by Dr. Mohamed Isa Abd. Majid
The Sun, May 10, 1997
GLYPHOSATE IS A BROAD-SPECTRUM, non-selective systemic herbicide. It is useful on essentially all annual and prennial plants including grasses, sedges, broad- leaved weeds and woody plants. It can be used on non-cropland and a variety of crops.
The chemical name of glyphosate is N-(phosphonomethyl) glycine. While it can be described as an organophosphorus compound, glyphosate is not an organophosphate ester, which is widelyused as an insecticide. Thus it does not inhibit cholinesterase activity.
The presence of a phosphono-group in the structure has been incorrectly interpreted as an organophosphate which suggests cholinesterase inhibition in poisoning cases. Retrospective studies on glyphosate poisoning have shown atropine and pralidoxime been mistakenly administered to counteract such poisoning cases.
Based on the approved pesticide listing in Malaysia, there are 172 herbicide products which contain glyphosate. These products can be classified into two main groups, based on the supplied concentrations.
Technical glyphosate us normally supplied as a white solid material which is poorly soluble in water. The concentration range for the technical grade is usually between 70-95%.
Besides the technical grade that is normally supplied to large plantations, the hebicides supplied to small scale plantations and farmers are in the concentration range of 13-41% w/w and require dilution with water before application. The majority of the glyphosate-containing herbicides are supplied as the isopropylamine salt in combination with various surfactants, including the polyethoxylated amine non-ionic surfactant that allows the herbicide to spread over the plant leaves.
In some reports, the toxicity arising from glyphosate products is said to be caused by the surfactant incorporated into the formulation rather than the active ingredient itself. Besides the isopropylamine salt, other glyphosate salts commonly found in Malaysia are the monoammonium, sodium and trimesium salts.
Besides the active ingredient and the surfactant which are thought to cause the clinical effects seen in poisoning exposures, the by-products that are found in glyphosate formulations are also responsible for some clinical effects.
It has been suggested that the clinical effects seen in glyphosate poisoning cases may be divided into minor to moderate abd significant exposures. By having the severity classification, a different treatment strategy could be employed to manage the poisoning cases.
The recommended strategy of classification is as follows:
- Minor to moderate
Symptoms are localised to oral mucous or the gastrointestinal symptoms is less than 24 hours, with inflammation of the oesophagus, oral ulceration, increase in urine output, liver or renal damage and acid base disturbance. - Severe
Respiratory failure, renal failure, reduction of blood pressure, cardiac arrest, coma and seizures could occur. - Dermal exposures
When an exposure to glyphosate occurs locally, the clinical effects seen are usually classified as mild to moderate effects. These local effects include erythema, piloerection and contact dermatitis. It is expected that the severity of a skin exposure will be significantly decreased with a less concentrated product. As the contact time with the product and the skin is decreased, the severity of a reaction will also be decreased. - Eye exposure
Corrosive effects would not be expected from the formulated consumer products, especially after dilution. Among the most common effect seen from eye contact with the herbicide is mild conjunctivitis which normally clears in one to two days. It is expected that the consequences of an eye exposure will be less severe with a less concentrated product. Rapid removal of the herbicide from the eye by irrigation reduces the likelihood of serious effects.
At present, the mechanism in which glyphosate exerts its toxic effects seems to be inconclusive. Although there have been various animal studies done to look into the toxic mechanism, the interpretation of the findings have produced conflicting evidence.
Several reports have indicated that following massive ingestion, a surfactant, non-ionic polyoxyethylene tallow amine used in a glyphosate products, is responsible for symptoms. Animal pharmacological studies indicate that the surfactant produces a hypotensive (reduction in blood pressure) effect when the surfactant was administered intravenously into dogs.
- Treatment for minor exposures
In cases of dermal exposure, the management of such exposure involves removing all contaminated clothing and flooding the skin surface with water. Following this, the exposed skin is then washed with soap and water. A close examination of the skin may be require if pain or irritation persists after decontamination. All contaminated clothing should be laundered before being worn again.In eye exposures, the exposed eyes should be irrigated with copious amounts of water or saline for at least 15 minutes. Pour the water from a cup or glass held 10 cm from the eye. A close examination of the eyes may be needed if pain or irritation persists after 15 minutes of irrigation with water or saline.
If an ingestion involves dilute preparation of glyphosate preparations, such as 2% w/w preparation, irrigate the mouth with water. other immediate action includes dilution with water or milk if the patient is able to swallow. If this is done, do not exceed 5ml/kg body weight in child or 250 ml in an adult. Further gastrointestinal decontamination is not needed, even if spontaneous vomiting has not occurred.
- Treatment for significant exposures
There is no available antidote for glyphosate poisoning and treatment is largely symptomatic is nature.In any significant ingestion exposure, the acute syndrome of glyphosate/ surfactant toxicity may occur within the first 24 hours of ingestion and may progress rapidly. These cases of significant ingestion, in particular those greater than a mouthful (> 0.5 ml/kg) of larger than 41% glyphosate concentrations SHOULD BE EVALUATED BY A PHYSICIAN AND CONSIDERED FOR HOSPITAL ADMISSION.
- Prevention of absorption
On admission to a hospital, normally, further absorption of the ingested herbicide would be prevented by performing gastric lavage, It is usually considered if no significant spontaneous vomiting has occurred. Gastric lavage may be very effective if performed within one to two hours post ingestion.However, if a co-ingestant has pharmacologic properties that slows gastrointestinal movement, lavage may be indicated even after a prolonged post-ingestion time.
Activated charcoal is also given to absorb remaining glyphosate. Cathartics speed gastrointestinal transit time and decrease the time that the drug or chemical is available for absorption. Cathartics also hasten the elimination of the charcoal/drug complex in the GI tract.
- Enhanced elimination
Glyphosate is excreted very well by the kidneys. Thus to increase the elimination of the glyphosate, adequate urine flow will ensure the rapid elimination of the glyphosate. This elimination can be enhanced by a technique known as forced diuresis. - Monitoring of the blood pressure
A poisoned patient would normally be monitored for signs of haemodynamic or blood pressure instability. If the patient has a reduced blood pressure, intravenous fluids administration would be instituted to ensure adequate blood volume. If the blood pressure reduction is severe, then blood vessel vasoconstrictors (otherwise known as vasopressors) would be given to maintain the blood pressure. This would include the administration of drugs such as dopamine, noradrenaline, adrenaline or phenylephrine, which would raise the blood pressure rapidly.
The writer is a pharmacist and head of the Toxicology Laboratory at the National Poison Centre, Universiti Sains Malaysia, 11800 Minden, Penang.
