Toxicology of Aflatoxins (eBook)

Front Cover 1
The Toxicology of Aflatoxins: Human Health, Veterinary, and Agricultural Significance 4
Copyright Page 
5 
Table of Contents 6
Contributor 18
Preface 22
Part I: Experimental Toxicology of Aflatoxins 28
Chapter 1. Acute Hepatotoxicity of Aflatoxins 30
HISTORY 30
BIOLOGICAL ACTIVITY—ACUTE AFLATOXICOSIS 32
FACTORS AFFECTING AFB1 TOXICITY 42
REFERENCES 48
Chapter 2. Biochemical Mechanismsand Biological Implications of the Toxicity of Aflatoxins as Related to Aflatoxin Carcinogenesis 54
ACUTE AND CHRONIC TOXICITY OF AFLATOXINS 54
MECHANISMS OF TOXICITY 60
ROLE OF ACUTE AND CHRONIC TOXICITY IN CARCINOGENESIS 63
CELL REPLICATION IN RESPONSE TO AFLATOXINS 66
IMPLICATIONS OF AFLATOXIN TOXICITY FOR HEPATIC CARCINOGENESIS 67
REFERENCES 68
Chapter 3. Biotransformation of Aflatoxins 72
INTRODUCTION 72
OXIDATION 74
REDUCTION 84
CONJUGATION 84
INTEGRATION OF AFLATOXIN BIOTRANSFORMATION PATHWAYS 87
FACTORS AFFECTING AFLATOXIN BIOTRANSFORMATION 89
SUMMARY 92
REFERENCES 92
Chapter 4. Pharmacokinetics and Excretion of Aflatoxins 100
INTRODUCTION 100
ABSORPTION 101
DISTRIBUTION 105
BIOTRANSFORMATION 108
EXCRETION 108
REFERENCES 112
Chapter 5. Nonhepatic Disposition and Effects of Aflatoxin B1 116
INTRODUCTION 116
RESPIRATORY SYSTEM 116
RENAL SYSTEM 119
GASTROINTESTINAL SYSTEM 120
NERVOUS SYSTEM 121
REPRODUCTIVE SYSTEM 122
IMMUNE SYSTEM 123
MISCELLANEOUS 124
SUMMARY 124
REFERENCES 125
Chapter 6. Carcinogenicity of Aflatoxins in Nonmammalian Organisms 130
INTRODUCTION 130
NONMAMMALIAN ANIMALS OTHER THAN SALMONID FISHES 131
SALMONID FISHES 136
SUMMARY 154
REFERENCES 154
Chapter 7. Role of Aflatoxin—DNA Adducts in the Cancer Process 164
AFLATOXIN B1 COVALENT BINDING TO DNA IN VIVO 164
REPAIR AND PERSISTENCE OF AFLATOXIN B1-DNA ADDUCTS:MECHANISMS OF ADDUCT LOSS 166
NONRANDOM GENOMIC DAMAGE BY AFLATOXINS 168
MOLECULAR DOSIMETRY AND PROTO-ONCOGENE ACTIVATIONIN EXPERIMENTAL ANIMAL MORIGENESIS 169
SUMMARY 173
REFERENCES 173
Chapter 8. Mechanisms by Which Aflatoxins and Other Bulky Carcinogens Induce Mutations 176
INTRODUCTION 176
STUDIES ON INDIVIDUAL ADDUCTS OF BULKYMUTAGENS/CARCINOGENS 178
CAN DNA SEQUENCE CONTEXT INFLUENCE MUTATIONS INDUCED BY BULKY ADDUCTS 180
HOW MUTAGENIC SPECIFICITY MIGHT BE CONTROLLEDBY SEQUENCE CONTEXT 190
POSSIBLE MECHANISMS OF MUTAGENESIS BY BULKY ADDUCTS 192
DOES AFB1 INDUCE G . A MUTATIONS VIA ADDUCT-INDUCED BASE IONIZATION 195
MISINFORMATIONAL COMPARED WITH NONINFORMATIONAL MECHANISMS OF MUTAGENESIS 196
CONCLUSIONS 199
REFERENCES 200
Chapter 9. Aflatoxin Carcinogenesis in the Context of the Multistage Nature of Cancer 206
HISTORICAL PERSPECTIVE ON DEVELOPMENT OF MODELS OF EXPERIMENTAL CARCINOGENESIS 206
AFLATOXINS AS CARCINOGENS 210
SUMMARY AND CONCLUSIONS 222
REFERENCES 225
Chapter 10. Nutritional Modulation of Aflatoxin Carcinogenesis 234
INTRODUCTION 234
DIETARY DEFICIENCY OF METHYL DONORS 236
DIETARY PROTEIN DEFICIENCY 245
VITAMINS AND MINERALS IN THE DIET 247
ETHANOL 249
NONNUTRIENT FOOD COMPONENTS 250
FEED RESTRICTION 251
METHYL-SUPPLEMENTED DIET 251
CONCLUSION 252
REFERENCES 252
Part II: Human Carcinogenicity and Toxicity 258
Chapter 11. Epidemiology of Aflatoxin-Related Disease 260
INTRODUCTION 260
EXPOSURE MEASUREMENT 261
BIOLOGICAL EFFECTS OF EXPOSURE 270
PUTATIVE DISEASE OUTCOMES 271
CAUSALITY 274
POSSIBLE FUTURE RESEARCH STRATEGIES 276
REFERENCES 280
Chapter 12. Molecular Dosimetry Methods for Assessing Human Aflatoxin Exposures 286
INTRODUCTION 286
INTERNAL DOSE MEASUREMENTS IN RELATION TO EXPOSURE MEASUREMENTS 289
MARKERS OF BIOLOGICALLY EFFECTIVE DOSE 291
MOLECULAR DOSIMETRY FOR MARKERS OF SUSCEPTIBILITY 299
MARKERS OF EARLY BIOLOGICAL EFFECT 300
EPIDEMIOLOGICAL STUDIES 301
FUTURE PROSPECTS 302
REFERENCES 303
Chapter 13. Strategies for Chemoprotection against Aflatoxin-Induced Liver Cancer 308
INTRODUCTION 308
FACTORS AFFECTING EXPERIMENTAL AFB1HEPATOCARCINOGENESIS 309
CLINICAL CONSIDERATIONS FOR CHEMOPROTECTION IN HUMANS 318
CONCLUSIONS 327
REFERENCES 328
Part III: Agricultural and Veterinary Problems 334
Chapter 14. Factors Affecting Aspergillus flavus Group Infection and Aflatoxin Contamination of Crops 336
INTRODUCTION 336
AFLATOXIGENIC FUNGI 337
FACTORS AFFECTING ASPERGILLUS FLAVUS GROUP INOCULUM AND INITIAL COLONIZATION 340
CONDITIONS AFFECTING ASPERGILLUS FLAVUS INVASION,GROWTH, AND AFLATOXIN ACCUMULATION 343
AFLATOXIN CONTAMINATION OF STORED PRODUCTS 348
SUMMARY 348
REFERENCES 349
Chapter 15. Mycological Aspects of Aflatoxin Formation 354
INTRODUCTION 354
FIELD BIOLOGY OF AFLATOXIGENIC FUNGI 355
AFLATOXIN BIOSYNTHESIS 356
INTRASPECIFIC VARIATION 363
INTERFERENCE WITH AFLATOXIN BIOSYNTHESIS 364
CONCLUSION 367
REFERENCES 367
Chapter 16. Veterinary Diseases Related to Aflatoxins 374
INTRODUCTION 374
CLINICAL SIGNS 375
PATHOLOGY 376
CLINICAL PATHOLOGY 383
IMMUNE SYSTEM 383
OTHER DISEASES 385
AFLATOXIN INTAKE AND DISEASE RISK 386
CONCLUSIONS 387
REFERENCES 387
Chapter 17. Aflatoxins in Milk 392
INTRODUCTION 392
CONVERSION OF AFLATOXIN B1 TO AFLATOXIN M1 393
TOXICOLOGY 395
ANALYSIS 398
REGULATION AND OCCURRENCE 402
STABILITY AND DEGRADATION 404
REFERENCES 407
Chapter 18. Approaches to Reduction of Aflatoxins in Foods and Feeds 410
INTRODUCTION 410
AFLATOXIN REDUCTION STRATEGIES 411
CONCLUSIONS 425
REFERENCES 426
Part IV: Analytical Identification of Aflatoxins 434
Chapter 19. Recent Methods of Analysis for Aflatoxins in Foods and Feeds 436
INTRODUCTION 436
SAMPLING AND SAMPLE PREPARATION 437
SOLID-PHASE EXTRACTION 438
THIN-LAYER CHROMATOGRAPHY 438
LIQUID CHROMATOGRAPHY 440
IMMUNOCHEMICAL METHODS 443
METHODS FOR AFLATOXIN M1 DETERMINATION IN MILK AND MILK PRODUCTS 447
CONFIRMATION OF IDENTITIES OF THE AFLATOXINS 448
AUTOMATION 451
SAFETY ISSUES IN HANDLING MOLDY GRAINS AND AFLATOXINS 452
CONCLUSIONS 453
REFERENCES 453
Chapter 20. Problems Associated with Accurately Measuring Aflatoxin in Food and Feeds: Errors Associated with Sampling, Sample Preparation, and Analysis 460
INTRODUCTION 460
VARIATION AMONG TEST RESULTS 461
SAMPLING VARIABILITY 463
SUBSAMPLING VARIABILITY 464
ANALYTICAL VARIABILITY 466
REDUCING VARIABILITY OF TEST RESULTS 467
DESIGNING AFLATOXIN TESTING PROGRAMS 469
SELECTING SAMPLES 473
CONCLUSIONS 475
REFERENCES 475
Chapter 21. Development of Antibodies against Aflatoxins 478
INTRODUCTION 478
METHODS FOR PREPARATION OF AFLATOXIN-PROTEIN CONJUGATES 479
PRODUCTION OF ANTIBODIES AGAINST AFLATOXINS 484
CHARACTERIZATION OF ANTIBODIES AGAINST AFLATOXINS 486
USE OF AFLATOXIN ANTIBODIES IN VARIOUS INVESTIGATIONS 494
SUMMARY AND CONCLUDING REMARKS 508
REFERENCES 509
Part V: Economic and Regulatory Aspectsof Aflatoxins 518
Chapter 22. Human Risk Assessment Based on Animal Data:Inconsistencies and Alternatives 520
INTRODUCTION 520
COMPARISON OF RODENT AND HUMAN DATA FOR RISK ASSESSMENT 520
USE OF EPIDEMIOLOGICAL DATA AS AN ALTERNATIVE TOANIMAL DATA FOR ASSESSING HUMAN RISK 529
SUMMARY 534
REFERENCES 535
Chapter 23. Economic Issues Associated with Aflatoxins 540
INTRODUCTION 540
AGRONOMIC ASPECTS OF AFLATOXINS 541
ECONOMIC EFFECTS OF AFLATOXINS IN DOMESTIC ANIMALS 543
ECONOMIC IMPACT OF AFLATOXINgfsS IN HUMAN POPULATIONS 549
REFERENCES 551
Index 556