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Index

A

Abrams tanks, 15, 9394, 9697

ventilation in, 16, 95

Absorption, 2527

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, 9394

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, 8182

Asthma, 113114

Atomic Weapons Establishment workers, 142

Automated Neuropsychological Assessment Metrics Test Library, 148

B

Background, 1322

dose-response modeling and risk assessment, 2021

exposure of military personnel to depleted uranium, 1416

radiologic and chemical effects of exposure to depleted uranium, 1720

uses of depleted uranium, 14

Balkans studies, 151153

Baltimore Veterans Affairs Medical Center (BVAMC), 15, 97, 143151, 204, 209210, 212

Beck Depression Inventory (BDI), 145, 147, 209

Becquerel (Bq), 17

Beta particles, 18

Bias

control of, 8283

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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Index A B Abrams tanks, 15, 93–94, 96–97 Background, 13–22 ventilation in, 16, 95 dose-response modeling and risk Absorption, 25–27 assessment, 20–21 increased by skin excoriation, 27 exposure of military personnel to depleted skin, 27 uranium, 14–16 via deep wounds, 27 radiologic and chemical effects of exposure Accuracy impairment (A-IIac), 209 to depleted uranium, 17–20 Acute lymphocytic leukemia, 107 uses of depleted uranium, 14 Acute myeloid leukemia, 107 Balkans studies, 151–153 Aerosols, inhalable, 93–94 Baltimore Veterans Affairs Medical Center Afghanistan. see Operation Enduring Freedom (BVAMC), 15, 97, 143–151, 204, in Afghanistan 209–210, 212 A-IIac. see Accuracy impairment Beck Depression Inventory (BDI), 145, 147, Alpha particles, 17 209 Amyotrophic lateral sclerosis, 114 Becquerel (Bq), 17 Animal studies. see Nonhuman studies Beta particles, 18 Association Bias defining, 75 control of, 82–83 tests of, 81–82 studies vulnerable to, 86 Asthma, 113–114 Biokinetic models of exposure, 25 Atomic Weapons Establishment workers, Biologic plausibility, 80 142 of neurologic effects, 36 Automated Neuropsychological Assessment Biomarkers, 80, 160 Metrics Test Library, 148 Biotransformation, 27 26

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26 inDex Birth defects, and other adverse reproductive Categories of strength of association, 90–91 outcomes, 114–115 inadequate/insufficient evidence to Bladder cancer, 109–110, 199 determine whether an association exists, Blood-brain barrier, 31 4, 91, 195–202, 207, 209–211, 214–215 BNFL. see British Nuclear Fuels PLC limited/suggestive evidence of an Bone, a primary reservoir of uranium, 28–29 association, 4, 91 Bone cancer, 108–109, 153, 198 limited/suggestive evidence of no Bosnia-Herzegovina war, 14, 16, 153 association, 4, 91 Bq. see Becquerel origin of, 90 Bradley fighting vehicles, 15, 93, 95, 97 sufficient evidence of a causal relationship, Brain and other central nervous system cancers, 4, 90 110, 200 sufficient evidence of an association, 4, 91 Brain lipid oxidation, 35 Causation Brain regions, accumulation in, 28 defining, 75 Breast cancer, 106 true cause-effect association, 80 British Nuclear Fuels PLC (BNFL), 136–137, CEDR. see Comprehensive Epidemiology Data 204 Resource Bronchial cancer, 123 Cell toxicity, evaluating, 80 BVAMC. see Baltimore Veterans Affairs Central nervous system cancers, 110, 200 Medical Center Chemical effects, of exposure to depleted uranium, 17–20 Chemical toxicity, 19–20 C Chest X-ray testing, 114 Chondrosarcoma, 109 Camp Doha fire, 15, 94–95 Chordoma, 109 Cancer Chromosomal aberrations, 30–31 biological latency of, 80 Chronic bronchitis, 113 causes of, 105 Chronic kidney disease (CKD), 111 incidence of, 193 Chronic lymphocytic leukemia, 107 Cancer outcomes, 105–111, 193–203 Chronic myeloid leukemia, 107 bladder cancer, 109–110, 199 Chronic nephritis, 132, 203–204 bone cancer, 108–109, 153, 198 Chronic obstructive pulmonary disease brain and other central nervous system (COPD), 113–114 cancers, 110, 200 CKD. see Chronic kidney disease in depleted-uranium–exposed animals, Cleft lip and palate, 114 29–30 Clinical end points of interest, 105–116 leukemias, 107, 196 cancer outcomes, 105–111 lung cancer, 88–89, 106–107, 123, noncancer outcomes, 111–115 126–135, 138, 194–196 Clinical outcomes, adverse, 81 lymphomas, 107–108, 197–198 Coexposures, 83–84 male genital cancers, 111, 201–202 to other agents, 89 other cancers, 203 synergism, 83–84 renal cancer, 109, 132, 198–199 Cohort descriptions, 117–192 stomach cancer, 110, 134, 200–201 depleted-uranium studies, 143–153 Capstone report, 16, 24, 93–96, 98, 208 environmental-exposure studies, 153–163 Carcinogenic effects, 29–30 summary, 163–190 Cardiovascular effects, 39, 126, 212 uranium-processing cohorts, 118–143 Case-control studies, 75, 85–86 Cohort studies, 75, 84–85 nested, 86, 130, 161, 163 prospective, 85 retrospective, 133 retrospective, 83, 85, 135, 140, 151 Case reports and case series, 87 Colon cancer, 156

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26 inDex Colorado Plateau uranium-mill workers, DOD. see US Department of Defense 119–123, 203, 208, 212 DOE. see US Department of Energy Committee Dose reconstruction, 89 approach to its charge, 3–4 Dose-response modeling and risk assessment, charge to, 3 20–21, 79, 128, 131–132, 139, 159, 195 task of, 10 Dosimeter, thermoluminescent, 100 Comparison-group issues, in study populations, Down syndrome, 114 77 Drinking water and residential exposure, 206 Comprehensive Epidemiology Data Resource Dupree-Ellis et al., 2000, 198, 200, 203 (CEDR), 124–125 Dusts, uranium-particle-containing, 25 Computerized Occupational Referent Population System (CORPS), 126 E Conclusions, 193–262 cancer outcomes, 193–203 Ecologic studies, 87 noncancer outcomes, 203–214 Effective dose equivalent, 19 summary, 214–215 Egyptian processors, 142–143, 207 Conditional logistic regression, 130 Electromagnetic separation, 127 Confidence interval, 204 Emphysema, 113, 123, 126 Control of bias, 82–83 End Stage Renal Disease Program Management information bias, 83 and Medical Information System selection bias, 77, 83 (ESRD), 122–123 COPD. see Chronic obstructive pulmonary Environmental-exposure studies disease cohort descriptions, 153–163 CORPS. see Computerized Occupational Finnish well-water studies, 157–163 Referent Population System residential studies, 153–157 Cox proportional-hazard models, 140 Environmental monitoring, 80 Cox regression analyses, 141 Epidemiologic studies Cross-sectional studies, 75, 86–87 controlling for risk factors, 75 principal objectives of, 75–76 Epidemiologic-study designs, 84–87 D case-control studies, 85–86 Danish Cancer Society, 152 case reports and case series, 87 Death-certificate data, 113, 119–121, 127–128, cohort studies, 84–85 132, 137 cross-sectional studies, 86–87 Depleted Uranium Follow-up Program, 15, ecologic studies, 87 143–144, 148, 209–210, 212 ESRD. see End Stage Renal Disease Program Depleted-uranium studies Management and Medical Information Balkans studies, 151–153 System Baltimore Veterans Affairs Medical Center, EUROCAT Protocol, 153 15, 143–151 Ewing tumor, 109 cohort descriptions, 143–153 Excretion and retention, 28–29 UK Gulf War studies, 151 Exposure assessment, 77–80, 93–103. see Deposition pattern in the human body, Levels I, II, III especially airways, 89 classifying workers by maximum exposure, Dermal effects, 40 78–79 Developmental studies. see Reproductive and direct measurement in individual workers, 78 developmental studies estimation of exposure to depleted uranium Direct measurement, in individual workers, during the Gulf War, 93–100 78, 95 exposure-monitoring methods, 100–102 Disease occurrence, 86–87 exposure of military personnel to depleted Distribution issues, 27–28 uranium, 14–16

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266 inDex H other methods of estimating exposures, 79–80 Half-life, radioactive, 17 self-reporting in, 79 Hazard ratios (HRs), 161–163 using work history to model cumulative Healthy-warrior effect, 77, 85 exposure, 78 Healthy-worker effect, 77, 204 Heavy-armor tanks, 14. see also individual vehicle listings F Hematologic effects, 41, 213 False-negative results, 79 Hematopoietic cancer, 123, 134 Fernald Feed Materials Production Center Hepatotoxicity, 36–37 (FFMPC) workers, 97, 123–126, 133, Hodgkin lymphoma, 107, 121, 123, 152, 197 156, 206, 208, 212 HPRT mutation frequency, 148–150 Fernald Resident Medical Monitoring Program HRs. see Hazard ratios (FMMP), 156–157 Human Respiratory Tract Model, 101 FFMPC. see Fernald Feed Materials Production Center I Fibrosarcoma, 109 Finnish well-water studies, 157–163 IARC. see International Agency for Research FMMP. see Fernald Resident Medical on Cancer Monitoring Program ICP-MS. see Inductively coupled plasma-mass Friendly-fire incidents, 94 spectrometry Immune system effects, 38–39, 213 In vitro models, 24 G to assess neurologic effects, 33–34 Gamma rays, 18 In vivo models, to assess neurologic effects, Gastric cancer, 110 34–36 Gastrointestinal effects, 36 Inadequate/insufficient evidence to determine absorption of uranium, 26 whether an association exists, 4, 91, Genitourinary diseases, 204 195–202, 207, 209–211, 214–215 Genotoxic effects, 26, 30–31, 147, Inclusion criteria, 88 212 Inductively coupled plasma-mass spectrometry tests for, 148 (ICP-MS), 26, 28, 31, 33–35 Geographic proximity modeling, 80 Information bias, 83 German peacekeeping personnel, 16 Information-gathering strategy, 73–74 Glomerular filtration rate (GFR), 111–112 Inhalation studies, 26 Greenham Common US Air Force base, Interaction. see Synergism 153 Internal comparison groups, 77 Gulf war and Health, volume 1: Depleted Internal dose, of radiation, 78 Uranium, Pyridostigmine Bromide, International Agency for Research on Cancer sarin, vaccines, 2–5, 9–10, 24, 27, (IARC), 75, 90 29–32, 36–41, 73, 88–89, 117–118, 144, international Classification of Diseases 193, 195, 203, 207–208 ICD-6, 120 summary of findings in the section on ICD-8, 127–128 depleted uranium in, 9 ICD-9, 122, 151, 156–157 Gulf War veterans, 3, 7–8, 14, 20–21, 30, 76, ICD-10, 107–108 81, 93, 97–98, 106, 114, 117–118, international Classification of Diseases 143–144, 146, 148–151, 193, 201–203, adapted for Use in the United states, 209–210, 212–213 ICDA-8, 130 depleted-uranium surveillance study of, International Commission on Radiological 204–206 Protection, 13, 25, 102, 140, 162

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26 inDex International Red Cross and Red Crescent Medical Subject Heading (MeSH), 73 Movement, 16 Metallotoxic effects, 31 Intervention strategies, 20 Metastasis, from other primary cancers, 131 Italian Ministry of Defense, 152 Methodology, 73–92 categories of strength of association, 90–91 considerations in statistical inference, 81–84 K epidemiologic-study designs, 84–87 exposure assessment, 77–80 Kidneys, a primary reservoir of uranium, 28–29 factors influencing the relevance and quality Kinetic-energy cartridges and ammunition of studies, 76–84 rounds, 2, 14 inclusion criteria, 88 Kosovo war, 2, 14, 16 information-gathering strategy, 73–74 Kuwait, invasion of, 7 outcome assessment, 80–81 principal objectives of epidemiologic studies, 75 L rationale for not including studies of uranium miners, 88–90 Leukemias, 107, 196 study populations, 76–77 Level I exposure, 15, 94 Monson’s life-table analysis, 125 Level II exposure, 15, 94, 98–100 Morbidity, 204–207 Level III exposure, 15–16, 94–95, 117 drinking water and residential exposure, 206 Life Table Analysis System (LTAS) Gulf War veterans depleted-uranium modified, 120–122 surveillance study, 204–206 Monson’s, 125 occupational uranium exposure, 206–207 Limited/suggestive evidence of an association, Mortality, 113, 119, 123, 129–131, 133, 135, 4, 91 138–139, 141, 203–204 Limited/suggestive evidence of no association, all-cause, 81, 126–127 4, 91 cause-specific, 120, 128 Linear no-threshold model, validity of, 21 patterns of, 118 Linear regression, 143, 160 Motor vehicle department records (state), 128, Longitudinal studies, 84 134 LTAS. see Life Table Analysis System Musculoskeletal effects, 40–41 Lung cancer, 88–89, 106–107, 123, 126–135, Mutations, 105. see also HPRT mutation 138, 194–196 frequency Lymphatic cancer, 123, 134 Lymphomas, 107–108, 197–198. see also Hodgkin lymphoma; Non-Hodgkin N lymphoma Lymphosarcoma, 123 National Center for Health Statistics, 154 National Council on Radiation Protection and Measurements, 98 M National Death Index (NDI), 122, 125, 130, 132, 139 Male genital cancers, 111, 201–202 National Health and Nutrition Examination Malignant fibrous histiocytoma, 109 Survey, 111 Malignant neoplasms, 126 National Health Interview Survey, 209 Mallinckrodt Chemical Workers (MCW), National Health Services Central Register 131–133, 203, 212 (NHSCR), 136–138, 151 MCW. see Mallinckrodt Chemical Workers National Institute for Occupational Safety and Mechanism-of-action studies, 23 Health (NIOSH), 121–122, 124, 126, Mechanisms of toxicity, radiologic vs chemical, 134 89

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268 inDex O national report on Human exposure to environmental Chemicals, 101 Oak Ridge nuclear facilities workers, 126–131, National Research Council, 16, 20, 24, 96, 162, 194, 204 208 Occupational studies, 84 National Technical Information Service, 73 of uranium exposure, 206–207 NDI. see National Death Index Ocular effects, 40 Nephrotoxic effects, 208 Office for National Statistics (ONS), Nested case-control studies, 86, 130, 161, 163 136–138 Neurobehavioral and neurocognitive effects, Office of the Special Assistant for Gulf War 114 Illnesses, 15 Neurocognitive tests, 147 OIF. see Operation Iraqi Freedom Neurologic effects, 32–36, 114, 209–210 ONS. see Office for National Statistics biologic plausibility, 36 Operation Enduring Freedom in Afghanistan, 9 in vitro models to assess, 33–34 Operation Iraqi Freedom (OIF), 2, 9, 14, 76, in vivo models to assess, 34–36 117, 144 Neuronal lethality, 33 Osteosarcoma, 109 Neuropsychologic tests, 146 Outcome assessment, 80–81 NHANES III. see Third National Health and adequate followup period, 80–81 Nutrition Examination Survey adverse clinical outcomes, 81 NHIS. see US National Health Interview Study biological plausibility, 80 NHL. see Non-Hodgkin lymphoma biomarkers, 80 NHSCR. see National Health Services Central Outcomes, 105–116, 193–262 Register cancer outcomes, 105–111, 193–203 NIOSH. see National Institute for Occupational noncancer outcomes, 111–115, 203–214 Safety and Health specificity of, 81 Noncancer outcomes, 111–115, 203–214 summary, 214–215 birth defects and other adverse reproductive outcomes, 114–115 neurobehavioral and neurocognitive effects, P 114 neurologic effects, 114, 209–210 p values, 82 nonmalignant renal disease, 111–112, Pension Benefit Information, 132 203–208 Persian Gulf War. see Gulf War veterans nonmalignant respiratory disease, 113–114, Persian Gulf War Veterans Act, 1, 7 208–209 Person-years at risk (PYARs), 134–135, 142 other health outcomes, 211–214 Peyer’s patches, 26, 29 reproductive and developmental effects, Pharmacokinetics, of uranium, 28 210–211 Phosphate-fertilizer production workers, Non-Hodgkin lymphoma (NHL), 107–108, 197 134–135 Nonhuman studies, 23–24, 29–30 Physicochemical properties, differences in, 89 Nonmalignant renal disease, 111–112, 203–208 Pleura, cancer of, 138 conclusion, 207–208 Pneumoconiosis, 113, 123 morbidity, 204–207 Pneumonia, 113 mortality, 203–204 Poisson regression analysis, 128–129 Nonmalignant respiratory disease, 113–114, Portsmouth Uranium Enrichment facility 122–123, 208–209 workers, 133–134 North Atlantic Treaty Organization, 14 Prevalence odds ratios, 86–87 No-threshold model, linear, 21 Prospective cohort studies, 85 Nuclear-fuels fabrication workers, 135–136 Prostatic cancer, 106, 111, 142, 201–202 Nuclear Regulatory Commission, 140 PubMed, 73 Null hypotheses, 81–82

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26 inDex Pulmonary fibrosis, uranium’s ability to induce, Rocketdyne/Atomics International (RAI) 30–31 workers, 139–141, 212 PYARs. see Person-years at risk Royal Society report, 16, 93–96, 98, 100 RRs. see Risk ratios R S Radiation estimates of risk, 19 Sandia report, 93–96, 98, 100 film badges measuring, 78, 100, 132 Savannah River Plant workers, 141–142, internal dose of, 78 204 Radioactive decay, 17 SCEs. see Sister-chromatid exchanges Radioactivity, 17 Selection bias, 77, 83 Radiogenic-cancer risk estimation, 20 Self-reporting, 79 Radiologic considerations, 17–19 Sievert, 19 Radiologic effects, of exposure to depleted SIRs. see Standardized incidence ratios uranium, 17–20 Sister-chromatid exchanges (SCEs), 212 Radiologic vs chemical mechanisms of toxicity, Skeletal effects, 213 89 Sleep-wake cycle disturbances, 35 RAI. see Rocketdyne/Atomics International Smoking, a confounding variable, 89 workers SMRs. see Standardized mortality ratios RCCs. see Renal-cell carcinomas Springfields processing plant, 201 Rectal cancer, 156 Standardized incidence ratios (SIRs), 135, 152, Regression analyses, 146 155, 198, 202 Cox, 141 Standardized mortality ratios (SMRs), 77, REM sleep, 35–36 81, 85, 120–122, 128–142, 154–155, Renal cancer, 109, 132, 198–199 194–196, 198 Renal-cell carcinomas (RCCs), 109 cause-specific, 135 Renal disease, 157 Statistical inference, 81–84 Renal dysfunction, evaluating, 80 coexposures, 83–84 Renal effects, 31–32 control of bias, 82–83 Renal toxicants, 19–20 the p value, 82 Reproductive and developmental studies, tests of association, 81–82 37–38, 145, 210–211 type I and type II, 82 multigenerational, 39 Stomach cancer, 110, 134, 200–201 Residential studies, 100, 153–157 Structure-activity relationships, 23 Respiratory effects, 31 Study populations, 76–77 neoplasms, 129 comparison-group issues, 77 Reticulosarcoma, 123 relevance to veteran populations, 76 Retrospective case-control studies, 133 Sufficient evidence of a causal relationship, Retrospective cohort studies, 83, 85, 135, 140, 4, 90 151 Sufficient evidence of an association, 4, 91 review of toxicologic and radiologic risks to Summary, 1–5, 214–215 military Personnel from exposure to of findings in the section on depleted Depleted Uranium During and after Combat, 16, 24, 208 uranium in Gulf war and Health, Risk estimates, 20–21 volume 1, 9 of radiation, 19 Swedish Armed Forces, 151 Risk ratios (RRs), 84, 131, 136–138, 141, 155, Swedish Cancer Registry, 152 198 Swedish Rescue Services Agency, 151–152 Risk transfer, 89 Synergism, 83–84, 89

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20 inDex T Uranium, 13 accumulations of, 28 Tennessee Eastman Corporation (TEC), isotopes of, 18–19 126–127, 133 naturally occurring, 101 Test statistics, 82 pharmacokinetics of, 28 Testicular cancer, 106, 111, 138, 202 Uranium intoxication, 40 Tests of association, 81–82 Uranium miners’ studies Texas Department of Health, 155 coexposures to other agents, 89 Third National Health and Nutrition deposition pattern in the human body, Examination Survey (NHANES III), especially airways, 89 157 differences in physicochemical properties, Thyroid diseases, 157 89 Toxicity studies, 29–41 radiological vs chemical mechanisms of application of the toxicologic data, toxicity, 89 41–66 rationale for not including, 88–90 carcinogenic effects, 29–30 Uranium-processing cohorts, 118–143 cardiovascular effects, 39 Atomic Weapons Establishment workers, dermal effects, 40 142 gastrointestinal effects, 36 Colorado Plateau uranium-mill workers, genotoxic effects, 30–31 119–123 hematologic effects, 41 Egyptian processors, 142–143 hepatotoxicity, 36–37 Fernald Feed Materials Production Center immune system effects, 38–39 workers, 123–126 musculoskeletal effects, 40–41 Mallinckrodt Chemical Workers, 131–132 neurologic effects, 32–36 nuclear-fuels fabrication workers, 135–136 ocular effects, 40 Oak Ridge nuclear facilities workers, renal effects, 31–32 126–131 reproductive and developmental effects, phosphate-fertilizer production workers, 37–38 134–135 respiratory effects, 31 Portsmouth Uranium Enrichment facility as secondary information sources, 42 workers, 133–134 summary of previous report, 24 Rocketdyne/Atomics International workers, Toxicokinetics, 25–29. see also Mechanisms 139–141 of toxicity Savannah River Plant workers, 141–142 absorption, 25–27 United Kingdom processors, 136–137 distribution issues, 27–28 workers at four uranium-processing excretion and retention, 28–29 operations, 133 transport and biotransformation, 27 US Army, 2, 14, 16, 24, 208 Toxicology, 23–72 US Congress, 1 Toxicology Literature Online (TOXLINE), 73 US Department of Defense (DOD), 2, 15, 94, Tracheal cancer, 123 144 Transport and biotransformation, 27 US Department of Energy (DOE), 16, 97, 124, Type I and type II statistical inference, 82 140 US Department of Veterans Affairs (VA), 1, 7, 143 u request for this study, 9–10 US Environmental Protection Agency, 38 Union Carbide, 127 US National Guard, 16 United Kingdom (UK) Gulf War studies, 151 US National Health Interview Study (NHIS), United Kingdom (UK) Ministry of Supply, 138 157 United Kingdom (UK) processors, 136–137 US Nuclear Regulatory Commission, 19, 98

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21 inDex US Postal Service, 122 volume 1. see Gulf war and Health, volume US Public Health Service, 119 1: Depleted Uranium, Pyridostigmine US Surgeon General, 119 Bromide, sarin, vaccines Uterine cancer, 138 W v WHO. see World Health Organization VA. see US Department of Veterans Affairs Whole-body radiation counting, 97 Vaccines, given to US troops, health effects Wide Range Achievement Test 3 Reading of, 90 (WRAT-3), 145, 147, 209 Ventilation, in tanks, 16, 93 Work history, using to model cumulative Veteran populations exposure, 78 applicability of study results to, 76 World Health Organization (WHO), 90, 105, Veterans Programs Enhancement Act, 1, 7 145, 210 WRAT-3. see Wide Range Achievement Test 3 Reading

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