Organophosphate
Overview
 
An organophosphate is the general name for ester
Ester
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...

s of phosphoric acid
Phosphoric acid
Phosphoric acid, also known as orthophosphoric acid or phosphoric acid, is a mineral acid having the chemical formula H3PO4. Orthophosphoric acid molecules can combine with themselves to form a variety of compounds which are also referred to as phosphoric acids, but in a more general way...

. Phosphates are probably the most pervasive organophosphorus compounds. Many of the most important biochemicals are organophosphates, including DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 and RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....

 as well as many cofactor
Cofactor (biochemistry)
A cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes, and cofactors can be considered "helper molecules" that assist in biochemical transformations....

s that are essential for life. Organophosphates are the basis of many insecticide
Insecticide
An insecticide is a pesticide used against insects. They include ovicides and larvicides used against the eggs and larvae of insects respectively. Insecticides are used in agriculture, medicine, industry and the household. The use of insecticides is believed to be one of the major factors behind...

s, herbicide
Herbicide
Herbicides, also commonly known as weedkillers, are pesticides used to kill unwanted plants. Selective herbicides kill specific targets while leaving the desired crop relatively unharmed. Some of these act by interfering with the growth of the weed and are often synthetic "imitations" of plant...

s, and nerve gases. The EPA lists organophosphates as very highly acutely toxic to bees, wildlife, and humans.
Encyclopedia
An organophosphate is the general name for ester
Ester
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...

s of phosphoric acid
Phosphoric acid
Phosphoric acid, also known as orthophosphoric acid or phosphoric acid, is a mineral acid having the chemical formula H3PO4. Orthophosphoric acid molecules can combine with themselves to form a variety of compounds which are also referred to as phosphoric acids, but in a more general way...

. Phosphates are probably the most pervasive organophosphorus compounds. Many of the most important biochemicals are organophosphates, including DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 and RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....

 as well as many cofactor
Cofactor (biochemistry)
A cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes, and cofactors can be considered "helper molecules" that assist in biochemical transformations....

s that are essential for life. Organophosphates are the basis of many insecticide
Insecticide
An insecticide is a pesticide used against insects. They include ovicides and larvicides used against the eggs and larvae of insects respectively. Insecticides are used in agriculture, medicine, industry and the household. The use of insecticides is believed to be one of the major factors behind...

s, herbicide
Herbicide
Herbicides, also commonly known as weedkillers, are pesticides used to kill unwanted plants. Selective herbicides kill specific targets while leaving the desired crop relatively unharmed. Some of these act by interfering with the growth of the weed and are often synthetic "imitations" of plant...

s, and nerve gases. The EPA lists organophosphates as very highly acutely toxic to bees, wildlife, and humans. Recent studies suggest a possible link to adverse effects in the neurobehavioral development of fetuses and children, even at very low levels of exposure. Organophosphates are widely used as solvent
Solvent
A solvent is a liquid, solid, or gas that dissolves another solid, liquid, or gaseous solute, resulting in a solution that is soluble in a certain volume of solvent at a specified temperature...

s, plasticizer
Plasticizer
Plasticizers or dispersants are additives that increase the plasticity or fluidity of the material to which they are added; these include plastics, cement, concrete, wallboard, and clay. Although the same compounds are often used for both plastics and concretes the desired effects and results are...

s, and EP additives.

Organophosphates are widely employed both in natural and synthetic applications because of the ease with which organic groups can be linked together. Being a triprotic acid, phosphoric acid can form triester
Ester
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...

s whereas carboxylic acids only form monoesters. Esterification entails the attachment of organic groups to phosphorus through oxygen linkers. The precursors to such esters are alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....

s. Encompassing many thousands of natural and synthetic compounds, alcohols are diverse and widespread.
OP(OH)3 + ROH → OP(OH)2(OR) + H2O
OP(OH)2(OR) + R'OH → OP(OH)(OR)(OR') + H2O
OP(OH)(OR)(OR') + R"OH → OP(OR)(OR')(OR") + H2O

The phosphate esters bearing OH groups are acid
Acid
An acid is a substance which reacts with a base. Commonly, acids can be identified as tasting sour, reacting with metals such as calcium, and bases like sodium carbonate. Aqueous acids have a pH of less than 7, where an acid of lower pH is typically stronger, and turn blue litmus paper red...

ic and partially deprotonated
Deprotonation
Deprotonation is the removal of a proton from a molecule, forming the conjugate base.The relative ability of a molecule to give up a proton is measured by its pKa value. A low pKa value indicates that the compound is acidic and will easily give up its proton to a base...

 in aqueous solution. For example, DNA and RNA are polymers of the type [PO2(OR)(OR')-]n. Polyphosphates also form esters; an important example of an ester of a polyphosphate is ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

, which is the monoester of triphosphoric acid (H5P3O10).

Alcohols can be detached from phosphate esters by hydrolysis
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...

, which is the reverse of the above reactions. For this reason, phosphate esters are common carriers of organic groups in biosynthesis
Biosynthesis
Biosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...

.

Organophosphate pesticides

In health, agriculture, and government, the word "organophosphates" refers to a group of insecticides or nerve agents acting on the enzyme acetylcholinesterase (the pesticide group carbamates also act on this enzyme, but through a different mechanism). The term is used often to describe virtually any organic phosphorus(V)-containing compound, especially when dealing with neurotoxic compounds. Many of the so-called organophosphates contain C-P bonds. For instance, sarin
Sarin
Sarin, or GB, is an organophosphorus compound with the formula [2CHO]CH3PF. It is a colorless, odorless liquid, which is used as a chemical weapon. It has been classified as a weapon of mass destruction in UN Resolution 687...

 is O-isopropyl methylphosphonofluoridate, which is formally derived from phosphorous acid
Phosphorous acid
Phosphorous acid is the compound described by the formula H3PO3. This acid is diprotic , not triprotic as might be suggested by this formula. Phosphorous acid is as an intermediate in the preparation of other phosphorus compounds.-Nomenclature and tautomerism:H3PO3 is more clearly described with...

 (HP(O)(OH)2), not phosphoric acid (P(O)(OH)3). Also, many compounds which are derivatives of phosphinic acid are used as neurotoxic organophosphates.

Organophosphate pesticides (as well as sarin
Sarin
Sarin, or GB, is an organophosphorus compound with the formula [2CHO]CH3PF. It is a colorless, odorless liquid, which is used as a chemical weapon. It has been classified as a weapon of mass destruction in UN Resolution 687...

 and VX
VX (nerve agent)
VX, IUPAC name O-ethyl S-[2-ethyl] methylphosphonothioate, is an extremely toxic substance whose only application is in chemical warfare as a nerve agent. As a chemical weapon, it is classified as a weapon of mass destruction by the United Nations in UN Resolution 687...

 nerve agent) irreversibly inactivate acetylcholinesterase, which is essential to nerve function in insects, humans, and many other animals. Organophosphate pesticides affect this enzyme in varied ways, and thus in their potential for poisoning. For instance, parathion
Parathion
Parathion, also called parathion-ethyl or diethyl parathion, is an organophosphate compound. It is a potent insecticide and acaricide. It was originally developed by IG Farben in the 1940s. It is highly toxic to non-target organisms, including humans. Its use is banned or restricted in many...

, one of the first OPs commercialized, is many times more potent than malathion
Malathion
Malathion is an organophosphate parasympathomimetic which binds irreversibly to cholinesterase. Malathion is an insecticide of relatively low human toxicity, however one recent study has shown that children with higher levels of organophosphate pesticide metabolites in their urine are more likely...

, an insecticide used in combatting the Mediterranean fruit fly (Med-fly) and West Nile Virus
West Nile virus
West Nile virus is a virus of the family Flaviviridae. Part of the Japanese encephalitis antigenic complex of viruses, it is found in both tropical and temperate regions. It mainly infects birds, but is known to infect humans, horses, dogs, cats, bats, chipmunks, skunks, squirrels, domestic...

-transmitting mosquitoes.

Organophosphate pesticides degrade rapidly by hydrolysis on exposure to sunlight, air, and soil, although small amounts can be detected in food and drinking water. Their ability to degrade made them an attractive alternative to the persistent organochloride
Organochloride
An organochloride, organochlorine, chlorocarbon, chlorinated hydrocarbon, or chlorinated solvent is an organic compound containing at least one covalently bonded chlorine atom. Their wide structural variety and divergent chemical properties lead to a broad range of applications...

 pesticides, such as DDT
DDT
DDT is one of the most well-known synthetic insecticides. It is a chemical with a long, unique, and controversial history....

, aldrin
Aldrin
Aldrin is an organochlorine insecticide that was widely used until the 1970s, when it was banned in most countries. It is a colourless solid. Before the ban, it was heavily used as a pesticide to treat seed and soil...

 and dieldrin
Dieldrin
Dieldrin is a chlorinated hydrocarbon originally produced in 1948 by J. Hyman & Co, Denver, as an insecticide. Dieldrin is closely related to aldrin, which reacts further to form dieldrin. Aldrin is not toxic to insects; it is oxidized in the insect to form dieldrin which is the active compound...

. Although organophosphates degrade faster than the organochlorides, they have greater acute toxicity, posing risks to people who may be exposed to large amounts (see the Toxicity section below).

Commonly used organophosphates have included parathion
Parathion
Parathion, also called parathion-ethyl or diethyl parathion, is an organophosphate compound. It is a potent insecticide and acaricide. It was originally developed by IG Farben in the 1940s. It is highly toxic to non-target organisms, including humans. Its use is banned or restricted in many...

, malathion
Malathion
Malathion is an organophosphate parasympathomimetic which binds irreversibly to cholinesterase. Malathion is an insecticide of relatively low human toxicity, however one recent study has shown that children with higher levels of organophosphate pesticide metabolites in their urine are more likely...

, methyl parathion, chlorpyrifos
Chlorpyrifos
Chlorpyrifos is a crystalline organophosphate insecticide that inhibits acetylcholinesterase and is used to control insect pests. It is known by many trade names...

, diazinon
Diazinon
Diazinon , a colorless to dark brown liquid, is a thiophosphoric acid ester developed in 1952 by Ciba-Geigy, a Swiss chemical company...

, dichlorvos
Dichlorvos
Dichlorvos or 2,2-dichlorovinyl dimethyl phosphate is a highly volatile organophosphate, widely used as a insecticide to control household pests, in public health, and protecting stored product from insects. It is effective against mushroom flies, aphids, spider mites, caterpillars, thrips, and...

, phosmet
Phosmet
Phosmet is a phthalimide-derived, non-systemic, organophosphate insecticide used on plants and animals. It is mainly used on apple trees for control of coddling moth, though it is also used on a wide range of fruit crops, ornamentals, and vines for the control of aphids, suckers, mites, and fruit...

, fenitrothion
Fenitrothion
Fenitrothion is a phosphorothioate insecticide....

 tetrachlorvinphos, and azinphos methyl. Malathion is widely used in agriculture, residential landscaping, public recreation areas, and in public health pest control programs such as mosquito eradication. In the US, it is the most commonly used organophosphate insecticide. Forty organophosphate pesticides are registered in the U.S., with at least 73 million pounds used in agricultural and residential settings.

They are of concern to both scientists and regulators because they work by irreversibly blocking an enzyme that’s critical to nerve function in both bugs and people.
Even at relatively low levels, organophosphates may be most hazardous to the brain development of fetuses and young children. The EPA banned most residential uses of organophosphates in 2001, but they are still sprayed agriculturally on fruits and vegetables. They’re also used to control pests like mosquitos in public spaces such as parks. They can be absorbed through the lungs or skin or by eating them on food.

History of nerve agents

Early pioneers in the field include Jean Louis Lassaigne
Jean Louis Lassaigne
Jean Louis Lassaigne was a French chemist. He is best known for the sodium fusion test named after him.-Early life:...

 (early 19th century) and Philippe de Clermont
Philippe de Clermont
Philippe de Clermont was a French organic chemist. He was known for the synthesis of the first organophosphate cholinesterase inhibitor . He worked in Adolphe Wurtz's laboratory in Paris.-References:...

 (1854). In 1932, German chemist Willy Lange and his graduate student, Gerde von Krueger, first described the cholinergic
Cholinergic
The word choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation. Found in most animal tissues, choline is a primary component of the neurotransmitter acetylcholine and functions with inositol as a basic constituent of lecithin...

 nervous system effects of organophosphates, noting a choking sensation and a dimming of vision after exposure. This discovery later inspired German chemist Gerhard Schrader
Gerhard Schrader
Dr. Gerhard Schrader was a German chemist specializing in the discovery of new insecticides, hoping to make progress in the fight against hunger in the world. However, Dr...

 at company IG Farben
IG Farben
I.G. Farbenindustrie AG was a German chemical industry conglomerate. Its name is taken from Interessen-Gemeinschaft Farbenindustrie AG . The company was formed in 1925 from a number of major companies that had been working together closely since World War I...

 in the 1930s to experiment with these compounds as insecticides. Their potential use as chemical warfare agents soon became apparent, and the Nazi government put Schrader in charge of developing organophosphate (in the broader sense of the word) nerve gases. Schrader's laboratory discovered the G series of weapons, which included Sarin
Sarin
Sarin, or GB, is an organophosphorus compound with the formula [2CHO]CH3PF. It is a colorless, odorless liquid, which is used as a chemical weapon. It has been classified as a weapon of mass destruction in UN Resolution 687...

, Tabun
Tabun
Tabun may refer to:* Tabun Cave, a cave near Tabun, Israel where remains of Neanderthal Man were found.* A tabun oven, a clay oven used to make tabun bread...

, and Soman
Soman
Soman, or GD , is an extremely toxic chemical substance. It is a nerve agent, interfering with normal functioning of the mammalian nervous system by inhibiting the cholinesterase enzyme. As a chemical weapon, it is classified as a weapon of mass destruction by the United Nations according to UN...

. The Nazis produced large quantities of these compounds, though did not use them during World War II. British scientists experimented with a cholinergic
Cholinergic
The word choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation. Found in most animal tissues, choline is a primary component of the neurotransmitter acetylcholine and functions with inositol as a basic constituent of lecithin...

 organophosphate of their own, called diisopropylfluorophosphate
Diisopropylfluorophosphate
Diisopropyl fluorophosphate is an oily, colorless liquid with the chemical formula C6H14FO3P. It is used in medicine and as an organophosphorus insecticide...

 (DFP), during the war. The British later produced VX
VX (nerve agent)
VX, IUPAC name O-ethyl S-[2-ethyl] methylphosphonothioate, is an extremely toxic substance whose only application is in chemical warfare as a nerve agent. As a chemical weapon, it is classified as a weapon of mass destruction by the United Nations in UN Resolution 687...

 nerve agent, which was many times more potent than the G series, in the early 1950s, almost 20 years after the Germans had discovered the G series.

After World War II, American companies gained access to some information from Schrader's laboratory, and began synthesizing organophosphate pesticides in large quantities. Parathion
Parathion
Parathion, also called parathion-ethyl or diethyl parathion, is an organophosphate compound. It is a potent insecticide and acaricide. It was originally developed by IG Farben in the 1940s. It is highly toxic to non-target organisms, including humans. Its use is banned or restricted in many...

 was among the first marketed, followed by malathion
Malathion
Malathion is an organophosphate parasympathomimetic which binds irreversibly to cholinesterase. Malathion is an insecticide of relatively low human toxicity, however one recent study has shown that children with higher levels of organophosphate pesticide metabolites in their urine are more likely...

 and azinphosmethyl. The popularity of these insecticides increased after many of the organochlorine insecticides like DDT
DDT
DDT is one of the most well-known synthetic insecticides. It is a chemical with a long, unique, and controversial history....

, dieldrin
Dieldrin
Dieldrin is a chlorinated hydrocarbon originally produced in 1948 by J. Hyman & Co, Denver, as an insecticide. Dieldrin is closely related to aldrin, which reacts further to form dieldrin. Aldrin is not toxic to insects; it is oxidized in the insect to form dieldrin which is the active compound...

, and heptachlor
Heptachlor
Heptachlor is an organochlorine compound that was used as an insecticide. Usually sold as a white or tan powder, heptachlor is one of the cyclodiene insecticides. In 1962, Rachel Carson's Silent Spring questioned the safety of heptachlor and other chlorinated insecticides. Due to its highly...

 were banned in the 1970s.

Structural features of organophosphates

Effective organophosphates have the following structural features:
  • A terminal oxygen
    Oxygen
    Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...

     connected to phosphorus by a double bond, i.e. a phosphoryl group
  • Two lipophilic groups bonded to the phosphorus
  • A leaving group
    Leaving group
    In chemistry, a leaving group is a molecular fragment that departs with a pair of electrons in heterolytic bond cleavage. Leaving groups can be anions or neutral molecules. Common anionic leaving groups are halides such as Cl−, Br−, and I−, and sulfonate esters, such as para-toluenesulfonate...

     bonded to the phosphorus, often a halide
    Halide
    A halide is a binary compound, of which one part is a halogen atom and the other part is an element or radical that is less electronegative than the halogen, to make a fluoride, chloride, bromide, iodide, or astatide compound. Many salts are halides...


Terminal oxygen vs. terminal sulfur

Thiophosphoryl compounds, those bearing the P=S functionality, are much less toxic than related phosphoryl derivatives, which include sarin
Sarin
Sarin, or GB, is an organophosphorus compound with the formula [2CHO]CH3PF. It is a colorless, odorless liquid, which is used as a chemical weapon. It has been classified as a weapon of mass destruction in UN Resolution 687...

, VX
VX (nerve agent)
VX, IUPAC name O-ethyl S-[2-ethyl] methylphosphonothioate, is an extremely toxic substance whose only application is in chemical warfare as a nerve agent. As a chemical weapon, it is classified as a weapon of mass destruction by the United Nations in UN Resolution 687...

 and tetraethyl pyrophosphate
Tetraethyl pyrophosphate
Tetraethyl pyrophosphate, abbreviated TEPP, is an organophosphate compound. It is used as a pesticide.This compound is a clear, colorless liquid. It is soluble in water, but hydrolyzes rapidly. It was first synthesized by Philippe de Clermont...

. Thiophosphoryl compounds are not active inhibitors
Enzyme inhibitor
An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...

 of acetylcholinesterase
Acetylcholinesterase
"Acetylcholinesterase, also known as AChE or acetylcholine acetylhydrolase, is an enzyme that degrades the neurotransmitter acetylcholine, producing choline and an acetate group. It is mainly found at neuromuscular junctions and cholinergic nervous system, where its activity serves to terminate...

 in either mammals or insects; in mammals, metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

 tends to remove lipophilic
Lipophilic
Lipophilicity, , refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. These non-polar solvents are themselves lipophilic — the axiom that like dissolves like generally holds true...

 side groups from the phosphorus atom while in insects it tends to oxidize the compound, thus removing the terminal sulfur and replacing it with a terminal oxygen, which allows the compound to more efficiently act as an acetylcholinesterase inhibitor.

Fine tuning

Within these requirements, a large number of different lipophilic and leaving groups have been used. The variation of these groups is one means of fine tuning the toxicity of the compound. A good example of this chemistry are the P-thiocyanate
Thiocyanate
Thiocyanate is the anion [SCN]−. It is the conjugate base of thiocyanic acid. Common derivatives include the colourless salts potassium thiocyanate and sodium thiocyanate. Organic compounds containing the functional group SCN are also called thiocyanates...

 compounds which use an aryl
Aryl
In the context of organic molecules, aryl refers to any functional group or substituent derived from an aromatic ring, be it phenyl, naphthyl, thienyl, indolyl, etc....

  (or alkyl) group and an alkylamino group as the lipophilic groups. The thiocyanate is the leaving group.
It was claimed in a German patent that the reaction of 1,3,2,4-dithiadiphosphetane 2,4-disulfides with dialkyl cyanamides formed plant protection agents which contained six membered (P-N=C-N=C-S-) rings. It has been proven in recent times by the reaction of diferrocenyl 1,3,2,4-dithiadiphosphetane 2,4-disulfide (and Lawesson's reagent) with dimethyl cyanamide
Cyanamide
Cyanamide is an organic compound with the formula CN2H2. This white solid is widely used in agriculture and the production of pharmaceuticals and other organic compounds. It is also used as an alcohol deterrent drug in Canada, Europe and Japan. The molecule features a nitrile group attached to an...

 that, in fact, a mixture of several different phosphorus-containing compounds is formed. Depending on the concentration of the dimethyl cyanamide in the reaction mixture, either a different six membered ring compound (P-N=C-S-C=N-) or a nonheterocylic compound (FcP(S)(NR2)(NCS)) is formed as the major product; the other compound is formed as a minor product.

In addition, small traces of other compounds are also formed in the reaction. It is unlikely that the ring compound (P-N=C-S-C=N-) {or its isomer} would act as a plant protection agent, but (FcP(S)(NR2)(NCS)) compounds can act as nerve
Nerve
A peripheral nerve, or simply nerve, is an enclosed, cable-like bundle of peripheral axons . A nerve provides a common pathway for the electrochemical nerve impulses that are transmitted along each of the axons. Nerves are found only in the peripheral nervous system...

 poisons in insects.

Organophosphate poisoning

Many organophosphates are potent nerve agents, functioning by inhibiting the action of acetylcholinesterase (AChE) in nerve cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

. They are one of the most common causes of poisoning worldwide, and are frequently intentionally used in suicides in agricultural areas. Organophosphorus pesticides can be absorbed by all routes, including inhalation, ingestion, and dermal absorption. Their toxicity is not limited to the acute phase, however, and chronic effects have long been noted. Neurotransmitters such as acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...

 (which is affected by organophosphate pesticides) are profoundly important in the brain's development, and many OPs have neurotoxic effects on developing organisms, even from low levels of exposure
Toxicity
Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...

. Other organophosphates are not toxic, yet their main metabolites, such as their oxons are.

Chronic Toxicity

Repeated or prolonged exposure to organophosphates may result in the same effects as acute exposure including the delayed symptoms. Other effects reported in workers repeatedly exposed include impaired memory and concentration, disorientation, severe depressions, irritability, confusion, headache, speech difficulties, delayed reaction times, nightmares, sleepwalking and drowsiness or insomnia. An influenza-like condition with headache, nausea, weakness, loss of appetite, and malaise has also been reported.

Low level exposure

Even at relatively low levels organophosphates may be hazardous to human health. The pesticides act on a set of brain chemicals closely related to those involved in ADHD, thus
fetuses and young children, where brain development depends on a strict sequence of biological events, may be most at risk. They can be absorbed through the lungs or skin or by eating them on food. According to a 2008 report from the U.S. Department of Agriculture, in a representative sample of produce tested by the agency, 28 percent of frozen blueberries, 20 percent of celery, 27 percent of green beans, 17 percent of peaches, 8 percent of broccoli and 25 percent of strawberries contained traces of organophosphate.

The United States Environmental Protection Agency
United States Environmental Protection Agency
The U.S. Environmental Protection Agency is an agency of the federal government of the United States charged with protecting human health and the environment, by writing and enforcing regulations based on laws passed by Congress...

 lists the organophosphate parathion as a possible human carcinogen
Carcinogen
A carcinogen is any substance, radionuclide, or radiation that is an agent directly involved in causing cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes...

.

Chronic fatigue is common amongst those who consider their health is affected by pesticides and research from 2003 suggested there was an association between exposure to organophosphates and chronic fatigue symptoms.

A 2007 study linked the organophosphate insecticide chlorpyrifos
Chlorpyrifos
Chlorpyrifos is a crystalline organophosphate insecticide that inhibits acetylcholinesterase and is used to control insect pests. It is known by many trade names...

, which is used on some fruits and vegetables, with delays in learning rates, reduced physical coordination, and behavioral problems in children, especially ADHD.

A 2010 study has found that organophosphate exposure is associated with an increased risk of Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...

.

A 2010 study found that each 10-fold increase in urinary concentration of organophosphate metabolites was associated with a 55% to 72% increase in the odds of ADHD in children. The study found that organophosphate exposure is associated with an increased risk of ADHD
Attention-deficit hyperactivity disorder
Attention deficit hyperactivity disorder is a developmental disorder. It is primarily characterized by "the co-existence of attentional problems and hyperactivity, with each behavior occurring infrequently alone" and symptoms starting before seven years of age.ADHD is the most commonly studied and...

 in children. Researchers analyzed the levels of organophosphate residues in the urine of more than 1,100 children aged 8 to 15 years old, and found that those with the highest levels of dialkyl phosphates, which are the breakdown products of organophosphate pesticides, also had the highest incidence of ADHD. Overall, they found a 35% increase in the odds of developing ADHD with every 10-fold increase in urinary concentration of the pesticide residues. The effect was seen even at the low end of exposure: children who had any detectable, above-average level of pesticide metabolite in their urine were twice as likely as those with undetectable levels to record symptoms of ADHD.

Another 2010 study found that children who were exposed to organophosphate pesticides while still in their mother's womb were more likely to develop attention disorders years later. The researchers evaluated the children at age 3.5 and 5 years for symptoms of attention disorders and ADHD using maternal reports of child behavior, performance on standardized computer tests, and behavior ratings from examiners. Each tenfold increase in prenatal pesticide metabolites was linked to having five times the odds of scoring high on the computerized tests at age 5, suggesting a greater likelihood of a child having ADHD. The effect appeared to be stronger for boys than for girls.

In 2011 the results of three government-funded studies that charted "everyday" environmental exposures in hundreds of women and their children through pregnancy and into their grade school years was released. Though each study used a somewhat different way to track the pesticide exposures, they all reached strikingly similar conclusions—that many children exposed to higher levels of organophosphates during pregnancy than their peers are more likely to have lower IQs and may have more difficulty focusing on tasks or solving problems. In one study children who were exposed to the highest levels of organophosphates during pregnancy had IQ scores that were an average of 7 points lower than the IQ scores of those with the lowest pesticide exposures. It was found that genetics appear to play a strong role in whether exposure to organophosphates will cause damage. Two studies found that children exposed to higher levels of organophosphate pesticides than their peers were more likely to be diagnosed with attention deficit hyperactivity disorder.

Proposals to ban and restrictions of use

According to the non-governmental organisation Pesticide Action Network
Pesticide Action Network
Pesticide Action Network is "an international coaltion of around 600 NGOs, citizens' groups, and individuals in about 60 countries."PAN is involved in fighting problems caused by pesticide use, and advocates ecologically sound alternatives. Branches include PAN North America, U...

, the organophosphate parathion is one of the most dangerous pesticides. In the US alone more than 650 agricultural workers have been poisoned since 1966, of which 100 died. In underdeveloped countries many more people have suffered fatal and nonfatal intoxications. The World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

, PAN and numerous environmental organisations propose a general and global ban. Its use is banned or restricted in 23 countries and its import is illegal in a total of 50 countries. Its use was banned in the U.S. in 2000 and it has not been used since 2003.

Other than for agricultural use, the organophosphate diazinon has been banned in the U.S. Agriculturally, more than one million pounds of diazinon were used in California to control agricultural pests in 2000. The areas and crops on which diazinon are most heavily applied are structural pest control, almonds, head lettuce, leaf lettuce and prunes.

In May 2006 the Environmental Protection Agency reviewed the use of the organophosphate dichlorvos
Dichlorvos
Dichlorvos or 2,2-dichlorovinyl dimethyl phosphate is a highly volatile organophosphate, widely used as a insecticide to control household pests, in public health, and protecting stored product from insects. It is effective against mushroom flies, aphids, spider mites, caterpillars, thrips, and...

 and proposed its continued sale, despite concerns over its safety and considerable evidence suggesting it is carcinogenic and harmful to the brain and nervous system, especially in children. Environmentalists charge that the latest decision was the product of backroom deals with industry and political interference.

In 2001 the EPA placed new restrictions on the use of the organophosphates phosmet and azinphos-methyl to increase protection of agricultural workers. The crop uses reported at that time as being phased out in four years included those for almonds, tart cherries, cotton, cranberries, peaches, pistachios, and walnuts. The crops with time-limited registration included apples/crab apples, blueberries, sweet cherries, pears, pine seed orchards, brussels sprouts, cane berries, and the use of azinphos-methyl by nurseries for quarantine requirements. The labeled uses of phosmet include alfalfa, orchard crops (e.g. almonds, walnuts, apples, cherries), blueberries, citrus, grapes, ornamental trees (not for use in residential, park, or recreational areas) and non-bearing fruit trees, Christmas trees and conifers (tree farms), potatoes and peas. Azinphos-methyl has been banned in Europe since 2006.

See also

  • Organophosphate poisoning
    Organophosphate poisoning
    Organophosphate poisoning results from exposure to organophosphates , which cause the inhibition of acetylcholinesterase leading to the accumulation of acetylcholine in the body. Organophosphate poisoning most commonly results from exposure to insecticides or nerve agents...

  • Activity based protein profiling using organophosphate-containing activity based probes
  • Mark Purdey
    Mark Purdey
    John Mark Purdey was a British organic farmer who came to public attention in the 1980s, when he began to circulate his own theories regarding the causes of bovine spongiform encephalopathy .Purdey's interest in the disease was triggered when four cows he purchased for his farm developed the...

  • Pesticide toxicity to bees
    Pesticide toxicity to bees
    Pesticides vary in their effects on bees. Contact pesticides are usually sprayed on plants and can kill bees when they crawl over sprayed surfaces of plants or other media...

  • Toxic Syndrome (Spain)
    Toxic oil syndrome
    Toxic Oil Syndrome or simply Toxic Syndrome was the name given to a disease outbreak in Spain in 1981, which killed over 600 people. Its first appearance was as a lung disease, with unusual features: though the symptoms initially resembled a lung infection, antibiotics were ineffective...


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