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CRC PR ESS
Boca Raton London New York Washington, D.C.
Stan ley T. Omaye
Food and
Nutritional
Toxicology
© 2004 by CRC Press LLC
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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
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© 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
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© 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
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© 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.
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© 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
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© 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
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© 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
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© 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
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© 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
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© 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
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