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From page 313... ... , 70, 83, 149, 150, 151195, 198-199, 203, 204, 210, 225227, 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, 239-240 313 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, 4041, 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, 35,40-41,42,45-46,50,54,55,5657, 120, 141-143, 157, 159, 178, 187-188, 195-201 (passim) Read the entire page →
From page 314... ... , 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 INDEX 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, 281282 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, 152153, 154, 156-161 (passim) Read the entire page →
From page 315... ... , 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 Read the entire page →
From page 316... ... , 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, 159160,205,207,210,214,216 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, 4041, 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) Read the entire page →
From page 317... ... , 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, 85 317 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) Read the entire page →
From page 318... ... , 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, 180181, 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) Read the entire page →
From page 319... ... 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 Proj ect, 14- 15, 92- 100, 212-213, 214, 284 infectious diseases, 93 legal and ethical issues, 93 microarray technology, 93-98, 100, 159160,205,207,210,214,216 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, 212214, 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 Read the entire page →
From page 320... ... , 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 Read the entire page →
From page 321... ... , 8, 13, 22, 35, 40, 45, 48, 54, 55, 62, 125, 128136, 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, 212214, 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) Read the entire page →
From page 322... ... , 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 Read the entire page →
From page 323... ... , 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 Read the entire page →
From page 324... ... , 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 INDEX 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, 2658, 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, 5657, 120, 141-143, 157, 159, 178, 187- 188, 195-201 (pas sim) , 206, 214, 215, 216, 222, 224, 229, 236, 238, 240-241, 242-243 from high to low doses, 8, 34, 35, 4041, 55-57, 197, 225, 226, 231, 238, 241 toxicokinetics, 7-8, 45-46, 225 framework, diagram, 43 genomics, 100, 101-104 (passim) Read the entire page →
From page 325... ... , 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, 325 187, 189, 197-209 (passim) , 214, 215, 223, 227, 228-231, 234, 237238, 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, 179180, 184, 206, 300 nuclear hormone, 30, 63, 65, 66, 77, 86, 126, 127, 203, 204, 219, 223, 229, 301 receptor tyrosine kinase (RTK) Read the entire page →
From page 326... ... 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) Read the entire page →
From page 327... ... G., 60-63, 110 327 WNT (Wet) 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, 216217, 293 z Zebrafish, 3-7 (passim) Read the entire page →

From page 313...

... , 70, 83, 149, 150, 151195, 198-199, 203, 204, 210, 225227, 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, 239-240 313 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, 4041, 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, 35,40-41,42,45-46,50,54,55,5657, 120, 141-143, 157, 159, 178, 187-188, 195-201 (passim)

Index Pages 313-327

Index
Pages 313-327