PRINCIPLES OF TOXICOLOGY

7.4 INTERACTIONS OF INDUSTRIAL CHEMICAL WITH OTHER SUBSTANCES 151
When the affected neurons are those of the brain, the results are usually serious, as described in the
previous section. However, life-threatening effects may also result from damage to the autonomic
nerves, such as those controlling breathing and heart rate. This is often the effect of cyanide or hydrogen
sulfide, which leads to death.
7.3 AGENTS THAT ACT ON THE SYNAPSE
Anticholinesterase Agents
When the enzyme acetylcholinesterase (AChE) is prevented from hydrolyzing acetylcholine (ACh),
overstimulation of the postsynaptic cell results. This is an important mode of action for a variety of
insecticides, two groups of which are the organophosphorus and the carbamate esters. However, as is
the case with the organochlorines, what makes these anticholinesterase compounds effective insecticides
also makes them potentially hazardous to humans who come into contact with them.
Organophosphorus esters, or organophosphates, include malathion and parathion. These compounds
bind to acetylcholinesterase (AChE), rendering it inactive in what is generally considered an
irreversible reaction. Carbamate esters, such as sevin and aldicarb, also inactivate AChE by binding to
it, although this reaction is considered reversible. Thus, carbamate poisoning is usually less severe than
organophosphate poisoning.
Since ACh is such a ubiquitous neurotransmitter in the body, the symptoms of anticholinesterase
toxicity may take on a variety of forms. These may include decreased cognitive and motor skills and
loss of autonomic nervous function, resulting in vomiting and diarrhea, seizures, tremors, and fatigue.
Neurotransmitter Inhibitors and Receptor Antagonists
Although many neurotoxic insecticides target AChE and thus the function of the neurotransmitter ACh,
other insecticides exert their effects on other neurotransmitters. An example is the chlorinated
cyclodienes, such as chlordane and endosulfan, which block the binding of the inhibitory neurotransmitter
γ-aminobutyric acid (GABA) to its postsynaptic receptor. The indicators of toxicity are again
the generalized symptoms of seizures, nausea, dizziness, and mood swings.
Other chemicals that are implicated in neurotransmitter inhibition include carbon disulfide and
DDT, which inhibit norepinephrine function, and manganese, which inhibits serotonin, norepinephrine,
and dopamine function. Another commonly encountered chemical, nicotine, which is
found in tobacco products and some insecticides, binds to a subset of ACh receptors that bear its name.
These “nicotinic receptors” are found throughout the central and autonomic nervous systems and at
neuromuscular junctions. Their increased stimulation can lead to the well-known and often contrary
symptoms of nicotine poisoning, such as excitability, nausea, and increased heart rate, followed by
muscle relaxation, decreased heart rate, and sometimes coma or death.
7.4 INTERACTIONS OF INDUSTRIAL CHEMICAL WITH OTHER SUBSTANCES
The effects of nicotine on the nervous system have already been discussed. While truly severe effects
are expected only at high acute exposures, the lower but chronic exposure of a smoker to nicotine may
combine with workplace exposure to other chemicals to produce an additive or even synergistic effect
on the nervous system. The same is true for other neurotoxic chemicals to which a worker may be
exposed outside the workplace, but that nonetheless serve to exacerbate the symptoms of neurotoxicity
resulting from workplace chemical exposure.
Perhaps the most common neurotoxicant of this sort is ethanol, which impairs axonal signal
transmission by disrupting the sodium and potassium channels. This results in general CNS
depression and uncoordination. It may also have serious consequences when combined with other