title: Mechanisms of toxicity, clinical features, and management of acute chlorophenoxy herbicide poisoning: a review.
abstract: BACKGROUND
  Chlorophenoxy herbicides are used widely for the control of broad-leaved weeds. They exhibit a variety of mechanisms of toxicity including dose-dependent cell membrane damage, uncoupling of oxidative phosphorylation, and disruption of acetylcoenzyme A metabolism. Between January 1962 and January 1999, 66 cases of chlorophenoxy herbicide poisoning following ingestion were reported in the literature. FEATURES FOLLOWING INGESTION: Adjuvants in the formulations may have contributed to some of the features observed. Vomiting, abdominal pain, diarrhea, and, occasionally, gastrointestinal hemorrhage were early effects. When present, hypotension was predominantly due to intravascular volume loss, although vasodilation and direct myocardial toxicity may have contributed in some cases. Neurotoxic features included coma, hypertonia, hyperreflexia, ataxia, nystagmus, miosis, hallucinations, convulsions, fasciculation, and paralysis. Hypoventilation occurred not infrequently, usually in association with central nervous system depression, but respiratory muscle weakness was a factor in the development of respiratory failure in some patients. Myopathic symptoms including limb muscle weakness, loss of tendon reflexes, and myotonia were observed and increased creatine kinase activity was noted in some cases. Other clinical features reported included metabolic acidosis, rhabdomyolysis, renal failure, increased aminotransferase activities, pyrexia, and hyperventilation. Twenty-two of 66 patients died. FEATURES FOLLOWING DERMAL AND INHALATIONAL EXPOSURE: Substantial dermal or inhalational 2,4-dichlorophenoxyacetic acid exposure has occasionally led to systemic features but no such reports have been published in the last 20 years and no fatalities have been reported at any time. Substantial dermal exposure has been reported to cause mild gastrointestinal irritation after a latent period followed by progressive mixed sensory-motor peripheral neuropathy. Mild, transient gastrointestinal and peripheral neuromuscular symptoms have also occurred after occupational inhalation exposure, with or without dermal exposure.
  
  
  RESULTS
  In addition to supportive care, alkaline diuresis to enhance herbicide elimination should be considered in all seriously poisoned patients. Limited clinical data suggest that hemodialysis produces similar herbicide clearance to alkaline diuresis without the need for urine pH manipulation and the administration of substantial amounts of intravenous fluid in an already compromised patient.
  
  
  CONCLUSIONS
  While chlorophenoxy herbicide poisoning is uncommon, ingestion of a chlorophenoxy herbicide can result in serious and sometimes fatal sequelae. In severe cases of poisoning, alkaline diuresis or hemodialysis to increase herbicide elimination should be considered.
authors.affiliation: National Poisons Information Service (Birmingham Centre), City Hospital, United Kingdom.
authors.forename: S M
authors.initials: SM
authors.lastname: Bradberry
authors.forename: B E
authors.initials: BE
authors.lastname: Watt
authors.forename: A T
authors.initials: AT
authors.lastname: Proudfoot
authors.forename: J A
authors.initials: JA
authors.lastname: Vale
mesh_terms: D015084:2,4-Dichlorophenoxyacetic Acid / Q000506:poisoning*; D000105:Acetyl Coenzyme A / Q000378:metabolism; D000279:Administration, Cutaneous; D000280:Administration, Inhalation; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D004232:Diuretics / Q000494:pharmacology; D006464:Hemoperfusion; D006540:Herbicides / Q000506:poisoning*; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D020258:Neurotoxicity Syndromes / Q000175:diagnosis / Q000378:metabolism / Q000628:therapy; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010956:Plasmapheresis; D011041:Poisoning / Q000175:diagnosis / Q000378:metabolism / Q000628:therapy; D006435:Renal Dialysis; D015996:Survival Rate; D014475:Uncoupling Agents / Q000506:poisoning; D006113:United Kingdom
chemical_list: D004232:Diuretics; D006540:Herbicides; D014475:Uncoupling Agents; D015084:2,4-Dichlorophenoxyacetic Acid; D000105:Acetyl Coenzyme A