24. Acute and chronic intoxications with pesticides – classification, pathogenesis, specific toxicity, clinical manifestations of the most common intoxications (organophosphate, chlorinated pesticides, carbamates, dithiocarbamates), occupational risk, diagnostic and therapeutic algorithm.

Introduction

This topic covers acute and chronic poisoning with pesticides, the chemicals used to kill pests, fungi and weeds. Most cases in practice involve agricultural and greenhouse workers, and the main exam focus is on the four classic groups: organophosphates, organochlorines, carbamates and dithiocarbamates. For each group you should know the mechanism, the clinical picture, the diagnostic tests and the specific treatment.

Definition and classification

A pesticide is any substance or mixture intended to prevent, destroy or control pests. Pesticides are classified by chemical group, and the group largely determines the toxic mechanism, the duration of toxicity and the treatment.

Pathogenesis

Absorption occurs through the skin (the most important route in occupational exposure), the respiratory tract and the gastrointestinal tract. Many pesticides are lipophilic, so they penetrate membranes and, in the case of organochlorines, accumulate in adipose tissue. Toxicity depends on the agent, the dose, the route and the duration of exposure.

Organophosphates

Organophosphates phosphorylate the serine site of acetylcholinesterase, so acetylcholine accumulates at muscarinic and nicotinic synapses and in the central nervous system. Inhibition is practically irreversible; the phosphorylated enzyme may undergo ageing, after which oxime reactivation is no longer possible.

• Muscarinic signs: salivation, lacrimation, urination, defecation, vomiting, abdominal cramps, bronchorrhoea, bronchospasm, bradycardia, miosis and sweating.
• Nicotinic signs: muscle fasciculations, weakness progressing to flaccid paralysis, tachycardia and hypertension.
• CNS signs: anxiety, confusion, convulsions, coma and central respiratory depression, which is the usual cause of death.
• Intermediate syndrome: proximal limb, neck and respiratory muscle weakness with cranial nerve palsies, appearing about 24 to 96 hours after exposure.
• Organophosphate-induced delayed polyneuropathy: a distal, predominantly sensorimotor axonal neuropathy appearing 1 to 3 weeks after exposure, caused by inhibition and ageing of neuropathy target esterase (NTE).

Chronic exposure may cause a neurasthenic syndrome (fatigue, headache, irritability, poor concentration, sleep disturbance), mild hepatic effects and dermatitis.