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
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
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
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
Association
measures of, 24–25
See also Categories of association
Audiometry, 581
Azamethiphos, chemical structure of, 41
B
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
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
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
acute human exposure, 52–53
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
mutagenicity, 54
neurotoxic effects, 53–54
reproductive effects, 54–55
serum complement-fixing activity changes, 55
toxicokinetics, 51–52
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
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
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
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
Chloroform, 88–89
brain and CNS tumors and, 281
metabolic pathways of biotransformation, 89
chemical structure of, 41
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
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
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
chemical structure of, 41
chemical structure of, 41
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
pathogenic Escherichia coli, 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
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
Female reproductive cancers, 114–115
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
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
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
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
Hydrocarbons
aromatic, 84–85
chronic renal failure and, 508
glomerulonephritis and, 508
halogenated, 85–89
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
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
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
acute lymphocytic, 336
acute nonlymphocytic, 336
childhood, 140–142, 145–146, 332, 335–336
hairy cell, 325–326
lymphatic, 323–325
acute human exposures, 64–65
carcinogenicity, 65
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
Liver cancer, See also Hepatobiliary cancers, 105
and insecticide exposure, 106–107
and solvent exposure, 207–214
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
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
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
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
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
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
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
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
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
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
and dermatitis, 49
developmental effects, 48–49
experimental data on, 46–49
genetic polymorphisms and susceptibility, 42
genotoxicity, 48
and hypersensitivities, 49
immunotoxic effects, 49
interactions with other agents, 50
mechanism of action, 43
mutagenicity, 48
neurotoxic effects, 46–47
and peripheral neuropathy, 365–367
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
chemical structure of, 58
interactions with DEET, 69
Pesticides
chlorinated-hydrocarbons, 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
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
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
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 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
radiofrequency radiation, 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
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
S
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
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
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
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
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
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
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
of organophosphorous compounds, 40–41
of pyrethrins and pyrethroids, 58
of solvents, 83
Toxicology
of insecticides, 39–81
of solvents, 82–97
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
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