Table of Contents
SUBSTANCES INCLUDED IN THIS CATEGORY
Glyphosate is a herbicide which is supplied as a concentrate with surfactant (Roundup®). The concentrate is 41% glyphosate, 10-20% polyoxyethylamine (surfactant) and water. In use the product is diluted 40 fold to a 1% concentration of glyphosate.
Some glyphosate is sold as a potassium salt and cause lifethreatening hyperkalaemia.
It is also available in a 10% solution as Zero® Weed Killer.
It is unclear whether toxicity from ingestion to herbicide results from glyphosate but the surfactant certainly appears to be toxic. It is most likely both components contribute to toxicity.
MECHANISM OF TOXIC EFFECTS
Glyphosate is an organophosphate compound however it does not act as an acetylcholinesterase inhibitor in man. There is some evidence that glyphosate has a direct cardiotoxic effect and it is locally toxic to the gastrointestinal tract. The surfactant is approximately three times as toxic weight for weight as glyphosate and may be responsible for the pulmonary complications.
KINETICS IN OVERDOSE
Kinetics in man after overdose is unknown but only one fifth to one third of glyphosate appears to be absorbed in animals.
The volume of distribution is low - 0.28 L/kg in dogs.
Metabolism - Elimination
There is one major metabolite of unknown toxicity (aminomethyl phosphonic acid) and both glyphosate and its metabolite are excreted in the urine.
Concentrated Roundup® is locally irritating and the initial presentation is with gastrointestinal toxicity. In severe poisoning hypotension, pulmonary dysfunction, renal failure, Cardiac arrest, coma, repeated seizures or death may occur.
Spontaneous vomiting, nausea, epigastric and abdominal pain and diarrhoea are seen with erosions of the pharynx, larynx and oesophagus frequently present on endoscopy. Similarly gastritis, gastric ulceration and duodenitis have also been observed.
Initial mild hypoxaemia may be followed by evidence of acute pulmonary oedema and respiratory failure requiring intubation and ventilation.
Hypotension is frequent and in severe poisonings may require pressor amines (such as dopamine and adrenaline). Some cases progress to refractory hypotension which can be a cause of death. This refractory hypotension in the presence of normovolaemia unresponsive to pressor amines suggests a direct myocardial depressant effect.
For some preparations hyperkalaemia may contribute to the cardiotoxicity
Central nervous system effects
Confusion, coma and seizures may occur.
In seriously poisoned patients a metabolic acidosis is frequent. Some data indicate glyphosate may interfere with oxidative phosphorylation. Hyperglycaemia is frequent. Leucocytosis is common. Severe hyperkalaemia has been reported.
A variety of renal abnormalities occur including oliguria and occasional elevated serum creatinine. Liver enzymes may become abnormal although severe hepatitis is unusual. Acute pancreatitis has been reported.
DETERMINATION OF SEVERITY
The assessment of severity of toxicity is determined by dose ingested and clinical grading of toxicity.
The ingestions of 5-50 mL may result in no symptoms or minor gastrointestinal symptoms only. Moderate symptoms occur with 50-100 mL of the concentrate and severe symptoms are likely when 100 mL or more of the concentrate are ingested.
Clinical grading of toxicity
Asymptomatic: No abnormalities on physical or laboratory examination
Mild: Predominantly gastrointestinal symptoms with stable vital signs and no other organ involvement
Moderate: Gastrointestinal symptoms lasting longer than 24 hours Hypotension, responsive to intravenous fluids. Pulmonary dysfunction not requiring intubation. Acid base disturbance. Evidence of transient hepatic renal damage or temporary oliguria
Severe: Pulmonary dysfunction requiring intubation. Renal failure requiring dialysis Hypotension requiring pressor amines. Cardiac arrest. Coma Repeated seizures. Death
Clinical presentation of glyphosate poisoning (adapted from Roberts 2010)
No abnormalities on physical or laboratory examination
Predominantly gastrointestinal symptoms including mild corrosive injury with stable vital signs, without involvement of other organs
Gastrointestinal symptoms lasting longer than 24 hours
Hypotension responsive to intravenous fluids
Respiratory dysfunction not requiring intubation
Evidence of transient liver or kidney damage, or temporary oliguria
Respiratory dysfunction requiring intubation
Kidney failure requiring dialysis
Hypotension requiring inotropic support
Coma (Glasgow Coma Score less than 10)
Patients should have serum electrolytes, creatinine, urea, liver function tests, glucose and arterial blood gases.
Baseline then as indicated clinically.
Chest X-ray should be performed in any patient with abnormal gas exchange or clinical signs of pulmonary involvement.
Hypotension may develop several hours after ingestion. Cardiac monitoring should be available. Hypotension should be treated initially with intravenous fluids and if unresponsive with pressor amines. There is a risk of pulmonary oedema so aggressive fluid resuscitation is inadvisable. Hyperkalaemia should be corrected.
Respiratory function should be monitored closely, oxygenation assured and intubation with assisted ventilation may be required. If pulmonary oedema occurs positive respiratory pressure may be of value. Urine output should be monitored and prevention of hypovolaemia and hypotension should be a priority. Acidosis usually responds to bicarbonate therapy but may on occasion be resistant.
There are no specific antidotes.
Oral activated charcoal should only be given if the patient presents within 1 hour of ingestion. Since endoscopy is an option for assessment of oesophageal burns, charcoal should not be given unless there is significant chance of benefit.
From the pharmacokinetic parameters of glyphosate, haemodialysis may be of theoretical value but there are no data to support its use. Haemodialysis may be of value for renal failure or acidosis which does not respond to bicarbonate.
The differential diagnosis should include any garden shed poisonings and depending on regional availability, paraquat.
LATE COMPLICATIONS, PROGNOSIS - FOLLOW UP
There is the potential for long term lung injury if significant ARDS occurs.
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