PRINCIPLES OF TOXICOLOGY

152 NEUROTOXICITY: TOXIC RESPONSES OF THE NERVOUS SYSTEM
chemicals with depressive effects. Prescribed sedatives, such as barbiturates, may produce similar
results.
Caffeine is another commonly encountered substance with mild stimulatory effects resulting from
the inhibition of cyclic AMP metabolism, a second messenger in the response cascade of postsynaptic
nerve cells. However, the effects of caffeine on the nervous system are relatively mild, and are not
thought to be particularly hazardous. More potent, and often illegal, stimulatory drugs, such as
amphetamines and cocaine, may produce additive effects when taken in conjunction with workplace
exposure to other neurotoxicants. The resulting symptoms may be life-threatening alterations in
breathing and heart rates, or violent mood swings.
7.5 GENERAL POPULATION EXPOSURE TO ENVIRONMENTAL
NEUROTOXICANTS
Besides being workplace hazards, many neurotoxicants find their way into the environment through
either deliberate or inadvertent release. Thus the general population may become exposed to these
chemicals through the air, food, or drinking water. The infamous Minamata incident of the 1950s, in
which residents of a coastal Japanese town suffered severe and occasionally fatal neurotoxicity from
methyl mercury poisoning is only one example. In this case, exposure was due to ingestion of fish
contaminated by discharge from a local acetaldehyde plant.
Because humans are exposed to a variety of environmental chemicals, pinpointing the culprit
causing a particular toxic effect can be difficult. Also, environmental exposure levels are usually, except
in extreme cases, not so high as to cause blatant symptomology in all individuals. More often, the
situation is such that only some members of an exposed population (presumably those that are most
highly exposed or sensitive) show symptoms of varying degrees. In the case of neurotoxic effects,
these often appear as changes in behavior that may serve as early warning signs of further toxicity
possibly occurring if exposure is continued.
Neurotoxic effects may be found among individuals exposed to dissolved metals such as lead and
arsenic in their drinking water. Likewise, organic solvents, such as trichloroethylene and carbon
tetrachloride, are now seen at various concentrations in most groundwater and surface water supplies.
Often, these levels are not considered high enough to pose a serious risk, although we still do not know
enough about the effects of low-level, chronic exposure to these chemicals on the developing nervous
systems of fetuses and infants. Several epidemiological studies of populations living near water
supplies contaminated with industrial solvents have reported elevated symptoms of neurotoxicity (e.g.,
decreased reaction times, reduced cognitive skills, mood disorders), although usually not at levels high
enough as to be incontrovertible.
Exposure to neurotoxicants through inhalation is seldom considered to be a serious threat outside
an industrial setting. This is because volatile chemicals are easily dispersed in the atmosphere, so that
only people living near industrial sources of air pollution may be subject to breathing elevated levels
of neurotoxic chemicals. Usually, the primary concern is exposure within a confined space, such as
the potential inhalation of volatile organic compounds from showering with contaminated water.
Substantially increased levels of tetrachloroethylene have been measured in houses or automobiles in
which newly dry-cleaned clothes are being stored or transported. However, the correlation between
exposure to such levels and possible neurotoxic effects is as yet unknown.
7.6 EVALUATION OF INJURY TO THE NERVOUS SYSTEM
Clinical Signs
Taken as a whole, the evaluation of an individual for possible neurotoxicant exposure can generally
be described as a series of steps, such as