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wikitox:glyphosate

Glyphosate

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.

It is also available in a 10% solution as Zero® Weed Killer.

OVERVIEW

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

Absorption

Kinetics in man after overdose is unknown but only one fifth to one third of glyphosate appears to be absorbed in animals.

Distribution

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.

CLINICAL EFFECTS

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.

Gastrointestinal effects

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.

Pulmonary effects

Initial mild hypoxaemia may be followed by evidence of acute pulmonary oedema and respiratory failure requiring intubation and ventilation.

Cardiac effects

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.

Central nervous system effects

Confusion, coma and seizures may occur.

Metabolic effects

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.

Other effects

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.

Ingested dose

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

INVESTIGATIONS

Biochemistry

Patients should have serum electrolytes, creatinine, urea, liver function tests, glucose and arterial blood gases.

ECG

Baseline then as indicated clinically.

Imaging

Chest X-ray should be performed in any patient with abnormal gas exchange or clinical signs of pulmonary involvement.

TREATMENT

Supportive

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

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.

Antidotes

There are no specific antidotes.

GI Decontamination

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.

Elimination enhancement

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.

DIFFERENTIAL DIAGNOSIS

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.

REFERENCES

Adam A, Marzuki A, Rahman HA, Aziz MA. The oral and intratracheal toxicities of Roundup and its components to rats. Vet Hum Toxicol 1997; 39(3):147-151.
Bolognesi C, Bonatti S, Degan P, Gallerani E, Peluso M, Rabboni R et al. Genotoxic activity of glyphosate and its technical formulation roundup. J Agric Food Chem 1997; 45(5):1957-1962.
Chang C-Y, Peng Y-C, Hung D-Z, Hu W-H, Yang D-Y, Lin T-J. Clinical impact of upper gastrointestinal tract injuries in glyphosate-surfactant oral intoxication. Hum Exp Toxicol 1999; 18(8):475-478.
Hung D-Z, Deng J-F, Wu T-C. Laryngeal survey in glyphosate intoxication: a pathophysiological investigation. Hum Exp Toxicol 1997; 16(10):596-599.
Lee HL, Chen KW, Chi C-H. Clinical Presentations and Prognostic Factors of a Glyphosate - Surfactant Herbicide Intoxication: A Review of 131 Cases. Acad Emerg Med 2000; 7:906-910.
Lin C-M, Lai C-P, Fang T-C, Lin C-L. Cardiogenic shock in a patient with glyphosate-surfactant poisoning. J Formos MEd Assoc 1999; 98(10):698-700.
Pushnoy LA, Avnon LS, Carel RS. Herbicide (Roundup) pneumonitis. Chest 1998; 114(6):1769-1771.
Tominack RL. Glyphosate - contemporary clinical features. EAPCCT XIX International Congress abstract. J Toxicol Clin Toxicol 1999; 37(3):374-375.
Sorensen FW, Gregersen M. Rapid lethal intoxication caused by the herbicide glyphosate-trimesium (Touchdown). Hum Exp Toxicol. 1999;18:735-7.
Stella J, Ryan M. Glyphosate herbicide formulation: a potentially lethal ingestion. Emerg Med Australasia. 2004;16:235-9.

wikitox/glyphosate.txt · Last modified: 2018/09/01 09:01 (external edit)