Organophosphate Toxicity




Organophosphate (OP) compounds are a diverse group of chemicals used in both domestic and industrial settings. Examples of organophosphates include the following:

Thus, organophosphate toxicity can result from household or occupational exposure, military or terrorist action, or iatrogenic mishap. 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. [1, 2]

Signs and symptoms of organophosphate poisoning can be divided into three broad categories: (1) muscarinic effects, (2) nicotinic effects, and (3) central nervous system (CNS) effects. See Presentation.

Organophosphate toxicity is a clinical diagnosis. Confirmation of organophosphate poisoning is based on the measurement of cholinesterase activity; but typically, these results are not readily available. See Workup.

Treatment begins with decontamination. Airway control and oxygenation are paramount. The mainstays of pharmacological therapy include atropine, pralidoxime (2-PAM), and benzodiazepines (eg, diazepam). Initial management must focus on adequate use of atropine. Optimizing oxygenation prior to the use of atropine is recommended to minimize the potential for dysrhythmias. See Treatment and Medication.



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.

Severe organophosphate intoxication from suicide attempts and outbreaks of unintentional poisoning, such as the Jamaican ginger palsy incident in 1930, led to the discovery of the mechanisms of acute and chronic toxicity 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. [3] 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, , attention, processing speed, visual-spatial functioning, and coordination. [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 (RBCs).

Organophosphates inactivate AChE by phosphorylating the serine hydroxyl group located at the active site of AChE. Over a period of time, phosphorylation is followed by of an organophosphate leaving group and the bond with AChE becomes irreversible, a process known as aging.

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 2016, the American Association of Poison Control Centers reported 1994 single exposures to organophosphate insecticides alone, with 17 major outcomes and one death. In addition, 537 single exposures to organophosphate insecticides in combination with carbamate or non-carbarbamate insecticides were reported, with two 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 . 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 identify the true risk potential. [9]

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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.

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.

W Wiener, MD Assistant Professor, Department of Emergency Medicine, State University of New York Downstate Medical Center; Director of Medical Toxicology, Department of Emergency Medicine, Kings County Hospital Center

W Wiener, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Medical Toxicology, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Lisa Kirkland, MD, FACP, FCCM, MSHA Assistant Professor, Department of Internal Medicine, Division of Hospital Medicine, Mayo Clinic; 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 Critical Care Medicine, Society of Hospital 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.

Organophosphate Toxicity

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