Organophosphorus Compounds

R.J. Richardson, G.F. Makhaeva, in Encyclopedia of Toxicology (Third Edition), 2014

Abstract

Organophosphorus (OP) compounds include trivalent and pentavalent phosphorus; this article covers only the more common pentavalent phosphorus compounds. These chemicals are often thought of as insecticides or nerve agents whose acute toxicity arises from inhibition of acetylcholinesterase (AChE), but OP compounds are also widely used as flame retardants, fuel additives, lubricants, plasticizers, and pharmaceuticals. In addition to their acute effects, some anti-AChE OP compounds have been associated with the intermediate syndrome. Finally, OP compounds that inhibit and age neuropathy target esterase produce OP compound–induced delayed neurotoxicity, a distal degeneration of sensory and motor axons in peripheral nerves and spinal cord.

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Biodegradation of organophosphates: biology and biotechnology

Sunil Parthasarathy, ... Dayananda Siddavattam, in Microbial Biodegradation and Bioremediation (Second Edition), 2022

7.1.5.4 Phosphotriesterases in the treatment of organophosphate poisoning

OP poisoning is an important clinical problem. As stated in the earlier section, it kills an estimated 200,000 people every year (Sinha & Sharma, 2003). PTEs are considered as one of the potential options in the treatment of OP-poisoning cases. The PEGylated OPH not only showed less immune response, compared to the free enzyme, but also showed improved thermostability and retained catalytic properties like a free enzyme. These properties of the PEGylated OPH provided a new opportunity for the in vivo detoxification of OP insecticides and nerve agent (Novikov, Grimsley, Kern, Wild, & Wales, 2010). The guinea pigs administered with 500–1000 units of OPH activity have shown a decreased mortality rate against paraoxon toxicity. Likewise, rats injected with diisopropylfluorophosphatase have shown resistance to nerve agents sarin and soman, demonstrating its therapeutic potential against OP poisoning (Melzer et al., 2012).

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Phosphorus containing compounds in nonsaline waters

T.R. Crompton, in Determination of Toxic Organic Chemicals in Natural Waters, Sediments and Soils, 2019

Miscellaneous

Gas chromatographic detection with supported copper–cuprous oxide island film

Organophosphorus compounds have been detected in environmental waters at the parts per million level using a supported copper–cuprous oxide island film gas chromatographic detector. Both alternating current [10] and direct current studies were used [11].

Conducted chemiresistant sensors for gas chromatographic detection

Grate et al. [12] have studied the role of selective sorption in chemiresistant sensors for the gas chromatographic detection of organophosphorus compounds.

Surface acoustic wave sensors for gas chromatographic detection

Grate et al. [13] have described a smart sensor system for detecting traces of organophosphorus compounds. Vapour detection of these compounds is achieved employing a temperature-controlled array of surface wave detectors, automated sampled preconcentrations and pattern recognition. Down to 0.01 mg m−3 of organophosphorus compounds can be detected on the detector surface.

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Biodegradation of Pesticides

Mukesh Doble, Anil Kumar, in Biotreatment of Industrial Effluents, 2005

Organophosphates

Organophosphates include all insecticides containing phosphorus. They are the most toxic of all pesticides to vertebrates; however they are unstable or nonpersistent. They contain compounds like malathion, ethyl parathion, and diazinon. In 1989 almost 40% of the $6.2 billion global insecticide market was composed of organophosphates.

Acetylcholine esterase is able to degrade malathion, methylparathion, and diazinon. During hydrolysis, the aromatic ring is used as a carbon source and the alkyl moiety (dithiomethyl phosphorothioate) is used as a source of phosphorus. Enzymatic degradation of organophosphates occurs either by the action of organophosphate acid hydrolases (OPH) or by organophosphate acid anhydrolases (OPAA). The OPH enzymes isolated from the organisms Pseudomonas diminuta, Pseudomonas sp., and Flavobacterium sp. ATCC 27551 showed high activity. The thermophilic bacteria Altermonas as well as the fungus Pleurotus ostreatus exhibit high activity of OPAA.

During the hydrolysis reaction, an alkyl thiol is liberated, whereas during oxidation, an alkyl sulfonate is produced (Fig. 8-6). The thiol product has an undesirable smell as well as a reasonable amount of toxicity; hence the oxidation reaction is preferred. The fungus Pleurotus ostreatus is able to degrade 75 % of the pesticide in 16-20 h.

FIGURE 8-6. Organophosphate degradation.

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Insecticides and Acaricides

Rosalind Dalefield BVSc PhD DABVT DABT, in Veterinary Toxicology for Australia and New Zealand, 2017

Toxicokinetics

Both OPs and carbamates are readily absorbed through the skin, gastrointestinal tract, and respiratory surfaces. They are widely distributed in the body but, unlike chlorinated hydrocarbons, do not sequester in adipose tissues. Phase I metabolism by mixed-function oxidases (MFOs) increases toxicity, but hydrolysis of the ester linkage decreases toxicity. Both OPs and carbamates are rapidly excreted, although chlorinated OPs such as chlorpyrifos are somewhat more persistent. Excretion is usually as products of hydrolysis in the urine. OPs and carbamates may be excreted in the milk.

The range of toxicity of these insecticides is very wide.

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Pyridinium oximes in the treatment of poisoning with organophosphorus compounds

Milan Jokanović, ... Dragana Ristić, in Handbook of Toxicology of Chemical Warfare Agents (Third Edition), 2020

Abstract

Organophosphorus compounds (OPs) have been used as pesticides and developed as warfare nerve agents such as tabun, soman, sarin, VX, and others. Exposure to even small amounts of an organophosphorus compound can be fatal and death is usually caused by respiratory failure resulting from paralysis of the diaphragm and intercostal muscles, depression of the brain respiratory center, bronchospasm, and excessive bronchial secretions. The mechanism of OP poisoning involves phosphorylation of the serine hydroxyl group in the active site of acetylcholinesterase (AChE) leading to inactivation of this essential enzyme which has an important role in neurotransmission. AChE inhibition results in the accumulation of acetylcholine at cholinergic receptor sites, producing continuous stimulation of cholinergic fibers throughout the central and peripheral nervous systems. Presently, a combination of an antimuscarinic agent, for example, atropine, AChE reactivator, such as one of the recommended pyridinium oximes (PAM-2, TMB-4, HI-6, LüH-6), and diazepam are used for the treatment of organophosphate poisoning in humans. In this chapter we review the mechanisms of action of OP and the role of pyridinium oximes used as AChE reactivators in the treatment of OP poisonings.

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Humans & Conservation

Paul C. Jepson, in Encyclopedia of Biodiversity (Third Edition), 2013

Organophosphates

Organophosphates, or OPs, are esters of phosphoric acid. Many have high mammalian toxicity and may require frequent application because they are generally not persistent. Organophosphates are nerve poisons, acting through inhibition of cholinesterase. They fall into three groups: (1) Aliphatic organophosphates, which are the oldest group, some with low mammalian toxicity (e.g., malathion, which has been in use for 40 years) but others having high mammalian toxicity, but short persistence. Short persistence makes many OPs of use in short-season crops, where the plant or the consumer has a low tolerance for pests (e.g., vegetable crops). Examples include, acephate, dichlorvos, dimethoate, malathion, and phorate. (2) Phenyl organophosphates, which are more stable and persistent but which include materials with high mammalian toxicity. Examples include fenitrothion, methyl parathion, and temephos. (3) Heterocyclic organophosphates, which may be more persistent and active in soil. Examples include azinphos-methyl, chlorpyriphos, phosmet, and pyrazophos.

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Sampling Theory and Methodology

C. Garcia-Jares, ... M. Llompart, in Comprehensive Sampling and Sample Preparation, 2012

1.08.1.7.2 Organophosphate Esters

Organophosphate esters (OPs) are manufactured on a large scale to be used as flame-retarding agents and/or plasticizers in a variety of products such as electronic equipment, lubricants, plastics, glues, varnishes, and furnishing fabrics, from which phosphate flame retardants as well as their degradation products can be emitted. As additives, they may diffuse at rates depending on their vapor pressure and the ambient temperature, and are thus emitted to the surrounding air. Consequently, there are abundant sources of OPs in both public and domestic buildings, including diverse building materials and consumer products. The indoor environment represents the main source of human exposure to these pollutants through inhalation of air and inadvertent ingestion of dust. The most volatile OPs are found in the gas phase, whereas the OPs with higher molecular mass are mainly associated with the suspended particulate matter and dust. Although very little is known about their human health effects, certain organophosphate triesters such as tri-n-butyl phosphate (TBP), tris(2-chloroethyl) phosphate (TCEP), and tris(2-chloropropyl) phosphate (TCPP) might negatively affect human health.

Organophosphate flame retardants have been found in indoor air at concentrations ranging from less than 1 ng m−3 up to several μg m−3.

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Toxic Encephalopathies I: Cortical and Mixed Encephalopathies

Tracy J. Eicher, in Clinical Neurotoxicology, 2009

Organophosphates

Organophosphates (OPs) are present in nearly 40% of all pesticides used in this country. They are highly lipid soluble and are easily absorbed through the skin and respiratory tract. Toxic exposures occur commonly in farmers, gardeners, crop dusters, and pesticide handlers. OPs are also readily absorbed through the GI tract. Accidental ingestion by children and intentional ingestion in suicide attempts represent an unfortunately high number of exposures annually. Their ability to produce paralysis of smooth and striated muscles has made them useful as agents of chemical warfare.8

OPs produce their toxic effects by binding to acetylcholinesterase (AChE). Inhibition of this important enzyme results in excess acetylcholine at neuromuscular junctions and at certain locations in the brain. The peripheral nervous system effects, including excessive salivation, lacrimation, sweating, and diarrhea, are widely recognized as signs of OP toxicity. The acute CNS effects may be mild and are often overshadowed by the peripheral effects at lower levels of exposure. With increased exposure levels, however, encephalopathy, dizziness, and hallucinations become more apparent. Severe encephalopathy, seizures, coma, and death may occur in cases of high levels of exposure. Different OP compounds may result in varied CNS effects, reflecting the distribution of different types of AChE throughout the brain.8,67

The delayed effects of OP toxicity on the peripheral nervous system can be debilitating and have been the focus of much attention in the literature. Prolonged CNS dysfunction is also a matter for concern. Studies indicate that cholinesterase inhibitors can cause changes in the mediation of cholinergic neurotransmission in the brain. Victims of high levels of OP exposure later score worse on mood inventories and on tests of sustained visual attention than their nonexposed counterparts.68,69 Case reports suggest that executive function, memory, and certain learning domains may be impaired for prolonged periods in some individuals, but slow recovery of most functions is the trend.70–73 Further studies are needed before conclusions can be drawn with regard to long-term brain dysfunction in the setting of chronic, low-level OP exposure.

Given the ease of absorption through the skin and respiratory tract, use of protective masks, gloves, and proper clothing is paramount to preventing toxic OP exposure. OPs should be kept well out of the reach of children and should be stored in well-marked containers. The ACGIH suggests monitoring of OP exposure in high-risk settings. Plasma cholinesterase activity levels are more sensitive to low-level exposure, but erythrocyte AChE activity is a better indicator of neuronal AChE inhibition.8

In the event of skin exposure, the skin should be immediately and thoroughly cleansed with soap and water. Any saturated clothing should be removed. In cases of OP ingestion, immediate gastric lavage is warranted to remove as much of the toxin as possible before absorption is complete. Cathartics should also be considered. When given early, oximes such as pralidoxime or obidoxime chloride are useful in minimizing subsequent peripheral neuropathy. These agents do not readily cross the BBB and are therefore less effective in reversing CNS toxicity. Atropine may be used to counteract the muscarinic effects of OPs, but it will not reverse the nicotinic effects and muscle weakness will therefore not improve. Atropine should be administered in small doses (0.5 to 1.0 mg) at 15-minute intervals until signs of OP reversal are apparent. Cessation of sweating and salivation, facial flushing, and papillary dilation signal effective reversal of toxicity. Due to the tendency for OPs to be stored in fatty tissues, continued observation and less frequent dosing of IV atropine (1 to 2 mg every hour) may be needed.8,74 It should be noted that when seizures occur as a result of OP exposure, the mechanism is increased neuronal stimulation by excessive acetylcholine. These seizures do not respond robustly to dilantin or other antiepileptics and should be treated with atropine.75

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Foods, Materials, Technologies and Risks

A Moretto, in Encyclopedia of Food Safety, 2014

Abstract

Organophosphate and carbamate insecticides are designed to kill different insects and other pests. They share the same target in both insects and mammals, including humans; in fact, they act by inhibiting the neural enzyme acetylcholinesterase. Despite the structural similarity, their toxic potencies are quite different. The use of organophosphates and carbamates is very widespread: There is evidence of a substantial decline over the years in the developed countries, whereas in developing countries, their use is still rising. It should be noted that these compounds are also used in public health and indoors for the control of vectors of diseases. Residues of organophosphates and carbamates in food are generally low, and human intakes, as based on monitoring data of residues in food, are normally below acceptable exposure levels.

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