A Small Dose of Toxicology: The Health Effects of Common Chemicals

262 Pages·2004·9.373 MB·English

by  Steven G. Gilbert

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 PR E S S
Boca Raton London New York Washington, D.C.
© 2004 by CRC Press LLC
TF1691_disc.fm Page 1 Thursday, January 15, 2004 3:28 PM
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. 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
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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
Printed in the United States of America 1 2 3 4 5 6 7 8 9 0
Printed on acid-free paper
© 2004 by CRC Press LLC
ASDA01 14/1/04 11:16 AM Page v
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
© 2004 by CRC Press LLC
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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
© 2004 by CRC Press LLC
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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
© 2004 by CRC Press LLC
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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.
© 2004 by CRC Press LLC
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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. We are constantly being dosed
or exposed to all manners of things to which we respond. For example, you are
getting a small dose of this book right now. What is your response? Will you read
further or close the book? Most of you have already had a first dose of this book
from a quick scan of the Contents or from flipping through the pages; from there
the response was to read more.
I developed a very expansive view of toxicology in which the basic principles
were applicable from the smallest to the most encompassing issues. The utility of
using toxicology to demystify many current and historical issues developed gradu-
ally for me, while trying to teach students and other groups about toxicology.
University lectures are often highly focused on very specific topics such as changes
in the developing nervous system following lead exposure. But the real challenge
lies in teaching the basic principles of toxicology to interested adults, high school,
and even elementary school pupils. My early effort to share the explanatory powers
of toxicology began when I joined the Master Home Environmentalist program.
This group held classes to instruct homeowners and renters about how to reduce
exposures to toxic substances in and around the home. The challenge was to make
toxicology both interesting and relevant. Teaching in high school and elementary
school classes further emphasized the importance of making toxicology relevant to
our daily lives.
I soon discovered that most people already know a great deal about toxicology,
even though they may not realize it. The ultimate purpose of this book is to bring
this knowledge to light by putting a conceptual framework around our everyday
knowledge of toxicology. This book is a tool to help people learn about toxico-
logy so they can form their own opinions about the potential harm from any
exposure and develop ways to reduce exposure. Knowing the underlying principles
of toxicology allows for far more effective analysis of a problem or situation and
© 2004 by CRC Press LLC
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x PREFACE
thus more effective decision-making. This book is not a comprehensive survey of
hazardous chemicals but uses everyday examples to illustrate the principles of
toxicology. The field of toxicology has many textbooks addressing the finer points
of chemistry, biology, and mechanisms of action but few that explain toxicology as
part of our day-to-day issues of living. To facilitate learning or teaching this material,
additional references and a PowerPoint presentation are available for each chapter
at www.asmalldoseof.org or at http://www.crcpress.com/e_products/ (follow the links
to downloads and then the catalog number TF1691).
I hope you find this book a useful tool for exploring toxicology, that it provides
you with insight into your everyday choices, and that it adds to the foundation and
power of your individual decision-making.
© 2004 by CRC Press LLC
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Acknowledgments
The idea for this book germinated while preparing to teach a continuing educa-
tion course on toxicology for the Department of Environmental and Occupational
Health Sciences at the University of Washington. I wish to thank the staff in the
Continuing Education program for the opportunity to develop some of this material
as well as many of the instructors who gave lectures. In particular I want to thank
Gerald van Belle, at that time Chair of the Department of Environmental Health,
for introducing one of the continuing education programs as “A Small Dose of
Toxicology”. Parts of the first two chapters were originally developed for the Master
Home Environmentalist (MHE) program as a section of their training manual. The
MHE program trains volunteers to help people reduce hazardous exposure in their
homes. This book is for the volunteers. Philip Dickey encouraged me to “get on with
it.” He provided a first draft of the chapter on home toxics, read all the chapters
and provided many substantive and editorial comments. Finally, I want to thank
Janice Camp for her ongoing support in all ways large and small.
© 2004 by CRC Press LLC
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Abbreviations
Abbreviations used in the text
Abbreviation Definition
ARND Alcohol-related neurodevelopmental disorder
CNS Central nervous system
BLL Blood lead level
FAE Fetal alcohol effect
FAS Fetal alcohol syndrome
IARC International Agency for Research on Cancer
MCS Multiple chemical sensitivity
MSDS Material Safety Data Sheet
MRLs Minimal risk levels (ATSDR)
NOAEL No observed adverse effect level
PEL Permissible exposure limits (OSHA)
ppm Part per million
RfD Reference dose
TLV Threshold limit value
TWA Time-weighted average
© 2004 by CRC Press LLC