Organophosphorous insecticides kill insects by affecting their nervous system. Specifically, they inhibit acetylcholinesterase, the enzyme that is responsible for the breakdown of acetylcholine and therefore the termination of its activity. Acetylcholine is a neurotransmitter that acts at two major receptor subtypes, nicotinic and muscarinic. Binding of acetylcholine to receptors at neuromuscular synapses leads to the activation of muscles. Failure to break down acetylcholine results in sustained activity and consequent overstimulation of cholinergically-mediated synapses, particularly nicotinic neuromuscular synapses, muscarinic parasympathetic synapses, and cholinergic synapses of the central nervous system (CNS). That mechanism of toxicity is the same in mammals, birds, and fish, so the acute effects are similar in humans and animals (Ecobichon, 2001).
Organophosphates inhibit acetylcholinesterase when the oxygen with the coordinate bond on the organophosphate molecule (see Figure 3.1) binds to the esteratic site of the acetylcholinesterase enzyme. That binding is initially reversible, but within a matter of minutes, part of the organophosphate molecule may be cleaved from the phosphorus group, and the remainder of the molecule will become essentially irreversibly attached at the esteratic site of the enzyme. The production of the essentially irreversible bond is called aging (Abou-Donia, 1995; Ballantyne and Marrs, 1992; Chambers and Levi, 1992; Ecobichon, 2001; Ecobichon and Joy, 1994; Gallo and Lawryk, 1991; Marrs, 1996). Once aging has occurred, enzyme activity can be recovered only with the synthesis of new enzyme.
Clinical signs of toxicity associated with organophosphate-induced inhibition of acetylcholinesterase depend on dosage. Toxicity in humans and animals includes the signs associated with overstimulation of muscarinic receptors of the autonomic nervous system by acetylcholine (SLUD—salivation and sweating, lacrimation, urination, and defecation—as well as emesis and bradycardia). Acetylcholinesterase inhibition can also cause overstimulation (which can be followed by depression) of nicotinic receptors at neuromuscular junctions and autonomic ganglia and result in ataxia and fasciculations that, at higher dosages, can be followed by flaccid paralysis. Electromyographic changes can be observed after acute poisoning because nicotinic sites in muscles are affected; the changes include decreases in amplitude and increases in peak latencies in nerve conduction (Baker and Wilkinson, 1990; Gallo and Lawryk, 1991; Kaloianova and El Batawi, 1991). Stimulation of autonomic ganglia can also cause hypertension. As is the case at neuromuscular junctions, excess acetylcholine in the CNS causes stimulation that can be followed by depression. Overstimulation can be manifested as nervousness, delirium, hallucinations, and psychoses. Obvious signs do not generally appear until nervous system acetylcholinesterase inhibition approaches 70%.
Not all exposed people show all signs, and signs can vary with the organophosphorous compound, dose, route of exposure, and species. Signs often appear within minutes or hours, but they might not appear for several days. Duration can vary from minutes to weeks and can be followed by full recovery from obvious manifestations of