PRINCIPLES OF TOXICOLOGY

7 Neurotoxicity: Toxic Responses of the
Nervous System
NEUROTOXICITY: TOXIC RESPONSES OF THE NERVOUS SYSTEM
STEVEN G. DONKIN and PHILLIP L. WILLIAMS
Neurotoxic chemicals are significant contributors to the human health effects that result from
environmental and workplace chemical exposures. The National Institute for Occupational Safety and
Health (NIOSH) reports that exposure to neurotoxic chemicals is one of the 10 leading causes of
work-related disease and injury and that over 25 percent of the chemicals for which the American
Conference of Governmental Industrial Hygienists (ACGIH) has established Threshold Limit Values
(TLV) (trademarks) have demonstrated nervous system effects. Other sources have estimated that of
the 400 or so commonly used chemicals (primarily solvents and various pesticides), 42 percent are
neurotoxic. Thus neurotoxicity is an important consequence of human exposure to industrial chemicals.
Studying toxic effects in the nervous system presents many challenges not usually encountered
when working with other systems. Foremost is the sheer complexity of the human nervous system.
Indeed, it is this complexity that in large part distinguishes us from other organisms and accounts for
the exceedingly diverse spectrum of human behavior.
As a result of its complexity, the nervous system displays a variety of responses to toxicant exposure.
These may include changes in heart rate, breathing rate, sensory perception, coordination, mood, and
many other physiological, behavioral, cognitive, and emotional effects. Quantitating these effects is
sometimes difficult enough, but even when it is possible, the significance for human health may not
be clear. For example, are feelings of euphoria or drowsiness toxic effects? Also, while a temporary
decrease in reaction time may not in itself be life-threatening, in an industrial setting where the worker
is surrounded by other hazards, a loss in the ability to react may result in disaster. Considerations such
as these must become a part of the overall neurotoxicity assessment.
Not all industrial chemicals are neurotoxicants, but for those that are, neurotoxic effects are often
extremely sensitive indicators of low-level exposure. This, of course, depends on developing appropriate
methods for monitoring such subtle effects. Changes in behavior are commonly used as sensitive
and easily measured neurotoxic end points, although they may present some difficulty in terms of their
objective quantification and baseline variability among individuals. Some of the standard tests for
neurotoxicity are described later in this chapter.
Besides being complex, the nervous system is ubiquitous, its network extending throughout the
body. We can conveniently divide this network into the central nervous system, comprising mainly the
brain and spinal cord, and the peripheral nervous system, comprising all other components, including
sensory and motor nerves. This distinction is important for the purposes of neurotoxicity because, as
described later, some neurotoxicants appear to target only the central or peripheral nervous systems,
but not both. The brief overview of the nervous system in the next section will suggest several different
ways in which neurotoxic chemicals may impair nervous system function:
• Outright neuronal destruction may result in permanent damage since neurons do not usually
regenerate.
Principles of Toxicology: Environmental and Industrial Applications, Second Edition, Edited by Phillip L. Williams,
Robert C. James, and Stephen M. Roberts.
ISBN 0-471-29321-0 © 2000 John Wiley & Sons, Inc.
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