Synergism, 83–84, 89
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T
Tennessee Eastman Corporation (TEC), 126–127, 133
Test statistics, 82
Testicular cancer, 106, 111, 138, 202
Tests of association, 81–82
Texas Department of Health, 155
Third National Health and Nutrition Examination Survey (NHANES III), 157
Thyroid diseases, 157
Toxicity studies, 29–41
application of the toxicologic data, 41–66
carcinogenic effects, 29–30
cardiovascular effects, 39
dermal effects, 40
gastrointestinal effects, 36
genotoxic effects, 30–31
hematologic effects, 41
hepatotoxicity, 36–37
immune system effects, 38–39
musculoskeletal effects, 40–41
neurologic effects, 32–36
ocular effects, 40
renal effects, 31–32
reproductive and developmental effects, 37–38
respiratory effects, 31
as secondary information sources, 42
summary of previous report, 24
Toxicokinetics, 25–29.
See also Mechanisms of toxicity
absorption, 25–27
distribution issues, 27–28
excretion and retention, 28–29
transport and biotransformation, 27
Toxicology, 23–72
Toxicology Literature Online (TOXLINE), 73
Tracheal cancer, 123
Transport and biotransformation, 27
Type I and type II statistical inference, 82
U
Union Carbide, 127
United Kingdom (UK) Gulf War studies, 151
United Kingdom (UK) Ministry of Supply, 138
United Kingdom (UK) processors, 136–137
Uranium, 13
accumulations of, 28
isotopes of, 18–19
naturally occurring, 101
pharmacokinetics of, 28
Uranium intoxication, 40
Uranium miners’ studies
coexposures to other agents, 89
deposition pattern in the human body, especially airways, 89
differences in physicochemical properties, 89
radiological vs chemical mechanisms of toxicity, 89
rationale for not including, 88–90
Uranium-processing cohorts, 118–143
Atomic Weapons Establishment workers, 142
Colorado Plateau uranium-mill workers, 119–123
Egyptian processors, 142–143
Fernald Feed Materials Production Center workers, 123–126
Mallinckrodt Chemical Workers, 131–132
nuclear-fuels fabrication workers, 135–136
Oak Ridge nuclear facilities workers, 126–131
phosphate-fertilizer production workers, 134–135
Portsmouth Uranium Enrichment facility workers, 133–134
Rocketdyne/Atomics International workers, 139–141
Savannah River Plant workers, 141–142
United Kingdom processors, 136–137
workers at four uranium-processing operations, 133
US Army, 2, 14, 16, 24, 208
US Congress, 1
US Department of Defense (DOD), 2, 15, 94, 144
US Department of Energy (DOE), 16, 97, 124, 140
US Department of Veterans Affairs (VA), 1, 7, 143
request for this study, 9–10
US Environmental Protection Agency, 38
US National Guard, 16
US National Health Interview Study (NHIS), 157
US Nuclear Regulatory Commission, 19, 98
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US Postal Service, 122
US Public Health Service, 119
US Surgeon General, 119
Uterine cancer, 138
V
VA. See US Department of Veterans Affairs
Vaccines, given to US troops, health effects of, 90
Ventilation, in tanks, 16, 93
Veteran populations
applicability of study results to, 76
Veterans Programs Enhancement Act, 1, 7
Volume 1. See Gulf War and Health, Volume 1: Depleted Uranium, Pyridostigmine Bromide, Sarin, Vaccines
W
WHO. See World Health Organization
Whole-body radiation counting, 97
Wide Range Achievement Test 3 Reading (WRAT-3), 145, 147, 209
Work history, using to model cumulative exposure, 78
World Health Organization (WHO), 90, 105, 145, 210
WRAT-3. See Wide Range Achievement Test 3 Reading
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