Insecticides

Organophosphates are still the most widely used insecticides in the United States and the world, but botanical insecticides and insect growth regulators are becoming much more widely used, due to their lower toxicity. Also included in this category are the organochlorines (such as DDT), the carba-mates, and insect repellants (DEET and p-dichlorobenzene).

Organophosphates (OPs) are the most common cause of insecticide poisoning and cause a few deaths each year in the United States. OPs are used for suicide in both the United States and particularly in the Third World, where more than 100,000 people per year are estimated (by the World Health Organization) to take their own lives using this group of chemicals.

Organophosphates are so widely used because of their effectiveness against a wide variety of insects and their lack of persistence in the environment (compared to organochlorines). The toxicity of OPs varies greatly—a drop of the OP nerve agents VX, soman, or sarin may be lethal, while malathion has an oral median lethal dose (LD50) of approximately 1 g/kg. Most of the OPs are rapidly absorbed by all routes. They may be classified as direct (the nerve gases) or indirect (most commercially used crop, animal, and home products) cholinesterase inhibitors. Metabolism, primarily by the CYP450 system, is required to activate the indirect inhibitors. Direct inhibitors may have almost immediate effects, or up to 2 to 3 hours delay after dermal absorption. Indirect inhibitors may not produce symptoms until 6 to 24 hours after exposure.

The toxicologic effects of OPs are almost entirely due to inhibition of acetylcholinesterase in the nervous system, which causes acetylcholine to accumulate in the synapses and myoneural junctions. Muscarinic, central nervous system, and nicotinic effects are produced as outlined in Table 16.1, usually in that order. The most common clinical presentation is a patient with an odor similar to garlic, with miosis, increased airways secretion, lacrimation, bradycardia, and GI complaints (7). This constellation of findings should be managed as OP poisoning until proven otherwise (8).

Serum and red blood cell (RBC) cholinesterase levels should be obtained early, but therapy should not be delayed pending laboratory confirmation. Treatment should include attention to the airway and adequate oxygenation with atropine administered until secretions dry. The initial dose of atropine should be 1 to 2 mg for adults and 0.05 mg/kg for children, administered intravenously if possible, and repeated every 15 to 30 minutes until signs of atropinization develop (flushing, drying of secretions, and dilation of pupils, if they were miotic at presentation). Atropine may be required for 24 hours and should be tapered, rather that abruptly stopped. Pralidoxine (2-PAM) is a specific OP antidote. It should be administered as soon as possible in all

Table 16.1. Clinical effects of organophosphate poisoning.

Site

Physiologic Effect

Muscarinic effects

Sweat glands

Sweating

Pupils

Miosis

Ciliary body

Blurred vision

Lacrimal glands

Lacrimation

Salivary glands

Salivation

Bronchi

Constriction with wheezing

Gastrointestinal

Cramping, vomiting, diarrhea, tenesmus

Cardiovascular

Bradycardia, hypotension

Bladder

Incontinence

CNS Effects

Anxiety, restlessness, ataxia, convulsions, coma

Nicotinic Effects

Decreased reflexes, respiratory/circulatory depression

Striated muscle

Fasciculations, cramps, weakness, paralysis, respiratory

depression, hypoxia, respiratory arrest

Sympathetic ganglia

Tachycardia, hypertension

clinically significant poisonings. The initial dose is 1 to 2 mg for adults and 25 to 50 mg/kg for children given intravenously over 15 to 30 minutes. A continuous infusion of 10 to 20 mg/kg, up to 500 mg/h, is then used in severe OP poisoning. More detailed information on OP poisoning management is found in standard texts on poisoning and drug overdose. Severe OP poisoning has been associated with chronic neurological sequelae including cognitive impairment, depression, and peripheral neuropathies. An intermediate syndrome, termed organophosphate-induced delayed-onset neuropathy (OPDIN) associates hyperreflexia and hypertonicity with long-term, low-dose exposure to OPs. Both syndromes are rarely recognized (7,9).

Carbamates are also cholinesterase inhibitors, producing the syndrome of cholinergic crisis as described for OPs. The syndrome is of shorter duration and more benign than with OPs because carbamates dissociate from the cholinesterase much more readily than OPs, producing a reversible inhibition. Carbamates also poorly penetrate the central nervous system (CNS), rarely producing seizures, ataxia, and central depression of the respiratory and circulatory centers. Red blood cell and serum cholinesterase levels return to normal within hours of exposure. Treatment of carbamate poisoning is also with atropine (in doses identical to those used for OPs but for only 6 to 12 hours because of the shorter duration of enzyme inhibition) and oxygen supplementation. Pralidoxime is not indicated in pure carbamate poisoning, but if the poison is not known for certain and cholinergic symptoms exist, it can be used, pending identification of the poison.

Because of their persistence in the environment, organochlorine insecticides are in limited use in the United States. They are, however, used around the world in mosquito control. Lindane is still used in the United States as a general garden insecticide, for control of ticks, scabies, and lice and for extermination of powderpost beetles. It is absorbed by inhalation and ingestion and less well by dermal contact, unless the skin is abraded or treated repeatedly.

Lindane interferes with normal nerve impulse transmission by disruption of sodium and potassium channels in the axon membrane, leading to multiple action potentials for each stimulus. Clinically this may result in confusion, apprehension, tremors, muscle twitching, paresthesias, dizziness, seizures, or coma—usually in the face of a history of repeated treatment for scabies or lice. Wheezing, rales, or cyanosis may be found if hydrocarbon (a frequent vehicle) aspiration has occurred. Diagnosis is based on a history of exposure or intentional ingestion with physical manifestations of CNS hyperexcitabil-ity. Treatment is decontamination with supportive and symptomatic care. Seizures may require lorazepam or diazepam. Arrhythmias should be treated with lidocaine.

Commonly used botanical insecticides include pyrethrum, nicotine, rotenone, and Bacillus thuringiensis. Other botanicals are used in small quantities but are rarely associated with adverse health effects. Pyrethrum is the oleoresin extract of dried chrysanthemum flowers. It contains about 50%

active insecticidal ingredients known as pyrethrins. Synthetic derivatives of these compounds, called pyrethroids, are much more widely used today. Most insecticides containing pyrethroids also contain piperonyl butoxide, a synergist that increases their effectiveness by retarding enzymatic degradation of the active ingredient.

Pyrethrum-based insecticides are considered to have low toxicity, but they can produce nausea, vomiting, diarrhea, tremors, muscle weakness, and paresthesias. Very high levels of exposure can produce temporary paralysis and respiratory failure. Treatment is supportive. Allergic reactions to the pyrethroids are more common, with about 50% of patients sensitive to ragweed, and cross-reacting to pyrethrum. Pyrethrum and the pyrethroids are well absorbed from the GI tract and minimally absorbed from dermal exposure. They are rapidly metabolized by the liver, leading to their relative lack of systemic toxicity in humans. Persons exposed to prolonged contact with high concentrations of pyrethroids report paresthesias in unprotected skin. Vitamin E oil has been reported to relieve these paresthesias, by an unknown mechanism. Otherwise treatment of toxicity is symptomatic and supportive. Allergic symptoms are treated as with other allergens, by avoidance and anti-histamines for mild symptoms, and corticosteroids and epinephrine for severe bronchospasm (10).

Nicotine, usually derived from tobacco, was used as an insecticide in the past. Now rarely used, most nicotine poisoning is as a result of ingestion of tobacco products or incorrect use of nicotine patches, gum, or nasal sprays. Decontamination is the treatment of choice. Care is supportive, since there is no specific antidote for nicotine. Severe hypersecretion or bradycardia may be treated with atropine.

Rotenone, prepared from the roots of derris, Lonchocarpus, and Tephrosia plants, is used as a household and horticultural insecticide. Piperonyl butox-ide is also used as a synergist with this compound. Toxic to fish, bird, and insect nervous systems, it has produced little human toxicity in decades of use. However, fresh derris root from Malaya has been used for suicides. Numbness of mucous membranes has been reported in exposed workers, along with dermatitis and respiratory tract irritation. Treatment of these symptoms is with decontamination and supportive care.

Several subspecies of Bacillus thuringiensis (BT) are pathogenic to some insects. The product is used both as a spray to be applied to certain food crops and, incorporated into the genetic material of certain plants as a "built-in" insecticide. Infections of humans with these organisms is extremely rare. One volunteer ingesting a BT variety not used as a pesticide developed fever and GI symptoms. A single corneal ulcer has been associated with a splash of BT suspension in the eye. The GI symptoms resolved spontaneously; the ulcer resolved with antibiotic treatment (11).

Insect repellants are intended for human use and are therefore designed to be nontoxic in routine use. Two insect repellants have produced poisoning syndromes: DEET (AA-diethyltoluamide) and p-dichlorobenzene. DEET is minimally absorbed through the skin and is rapidly eliminated, primarily in the urine. Excessive use of high concentrations of this compound has been associated with a idiopathic toxic encephalopathy, particularly in girls and female infants. Symptoms may include lethargy, anxiety, opisthotonos, athetosis, ataxia, seizures, and coma. Ingestion of 50 mL of high concentration DEET (50% to 90%) has produced coma, seizures, and hypotension within an hour of ingestion and death in at least two cases. Irritant contact dermatitis and conjunctivitis have also been reported, as has an anaphylactic reaction in one case. There are no characteristic physical findings. Treatment is symptomatic and supportive.

Originally used as a moth repellant and insecticide, ^-dichlorobenzene is now more commonly used as a deodorizer. Ingestion is fairly common when children eat a part of a deodorant cake in a toilet bowl or diaper pail. It is a mucous membrane irritant and can produce allergic symptoms. Massive ingestions may produce tremors and hepatic or renal injury. There are no characteristic features on physical examination or laboratory studies. Diagnosis is by history of ingestion, and treatment is supportive.

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