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Suggested Citation:"Index." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
×

Index

A

Abortion (spontaneous), early fetal/embryo loss, 7, 11, 18, 19, 23, 38, 62, 103, 185, 233

DES, 23, 73, 223

Acceptable daily intake, 26, 40, 55

defined, 281

pharmaceutical agents, 41

Acetylaldehyde dehydrogenase, 103

Adenosine triphosphate, 114

Agency for Toxic Substances and Disease Registry, 217

Alcohol dehydrogenase, 103

Alcohol use and abuse, 20, 22, 41, 60, 103, 233

dose-response, 41

historical perspectives, 60

American Chemical Society, 24

Ames test, 176-177

Aminopterin, 23

Androgen, 34, 66, 67, 105

Angiotensin-converting enzymes, 23, 69-70

Animal models, 76, , 16, 21, 24-25, 27, 28, 29-34 (passim), 70, 83, 149, 150, 151-195, 198-199, 203, 204, 210, 225-227, 233, 234, 296-306

Ames test, 177

bioassays, 3, 5, 6, 12, 16, 24, 28, 32, 34-37, 40, 54, 100, 153, 164, 167, 170, 176, 177, 186-187, 191, 200, 203-208 (passim), 221, 236, 237, 239-240

cell differentiation, 149, 150, 152, 168, 185

committee charge and methodology, 3, 4-6, 225-226

cost of research, 27, 152, 153, 167, 176, 177, 191, 203, 205-206, 208, 224, 225-226, 238

databases, 8, 15, 31, 40, 155, 157, 216, 218, 292, 293, 294

dose and dose-response, 7, 8, 38, 34, 35, 40-41, 178, 182, 197, 200, 201, 206, 209

extrapolation from high to low doses, 8, 34, 35, 40-41, 55-57, 197, 225, 226, 231, 238, 241

epidemiological studies and, 38, 233, 234

exposure indices, 34, 36, 207, 236

extrapolation, interspecies, 6, 7-8, 12, 34, 35, 40-41, 42, 45-46, 50, 54, 55, 56-57, 120, 141-143, 157, 159, 178, 187-188, 195-201 (passim), 206, 214, 215, 216, 222, 224, 229, 236, 238, 240-241, 242-243

from high to low doses, 8, 34, 35, 40-41, 55-57, 197, 225, 226, 231, 238, 241

toxicokinetics, 7-8, 45-46, 225

forward genetics, 154-156, 161, 284

gene expression and regulation, 4, 5, 115, 116-119, 128, 157, 165, 168, 170, 171, 188-189, 223, 224, 237

Suggested Citation:"Index." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
×

genetic factors, general, 153-195, 180, 223-224, 234-235

genomics, 4, 5, 8, 13, 14, 15, 92, 97, 101, 104, 106, 114-115, 123, 127-128, 143, 153, 155-157, 159-160, 163, 168, 169, 171, 172, 182, 195, 209, 216, 217-218, 227, 233, 292

historical perspectives, 11, 12, 35, 113-114, 115, 120-121, 123, 145-146, 151-152, 153, 161-163

mechanism-based toxicity results, 6-7, 63, 65, 70, 73-81 (passim), 195, 198-199, 225, 227

methylmercury, 75

musculoskeletal system, 34, 180

retinoids, 77

reverse genetics, 94, 156-157, 287

single-celled organisms, 151-152

bacteria, 151, 158, 163, 174, 176, 193, 204, 227

yeast, 14-15, 41, 92, 93, 94-97, 114, 143, 151-152

toxicokinetics, 42, 44-47

valproic acid, 82

see also Knockout mutations;

Mouse and rat models;

Nonmammalian models;

Sensitization;

Transgenics

Antiarrhythmic drugs, 72

Anticonvulsants, 23, 73, 80

diphenylhydantoin, 4, 23, 66, 73-74, 87, 102-103, 210

valproic acid, 23, 46, 48, 60, 82-83, 85-86

Apoptosis, 8, 61, 52, 71, 77-78, 83-84, 87, 134, 139, 140, 180, 189, 231, 302

Aryl hydrocarbon hydroxylase, 53

Aryl hydrocarbon receptor (AHR), 65, 80-82, 106, 182

Autism, 18, 84-86

B

Bacteria, 114, 158, 163, 174, 176, 193, 204, 227

bacteriophages, 110, 151, 210

genomics, 93, 143

transfection, 174, 193-195, 205

Basic Local Alignment Search Tool, 115, 293

Behavioral assays, 113, 180-181, 185-186, 187, 190, 200, 207, 209

Behavioral factors, see Life-style risk factors

Benchmark dose, 40, 54, 55-56, 281

Benzo[a]pyrene, 28, 51, 53, 63

Bioinformatics, 15, 99-100, 214-215, 216

defined, 281

see also Databases

Biologic Markers in Reproductive Toxicology, 49

Biomarkers, 49-54, 202, 242

carcinogenesis, 51-52, 215

databases, 214-215

defined, 49-50, 53, 214, 281-282

dose and, 50, 214, 215

effect, 49, 51, 52, 53, 214, 215, 281

birth weight, 1, 18, 34, 40, 52, 74

exposure, 42, 49, 50-52, 53, 214, 281

functional deficits, 51, 214

gene expression and regulation, 51, 52, 214

placental, 52, 53

smoking, 51, 52, 53

susceptibility, 49, 50, 53-54, 214, 215, 281-282

see also Drug-metabolizing enzymes

Biotechnology, see Genetic engineering

Bipolar disorder, lithium, 23

Birth weight, 1, 18, 34, 52

dose-response, 40

methotrexate, 74

Brain, 130, 133, 135, 145-146

alternatives to testing pregnant mammals, 33

autism, 85

mental defects, 1, 18, 19, 23

methylmercury, 74-75

neural tube defects, 19, 23, 48, 52, 62-63, 82, 84, 144

retinoids, 76, 79

C

Caenorhabditis elegans, 14-15, 63, 101, 104, 113, 114, 123, 124, 143, 150, 152-153, 154, 156-161 (passim), 163, 167, 178-182, 191, 195, 216, 224, 178-182, 206-207, 226, 231, 234, 293, 297-298, 300, 303

genomics, 14-15, 88, 93, 94, 101, 104, 195, 216, 226, 234

Cancer and carcinogenesis, 48, 133, 134, 209, 213, 217, 234

Ames test, 176-177

biomarkers, 51-52, 215

DES, 73

Suggested Citation:"Index." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
×

methotrexate, 74

ovarian cancer, 32, 33

Cancer Genome Anatomy Project, 98, 217, 294

Cardiovascular system, 17, 18, 23, 130, 132, 133, 145

antiarrhythmic drugs, 72

retinoids, 77-78

Case-control studies, 38

Case series, 37

Cell cultures, 3, 6, 7, 12, 28-34, 77, 192-195, 197, 198, 200, 204, 205, 237

methylmercury, 75

retinoids, 78

Cell death, see Apoptosis

Cell differentiation, 12, 19, 64, 99, 101, 109, 112, 124, 127, 128, 129, 149-150

animal models, 149, 150, 152, 168, 185

retinoids and, 79-80

risk assessment, 33, 52, 224, 228-229

stem cells, 32, 111, 172, 173-174, 283

see also Organogenesis

Cell proliferation, 4, 14, 28, 32, 33, 34, 52, 64, 66, 71, 87, 148, 149, 228

see also Cancer and carcinogenesis

Cell-to-cell signaling, 4, 5, 6-7, 8, 13, 14, 16, 87, 111-112, 126-136, 143, 149-150, 158-159

history of developmental biology, 110, 111

in vitro models, 30

organogenesis, 144, 146

see also Checkpoint pathways;

Molecular-stress pathways;

Receptor-mediated actions;

Signaling pathways;

Transduction

Cellular processes, general, 14, 28-29, 64, 65-71, 86, 88, 109-113, 143, 185, 222, 225

apoptosis, 8, 61, 52, 71, 77-78, 83-84, 87, 134, 139, 140, 180, 189, 231, 302

cleavage, 72, 83-84, 109, 116, 140, 170, 228

cytochrome P450, 66, 74, 80, 104, 293

epidermal cells, general, 142, 146

epidermal growth factor, 63, 81, 179

eukaryotic, 93, 127, 138, 139, 143, 152, 161, 192, 193, 194, 283

history of developmental biology, 109-110, 111

methylmercury, 75

stem cells, 32, 111, 172, 173, 283

transduction, 14, 16, 55, 71, 72-73, 84, 86-87, 126, 150, 151, 237, 294

transfection, 174, 193-195, 205

transplantation technologies, 109. 111

see also Bacteria;

Gene expression and regulation;

Genetic factors, general;

Intracellular signaling;

Molecular-stress pathways;

Oocytes;

Receptor-mediated actions;

Secretion and secretory processes;

Signaling pathways;

Yeast;

Zygotes

Center for the Evaluation of Risks to Human Reproduction

Centers for Disease Control and Prevention, 211

Central nervous system, 23, 109, 132, 149, 187, 190

autism, 84

fetal alcohol syndrome, 103

methylmercury, 74

retinoids, 76, 79

see also Brain

Cerebral palsy, 18

Checkpoint pathways, 7, 8, 16, 25, 75, 87, 127, 136-141, 152, 185, 189, 204, 208-209, 225, 227, 228, 229, 231, 233, 235, 238, 239, 241, 295, 231, 233, 235, 238, 239, 241, 295, 296, 302

Chickens, 33, 58-59, 125, 153, 216, 292

Chromosomes, 7, 17, 19, 20, 88, 93, 122, 139, 160, 161-162, 163, 168, 170

see also Genomics

Cleavage, 72, 83-84, 109, 116, 140, 170, 228

Clefting, see Oral clefting

Clinical trials, 37

Cloning, 13, 86, 94, 97, 111, 115, 153-157 (passim), 159-166 (passim), 168, 169, 173, 174, 176, 183, 184, 186, 192, 193

Cmax see Peak threshold concentration

CNS, see Central nervous system

Cohort studies, 37-38

Computer applications

extrapolation from animal models to humans, 242

forward genetics, 156

genetics, general, 157

see also Bioinformatics;

Databases;

Internet

Connective tissue, 23, 145, 148

cystic fibrosis, 106, 153

fibroblasts, 145, 176, 185, 193

Convulsions, see Anticonvulsants

Cost factors, see Economic factors

Suggested Citation:"Index." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
×

Coumarin derivatives, 23, 105

Covalent binding, 66

Craniofacial defects, 23, 71, 73, 74, 76, 77, 78, 79, 80, 85, 103

see also Oral clefting

Cyclopamine, 72-73, 87, 223, 229, 232

Cyclophosphamide, 23

Cystic fibrosis, 106, 153

Cytochrome P450, 66, 74, 80, 104, 293

Cytomegalovirus, 194

D

Danio rerio, see Zebrafish

Databases, 8, 12, 27, 31, 201-202, 210-219, 229, 243-244, 290-295

animal models, 8, 15, 31, 40, 155, 157, 216, 218, 292, 293, 294

bioinformatics, 15, 99-100, 214-215, 216, 281

biomarkers, 214-215

dose and dose-response, 201, 214

genetics, general, 16, 97, 98-100, 114-115, 155, 212-214, 216, 217-218, 243, 290-295

genomics, 16, 97, 98-100, 114-115, 155, 212-214, 216, 217-218, 243, 290, 292, 293, 294

bioinformatics, 15, 99-100, 214-215, 216, 281

Internet, 92, 218, 290, 292, 293. 294-295

minor defects, 18

multidisciplinary linkages, 100, 216-219, 229, 243-244, 290

organogenesis, 150

polymorphisms, 8, 98-99, 212-214, 216, 243, 291, 293, 294

proteomics, 15, 97, 114, 218, 290, 291, 293, 294

see also Internet

Death, see Mortality

Delta pathways, 66, 127, 129, 179-180, 300

Δ7-dehydrocholesterol, 72-73

Department of Energy, 93, 99-100

Department of Health and Human Services, see Agency for Toxic Substances and Disease Registry;

Centers for Disease Control and Prevention;

National Cancer Institute;

National Institutes of Health

DES (diethylstilbesterol), 23, 73, 223

Developmental and Reproductive Toxicological Database, 217

Diabetes, 38

Diet, see Nutrition

Diethylstilbesterol, see DES

Diphenylhydantoin (DPH), 4, 23, 66, 73-74, 87, 102-103, 210

DNA, 4, 65, 66, 70, 87, 123, 139, 151, 155, 156, 157, 159-160, 162-163, 166, 172-175, 192-193, 293, 296

adducts, 51, 52, 53, 66, 87, 204, 302

Ames test, 176-177

defined, 284

diphenylhydantoin, 73-74

introns, 88, 174, 175, 194, 217, 284

microarray technology, 93-98, 100, 159-160, 205, 207, 210, 214, 216

molecular-stress pathways, 138, 139, 140

polymorphism, 90-91, 291

retinoids, 78-79

transfection, 174, 193-195, 205

transposons, 115, 157, 163

see also Chromosomes;

Genomics;

Transcription

DNA Data Bank of Japan, 99

Dose and dose-response, 3, 7, 27, 28, 30-31, 32, 39-41, 45, 46, 61, 229

acceptable daily intake, 26, 40, 41, 55, 281

alcohol, 41

animal models, general, 7, 8, 38, 34, 35, 40-41, 178, 182, 197, 200, 201, 206, 209

extrapolation from high to low doses, 8, 34, 35, 40-41, 55-57, 197, 225, 226, 231, 238, 241

toxicokinetics, 7-8, 45-46, 225

benchmark dose, 40, 54, 55-56, 281

biomarkers, 50, 214, 215

birth weight, 40

databases, 201, 214

maximum tolerated dose, 36, 45

peak threshold concentration (Cmax), 46, 48, 49

reference dose, 39, 40, 41, 54, 55, 287

regulatory issues, 40, 45, 54

toxicokinetics, 40-41, 45, 46

wild-type, 115

see also Exposure

DPH, see Diphenylhydantoin

Suggested Citation:"Index." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
×

Drosophila melanogaster, 14-15, 63, 89-90, 93, 101, 104, 113-114, 115-128, 141, 142, 143, 153, 159, 161-166, 182-186, 191, 195, 206-207, 216, 224, 226, 230-235 (passim), 296, 297-304 (passim)

embryos, 115-128, 161, 159, 161, 182, 183, 185

genome, 14-15, 93, 101, 104, 233-234, 292

mutation, 113-114, 115-128, 161, 183, 184, 185, 186, 235

oocytes, 115, 116, 119, 120

structural defects, 14-15, 89-90, 93, 101, 104, 113-114, 115-127

Drug-metabolizing enzymes (DMEs), 6, 7, 8, 44, 49, 53-54, 66, 99, 102, 103-106, 107, 141, 177, 188, 188-189, 194-195, 197, 200-208 (passim), 213, 214, 215, 222, 227, 228, 231-232, 234, 236-237, 239-240, 243

defined, 283

Drugs, see Pharmaceuticals

E

Ecogenetics, 103-104, 105-106, 198, 232

genotype-environment interactions, 6, 25, 88, 175, 220, 228, 233, 234, 235

epidemiology and, 89, 99, 100-106, 215-216

defined, 283

Economic factors

developmental defects, costs of, 17-18

research costs, 27, 152, 153, 167, 176, 177, 191, 203, 205-206, 208, 224, 225-226, 238

risk assessment paradigm, 27, 198

Ectopic expression, 79, 170, 188, 234, 283

Effect (biomarkers), 49, 51, 52, 53, 214, 281

birth weight, 1, 18, 34, 40, 52, 74

Electroporation, 172, 173, 283

Embryos, 3, 4, 8, 10, 12, 14, 19, 32, 44, 47-49, 98, 111-112, 221, 223, 238

abortion (spontaneous), early fetal/embryo loss, 7, 11, 18, 19, 23, 38, 62, 103, 185, 233

DES, 23, 73, 223

animal models, 34, 62-63, 123, 124, 153, 158, 159-160, 161, 167, 169-170, 187, 188

autism, 85

gastrulation, 107, 116, 144, 145, 228, 232

history of developmental biology, 109, 110

history of developmental toxicology, 58-59

in vitro assessments, 28, 29, 30, 33

molecular-stress/checkpoint pathways, 141

neurulation, 109, 144, 228, 232

nonmammalian models, 6, 7, 28, 32, 33, 153, 115-128

Caenorhabditis elegans, 123, 124, 158, 159-160

chick embryotoxicity test, 33, 58-59

Drosophila melanogaster, 115-128, 161, 159, 161, 182, 183, 185

larvae, 127, 158, 159, 161, 179, 181, 182, 183, 185, 293

see also specific species

retinoids, 75-76, 79-80

TCCD, 81-82

see also Organogenesis

Embryonic stem cells, see Stem cells

Employment, see Occupational health and safety

Endocrine Disruption Screening Program (EDSP), 198, 203, 205

Education and training, 9, 293

Environmental agents, general, 4, 8, 10, 11, 28, 35, 52, 61-64

committee charge and methodology, 1-2, 20

ecogenetics, 103-104, 105-106, 198, 232, 283

genotype-environment interactions, 6, 25, 88, 175, 220, 228, 233, 234, 235

epidemiology and, 89, 99, 100-106, 215-216

number of, 11, 21-22, 36, 238

see also Risk assessment;

specific agents

Environmental Genome Project, 98-99, 217, 294-295

Environmental Health Commission, 211

Environmental Protection Agency (EPA), 26, 34, 64, 221

Environment and Birth Defects, 60, 110

Enzymes, 24, 53, 103, 105, 188, 193, 197, 233, 234, 290-291

see also Drug-metabolizing enzymes

Epidemiology, 7, 28, 36, 37-39, 57, 202, 210-212, 213, 219, 233-234

animal studies and, 38, 233, 234

biomarkers of effect, 52

biomarkers of exposure, 42, 51

cohort studies, 37-38

Suggested Citation:"Index." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
×

dose-response, 40

genomics and, 7, 89, 99, 100-106

historical perspectives, 11, 37

molecular genetics and, 89, 99, 100-106, 107, 286

natural toxins, 1, 10, 13, 20, 24, 203, 223, 224-225, 238

professional education, 9

race/ethnicity, 213, 233

Epidermal cells, general, 142, 146

Epidermal growth factor, 63, 81, 179

Epigenetic factors, 6, 25, 88, 175, 220, 228, 233, 234, 235

epidemiology and, 89, 99, 100-106, 215-216

Epistasis, 113, 155, 163, 283

Epstein-Barr virus, 194

Estrogen, 23, 34, 65, 67, 73, 105, 204

Ethical issues, see Legal and ethical issues

Ethnicity, see Race/ethnicity

Ethylene glycol ethers, 47

Ethylene oxide, 40

Etretinate, 23

Eukaryote, 93, 127, 138, 139, 143, 152, 161, 192, 193, 194, 283

European Bioinformatics Institute, 100

European Molecular Biology Library, 99

Exons, 194, 217, 284

Exposure, 4, 16, 27, 28, 30, 32, 38, 41-42, 43, 45, 220, 222, 226

animal bioassays, 34, 36, 207, 236

biomarkers, 49, 50-52, 53, 214, 281

defined, 281

risk assessment paradigm, 27, 198, 200, 204, 207

timing and duration of, 5, 8, 27, 31, 41, 46, 48, 50, 51, 61, 221

see also Dose and dose-response

Expressed sequence tag (EST) libraries, 92, 94-95, 97, 99, 157, 168, 218, 284, 293, 294

Eye defects, 77, 83, 87, 106, 109, 124, 140, 144, 145, 164, 182, 184, 185, 187, 206, 207, 232, 233

F

Federal government, see Legislation;

Regulatory issues;

specific departments and agencies

Fetal alcohol effects, see Alcohol use and abuse

Fetuses, 3, 4, 10, 12, 14, 19, 34, 40, 44, 98, 132, 221

abortion (spontaneous), early fetal/embryo loss, 7, 11, 18, 19, 23, 38, 62, 103, 185, 233

DES, 23, 73, 223

diphenylhydantoin, 73-74

fetal alcohol syndrome, 20, 22, 41, 60, 103, 233

protein function, 69-70

Fibroblasts, 145, 176, 185, 193

Food additives, 20, 22, 26

Food and Drug Administration (FDA), 26, 34, 59

Food Quality Protection Act, 40

Forward genetics, 154-156, 161, 284

Free radicals, 69, 139

Frogs, 4, 32, 33, 111, 113, 121, 123, 124, 129, 142, 153, 178, 216

Fruit fly, see Drosophila melanogaster

Functional deficits, general, 7, 18, 27, 34, 35, 39, 61, 63, 87, 129, 130, 149, 180-181, 185-186, 200, 222, 232

behavioral assays, 113, 180-181, 185-186, 187, 190, 207, 209

biomarkers, 51, 214

see also Neurological defects;

specific deficits

G

Gastrulation, 107, 116, 144, 145, 228, 232

GenBank, 99-100

Gene expression and regulation, 5, 13-14, 29, 63, 71, 86-87, 111, 112, 148, 174, 192-195, 204, 207-208, 229, 230, 237, 244

animal models, 4, 5, 115, 116-119, 128, 157, 165, 168, 170, 171, 188-189, 223, 224, 237

biomarkers, 51, 52, 214

ectopic expression, 79, 170, 188, 234, 283

expressed sequence tag (EST) libraries, 92, 94-95, 97, 99, 157, 168, 218, 284, 293, 294

genomics, 88, 92, 94, 98, 107, 216, 217-218

history of developmental biology, 110, 111

Hox genes, 79, 86, 87, 116-117, 120-123, 141, 213

microarray technology, 93-98, 100, 159-160, 205, 210, 214, 216

Suggested Citation:"Index." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
×

proteomics, 15, 92-93, 97-98, 114, 291, 293, 294

retinoids, 79, 86

TCCD, 81-82, 86

valproic acid, 85-86

see also Transcription

Genetic engineering, 5, 49. 92, 169-176, 289

transfection, 174, 193-195, 205

see also Transgenics

Genetic factors, general, 10, 13, 16, 21, 22, 25, 64, 88-107 (passim), 223-224, 233-234

animal models, 153-195, 180, 223-224, 234-235

autism, 84

cytochrome P450, 66, 74, 80, 104, 293

databases, 16, 97, 98-100, 114-115, 155, 212-214, 216, 217-218, 243, 290-295

epidemiological studies, 38, 89, 99, 100-106

history of developmental biology, 110

environment-genotype interactions, 6, 25, 88, 175, 220, 228, 233, 234, 235

ecogenetics, 103-104, 105-106, 198, 232, 283

epidemiology and, 89, 99, 100-106, 215-216

Mendelian rules, 21

multifactoral inheritance, 10, 21, 22, 89, 90, 101-102, 216, 220

pharmacogenetic factors, 94, 103-104, 105-106

see also Chromosomes;

Cloning;

DNA;

Gene expression and regulation;

Genomics;

Multidisciplinary approaches;

Mutation and mutants;

Polymorphisms;

RNA;

Transcription;

Transduction

Genomics, 1, 5, 13, 14-15, 16, 21, 88, 89, 91, 92-107, 111, 114-115, 195, 223, 233-234, 235

animal models, 4, 5, 8, 13, 14, 15, 92, 97, 101, 104, 106, 114-115, 123, 127-128, 143, 153, 155-157, 159-160, 163, 168, 169, 171, 172, 182, 195, 209, 216, 217-218, 227, 233, 292

bacterial, 93, 143

bioinformatics, 15, 99-100, 214-215, 216, 281

Caenorhabditis elegans, 14-15, 88, 93, 94, 101, 104, 195, 216, 226, 234

Cancer Genome Anatomy Project, 98, 217, 294

committee charge and methodology, 2, 4, 11, 226

databases, 16, 97, 98-100, 114-115, 155, 212-214, 216, 217-218, 243, 290, 292, 293, 294

bioinformatics, 15, 99-100, 214-215, 216, 281

Internet, 92, 218, 290, 292, 293. 294-295

defined, 92, 284

DNA Data Bank of Japan, 99

Drosophila melanogaster, 14-15, 93, 101, 104, 233-234, 292

Environmental Genome Project, 98-99, 217, 294-295

epidemiology, 7, 89, 99, 100-106

gene expression regulation, 88, 92, 94, 98, 107, 216, 217-218

expressed sequence tag (EST) libraries, 92, 94-95, 97, 99, 157, 168, 218, 284, 293, 294

Genome Sequence Database, 99, 100

historical perspectives, 14-15, 92, 93, 98, 99-100

Human Genome Project, 14-15, 92-100, 212-213, 214, 284

infectious diseases, 93

legal and ethical issues, 93

microarray technology, 93-98, 100, 159-160, 205, 207, 210, 214, 216

mouse and rat models, 8, 13, 15, 97, 124, 169, 226, 292

multidisciplinary/multilevel approaches to risk assessment, 197, 198, 205, 207, 210, 212-214, 216, 218, 243

National Center for Genome Resources, 100

National Human Genome Research Institute, 93

professional education, 9

proteomics, 15, 92-93, 97-98, 114, 291, 293, 294

risk assessment, 100, 101-104 (passim), 107, 197, 198, 205, 207, 210, 212-214, 216, 218, 243

Genome Sequence Database, 99, 100

Glucocorticoids, 34, 62, 65-66, 67, 81, 105, 194

Good Laboratory Practices, 35

Growth retardation, 1, 23, 26, 34, 35, 39, 61, 63, 70, 132, 133, 134, 206, 222, 225

see also Transforming growth factor

Suggested Citation:"Index." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
×

H

“Healthy from the Start: Why Americans Need a Better System to Track and Understand Birth Defects and the Environment,” 211

Heart, see Cardiovascular system

Heat shock, 1, 10, 20, 25, 83, 84, 105, 138, 141

neural tube defects, 62-63

Hedgehog pathways, 66, 115, 123, 126, 127, 129, 145, 161, 167, 184, 191, 203, 206, 213, 223, 229, 232, 235, 237, 298

Herpes virus, 194

His, W., Sr., 109

Historical perspectives, 11, 16, 17, 58-60

alcohol abuse, 60

animal models, 11, 12, 35, 113-114, 115, 120-121, 123, 145-146, 151-152, 153, 161-163

costs of developmental defects, 17-18

DES, 23, 73

developmental biology, 16, 108-111, 113-114, 115, 120-121, 123, 145-146

developmental toxicology, 11, 58-60, 62, 86, 220

epidemiology, 11, 37

genomics, 14-15, 92, 93, 98, 99-100

government regulation, 26

Human Genome Project, 92

Mendelian theory, 89

regulatory issues, 59

risk assessment, 11-12

teratology, 11, 58-63

thalidomide, 11, 23, 36, 38-39, 59, 60, 85, 87, 149

Hox genes, 79, 86, 87, 102, 116-117, 120-123, 141, 213

Human Genome Project, 14-15, 55, 92-100, 212-213, 214, 284

Hydra assay, 32

Hyperthermia, see Heat shock

I

Immune system effects, 52, 53, 130, 303

In vitro systems, 3, 6, 12, 24, 28-34, 77, 192-193, 197, 198, 199, 219, 221

see also Cell cultures;

Tissue assays

In vivo systems, see Animal models

Infectious diseases, 20, 58, 106

genomics, 93

herpes, 194

Information dissemination, see Computer applications;

Databases;

Education and training;

Internet

Integrated Risk Information System, 217

Interagency Center for Evaluation of Alternative Toxicological Methods, 32

Intercellular signaling, see Cell-to-cell signaling;

Signaling pathways

Interdisciplinary approaches, see Multidisciplinary approaches

International Agency for Research, 217

International perspectives

birth defect surveillance, 211

genomics, 93

International Programme on Chemical Safety, 64, 221

Internet, 290-295

Basic Local Alignment Search Tool, 115

biomarker database, 214

genomics, 92, 218, 290, 292, 293. 294-295

signal transduction, 244

Intracellular signaling, 13, 66, 74, 83, 84, 112, 126, 134, 185

see also Molecular-stress pathways

Introns, 88, 174, 175, 194, 217, 284

K

Knockout mutations, 124, 126, 128, 154-155, 156, 161, 178, 189, 230, 234-235

defined, 156, 284

embryonic stem cell technology, 104, 173-174

mouse, 73, 76, 77-78, 85, 104, 105, 112, 121, 123, 124, 129, 169, 173-174, 188, 189, 190, 209, 218, 232-235 (passim), 244, 292

yeast, 94

L

Larvae, 127, 158, 159, 161, 179, 181, 182, 183, 185, 293

Lead, 1, 20, 22, 23, 60, 106, 214, 215

Legal and ethical issues

genomics, 93

Suggested Citation:"Index." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
×

risk assessment paradigm, 27

see also Ethical issues

Legislation, 40

see also Regulatory issues

Life-style risk factors, 20, 22

see also Alcohol use and abuse;

Smoking

Ligands, 78, 86, 115, 116, 127, 136, 137, 297. 300, 301, 306

environmental agents, metabolism of, 24

hormone-dependent, 30, 77

methylmercury, 74

receptor interactions, general, 65-66, 70, 126, 137

tyrosine kinase, 95, 102, 116, 165

WNT (Wnt) pathways, 66, 73, 74, 126, 129, 136, 141, 145, 148, 180, 184, 206, 213, 234, 297

Lithium, 23

Los Alamos National Laboratory, 99-100

M

Mass media, 59

Maximum tolerated dose, 36, 45

Mechanistic information, general, 6-7, 63-87, 195, 198-199, 201, 220-224, 225, 227, 228, 236, 238

Medical treatment, see Treatment

Mendelian rules, 21, 291

Mental defects, 1, 18, 19, 23

Mercury, 20, 23, 50-52, 69, 74-75

Metabolic processes, 3, 4, 5, 8, 20, 31, 32, 51, 178, 203, 216, 222, 228, 233-234, 236-237

see also Drug-metabolizing enzymes;

Enzymes;

Toxicokinetics

Methylmercury, 23, 50-52, 69, 74-75

2-Methoxyacetic acid, 47, 48

Mice, see Mouse models

Microarray technology, 93-98, 100, 159-160, 205, 210, 214, 216

Minor defects, general, 18

Molecular-stress pathways, 7, 8, 16, 69, 136, 138-141, 180-181, 185, 189, 197, 200, 204, 208-209, 215, 225, 227, 228, 229, 231, 235, 238, 241, 299

Mortality, 17, 19, 39, 61, 63, 130, 134, 162, 206

abortion (spontaneous), early fetal/embryo loss, 7, 11, 18, 19, 23, 38, 62, 103, 185, 233

DES, 23, 73, 223

Mouse and rat models, 3-7 (passim), 8, 13, 22, 35, 40, 45, 48, 54, 55, 62, 125, 128-136, 141-142, 153-154, 184, 187-191, 195, 208, 209, 216, 217, 218, 225, 231, 234, 235, 237, 238, 239-240

Ames test, 177

autism, 85

diphenylhydantoin, 74

genomics, 8, 13, 15, 97, 124, 169, 226, 292

Hox genes, 121, 123, 141

knockout mutations, 73, 76, 77-78, 85, 104, 105, 112, 121, 123, 124, 129, 169, 173-174, 188, 189, 190, 209, 218, 232-235 (passim), 244, 292

methylmercury, 74-75

ovarian tumors, 32, 33

polymorphisms, 4, 7, 104, 106, 225, 234

retinoids, 77-78

single-gene defects, 101

TCCD, 80-82

transgenic, 159, 168-176, 187-191, 208, 237-238, 244, 294

Multidisciplinary approaches, 8-9, 16, 86, 176, 196-219, 220, 221, 229, 243-244

committee study, methodology, 15

databases, 100, 216-219, 229, 243-244, 290

genomics in, 197, 198, 205, 207, 210, 212-214, 216, 218 , 243

historical perspectives, 59

Multifactoral inheritance, 10, 21, 22, 63, 89, 90, 101-102, 216, 220

Musculoskeletal system, 17, 18, 27, 47-48, 34, 56, 102, 130-134 (passim), 145, 180, 187

craniofacial, 23, 71, 73, 74, 76, 77, 78, 79, 80, 85, 103

diphenylhydantoin, 73-74

history of developmental toxicology, 59, 62

methotrexate, 74

oral clefting, 21, 38, 54, 62, 63, 80, 81, 102, 213, 242

retinoids, 78, 79, 80

thalidomide, 11, 23, 36, 38-39, 59, 60, 85, 87, 149

Mutation and mutants, 20, 124, 148, 164, 167-168, 171, 172, 174-175, 177-178, 187, 189, 229, 232-233, 240, 291

Ames test, 176-177

biomarkers of exposure, 51-52

Drosophila melanogaster, 113-114, 115-128, 161, 183, 184, 185, 186, 235

Suggested Citation:"Index." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
×

forward genetics, 154-156, 161, 284

genomics, 92, 218

Hox genes, 79, 86, 87, 116-117, 120-123

molecular-stress pathways, 138-140

reverse genetics, 94, 154, 156-157, 178-179, 287

signaling pathways, 8, 126-136, 137, 139, 177-178, 183, 184, 185, 187

see also Knockout mutations;

Polymorphisms;

Sensitization;

Transgenics

N

National Cancer Institute, 98-99, 212, 213, 217

National Center for Biotechnology Information, 100, 290

National Center for Genome Resources, 100

National Center for Human Genome Research, 93

National Center for Toxicological Research, 35

National Human Genome Research Institute, 93

National Institute of Environmental Health Sciences, 98, 217, 242

National Institute of General Medical Sciences, 100

National Institutes of Health, 290

see also Human Genome Project;

National Cancer Institute

National Library of Medicine, 100, 290

National Toxicology Program, 32, 35, 217

Natural toxins, 1, 10, 13, 20, 24, 203, 223, 224-225, 238

Nematodes, see Caenorhabditis elegans

Neurological defects, 1, 10, 17, 18, 23, 47-48, 130, 134, 145-146, 180-181, 190

autism, 18, 84-86

cerebral palsy, 18

cyclopamine, 72-73

fetal alcohol syndrome, 103

methotrexate, 74

methylmercury, 74-75

neural tubes, 1, 19, 23, 48, 52, 62-63, 82, 84, 130, 144

retinoids, 76, 79

spina bifida, 18

see also Anticonvulsants;

Brain;

Central nervous system

Neurulation, 109, 144, 228, 232

Nicotine, see Smoking

Nonmammalian models, 6, 7, 28, 32, 33, 63, 153, 198, 200, 205-208, 216, 224-226, 230, 236, 240

Ames test, 177

bioassays, 32, 153, 178, 180, 181, 182, 183, 206, 218, 221, 237

Caenorhabditis elegans, 63, 101, 104, 113, 114, 123-124, 143, 150, 153, 154, 156-161 (passim), 163, 167, 178-182, 191, 195, 216, 224

genomics, 14-15, 88, 93, 94, 101, 104, 195, 216, 226, 234

chick, 33, 58-59, 125, 153, 216, 292

Drosophila melanogaster, 63, 89-90

genomics, 14-15, 93, 101, 104, 233-234, 292

frog, 4, 32, 33, 111, 113, 121, 123, 124, 129, 142, 153, 178, 216

Hox genes, 116-117, 120-123

larvae, 127, 158, 159, 161, 179, 181, 182, 183, 185, 293

puffer fish, 153

pupae, 161, 182, 183, 185, 191

single-celled organisms, 151-152

yeast, 14-15, 41, 94, 92, 93, 94-97, 114, 143, 151-152

zebrafish, 3-7 (passim), 33, 93, 101, 113, 142, 150, 153, 154, 158, 159, 167, 168, 186-187, 191, 206, 207, 216, 217, 225, 226, 230, 231, 234, 237, 239, 240, 241, 292-293

North American Registry for Epilepsy and Pregnancy, 211

Notch pathways, 126, 127, 129, 164, 179-180, 184, 206, 300

Nuclear-hormone receptors, 30, 63, 65, 66, 77, 86, 126, 127, 203, 204, 219, 223, 229, 301

Null mutations, see Knockout mutations

Nutrition, 1, 10, 20, 53, 58, 64, 70, 75, 90, 139, 197, 220, 233, 235

O

Occupational health and safety, 21

On Line Mendelian Inheritance in Man, 211

Oocytes, 13

Drosophila melanogaster, 115, 116, 119, 120

early death, 62

Suggested Citation:"Index." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
×

gastrulation, 107, 116, 144, 145, 228, 232

transgenic technology, 159-160

Oral clefting, 21, 38, 54, 62, 63, 80, 81, 102, 213, 242

Organization for Economic Cooperation and Development (OECD), 34

Organogenesis, 36, 62, 87, 110-111, 124, 126, 142, 144-150, 167-168, 207, 209, 226, 228, 230-231, 232, 233, 239

defined, 286

eyes, 77, 83, 87, 106, 109, 124, 140, 144, 145, 164, 182, 184, 185, 187, 206, 207, 232, 233

history of developmental biology, 109

retinoids, 79, 87

Ovarian cancer, 32, 33

Oxidants and oxidation, 51, 69, 76, 83, 91, 103, 104, 105, 138, 139, 140-141, 188, 204-205, 208-209, 233, 236

P

PAHs, see Polycyclic aromatic hydrocarbons

PCR, see Polymerase chain reaction

Peak threshold concentration (Cmax), 46, 48, 49

Penicillamine, 23

Pesticides, 20, 26, 40

Pharmaceuticals, general, 20, 24, 31, 36, 204

cohort studies, 38

dose-response, 41

public opinion, 59

toxicokinetics, 44, 46

see specific drugs

Pharmacogenetics, 94, 103-104, 105-106

Pharmacokinetics, 44, 46, 73, 77, 83

see also Drug-metabolizing enzymes

Phenytoin, see Diphenylhydantoin

Placenta, 11, 28, 30, 33, 61, 90, 94, 132, 133, 142, 152, 153, 159, 168

biomarkers, 52, 53

retinoids, 78

Polychlorinated biphenyls, 20, 23

Polycyclic aromatic hydrocarbons, 52, 53

benzo[a]pyrene, 28, 51, 53, 63

Polymerase chain reaction, 94, 214

Polymorphisms, 4, 7, 90-91, 102, 103, 104-106, 141, 192, 195, 200, 202, 215, 225, 234

biomarkers of susceptibility, 53

databases, 8, 98-99, 212-214, 216, 243, 291, 293, 294

defined, 287

DNA, 90-91, 291

mouse and rat models, 4, 7, 104, 106, 225, 234

proteins, 8, 90-91

RNA, 91

zygotes, 90

see also Transforming growth factor

Polyphodiersterase (PDE), 291

Prenatal period, 1, 3, 4, 19-20, 21, 31, 34, 35, 60-61, 190

alcohol use and abuse, 20, 22, 41, 60, 103, 233

biomarkers, 50, 52

exposure assessment, 41-42, 50-52

mechanisms of toxicity, 64, 70

placenta, 11, 28, 30, 33, 52, 53, 61, 90, 94, 142, 152, 153, 159, 168

smoking, 21, 23, 38, 54, 63, 102, 213, 230, 233

biomarkers, 51, 52, 53

timing and duration of exposure, 5, 8, 27, 31, 41, 46, 48, 50, 51

toxicokinetics, 42, 44-48

uterine factors, 20, 21, 34, 35, 41, 50-52, 70, 73-74, 168

see also Embryos;

Fetuses;

Oocytes;

Organogenesis;

Placenta;

Zygotes

Professional education, see Education and training

Proteins and protein function, 4, 5, 15, 25, 53, 63, 66, 69-70, 108, 112, 114, 116, 119, 120, 126, 128, 135, 142, 193, 208, 297-308 (passim)

cytochrome P450, 66, 74, 80, 104, 293

databases, 15, 97, 114, 218, 290, 291, 293, 294

fetal protein function, 69-70

fetoproteins, 50, 52

methylmercury, 74

polymorphisms, 8, 90-91

translation, 88

see also Drug-metabolizing enzymes;

Transforming growth factor

Proteomics, 15, 92-93, 97-98, 114, 291, 293, 294

Puffer fish, 153

Pupae, 161, 182, 183, 185, 191

Suggested Citation:"Index." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
×

Q

Qualitative risk assessment, 2, 5, 11, 34, 44, 56, 151, 176, 195, 196, 224-226, 229, 238-239

R

Race/ethnicity, 213, 233

Radiation, 1, 20, 60, 69, 187

Rat models, see Mouse and rat models

Receptor-mediated actions, 41, 53, 56, 86, 114, 126, 128, 133-134, 137, 199, 204

aryl hydrocarbon receptor (AHR), 65, 80-82, 106, 182

Drosophila melanogaster, 116, 117, 119, 165

in vitro models, 30, 32, 34

mechanisms of toxicity, 65-68

molecular-stress pathways, 139

retinoids, 76, 77-78, 86, 223

TCCD, 80-82, 86

see also Ligands;

Signaling pathways

Receptor tyrosine kinase (RTK), 95, 102, 114, 116, 126, 129, 136, 165, 179, 185, 204, 206, 230, 298, 299, 300

Red Book, see Risk Assessment in the Federal Government: Managing the Process

Reference concentration, 39, 40, 41, 54, 55, 287

Registry of Toxic Effects of Chemical Substances, 217

Regulatory issues, 10, 26, 30

acceptable daily intake, 26, 40, 41, 55, 281

animal studies, 34, 45, 54

dose, 40, 45, 54

Environmental Protection Agency (EPA), 26, 34, 64, 221

Food and Drug Administration (FDA), 26, 34, 59

Food Quality Protection Act, 40

historical perspectives, 59

reference concentration, 39, 40, 41, 54, 55, 287

risk assessment paradigm, 27

Reproductive system and behavior, 2, 15, 18, 20, 34, 131, 135, 162, 186, 217

ovarian cancer, 32, 33

retinoids, 77-78

see also Prenatal period

Reproductive Toxicology, 2, 15

REPROTEXT, 217

REPROTOX, 217

Respiratory system, 17, 90, 106, 129, 145

Retinoids, 23, 44, 51, 60, 65-66, 67, 75-80, 86, 148, 204, 223, 229-230

Reverse genetics, 94, 154, 156-157, 178-179, 287

Risk assessment, general, 2, 12-13, 15-16, 26-58, 195, 221-222, 224-226, 228-229, 235-236, 239-243

cell differentiation, 33, 52, 224, 228-229

committee study, charge and methodology, 2-3, 6-9, 11, 15, 224, 226

cost factors

research costs, general, 27, 152, 153, 167, 176, 177, 191, 203, 205-206, 208, 224, 225-226, 238

risk assessment paradigm, 27, 198

defined, 26-27, 288

exposure, 27, 198, 200, 204, 207

extrapolation, interspecies, 6, 7-8, 12, 34, 35, 40-41, 42, 45-46, 50, 54, 55, 56-57, 120, 141-143, 157, 159, 178, 187-188, 195-201 (passim), 206, 214, 215, 216, 222, 224, 229, 236, 238, 240-241, 242-243

from high to low doses, 8, 34, 35, 40-41, 55-57, 197, 225, 226, 231, 238, 241

toxicokinetics, 7-8, 45-46, 225

framework, diagram, 43

genomics, 100, 101-104 (passim), 107, 197, 198, 205, 207, 210, 212-214, 216, 218, 243

historical perspectives, 11-12

in vitro systems, 3, 6, 12, 24, 28-34;

see also Cell cultures;

Tissue assays

legal and ethical issues, 27

mechanisms of toxicity, 63-65

multilevel/multidisciplinary approach, 6, 8-9, 16, 59, 86, 100, 176, 196-219

paradigm, 27

professional education, 9

qualitative, 2, 5, 11, 34, 44, 56, 151, 176, 195, 196, 224-226, 229, 238-239

relative risk, 287

uncertainty, 3, 6, 12, 15-16, 23, 27, 34, 37-38, 238

see also Animal models;

Biomarkers;

Cell cultures;

Dose and dose-response;

Epidemiology;

Exposure;

Susceptibility;

Toxicokinetics

Suggested Citation:"Index." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
×

Risk Assessment in the Federal Government: Managing the Process (Red Book), 26, 27

Risk characterization, 3, 27, 41, 42, 59, 64

bioassays used for regulatory assessment, 54

defined, 288

DNA microarrays, 95-96, 205, 207, 210, 214, 216

methylmercury, 75

retinoids, 77

toxicokinetics and, 44, 49

see also Biomarkers;

Exposure

RNA, 13, 94, 95, 96, 97, 98, 111, 116, 155, 156-157, 160-161, 178, 182, 192, 207

anti-sense, 29

defined, 287

methylmercury, 75

molecular-stress pathways, 139

organogenesis, 144

polymorphism, 91

see also Transcription

Rodent models, see Mouse and rat models

S

SARs, see Structure-activity relationships

Science and Judgment, 199, 243

Secretion and secretory processes, 4, 69, 71, 80, 112, 114, 115, 116, 126, 141, 146, 148, 150, 228

see also Transforming growth factor

Seizures, see Anticonvulsants

Sensitization, 7, 39, 45, 50, 54, 61, 76, 104, 202, 208, 234, 242

animal models, 8, 12, 34, 35, 40, 62-63, 81, 154, 155, 163-164, 176-180, 183-185, 186, 187, 189, 191, 197, 206, 209, 226, 229, 233-239 (passim), 242

methylmercury, 75

placenta, 53

temporal, 50, 51, 56, 191, 220-221, 227

valproic acid, 82

see also Knockout mutations

Signaling pathways, 4, 5, 6-7, 8, 13, 14, 16, 30, 34, 63, 80, 87, 111-113, 123, 124, 126-136, 137, 139, 140, 145, 148, 149-150, 151, 159, 161, 163-166, 177-178, 179-181, 183-184, 185, 187, 189, 197-209 (passim), 214, 215, 223, 227, 228-231, 234, 237-238, 241, 244

apoptosis, 8, 61, 52, 71, 77-78, 83-84, 87, 134, 139, 140, 180, 189, 231, 302

checkpoint pathways, 7, 8, 16, 25, 75, 87, 127, 136-141, 152, 185, 189, 204, 208-209, 225, 227, 228, 229, 231, 233, 235, 238, 239, 241, 295, 231, 233, 235, 238, 239, 241, 295, 296, 302

Delta pathways, 66, 127, 129, 179-180, 300

epidermal growth factor, 63, 81, 179

Hedgehog pathways, 66, 115, 123, 126, 127, 129, 145, 161, 167, 184, 191, 203, 206, 213, 223, 229, 232, 235, 237, 298

illustrations of 17 currently known, 296-308

molecular-stress pathways, 7, 8, 16, 69, 136, 138-141, 180-181, 185, 189, 197, 200, 204, 208-209, 215, 225, 227, 228, 229, 231, 235, 238, 241, 299

mutations, 8, 126-136, 137, 139, 177-178, 183, 184, 185, 187

Notch pathways, 126, 127, 129, 164, 179-180, 184, 206, 300

nuclear hormone, 30, 63, 65, 66, 77, 86, 126, 127, 203, 204, 219, 223, 229, 301

receptor tyrosine kinase (RTK), 95, 102, 114, 116, 126, 129, 136, 165, 179, 185, 204, 206, 298, 299, 300

transforming growth factor, 21, 63, 102, 126, 129, 179, 184, 206, 298

WNT (Wnt) pathways, 66, 73, 74, 126, 129, 136, 141, 145, 148, 180, 184, 206, 213, 234, 297

see also Cell differentiation;

Cell proliferation;

Secretion and secretory processes;

Transcription

Signal transduction, see Transduction

Simian virus 40 (SV40), 194

Skeletal system, see Musculoskeletal system

Smoking, 21, 23, 38, 54, 63, 102, 213, 230, 233

biomarkers, 51, 52, 53

Society of Toxicology, 205

Spemann organizer, 141, 288

Spina bifida, 18, 134

State government

California EPA Hazard Identification Documents, 217

tracking systems, 211

Suggested Citation:"Index." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
×

Statistics

causes of defects, 20-21

chemicals in use, 24

costs of developmental defects, 17-18

developmental defects, general, 1, 10, 17, 25

in vitro testing, 30

see also Epidemiology

Stem cells, 32, 111, 172, 173-174, 283

Structure-activity relationships (SARs), 28, 29, 201, 204, 207, 209, 216, 217

Structural defects, general, 1, 7, 10, 18, 23, 34, 54, 56, 148-149, 232-233

dose-response, 39

Drosophila melanogaster, 14-15, 89-90, 93, 101, 104, 113-114, 115-127

mechanisms of toxicity, 63

principles of teratology, 61, 62

see also Musculoskeletal system;

specific defects and anatomical categories

Sulfhydryl groups, 69, 74

Surveillance, see Epidemiology

Susceptibility, 48, 61-62, 101-102, 202, 222, 226, 236

biomarkers, 49, 50, 53-54, 214, 215, 281-282

dose-response, 40

environment-genotype interactions, 6, 25, 88, 175, 220, 228, 233, 234, 235

epidemiology and, 89, 99, 100-106, 215-216

toxicokinetics, species concordance, 44-45

see also Drug-metabolizing enzymes;

Sensitization

SV40, see Simian virus 40

T

TCDD (2,4,5-trichlorophenoxyacetic acid), 28, 66, 80-82, 86

Teratogen Information Service, 217

Teratology Society, 59

TGF, see Transforming growth factor

Thalidomide, 11, 23, 36, 38-39, 59, 60, 85, 87, 149

Therapeutic measures, see Treatment

Thyroid hormones, 34, 67, 107, 145

Timing and duration of exposure, 5, 8, 27, 31, 41, 46, 48, 50, 51, 61, 221

Tissue assays, 12, 28, 42, 46, 83, 94, 95, 97, 205, 207, 217-218

Tissue transplantation, 109, 146, 148, 153

Tobacco use, see Smoking

Toxicodynamics, 3, 5, 43, 45, 196, 198, 199, 203, 215, 222-229 (passim), 234-235, 237-238, 242

Toxicokinetics, 3, 5, 7, 32, 42-49, 87, 196, 197, 198, 199, 200, 203, 208, 214, 222, 226, 228, 229, 231-232, 233-234, 236-237, 239, 242

defined, 289

dose-response, 40-41, 45

exposure assessment, 41-42, 214

extrapolation from animal models, 7-8, 45-46, 225

see also Drug-metabolizing enzymes;

Pharmacokinetics

TOXNET, 294

Training, see Education and training

Transcription, 6-7, 15, 66, 88, 91, 92, 94, 112, 126, 137, 151, 174, 197, 199, 223, 229-230, 298, 299, 301-308 (passim)

defined, 289

Drosophila melanogaster, 116, 117, 121

exons, 194, 217, 284

history of developmental biology, 110

molecular-stress pathways, 139

retinoids, 79

Transduction, 14, 16, 55, 71, 72-73, 84, 86-87, 126, 150, 151, 237, 294

see also Signaling pathways

Transfection, 174, 193-195, 205

Transforming growth factor (TGF), 21, 63, 102, 126, 129, 179, 184, 206, 213, 230

receptor tyrosine kinase (RTK), 95, 102, 114, 116, 126, 129, 136, 165, 179, 185, 204, 206, 230, 298, 299, 300

Transgenics, 5, 49. 92, 159-161, 163, 169-176, 178, 203, 206, 208, 237-238, 289, 240

mouse and rat models, 159, 168-176, 187-191, 208, 237-238, 244, 294

viruses, 106, 169

see also Knockout mutations;

Sensitization

Transplantation technologies

cell, 109. 111

tissue, 109, 146, 148, 153

Transposons, 115, 157, 163

Treatments

animal models, 176

see also Pharmaceuticals;

specific drugs

2,4,5-Trichlorophenoxyacetic acid, see TCDD

Suggested Citation:"Index." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
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U

Ultrasound, 60

Ultraviolet radiation, 1, 20, 139

Uterine factors, 20, 21, 34, 35, 41, 50-52, 70, 73-74, 168

V

Valproic acid, 23, 46, 48, 60, 82-83, 85-86

Viruses, 33

bacteriophages, 110, 151, 210

baculoviruses, 193

herpes, 194

simian virus 40 (SV40), 194

transduction, 14, 16, 55, 71, 72-73, 84, 86-87, 126, 150, 151, 237, 294

transfection, 174, 193-195, 205

transgenic, 106, 169

Vitamin A, see Retinoids

W

Wild types, 115, 289

Wilson, J. G., 60-63, 110

WNT (Wnt) pathways, 66, 73, 74, 126, 129, 136, 141, 145, 148, 180, 184, 206, 213, 234, 297

Workers, see Occupational health and safety

World Wide Web, see Internet

X

X-rays, 1, 20

Y

Yeast, 14-15, 41, 94, 92, 93, 94-97, 114, 143, 151-152, 195, 216 217, 293

Z

Zebrafish, 3-7 (passim), 33, 93, 101, 113, 125, 142, 150, 153, 154, 158, 159, 166-168, 186-187, 191, 206, 207, 216, 217, 225, 226, 230, 231, 234, 237, 239, 240, 241, 292-293

Zygotes, 62, 103, 111, 171

defined, 289

mutant, 113

polymorphisms, 90

Suggested Citation:"Index." National Research Council. 2000. Scientific Frontiers in Developmental Toxicology and Risk Assessment. Washington, DC: The National Academies Press. doi: 10.17226/9871.
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Scientific Frontiers in Developmental Toxicology and Risk Assessment reviews advances made during the last 10-15 years in fields such as developmental biology, molecular biology, and genetics. It describes a novel approach for how these advances might be used in combination with existing methodologies to further the understanding of mechanisms of developmental toxicity, to improve the assessment of chemicals for their ability to cause developmental toxicity, and to improve risk assessment for developmental defects. For example, based on the recent advances, even the smallest, simplest laboratory animals such as the fruit fly, roundworm, and zebrafish might be able to serve as developmental toxicological models for human biological systems. Use of such organisms might allow for rapid and inexpensive testing of large numbers of chemicals for their potential to cause developmental toxicity; presently, there are little or no developmental toxicity data available for the majority of natural and manufactured chemicals in use. This new approach to developmental toxicology and risk assessment will require simultaneous research on several fronts by experts from multiple scientific disciplines, including developmental toxicologists, developmental biologists, geneticists, epidemiologists, and biostatisticians.

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