Index
A
3-Acetyl-2,5-hexandedione (AcHD), 38
Acetylcholinesterase, 47, 48, 79
Acrylamide, 76, 80, 98, 101, 116, 119
Agency for Toxic Substances and Disease Registry (ATSDR), 1, 108-109
Alcohol, see Ethanol
Alzheiner's disease, 15, 40, 47, 48, 51, 83
American Conference of Governmental Industrial Hygienists (ACGIH), 17, 53
γ-Aminobutyric acid (GABA), 35, 63, 79, 117, 118
Amyotrophic lateral sclerosis (ALS), 15, 40, 51
Animals
FOB end points, list, 71
neurotoxicity testing, 49-50, 53-93, 118, 119, 124, 125
neurotoxic effects of representative agents, list, 67-68
see also Testing
Annual Survey of Hiness and Injury, 106
Antidepressants, tricyclic, 16
Australian information-processing theory test battery, 97, 102, 103
Axons, see under Neurons
B
Behavioral assessment, 66, 69-70, 72-73, 87
Benchmark dose (BD), 114
Biochemical assays, 59-62
Biologic markers,
disease surveillance, 108,
concepts and definitions, 43-48, 51-52
of exposure, 16, 36, 43, 44, 45, 46-47, 51
for in vitro systems, list, 63
of neurotoxicity, list, 45
quality assurance and quality control, 49-50
selected, illustration, 92
of susceptibility, 44, 45, 48, 51
use in risk assessment, 43, 50-51, 124
validation, 44, 48-50, 56, 124
Blood-brain barrier, 16, 28-29, 39, 55, 64
Brain, imaging procedures, 81-83
Bureau of Labor Statistics (BLS), 106
C
Carbamates, 58-59
Carbon disulfide, 11
Cells
culture techniques, 61-62, 63-64
ganglia, 27-28
glial, 21, 22, 24, 39, 61, 62, 63, 64, 79
loss, 51
see also Nervous system;
Neurons
Centers for Disease Control, 50
Central nervous system (CNS), 27-29, 30, 32, 34, 35, 40, 47, 55, 64, 80, 81, 82, 84, 97, 103, 111, 115-116, 120
see also Nervous system
Cerebral cortex, 27-28
Cerebral glucose, 83
Chemicals
diagram of MPTP toxicity, 39
exposure response characteristics, list, 98-99
neurobehavioral effects, list, 11, 69-70
neurotoxic effects in humans and animals, list, 67-68
neurotoxicants, list, 10
receptors, list, 118
regulation and testing, 18-19, 53-93, 95, 97, 123-127
see also Exposure;
Nervous system;
Risk assessment;
Testing;
and specific chemicals
Comprehensive Environmental response, Compensation, and Liability Act (CERCLA), 109
Computed axial tomography (CAT), 31, 81, 82, 83, 109-110
Consumer Product Safety Commission, 86, 124
Cycad (Cycas circinalis), 15
D
Department of Veterans Affairs, 126
Developmental neurotoxicology, 84
Dieldrin, 117
Diisopropyl fluorophosphate (DFP), 75
γ-Diketones, 31, 32-33, 36-39, 40, 46, 48, 59, 64, 77, 79
3,4-Dimethyl-2,5-hexanedione (DMHD), 37, 38
Disease surveillance
biologic markers, 108
clinical neurologic examination, list of components, 100
disease and exposure registries, 108-109
identification and prevention efforts, 95-97, 120
imaging techniques, 109-110
medical training, 107
recommendations, 126-127
sentinel health events (SHEs), 108, 127
standardized disease definitions, 107-108
surveillance efforts, 105-110
Dopamine, 29, 31, 33, 39, 40, 47, 78-79
Dose-response relationships, 2-3, 5, 6, 16, 43, 50, 51, 56, 72, 111 , 112, 113, 114-116, 120, 125
E
Electroencephalography (EEG), 78
Electrophysiology, 31
Environmental Protection Agency (EPA)
premanufacturing notice (PMN) program, 86
regulation and testing of chemicals, 18, 19, 50, 53-54, 58, 86-87, 89, 105, 124
review of substances, 53, 86-87
Epinephrine, 48
Exposure
biologic markers, 16, 36, 43, 44, 45, 46-47, 51, 126
characteristics of neurotoxicant exposure responses, list, 98-99
detection and control, 18-19, 43, 95-110
environmental, 1-2, 16-19, 95, 96
magnitude of problem, 17-18
see also Risk assessment
F
Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA), 86, 87
Finland Institute of Occupational Health test battery, 97, 101, 102
Food and Drug Administration (FDA), 50, 58, 84, 87, 124
Functional observational batteries (FOBs), 66-72, 73, 74, 89, 90
G
Glial fibrillary acidic protein (GFAP), 79
Glucose, in nervous system, 32
Good laboratory practices (GLPs), 50
H
Hazard identification, in neurotoxicity risk assessment, 4, 112, 120, 125-126
Health Care Financing Administration (U.S. Department of Health and Human Services), 18
Health Hazard Evaluation Program, 97, 104, 107
Hemoglobin adducts, 79
n-Hexane, 33-34, 36, 37, 38, 59, 77, 98, 101, 121
2,5-Hexanedione (HD), 36, 37, 38, 47, 80
Homovanillic acid (HVA), 78
Hormone production, 80
Humans
effects of representative neurotoxic agents, 67-68
neurotoxicity testing, 95-110, 118-119, 124, 125
see also Risk Assessment;
Screening;
Surveillance;
Testing
Hypothalmus, 27-28
I
Imaging procedures, 81-83, 109-110
In vitro and in vivo testing, see Screening;
Testing
Insecticides, 25, 34-36, 44, 59
see also specific insecticides
Integrated Management Information Systems (IMIS), 104, 105
Integrative functions
motor performance, 65, 69, 72, 73
neurotoxic effects, 65-66, 69-70
sensory acuity, 65-66, 69, 72, 73-74
Intelligence quotient (IQ), 9, 64, 112, 13
L
Lathyrism (spastic paraparesis), 11
Lead, 1, 2, 11, 15, 55, 58, 72, 78-79, 80-81, 98, 105, 108, 113, 116, 121
Learning/memory function, 66, 70, 74-76
Lowest-observed-adverse-effect level (LOAEL), 56, 114-116
Lymphocyte neurotoxic esterase (NTE), 79
Lysergic acid diethylamide (LSD), 33
M
Magnetic resonance imaging (MRI), 31, 81-82, 83, 110
Malathions, 31
Manganese, 15
Mental retardation, 15
Mercury, 1, 2, 15, 51, 58, 79, 98
Metabolism, in central nervous system, 28
Methyl n-butylketone, 36, 37, 48, 59, 77, 101
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, see MPTP
Methylmercury, 49, 51, 55, 64, 72, 80, 85, 98, 101, 120
Microencephaly, 15
Modifying variables, in neurotoxicity testing
age at exposure, 83-84
age at testing, 84-85
genetic differences, 85
sex, 85
Motor activity and function, 65, 69, 72, 73, 77
MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahy-dropyridine), 15, 31, 34, 39-40, 49, 51, 58, 82-83, 98, 110, 119
Myelin, 24, 30, 31, 38, 64, 80-81
N
National Center for Health Statistics (NCHS), 106, 108, 126
National Center for Toxicological Research (NCTR)
behavioral-teratology tests, list, 83
Collaborative Study, 84
National Death Index, 106
National Health and Nutrition Examination Surveys (NHANES), 105, 106
National Health Interview Survey, 106
National Human Adipose Tissue Survey (NHATS), 105
National Institute for Occupational Safety and Health (NIOSH), 17, 97, 104-105, 107, 108
National Institute of Standards and Technology, 50
National Occupational Exposure Survey (NOES), 104-105, 109
National Occupational Hazard Survey (NOHS), 104-105, 109
National Toxicology Program (NTP), 87-88
Nerve-conduction studies, 76-77
Nervous system
biologic markers, 43-52
cellular anatomy and physiology, 15-16, 21-27, 61, 62, 63-64
effects of toxicants on, 2, 9-17, 21, 25, 30-40
examples of neurotoxic mechanisms, 33-40
lipid-soluble toxicants, 31-32
neuropathic evaluation areas, list, 81
repair limitations, 31, 40, 51, 55
structure and function, 15-16, 21, 27-30, 40-41
tissues used in neurophatologic evaluation, list, 82
see also Central Nervous System;
Neurons;
Neurotransmitters;
Peripheral Nervous System
Neurobehavioral Core Test Battery (NCTB), 97-101, 102, 103-104
Neurobehavioral Evaluation System (NES), 101, 102, 104
Neurobehavioral test batteries, 97-104
see also specific test batteries
Neurochemical procedures, 78-79
Neuroendocrine interactions, 79-80, 125
Neurons
axons, 22-24, 25, 30, 31, 32-33, 38, 55, 64, 77, 80
development and functions, 21-22, 29-30 , 51
glucose, 32
integrative functions, 65-66
structure, 22-24
synaptic messengers, 26-27, 33, 55
synaptic transmission, 25-26, 27, 33, 77
trophic interactions, 30
see also Nervous system;
Neurotransmitter
Neuropathology, 80-81
Neurophysiologic procedures, 76
Neurotoxicity events, list of major, 12-14
Neurotransmitters, 25-27, 31, 32, 33, 40, 47, 55, 61, 78, 111-112, 116
see also Nervous system;
Neurons
No-observed-adverse-effect level (NOAEL), 56, 114-116
Nuclear magnetic resonance spectroscopy (MRS), 81, 82
O
Occupational Safety and Health Administration (OSHA), 104, 105, 109 , 124
Office of Technology Assessment (OTA), 90
Office of Toxic Substances (EPA), 87
Organization for Economic Cooperation and Development (OECD), 50, 86, 90
Organ cultures, 61-62
Organophosphates, 47, 58-59, 77, 98
Organophosphorus (OP) esters, 59-60, 79, 81, 86
P
Parkinsonism, 15, 31, 34, 39-40, 49, 51, 85, 119
Peripheral nervous system, 27, 31, 35, 81, 116
see also Nervous system
Pesticides, 1, 2, 17, 31-32, 33, 34, 47, 72, 79, 86, 95, 105, 117
see also specific pesticides
Pharmaceuticals, 2, 9, 16, 18, 33, 54
Phenylalanine, 85
Poisoning, pyrethroid, 34-36
Positron-emission tomography (PET), 31, 40, 81, 82, 83, 110
Prevention (primary and secondary), 18, 53, 95-96
Psychosis, toxic, 15
Pyrethroids, 25, 31, 33, 34-36, 44, 59
R
Risk assessment
approaches to, 114-116
biologic markers, 43, 50-51, 124, 124, 125
cognitive model, 113
curve-fitting, 114, 116-117, 120
carcinogenicity models, 111-113, 119
hockey-stick model, 116-117
neurotoxicity models, 111-113, 117-119, 120
neurotoxicity receptors, 117-118
no-threshold model, 117-118
NRC paradigm, 56
problems, 17-18, 19, 50-51, 111-112
safety-factor approach, 114-117
statistical models, 114-116, 121
strategy, 2-3
see also Screening;
Surveillance;
Testing
S
Schedule-controlled operant behavior (SCOB), 72-73
Screening
applications, 57-58
evaluation of in vitro tests, 91-92
in vitro batteries, 62-65, 90-92
in vivo batteries, 66-71
multitiered testing, 2-3, 88-89, 124-125
priority-setting and implementation, 90
protocol for in vitro system, 65
sensitivity, 56-57
specificity, 56-57
strategies for improved testing, 88-89, 124-125
see also Testing
Sensory-evoked potentials, 77-78
Sensory function, 65-66, 69, 72, 73-74, 77-78
Sentinel Event Notification System (SENSOR), 108
Social Security Administration, 126
Sodium ions, 24-25, 33, 34, 35-36, 44, 59, 63
Stimulus-response techniques, 74, 75-76
Structure-activity relationships (SARs), 4, 19, 54, 56, 58-59, 117 , 124, 125
Superfund Amendments and Reauthorization Act (SARA), 105
Surveillance
of disease, 105-110
of exposure, 104-105
neurobehavioral test batteries, 97-104
see also Disease surveillance;
Risk Assessment
T
Testing
behavioral assessment, 66
diagnostic techniques, 31, 47-48
difficulties, 54-55
effects of age, 83-85
effects of genetic differences, 85
effects of sex, 85
electroencephalography, 78
functional observational batteries (FOBs), 66-72, 73, 74, 89, 90
hazard characterization, 56
imaging procedures, 81-83
in vitro, 4, 5, 18-19, 54, 59-65, 90-92, 124, 125
in vivo, 5, 18-19, 54, 65-85, 124, 125
laboratory, 49-50;
see also Animals
modifying variables, 83
motor-activity, 72
nerve-conduction studies, 76-77
neurochemical procedures, 78-79
neuroendocrine interactions, 79-80, 125
neuropathology, 80-81
neurophysiologic procedures, 76
recommendations, 2-5
regulatory approaches, 86-93
schedule-controlled operant behavior, 72-73
screening characteristics and applications, 56-58
sensory evoked potentials, 77-78
specialized function tests, 73-76
standards and guidelines, 18, 19, 49-50, 53-54
structure-activity relationships, 19, 54, 56, 58-59
see also Animals;
Environmental Protection Agency;
Humans;
Screening;
Surveillance
Toxic Release Inventory (TRI), 105
Toxic Substances Control Act (TSCA), 19, 86, 95
Tri-o-cresylphosphate (TOCP), 15
W
World Health Organization (WHO)
recommendations for neuropathologic evaluation, 81
