Paraquat
Overview
 
Paraquat is the trade name for N,N′-dimethyl-4,4′-bipyridinium dichloride, one of the most widely used herbicides in the world. Paraquat, a viologen
Viologen
Viologens are toxic bipyridinium derivatives of 4,4'-bipyridyl. The name is because this class of compounds is easily reduced to the radical mono cation, which is intensely blue coloured....

, is quick-acting and non-selective, killing green plant tissue on contact. It is also toxic to human beings and animals. Research has shown that it is linked to development of Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...

.
Pyridine
Pyridine
Pyridine is a basic heterocyclic organic compound with the chemical formula C5H5N. It is structurally related to benzene, with one C-H group replaced by a nitrogen atom...

 is coupled with sodium in anhydrous ammonia to give 4,4'-bipyridine
4,4'-Bipyridine
4,4'-Bipyridine is a bipyridine which is mainly used as a precursor to N,N'-dimethyl-4,4'-bipyridinium [2]2+, known as paraquat. This species is electroactive, and its toxicity arises from the ability of this dication to interrupt biological electron transfer...

, which is then methylated with chloromethane
Chloromethane
Chloromethane, also called methyl chloride, R-40 or HCC 40, is a chemical compound of the group of organic compounds called haloalkanes. It was once widely used as a refrigerant. It is a colorless extremely flammable gas with a minorly sweet odor, which is, however, detected at possibly toxic levels...

 to give the desired compound:

Although first synthesized in 1882, paraquat's herbicidal properties were not recognized until 1955.
Encyclopedia
Paraquat is the trade name for N,N′-dimethyl-4,4′-bipyridinium dichloride, one of the most widely used herbicides in the world. Paraquat, a viologen
Viologen
Viologens are toxic bipyridinium derivatives of 4,4'-bipyridyl. The name is because this class of compounds is easily reduced to the radical mono cation, which is intensely blue coloured....

, is quick-acting and non-selective, killing green plant tissue on contact. It is also toxic to human beings and animals. Research has shown that it is linked to development of Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...

.

Production

Pyridine
Pyridine
Pyridine is a basic heterocyclic organic compound with the chemical formula C5H5N. It is structurally related to benzene, with one C-H group replaced by a nitrogen atom...

 is coupled with sodium in anhydrous ammonia to give 4,4'-bipyridine
4,4'-Bipyridine
4,4'-Bipyridine is a bipyridine which is mainly used as a precursor to N,N'-dimethyl-4,4'-bipyridinium [2]2+, known as paraquat. This species is electroactive, and its toxicity arises from the ability of this dication to interrupt biological electron transfer...

, which is then methylated with chloromethane
Chloromethane
Chloromethane, also called methyl chloride, R-40 or HCC 40, is a chemical compound of the group of organic compounds called haloalkanes. It was once widely used as a refrigerant. It is a colorless extremely flammable gas with a minorly sweet odor, which is, however, detected at possibly toxic levels...

 to give the desired compound:

History

Although first synthesized in 1882, paraquat's herbicidal properties were not recognized until 1955. Paraquat was first manufactured and sold by ICI
Imperial Chemical Industries
Imperial Chemical Industries was a British chemical company, taken over by AkzoNobel, a Dutch conglomerate, one of the largest chemical producers in the world. In its heyday, ICI was the largest manufacturing company in the British Empire, and commonly regarded as a "bellwether of the British...

  in early 1962, and is today among the most commonly used herbicides.

The European Union
European Union
The European Union is an economic and political union of 27 independent member states which are located primarily in Europe. The EU traces its origins from the European Coal and Steel Community and the European Economic Community , formed by six countries in 1958...

 approved the use of paraquat in 2004. Subsequently Sweden, supported by Denmark, Austria, and Finland, brought the European Union commission to court. In 2007, the court annulled the directive authorizing paraquat as an active plant protection substance.

Herbicide use

Paraquat is used as a quaternary ammonium herbicide, one of the most widely used herbicides in the world. It is quick-acting, non-selective, and kills green plant tissue on contact. It is redistributed within the plant, but does not harm mature bark. Herbicides are used to protect crops by controlling a wide range of annual and certain perennial weed
Weed
A weed in a general sense is a plant that is considered by the user of the term to be a nuisance, and normally applied to unwanted plants in human-controlled settings, especially farm fields and gardens, but also lawns, parks, woods, and other areas. More specifically, the term is often used to...

s that would otherwise reduce compete with the crop for water, nutrients, and light.

The key characteristics that distinguish the non-selective contact herbicide paraquat from other active ingredients used in plant protection products are:
  • It is non-selective, which means it kills a wide range of annual grass
    Grass
    Grasses, or more technically graminoids, are monocotyledonous, usually herbaceous plants with narrow leaves growing from the base. They include the "true grasses", of the Poaceae family, as well as the sedges and the rushes . The true grasses include cereals, bamboo and the grasses of lawns ...

    es and broad-leaved weeds and the tops of established perennial weeds.
  • It is very fast-acting.
  • It is rain-fast within minutes of application.
  • It becomes biologically inactive upon contact with soil.


These properties, especially broad-spectrum weed control and inactivation upon contact with soil, made paraquat an essential tool in the development of no-till farming
No-till farming
No-till farming is a way of growing crops from year to year without disturbing the soil through tillage. No-till is an agricultural technique which increases the amount of water and organic matter in the soil and decreases erosion...

.

In the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

, paraquat is available primarily as a liquid in various strengths. It is classified as "restricted use," which means that it can be used only by licensed applicators. In the European Union
European Union
The European Union is an economic and political union of 27 independent member states which are located primarily in Europe. The EU traces its origins from the European Coal and Steel Community and the European Economic Community , formed by six countries in 1958...

, paraquat has been forbidden since 2007.

Mode of action

Paraquat inhibits photosynthesis. In light-exposed plants, it accepts electrons from photosystem I
Photosystem I
Photosystem I is the second photosystem in the photosynthetic light reactions of algae, plants, and some bacteria. Photosystem I is so named because it was discovered before photosystem II. Aspects of PS I were discovered in the 1950s, but the significances of these discoveries was not yet known...

 (more specifically Fd which is presented with electrons from PS I) and transfers them to molecular oxygen. In this manner, destructive reactive oxygen species
Reactive oxygen species
Reactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....

 are produced. In forming these reactive oxygen species, the oxidized form of paraquat is regenerated, and is again available to shunt electrons from photosystem I
Photosystem I
Photosystem I is the second photosystem in the photosynthetic light reactions of algae, plants, and some bacteria. Photosystem I is so named because it was discovered before photosystem II. Aspects of PS I were discovered in the 1950s, but the significances of these discoveries was not yet known...

 to start the cycle again.

Weed resistance management

Problems with herbicide resistant weeds may be addressed by applying herbicides with different modes of action, along with cultural methods such as crop rotation, in integrated weed management (IWM) systems. Paraquat, with its distinctive mode of action, is one of few chemical options that can be used to prevent and mitigate problems with weeds that have become resistant to the very widely used non-selective herbicide glyphosate. ,

One example is the ‘Double Knock’ system used in Australia. Before planting a crop, weeds are sprayed with glyphosate first, then followed seven to ten days later by a paraquat herbicide. Although twice as expensive as using a single glyphosate spray, the ‘Double Knock’ system is an important resistance management strategy widely relied upon by farmers.

A computer simulation conducted by researchers at the Western Australian Herbicide Research Initiative (WAHRI) calculated that if the herbicide used in land preparation was alternated annually between glyphosate and paraquat, only one field in five would be expected to have glyphosate resistant annual ryegrass (Lolium rigidum) after 30 years, compared to nearly 90% of fields sprayed only with glyphosate. A ‘Double Knock’ regime with paraquat cleaning-up after glyphosate was predicted to keep all fields free of glyphosate resistant ryegrass for at least 30 years.

Scientific use

Paraquat is often used in science to catalyze the formation of reactive oxygen species
Reactive oxygen species
Reactive oxygen species are chemically reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons....

 (ROS), more specifically, the superoxide
Superoxide
A superoxide, also known by the obsolete name hyperoxide, is a compound that possesses the superoxide anion with the chemical formula O2−. The systematic name of the anion is dioxide. It is important as the product of the one-electron reduction of dioxygen O2, which occurs widely in nature...

 free radical. Paraquat will undergo redox cycling in vivo, being reduced by an electron donor such as NADPH, before being oxidized by an electron receptor such as dioxygen to produce superoxide
Superoxide
A superoxide, also known by the obsolete name hyperoxide, is a compound that possesses the superoxide anion with the chemical formula O2−. The systematic name of the anion is dioxide. It is important as the product of the one-electron reduction of dioxygen O2, which occurs widely in nature...

, a major ROS.

"Paraquat pot"

During the late 1970s, a controversial program sponsored by the US government sprayed paraquat on marijuana
Cannabis (drug)
Cannabis, also known as marijuana among many other names, refers to any number of preparations of the Cannabis plant intended for use as a psychoactive drug or for medicinal purposes. The English term marijuana comes from the Mexican Spanish word marihuana...

 fields in Mexico. Since much of this marijuana was subsequently smoked by Americans, the US government's "Paraquat Pot" program stirred much debate. Perhaps in an attempt to deter people from using marijuana, representatives of the program warned that spraying rendered the crop unsafe to smoke.

However, independent bodies have studied paraquat in this use. Jenny Pronczuk de Garbino, stated: "no lung or other injury in marijuana users has ever been attributed to paraquat contamination". Also a 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...

 manual states: "... toxic effects caused by this mechanism have been either very rare or nonexistent. Most paraquat that contaminates marijuana
Cannabis (drug)
Cannabis, also known as marijuana among many other names, refers to any number of preparations of the Cannabis plant intended for use as a psychoactive drug or for medicinal purposes. The English term marijuana comes from the Mexican Spanish word marihuana...

 is pyrolyzed during smoking to dipyridyl, which is a product of combustion of the leaf material itself (including marijuana
Cannabis (drug)
Cannabis, also known as marijuana among many other names, refers to any number of preparations of the Cannabis plant intended for use as a psychoactive drug or for medicinal purposes. The English term marijuana comes from the Mexican Spanish word marihuana...

) and presents little toxic hazard."

In suicide

A large majority (93%) of fatalities from paraquat poisoning are cases of intentional self-administration, i.e., suicide
Suicide
Suicide is the act of intentionally causing one's own death. Suicide is often committed out of despair or attributed to some underlying mental disorder, such as depression, bipolar disorder, schizophrenia, alcoholism, or drug abuse...

s. In third world countries, paraquat is a "major suicide agent". For instance, in Samoa
Samoa
Samoa , officially the Independent State of Samoa, formerly known as Western Samoa is a country encompassing the western part of the Samoan Islands in the South Pacific Ocean. It became independent from New Zealand in 1962. The two main islands of Samoa are Upolu and one of the biggest islands in...

 from 1979–2001, 70% of suicides were by paraquat poisoning. In southern Trinidad
Trinidad
Trinidad is the larger and more populous of the two major islands and numerous landforms which make up the island nation of Trinidad and Tobago. It is the southernmost island in the Caribbean and lies just off the northeastern coast of Venezuela. With an area of it is also the fifth largest in...

 from 1996–1997, 76% of suicides were by paraquat.

The reason paraquat is such a widely used suicide agent in third-world countries is due to its widespread availability, low toxic dose (10 ml or 2 teaspoons is enough to kill) and relative low cost. There are campaigns to control or even ban paraquat outright, and there are moves to restrict its availability by requiring user education and the locking up of paraquat stores.

Toxicity

Pure paraquat, when ingested, is highly toxic to mammals, including humans; potentially leading to acute respiratory distress syndrome (ARDS), and there are no specific antidotes. However, fuller's earth
Fuller's earth
Fuller's earth is any non-plastic clay or claylike earthy material used to decolorize, filter, and purify animal, mineral, and vegetable oils and greases.-Occurrence and composition:...

 or activated charcoal is an effective treatment, if taken in time. Death may occur up to 30 days after ingestion. Diluted paraquat used for spraying is less toxic; thus, the greatest risk of accidental poisoning is during mixing and loading paraquat for use.


In acute toxicity studies using laboratory animals, paraquat has been shown to be highly toxic by the inhalation route and has been placed in Toxicity Category I (the highest of four levels) for acute inhalation effects. However, the EPA has determined that particles used in agricultural practices (400 to 800 μm) are well beyond the respirable range and therefore inhalation toxicity is not a toxicological endpoint of concern. Paraquat is toxic (Category II) by the oral route and moderately toxic (Category III) by the dermal route. Paraquat will cause moderate to severe eye irritation and minimal dermal irritation, and has been placed in Toxicity Categories II and IV (slightly toxic) respectively for these effects.


Even a single swig, immediately spat out, can cause death from fibrous tissue developing in the lungs, leading to asphyxiation.

According to the Center for Disease Control, ingesting paraquat causes symptom
Symptom
A symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...

s such as liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

, lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...

, heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...

, and kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...

 failure within several days to several weeks that can lead to death up to 30 days after ingestion. Those who suffer large exposures are unlikely to survive. Chronic exposure can lead to lung damage, kidney failure, heart failure, and oesophageal strictures. Accidental deaths and suicides from paraquat ingestion are relatively common. For example, there have been 18 deaths in Australia from paraquat poisoning since 2000. Long term exposures to paraquat would most likely cause lung and eye damage, but reproductive/fertility damage was not found by the United States Environmental Protection Agency‎ (EPA) in their review.

Humans

In 2011, a US National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...

 study showed a link between paraquat use and Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...

 in farm workers. A co-author of the paper said that paraquat increases production of certain oxygen derivatives that may harm cellular structures, and that people who used paraquat, or other pesticides with a similar mechanism of action, were more likely to develop Parkinson's disease.

Other mammals

Paraquat-induced toxicity in rats has also been linked to Parkinson's-like neurological degenerative mechanisms. A study by the Buck Institute showed a connection between exposure to paraquat and iron in infancy and mid-life Parkinson's in laboratory mice.

Invertebrates

Paraquat also induces oxidative stress
Oxidative stress
Oxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...

 in invertebrates such as Drosophila melanogaster
Drosophila melanogaster
Drosophila melanogaster is a species of Diptera, or the order of flies, in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting from Charles W...

. Paraquat-fed flies suffer early-onset mortality, and significant increases in Superoxide dismutase
Superoxide dismutase
Superoxide dismutases are a class of enzymes that catalyze the dismutation of superoxide into oxygen and hydrogen peroxide. As such, they are an important antioxidant defense in nearly all cells exposed to oxygen...

activity.
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