Medicolegal Aspects of Agricultural Poisons

Fatal Dose

• Malathion about 1 gm orally
• TEPP Tetraethyl pyrophosphate 45-50 mg IM or IV 100 mg orally
• OMPA Octa methyl pyrophosphate 80 mg by IM or IV 175 mg orally
• Parathion 80mg by IV or IM and 175 mg orally
• HETP Hexa ethyl tetraphosphate 160 mg by IV or IM; 350 mg orally
• Diazinon 1 gm orally

Fatal period:

• Fatal doses: death in half to three hours or few more hours
• In acute effects: non fatal dose: 48 to 72 hours or 3 weeks

Clinical Features

Organophosphate insecticide poisoning in human can produce:

• Acute poisoning: due to acute peripheral and central cholinergic block
• An intermediate syndrome with weakness
• A delayed distal polyneuropathy

Acute Poisoning

1. Muscarinic effects: Due to muscarinic like action, following clinical features are observed
   1. Bronchial tree — cough, increased secretions, bronchoconstriction, wheezing, dyspnea, pulmonary edema.
   2. Gastrointestinal — nausea, vomiting, abdominal cramp, diarrhea.
   3. Sweat glands — increased sweating.
   4. Salivary glands — increased salivation. Mnemonic: “DUMBELS”: Diarrhoea, Urination, Miosis, Bronchospasm, bradycardia, Emesis, Lacrimation, Salivation
   5. Lacrimal glands — increased lacrimation. Chromodacryorrhea (shedding of red tears) due to accumulation of porphyrin in the lachrymal glands is seen very rarely.
   6. Eyes — miosis, blurring of vision or dimness of vision. Miosis develops due to the inhibition of cholinesterase and marked parasympathomimetic stimulation of iris. However, dilatation of pupil in organophosphate intoxication have been recorded, therefore, it is essential not to rely only on pupillary size as diagnostic criteria for organophosphate compound poisoning.
   7. Heart — slow pulse, hypotension.
   8. Urinary bladder — frequency of micturation increases and there is urinary incontinence.
2. Nicotinic Effects:

   1. The nicotinic effects are as follows:

      1. Striated muscles: easy fatigue, weakness, muscular twitching, fasciculation, cramps
      2. Sympathetic ganglia: pallor, occasional elevation of blood pressure (hypertension), tachycardia
      3. Increased adrenal medulla activity

      Mnemonic: “MATCH”

      Muscle weakness, Adrenal medulla activity, Tachycardia, Cramps in muscles, Hypertension

3. CNS effects

   • Irritability

   • Apprehension

   • Restlessness

   • Fine fibrillary tremors of hands, eyelids, face or tongue

   • Muscular weakness

   • Convulsions — the convulsions may be tonic (limbs stretched and rigid) or may be clonic (rapid repetitive movement). Clonic convulsions are more common.
   • Mental confusion progressing to stupor to coma
   • Depression of respiratory and circulatory centers

Causes of death

1. Respiratory failure
2. Cerebral hypoxia
3. Hyperthermia
4. Hepatic failure
5. Renal failure

Intermediate syndrome

• Intermediate syndrome is a neurotoxic effect that appears after acute cholinergic crisis but before the expected onset of delayed neuropathy.
• The cardinal feature of the syndrome is muscular weakness, affecting predominantly the proximal limb muscles and the neck flexors. Cranial nerve palsies are common. (The intermediate syndrome predominantly affect muscles innervated by the cranial nerves — neck flexors, proximal muscles of the limb and the muscles of respiration).
• This syndrome carries a risk of death because of the associated respiratory depression.
• The muscle weakness has an acute onset, noticed within 24 to 96 hours after poisoning.

Delayed polyneuropathy:

• Delayed polyneuropathy appears 2 to 3 weeks after poisoning.
• The delayed polyneuropathy is due to inhibition of enzyme neurotoxic esterase with nerve demyelination.
• In delayed polyneuropathy, the paralysis is usually limited to the distal muscles of the limbs; cranial nerves and respiratory muscles are spared.
• The disorder is characterized by flaccid weakness and atrophy of distal limb muscles or spasticity and ataxia.

Diagnosis:

1. Cholinesterase levels
   • Depression of RBC cholinesterase level more than 50 percent of normal indicates organophosphate poisoning.
   • The decrease is due to binding by phosphate group of pesticide. It is better parameter than plasma cholinesterase.
   • Depression of plasma (serum) cholinesterase activity more than 50 percent of normal indicates Organophosphate poisoning. This test is not specific as plasma cholinesterase activity is also depressed in cirrhosis of liver, neoplasia, malnutrition, septicemia due to burns, obstructive jaundice.
2. Colorimetric method
   • 1 ml sample urine is taken and 1 ml of NBB(Napthol Blue Black) {45% in acetone 4-(nitrobenzyl) pyridine} added and mixed for 30 seconds in vortex mixer. The mixture is heated at 100o C for 20 minutes. Organophosphate insecticide shows a characteristic purplish blue color that can be read using spectrophotometer.

3. P-nitrophenol test

4. Paper chromatography

5. Thin layer chromatography (TLC)
6. Gas chromatography (GC)
7. Gas chromatography-mass spectrometry (GC-MS)
8. High performance liquid chromatography (HPLC)
9. ECG may show right axis deviation, ST segment depression and T wave inversion

Management

The principles of treatment are as follows:

• Stabilization of patient
• Decontamination
• Antidote administration
• Supportive measures
• Nursing care

Stabilization of the patient: ABC (airway breathing and circulation is checked and restored and the vitals are constantly monitored.

Decontamination:

• Skin — the affected part should be washed thoroughly with copious water

• Ocular — copious eye irrigation with normal saline or tap water

• Ingestion — gastric lavage and administration of activated charcoal.

Antidote administration: 

• Atropine is competitive antagonist of acetylcholine and blocks muscarinic manifestations of Organophosphate.
• It does not reverse peripheral muscular paralysis, which is nicotinic action. The atropine should be given 2 mg intravenous promptly with dose repeated every 10 or 15 to 30 minutes till pupil dilates (up to 200 mg has been administered in a day).
• Some authorities recommend administration of atropine until bronchial and other secretions have dried. According to them pupil size and heart rate cannot be used as end-points. Continued treatment with maintenance doses may be required for 1 to 2 weeks
• Oximes are used as they helps to regenerate acetylcholinesterase at muscarinic, nicotinic and CNS sites.
• Pralidoxime (2-PAM) is given intravenously as 500- mg/20 ml (5% isotonic solution) infusion in a dose of 1 to 2 gm (children 20 to 40 mg/kg). Given every 12 hours.

Supportive measures:

• Oxygen administration, ventilator assistance
• Maintain vital parameters, hydration, urine output
• Convulsions should be controlled with judicious use of diazepam

• Avoid giving Other acetylcholinesterase inhibitors such as Physostigmine, Endorphonium (competitive AchE inhibitor), Succinylcholine for rapid intubation

Autopsy Findings

• • Insecticide like smell (sometimes garlicky or kerosene like)
  • Froth at mouth and nostrils
  • Cyanosis
  • Constricted pupils
  • Stomach contents have insecticide like smell. Mucosa stained with compound color, congested and eroded
  • Congestion of organs
  • Pulmonary edema
  • Cerebral edema
  • Features of toxic myocarditis had also been reported.
  • Microscopic examination of heart reveals dilatation of pericardial blood vessels with hemorrhages in the surrounding tissues,
  • Interstitial edema of myocardium, inflammatory cells, hemosiderin-laden macrophages and fatty infiltration of the myocardium.

Medicolegal Importance

• Accidental poisoning may occur in farmers while spraying in the fields or opening the lid of the containers.
• Suicidal poisoning is common with this insecticide.
• Homicidal is rare as it is difficult to mask the smell of insecticide.
• Even though sometimes mixed with alcohol for homicidal purposes