Paraquat
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| Names | |
|---|---|
| Preferred IUPAC name
1,1′-Dimethyl[4,4′-bipyridine]-1,1′-diium dichloride | |
| Other names
Paraquat dichloride; Methyl viologen dichloride; MVCl2; Crisquat; Dexuron; Esgram; Gramuron; Ortho Paraquat CL; Para-col; Pillarxone; Tota-col; Toxer Total; PP148; Cyclone; Gramixel; Gramoxone; Pathclear; AH 501; Bai Cao Ku. | |
| Identifiers | |
3D model (JSmol) |
|
| ChEBI | |
| ChEMBL | |
| ChemSpider | |
| ECHA InfoCard | 100.016.015 |
PubChem CID |
|
| UNII | |
CompTox Dashboard (EPA) |
|
| |
| |
| Properties | |
| C12H14Cl2N2 | |
| Molar mass | 257.16 g·mol−1 |
| Appearance | Yellow solid[1] |
| Odor | faint, ammonia-like[1] |
| Density | 1.25 g/cm3 |
| Melting point | 175 to 180 °C (347 to 356 °F; 448 to 453 K)[2] |
| Boiling point | > 300 °C (572 °F; 573 K)[2] |
| High | |
| Vapor pressure | <0.0000001 mmHg (20 °C)[1] |
| Hazards | |
| Occupational safety and health (OHS/OSH): | |
Main hazards |
Toxic, environmental hazard |
| GHS labelling: | |
   | |
| H301, H311, H315, H319, H330, H335, H372, H410[3] | |
| P260, P273, P280, P284, P301+P310, P305+P351+P338 | |
| NFPA 704 (fire diamond) | |
| Lethal dose or concentration (LD, LC): | |
LD50 (median dose) |
57 mg/kg (rat, oral) 120 mg/kg (mouse, oral) 25 mg/kg (dog, oral) 22 mg/kg (guinea pig, oral)[4] |
LC50 (median concentration) |
3 mg/m3 (mouse, 30 min respirable dust) 3 mg/m3 (guinea pig, 30 min respirable dust)[4] |
LCLo (lowest published) |
1 mg/m3 (rat, respirable dust, 6 h) 6400 mg/m3 (rat, nonrespirable dust, 4 h)[4] |
| NIOSH (US health exposure limits): | |
PEL (Permissible) |
TWA 0.5 mg/m3 (resp) [skin][1] |
REL (Recommended) |
TWA 0.1 mg/m3 (resp) [skin][1] |
IDLH (Immediate danger) |
1 mg/m3[1] |
| Safety data sheet (SDS) | Aldrich MSDS |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
| |
Paraquat (trivial name; /ˈpærəkwɒt/), or N,N′-dimethyl-4,4′-bipyridinium dichloride (systematic name), also known as methyl viologen, is a toxic organic compound with the chemical formula [(C6H7N)2]Cl2. It is classified as a viologen, a family of redox-active heterocycles of similar structure.[5] It is one of the most widely used herbicides worldwide. It is quick-acting and non-selective, killing green plant tissue on contact.
Paraquat is highly toxic to humans and other animals. The toxicity and lethality depends on the dose and how the herbicide is absorbed by the body. In humans, paraquat damages the mouth, stomach, and intestines if it is ingested orally.[6] Once absorbed in the body, paraquat causes particular damage to the lungs, kidneys, and liver.[6] Paraquat's lethality is attributed to its enhancing production of superoxide anions and human lung cells can accumulate paraquat. Paraquat exposure has been strongly linked to the development of Parkinson's disease.[7]
Paraquat may be in the form of salt with chloride or other anions; quantities of the substance are sometimes expressed by cation mass alone (paraquat cation, paraquat ion). The name is derived from the para positions of the quaternary nitrogens.
Production and redox reactions
[edit]Pyridine is coupled by treatment with sodium in ammonia followed by oxidation to give 4,4′-bipyridine. This chemical is then dimethylated with chloromethane to give the final product as the dichloride salt.[8]
Use of other methylating agents gives the bispyridinium with alternate counterions. For example, Hugo Weidel's original synthesis used methyl iodide to produce the diiodide.[9]
Herbicide use
[edit]Although first synthesized by Weidel and Russo in 1882,[9] paraquat's herbicidal properties were not recognized until 1955 in the Imperial Chemical Industries (ICI) laboratories at Jealott's Hill, Berkshire, England.[10][11] Paraquat was first manufactured and sold by ICI in early 1962 under the trade name Gramoxone, and is today among the most commonly used herbicides.
Paraquat is classified as a non-selective contact herbicide. The key characteristics that distinguish it from other agents used in plant protection products are:
- It kills a wide range of annual grasses and broad-leaved weeds and the tips of established perennial weeds.
- It is very fast-acting.
- It is rain-fast within minutes of application.
- It is partially inactivated upon contact with soil.[12][13]
These properties led to paraquat being used in the development of no-till farming.[14][15][16]
The European Union approved the use of paraquat in 2004 but Sweden, supported by Denmark, Austria, and Finland, appealed this decision.[17] In 2007, the court annulled the directive authorizing paraquat as an active plant protection substance stating that the 2004 decision was wrong in finding that there were no indications of neurotoxicity associated with paraquat and that the studies about the link between paraquat and Parkinson's disease should have been considered.[18][19] Thus, paraquat has been banned in the European Union since 2007.[20]
China also banned the domestic use of Paraquat in 2017; Thailand followed soon after in 2019 and Brazil, Chile, Malaysia, Peru and Taiwan between 2020 and 2022.[21] India banned it in Odisha in 2023, and temporarily banned it in Kerala in 2011, though the pesticide is still widely used throughout the majority of the country.[22] In May 2026 the U.S. state of Vermont banned it, with limited exceptions for certain fruit orchards until 2030, when the chemical will be banned entirely.[23]
China, the United Kingdom, and Switzerland are responsible for the production of the majority of paraquat for worldwide usage, despite the fact that each of these countries has banned its usage domestically.[24]
In the United States, paraquat is available primarily as a solution in various strengths. It is classified as a restricted use pesticide, which means that it can be used by licensed applicators only. According to an October 2021 estimate, the use of paraquat in US agriculture as mapped by the U.S. Geological Survey showed a doubling from 2013 to 2018, reaching 10,000,000 pounds (4,500,000 kg) annually, up from 1,054,000 pounds (478,000 kg) in 1974.[25][26]
There is an ongoing international campaign for a global ban, but the cheap and popular paraquat continues to be unrestricted in most developing countries.[27] The Chemical Review Committee (CRC) of the Rotterdam Convention recommended to the Conference of the Parties (COP) paraquat dichloride formulations for inclusion in Annex III to the Convention in 2011.[28] A small group of countries, including India and Guatemala and supported by manufacturers, have since blocked the listing of paraquat as a hazardous chemical for the purposes of the Rotterdam Convention.[29]
In Australia, paraquat is used as a herbicide to control annual grasses, broadleaf weeds and ryegrass in crops of chickpeas, faba beans, field peas, lupins, lentils and vetch. Aerial spraying is forbidden, as is harvesting within 2 weeks of application in some crops.[30] The APVMA, circa 2026, decided to continue the use of paraquat and diquat, but cut the maximum permitted to spray on crops down from 1,150 g/Ha to 231 g/Ha, although spot-spraying techniques are excepted from that.[31]
In India, paraquat dichloride 24% SL is widely used for broad-spectrum control of weeds on potato, cotton, rubber, wheat, tea, maize, rice, grapes, apple and aquatic weeds.[32]
Regulation in the United States
[edit]In the United States paraquat was registered in 1964 and reregistered in 1997. EPA initiated registry review in 2011.[33] Proposed Interim Mitigation Decisions were issued in 2016, requiring that the applicators be certified after completing new training requirements, and creating a new closed package system that prevents spills and new warning labels.[34] The EPA released a draft human health and ecological assessment for public comment in October 2019[35][36] followed by the Proposed interim decision in October 2020[37][38] and Interim decision in July 2021.[39] The Interim Decision included stricter measures to mitigate exposure to paraquat, including the use of respirators, time of use, level of use and proper licensing. A Petition for Review filed in September 2021 resulted in the EPA issuing a Preliminary Supplemental Consideration and a solicitation for public comments in February 2024.[40]
Regulation elsewhere
[edit]Paraquat is banned in several countries in South America, West Africa, East Asia and the Middle East.[41]
Reactivity and mode of action
[edit]
Paraquat is an oxidant that interferes with electron transfer, a process that is common to all life. Addition of one electron gives the radical cation:
- [paraquat]2+ + e− [paraquat]•+
The radical cation is also susceptible to further reduction to the neutral [paraquat]0:[42]
- [paraquat]•+ + e− [paraquat]0
As an herbicide, paraquat acts by inhibiting photosynthesis. In light-exposed plants, it accepts electrons from photosystem I (more specifically ferredoxin, which is presented with electrons from PS I) and transfers them to molecular oxygen. In this manner, destructive reactive oxygen species (ROS) 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 to restart the cycle.[43] This induces necrosis, and unlike with some mechanisms of necrosis, does not produce double-stranded breaks.[44] Target weeds die within 4 days; symptoms can show after as little as a few hours.[30]
Paraquat is often used in science to catalyze the formation of ROS, more specifically, the superoxide 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, a major ROS.[45]
Weed resistance management
[edit]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.[46] 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.[47][48] Paraquat is a Group L (Aus), D (global), 22 (numeric) resistance class herbicide, which it shares with diquat and cyperquat.[49]
One example is the "double knock" system used in Australia.[50] 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 widely relied upon by farmers as a resistance management strategy.[51] Nevertheless, herbicide resistance has been seen for both herbicides in a vineyard in Western Australia[52] – though this singular report gives no indication of what regimen was being followed, particularly if the two herbicides were being used in a "double knock" tandem.[53]
A computer simulation reported in the scientific journal Weed Research showed that with alternating annual use 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.[54] 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.
Toxicity
[edit]Paraquat is toxic to humans (Category II) by the oral route and moderately toxic (Category III) through the skin.[55] Pure paraquat, when ingested, is highly toxic to mammals, including humans, causing severe inflammation and potentially leading to severe lung damage (e.g., irreversible pulmonary fibrosis, also known as 'paraquat lung'), acute respiratory distress syndrome (ARDS), and death.[56][57] The mortality rate is estimated between 60% and 90%.[56]
Exposure to paraquat can cause a wide range of serious health effects, including confusion, acute kidney failure, liver failure, increased blood pressure or heart rate, damage to the heart, damage to the lungs leading to fluid-filled lungs and respiratory failure, weak muscles, extreme fatigue and lethargy, nausea or vomiting, diarrhea, and in severe cases, coma.[58]
Paraquat is also toxic when inhaled and is in the Toxicity Category I (the highest of four levels) for acute inhalation effects.[55] For agricultural uses, the United States Environmental Protection Agency (EPA) determined that particles used in agricultural practices (400–800 μm) are not in the respirable range.[55] Paraquat also causes moderate to severe irritation of the eye and skin.[55] Diluted paraquat used for spraying is less toxic; thus, the greatest risk of accidental poisoning is during mixing and loading paraquat for use.[11]
The standard treatment for paraquat poisoning is first to remove as much as possible by pumping the stomach.[59] Fuller's earth or activated charcoal may also improve outcomes depending on the timing. Haemodialysis, haemofiltration, haemoperfusion, or antioxidant therapy may also be suggested.[56] Immunosuppressive therapy to reduce the inflammation is an approach suggested by some, however only low certainty evidence supports using medications such as