Table Of ContentThe Vulnerable Brain and
Environmental Risks
Volume 2
Toxins in Food
The Vulnerable Brain and
Environmental Risks
Volume 2
Toxins in Food
Edited by
Robert L. Isaacson
Binghamton University
Binghamton. New York
and
Karl F. Je nsen
U. S. Environmental Protection Agency
Research Triangle Park. North Caro/ina
Springer Science+Business Media, LLC
Llbrary of Congress Cataloglng-ln-Publlcatlon Data
The Vulnerable bra1n and environmental r1sks I ed1ted by Robert L.
Isaacson and Karl F. Jensen.
p. CI.
Includes b1bliograph1cal references and 1ndex.
Contents: v. 1. Malnutr1t1on and hazard assessment -- v. 2. Tox1ns
1n food.
ISBN 978-1-4613-6467-2 ISBN 978-1-4615-33306 (eBook)
DOI 10.1007/978-1-4615-3330-6
1. Neurotox1cology. 2. Neurotox1cology--Env1ronmental aspects.
1. Isaacson, Robert L., 192B- II. Jensen, Karl F.
[ONLM: 1. Env1ronmental Exposure. 2. Nervous System 01seases
-chel1cally 1nduced. 3. Neurotox1ns. 4. Prote1n-Energy
Malnutr1t1on--compI1cat1ons. HL 100 V991]
RC347.6.V86 1992
616.8--dc20
DNLM/DLC
for L1brary of Congress 92-49396
CIP
ISBN 978-1-4613-6467-2
© 1992 Springer Science+Business Media New York
Originally published by Plenum Press, New York in 1992
Softcover reprint of the hardcover 1s t edition 1992
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted
in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording, or otherwise, without written permission from the Publisher.
Contributors
Judy L. Aschner • Department of Pediatrics, Albany Medical College, Albany, New
York 12208
Michael Aschner • Department of Pharmacology and Toxicology, Albany Medical
College, Albany, New York 12208
Blaine L. Bearnan • Department of Medical Microbiology and Immunology, Univer
sity of Califomia School of Medicine, Davis, Califomia 95616
Stephen C. Bondy • Department of Community and Environmental Medicine, Univer
sity of Califomia, Irvine, Califomia 72717
Richard G. Burright • Environmental Neuropsychology Laboratory, Department of
Psychology, State University of New York, Binghamton, New York 13902
Steven J. Bursian • Department of Animal Science, Michigan State University, East
Lansing, Michigan 48824
Louis W Chang • Departments of Pathology, Pharmacology, and Toxicology, Univer
sity of Arkansas for Medical Sciences, Little Rock, Arkansas 72205
Peter J. Donovick • Environmental Neuropsychology Laboratory, Department of Psy
chology, State University of New York, Binghamton, New York 13902
Per Eriksson • Department of Zoophysiology, Uppsala University, S-751 22 Uppsala,
Sweden
Clayton P. Gillette • University of Virginia School of Law, Charlottesville, Virginia
22908
Harold K. Kirnelberg • Division of Neurosurgery, Albany Medical College, Albany,
New York 12208
v
vi CONTRIBUTORS
James E. Krier • University of Michigan Law School, Ann Arbor, Michigan 48109
earl P. LeBel • Alkermes, Cambridge, Massachusetts 02139
Ellen J. Lehning • Department of Animal Science, Michigan State University, East
Lansing, Michigan 48824
Joan Massiah • Centre for Research in Neurodegenerative Diseases, University of
Toronto, Toronto, Ontario, Canada M5S lA8
D. R. McLachlan • Centre for Research in Neurodegenerative Diseases, University of
Toronto, Toronto, Ontario, Canada M5S lA8
Daniel Minnema • Hazleton Washington, Vienna, Virginia 22182
Herbert L. Needleman • University of Pittsburgh School of Medicine, Pittsburgh,
Pennsylvania 15213
John R. O'Kusky • Department of Pathology, University of British Columbia, Van
couver, British Columbia, Canada V5Z IM9
John W. Olney • Department of Psychiatry, Washington University Medical School,
St. Louis, Missouri 6311 0
David H. Overstreet • Center for Alcohol Studies, Department of Psychiatry, Univer
sity of North Carolina, Chapei Hill, North Carolina 27599
Julie A. Riess • University ofPittsburgh School ofMedicine, Pittsburgh, Pennsylvania
15213
Grant D. Schiller • School of Biological Sciences, Flinders University, Adelaide,
S.A. 5001 Australia
J. S. Schneider • Center for Neurological Research of the Department of Neurology,
Hahnemann University School of Medicine, Philadelphia, Pennsylvania 19102
Richard F. Seegal • New York State Department of Health, Wadsworth Center for
Laboratories and Research, Albany, New York 12201, and School of Public Health,
State University of New York at Albany, Albany, New York 12203
William Shain • New York State Department of Health, Wadsworth Center for Labora
tories and Research, Albany, New York 12201, and School of Public Health, State
University of New York at Albany, Albany, New York 12203
Duke Tanaka, Jr. • Department of Anatomy, Michigan State University, East Lansing,
Michigan 48824
CONTRIBUTORS vü
Gijsbert B. van der Voet • Toxicology Laboratory, University Hospital, Leiden, The
Netherlands
Charles F. Zorumski • Department of Psychiatry, Washington University Medical
School, St. Louis, Missouri 63110
General Introduction
This series was undertaken because of our awareness that environmental pollution is
adversely affecting brain function and behavior. The degree and nature of these effects in
many instances remain uncertain but are active targets of investigation by scientists
working in many domains of neuroscience. Different techniques, approaches, and concep
tual frameworks are being used, many of a specialized nature. As a result, it is difficult for
experts or for students in any one field to gain an overview of these various efforts and to
be aware of points of convergence among investigations. We believe that the sharing of
information among those using different approaches is necessary to a full understanding of
the nature of the problems confronting the human species. We believe that gaining a more
complete understanding of the effects of environmental toxins and pollutants is essential to
world health.
As demonstrated in the chapters of these books, pollutants affect sensory, motor, and
emotional functions, as weIl as learning, memory, and intellectual capacities. These
effects can range from the subtle to the profound. Very little is known about the mecha
nisms by which pollutants affect the nervous system, and little is known about the number
of compounds causing such effects. According to the V.S. Congress's Office of Technolo
gy Assessment, "The number of neurotoxic substances that pose a significant public
health risk is unknown because the potential neurotoxicity of only a small number of
chemicals has been evaluated adequately."*
There is an urgent need for understanding the effects of pollutants on the nervous
system at every level of analysis. By bringing together contributions from scientists in
both basic and applied neuroscience, we hope that investigators of all ages and disci
plines, including graduate and undergraduate students, will become interested in these
problems and their solutions. These books demonstrate the fruitfulness of using diverse
methods to study the effects of environmental pollutants, and by so doing suggest new
ways in which scientists of many persuasions can join in the attempt to understand the
vulnerability of the brain and the behavioral sequelae of this vulnerability.
Vnfortunately, almost all of the chapters assume some degree of familiarity with the
topics being presented. With a few exceptions, the chapters have been written so as to be
credible to those working in the field and may be difficult for the nonspecialist in some
aspects. But how else can current science be presented in a faithful manner? We believe
*V.S. Congress, Office ofTechnology Assessment, 1990, Neurotoxicity: Identifying and Controlling Poisons 0/
the Nervous System, OTA-BA-436 V.S. Govemment Printing Office, Washington, De.
ix
x
GENERAL INTRODUCTION
that it is wisest to present the best and most current information as seen by leaders in the
field. Even though the books may be considered to be "sampies of ideas and methods," we
believe they sampie the best.
These volumes reflect our belief that an adequate description of current risk from
environmental pollutants requires full use of current knowledge of behavior, physiology,
anatomy, biochemistry, and pharmacology to assess the integrity of the nervous system.
Thus, for all types of toxins we have tried to put together an interdisciplinary body of
information from closely related, but distinct, arenas of research. In a number of cases,
we have intentionally selected topics or perspectives that are controversial, since it is
controversy that often reveals the most interesting facets of scientific investigation.
We hope the reader, on finishing these books, will have a better understanding of a
number of issues conceming the effects of nutrients and pollutants on brain and behavior,
that is, the many substances in our environment that endanger OUf functional capabilities.
The goal of adequately assessing large numbers of substances for potential effects on brain
and behavior faces substantial challenges. These challenges can be addressed only by
approp,riately focused and interdisciplinary research efforts in neurotoxicology.
Robert L. Isaacson
Karl F. Jensen
Binghamton, New York
Research Triangle Park, North Carolina
Introduction to Volume 2
This second book of the series The Vulnerable Brain and Environmental Risks deals with
the specific effects of common toxins, pollutants, and poisons on brain function and
behavior. The chapters by Michael Aschner, Judy Aschner, and Harold Kimelburg, and
John O'Kusky describe neurotoxic effects of methylmercury. The episode of methylmer
cury poisoning that occurred in Minamata Bay, Japan, in the 1950s is an example of an
outbreak of neurotoxic disease resulting from food contaminants. Industrial refuse con
taining mercury was dumped directly into the bay. The most severely affected people were
those for whom the fish and shellfish in the bay served as their primary food source. Over
121 people were sufficiently affected to be diagnosed as suffering from mercury toxicity.
Forty-six people died. Many infants were born with nervous system damage, even though
their mothers showed no obvious signs of poisoning. But neurological diseases caused by
food contamination by metals are not limited to populations dependent on restricted,
easily contaminated food sources.
With the increase in the average age of the population, there is a growing interest in
neurodegenerative disorders that appear later in -life. Of these, Alzheimer's dementia is
one of the most frightening, primarily because it gradually diminishes the ability of a
physically healthy individual to function in a day-to-day situation, eventually eliminating
even the most basic cognitive and biological functions. The finding of high levels of
aluminum in the brains of Alzheimer patients, as weIl as symptomatic similarities to
dialysis encephalopathy produced by aluminum toxicity, has suggested a link between
aluminum accumulation and this dementia. The factors that influence the uptake, distribu
tion, and accumulation of aluminum by the nervous system are discussed by Gijsbert van
der Voet, and the relationship between neurological disorders and aluminum neurotoxicity
is presented by D.R. McLachlan and Joan Massiah.
Neurotoxic metals can have a variety of targets within neurons. Damage to some of
these targets may transiently impair the function of the neuron, while damage to other
targets may result in the death of the neuron.
Louis Chang points out that it is important to recognize when damage to certain
regions of the nervous system may be indirect or secondary to the damage to another
region of the nervous system (see also Chapter 10 by Balaban in Volume 1). Another
The material presented in this introduction has not been submitted to the Environmental Proteetion Agency's
peer and administrative review; therefore, the views and opinions expressed are those of the editors and should
not be construed to reflect the policy of the agency.
xi
xii INTRODUCTION TO VOLUME 2
concept discussed by Chang is that toxic metals may produce some of their effects by
displacing endogenous metals that are essential to normal cell functions. In support of this
idea, he points out that the symptoms of some metal toxicities are very much like those
produced by deficiencies of such essential elements.
In the following chapter, Daniel Minnema describes a number of such targets in
volved in the biochemical pathways by which signals between neurons are transduced.
His emphasis is on the interruption of the indirect, second-messenger systems by toxic
metals. Lead is an environmental pollutant to which the human nervous system is particu
larly vulnerable during prenatal and early postnatal development. Undoubtedly, it is the
most common environmental cause of mental and physical impairments of children even
today. Julie Riess and Herbert Needleman review the ongoing investigations that bear on
the question of whether or not there can be a "safe" level of lead in our blood. One
approach is to study cohorts of people with different levels of exposure using an epi
demiological approach. As the sophistication of epidemiological studies increases, the
level of lead in blood that is considered safe continues to decrease. The possibility exists
that there may not be any safe level of lead, that is, a dose below which there are no
adverse biological effects. But in spite of the long-standing and overwhelming evidence
that lead exposure has and continues to retard the neurological development of millions of
children, the problem persists.
Riess and Needleman also point out that there appears to be a significant interaction
between malnutrition and lead exposure. Such an interaction may have its most devastat
ing effects in our inner cities. While lead has now been banned from paints, leaded paint
still remains a problem in older buildings, particularly in ghetto areas.
In the subsequent chapter, Peter Donovick and Richard Burright present arguments
that the consumption of leaded paint chips may contribute to abnormal behavior, such as
"pica." Pica is the eating of nonnutritional substances such as paint chips and dirt. Thus,
the very lead consumed by children may predispose them to increase further their con
sumption of lead-containing paint chips and other hazardous substances. This increased
intake of lead may compromise the immune system, reducing the body's defenses against
parasitic, viral, and bacterial infections. The possibility that such infectious agents may
also be involved in neurological syndromes such as Parkinson's disease is discussed by
Blaine Beaman in his chapter on Nocardia infections of the brain. From a toxicological
perspective, it is an intriguing observation that brain damage can be induced by a toxin
produced by this bacterium. How many other bacteria or viral agents or fragments have
the same capacity to generate neurotoxins?
Part 11 of this volume discusses the effects of toxicants on brain function and be
havior. Each chapter will, to varying degrees, discuss the environmental sources of these
agents, how they reach the nervous system, the patterns of damage seen, and the function
deficits they produce.
The word toxicant may not be familiar to all readers. A brief summary of its use may
be useful. Most dictionaries define toxins as poisons produced by living organisms. The
term toxicant is often used when referring to agents that have been purposefully made to
produce a desired effect, such as the elimination of agricultural pests. But the term toxicant
can also be used in a broader sense to refer to all poisonous substances that are not produced
by living organisms, including substances that occur naturally (e.g., lead), as weIl as those
that do not [e.g., organophosphates, polychlorinated biphenyls (PCBs)]. In spite of these
distinctions, both terms clearly refer to substances that act as poisons to the nervous system.
In this section of the book, toxicants not naturally originating in nature, and fre
quently agents formulated to kill unwanted animal or plant life, are considered. Since
