Glyphosate (N-[phosphonomethyl]glycine) is the most widely used herbicide worldwide with applications in agriculture, forestry, and commercial weed control. It is one of the first herbicides against which crops have been genetically modified to increase their tolerance. There are over 750 commercial glyphosate-based products marketed for sale in the United States. Concentrations of glyphosate range from 0.5% to 41% or higher and most products consist of an aqueous mixture of the isopropylamino salt of glyphosate, a surfactant, and various minor components. Concentrated Roundup, the most commonly used glyphosate preparation in the United States, contains 41% glyphosate and 15% polyoxyethyleneamine (POEA).

The precise mechanisms of toxicity of glyphosate formulations are complicated and not entirely known. There are five different glyphosate salts, and commercial formulations contain surfactants that vary in chemical structure and concentration.

1. It has been hypothesized that toxicity is related to the presence of the surfactant rather than to the glyphosate itself. Surfactants may impair cardiac contractility and increase pulmonary vascular resistance.
2. Some have postulated that glyphosate or the surfactants may uncouple mitochondrial oxidative phosphorylation.
3. Glyphosate is a phosphorus-containing compound, but it does not inhibit acetylcholinesterase.

Glyphosate itself has very low toxicity by the oral and dermal routes, with 50% lethal dose (LD₅₀) values in animals of more than 5,000 and more than 2,000 mg/kg, respectively. However, the surfactant (POEA) is more toxic, with an oral LD₅₀ of 1,200 mg/kg. Ingestion of >85 mL of a concentrated formulation is likely to cause significant toxicity in adults.

Most patients with acute unintentional glyphosate exposures are asymptomatic or have only mild toxicity, and basic supportive care is generally effective. However, large intentional ingestions may cause serious toxicity and death. The case fatality rate in acute intentional poisoning has been documented in various studies to be between 3% and 8%. In one large prospective observational study involving 601 patients, there were 19 deaths. Death was associated with older age (>40 years), larger ingestions (>190 mL) and high plasma glyphosate concentrations on admission. Gastrointestinal symptoms, respiratory distress, hypotension, altered level of consciousness, and oliguria were observed in fatal cases.

1. Dermal exposure. Prolonged exposure to the skin can cause dermal irritation. Severe skin burns are rare. Glyphosate is poorly absorbed across the skin, with only 3% of patients with dermal exposure developing systemic symptoms.
2. Ocular exposure can cause a mild conjunctivitis and superficial corneal injury. No serious eye injury occurred among 1,513 consecutive ocular exposures reported to a poison control center.
3. Inhalation is a minor route of exposure. Aerosolized mist can cause oral or nasal discomfort and throat irritation.
4. Ingestion. After acute ingestion of a large amount of a glyphosate/surfactant-containing product, serious GI, cardiopulmonary, and other organ system toxicity may occur.
   1. Gastrointestinal corrosive effects include mouth, throat, and epigastric pain and dysphagia. Vomiting and diarrhea are common. Esophageal and gastric mucosal injury may occur.
   2. Cardiovascular. Glyphosate/surfactant-induced myocardial depression can result in cardiogenic shock.
   3. Ventilatory insufficiency can occur secondary to pulmonary aspiration of the product or noncardiogenic pulmonary edema.
   4. Other. Renal and hepatic impairment and a diminished level of consciousness may occur secondary to reduced organ perfusion, although a direct toxic effect of glyphosate or surfactant may contribute. Dilated pupils, convulsions, confusion, a neutrophil leukocytosis, fever, and increased serum amylase have also been reported. In a series of 131 cases of glyphosate ingestion, metabolic acidosis was present in 48% of cases and ECG abnormalities (sinus tachycardia and/or nonspecific ST-T-wave changes most commonly) occurred in up to 20% of cases.
5. The International Agency for Research on Cancer (IARC) has classified glyphosate as probably carcinogenic to humans (Group 2A) based on “limited” evidence of cancer in humans and “sufficient” evidence of cancer in animals.

Is based on the history of contact with or ingestion of glyphosate-containing products.

1. Specific levels. Although unlikely to affect clinical management, serum and urine glyphosate levels may be obtained from a reference laboratory or the manufacturer of Roundup (Monsanto, St. Louis, MO). Initial serum concentrations greater than 731 mcg/mL were associated with fatal outcome in one case series.
2. Other useful laboratory studies include chest radiography, electrolytes, renal function studies, and arterial blood gases or pulse oximetry to assess oxygenation.

1. Emergency and supportive measures
   1. Maintain an open airway and assist ventilation if necessary.
   2. Treat hypotension and coma if they occur. Intravenous lipid emulsion was effective in reversing hypotension in one reported case.
   3. If corrosive injury to the GI tract is suspected, consult a gastroenterologist for possible endoscopy.
2. Specific drugs and antidotes. No specific antidote is available.
3. Decontamination
   1. Skin and eyes. Remove contaminated clothing and wash exposed skin with water. Flush exposed eyes with copious tepid water or saline.
   2. Ingestion. For small ingestions of a diluted or low-concentration product, no decontamination is necessary. For larger ingestions, place a flexible nasogastric tube and aspirate gastric contents, then lavage with tepid water or saline. The efficacy of activated charcoal is unknown.
4. Enhanced elimination. Extracorporeal techniques are not expected to augment the clearance of the surfactant due to its large molecular weight. Several case reports describe the use of hemodialysis primarily to support renal function, to treat significant acidosis, and to correct electrolyte abnormalities. There is insufficient evidence to routinely recommend its use.