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Excessive and spontaneous release of acetylcholine

Inhibits acetylcholinesterase and pseudoCholinesterase

Central analeptic agent; GABA antagonist postsynaptic inhibitor

Blood 2.8 Fg/dl

Blood low Cholinesterase activity (70% of baseline)

Pulmonary and dermal irritant; renal effects; pulmonary effects: cardiac effects; GI distress; garlic or rotten fish odor

Metallic taste; thirst; burning eyes

GI distress; excessive sweating and salivation; hypothermia; liver dysfunction

GI distress; respiratory failure

Mania; hallucinations; delinum; headache; vertigo; cognitive decline; amnesia; aphasia; incoordination; myoclonus; tremors

Resembles Reye's syndrome in children; drowsiness; optic neuropathy; night blindness; tremors; seizures; mononeuropathy; polyneuropathy

Headache; fatigue; dizziness; decreased consciousness; sleep disturbance cognitive decline; blurred vision; absent pupillary response; muscular fasciculations; tremor; delayed polyneuropathy (OPIDP)

Irritability; excitement; decreased consciousness; paresthesias; muscular stiffness; fasciculations; seizures; rigidity

Removal from exposure

Anticonvulsants for patients with seizures

Administer atropine sulfate and pralidoxime

Respiratory support; seizure prevention; administer diazepam; morphine and apomorphine are contraindicated

Affects cortical, cerebellar, and basal ganglia structures

With chlordecone, electron-dense particle accumlation in Schwann cells

Axonal neuropathy and nonspecific CNS changes

Small subarachnoid hemorrhages;

capillary proliferation;

demyelinization

* Biological exposure indices (BEls) Amencan Conference of Governmental Industna] Hygienists (ACGIH) values from AcGIH Threshold Limit Values and Biological Ex,oosure Indices for 1994 1995 Cincinnati, ACGIH, 1994. CNS, Central nervous system; GABA, gamma-aminobutync acid; GL gastrointestional.

acetylcholine. This is in contrast to the acute actions of organophosphates, which block the metabolism of acetylcholine extracellularly. Interestingly, because exposure to both organochlorines and organophosphates produces cholinergic overactivation, these chemicals can cause similar symptomatology.

Epidemiology and Risk Factors. Chlorinated hydrocarbon insecticides are highly soluble in fats and oils. In addition, they last an extremely long time in the environment, thus contributing to chronic toxicity. Commonly used organochlorine insecticides include aldrin, chlordane, DDT, endrin, heptachlor, chlordecone (kepone), and lindane. Most of these insecticides have been banned or restricted in the United States because of their persistence in the food chain, which leads to deleterious effects on wildlife. DDT was banned in the United States in 1973 but is still used in the Third World. Absorption may occur through respiration or through the oral or skin route.

Clinical Features and Associated Findings. Clinical manifestations of organochlorine neurotoxicity have been associated with an oral dose of 10 mg/kg. With acute DDT toxicity, patients report a metallic taste in the mouth. Within 1 hour they complain of dryness of the mouth and extreme thirst. Drowsiness or extreme insomnia, burning eyes, and a gritty sensation in the eyelid are also reported. Other symptoms may include aching of the limbs, muscular spasms, tremors, stiffness and pain in the jaw, difficulty with concentration, and night blindness. Chronic exposure to these compounds can cause tremor and convulsions. Upper extremity weakness, which progresses to wrist drop, may also occur. Mononeuropathy, optic neuropathy, and polyneuropathy have all been described in patients with chronic exposure. In workers in industrial settings that produce DDT and other chlorinated hydrocarbon insecticides, abnormal EEGs marked by bitemporal, sharp wave activity and shifting lateralization have been reported. '331

Differential Diagnosis and Evaluation. The diagnosis is made by the history. Although organochlorines and their metabolites can be found in the blood, this test is generally unavailable.

Management. Treatment is supportive. For patients with intractable seizures, diazepam and pentobarbital may be useful. Pentobarbital may also accelerate the metabolism of organochlorines. Atropine and adrenergic amines are contraindicated because they may potentiate myocardial irritability.

Prognosis. With the exception of anticonvulsants in patients in whom seizures are prominent features, there are no specific antidotes for DDT.

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