Metabolic aspects of food safety

Front Cover......Page 1
Title Page
......Page 4
Copyright Page......Page 5
Table of Contents......Page 8
Editor's Preface......Page 12
List of Participants in Second Nuffield Conference......Page 16
From Sir Ernst Chain......Page 22
From Sir Frank Engledow......Page 23
Specifications and analytical methods......Page 26
Interaction with food components......Page 27
Alterations in the food additive or derivatives in the gastro-intestinal lumen......Page 29
Metabolic modification in the body......Page 30
Analytical methods......Page 32
Relationship of biochemical studies to choice of animals for experiment......Page 34
REFERENCES......Page 35
DISCUSSION......Page 36
REFERENCE......Page 40
CHAPTER 2.The Small Intestine......Page 42
THE INTESTINAL MUCOSA (Laster & Ingelfinger 1961 and Trier 1968)......Page 43
CLINICAL ILLUSTRATIONS......Page 51
SUMMARY......Page 59
REFERENCES......Page 60
DISCUSSION......Page 61
REFERENCES......Page 64
CHAPTER 3. The Physiology of Gastrointestinal Absorption......Page 66
MICHAELIS-MENTEN KINETICS......Page 67
SPECIFICITY......Page 69
COMPETITION AND INHIBITION......Page 73
KINETICS OF MULTIPLE CARRIER TRANSPORT......Page 75
ACTIVE TRANSPORT......Page 76
ENERGY FOR INTESTINAL TRANSFER......Page 80
COUPLING......Page 81
REFERENCES......Page 83
DISCUSSION......Page 85
CHAPTER 4. Absorption from the Gastrointestinal Tract, as Applied to Food Additives......Page 88
METHODS OF INVESTIGATION......Page 90
PHYSICAL FACTORS AFFECTING ABSORPTION......Page 94
BIOLOGICAL FACTORS AFFECTING ABSORPTION......Page 98
INTERACTIONS AND ABSORPTION......Page 104
ABSORPTION STUDIES IN TOXICOLOGY......Page 106
SUMMARY......Page 108
REFERENCES......Page 109
DISCUSSION......Page 113
REFERENCES......Page 117
CHAPTER 5. Transport and Fate of Substances Absorbed in the Gastrointestinal Tract with Special Reference to Blood and Tissue Levels......Page 118
Transport of absorbed substances......Page 119
Substances absorbed in unmetabolized form......Page 120
Metabolism by intestinal micro-organisms......Page 122
Patterns of metabolism of some food additives......Page 123
Fate of absorbed substances......Page 131
Comments......Page 141
REFERENCES......Page 142
DISCUSSION......Page 145
ABBREVIATIONS USED IN TEXT......Page 148
COLLECTION OF BLOOD AND URINE......Page 151
FUNCTION TESTS......Page 153
CORRELATION BETWEEN STRUCTURAL AND FUNCTIONAL CHANGES IN TOXIC RENAL DAMAGE......Page 180
SUMMARY......Page 186
REFERENCES......Page 188
DISCUSSION......Page 197
REFERENCES......Page 200
INTRODUCTION......Page 202
TESTS OF FUNCTION......Page 203
PROTEINURIA......Page 211
METABOLIC BALANCE DATA......Page 213
CONCLUSIONS......Page 215
REFERENCES......Page 216
DISCUSSION......Page 217
REFERENCE......Page 219
CHAPTER 8. Specification of Food Additives: Application and Limitation of Analytical Methods......Page 220
Specifications for arsenic, lead and 'heavy metals'......Page 226
Substances that may be contaminated with carcinogenic polycyclic aromatic hydrocarbons......Page 228
Emulsifiers and stabilizers with special reference to modified starches......Page 229
Nitrosamines......Page 231
Types of food colours......Page 233
General principles for establishing identity and purity......Page 235
Natural and synthetic organic dyes (examples)......Page 237
REFERENCES......Page 239
DISCUSSION......Page 240
REFERENCE......Page 243
The biphasic metabolism of foreign compounds......Page 244
Biological consequences of metabolism......Page 245
Phase I reactions......Page 249
Phase II reactions or conjugations (Williams 1967b)......Page 252
Spontaneous reactions......Page 256
Compounds which are not metabolized......Page 259
The excretion of foreign compounds......Page 262
REFERENCES......Page 263
DISCUSSION......Page 265
REFERENCE......Page 272
CHAPTER 10. The Significance of the Gut Flora in Safety Testing of Food Additives......Page 274
The bacterial flora of the intestine......Page 275
Some activities of intestinal bacteria......Page 279
The metabolism of organic compounds......Page 282
REFERENCES......Page 283
DISCUSSION......Page 284
Mechanisms of drug metabolism......Page 290
Inhibition of drug metabolism......Page 295
Hormonal control of liver microsomal enzymes......Page 296
Induction of microsomal enzyme system......Page 298
The mechanism of induction by phenobarbitone and 3-methylcholanthrene......Page 300
Modifications of induction......Page 301
Tests for inhibition and induction......Page 302
Importance of induction and inhibition in foreign compound elimination......Page 304
REFERENCES......Page 305
DISCUSSION......Page 309
REFERENCES......Page 312
INTRODUCTION......Page 314
ACUTE TOXICITY STUDIES......Page 315
FACTORS UNDERLINING THE INFLUENCE OF AGE ON TOXICITY......Page 320
SPECIFIC TOXIC MANIFESTATIONS......Page 325
COMMENTS......Page 327
CONCLUSIONS......Page 330
REFERENCES......Page 331
DISCUSSION......Page 335
EXPERIMENTS WITH N-2-FLUORENYLDIACETAMIDE......Page 338
INDUCTION OF DIPLOID HEPATOMAS BY CHEMICAL CARCINOGENS......Page 349
REFERENCES......Page 354
DISCUSSION......Page 355
INTRODUCTION......Page 358
REGULATION OF PROTEIN METABOLISM IN THE LIVER......Page 359
INFLUENCE OF PROTEIN INTAKE ON TISSUE FUNCTION......Page 369
SPECIES DIFFERENCES IN MAMMALIAN METABOLISM......Page 374
REFERENCES......Page 382
DISCUSSION......Page 387
INTRODUCTION......Page 392
CIRCUMSTANCES WHICH LEAD TO LIVER ENLARGEMENT......Page 393
IDENTIFICATION OF CHANGES IN LIVER SIZE AND STRUCTURE......Page 394
PATTERNS OF CHANGE DURING DEVELOPMENTAL GROWTH OF THE NORMAL LIVER......Page 397
PATTERNS OF CHANGE DURING HYPERFUNCTIONAL LIVER ENLARGEMENT DUE TO FOREIGN CHEMICALS......Page 402
PATTERNS OF CHANGE DURING THE HYPERFUNCTIONAL LIVER ENLARGEMENT OF PREGNANCY AND LACTATION......Page 407
PHYSIOLOGICAL SIGNIFICANCE OF HYPERFUNCTIONAL LIVER ENLARGEMENT......Page 435
ACKNOWLEDGEMENTS......Page 440
REFERENCES......Page 441
DISCUSSION......Page 447
REFERENCES......Page 452
CHAPTER 16. Significance of Organ-Weight Changes in Food Safety Evaluation......Page 454
Hypertrophy, numbers of cells and stress......Page 457
Factors influencing the weight of organs......Page 458
Relationship of organ weights to physiology, biochemistry and pathology......Page 460
Statistical considerations......Page 462
Retrospective and prospective studies......Page 468
REFERENCES......Page 482
DISCUSSION......Page 484
REFERENCES......Page 489
Hepatocellular and biliary-excretory function......Page 490
Serum bilirubin......Page 493
Estimation of glucuronyl transferase......Page 494
Estimates of drug detoxication in the liver......Page 495
Cholesterol and bile salt metabolism......Page 496
Protein metabolism......Page 497
Serum α1 fetoglobulin......Page 501
The place of needle hepatic biopsy......Page 502
Methods for screening for hepatotoxic effects in man......Page 503
REFERENCES......Page 504
DISCUSSION......Page 506
REFERENCES......Page 514
HEPATOCARCINOGENS WHICH MAY BE OF SIGNIFICANCE IN MAN......Page 516
LIVER TUMOURS IN NON-LABORATORY ANIMALS......Page 534
LIVER TUMOURS IN RATS AND MICE......Page 537
GEOGRAPHICAL AND TEMPORAL DISTRIBUTION OF LIVER TUMOURS IN MAN......Page 538
RELEVANCE OF LABORATORY STUDIES TO THE PROBLEM OF LIVER CANCER IN MAN AND DOMESTIC ANIMALS......Page 540
SUMMARY......Page 544
REFERENCES......Page 545
DISCUSSION......Page 564
REFERENCES......Page 568
INTRODUCTION......Page 570
HEPATIC CARCINOGENS: THEIR EFFECTS ON THE MORPHOLOGY AND FUNCTION OF LIVER CELLS......Page 572
THE RESPONSES OF LIVER CELL ORGANELLES TO CHEMICAL CARCINOGENS......Page 597
TUMOURS......Page 603
SUMMARY......Page 605
REFERENCES......Page 606
DISCUSSION......Page 614
REFERENCES......Page 616
CHAPTER 20. Induced Subcutaneous Sarcomata: Their Development and Critical Appraisal......Page 618
THE NORMAL SUBCUTANEOUS TISSUES......Page 619
TISSUE RESPONSES TO KNOWN AND PUTATIVE CARCINOGENS......Page 620
THE APPRAISAL OF INDUCED SARCOMATA......Page 644
SOME GENERAL CONCLUSIONS......Page 648
ACKNOWLEDGEMENTS......Page 649
REFERENCES......Page 650
DISCUSSION......Page 654
REFERENCES......Page 657
General Discussion......Page 660
REFERENCES......Page 662
Author Index......Page 664
Subject Index......Page 666