CRC PR ESS Boca Raton London New York Washington, D.C. Stan ley T. Omaye Food and Nutritional Toxicology © 2004 by CRC Press LLC This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequences of their use. Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming, and recording, or by any information storage or retrieval system, without prior permission in writing from the publisher. The consent of CRC Press LLC does not extend to copying for general distribution, for promotion, for creating new works, or for resale. Specific permission must be obtained in writing from CRC Press LLC for such copying. Direct all inquiries to CRC Press LLC, 2000 N.W. Corporate Blvd., Boca Raton, Florida 33431. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation, without intent to infringe. Visit the CRC Press Web site at www.crcpress.com © 2004 by CRC Press LLC No claim to original U.S. Government works International Standard Book Number 1-58716-071-4 Library of Congress Card Number 2003065211 Printed in the United States of America 1 2 3 4 5 6 7 8 9 0 Printed on acid-free paper Library of Congress Cataloging-in-Publication Data Omaye, Stanley T. Food and nutritional toxicology / Stanley T. Omaye. p. ; cm. Includes bibliographical references and index. ISBN 1-58716-071-4 1. Food—Toxicology. I. Title. [DNLM: 1. Food—adverse effects. 2. Food Additives—adverse effects. 3. Food Analysis—methods. 4. Food Contamination. 5. Food Hypersensitivity. 6. Food Poisoning. WA 701 O54f 2004] RA1258.O46 2004 615.9 ¢ 54—dc22 2003065211 TX714_C00.fm Page 4 Wednesday, January 21, 2004 8:06 AM © 2004 by CRC Press LLC Preface Food can be defined as the nutritive material taken into an organism for growth, work, or repair and for maintaining the vital processes. Food sustains life, and, as such, many individuals view food as an uncomplicated, pure source of nutrition. Therefore, such individuals are often bewildered to learn that food is comprised of an array of natural chemicals, and not all the chemicals are nutrients or enhance nutritive value, but in fact may decrease nutritional value or, worse still, are toxic (e.g., naturally occurring toxicants). Also, chemicals can be added to food, either intentionally or unintentionally, during production and processing. Cooking, storing, and preparing food in our kitchens create new components and different chemical compounds, which may have a toxic effect, an improvement or enhancement effect, or no effect at all on the meal quality. Food and nutritional toxicology is the field devoted to studying the complexity of the chemicals in food, particularly those that have the potential of producing adverse health effects. One begins to appreciate the complexity of the field when one recognizes that food chemicals can interact with body fluids and other compo- nents of the diet and that such interactions may have a multitude of effects, beneficial or harmful. For example, the endogenous secretions of the stomach have the ability to inactivate or break down many chemicals; however, chemicals such as nitrate can be reduced to nitrite, which has the potential of reacting with proteins in the stomach to produce carcinogenic nitrosamines. This may be inconsequential if vitamin C or E is present in the stomach, because of its capacity to inhibit the nitrosation process. Thus, interactions between food components and other chemicals are complicated but have dire implications as regards health and adverse effects. Overall, because of the diversity of the field, food and nutritional toxicology spans a number of disciplines, such as nutrition, toxicology, epidemiology, food science, environmental health, biochemistry, and physiology. The field includes studies of human health impacts of food containing environmental contaminants or natural toxicants. The field includes investigations of food additives, migration of chemicals from packaging materials into foods, and persistence of feed and food contaminants in food products. Also, the field covers examining the impact of contaminants on nutrient utilization, adverse effects of nutrient excesses, metabolism of food toxicants, and the relationship of the body’s biological defense mechanisms to such toxicants. Finally, because the study of food and nutritional toxicology has obvious societal implication, one must examine the risk determination process, how food is regulated to ensure safety, and the current status of regulatory processes. This book is intended as a text for advanced undergraduate or graduate students in nutrition, food sciences, environment, or toxicology, and professionals in the areas of nutrition, environmental health and sciences, and life or health and medical sciences. The objective of this text is to present an in-depth study of toxicants found TX714_C00.fm Page 5 Wednesday, January 21, 2004 8:06 AM © 2004 by CRC Press LLC in foods by (1) providing the general principles of toxicology, including methods for food safety assessment and biochemical and physiological mechanisms of action of food toxicants; (2) developing an understanding of foodborne intoxications and infections and of diseases linked to foods; (3) applying the principles to the preven- tion of foodborne disease; and (4) providing a background about the regulation of food safety. For nearly a decade, I have been working with students, in and out of the classroom, on many facets of this evolving area of toxicology. This textbook has evolved from my experiences while conducting a course on food and nutritional toxicology and is designed to be a teaching tool. Stanley T. Omaye TX714_C00.fm Page 6 Wednesday, January 21, 2004 8:06 AM © 2004 by CRC Press LLC Acknowledgments This book is dedicated to students of food and nutritional toxicology — past, present, and future. Special thanks go to C.C. Bjerke for his contributions in writing Chapters 4 and 5. I am indebted to the encouragement from my mentors and colleagues and grateful for the support and understanding of my family and friends. TX714_C00.fm Page 7 Wednesday, January 21, 2004 8:06 AM © 2004 by CRC Press LLC Contents SECTION I Fundamental Concepts Chapter 1 An Overview of Food and Nutritional Toxicology Defining the Terms and Scope of Food and Nutritional Toxicology Toxicology Food and Nutritional Toxicology Toxicants in Foods and Their Effects on Nutrition Nutrients Naturally Occurring Toxicants Food Additives and Contaminants Impact of Diet on the Effects of Toxicants Study Questions and Exercises Recommended Readings Chapter 2 General Principles of Toxicology Phases of Toxicological Effects Exposure Phase Toxicokinetic Phase Toxicodynamic Phase Dose–Response Relationship Frequency Response Potency and Toxicity Categories of Toxicity Reversibility of Toxicity Response Hypersensitivity vs. Hyposensitivity Study Questions and Exercises Recommended Readings Chapter 3 Factors That Influence Toxicity Diet and Biotransformation Effect of Macronutrient Changes Protein Lipids Carbohydrates Effect of Micronutrient Changes Vitamins TX714_C00.fm Page 9 Wednesday, January 21, 2004 8:06 AM © 2004 by CRC Press LLC Minerals Gender and Age Species Study Questions and Exercises Recommended Readings Chapter 4 Food Safety Assessment Methods in the Laboratory: Toxicological Testing Methods Analysis of Toxicants in Foods Oral Ingestion Studies Acute Toxicity Testing Toxicology Screen Dose-Range-Finding and Dose–Response Curve for Lethality Subchronic Toxicity Testing Chronic Toxicity Testing Genetic Toxicity Ames Tests Host-Mediated Assays Eukaryotic Cells, In Vitro DNA Damage and Repair Forward Mutations in Chinese Hamster Cells Mouse Lymphoma Cell Assay Sister Chromatid Exchanges Eukaryotic Cells, In Vivo Drosophila melanogaster Micronucleus Test Specialized Oral Ingestion Studies Developmental Toxicity — Teratogenesis Reproductive Metabolic — Toxicokinetics Study Questions and Exercises Recommended Readings Chapter 5 Food Safety Assessment: Compliance with Regulations Good Laboratory Practices (GLPs) General Provisions: Subpart A Section 58.1 — Scope Organization and Personnel: Subpart B Personnel Testing Facility Management Study Director Quality Assurance Unit Facility: Subpart C Section 58.41 — General TX714_C00.fm Page 10 Wednesday, January 21, 2004 8:06 AM © 2004 by CRC Press LLC Equipment: Subpart D Equipment Design Maintenance and Calibration of Equipment Testing Facilities Operation: Subpart E Standard Operating Procedures Reagents and Solutions Animal Care Test and Control Articles: Subpart F Test and Control Article Characterization Test and Control Article Handling Mixtures of Articles with Carriers Protocol for and Conduct of a Nonclinical Laboratory Study: Subpart G Protocol — Section 58.120 Conduct of a Nonclinical Laboratory Study — Section 58.130 Records and Reports: Subpart J Reporting of Nonclinical Laboratory Study Results — Section 58.185 Storage and Retrieval of Records and Data — Section 58.190 Retention of Records — Section 58.195 Good Manufacturing Practices Regulatory Agencies The Food and Drug Administration Centers for Disease Control and Prevention U.S. Department of Agriculture U.S. Environmental Protection Agency Occupational Safety and Health Administration The National Marine Fisheries Service Local and State Agencies International Agencies U.S. Food Laws Study Questions and Exercises Recommended Readings Chapter 6 Risk Risk–Benefit Hazard Identification, Dose–Response, and Exposure Assessment Dose–Response Assessment Exposure Assessment Risk Characterization Threshold Relationships Nonthreshold Relationships Risk Put into Perspective Study Questions and Exercises Recommended Readings TX714_C00.fm Page 11 Wednesday, January 21, 2004 8:06 AM © 2004 by CRC Press LLC Chapter 7 Epidemiology in Food and Nutritional Toxicology Descriptive Strategies Ecological Studies Case Reports Analytical Strategies Cross-Sectional Studies Prospective Studies Retrospective Studies Meta-Analysis Molecular Epidemiology Exposure–Dose Studies Physiological Studies Gene–Environment Interactions Foodborne Diseases and Epidemiology Study Questions and Exercises Recommended Readings Chapter 8 GI Tract Physiology and Biochemistry Anatomy and Digestive Functions Gut Absorption and Enterocyte Metabolism Passive Diffusion Carrier Mediated Endocytosis and Exocytosis Movement of Substances across Cellular Membranes Lipid-to-Water Partition Coefficient Ionization and Dissociation Constants Transport into the Circulation Delivery of Toxicant from the Systemic Circulation to Tissues Storage Sites Plasma Proteins Liver and Kidney Bone Lipid Depots Physiologic Barriers to Toxicants Fluid Balance and Diarrhea Treatment Study Questions and Exercises Recommended Readings Chapter 9 Metabolism and Excretion of Toxicants Metabolism of Toxicants Conversion with Intent to Excrete Biotransformation Enzymology Phase I or Type I Reactions TX714_C00.fm Page 12 Wednesday, January 21, 2004 8:06 AM © 2004 by CRC Press LLC Reduction Reactions Hydrolysis Phase II or Type II Reactions Oxidative Stress Cellular Reductants and Antioxidants Enzymatic Antioxidant Systems Targets of Oxidative Stress Products Excretion Urinary Excretion Biliary and Fecal Excretion Pulmonary Gases Other Routes of Excretion Milk Sweat and Saliva Principles of Toxicokinetics Design of a TK Study One-Compartment TK Volume of Distribution Multicompartment Models Study Questions and Exercises Recommended Readings Chapter 10 Food Intolerance and Allergy Allergy and Types of Hypersensitivity Primary Food Sensitivity Nonimmunological Primary Food Sensitivities Secondary Food Sensitivity Symptoms and Diagnosis Treatment Study Questions and Exercises Recommended Readings SECTION II Toxicants Found in Foods Chapter 11 Bacterial Toxins Intoxications Bacillus cereus Mode of Action Clinical Symptoms Clostridium botulinum Mode of Action Clinical Symptoms TX714_C00.fm Page 13 Wednesday, January 21, 2004 8:06 AM © 2004 by CRC Press LLC [...]... and subsequently were rich in diversity Food and nutritional toxicology can be considered an emerging subdiscipline of toxicology The area of food and nutritional toxicology bridges traditional sciences and can be regarded as a branch of either nutrition, food science, or toxicology In addition, there are significant contributions from other sciences, both new and emerging, to food and nutritional toxicology, ... advances, we can expect to see the field of food and nutritional toxicology at the forefront, addressing issues of mechanisms of action, risk, and safety and what is appropriate for optimal health STUDY QUESTIONS AND EXERCISES 1 Define toxicology, food toxicology and nutritional toxicology, phytochemical, and toxin 2 Describe how toxicants might affect nutrition and health 3 How might an organism’s diet... organisms, i.e., xenobiotic or foreign compounds Food and nutritional toxicologists deal with toxicants in food, the health effects of high nutrient intakes, and the interactions between toxicants and nutrients FOOD AND NUTRITIONAL TOXICOLOGY Development of toxicology as a distinct science has been slow as compared with the sciences of pharmacology, biochemistry, and nutrition Many toxicologists were © 2004... occasions, common foods are contaminated with unacceptably high levels of toxicants Such substances can be inherent toxicants, substances naturally found in foods, or contaminants, which are substances that find their way into food either during the preparation or processing of such foods Nutritional toxicology is the study of the nutritional aspects of toxicology Nutritional toxicology is related to and might... 2004 8:08 AM Section I Fundamental Concepts © 2004 by CRC Press LLC TX714_C01.fm Page 3 Wednesday, January 21, 2004 8:09 AM 1 An Overview of Food and Nutritional Toxicology DEFINING THE TERMS AND SCOPE OF FOOD AND NUTRITIONAL TOXICOLOGY TOXICOLOGY In essence, toxicology is the science of poisons, toxicants, or toxins A poison, toxicant, or toxin is a substance capable of causing harm when administered... health, immunology, and microbiology In the following chapters we will discuss some current research that deals with the effects, both good and bad, of food components on the modulation of the immune response or alterations of behavior Food safety is another area that can be encompassed within food and nutritional toxicology Within the food safety arena we deal with the regulatory and consumer or economic... Nutritional toxicology is related to and might even overlap but is not synonymous with food toxicology Food toxicology emphasizes toxicants or toxins found in foods, whereas nutritional toxicology targets the interrelations that toxicants or toxins have with nutrients in the diet, which affect nutritional status Nutritional toxicology can refer to the means by which the diet or components of the diet prevent... lipid-energy and nucleic acid metabolism, and synthesis It is likely that secondary metabolites evolved in response to and interaction with organisms of the animal and plant kingdoms or certain herbivores and pathogens Recent advances in genetically modified foods have used such knowledge for developing plants with the ability to better defend themselves against disease and predators FOOD ADDITIVES AND CONTAMINANTS... put into perspective, one can understand why the U.S still has the safest, cheapest, and most varied food in the world TOXICANTS IN FOODS AND THEIR EFFECTS ON NUTRITION Potential sources of toxicants in food include nutrients, natural food toxicants, contaminants, and chemicals or substances intentionally added to food (food additives) NUTRIENTS One usually does not relate the ingestion of a specific nutrient... J.N., Nutritional Toxicology, Academic Press, New York, 1982 Institute of Medicine, Food and Nutrition Board, Dietary Reference Intake, National Academy Press, Washington, D.C., 1997, 1998, 2000, 2001, and 2002 Jones, J.M., Food Safety, Egan Press, St Paul, MN, 1992 Ottoboni, M.A., The Dose Makes the Poison, 2nd ed., John Wiley & Sons, New York, 1997 Shibamoto, T and Bjeldanes, L.F., Introduction to Food . Overview of Food and Nutritional Toxicology Defining the Terms and Scope of Food and Nutritional Toxicology Toxicology Food and Nutritional Toxicology Toxicants. Overview of Food and Nutritional Toxicology DEFINING THE TERMS AND SCOPE OF FOOD AND NUTRITIONAL TOXICOLOGY T OXICOLOGY In essence, toxicology is