Etiology

• Organophosphate insecticide poisoning in cattle may occur in various circumstances.
  • Spills of pesticide near food stores or feeding areas.
  • Contamination of feed or water sources.
  • Animals breaking into storage areas and accessing pesticide products.
  • Using pour on ectoparasiticide products at incorrect concentration/dilution.
  • Overzealous use of spray products leading to inhalation and conjunctival contamination in poor environmental conditions (eg windy).
  • Use of agricultural products on animals in error.
  • Exposure from airplane dusting of insecticides.
  • Inappropriate disposal of empty pesticide containers or use of old insecticide containers as feed utensils.
  • Grazing in recently sprayed land or on land contaminated with spray drift.
  • Use of old products where the original organophosphate insecticide has decomposed to a more toxic compound.

Predisposing factors

General

• The following may be at increased risk of poisoning:
  • Tired or stressed animals. 
  • Water-deprived animals.
  • Chilled animals.

Specific

• Organophosphate insecticides have two main toxic effects: 
  1. Cholinesterase inhibition.
  2. Delayed neurotoxicity.

Cholinesterase inhibition

• Organophosphate insecticides bind to and inhibit acetylcholinesterase resulting in accumulation of acetylcholine.
• This results in central effects (as organophosphate compounds cross the blood brain barrier), nicotinic and muscarinic effects:
  • Muscarinic effects usually occur first with bronchial constriction and increased mucous secretion. In the gut there is increased peristalsis and salivation. These signs are commonly referred to by the acronyms: 
    • SLUDGE: salivation, lacrimation, urination, defecation/dyspnea, gastrointestinal upset and emesis (in animals that can vomit).
    • DUMBELS: diaphoresis/diarrhea, urination, miosis, bradycardia, bronchospasm/bronchorrhea, emesis/excess lacrimation and salivation.
  • Nicotinic effects involve skeletal muscle responses with twitching, tremor, seizures, weakness and paralysis. 
• Spontaneous reversal of enzyme inhibition by organophosphate insecticides can occur depending on the compound involved. 
  • This occurs after hydrolysis of the phosphorylated cholinesterase. 
• Some compounds, however, undergo ‘aging’ where the phosphorylated enzyme is very stable (and irreversibly inhibited). 
  • Recovery of cholinesterase activity occurs through synthesis of new enzyme. 
• There are two antidotes to organophosphate insecticide poisoning:
  1. Atropine acts as a non-competitive antagonist by blocking the effect of the muscarinic receptors on target organs. 
  2. Oximes such as pralidoxime, accelerate the hydrolysis of the phosphorylated enzyme to reverse inhibition but have no effect on an ‘aged’ phosphorylated enzyme. 

Delayed neurotoxicity

• Organophosphorus-induced intermediate syndrome (IMS):
  • Poorly described in animals, although it has been reported in humans, cats and dogs. 
  • It does not appear to have been reported in cattle; it was only recognized in humans in the 1980s. 
  • There is severe acetylcholinesterase inhibition but muscle fasciculations and hypersecretion associated with muscarinic receptor effects are absent.
• Organophosphorus-induced delayed neurotoxicity (OPIDN):
  • This form of organophosphate poisoning is characterized by distal degeneration of axons of both the peripheral and central nervous systems and involves phosphorylation and then aging of neuropathy target esterase (NTE) in peripheral nerves.

Timecourse

• Acute poisoning:
  • Variable, depending on the circumstances: 
    • It can be 15-30 minutes or 6-12 hours, sometimes 1-4 days after dermal exposure or days or weeks after low level chronic exposure.
  • In many incidents reported in cattle deaths began within hours of exposure.  
• Organophosphorus-induced intermediate syndrome (IMS):
  • 2-4 days after apparent recovery from poisoning.
• Organophosphorus-induced delayed neurotoxicity (OPIDN):
  • At least 8 days, usually 1-2 weeks but sometimes up to 4 weeks after exposure.

Epidemiology

• Organophosphate insecticides are very widely used as pesticides.
• In veterinary medicine they are used as ectoparasiticides and anthelmintics.