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

Ames test, 59, 112

γ-Aminobutyric acid (GABA), 35, 63, 79, 117, 118

Amyotrophic lateral sclerosis (ALS), 15, 40, 51

Animals

FOB end points, list, 71

models, 49, 54, 79

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,

animal models, 49, 54

disease surveillance, 108,

concepts and definitions, 43-48, 51-52

of effect, 44, 45, 47-48, 51

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

recommendations, 5, 124

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



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Environmental Neurotoxicology 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 Ames test, 59, 112 γ-Aminobutyric acid (GABA), 35, 63, 79, 117, 118 Amyotrophic lateral sclerosis (ALS), 15, 40, 51 Animals FOB end points, list, 71 models, 49, 54, 79 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, animal models, 49, 54 disease surveillance, 108, concepts and definitions, 43-48, 51-52 of effect, 44, 45, 47-48, 51 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 recommendations, 5, 124 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

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Environmental Neurotoxicology Cells culture techniques, 61-62, 63-64 ganglia, 27-28 glial, 21, 22, 24, 39, 61, 62, 63, 64, 79 loss, 51 nuclei, 27, 28 plasticity, 29, 30 Schwann, 22, 24 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 DDT, 25, 31, 34 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 Dyskenesia, 15, 54 E Electroencephalography (EEG), 78 Electrophysiology, 31 Environmental Protection Agency (EPA) guidelines, 84, 87 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 Ethanol, 16, 17-18, 98 Explant cultures, 61, 62 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 occupational, 2, 9, 16, 17, 96

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Environmental Neurotoxicology during pregnancy, 15, 50-51 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 cognitive processes, 66, 70 motor performance, 65, 69, 72, 73 neurotoxic effects, 65-66, 69-70 sensory acuity, 65-66, 69, 72, 73-74 memory, 66, 70, 74-76 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 Methanol, 1, 120 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

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Environmental Neurotoxicology 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 complexity, 29-30, 31 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 receptor sites, 46, 47 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 communication, 24-27, 33, 55 development and functions, 21-22, 29-30 , 51 glucose, 32 illustrations, 23, 26 integrative functions, 65-66 ions, 24-25, 29, 33, 116 nerve impulse, 24-25, 26 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

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Environmental Neurotoxicology 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 Potassium ions, 24, 25, 33 Pregnancy, 15, 50-51 Prevention (primary and secondary), 18, 53, 95-96 Psychosis, toxic, 15 Pyrethroids, 25, 31, 33, 34-36, 44, 59 Pyrrole, 37-38, 59 R Radiation, 9, 15 Reaggregate cultures, 61, 62 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 recommendations, 5-6, 123-127 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 research needs, 2-3, 90-93 sensitivity, 56-57 specificity, 56-57 strategies for improved testing, 88-89, 124-125 validation, 3, 57, 89-90, 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 need, 95-97, 126 neurobehavioral test batteries, 97-104 recommendations, 4-5, 126-127 see also Disease surveillance; Risk Assessment

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Environmental Neurotoxicology 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 strategy, 2-4, 56, 125 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 Neurobehavioral Core Test Battery, 97-101, 102, 103-104