Search citation statements
Paper Sections
Citation Types
Year Published
Publication Types
Relationship
Authors
Journals
Organophosphates (OP) inhibit serine hydrolases by phosphorylating serine residue. Exposure to OPs always involves acetylcholine esterase (AChE) inhibition, which is responsible for the degradation of acetylcholine (ACh), controlling the levels of ACh at the nerve endings. Inactivation/inhibition of AChE causes excessive accumulation of ACh at the neuromuscular junctions and synapses activating both sympathetic and parasympathetic processes causing both muscarinic and nicotinic toxicity. The muscarinic symptoms include salivation, diaphoresis, abdominal cramps, diarrhea, vomiting, miosis, bronchorrhea, bradycardia, coma, and seizure. Nicotinic symptoms are fasciculations, flaccid paralysis, and tachycardia. The most common cause of death is respiratory failure with refractory hypotension. Recovery from OP toxicity is linked to the restoration of OP‐inhibited AChE, which can be revived by oximes or regeneration of the enzyme, certain OPs bind irreversibly with AChE render it permanently inactive. The secondary OP targets in humans are butyrylcholinesterase (BChE), a sink for OP, and neuropathy target esterase, inhibition of which causes delayed neuropathy. The OPs are not only used for the management of pests in agriculture but also used in the treatment of human diseases, such as glaucoma with echothiophate to increase drainage of intraocular fluid reducing ocular pressure, schistosomiasis, and Alzheimer's with metrifonate. Metrifonate inhibits AChE in schistosomes, which is abundant in the muscles of the parasite. Metrifonate enhances central nervous system (CNS) cholinergic neurotransmission improving cognitive function in Alzheimer's patients. This chapter describes the AChE inhibition and toxicity of each OP and regeneration of AChE by oximes along with regulations based on the available data for individual OPs.
Organophosphates (OP) inhibit serine hydrolases by phosphorylating serine residue. Exposure to OPs always involves acetylcholine esterase (AChE) inhibition, which is responsible for the degradation of acetylcholine (ACh), controlling the levels of ACh at the nerve endings. Inactivation/inhibition of AChE causes excessive accumulation of ACh at the neuromuscular junctions and synapses activating both sympathetic and parasympathetic processes causing both muscarinic and nicotinic toxicity. The muscarinic symptoms include salivation, diaphoresis, abdominal cramps, diarrhea, vomiting, miosis, bronchorrhea, bradycardia, coma, and seizure. Nicotinic symptoms are fasciculations, flaccid paralysis, and tachycardia. The most common cause of death is respiratory failure with refractory hypotension. Recovery from OP toxicity is linked to the restoration of OP‐inhibited AChE, which can be revived by oximes or regeneration of the enzyme, certain OPs bind irreversibly with AChE render it permanently inactive. The secondary OP targets in humans are butyrylcholinesterase (BChE), a sink for OP, and neuropathy target esterase, inhibition of which causes delayed neuropathy. The OPs are not only used for the management of pests in agriculture but also used in the treatment of human diseases, such as glaucoma with echothiophate to increase drainage of intraocular fluid reducing ocular pressure, schistosomiasis, and Alzheimer's with metrifonate. Metrifonate inhibits AChE in schistosomes, which is abundant in the muscles of the parasite. Metrifonate enhances central nervous system (CNS) cholinergic neurotransmission improving cognitive function in Alzheimer's patients. This chapter describes the AChE inhibition and toxicity of each OP and regeneration of AChE by oximes along with regulations based on the available data for individual OPs.
Most organophosphorus compounds today fall into two general groups: the so‐called nerve agents, that are very acutely toxic and organophosphorus pesticides that are less toxic. Nerve agents were generally the first toxic organophosphorus developed, and were the original basis for organophosphorus pesticides. Interest about nerve agents has increased lately given concerns about their potential use in terrorist acts. Organophosphate nerve agents and pesticides are a highly diverse group of chemicals. They are all characterized by their ability to inhibit the enzyme acetylcholinesterase (AChE) that deactivates the neurotransmitter acetylcholine (ACh). At present, the widest use of organophosphorus compounds is as pesticides, although they have also been used as therapeutic agents, gasoline additives, hydraulic fluids, cotton defoliants, fire retardants, plastic components, growth regulators, and industrial intermediates to a much smaller extent. Compounds in this class are numerous and have been categorized in many ways according to the nature of the substituents. Gallo and Lawryk (1991) [2], for example, categorized them into four main groups I–IV based on the characteristics of the leaving group (X). Group I compounds, phosphorylcholines, have a leaving group that contains a quaternary nitrogen and are among the most potent organophosphates (e.g., Shradan). Group II compounds, fluorophosphates, have a fluoride leaving group and are also generally highly toxic (e.g., diisopropyl fluorophosphate). Group III compounds have leaving groups that contain cyanide or a halogen other than fluoride and are generally less potent than group I or II (e.g., Parathion). Group IV contains most of the organophosphates used as insecticides today. These compounds have alkoxy, alkylthio, aryloxy, arylthio, or heterocyclic leaving groups and a wide variety of other substituents. Another classification scheme is based on the nature of the atoms that immediately surround the central phosphorus atom and results in 14 different categories. According to this scheme, phosphates are the prototype for the entire class and are those compounds where all four atoms that surround the phosphorus atom are oxygen (e.g., dichlorvos, mevinphos). Sulfur‐containing organophosphate compounds (phosphorothioates, phosphorothiolates, phosphorodithioates, and phosphorodithiolates) are far more numerous than phosphates and include well‐recognized organophosphate insecticides such as parathion, diazinon, chlorpyrifos, etc. Other groups contain nitrogen (phosphoramides and phosphorodiamides), nitrogen and sulfur (phosphoramidothionates and phosphoramidothiolates), carbon (phosphonates and phosphinates), or carbon and sulfur (phosphonothionates, phosphonothionothiolates, and phosphinothionates). All aspects of organophosphate chemistry, toxicity, analysis, and exposure potential have been previously and comprehensively reviewed. In addition, information regarding the toxicity of organophosphorus pesticides in particular has expanded greatly in recent years as a result of toxicity data supplied by registrants to the U.S. EPA's Office of Pesticides to support reregistration. These data have been made publicly available by the U.S. EPA on its Internet Web site ( www.epa.gov/pesticides ). The following discussion draws heavily from recent reviews and also includes summaries of relevant toxicity data submitted to, and made available by, the U.S. EPA.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.