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INTRODUCTION

Glyphosate (N-[phosphonomethyl]glycine) is an herbicide that is used widely 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. U.S. poison control center data from 2014 report glyphosate to be the most common herbicide exposure. There are over 750 commercial glyphosate-based products (Roundup, Vantage, and many others) 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).

MECHANISM OF TOXICITY

The precise mechanisms of toxicity of glyphosate formulations are complicated. 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.

TOXIC DOSE

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.

CLINICAL PRESENTATION

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 ...

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