Mode of Action, Metabolism and Toxicology (eBook)

Front Cover 1
Mode of Action, Metabolism and Toxicology 4
Copyright Page 5
Table of Contents 6
Organizing Committee 11
Preface 12
PART 1: BIOCHEMISTRY OF PESTS AND MODE OF ACTION OF PESTICIDES 14
INFLUENCE OF CHLORINATED AND PYRETHROID INSECTICIDES ON CELLULAR CALCIUM REGULATORY MECHANISMS 16
INTRODUCTION 16
GENERAL MECHANISMS OF CALCIUM REGULATION 16
DDT INHIBITION OF Na-Ca ATPASE 17
INHIBITION OF Na-Ca AND Ca-Mg ATPASE BY VARIOUS PYRETHRIN ANALOGS 20
HEPTACHLOR EPOXIDE INHIBITION OF Ca-Mg ATPASE IN SYNAPTOSOME 22
ACTION OF CYCLODIENE-TYPE INSECTICIDES ON PICROTOXININ RECEPTOR 23
DISCUSSION 24
REFERENCES 26
BEHAVIORAL AND LETHAL ACTIONS OF AMIDINES ON INVERTEBRATES 28
INTRODUCTION 28
ACTIONS ON MEMBRANE ION CHANNELS 29
OCTOPAMINE RECEPTORS IN THE ACTIONS OF AMIDINES 32
CONCLUSION 36
REFERENCES 37
INSECT CHITIN SYNTHETASE AS A BIOCHEMICAL PROBE FOR INSECTICIDAL COMPOUNDS 38
CHITIN SYNTHESIS AS A TARGET FOR PESTICIDE ACTION 38
CHITIN SYNTHESIS AND FIBRILLOGENESIS 39
INHIBITORS OF CHITIN SYNTHETASE ACTIVITY 42
BENZOYLPHENYL UREAS AS INSECTICIDES 43
ACKNOWLEDGMENTS 44
REFERENCES 44
BIOSYNTHETIC PROCESSES OF ERGOSTEROL AS THE TARGET OF FUNGICIDES 46
INTRODUCTION 46
COMPARATIVE ASPECTS OF INHIBITORS OF ERGOSTEROL BIOSYNTHESIS 47
MECHANISM OF INHIBITION OF C-14 DEMETHYLASE 52
CONCLUSIONS 53
REFERENCES 53
RESISTANCE TO PYRIMIDINE FUNGICIDES WHICH INHIBIT ERGOSTEROL BIOSYNTHESIS 56
INTRODUCTION 56
CHARACTERIZATION OF EBI-RESISTANT MUTANTS 56
MECHANISM OF RESISTANCE 57
ANTAGONISM AND SYNERGISM OF FENARIMOL TOXICITY 60
DISCUSSION 61
REFERENCES 62
MOLECULAR CHARACTERIZATION OF THE TARGET SITE(S) FOR HERBICIDES WHICH AFFECT PHOTOSYNTHETIC ELECTRON TRANSPORT 64
INTRODUCTION 64
EXPERIMENTAL 65
REFERENCES 71
TOXIC OXYGEN SPECIES AND HERBICIDE ACTION 72
INTRODUCTION 72
THE DIVERSION OF ELECTRON TRANSPORT 73
INHIBITORS OF ELECTRON TRANSPORT 75
INHIBITORS OF CAROTENOID BIOSYNTHESIS 76
CONCLUSION 77
REFERENCES 78
DIAGNOSTIC TECHNIQUES FOR NERVE POISON MODE OF ACTION 80
INTRODUCTION 80
REFERENCES 81
PHARMACOKINETIC APPROACHES TO THE ACTION OF PYRETHROIDS 
82 
INTRODUCTION 82
EXPERIMENTAL APPROACH 82
PHARMACOKINETIC COMPARISON OF ACTIVE AND INACTIVE ENANTIOMERS 84
PHARMACOKINETIC COMPARISON OF ACTIVE DIASTEREOMERS 85
CONCLUSIONS 87
REFERENCES 87
PYRETHROID- AND DDT-EVOKED RELEASE OF GABA F 
88 
INTRODUCTION 88
MATERIALS AND METHODS 88
RESULTS 89
DISCUSSION 91
REFERENCES 91
MODE OF ACTION OF HERBICIDES THAT AFFECT 
92 
INTRODUCTION 92
CELL DIVISION IN HIGHER PLANTS 93
HERBICIDE AFFECTS ON CELL DIVISION 94
CONCLUSION 97
REFERENCES 97
MODE OF ACTION AND MO CALCULATION OF TWO CLASSES OF HERBICIDES INTERACTING WITH THE REDUCING SIDE OF PHOTOSYSTEM II 98
REFERENCES 103
EVIDENCE FOR TWO DIFFERENT HERBICIDE BINDING PROTEINS AT THE REDUCING SIDE OF 
104 
INTRODUCTION 104
MATERIALS AND METHODS 104
RESULTS AND DISCUSSION 105
CONCLUDING REMARKS 108
REFERENCES 109
MODE OF ACTION OF NITRODIPHENYLETHERS AFFECTING PIGMENTS AND MEMBRANE 
110 
INTRODUCTION 110
DETERMINATION OF PEROXIDATION 110
MODE OF ACTION 112
CONCLUSION 114
REFERENCES 114
SITE OF ACTION OF PYRETHROID INSECTICIDES IN NEURONAL MEMBRANES AS REVEALED BY 
116 
INTRODUCTION 116
THE SENSORY NERVE PREPARATION 117
RESULTS 117
DISCUSSION 118
REFERENCES 120
NERVE MEMBRANE SODIUM CHANNELS AS THE 
122 
INTRODUCTION 122
SITE OF ACTION 122
EFFECTS ON NERVE FIBERS 123
MECHANISM OF NERVE EXCITATION 124
EFFECTS ON MEMBRANE SODIUM CONDUCTANCE 124
MODIFICATION OF SODIUM CHANNEL BY TETRAMETHRIN 125
PROCESS OF CHANNEL MODIFICATION 125
COMPARISON OF DDT AND SEVERAL PYRETHROIDS 126
EFFECTS ON SINGLE SODIUM CHANNELS 126
REFERENCES 127
INTERACTION OF PYRETHROIDS AND DDT-LIKE COMPOUNDS WITH THE SODIUM CHANNELS IN THE NERVE MEMBRANE 128
INTRODUCTION 128
LATERAL-LINE SENSE ORGAN 128
MYELINATED NERVE FIBRES 130
CONCLUSIONS 133
REFERENCES 134
MODE OF ACTION OF TRIDEMORPH AND RELATED COMPOUNDS 136
INTRODUCTION 136
CHEMISTRY OF 2,6-DIMETHYLMORPHOLINES IN RELATION TO THEIR FUNGITOXICITY 136
MODE OF ACTION OF TRIDEMORPH AND RELATED COMPOUNDS IN VARIOUS CELLS 137
GENERAL DISCUSSION 138
REFERENCES 140
ERGOSTEROL BIOSYNTHESIS: 
142 
INTRODUCTION 142
FUNGICIDES ACTING ON SYNTHESIS OF MEMBRANE COMPONENTS 142
REFERENCES 146
KITAZIN P AND EDIFENPHOS, POSSIBLE INHIBITORS OF PHOSPHATIDYLCHOLINE BIOSYNTHESIS 148
INTRODUCTION 148
MATERIALS AND METHODS 148
INHIBITION OF PHOSPHOLIPID METHYLATION IN MYCELIA 150
INHIBITION OF PHOSPHOLIPID METHYLATION IN THE CELL-FREE SYSTEM 151
DISCUSSION 152
REFERENCES 153
SITE OF ACTION OF CARBOXAMIDES IN MITOCHONDRIAL COMPLEX II 154
INTRODUCTION 154
EXPERIMENTAL 155
CONCLUSION 158
REFERENCES 159
MODE OF ACTION OF RICE BLAST PROTECTANT, PROBENAZOLE 160
INTRODUCTION 160
CONCLUDING REMARKS 164
REFERENCES 165
MODE OF ANTIFUNGAL ACTION OF A NEW FUNGICIDE, TOLCLOFOS-METHYL 166
INTRODUCTION 166
EFFECTS ON USTILAGO MAYDIS 166
EFFECTS ON BOTRYTIS CINEREA 168
EFFECTS ON ZOOSPORES OF OOMYCETES FUNGI 168
DISCUSSION 169
REFERENCES 170
USE OF HETEROZYGOUS DIPLOID STRAINS OF ASPERGILLUS NIDULANS FOR THE RECOGNITION OF GENETICALLY ACTIVE PESTICIDES 172
INTRODUCTION 172
THE METHOD 173
PESTICIDES AFFECTING MITOTIC SEGREGATION 174
REFERENCES 176
METABOLISM OF A PHOSPHOROTHIOLATE FUNGICIDE IBP BY STRAINS OF PYRICULARIA ORYZAE WITH VARIED SENSITIVITY 178
INTRODUCTION 178
SENSITIVITY OF FIELD-ISOLATES TO IBP AND A PHOSPHORAMIDATE 179
METABOLISM OF IBP IN RELATION TO RESISTANCE 179
INDUCTION OF IBP METABOLISM 180
DISCUSSION 182
REFERENCES 183
CHARACTERIZATION OF A 32 KILODALTON HERBICIDE-BINDING POLYPEPTIDE 184
INTRODUCTION 184
EXPERIMENTAL 184
REFERENCES 188
BEHAVIOUR OF METRIBUZIN IN TOLERANT AND SUSCEPTIBLE SOYBEAN VARIETIES 190
INTRODUCTION 190
EXPERIMENTAL 190
METRIBUZIN BEHAVIOUR IN INTACT PLANTS 191
REFERENCES 195
EFFECT OF INSECTICIDE ROTATIONS ON EVOLUTION OF RESISTANCE 196
INTRODUCTION 196
MATERIALS AND METHODS 197
RESULTS AND DISCUSSION 198
CONCLUSION 201
REFERENCES 201
THE BIOCHEMISTRY OF INSECTICIDE RESISTANCE IN THE PEACH-POTATO APHID, MYZUS PERSICAE 204
INTRODUCTION 204
MATERIALS AND METHODS 204
RESULTS AND DISCUSSION 206
CONCLUSIONS 209
REFERENCES 209
THE PRESENCE OF TWO FORMS OF GLUTATHIONE S-TRANSFERASES WITH DISTINCT SUBSTRATE SPECIFICITY IN OP-RESISTANT AND -SUSCEPTIBLE HOUSEFLY STRAINS 210
INTRODUCTION 210
MATERIALS AND METHODS 210
RESULTS AND DISCUSSION 211
REFERENCES 214
CHANGED ACETYLCHOLINESTERASE AND RESISTANCE IN LEAF- AND PLANTHOPPERS 216
INTRODUCTION 216
METHOD OF DETERMINATION OF INDIVIDUAL ACHE SENSITIVITY 216
INDIVIDUAL VARIATION OF ACHE SENSITIVITY 217
RELATION OF CHANGED ACHE TO RESISTANCE 219
CHANGED ACHE AND CROSS-RESISTANCE 220
REFERENCES 221
DISCOVERY AND DEVELOPMENT OF ANTIDOTES TO IMPROVE HERBICIDE SELECTIVITY 222
INTRODUCTION 222
EARLY DISCOVERIES 222
REFERENCES 224
ON THE MODE OF ACTION OF EPTC AND ITS ANTIDOTES 226
INTRODUCTION 226
MATERIALS AND METHODS 227
RESULTS AND DISCUSSION 227
REFERENCES 231
INFLUENCE OF HERBICIDES AND ANTIDOTES ON THE GLUTATHIONE LEVELS OF MAIZE SEEDLINGS 232
INTRODUCTION 232
MATERIALS AND METHODS 233
RESULTS AND DISCUSSION 233
ACKNOWLEDGEMENTS 237
REFERENCES 237
RAPID MULTILEVEL INTERACTIONS OF A THIOCARBAMATE HERBICIDE AND ITS PROTECTANT IN MAIZE CELL CULTURES 238
INTRODUCTION 238
RESULTS 239
DISCUSSION 242
REFERENCES 243
EPTC INHIBITION OF GIBBERELLIN PRECURSOR BIOSYNTHESIS AND REVERSAL OF THE INHIBITION BY N,N-DIALLYL-2,2-DICHLOROACETAMIDE 246
INTRODUCTION 246
METHODS AND MATERIALS 247
RESULTS AND DISCUSSION 248
REFERENCES 249
PART 2: METABOLISM AND DEGRADATION OF PESTICIDES AND XENOBIOTICS 250
PROPESTICIDES: BIOACTIVATION IN PESTICIDE DESIGN AND TOXICOLOGICAL EVALUATION 252
PESTICIDE OR PROPESTICIDE 252
PROPESTICIDES BY DESIGN - BIODEGRADABLE PROTECTIVE GROUPS 252
MULTIPLE SITES OF ATTACK - COMPETING ACTIVATION AND DETOXIFICATION REACTIONS 253
PROXIMATE AND ULTIMATE PESTICIDES - REACTIONS OF ACTIVATED INTERMEDIATES 254
REFERENCES 258
SELECTIVE TOXICITY CONFERRED BY ACTIVATION 260
INTRODUCTION 260
AFLATOXIN B 261
2-ACETYLAMIN0FLU0RENE 262
DIISOPROPYL PARATHION 264
FLUOROACETATE PRECURSORS 265
N-ACETYLATED INSECTICIDES 266
DISCUSSION 266
REFERENCES 266
COMPARATIVE BIOCHEMISTRY OF ANIMAL,PLANT, AND MICROORGANISM OXIDASES 268
INTRODUCTION 268
OCCURRENCE OF CYTOCHROME P-450 MONOOXYGENASE SYSTEMS AMONGANIMALS, PLANTS, AND MICROORGANISMS 268
CONSTITUTION OF CYTOCHROME P-45 0 MONOOXYGENASE SYSTEMS 269
CONTRIBUTION OF CYTOCHROME P-450 TO THE METABOLISM OF XENOBIOTICS 272
INDUCTION OF MICROSOMAL CYTOCHROME P-450 AND MONOOXYGENASE ACTIVITIESBY XENOBIOTICS 272
REFERENCES 275
BIOACTIVATION INVOLVING CHEMICALLY REACTIVE OXYGENATED CARBON 276
INTRODUCTION 276
OXYGENATION OF ALKENES 277
OXIDATION OF ARENES AND AROMATIC HYDROXYLATION 279
OXIDATION AT CARBON LEADING TO CYCLIC ALCOHOLS AND KETONES 281
OXIDATION AT CARBON LEADING TO DEALKYLATION 283
MISCELLANEOUS ALIPHATIC HYDROXYLATION 285
CONCLUSIONS 286
REFERENCES 286
BIOACTIVATIONS INVOLVING HALOGENCONTAINING SUBSTITUENTS 288
INTRODUCTION 288
MODIFICATIONS IN SHAPE, SIZE AND PHYSICAL PROPERTIES(CLASS I BIOACTIVATION) 288
REFERENCES 291
BIOACTIVATION INVOLVING NITROGENCONTAINING SUBSTITUENTS 292
INTRODUCTION 292
EXPERIMENTAL 293
RESULTS 293
DISCUSSION 298
REFERENCES 299
METABOLISM AND DEGRADATION OF PESTICIDES AND XENOBIOTICS: BIOACTIVATIONS INVOLVINGSULFUR-CONTAINING SUBSTITUENTS 300
METABOLIC ACTIVATION OF SULFUR-CONTAINING PESTICIDES 300
THIOCARBAMATE HERBICIDE OXIDATIONS 301
THI0PH0SPH0RUS INSECTICIDE OXIDATIONS 303
N-TRIHAL0METHYLMERCAPT0 FUNGICIDES 305
REFERENCES 307
MALONYLCYSTEINE CONJUGATES AS END-PRODUCTS OF GLUTATHIONE CONJUGATE METABOLISM IN PLANTS 308
INTRODUCTION 308
EXPERIMENTAL 308
RESULTS AND DISCUSSION 309
CONCLUSIONS 313
REFERENCES 313
CONJUGATION REACTIONS OF PESTICIDE METABOLITES WITH LIPIDS IN ANIMALS 314
INTRODUCTION 314
CHAIN EXTENSION OF ACIDIC METABOLITES TO MODIFIED FATTY ACIDS 315
GLYCERIDE ESTERS 315
ESTERS OF CHOLESTEROL 316
FATTY ACID ESTERS QF XENOBIOTIC ALCOHOLS 317
CONJUGATION TO POLAR LIPIDS 317
CONCLUSIONS 319
REFERENCES 319
PYRETHROID DETOXIFICATION AND SYNERGISMIN IN SECTS 320
INTRODUCTION 320
MATERIALS AND METHODS 320
RESULTS AND DISCUSSION 321
REFERENCES 323
PHOTODEGRADATION OF PESTICIDES IN SOLUTION: ISOMERIZATION, DEHALOGENATION AND ESTER CLEAVAGE REACTIONS OF THE PYRETHROID INSECTICIDES 324
Acknowledgment 329
References 329
THERMAL DEGRADATION OF PESTICIDES AND XENOBIOTIGS: FORMATION OF POLYCHLORINATED DIOXINS AND DIBENZOFURANS 330
INTRODUCTION 330
EXPERIMENTAL 331
RESULTS 331
REFERENCES 335
LIGHT-INDUCED TRANSFORMATIONS OF PESTICIDES ON SILICA GEL AS A MODEL SYSTEM FOR PHOTODEGRADATION ON SOIL 336
INTRODUCTION 336
PHOTOMINERALIZATION TEST 337
PHOTODEGRADATION ON SILICA GEL CHROMATOPLATES 337
DISCUSSION OF THE RESULTS 338
REFERENCES 339
ATMOSPHERIC REACTIONS OF PESTICIDES 340
THE SETTING 340
THE REAGENTS 341
PESTICIDE REACTIONS 344
DISCUSSION AND CONCLUSIONS 344
REFERENCES 345
ASSESSMENT OF ABIOTIC TRANSFORMATION 346
INTRODUCTION 346
PHOTODEGRADATION IN THE ATMOSPHERE 347
PHOTODEGRADATION IN WATER 348
PHOTODEGRADATION ON SOIL 348
CONCLUSION 350
REFERENCES 350
BEHAVIOR AND FATE OF PESTICIDES IN PADDY ECOSYSTEMS 352
INTRODUCTION 352
FUNGICIDES 352
INSECTICIDES 352
HERBICIDES 354
STUDIES WITH RICE PADDY MODEL ECOSYSTEMS 356
REFERENCES 356
HUMUS-BOUND RESIDUES OF PHENYLAMIDE HERBICIDES: THEIR NATURE, PERSISTENCE AND MONITORING 358
INTRODUCTION 358
EXPERIMENTAL 359
RESULTS 359
DISCUSSION AND CONCLUSIONS 361
REFERENCES 362
ANAEROBIC MICROSITES IN SOILS AND THEIR POSSIBLE EFFECT ON PESTICIDE DEGRADATION 364
INTRODUCTION 364
THE MICROENVIRONMENTS OF SOILS 364
ANAEROBIC MICROSITES IN AEROBIC SOILS 365
ANAEROBIC MICROSITES AND THE DEGRADATION OF PESTICIDES 367
REFERENCES 368
BOUND PESTICIDE RESIDUES IN PLANTS 370
INTRODUCTION 370
SOURCE OP BOUND PESTICIDE RESIDUES IN PLANTS 370
RADIOACTIVE UNEXTRACTED RESIDUES 371
DISCOUNT OP NATURAL PRODUCTS PROM BOUND RESIDUES IN PLANTS 371
PROPOSED IUPAC DEFINITION OP BOUND RESIDUES IN PLANTS 371
CRITERIA FOR EVALUATION OP THE SIGNIFICANCE OP BOUND RESIDUES 371
SEQUENTIAL APPROACH TO DETERMINING THE SIGNIFICANCE OP BOUND PESTICIDERESIDUES IN PLANTS 373
RELEVANT METHODS TO ESTABLISH NATURE OF BOUND RESIDUES 374
CONTRIBUTION OP BOUND PESTICIDE RESIDUES TO A GIVEN RESIDUE SITUATION 375
REFERENCES 375
THE CAPABILITIES OF FISH AND OTHER AQUATIC ORGANISMS FOR XENOBIOTIC METABOLISM 376
INTRODUCTION 376
MATERIALS AND METHODS 377
RESULTS 377
DISCUSSION 380
REFERENCES 381
THE FATE OF PESTICIDE PLANT METABOLITES IN VERTEBRATES 382
GLUCOSIDES IN THE RAT 383
GLUCOSIDES IN THE RUMINANT 385
BOUND RESIDUES IN THE RAT 386
BOUND RESIDUES IN THE RUMINANT 387
REFERENCES 387
COMPARATIVE METABOLISM OF SULFAMETHAZINE [4-AMINO-N- (4,6-DIMETHYL-2-PYRIMIDINYL)BENZENESULFONAMIDE] IN THE RAT, CHICKEN, PIG AND SHEEP (Note a) 388
INTRODUCTION 388
RESULTS AND DISCUSSION 392
REFERENCES 393
THE USE OF NON-HUMAN PRIMATES AS MODELS FOR THE METABOLISM OF PESTICIDES AND XENOBIOTICS IN MAN 394
INTRODUCTION 394
ASPECTS OF COMPARATIVE METABOLISM 395
EXAMPLES OF COMPARATIVE METABOLISM 397
CONCLUSION 399
REFERENCES 399
ETHICAL CONSIDERATIONS INVOLVING STUDIES OF PESTICIDES AND OTHER XENOBIOTICS IN MAN 400
INTRODUCTION 400
SPECIES DIFFERENCES AND THE VALUE OF STUDIES IN MAN 401
DIFFERENT KINDS OF STUDY IN MAN 401
HISTORY 402
REFERENCES 407
METABOLISM STUDIES WITH LIVER HOMOGENATE, HEPATOCYTE SUSPENSION AND PERFUSED LIVER 408
INTRODUCTION 408
DELIVERY OF XENOBIOTICS TO HEPATOCYTES 409
HETEROGENEITY AND DIFFERENTIAL INVOLVEMENT OFHEPATOCYTES IN XENOBIOTIC METABOLISM 410
NEW APPROACHES TO THE STUDY OF HEPATICXENOBIOTIC METABOLISM 411
CONCLUSION 413
REFERENCES 413
DEUTERATION AS A TOOL IN THE STUDY OF XENOBIOTIC METABOLISM 414
REFERENCES 418
PART 3: TOXICOLOGY OF PESTICIDES AND XENOBIOTICS 420
THE ROLE OF BIOCHEMICAL STUDIES IN MODERN TOXICOLOGICAL ASSESSMENT OF PESTICIDES 422
INTRODUCTION 422
PHASES OF DEVELOPING TOXICITY 423
SPECIES DIFFERENCES IN TOXICITY 424
CORRELATION OF IN VITRO AND IN VIVO ACTIVITY 426
BIOLOGICAL MONITORING AND TISSUE DOSE 427
DOSE-RESPONSE RELATIONSHIPS 429
CONCLUSIONS 430
REFERENCES 430
NEUROPHYSIOLOGICAL AND BEHAVIORAL ASSESSMENT OF PESTICIDE TOXIGITY 432
INTRODUCTION 432
ELECTROPHYSIOLOGICAL ASSESSMENT OF OCP TOXICITY 432
BEHAVIORAL ASSESSMENT OF OCP TOXICITY 434
REFERENCES 437
GENETIC TOXICOLOGY APPLIED TO ASSESSMENT OF MUTAGENIC, CARCINOGENIC AND TERATOGENIC ACTION OF PESTICIDES AND RELATED COMPOUNDS 438
INTRODUCTION 438
MECHANISMS OF ACTION 438
TESTING METHODS 440
COMPARABILITY BETWEEN TEST SYSTEMS 442
THE USE OF MUTAGENICITY ASSAYS 443
REFERENCES 443
ASSESSING PESTICIDE TOXICITY IN MAN AND CORRELATIONS WITH LABORATORY ANIMAL STUDIES 446
AN ASSESSMENT OF THE HAZARD OF SYNTHETIC PYRETHROID INSECTICIDES TO FISH AND FISH HABITAT 450
INTRODUCTION 450
ENVIRONMENTAL BEHAVIOUR AND PATE 451
TOXICITY TO FISH AND AQUATIC INVERTEBRATES 456
CONCLUSIONS 460
REFERENCES 461
ABSORPTION AND TRANSPORT OF INSECTICIDES IN VERTEBRATES 464
INTRODUCTION 464
PENETRATION AND DISTRIBUTION 464
TRANSPORT 466
DISCUSSION 469
OXYGEN ACTIVATION AND LIPOPEROXIDATIVE MECHANISMS OF TOXICITY OF PESTICIDES AND OTHER XENOBIOTICS 470
INTRODUCTION 470
CHEMISTRY OF LIPID PEROXIDATION 471
BIOLOGICAL DEFENSES AGAINST LIPID PEROXIDATION 471
MECHANISMS OF XENOBIOTIC-MEDIATED ACTIVATED OXYGEN GENERATION AND LIPID PEROXIDATION 472
REFERENCES 475
MECHANISTIC STUDIES ON THE INHIBITION OF CYTOCHROME P-450-MEDIATED MIXED FUNCTION OXIDATION 476
INTRODUCTION 476
EXPERIMENTAL 476
RESULTS 477
DISCUSSION 480
REFERENCES 481
CHROMATOGRAPHIC TRANSLOBULAR MIGRATION OF XENOBIOTICS 482
INTRODUCTION 482
BACKGROUND 482
SIGNIFICANCE OF CTM IN VIVO 483
IMPLICATIONS OF CTM AND FUTURE RESEARCH NEEDS 485
REFERENCES 487
ORGANOCHLORINE PESTICIDES AND INHIBITION OF INTERCELLULAR COMMUNICATION AS THE MECHANISM FOR THEIR LIVER TUMOR PRODUCTION 488
INHIBITION OF INTERCELLULAR COMMUNICATION AS A MECHANISM OF TUMOR PROMOTION 490
ROLE OF PROMOTION IN THE CARCINOGENICITY OF ORGANOCHLORINE COMPOUNDS 491
ACKNOWLEDGEMENTS 491
REFERENCES 491
ASSESSMENT OF TERATOGENICITY OF ETHYLENETHIOUREA 492
INTRODUCTION 492
EXPERIMENTAL 492
RESULTS AND DISCUSSION 493
CONCLUSION 497
REFERENCES 497
TOXICOLOGY OF PYRETHROIDS 498
INTRODUCTION 498
TOXIC EFFECTS DISTINCT FROM THEIR MAIN AND COMMON ACTION IN INSECTSAND MAMMALS? 499
WHY ARE PYRETHROIDS MORE TOXIC TO INSECTS THAN MAMMALS? 500
BIOCHEMICAL CHANGES IN THE NERVOUS SYSTEM 501
THERAPY FOR POISONING BY PYRETHROIDS? 501
PROCEDURES FOR BIOLOGICAL MONITORING OF EXPOSURE OF MAN 502
DISCUSSION 502
ACKNOWLEDGEMENT 502
REFERENCES 503
NEUROTOXIG ESTERASE: CHARACTERIZATION AND POTENTIAL FOR A PREDICTIVE SCREEN FOR EXPOSURE TO NEUROPATHIC ORGANOPHOSPHATES 504
INTRODUCTION 504
MATERIALS AND METHODS 504
RESULTS AND DISCUSSION 505
REFERENCES 508
METHODS FOR TESTING IMMUNE EFFECTS OF TOXIC CHEMICALS: EVALUATION OF THE IMMUNOTOXICITY OF VARIOUS PESTICIDES IN THE RAT 510
INTRODUCTION 510
EXPERIMENTAL 510
RESULTS 511
DISCUSSION 516
REFERENCES 517
FUNCTIONAL, MORPHOLOGIC AND BIOCHEMICAL CORRELATES OF PULMONARY TOXICITY OF PARAQUATS 518
INTRODUCTION 518
CONCLUSIONS 523
REFERENCES 523
LIMITED IN VIVO LIVER BIOASSAYS FOR IDENTIFYING LONG-TERM BIOLOGICAL EFFECTS 524
LONG-TERM BIOLOGICAL EFFECTS 524
GENOTOXIC CARCINOGENS 525
TUMOR PROMOTING AGENTS 526
CONCLUSIONS 526
ACKNOWLEDGEMENTS 526
REFERENCES 527
INTERACTIONS BETWEEN PESTICIDES AND OTHER XENOBIOTICS IN THE KIDNEY 528
INTRODUCTION 528
DIRECT INTERACTIONS 528
INDIRECT INTERACTIONS 529
SUMMARY 532
REFERENCES 532
DIETARY FACTORS AFFECTING PESTICIDE TOXICITY 534
INTRODUCTION 534
PROTEIN 534
FAT 536
FIBER 537
VITAMIN C 537
MINERALS 537
CONCLUSIONS 538
REFERENCES 538
EFFECT OF PROTEIN MALNUTRITION ON THETOXICITY OF PESTICIDES 540
INTRODUCTION 540
MATERIALS AND METHODS 540
RESULTS AND DISCUSSIONS 540
CONCLUSIONS 541
REFERENCES 542
MECHANISMS OF TOLERANCE TO ANTICHOLINESTERASE INSECTICIDE TOXICITY 544
INTRODUCTION 544
TOLERANCE DEVELOPMENT WITHOUT ACUTE SIGNS 545
DISULFOTON TOLERANCE AND MUSCARINIC RECEPTORS 546
TOLERANCE TO A CARBAMATE INSECTICIDE 548
ACKNOWLEDGEMENT 548
REFERENCES 549
CONSECUTIVE SYSTEM OF TESTS FOR ASSESSMENT OF THE EFFECTS OF CHEMICAL AGENTS IN THE AQUATIC ENVIRONMENT 550
INTRODUCTION 550
COMPARISON OF COMBINATIONS OF SINGLE SPECIES TESTS WITH ONE MULTISPECIES TEST 554
CONCLUSIONS 556
ACKNOWLEDGEMENT 557
REFERENCES 557
STANDARDIZATION OF TEST PROCEDURES AND SPECIES IN ECOTOXICITY ASSESSMENTS:AN ALGAL TEST TO OBSERVE THE PHOTOSYNTHETIC ACTIVITY OF PORPHYRA SP.USING RADIO ISOTOPE TECHNIQUES 558
INTRODUCTION 558
MATERIALS AND MRTHODS 559
RESULTS AND DISCUSSION 560
REFERENCES 562
FATE AND BIOLOGICAL EFFECTS OF INSECTICIDES IN PONDS 564
INTRODUCTION 564
RESULTS AND DISCUSSION 565
REFERENCES 569
AUTHOR INDEX TO VOLUME 3 570
SUBJECT INDEX TO VOLUME 3 572