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Organophosphate Toxicity

  • Author: Kenneth D Katz, MD, FAAEM, ABMT; Chief Editor: Asim Tarabar, MD  more...
Updated: May 04, 2016


Organophosphate (OP) compounds are a diverse group of chemicals used in both domestic and industrial settings. Examples of organophosphates include insecticides (malathion, parathion, diazinon, fenthion, dichlorvos, chlorpyrifos, ethion), nerve gases (soman, sarin, tabun, VX), ophthalmic agents (echothiophate, isoflurophate), and antihelmintics (trichlorfon). Herbicides (tribufos [DEF], merphos) are tricresyl phosphate–containing industrial chemicals.

Organophosphate compounds were first synthesized in the early 1800s when Lassaigne reacted alcohol with phosphoric acid. Shortly thereafter in 1854, Philip de Clermount described the synthesis of tetraethyl pyrophosphate at a meeting of the French Academy of Sciences. Eighty years later, Lange, in Berlin, and, Schrader, a chemist at Bayer AG, Germany, investigated the use of organophosphates as insecticides. However, the German military prevented the use of organophosphates as insecticides and instead developed an arsenal of chemical warfare agents (ie, tabun, sarin, soman). A fourth agent, VX, was synthesized in England a decade later. During World War II, in 1941, organophosphates were reintroduced worldwide for pesticide use, as originally intended.

Massive organophosphate intoxication from suicidal and accidental events, such as the Jamaican ginger palsy incident in 1930, led to the discovery of the mechanism of action of organophosphates. In 1995, a religious sect, Aum Shinrikyo, used sarin to poison people on a Tokyo subway. Mass poisonings still occur today; in 2005, 15 victims were poisoned after accidentally ingesting ethion-contaminated food in a social ceremony in Magrawa, India.

Nerve agents have also been used in battle, notably in Iraq in the 1980s. Sarin, delivered by rockets, was used in the chemical warfare attack in Damascus, Syria in 2013.[1] Additionally, chemical weapons still pose a very real concern in this age of terrorist activity.

In farm workers, chronic occupational exposure to organophosphate insecticides has been linked to neuropsychological effects in some studies. These have included difficulties in executive functions, psychomotor speed, verbal, memory, attention, processing speed, visual-spatial functioning, and coordination.[2]

Exposure to organophosphates is also possible via intentional or unintentional contamination of food sources. Although no clinical effects of chronic, low-level organophosphate exposure from a food source have been shown, advancements in risk assessment and preparedness are ongoing.[3, 4]



The primary mechanism of action of organophosphate pesticides is inhibition of carboxyl ester hydrolases, particularly acetylcholinesterase (AChE). AChE is an enzyme that degrades the neurotransmitter acetylcholine (ACh) into choline and acetic acid. ACh is found in the central and peripheral nervous system, neuromuscular junctions, and red blood cells (RBCs).

Organophosphates inactivate AChE by phosphorylating the serine hydroxyl group located at the active site of AChE. The phosphorylation occurs by loss of an organophosphate leaving group and establishment of a covalent bond with AChE.

Once AChE has been inactivated, ACh accumulates throughout the nervous system, resulting in overstimulation of muscarinic and nicotinic receptors. Clinical effects are manifested via activation of the autonomic and central nervous systems and at nicotinic receptors on skeletal muscle.

Once an organophosphate binds to AChE, the enzyme can undergo one of the following:

  • Endogenous hydrolysis of the phosphorylated enzyme by esterases or paraoxonases
  • Reactivation by a strong nucleophile such as pralidoxime (2-PAM)
  • Irreversible binding and permanent enzyme inactivation (aging)

Organophosphates can be absorbed cutaneously, ingested, inhaled, or injected. Although most patients rapidly become symptomatic, the onset and severity of symptoms depend on the specific compound, amount, route of exposure, and rate of metabolic degradation.[5]




United States

In 2014, the American Association of Poison Control Centers reported 2180 single exposures to organophosphate insecticides, with 20 major outcomes and three deaths. In addition, 5138 single exposures to organophosphate insecticides in combination with carbamate or non-carbarbamate insecticides were reported, with three major outcomes and no deaths.[6]


Pesticide poisonings are among the most common modes of poisoning fatalities. In countries such as India and Nicaragua, organophosphates are easily accessible and, therefore, a source of both intentional and unintentional poisonings. The incidence of international organophosphate-related human exposures appears to be underestimated.[7]


Worldwide mortality studies report mortality rates from 3-25%.[8] The compounds most frequently involved include malathion, dichlorvos, trichlorfon, and fenitrothion/malathion.

Mortality rates depend on the type of compound used, amount ingested, general health of the patient, delay in discovery and transport, insufficient respiratory management, delay in intubation, and failure in weaning off ventilatory support.

Complications include severe bronchorrhea, seizures, weakness, and neuropathy. Respiratory failure is the most common cause of death.


Organophosphates (OPs) may affect children or other at-risk populations differently. The increased susceptibility has not been elucidated but may involve delayed or persistent effects. More work in this area is in progress and should help identify the true risk potential.[9]

Contributor Information and Disclosures

Kenneth D Katz, MD, FAAEM, ABMT Assistant Professor, Division of Medical Toxicology, Department of Emergency Medicine, University of Pittsburgh Medical Center; Medical Director, Pittsburgh Poison Center

Kenneth D Katz, MD, FAAEM, ABMT is a member of the following medical societies: American Academy of Emergency Medicine, American College of Medical Toxicology

Disclosure: Nothing to disclose.


Daniel E Brooks, MD Co-Medical Director, Banner Good Samaritan Poison and Drug Information Center, Department of Medical Toxicology, Banner Good Samaritan Medical Center

Daniel E Brooks, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Emergency Physicians, American College of Medical Toxicology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Asim Tarabar, MD Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

Additional Contributors

Lisa Kirkland, MD, FACP, FCCM, MSHA Assistant Professor, Department of Internal Medicine, Division of Hospital Medicine, Mayo Clinic; Vice Chair, Department of Critical Care, ANW Intensivists, Abbott Northwestern Hospital

Lisa Kirkland, MD, FACP, FCCM, MSHA is a member of the following medical societies: American College of Physicians, Society of Hospital Medicine, Society of Critical Care Medicine

Disclosure: Nothing to disclose.


The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors Marina C Furtado, MD, and Lisa Chan, MD, FACEP, to the development and writing of this article.

  1. Borger J. Syrian chemical attack used sarin and was worst in 25 years, says UN. The Guardian. September 17, 2013. Available at

  2. Muñoz-Quezada MT, Lucero BA, Iglesias VP, Muñoz MP, Cornejo CA, Achu E, et al. Chronic exposure to organophosphate (OP) pesticides and neuropsychological functioning in farm workers: a review. Int J Occup Environ Health. 2016 Apr 29. 1-12. [Medline].

  3. Bouvier G, Seta N, Vigouroux-Villard A, Blanchard O, Momas I. Insecticide urinary metabolites in nonoccupationally exposed populations. J Toxicol Environ Health B Crit Rev. 2005 Nov-Dec. 8(6):485-512. [Medline].

  4. Boobis AR, Ossendorp BC, Banasiak U, Hamey PY, Sebestyen I, Moretto A. Cumulative risk assessment of pesticide residues in food. Toxicol Lett. 2008 Aug 15. 180(2):137-50. [Medline].

  5. Yurumez Y, Durukan P, Yavuz Y, et al. Acute organophosphate poisoning in university hospital emergency room patients. Intern Med. 2007. 46(13):965-9. [Medline].

  6. Sudakin DL, Power LE. Organophosphate exposures in the United States: a longitudinal analysis of incidents reported to poison centers. J Toxicol Environ Health A. 2007 Jan 15. 70(2):141-7. [Medline].

  7. Corriols M, Marin J, Berroteran J, Lozano LM, Lundberg I, Thorn A. The Nicaraguan Pesticide Poisoning Register: constant underreporting. Int J Health Serv. 2008. 38(4):773-87. [Medline].

  8. Yamashita M, Yamashita M, Tanaka J, Ando Y. Human mortality in organophosphate poisonings. Vet Hum Toxicol. 1997 Apr. 39(2):84-5. [Medline].

  9. Abdel Rasoul GM, Abou Salem ME, Mechael AA, Hendy OM, Rohlman DS, Ismail AA. Effects of occupational pesticide exposure on children applying pesticides. Neurotoxicology. 2008 Sep. 29(5):833-8. [Medline].

  10. Levy-Khademi F, Tenenbaum AN, Wexler ID, Amitai Y. Unintentional organophosphate intoxication in children. Pediatr Emerg Care. 2007 Oct. 23(10):716-8. [Medline].

  11. Jayawardane P, Dawson AH, Weerasinghe V, Karalliedde L, Buckley NA, Senanayake N. The spectrum of intermediate syndrome following acute organophosphate poisoning: a prospective cohort study from Sri Lanka. PLoS Med. 2008 Jul 15. 5(7):e147. [Medline].

  12. Moretto A. Experimental and clinical toxicology of anticholinesterase agents. Toxicol Lett. 1998 Dec 28. 102-103:509-13. [Medline].

  13. Rajapakse BN, Thiermann H, Eyer P, Worek F, Bowe SJ, Dawson AH, et al. Evaluation of the Test-mate ChE (cholinesterase) field kit in acute organophosphorus poisoning. Ann Emerg Med. 2011 Dec. 58(6):559-564.e6. [Medline].

  14. Cha YS, Kim H, Go J, Kim TH, Kim OH, Cha KC, et al. Features of myocardial injury in severe organophosphate poisoning. Clin Toxicol (Phila). 2014 Sep. 52(8):873-9. [Medline].

  15. Liu JH, Chou CY, Liu YL, et al. Acid-base interpretation can be the predictor of outcome among patients with acute organophosphate poisoning before hospitalization. Am J Emerg Med. 2008 Jan. 26(1):24-30. [Medline].

  16. de Silva HJ, Wijewickrema R, Senanayake N. Does pralidoxime affect outcome of management in acute organophosphorus poisoning?. Lancet. 1992 May 9. 339(8802):1136-8. [Medline].

  17. Pawar KS, Bhoite RR, Pillay CP, Chavan SC, Malshikare DS, Garad SG. Continuous pralidoxime infusion versus repeated bolus injection to treat organophosphorus pesticide poisoning: a randomised controlled trial. Lancet. 2006 Dec 16. 368(9553):2136-41. [Medline].

  18. Peter JV, Moran JL, Graham P. Oxime therapy and outcomes in human organophosphate poisoning: an evaluation using meta-analytic techniques. Crit Care Med. 2006 Feb. 34(2):502-10. [Medline].

  19. Eisenkraft A, Gilat E, Chapman S, Baranes S, Egoz I, Levy A. Efficacy of the bone injection gun in the treatment of organophosphate poisoning. Biopharm Drug Dispos. 2007 Apr. 28(3):145-50. [Medline].

  20. Murray DB, Eddleston M, Thomas S, Jefferson RD, Thompson A, Dunn M, et al. Rapid and complete bioavailability of antidotes for organophosphorus nerve agent and cyanide poisoning in minipigs after intraosseous administration. Ann Emerg Med. 2012 Oct. 60(4):424-30. [Medline].

  21. Geller RJ, Lopez GP, Cutler S, Lin D, Bachman GF, Gorman SE. Atropine availability as an antidote for nerve agent casualties: validated rapid reformulation of high-concentration atropine from bulk powder. Ann Emerg Med. 2003 Apr. 41(4):453-6. [Medline].

  22. Rajpal S, Ali R, Bhatnagar A, Bhandari SK, Mittal G. Clinical and bioavailability studies of sublingually administered atropine sulfate. Am J Emerg Med. 2010 Feb. 28(2):143-50. [Medline].

  23. Yavuz, Y, Yurumez Y, Ciftci J et al. Effect of diphenhydramine on myocardial injury caused by organophosphate poisoning. Clin Tox. 2007. 46:67-70.

  24. Pajoumand A, Shadnia S, Rezaie A, Abdi M, Abdollahi M. Benefits of magnesium sulfate in the management of acute human poisoning by organophosphorus insecticides. Hum Exp Toxicol. 2004 Dec. 23(12):565-9. [Medline].

  25. Basher A, Rahman SH, Ghose A, Arif SM, Faiz MA, Dawson AH. Phase II study of magnesium sulfate in acute organophosphate pesticide poisoning. Clin Toxicol (Phila). 2013 Jan. 51(1):35-40. [Medline].

  26. Peter JV, Cherian AM. Organic insecticides. Anaesth Intensive Care. 2000 Feb. 28(1):11-21. [Medline].

  27. Weissman BA, Raveh L. Therapy against organophosphate poisoning: the importance of anticholinergic drugs with antiglutamatergic properties. Toxicol Appl Pharmacol. 2008 Oct 15. 232(2):351-8. [Medline].

  28. Raveh L, Eisenkraft A, Weissman BA. Caramiphen edisylate: An optimal antidote against organophosphate poisoning. Toxicology. 2014 Sep 6. 325C:115-124. [Medline].

  29. London L, Myers JE. Use of a crop and job specific exposure matrix for retrospective assessment of long-term exposure in studies of chronic neurotoxic effects of agrichemicals. Occup Environ Med. 1998 Mar. 55(3):194-201. [Medline].

  30. Tang W, Ruan F, Chen Q, Chen S, Shao X, Gao J, et al. Independent Prognostic Factors for Acute Organophosphorus Pesticide Poisoning. Respir Care. 2016 Apr 5. [Medline].

  31. Mowry JB, Spyker DA, Brooks DE, McMillan N, Schauben JL. 2014 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 32nd Annual Report. Clin Toxicol (Phila). 2015. 53 (10):962-1147. [Medline]. [Full Text].

  32. Barthold CL, Schier JG. Organic phosphorus compounds--nerve agents. Crit Care Clin. 2005 Oct. 21(4):673-89, v-vi. [Medline].

  33. Ben Abraham R, Rudick V, Weinbroum AA. Practical guidelines for acute care of victims of bioterrorism: conventional injuries and concomitant nerve agent intoxication. Anesthesiology. 2002 Oct. 97(4):989-1004. [Medline].

  34. Dart RC. Organophosphate Insecticides. The 5-minute Toxicology Consult. Philadelphia: Lippincott Williams & Wilkins; 2000. 554-5.

  35. Peter JV, Moran JL, Pichamuthu K, Chacko B. Adjuncts and alternatives to oxime therapy in organophosphate poisoning--is there evidence of benefit in human poisoning? A review. Anaesth Intensive Care. 2008 May. 36(3):339-50. [Medline].

  36. Shahar E, Bentur Y, Bar-Joseph G, Cahana A, Hershman E. Extrapyramidal parkinsonism complicating acute organophosphate insecticide poisoning. Pediatr Neurol. 2005 Nov. 33(5):378-82. [Medline].

  37. Solomon GM, Moodley J. Acute chlorpyrifos poisoning in pregnancy: a case report. Clin Toxicol (Phila). 2007 May. 45(4):416-9. [Medline].

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