herbicides

see also toxicology

• glyphosate is the most widely used general purpose herbicide in the world & is a common household product
• retail sale volumes exceed the volume of the next 6 leading herbicides combined
• marketed since 1974
• a broad spectrum, non-selective systemic herbicide, initially absorbed through the leaves facilitated by a surfactant component.
• it inhibits amino acid metabolism in the shikimic acid pathway which exists in plants and microorganisms but not in animals.
• commercial Roundup concentrate is 41% glyphosate and 15% polyoxyethleneamine (POEA), a surfactant
• ready to use concentrations are usually 0.36-10% glyphosate
• poisoning epidemiology in Victoria:
  • Vic. Poisons Info Centre logged 1235 calls over 5 yrs from 1998-2002, representing 0.91% of all calls, of these 521 were systemic oral exposures in humans

• bioavailability 30-36%
• not appreciably metabolised & is predominantly excreted by urine
• tissue concentration is maximal in kidneys
• lethality:
  • whilst it has minimal toxicity in humans, large doses may be fatal, thought to result from uncoupling of oxidative phosphorylation and/or direct cardiotoxicity due to either glyphosate or the POEA, with main reported mechanisms of death being intractable hypotension, renal failure & resp. complications (non-cardiogenic pulm. oedema & aspiration).
  • there is only a loose dose-response relationship:
    • mean fatal ingestions were 330ml of concentrate with lowest being 85ml
    • doses of 1000ml of concentrate have only resulted in mild toxicity
  • risk factors for lethality:
    • large doses
    • age of patient
    • suicidal intent

• attributable to POEA:
  • GIT pain, vomiting with aspiration
  • pulmonary oedema
  • impaired consciousness
  • haemolysis
• attributable to glyphosate:
  • corrosive GIT effects with likely nausea, vomiting, diarrhoea & possibly GIT bleeding
  • possible direct renal toxicity
  • metabolic acidosis
  • CNS depression
• poor prognostic signs:
  • abdominal pain
  • hypotension
  • resp. distress
  • renal failure
  • metabolic acidosis
  • hyperkalaemia

• ABC's as per usual
• eye & skin contamination generally do not produce systemic symptoms and require irrigation & symptomatic Rx
• activated charcoal may adsorb the surfactant component and should be considered in those who present early and who have a protected airway
• IV access, U&E, FBE
• IV fluids if hypotensive
• if poor prognostic signs are present:
  • early invasive monitoring & haemodynamic support
  • maintenance of euvolaemia
  • consider haemodialysis which may improve acidosis, hyperkalaemia & renal failure but does not remove glyphosate
  • there is no point in atropine, pralidoxine or in serum glyphosate levels
• disposition:
  • all patients with more than mild GIT symptoms should be admitted for monitoring for at least 12hrs as there is a possibility of late development of serious complications.

• Glyphosate herbicide formulation: A potentially lethal ingestion. Stella, Ryan. EMA 2004:16 p235-9