inactive. It is critical for the normal function of the nervous system. When AChE is inhibited, acetylcholine can accumulate causing overstimulation of the cholinergic junctions and organs controlled by cholinergic neurons. Tissues innervated by cholinergic neurons include muscles (both smooth and voluntary); glands such as salivary, pancreas, and lachrymal; and certain parts of the brain. Thus inhibition of cholinesterase can cause overactivity of a wide variety of bodily functions. This overactivity is characteristic of poisoning by cholinesterase inhibitors (Bardin et al., 1994).

EXPOSURES TO CHOLINESTERASE INHIBITORS AND OTHER PESTICIDES DURING THE GULF WAR

Pesticides

Pesticides are defined by the federal Fungicide Insecticide Fumigant Rodenticide Act as any substance that kills, repels, or mitigates a pest. Under this definition, insect repellents such as diethyltoluamide (DEET) would be considered pesticides. Several types of pesticides were used in the Gulf War theater, among the most common were organophosphates, carbamates, and pyrethroids.

Organophosphate pesticides are chemicals in wide use as insecticides in agricultural and nonagricultural applications. They were initially developed by German scientists prior to World War II. They range in toxicity from very mildly toxic to extremely toxic and are toxic by mouth, inhalation, or dermal absorption. Most organophosphate pesticides require activation by an enzyme system known as the cytochrome P450 system. This system oxidizes a portion of the molecule making it much more toxic than the parent compound. It is this active molecule that binds to the cholinesterase molecule, blocking the action of the enzyme and leading to the accumulation of the neurotransmitter acetylcholine. This accumulation of acetylcholine and the overstimulation of the nerves, glands, and muscles that are innervated by cholinergic neurons, lead to the signs and symptoms seen in organophosphate poisonings. The organophosphate binds to the active site and slowly forms a covalent bond with the enzyme, thus irreversibly inhibiting the cholinesterase enzyme. The enzyme is replaced by the body over time.

Carbamates are a group of chemicals that, like organophosphates, are commonly used as insecticides. They also inhibit cholinesterase. The inhibition they cause tends to be less long lasting than inhibition with organophosphates, because unlike organophosphates, they do not go through a permanent bonding (covalent bonding) with the cholinesterase molecule. They are short acting, and the enzyme reactivates when the concentration of the carbamate in the system is reduced.

Permethrin is a low to moderate toxicity pesticide in the class of pesticides known as pyrethroids. This class is derived from natural pesticides, which are found in chrysanthemums. Permethrin alters the function of nerve ion gates by destabilizing the neuronal ion balance. This instability results in neurons firing more easily and in uncoordinated neuronal discharges. These uncoordinated discharges are largely responsible for the insecticidal effect of the chemical.

The most serious consequence of overexposure to pyrethroids is seizure activity. This however, is rare in humans as the toxicity of pyrethroids is far less for warm-blooded animals than for cold-blooded ones. Acute exposure in humans is generally characterized by burning or irritating sensations in the fingers and lips.



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