INDEX

A

Acetone

hairy cell leukemia and, 326

multiple myeloma and, 306

rectal cancer and, 203

Acute human exposures

to carbamates, 52–53

to DEET, 67–68

delayed effects, 44–46

immediate effects, 43–44

to lindane, 64–65

organophosphorous compounds, 43–46

to pyrethrins and pyrethroids, 59–60

Acute leukemia, 134–135, 308

and benzene, 320–321

and mixtures of organic solvents, 321–322

and solvent exposure, 319–322

Acute lymphocytic leukemia, 336

Acute nonlymphocytic leukemia, 336

AD. See Alzheimer’s disease

Adult leukemia, 134–135, 308

acute, 319–322

and benzene, 315–316

chronic, 322–323

hairy cell, 325–326

and insecticide exposure, 134–139

lymphatic, 323–325

and mixtures of organic solvents, 317–319

and phenol, 317

and solvent exposure, 308–319

solvents, 317

and tetrachloroethylene and dry-cleaning and toluene, 317

and trichloroethylene, 316

Agents listed in PL 105–277 and PL 105–368, 1–2, 10–11

diseases endemic to the region, 2, 11

environmental particles and pollutants, 1, 10

live, “attenuated,” and toxoid vaccines, 2, 11

nerve agents and precursor compounds, 1, 10

pesticides, 1, 10

pyridostigmine bromide, 1, 10

radiation sources, 2, 10

synthetic chemical compounds, 1, 10

AhR action, interactions with carbamates, 56

Aircraft and aerospace workers, exposed to trichloroethylene, 165–166

Alcohols, 89–90

chemical structure of various, 90

cyclohexanol, 90

ethanol, 90

isopropanol, 90

methanol, 90

toxicology of, 89–90

Allergic contact dermatitis, 509–510, 512–513

ALS. See Amyotrophic lateral sclerosis

Alzheimer’s disease (AD)

and insecticide exposure, 420–421

and solvent exposure, 434–439

Amyotrophic lateral sclerosis (ALS)

and insecticide exposure, 418–419

and solvents, 424–429

Aplastic anemia, 484–491

and benzene, 487–490

and insecticide exposure, 485–486

and solvents, 489–491

Aromatic hydrocarbons, 84–85

benzene, 85

toluene, 85

toxicology of, 84–85

xylenes, 85



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Gulf War and Health: Insecticides and Solvents, Volume 2 INDEX A Acetone hairy cell leukemia and, 326 multiple myeloma and, 306 rectal cancer and, 203 Acute human exposures to carbamates, 52–53 to DEET, 67–68 delayed effects, 44–46 immediate effects, 43–44 to lindane, 64–65 organophosphorous compounds, 43–46 to pyrethrins and pyrethroids, 59–60 Acute leukemia, 134–135, 308 and benzene, 320–321 and mixtures of organic solvents, 321–322 and solvent exposure, 319–322 Acute lymphocytic leukemia, 336 Acute nonlymphocytic leukemia, 336 AD. See Alzheimer’s disease Adult leukemia, 134–135, 308 acute, 319–322 and benzene, 315–316 chronic, 322–323 hairy cell, 325–326 and insecticide exposure, 134–139 lymphatic, 323–325 and mixtures of organic solvents, 317–319 and phenol, 317 and solvent exposure, 308–319 solvents, 317 and tetrachloroethylene and dry-cleaning and toluene, 317 and trichloroethylene, 316 Agents listed in PL 105–277 and PL 105–368, 1–2, 10–11 diseases endemic to the region, 2, 11 environmental particles and pollutants, 1, 10 live, “attenuated,” and toxoid vaccines, 2, 11 nerve agents and precursor compounds, 1, 10 pesticides, 1, 10 pyridostigmine bromide, 1, 10 radiation sources, 2, 10 synthetic chemical compounds, 1, 10 AhR action, interactions with carbamates, 56 Aircraft and aerospace workers, exposed to trichloroethylene, 165–166 Alcohols, 89–90 chemical structure of various, 90 cyclohexanol, 90 ethanol, 90 isopropanol, 90 methanol, 90 toxicology of, 89–90 Allergic contact dermatitis, 509–510, 512–513 ALS. See Amyotrophic lateral sclerosis Alzheimer’s disease (AD) and insecticide exposure, 420–421 and solvent exposure, 434–439 Amyotrophic lateral sclerosis (ALS) and insecticide exposure, 418–419 and solvents, 424–429 Aplastic anemia, 484–491 and benzene, 487–490 and insecticide exposure, 485–486 and solvents, 489–491 Aromatic hydrocarbons, 84–85 benzene, 85 toluene, 85 toxicology of, 84–85 xylenes, 85

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Gulf War and Health: Insecticides and Solvents, Volume 2 Association measures of, 24–25 See also Categories of association “Attenuated” vaccines, 2, 11 Audiometry, 581 Azamethiphos, chemical structure of, 41 B Bait, for rodents, 1, 10 Balance, symptoms related to, 387–388 Behavioral alterations, organophosphorous-induced delayed, 46 Benzene acute leukemia and, 320–321 adult leukemia and, 315–316 aplastic anemia and, 487–490 bladder cancer and, 256 bone cancer and, 225 brain and CNS tumors and, 280 breast cancer and, 235 chemical structure of, 85 chronic leukemia and, 323 colon cancer and, 198–199 esophageal cancer and, 190 hairy cell leukemia and, 325 hepatobiliary cancers and, 213 Hodgkin’s disease and, 299–300 kidney cancer and, 270 lung cancer and, 221 lymphatic leukemia and, 324 multiple myeloma and, 305 myelodysplastic syndromes and, 330 non-Hodgkin’s lymphoma and, 291–292 pancreatic cancer and, 206 prostate cancer and, 245–246 rectal cancer and, 202 stomach cancer and, 193 time-to-pregnancy effects and, 461 Bias assessing the effect of, 26–27 information, 27–28 selection, 27 Bibliographic databases, 568 Biological interactions, research recommendations from Gulf War and Health, Volume 1, 564 Bladder cancer, 117 and benzene, 256 and insecticide exposure, 119–120 and mixtures of organic solvents, 257–259 and solvent exposure, 246–259 and tetrachloroethylene and dry-cleaning solvents, 255 and toluene, 256–257 and trichloroethylene, 254 and xylene, 257 Blood glucose concentrations, of pyrethrins and pyrethroids, 62 Bone cancer, 110 and benzene, 225 and insecticide exposure, 110–111 and mixtures of organic solvents, 225 and solvent exposure, 224–225 and trichloroethylene, 225 Brain and central nervous system (CNS) tumors, 121 and benzene, 280 and chloroform, 281 and insecticide exposure, 121–123 and methylene chloride, 279 and mixtures of organic solvents, 281 and phenol, 280 and solvent exposure, 272–282 and tetrachloroethylene and dry-cleaning solvents, 278–279 and toluene, 280 and trichloroethylene, 277–278 and xylene, 280 Breast cancer, 114 and benzene, 235 and insecticide exposure, 114–117 and methylene chloride, 236 and mixtures of organic solvents, 236 and solvent exposure, 230–236 and tetrachloroethylene and dry-cleaning solvents, 235 and trichloroethylene, 234 Bronchospasm, from organophosphorous compounds, 49 2-Butoxyethanol glycol, chemical structure of, 91

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Gulf War and Health: Insecticides and Solvents, Volume 2 n-Butyl acetate, chemical structure of, 93 C Canadian Study, of Gulf War veterans, 544 Cancer overview, 98–101 and insecticide literature, 99–100 and solvent literature, 156–157 toxicity and carcinogenicity, of insecticides, 100–101, 159 toxicity and carcinogenicity, of solvents, 157 Cancers and exposure to insecticides, 98–155 adult leukemia, 134–139 bone cancer, 110–111 brain and CNS tumors, 121–123 childhood cancer, 139–146 female reproductive cancers, 114–117 gastrointestinal tract cancers, 102–105 hepatobiliary cancers, 105–107 Hodgkin’s disease, 130–131 lung cancer, 107–110 multiple myeloma, 132–134 non-Hodgkin’s lymphoma, 123–130 oral, nasal, and laryngeal cancers, 101–102 skin cancer, 112–114 soft tissue sarcoma, 111–112 urologic cancers, 117–120 Cancers and exposure to organic solvents, 156–349 adult leukemia, 308, 313–319 bone cancer, 224–225 brain and CNS cancers, 272–282 breast cancer, 230–236 childhood cancers, 331–338 female reproductive cancers, 237–241 gastrointestinal tract tumors, 184–207 hepatobiliary cancers, 207–214 Hodgkin’s disease, 297, 299–301 lung cancer, 214–224 lymphatic and hematopoetic cancers, 282 multiple myleloma, 301–307 myelodysplastic syndromes, 326–331 non-Hodgkin’s lymphoma, 283, 288–296 oral, nasal, and laryngeal cancer, 179–184 skin cancer, 226–230 soft tissue sarcoma, 225 urologic cancers, 241–272 Carbamate interactions with other agents, 56–57 and AhR action, 56 cimetidine, 56 inhibitor SKF525A effects, 56 malathion coadministration, 56 phenobarbital, 56 Carbamates, 1, 10, 51–57 acute human exposure, 52–53 carbaryl, 1, 10 carcinogenicity, 54 chemical structure of, 51 chemistry of, 51 developmental effects, 54–55 experimental data on, 53–55 genetic polymorphisms and susceptibility, 52 genotoxicity, 54 immune function changes, 55 immunosuppression, 55 interactions with other agents, 56–57 lysozyme activity changes, 55 mechanism of action, 52 methomyl, 1, 10 mutagenicity, 54 neurotoxic effects, 53–54 proxpur, 1, 10 reproductive effects, 54–55 serum complement-fixing activity changes, 55 toxicokinetics, 51–52 Carbaryl, 1, 10 chemical structure of, 51 sperm and semen parameters and, 455 Carboxylesterase, interactions with organophosphorous compounds, 50 Carcinogenicity of carbamates, 54 of lindane, 65 of organophosphorous compounds, 47–48

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Gulf War and Health: Insecticides and Solvents, Volume 2 of pyrethrins and pyrethroids, 60–61 Cardiovascular effects and insecticide exposure, 491–492 and solvent exposure, 492–494 Categories of association, 18–21 Causal relationships or causality, 18–20 Central nervous system (CNS). See Brain and central nervous system (CNS) tumors Cervical cancer, 114 and methylene chloride, 239 and mixtures of organic solvents, 239 and solvent exposure, 237–239 and tetrachloroethylene and dry-cleaning solvents, 239 and trichloroethylene, 239 Chance, assessing the effect of, 26 Chemical interactions multiple exposures and, 13–14 research recommendations from Gulf War and Health, Volume 1, 564 See also Interactions with other agents Chemical structures azamethiphos, 41 benzene, 85 2-butoxyethanol, 91 n-butyl acetate, 93 carbamates, 51 carbaryl, 51 chlorpyrifos, 41 cyclohexanol, 90 DEET, 67 diazinon, 41 dichlorvos, 41 n,n-diethyl-3-methylbenzamide, 67 diethylene glycol, 91 diethylene glycol (mono) butyl ether, 91 ethanol, 90 ethylene glycol, 91 glycol ethers and their metabolites, 92 hexylene glycol, 91 iso-butyl acetate, 93 isopropanol, 90 ketones, 94 lindane, 63 malathion, 41 methanol, 90 1-methoxy-2-propanol acetate, 93 organophosphorous insecticides used in Gulf War, 41 permethrin, 58 d-phenothrin, 58 propylene glycol, 91 pyrethrins and pyrethroids, 58 sec-butyl acetate, 93 tert-butyl acetate, 93 toluene, 85 various alcohols, 90 various esters, 93 various glycols, 91 xylenes, 85 Chemistry of alcohols, 89–90 of aromatic hydrocarbons, 84–85 of carbamates, 51 of n,n-diethyl-3-methylbenzamide, 67 of esters, 93 of glycol ethers, 92 of glycols, 90–91 of ketones, 94 of lindane, 63 of organophosphorous compounds, 40 of pyrethrins and pyrethroids, 57–58 Childhood cancers, 139–140 brain cancer, 146, 337–338 childhood leukemia, 141–146, 332–336 and insecticide exposure, 141–146 neuroblastoma, 336–337 non-Hodgkin’s lymphoma, 146 and solvent exposure, 331–338 Chlorinated-hydrocarbons and other pesticides and repellents, 1, 10 DEET, 1, 10 lindane, 1, 10 permethrins, 1, 10 pyrethrins, 1, 10 rodenticides (bait), 1, 10 Chloroform, 88–89 brain and CNS tumors and, 281 metabolic pathways of biotransformation, 89 Chlorpyrifos, 1, 10 chemical structure of, 41

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Gulf War and Health: Insecticides and Solvents, Volume 2 Chronic glomerulonephritis, 507 Chronic leukemia, 134–135, 308 and benzene, 323 and mixtures of organic solvents, 323 and solvent exposure, 322–323 “Chronic multisymptom illness,” 383–384 Chronic renal failure, and hydrocarbons, 508 Cimetidine (Tagamet®), interactions with carbamates, 56 Cirrhosis, 501 CNS. See Brain and central nervous system (CNS) tumors Cognitive impairment, organophosphorous-induced delayed, 46 Colon or colorectal cancer, 102 and benzene, 198–199 and insecticide exposure, 103, 105 and methylene chloride, 199 and mixtures of organic solvents, 200 and phenol, 199 and solvent exposure, 195–200 and tetrachloroethylene and dry-cleaning solvents, 198 and toluene, 199 and trichloroethylene, 197–198 and xylene, 199 Color discrimination, 439–440 Color vision testing, 581 Concentration, symptoms related to, 384–387 Confounding, 28–30 Congenital malformations, 469 heart, 471–472, 475 and insecticide exposure, 470–473 and maternal exposure, 473, 477 multiple and other malformations, 472 neural-tube defects and other CNS anomalies, 470–471, 474 oral clefts, 475–476 other types of, 476 and paternal exposure, 473, 477 and solvent exposure, 474–477 Connective-tissue disorder, undifferentiated, 520 Cross-sectional studies, definition, 21–22 Cyclohexanol, chemical structure of, 90 D Danish Study, of Gulf War veterans, 547–548 Databases bibliographic, 566 factual, 566 Davis, Miriam, 533–561 DEET. See n,n-Diethyl-3-methylbenzamide Delayed effects of organophosphorous behavioral alterations, 46 cognitive impairment, 46 compounds, 44–46 intermediate syndromes, 45 neurologic deficits, 46 neuropathy, 45–46 tolerance, 44–45 visual deficits, 46 Demographic characteristics, of US Gulf War troops, 534 Depleted uranium (DU), 2, 10 research recommendations from Gulf War and Health, Volume 1, 564 Dermatitis, 509–514 allergic contact dermatitis, 509–510, 512–513 and insecticide exposure, 509–512 irritant contact dermatitis and other skin disorders, 510–511, 513–514 from organophosphorous compounds, 49 and solvent exposure, 512–514 Developmental effects, 450–483 of carbamates, 54–55 congenital malformations, 469–477 of DEET, 69 of lindane, 66 and organophosphorous compounds, 48–49 preconception, 450–461 during pregnancy, 461–469 of pyrethrins and pyrethroids, 61 Diazinon, 1, 10 chemical structure of, 41 Dichlorvos, 1, 10 chemical structure of, 41 Diesel heater fumes, 1, 10

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Gulf War and Health: Insecticides and Solvents, Volume 2 n,n-Diethyl-3-methylbenzamide (DEET), 1, 10, 66–69 acute human exposures, 67–68 chemical structure of, 67 chemistry, 67 developmental effects, 69 experimental data on, 68–69 genetic polymorphisms and susceptibility, 67 interactions with other agents, 69 interactions with pyrethrins and pyrethroids, 62–63 mechanism of action, 67 neurotoxic effects, 68–69 reproductive effects, 69 toxicokinetics, 67 Diethylene glycol, chemical structure of, 91 Diethylene glycol (mono) butyl ether, chemical structure of, 91 Diseases endemic to the Gulf region, 2, 11 leishmaniasis, 2, 11 pathogenic Escherichia coli, 2, 11 sandfly fever, 2, 11 shigellosis, 2, 11 Dizziness, symptoms related to, 387–388 DU. See Depleted uranium E Ecologic studies, definition, 21 Electroencephalography, 577 Electromyograms (EMG), 575–576 End-stage renal disease, and solvents, 508 Endometrial cancer, and methylene chloride, 241 Environmental particles and pollutants, 1, 10 diesel heater fumes, 1, 10 hydrogen sulfide, 1, 10 oil-fire byproducts, 1, 10 sand microparticles, 1, 10 Epidemiologic study designs, 21–24 case-control studies, 22–24 cohort studies, 22 cross-sectional studies, 21–22 ecologic studies, 21 experimental studies, 24 Escherichia coli, pathogenic, 2, 11 Esophageal cancer, 102 and benzene, 190 and insecticide exposure, 105 and methylene chloride, 190 and mixtures of organic solvents, 191 and phenol, 191 and solvent exposure, 184–191 and tetrachloroethylene and dry-cleaning solvents, 190 and toluene, 190 and trichloroethylene, 189 and xylene, 190 Esters, 93–94 chemical structure of various, 93 iso-butyl acetate, 93 1-methoxy-2-propanol acetate, 93 n-butyl acetate, 93 sec-butyl acetate, 93 tert-butyl acetate, 93 toxicology of, 93–94 Ethanol chemical structure of, 90 cohort studies of workers exposed to, 173, 178 Ethylene glycol, chemical structure of, 91 Ethylene glycol ethers, time-to-pregnancy effects and, 461 Evidence of associations. See Categories of association Experimental data on carbamates, 53–55 on DEET, 68–69 on lindane, 65–66 nature and value of, 34–36 on organophosphorous compounds, 46–49 on pyrethrins and pyrethroids, 60–62 Experimental studies, definition, 24 Exposure assessing, 30–32 lack of information on, 14 F Fatality rate, 33 Female Air Force Veterans Study, of Gulf War veterans, 548

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Gulf War and Health: Insecticides and Solvents, Volume 2 Female reproductive cancers, 114–115 cervical cancer, 114, 237–239 and insecticide exposure, 115–117 ovarian and uterine cancer, 114–115, 240–241 and solvent exposure, 237–241 G Gastrointestinal effects and solvent exposure, 502–503 Gastrointestinal tract cancers or tumors, 102–105 colon cancer, 195–200 esophageal cancer, 105, 184, 188–191 and insecticide exposure, 102–105 pancreatic cancer, 103–104, 105, 203–207 rectal cancer, 103, 105, 200–203 and solvent exposure, 184–207 stomach cancer, 191–195 Genetic polymorphisms and susceptibility, 84 from carbamates, 52 from DEET, 67 from organophosphorous compounds, 42 from pyrethrins and pyrethroids, 58 Genetic Susceptibility Study, of Gulf War veterans, 549–550 Genotoxicity of carbamates, 54 of organophosphorous compounds, 48 of pyrethrins and pyrethroids, 61 Glomerulonephritis, 504–508 and hydrocarbons, 508 and solvent exposure, 504–508 Glycol ethers chemical structure of, 92 toxicology of, 92–93 Glycols, 90–92 2-butoxyethanol glycol, 91 chemical structure of various, 91 diethylene glycol, 91 diethylene glycol (mono) butyl ether, 91 ethylene glycol, 91 hexylene glycol, 91 propylene glycol, 91 toxicology of, 90–92 Gulf War and Health, Volume 1, 2, 11, 563–566 conclusions, 563–564 research recommendations from, 564–565 Gulf War health issues, 13–15 complexities in addressing, 13 lack of exposure information, 14 literature on, 17–21, 565–568 multiple exposures and chemical interactions, 13–14 unexplained symptoms, 14 the war experience, 14–15 Gulf War veterans studies, 536–550 Canadian Study, 544 Danish Study, 547–548 Female Air Force Veterans Study, 548 Genetic Susceptibility Study, 549–550 “Iowa Study,” 538–541 major studies of Gulf War veterans’ symptoms and syndromes, 538 Massachusetts and New Orleans Veterans Study, 548 Naval Reservists Study, 548–549 Neurologic Dysfunction Study, 548–549 Oregon and Washington Veterans Study, 543–544 Pennsylvania and Hawaii Veterans Study, 548 University of London Study, 544–546 University of Manchester Study, 546–547 VA Study, 541–543 H Hairy cell leukemia, 135, 308 and acetone, 326 and benzene, 325 and mixtures of organic solvents, 326 and solvent exposure, 325–326 and trichloroethylene, 326 Halogenated hydrocarbons, 85–89 chloroform, 88–89 methylene chloride, 87–88 tetrachloroethylene, 86

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Gulf War and Health: Insecticides and Solvents, Volume 2 toxicology of, 85–89 trichloroethylene, 86–87 Hearing loss, 440–441 Hepatic effects, 499–502 cirrhosis, 501 liver function, 500 and solvent exposure, 499–502 Hepatic steatosis, 500–502 Hepatobiliary cancers, See also Liver cancer, 105 and benzene, 213 and insecticide exposure, 105–107 and methylene chloride, 212 and mixtures of organic solvents, 213–214 and phenol, 213 and solvent exposure, 207–214 and tetrachloroethylene and dry-cleaning solvents, 212 and toluene, 213 and trichloroethylene, 211–212 Hepatotoxic effects, of pyrethrins and pyrethroids, 62 Hexylene glycol, chemical structure of, 91 Hodgkin’s disease, 130 and benzene, 299–300 and insecticide exposure, 130–131 and mixtures of organic solvents, 300–301 and phenol, 300 and solvent exposure, 297–301 and tetrachloroethylene and dry-cleaning solvents, 300 and toluene, 300 and trichloroethylene, 299 and xylene, 300 Hospitalization studies, of Gulf War veterans, 551–552 Hydrazine, 1, 10 Hydrocarbons aromatic, 84–85 chronic renal failure and, 508 glomerulonephritis and, 508 halogenated, 85–89 Hydrogen sulfide, 1, 10 Hypersensitivities, from organophosphorous compounds, 49 I Illnesses in Gulf War veterans epidemiologic studies of veterans’ symptoms and general health status, 536–550 limitations of past and current studies, 555–556 overview of, 533–562 population-based studies, 537–550 registry programs, 534–536 Immune function changes, from carbamates, 55 Immunosuppression, of carbamates, 55 Immunotoxic effects of lindane, 66 from organophosphorous compounds, 49 of pyrethrins and pyrethroids, 61–62 Infertility, 453–455, 458–461 Information bias, 27–28 Inhibitor SKF525A effects, interactions with carbamates, 56 Insecticide exposure and specific cancers, 98–155 adult leukemia and, 134–139 aplastic anemia and, 486 bone cancer and, 110–111 brain and CNS tumors and, 121–123 breast cancer and, 116–117 cancers and, 98–155 childhood cancer and, 139–146 childhood leukemia and, 145–146 congenital malformations and, 473 female reproductive cancers and, 114–117 gastrointestinal tract cancers and, 102–105 hepatobiliary cancers and, 105–107 Hodgkin’s disease and, 130–131 lung cancer and, 107–110 multiple myeloma and, 132–134 non-Hodgkin’s lymphoma and, 123–130 oral, nasal, and laryngeal cancers and, 101–102

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Gulf War and Health: Insecticides and Solvents, Volume 2 pancreatic cancer and, 105 skin cancer and, 112–114 soft tissue sarcoma and, 111–112 urologic cancers and, 117–120 Insecticide literature, and cancer, 99–100 Insecticide toxicology, 39–81 carbamates, 51–57 chemistry of, 41 DEET, 66–69 lindane, 63–66 organophosphorous compounds, 39–50 pyrethrins and pyrethroids, 57–63 Insecticides and neurologic diseases, 411–421 Alzheimer’s disease, 420–421 amyotrophic lateral sclerosis, 418–419 Parkinson’s disease, 412–418 Insecticides and peripheral neuropathy, 356–370 Gulf War veterans and, 356–362 OP insecticides and, 362–370 Insecticides used in the Gulf War, 12–13, 571 Interactions with other agents of carbamates, 56–57 of DEET, 69 of organophosphorous compounds, 50 of pyrethrins and pyrethroids, 62–63 “Iowa Study,” 538–541 exposure-symptom relationships, 540 results of, 541 symptom clustering, 540 Irritant contact dermatitis and other skin disorders, 510–511, 513–514 Iso-butyl acetate, chemical structure of, 93 Isopropanol, chemical structure of, 90 Isopropyl alcohol kidney cancer and, 270 multiple myeloma and, 306 K Ketones chemical structure of, 94 toxicology of, 94 Kidney cancer, 117–118 and benzene, 270 and insecticide exposure, 118–120 and isopropyl alcohol, 270 and mixtures of organic solvents, 270–272 and solvent exposure, 259–272 and tetrachloroethylene and dry-cleaning solvents, 268–269 and toluene, 270 and trichloroethylene, 267–268 and xylene, 270 L Laryngeal cancers, 101 and insecticide exposure, 101–102 and solvent exposure, 180–183 Latency period, 33 Leishmaniasis, 2, 11 Leukemia, 134–135, 307–308 acute, 308, 319–322 acute lymphocytic, 336 acute nonlymphocytic, 336 adult, 307–308, 313–319 childhood, 140–142, 145–146, 332, 335–336 chronic, 308, 322–323 hairy cell, 325–326 lymphatic, 323–325 Lindane, 1, 10, 63–66 acute human exposures, 64–65 carcinogenicity, 65 chemical structure of, 63, 64 chemistry of, 63 developmental effects, 66 experimental data on, 65–66 immunotoxic effects, 66 mechanism of action, 64 mutagenicity, 65 neurotoxic effects, 65 reproductive effects, 66 toxicokinetics, 64 Live vaccines, 2, 11 Liver cancer, See also Hepatobiliary cancers, 105 and insecticide exposure, 106–107 and solvent exposure, 207–214

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Gulf War and Health: Insecticides and Solvents, Volume 2 Liver function, 500 Lung cancer, 107–108 and benzene, 221 and insecticide exposure, 108–110 and methylene chloride, 221 and mixtures of organic solvents, 223–224 and phenol, 222 and solvent exposure, 214–224 and tetrachloroethylene and dry-cleaning solvents, 220 and toluene, 222 and trichloroethylene, 219–220 Lymphatic and hematopoetic cancers, 282 Lymphatic leukemia and benzene, 324 and mixtures of organic solvents, 324 and solvent exposure, 323–325 Lysozyme activity changes, of carbamates, 55 M Malathion, 1, 10 chemical structure of, 41 coadministration, and interactions with carbamates, 56 Massachusetts and New Orleans Veterans Study, of Gulf War veterans, 548 Maternal exposure and congenital malformations, 473, 477 and pregnancy, 462–463, 465–466 MCS. See Multiple chemical sensitivity Mechanisms of action of carbamates, 52 of DEET, 67 of lindane, 64 of organophosphorous compounds, 43 of pyrethrins and pyrethroids, 58–59 Melanoma skin cancers, 112–113 and insecticide exposure, 113–114 and methylene chloride, 228 and mixtures of organic solvents, 229 and phenol, 229 and solvent exposure, 226–229 and tetrachloroethylene and dry-cleaning solvents, 228 and trichloroethylene, 228 Memory, symptoms related to, 384–387 Metabolic pathways, of chloroform biotransformation, 89 Methanol, chemical structure of, 90 Methodology, 2–3 Methomyl, 1, 10 1-Methoxy-2-propanol acetate, chemical structure of, 93 Methylene chloride, 87–88 brain and CNS tumors and, 279 breast cancer and, 236 cervical cancer and, 239 colon cancer and, 199 endometrial cancer and, 241 esophageal cancer and, 190 hepatobiliary cancers and, 212 lung cancer and, 221 melanoma skin cancers and, 228 multiple myeloma and, 306 ovarian cancer and, 240 pancreatic cancer and, 206 prostate cancer and, 246 rectal cancer and, 203 stomach cancer and, 194 uterine cancer and, 241 Microwave radiation, 2, 10 Mixtures of organic solvents acute leukemia and, 321–322 adult leukemia and, 317–319 bladder cancer and, 257–259 bone cancer and, 225 brain and CNS tumors and, 281 breast cancer and, 236 cervical cancer and, 239 chronic leukemia and, 323 colon cancer and, 200 esophageal cancer and, 191 hairy cell leukemia and, 326 hepatobiliary cancers and, 213–214 Hodgkin’s disease and, 300–301 kidney cancer and, 270–272 lung cancer and, 223–224 lymphatic leukemia and, 324 melanoma skin cancers and, 229 multiple myeloma and, 306–307

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Gulf War and Health: Insecticides and Solvents, Volume 2 myelodysplastic syndromes and, 330–331 non-Hodgkin’s lymphoma and, 290–296 nonmelanoma skin cancers and, 230 ovarian cancer and, 240 pancreatic cancer and, 206–207 prostate cancer and, 246 rectal cancer and, 203 stomach cancer and, 194–195 uterine cancer and, 241 Motor neuron disease. See Amyotrophic lateral sclerosis Multiple chemical sensitivity (MCS), 514–516 Multiple exposures, and chemical interactions, 13–14 Multiple myeloma, 132 and acetone, 306 and benzene, 305 and insecticide exposure, 132–134 and isopropyl alcohol, 306 and methylene chloride, 306 and mixtures of organic solvents, 306–307 and solvent exposure, 301–307 and tetrachloroethylene and dry-cleaning solvents, 306 and toluene, 306 and trichloroethylene, 304–305 Multiple sclerosis, 429–434 Mustard agents, 1, 10 Mutagenicity from carbamates, 54 from lindane, 65 from organophosphorous compounds, 48 from pyrethrins and pyrethroids, 61 Myelodysplastic syndromes, 326 and benzene, 330 and mixtures of organic solvents, 330–331 and solvent exposure, 327–331 N Nasal cancers, 101 and insecticide exposure, 101–102 and solvent exposure, 179–180 Naval Reservists Study, of Gulf War veterans, 548–549 NB. See Neurobehavioral effects Nerve agents and precursor compounds, 1, 10 sarin, 1, 10 tabun, 1, 10 Neural-tube defects (NTDs) and other CNS anomalies, 470–471, 474 Neurobehavioral (NB) effects, 377–388 “chronic multisymptom illness,” 383–384 electroencephalography, 580 OP insecticides and, 388–403 with past history of OP poisoning, 390 without past history of OP poisoning, 394–397 posturography, 580 and solvent exposure, 405–406 solvents and, 403–411 in studies of Gulf War veterans, 378–383 symptoms related to dizziness and balance, 387–388 symptoms related to memory and concentration, 384–387 tests for, 576–577, 579 Neuroblastoma, 336–337 Neurologic deficits, organophosphorous-induced delayed, 46 Neurologic diseases, 411–421 Alzheimer’s disease, 420–421 amyotrophic lateral sclerosis, 418–419 insecticides and, 411–421 Parkinson’s disease, 412–418 solvents and, 421–439 Neurologic Dysfunction Study, of Gulf War veterans, 548–549 Neurologic effects, 350–449 insecticides and neurologic diseases, 411–421 insecticides and peripheral neuropathy, 356–370 neurobehavioral effects, 377–388 OP insecticides and neurobehavioral effects, 388–403 short-term vs long-term effects of organophosphorous compounds, 352–353

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Gulf War and Health: Insecticides and Solvents, Volume 2 solvents and neurobehavioral effects, 403–411 solvents and neurologic diseases, 421–439 solvents and peripheral neuropathy, 371–377 solvents and sensory effects, 439–441 Neurologic examination, 574–579 of neurobehavioral effects, 576–577 of peripheral neuropathy, 574–576 of sensory effects, 578–579 Neuropathy, organophosphorous-induced delayed, 45–46 Neurotoxic effects of carbamates, 53–54 of DEET, 68–69 of lindane, 65 of organophosphorous compounds, 46–47 of pyrethrins and pyrethroids, 60 Nitric acid, red fuming, 1, 10 Non-Hodgkin’s lymphoma, 123–124, 282 and benzene, 291–292 and insecticide exposure, 123–130 and mixtures of organic solvents, 294–296 and phenol, 293 and solvent exposure, 283–296 and tetrachloroethylene and dry-cleaning solvents, 293 and toluene, 292–293 and trichloroethylene, 290–291 and xylene, 292–293 Nonmelanoma skin cancers, 112–113 and insecticide exposure, 113–114 and mixtures of organic solvents, 230 and phenol, 229 and solvent exposure, 226–230 and tetrachloroethylene and dry-cleaning solvents, 229 and trichloroethylene, 229 NTDs. See Neural-tube defects O Oil-fire byproducts, 1, 10 Olfactory function, 441 Online databases, 565–568 OP. See Organophosphorous compounds OP insecticides and neurobehavioral effects, 388–403 with a history of past OP poisoning, 389–393 without a history of past OP poisoning, 393–403 OP insecticides and peripheral neuropathy, 362–370 OP poisoning neurobehavioral effects with past history of, 390 neurobehavioral effects without past history of, 394–397 Oral cancers, 101 and insecticide exposure, 101–102 and solvent exposure, 179–181 Oral clefts, 475–476 Oregon and Washington Veterans Study, of Gulf War veterans, 543–544 Organic solvents. See Solvents Organophosphorous (OP) compounds, 1, 10, 39–50 acute human exposures, 43–46 and bronchospasm, 49 carcinogenicity, 47–48 chemical structures of, 41 chemistry of, 40 chlorpyrifos, 1, 10 and dermatitis, 49 developmental effects, 48–49 diazinon, 1, 10 dichlorvos, 1, 10 experimental data on, 46–49 genetic polymorphisms and susceptibility, 42 genotoxicity, 48 and hypersensitivities, 49 immunotoxic effects, 49 interactions with other agents, 50 malathion, 1, 10 mechanism of action, 43 mutagenicity, 48 neurotoxic effects, 46–47 and peripheral neuropathy, 365–367

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Gulf War and Health: Insecticides and Solvents, Volume 2 reproductive effects, 48–49 short-term vs long-term effects of, 352–353 toxicokinetics, 40–41 used in Gulf War, 41 Ovarian cancer, 114 and methylene chloride, 240 and mixtures of organic solvents, 240 and solvent exposure, 240–241 and tetrachloroethylene and dry-cleaning solvents, 240 and trichloroethylene, 240 P Pancreatic cancer, 102 and benzene, 206 and insecticide exposure, 103–105 and methylene chloride, 206 and mixtures of organic solvents, 206–207 and phenol, 206 and solvent exposure, 203–207 and tetrachloroethylene and dry-cleaning solvents, 205 and toluene, 206 and trichloroethylene, 205 and xylene, 206 Parental exposure, and pregnancy, 464 Parkinson’s disease (PD), 412–418, 421–424 Particles, environmental, 1, 10 Paternal exposure and congenital malformations, 473, 477 and pregnancy, 463–464, 467–469 PB. See Pyridostigmine bromide PD. See Parkinson’s disease Pennsylvania and Hawaii Veterans Study, 548 Peripheral neuropathy electromyograms, 575–576 insecticides and, 356–370 neurologic examination of, 574–576 and organophosphorous insecticide exposures, 365–367 solvents and, 371–377 vibrotactile threshold, 576 Permethrins, 1, 10 chemical structure of, 58 interactions with DEET, 69 Pesticides carbamate, 1, 10 chlorinated-hydrocarbons, 1, 10 organophosphorous, 1, 10 Petroleum distillates, toxicology of, 94–95 Phenobarbital, interactions with carbamates, 56 Phenol adult leukemia and, 317 brain and CNS tumors and, 280 colon cancer and, 199 esophageal cancer and, 191 hepatobiliary cancers and, 213 Hodgkin’s disease and, 300 lung cancer and, 222 melanoma skin cancers and, 229 non-Hodgkin’s lymphoma and, 293 nonmelanoma skin cancers and, 229 pancreatic cancer and, 206 rectal cancer and, 203 stomach cancer and, 194 d-Phenothrin, chemical structure of, 58 Piperonyl butoxide, interactions with pyrethrins and pyrethroids, 62 PL 105–277 and PL 105–368, agents listed in, 1–2, 10–11 Pollutants, environmental, 1, 10 Population-based studies, of Gulf War veterans, 537–550 Posturography, 580 Preconception effects, 450–461 infertility, 453–455, 458–461 sperm and semen characteristics, 451–453, 455–458 Preconception end points, 450–461 Precursor compounds, to nerve agents, 1, 10 Pregnancy effects, 461–469 maternal exposure, 462–463, 465–466 parental exposure, 464 paternal exposure, 463–464, 467–469 Pregnancy outcomes, 462–469 Propylene glycol, chemical structure of, 91 Prostate cancer, 117 and benzene, 245–246

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Gulf War and Health: Insecticides and Solvents, Volume 2 and insecticide exposure, 118–120 and methylene chloride, 246 and mixtures of organic solvents, 246 and solvent exposure, 241–246 and tetrachloroethylene and dry-cleaning solvents, 245 and toluene, 245 and trichloroethylene, 244–245 and xylene, 245 Proxpur, 1, 10 Pseudocholinesterase, interactions with organophosphorous compounds, 50 Psychological interactions, research recommendations from Gulf War and Health, Volume 1, 564 Pyrethrin I, chemical structure of, 58 Pyrethrins, 1, 10 Pyrethrins and pyrethroids, 57–63 acute human exposures, 59–60 blood glucose concentrations, 62 carcinogenicity, 60–61 chemical structures of, 58 chemistry of, 57–58 developmental effects, 61 experimental data on, 60–62 genetic polymorphisms and susceptibility, 58 genotoxicity, 61 hepatotoxic effects, 62 immunotoxic effects, 61–62 interactions with other agents, 62–63, 69 mechanism of action, 58–59 mutagenicity, 61 neurotoxic effects, 60 reproductive effects, 61 thyroid weight, 62 toxicokinetics, 58 Pyridostigmine bromide (PB), 1, 10 research recommendations from Gulf War and Health, Volume 1, 564 R Radiation sources, 2, 10 depleted uranium, 2, 10 microwave radiation, 2, 10 radiofrequency radiation, 2, 10 uranium, 2, 10 Radiofrequency radiation, 2, 10 Reactive airways dysfunction syndrome, 498 Rectal or colorectal cancer, 102 and acetone, 203 and benzene, 202 and insecticides exposure, 103, 105 and methylene chloride, 203 and mixtures of organic solvents, 203 and phenol, 203 and solvent exposure, 200–203 and tetrachloroethylene and dry-cleaning solvents, 202 and toluene, 203 and trichloroethylene, 202 and xylene, 203 Red fuming nitric acid, 1, 10 Registry programs for Gulf War veterans, 534–536 demographic characteristics of US Gulf War troops, 534 most frequent symptoms and diagnoses of participants in VA registry, 535 Renal effects, 504–508 Reproductive effects, 450–483 of carbamates, 54–55 congenital malformations, 469–477 of DEET, 69 of lindane, 66 of organophosphorous compounds, 48–49 preconception, 450–461 during pregnancy, 461–469 of pyrethrins and pyrethroids, 61 Research recommendations from Gulf War and Health, Volume 1, 564 biological, chemical, and psychological interactions, 564 depleted uranium, 564 pyridostigmine bromide, 564 sarin, 564 vaccines, 564 Respiratory effects, 494–498 Rheumatic diseases, systemic, 519–520 Rheumatoid arthritis, 520

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Gulf War and Health: Insecticides and Solvents, Volume 2 Rodenticides (bait), 1, 10 S Sand microparticles, 1, 10 Sandfly fever, 2, 11 Sarin, 1, 10 research recommendations from Gulf War and Health, Volume 1, 564 Scleroderma, 517–520 Sec-butyl acetate, chemical structure of, 93 Selection bias, 27 Self-reported exposures, in the VA Study, 543 Semen parameters, 451–453, 455–458 and carbaryl, 455 Sensory effects audiometry, 578 color vision testing, 578 neurologic examination of, 578–579 solvents and, 439–441 Serum complement-fixing activity changes, of carbamates, 55 Shigellosis, 2, 11 Skin cancer, 112 and insecticide exposure, 113–114 and solvent exposure, 226–230 Soft tissue sarcoma, 111 and insecticide exposure, 111–112 and solvent exposure, 225 Solvent exposure, 160–173 Alzheimer’s disease and, 435–437 bladder cancer and, 248–251 brain and CNS cancers and, 272–274 breast cancer and, 230–232 cancers from, 156–349 childhood cancer and, 331–334 gastrointestinal tract tumors and, 185–187 Hodgkin’s disease and, 297–298 kidney cancer and, 260–264 leukemia and, 308–312 liver cancer and, 207–208 lung cancer and, 215 melanoma skin cancers and, 226–227 multiple myeloma and, 301–302 multiple sclerosis and, 431–432 myelodysplastic syndromes and, 327–329 neurobehavioral effects and, 405–406 non-Hodgkin’s lymphoma and, 283–287 oral, nasal, and laryngeal cancer and, 180 peripheral neuropathy and, 372–374 prostate cancer and, 241–242 Solvent interactions, 84 Solvent toxicity, 83–84 Solvent toxicokinetics, 83 Solvent toxicology, 82–97 alcohols, 89–90 aromatic hydrocarbons, 84–85 esters, 93–94 glycol ethers, 92–93 glycols, 90–92 halogenated hydrocarbons, 85–89 ketones, 94 petroleum distillates, 94–95 Solvents, 1, 10 amyotrophic lateral sclerosis and, 425–427 aplastic anemia and, 489–491 and color discrimination, 439–440 end-stage renal disease and, 508 genetic polymorphisms and susceptibility, 84 glomerulonephritis and, 508 and hearing loss, 440–441 information about, 83–84 and neurobehavioral effects, 403–411 and olfactory function, 441 and peripheral neuropathy, 371–377 and sensory effects, 439–441 sent to the Gulf War, 13, 571 time-to-pregnancy effects and, 461 See also Mixtures of organic solvents; individual solvents Solvents and neurologic diseases, 421–439 Alzheimer’s disease, 434–439 amyotrophic lateral sclerosis, 424–429 multiple sclerosis, 429–434 Parkinson’s disease, 421–424 Sperm parameters, 451–453, 455–458 and carbaryl, 455 Stomach cancer, 102 and benzene, 193

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Gulf War and Health: Insecticides and Solvents, Volume 2 and insecticide exposure, 103 and methylene chloride, 194 and mixtures of organic solvents, 194–195 and phenol, 194 and solvent exposure, 191–195 and tetrachloroethylene and dry-cleaning solvents, 193 and toluene, 194 and trichloroethylene, 193 and xylene, 194 Stress-related disorders, 553–554 Structures of molecules. See Chemical structures Study designs, epidemiologic, 21–24 Susceptibility, genetic polymorphisms and, 84 Synthetic chemical compounds, 1, 10 hydrazine, 1, 10 mustard agents, 1, 10 red fuming nitric acid, 1, 10 solvents, 1, 10 volatile organic compounds, 1, 10 Systemic rheumatic diseases, 517–520 other rheumatologic diseases, 518–519 rheumatoid arthritis, 520 scleroderma, 517–520 undifferentiated connective-tissue disorder, 520 T Tabun, 1, 10 Tagamet®. See Cimetidine Tert-butyl acetate, chemical structure of, 93 Testicular cancer, 117 and insecticide exposure, 118–120 Tetrachloroethylene and dry-cleaning solvents, 86 adult leukemia and, 317 bladder cancer and, 255 brain and CNS tumors and, 278–279 breast cancer and, 235 cervical cancer and, 239 colon cancer and, 198 esophageal cancer and, 190 hepatobiliary cancers and, 212 Hodgkin’s disease and, 300 kidney cancer and, 268–269 lung cancer and, 220 melanoma skin cancers and, 228 multiple myeloma and, 306 non-Hodgkin’s lymphoma and, 293 nonmelanoma skin cancers and, 229 ovarian cancer and, 240 pancreatic cancer and, 205 prostate cancer and, 245 rectal cancer and, 202 stomach cancer and, 193 uterine cancer and, 241 Thyroid weight, of pyrethrins and pyrethroids, 62 Time-to-pregnancy effects and benzene, 461 and ethylene glycol ethers, 461 and insecticide exposure, 455 and solvents, 461 Toluene adult leukemia and, 317 bladder cancer and, 256–257 brain and CNS tumors and, 280 chemical structure of, 85 colon cancer and, 199 esophageal cancer and, 190 hepatobiliary cancers and, 213 Hodgkin’s disease and, 300 kidney cancer and, 270 lung cancer and, 222 multiple myeloma and, 306 non-Hodgkin’s lymphoma and, 292–293 pancreatic cancer and, 206 prostate cancer and, 245 rectal cancer and, 203 stomach cancer and, 194 Toxicity and carcinogenicity, 100–101 and determination of carcinogenicity, 157–159 Toxicokinetics of carbamates, 51–52 of DEET, 67 of lindane, 64

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Gulf War and Health: Insecticides and Solvents, Volume 2 of organophosphorous compounds, 40–41 of pyrethrins and pyrethroids, 58 of solvents, 83 Toxicology of insecticides, 39–81 of solvents, 82–97 Toxoid vaccines, 2, 11 Trichloroethylene, 86–87 adult leukemia and, 316 bladder cancer and, 254 bone cancer and, 225 brain and CNS tumors and, 277–278 breast cancer and, 234 cervical cancer and, 239 colon cancer and, 197–198 esophageal cancer and, 189 hairy cell leukemia and, 326 hepatobiliary cancers and, 211–212 Hodgkin’s disease and, 299 kidney cancer and, 267–268 lung cancer and, 219–220 melanoma skin cancers and, 228 multiple myeloma and, 304–305 non-Hodgkin’s lymphoma and, 290–291 nonmelanoma skin cancers and, 229 ovarian cancer and, 240 pancreatic cancer and, 205 prostate cancer and, 244–245 rectal cancer and, 202 stomach cancer and, 193 uterine cancer and, 241 U Undifferentiated connective-tissue disorder, 520 University of London Study, of Gulf War veterans, 544–546 University of Manchester Study, of Gulf War veterans, 546–547 Unmeasured confounding in cohort studies, 28–29 Uranium, 2, 10 depleted, 2, 10 Urologic cancers, 117–118 and insecticide exposure, 118–120 and solvent exposure, 241–272 Uterine cancer, 114–115 and methylene chloride, 241 and mixtures of organic solvents, 241 and solvent exposure, 240–241 and tetrachloroethylene and dry-cleaning solvents, 241 and trichloroethylene, 241 V VA registry, 535 VA Study, of Gulf War veterans, 541–543 Vaccines live, “attenuated,” and toxoid, 2, 11 research recommendations from Gulf War and Health, Volume 1, 564 Validity of findings, 25–33 assessing the effect of bias, 26–27 assessing the effect of chance, 26 confounding, 28–30 exposure assessment, 30–32 health outcome assessment, 32–33 information bias, 27–28 latency period and fatality rate, 33 selection bias, 27 Vibrotactile threshold, 576 Visual deficits, organophosphorous-induced delayed, 46 Volatile organic compounds, 1, 10 W War experience, 14–15 X Xylene bladder cancer and, 257 brain and CNS tumors and, 280 colon cancer and, 199 esophageal cancer and, 190 Hodgkin’s disease and, 300 kidney cancer and, 270 non-Hodgkin’s lymphoma and, 292–293 pancreatic cancer and, 206 prostate cancer and, 245 rectal cancer and, 203 stomach cancer and, 194