Organophosphate Toxicity 

  • Author: Kenneth D Katz, MD, FAAEM, ABMT; Chief Editor: Michael R Pinsky, MD, CM, FCCP, FCCM   more...
 
Updated: Jan 23, 2012
 

Background

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. Additionally, chemical weapons still pose a very real concern in this age of terrorist activity.

Exposure to organophosphates (OPs) is also possible via intentional or unintentional contamination of food sources. Although no clinical effects of chronic, low-level organophosphates (OPs) exposure from a food source have been shown, advancements in risk assessment and preparedness are ongoing.[1, 2]

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Pathophysiology

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.[3]

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Epidemiology

Frequency

United States

In 2007, The American Association of Poison Control Centers' received 96,307 calls (3.4% of all human exposures) related to pesticide exposures, many of which involved organophosphate (OP) agents and 80 uses of 2-PAM.[4] However, poison center – recorded exposures to organophosphates (OPs) from 1995 to 2004 have declined because of the United States Environmental Protection Agency phasing out commonly used household and agricultural organophosphate (OP) agents.[5]

International

Pesticide poisonings are among the most common modes of poisoning fatalities. In countries such as India and Nicaragua, organophosphates (OPs) 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.[6]

Mortality/Morbidity

  • Worldwide mortality studies report mortality rates from 3-25%. 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.

Age

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 underway and should help identify the true risk potential.[7]

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Contributor Information and Disclosures
Author

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 and American College of Medical Toxicology

Disclosure: Nothing to disclose.

Coauthor(s)

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, and American College of Medical Toxicology

Disclosure: Nothing to disclose.

Specialty Editor Board

Lisa Kirkland, MD, FACP, CNSP, MSHA  Assistant Professor, Department of Internal Medicine, Division of Hospital Medicine, Mayo Clinic; ANW Intensivists, Abbott Northwestern Hospital

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

Disclosure: Nothing to disclose.

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

Disclosure: Medscape Salary Employment

Om Prakash Sharma, MD, FRCP, FCCP, DTM&H  Professor, Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Southern California Keck School of Medicine

Om Prakash Sharma, MD, FRCP, FCCP, DTM&H is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Osler Society, American Thoracic Society, New York Academy of Medicine, and Royal Society of Medicine

Disclosure: Nothing to disclose.

Timothy D Rice, MD  Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, St Louis University School of Medicine

Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians

Disclosure: Nothing to disclose.

Chief Editor

Michael R Pinsky, MD, CM, FCCP, FCCM  Professor of Critical Care Medicine, Bioengineering, Cardiovascular Disease and Anesthesiology, Vice-Chair of Academic Affairs, Department of Critical Care Medicine, University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine

Michael R Pinsky, MD, CM, FCCP, FCCM is a member of the following medical societies: American College of Chest Physicians, American College of Critical Care Medicine, American Heart Association, American Thoracic Society, Association of University Anesthetists, European Society of Intensive Care Medicine, Shock Society, and Society of Critical Care Medicine

Disclosure: LiDCO Ltd Honoraria Consulting; iNTELOMED Intellectual property rights Board membership; Edwards Lifesciences Honoraria Consulting; Applied Physiology, Ltd Honoraria Consulting; Cheetah Medical Consulting fee Consulting

Additional Contributors

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

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