A SMALL DOSE OF TOXICOLOGY The Health Effects of Common Chemicals A SMALL DOSE OF TOXICOLOGY The Health Effects of Common Chemicals Steven G. Gilbert, PhD, DABT Director, Institute of Neurotoxicology and Neurological Disorders Seattle USA CRC PRESS Boca Raton London New York Washington, D.C. This edition published in the Taylor & Francis e-Library, 2005. “To purchase your own copy of this or any of Taylor & Francis or Routledge’s collection of thousands of eBooks please go to www.eBookstore.tandf.co.uk.” Library of Congress Cataloging-in-Publication Data Gilbert, Steven G., 1951- A small dose of toxicology / Steven G. Gilbert. p. cm. Includes bibliographical references and index. ISBN 0-415-31168-3 1. Toxicology—Popular works. I. Title. RA1213 .G54 2003 615.9—dc21 2003055232 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. 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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 0-415-31168-3 Library of Congress Card Number 2003055232 ISBN 0-203-46173-8 Master e-book ISBN ISBN 0-203-33713-1 (Adobe eReader Format) Contents Preface vii Acknowledgments xi 1 Toxicology and you 1 2 Principles of toxicology 15 PART 1 Toxic agents 3 Alcohol 39 4 Caffeine 50 5 Nicotine 63 6 Pesticides 70 7 Lead 86 8 Mercury 97 9 Arsenic 112 10 Metals 120 11 Solvents 135 12 Radiation 142 vi CONTENTS 13 Animal and plant toxins 155 14 Persistent environmental contaminants 172 PART 2 Targets of toxic agents 15 Neurotoxicology 183 16 Cancer and genetic toxicology 200 17 Pregnancy and developmental toxicology 215 PART 3 Applied toxicology 18 Toxics in the home 227 19 Risk assessment and risk management 238 Glossary 248 Abbreviations 253 Appendix – Demonstration of the principles of dose–response 255 Index 259 Preface Historically toxicology has focused on poisonous chemicals with death as the primary endpoint, but my interest in toxicology began when I realized that even small amounts of a chemical could irrevocably damage the brain of the developing child, result- ing in a lifetime of harm. Knowing that a high level of exposure to a chemical can kill an animal, insect, plant or human is no longer as relevant as the knowledge that repeated exposure to chemicals at low levels can cause brain damage or cancer. The knowledge that children exposed to commonly used chemicals could be per- manently affected for a lifetime seemed to me both profound and tragic. Thus, my initial interest and primary focus was on how chemicals affect the developing brain, particularly on the effects of exposure to lead and mercury. During the 1960s and 1970s researchers and physicians documented that heavy metals, such as lead and mercury, could seriously harm the developing infant. While high levels of exposure resulted in death or obviously serious consequences, the harm- ful effects from low levels of exposure remained unexplored. The laboratory I worked in designed and performed studies that ultimately demonstrated that even very low levels of exposure to lead or mercury could harm the developing nervous system. The fundamental issue was not death, but quality of life and the consequences for the individual, particularly sensitive individuals such as children. The results of our research were exciting, but immediately raised the issue of how to use this information to protect sensitive individuals, particularly children. The widespread use and environmental distribution of these agents meant that the health and well-being of the individual could be protected only by changes in government regulation. My perspective on toxicology had to broaden to include issues well outside the laboratory. At that time, lead was commonly used as a gasoline additive and mercury was common in many industrial applications, which resulted in widespread environmental distribution and subsequent human exposure. Convincing the various government and industry groups of the importance of drastically reducing environmental exposure was difficult because exposure did not appear to cause any overtly visible harm at low levels. Only the government could viii PREFACE establish broad policies or regulation that could reduce individual exposure to these chemicals and thus protect sensitive individuals. While the government has an essen- tial role to play, it is also clear that individuals need to understand the principles of toxicology involved in these issues. Knowledge about the adverse effects of agents or toxicology influences many deci- sions that ultimately shape our lives and guide our society. Medical drugs undergo extensive testing to ensure efficacy and to understand possible toxic side effects. Much of the government-mandated testing of commercial agents came only after a clear example of toxicity. Following a near disastrous experience with DDT, pes- ticides now must undergo a battery of tests to evaluate both environmental effects as well as effects on people, although many of these tests still only evaluate the active ingredients. However, the inherent toxicity of pesticides causes undesirable health and environmental effects when they are inappropriately or excessively util- ized, and in some cases even when used properly. Food additives, such as artificial sweeteners, are evaluated prior to use in the food supply to ensure that there are no long-term health effects for even the most sensitive individuals. Environmental contaminants, such as mercury, in the food supply result in restrictive local fishing rules as well as regulations on international fish stocks. National and international regulations are in place to reduce pollution in the air, water, and soil, but there is ongoing debate as to whether these regulations are adequate. These are but a few examples of how the science of toxicology influences our lives. Ultimately it is our individual understanding of the principles of toxicology and our willingness to become involved with the process that will have the greatest impact on our local and global environment. The basic principles of toxicology can explain many things in our lives as well as enlighten our understanding of current and historical events. As we shall see, there are sound physiological reasons why the coffee, tea, and cola industries make money from caffeine. The lens of toxicology brings a different focus to historical events. For example, the toxicological properties of opium are the subplot to many a war over drugs. The opium wars between Great Britain and China resulted in Hong Kong being ceded to Great Britain. Today, drug wars continue in various forms around the world and have enormous consequences for countries and indi- viduals. The daily news offers many current examples of the undesirable effects of agents and demonstrates the ongoing impact of the principles of toxicology. One of the most basic principles of toxicology is that the amount of exposure, or dose, determines the beneficial and harmful effects of a substance. In toxicology this is commonly referred to as dose–response or “the dose makes the poison.” Paracelsus (1493–1541) eloquently stated this concept as “All substances are poisons; there is none which is not a poison. The right dose differentiates a poison from a remedy”. For example, drugs taken to control or cure cancer are often very toxic, and it is only the amount taken that separates the beneficial effects from outright death. While this principle is accurate, it leaves out the very important concept of individual sensitivity. The sensitivity of the individual must be con- sidered when evaluating the potential harm of exposure to the agent. It is not par- ticularly important to know how much lead it takes to kill a child; the critical issue is how much lead it takes to cause brain damage and harm that child’s potential for a lifetime. PREFACE ix All life is born with a certain potential inscribed in its genes. Advances in mole- cular biology and genomic sciences are now letting us look directly at the coding of the gene. The toxicological sciences provide insight into how this genetic potential is damaged by its interaction with chemical or physical agents. Combining the knowledge gained through the toxicological and genomic sciences leads to a new definition of environmental health. Environmental Health Conditions that ensure that all living things have the best opportunity to reach and maintain their full genetic potential. Steven G. Gilbert, 1999 To ensure the health and well-being of our children and all life we must protect the genetic potential of the individual. Even a low level of lead exposure during child- hood may rob the child of its genetic potential. The concept of dose–response must be expanded to include the sensitive individual and protecting genetic potential. With a little imagination, the principle of dose and response easily expands beyond the normal concepts of toxicology and poisons.