Editing Parathion

{{chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 431610740
| Name = Parathion
| ImageFile=Methyl&Ethylparathion.png
| ImageFile1=Ethyl-parathion-from-AHRLS-2011-3D-balls.png
| PIN = ''O'',''O''-Diethyl ''O''-(4-nitrophenyl) phosphorothioate
| OtherNames = E605
|Section1={{Chembox Identifiers
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 27928
| SMILES = S=P(Oc1ccc(cc1)[N+]([O-])=O)(OCC)OCC
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 13844817
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 61G466064D
| InChI = 1/C10H14NO5PS/c1-3-14-17(18,15-4-2)16-10-7-5-9(6-8-10)11(12)13/h5-8H,3-4H2,1-2H3
| InChIKey = LCCNCVORNKJIRZ-UHFFFAOYAR
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 261919
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C10H14NO5PS/c1-3-14-17(18,15-4-2)16-10-7-5-9(6-8-10)11(12)13/h5-8H,3-4H2,1-2H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = LCCNCVORNKJIRZ-UHFFFAOYSA-N
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 56-38-2
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C06604
| PubChem = 991
| RTECS = TF4550000
| EC_number = 200-271-7
| UNNumber = 3018 2783
| Beilstein = 2059093
  }}
|Section2={{Chembox Properties
| C=10 | H=14 | N=1 | O=5 | P=1 | S=1
| Appearance = White crystals (pure form)
| Solubility = 24 mg/L
| SolubleOther = high solubility in [[xylene]] and [[1-Butanol|butanol]]
| Solvent = other solvents
| MeltingPtC = 6
  }}
|Section7={{Chembox Hazards
| ExternalSDS = [https://www.cdc.gov/niosh/ipcsneng/neng0006.html]
| NFPA-H = 4
| NFPA-F = 1
| NFPA-R = 2
| NFPA-S = 
| FlashPtC = 120
| GHSPictograms = {{GHS06}}{{GHS08}}{{GHS09}}
| GHSSignalWord = Danger
| HPhrases = {{H-phrases|300|311|330|372|410}}
| PPhrases = {{P-phrases|260|264|270|271|273|280|284|301+310|302+352|304+340|310|312|314|320|321|322|330|361|363|391|403+233|405|501}}
| PEL = none (methyl parathion),<ref name=PGCH|0427>{{PGCH|0427}}</ref> TWA 0.1 mg/m<sup>3</sup> [skin] (ethyl parathion)<ref name=PGCH|0479/>
| REL = TWA 0.2 mg/m<sup>3</sup> [skin] (methyl parathion)<ref name=PGCH|0427/> TWA 0.05 mg/m3 [skin] (ethyl parathion)<ref name=PGCH|0479/>
| IDLH = N.D. (methyl parathion)<ref name=PGCH|0427/> 10 mg/m<sup>3</sup> (ethyl parathion)<ref name=PGCH|0479>{{PGCH|0479}}</ref>
| LCLo = 50 mg/m<sup>3</sup> (rabbit, 2 hr)<br/>14 mg/m<sup>3</sup> (guinea pig, 2 hr)<br/>15 mg/m<sup>3</sup> (mouse)<ref name=IDLH>{{IDLH|56382|Parathion}}</ref>
| LC50 = 84 mg/m<sup>3</sup> (rat, 4 hr)<ref name=IDLH/>
| LD50 = 5 mg/kg (mouse, oral)<br/>10 mg/kg (rabbit, oral)<br/>3 mg/kg (dog, oral)<br/>0.93 mg/kg (cat, oral)<br/>5 mg/kg (horse, oral)<br/>8 mg/kg (guinea pig, oral)<br/>2 mg/kg (rat, oral)<ref name=IDLH/>
  }}<ref>{{cite web |url=http://www.ehs.neu.edu/laboratory_safety/general_information/nfpa_hazard_rating/documents/NFPAratingJR.htm |title=Hazard Rating Information for NFPA Fire Diamonds |access-date=2015-03-13 |url-status=dead |archive-url=https://web.archive.org/web/20150217114741/http://www.ehs.neu.edu/laboratory_safety/general_information/nfpa_hazard_rating/documents/NFPAratingJR.htm |archive-date=2015-02-17 }}</ref>
}}

'''Parathion''', also called '''parathion-ethyl''' or '''diethyl parathion''', is an [[organophosphate]] [[insecticide]] and [[acaricide]]. It was originally developed by [[IG Farben]] in the 1940s. It is highly toxic to non-target organisms, including humans, so its use has been banned or restricted in most countries. In response to safety concerns, the less toxic but still dangerous analogue [[parathion methyl]] was later developed.<ref>{{Cite web|url=http://www.fao.org/3/w5715e/w5715e05.htm|title=Parathion|website=www.fao.org|access-date=2020-04-17}}</ref>

==History==
[[File:E605-forte.jpg|thumb|Bottle with E605]]
Parathion was developed by [[Gerhard Schrader]] for the German trust [[IG Farben]] in the 1940s.  After [[World War II]] and the collapse of IG Farben due to the war crime trials, the Western allies seized the [[patent]], and parathion was marketed worldwide by different companies and under different brand names. The most common German brand was '''E605''' (banned in Germany after 2002); this was not a food-additive "[[E number]]" as used in the EU today. "E" stands for ''Entwicklungsnummer'' (German for "development number").  It is an irreversible [[acetylcholinesterase inhibitor]].

Safety concerns later led to the development of [[parathion methyl]], which is somewhat less toxic.

In the [[EU]], Parathion was banned after 2001. <ref> [https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32001D0520&from=DE Non-inclusion of parathion in Annex I to Council Directive 91/414/EEC]</ref> In [[Switzerland]], the substance is no longer approved as a pesticide.

==Handling properties==
Pure parathion is a white crystalline solid. It is commonly distributed as a brown [[liquid]] that smells of rotting [[Egg (food)|egg]]s or [[garlic]]. The insecticide is somewhat stable, although it darkens when exposed to sunlight.

==Industrial synthesis==
Parathion is synthesized from [[diethyl dithiophosphoric acid]] {{chem2|(C2H5O)2PS2H}} by [[Chlorination reaction|chlorination]] to generate diethylthiophosphoryl chloride ({{chem2|(C2H5O)2P(S)Cl}}), and then the chloride is treated with [[sodium 4-nitrophenolate]] (the [[sodium]] [[salt (chemistry)|salt]] of [[4-Nitrophenol|4-nitrophenol]]).<ref name = fee>{{cite book |last1=Fee |first1=D. C. |last2=Gard |first2=D. R. |last3=Yang |first3=C. |chapter=Phosphorus Compounds |title=Kirk-Othmer Encyclopedia of Chemical Technology |publisher=John Wiley & Sons |location=New York |year=2005 |doi=10.1002/0471238961.16081519060505.a01.pub2 |isbn=978-0471238966 }}</ref>

:{{chem2|2 (C2H5O)2P(S)SH + 3 Cl2 → 2 (C2H5O)2P(S)Cl + S2Cl2 + 2 HCl}}
:{{chem2|(C2H5O)2P(S)Cl + NaOC6H4NO2 → (C2H5O)2P(S)OC6H4NO2 + NaCl}}

==Applications==
As a pesticide, parathion is generally applied by spraying.  It is often applied to [[cotton]], [[rice]] and [[fruit]] trees. The usual concentrations of ready-to-use solutions are 0.05 to 0.1%. The chemical is banned for use on many food crops.

==Insecticidal activity==
Parathion acts on the enzyme [[acetylcholinesterase]] indirectly.  After an insect (or a human) ingests parathion, an [[oxidase]] replaces the double bonded sulfur with oxygen to give [[paraoxon]].<ref name = metcalf>{{cite book |last=Metcalf |first=R. L. |chapter=Insect Control |title=Ullmann's Encyclopedia of Industrial Chemistry |publisher=Wiley-VCH Verlag GmbH & Co. KGaA |location=New York |year=2002 |doi=10.1002/14356007.a14_263 |isbn=978-3527306732 }}</ref>

:{{chem2|(C2H5O)2P(S)OC6H4NO2 + 1/2 O2 → (C2H5O)2P(O)OC6H4NO2 + S}}

The phosphate ester is more reactive in organisms than the phosphorothiolate ester, as the phosphorus atoms become much more electropositive.<ref name = metcalf/>

Parathion {{visible anchor|Resistance|text=resistance}} is a special case of [[acetylcholinesterase inhibitor resistance]].

==Degradation==
Degradation of parathion leads to more water-soluble products.  [[Hydrolysis]], which deactivates the molecule, occurs at the [[aryl ester]] bond resulting in [[diethyl thiophosphate]] and [[4-nitrophenol]].<ref name = metcalf/>
:{{chem2|(C2H5O)2P(S)OC6H4NO2 + H2O → HOC6H4NO2 + (C2H5O)2P(S)OH}}
Degradation proceeds differently under [[Hypoxia (environmental)|anaerobic]] conditions: the nitro group on parathion is reduced to the [[amine]].
:{{chem2|(C2H5O)2P(S)OC6H4NO2 + 6 H → (C2H5O)2P(S)OC6H4NH2 + 2 H2O}}

==Safety==
Parathion is a [[cholinesterase inhibitor]]. It generally disrupts the [[nervous system]] by inhibiting [[acetylcholinesterase]]. It is absorbed via skin, mucous membranes, and orally. Absorbed parathion is rapidly metabolized to paraoxon, as described in [[Parathion#Insecticidal activity|Insecticidal activity]]. Paraoxon exposure can result in [[headache]]s, [[convulsions]], poor vision, [[vomiting]], abdominal pain, severe [[diarrhea]], [[unconsciousness]], [[tremor]], [[dyspnea]], and finally [[pulmonary edema]] as well as respiratory arrest.  Symptoms of poisoning are known to last for extended periods, sometimes months. The most common and very specific antidote is [[atropine]], in doses of up to 100&nbsp;mg daily. Because atropine may also be toxic, it is recommended that small frequently repeated doses be used in treatment. If human poisoning is detected early and the treatment is prompt (atropine and artificial respiration), fatalities are infrequent. Insufficient oxygen will lead to [[cerebral hypoxia]] and permanent brain damage.  [[Peripheral neuropathy]] including [[paralysis]] is noticed as late [[sequelae]] after recovery from acute intoxication. Parathion and related organophosphorus pesticides are used in hundreds of thousands of poisonings annually, especially suicides.<ref>Litchfield, M.H. "Estimates of acute pesticide poisoning in agricultural workers in less developed countries" Toxicology Reviews 2005, volume 24, pp. 271-8. {{PMID|16499408}}</ref> It is known as ''Schwiegermuttergift'' (mother-in-law poison) in Germany. For this reason, most formulations contain a blue dye providing warning.

Parathion was used as a [[chemical warfare]] agent, most notably by an element of the [[British South Africa Police#Composition|British South Africa Police]] attached to the [[Selous Scouts#Composition|Selous Scouts]] during the [[Rhodesian Bush War]]. They used it to poison clothing that was then supplied to anti-government guerrillas. When the enemy soldiers put on the clothes, they were poisoned by absorption through the skin.<ref>{{Cite web|url=https://openaccess.leidenuniv.nl/bitstream/handle/1887/68698/Poison%20in%20Rhodesia%2C%20Colm%20Wittenberg.pdf?sequence=1|title = Poison in Rhodesia|date = 31 January 2019}}</ref><ref>{{Cite web|url=http://cco.ndu.edu/News/Article/1506904/dirty-war-rhodesia-and-chemical-biological-warfare-1975-1980-book-review/|title=Dirty War: Rhodesia and Chemical Biological Warfare 1975-1980 (Book Review)|website=PRISM &#124; National Defense University}}</ref><ref>{{cite book|title=Dirty War: Rhodesia and Chemical Biological Warfare, 1975–1980|last=Cross|first=Glenn|year=2017|location=Solihull, UK|publisher=Helion & Company|isbn=978-1-911512-12-7}}</ref>

Based on animal studies, parathion is considered by the [[United States Environmental Protection Agency|U.S. Environmental Protection Agency]] to be a possible human [[carcinogen]].<ref name=epa>{{cite web | title = Parathion | work = Integrated Risk Information System | publisher = [[U. S. Environmental Protection Agency]] | date = 26 January 2007 | url = http://www.epa.gov/iris/subst/0327.htm}}</ref> Studies show that parathion is toxic to fetuses, but does not cause birth defects.<ref name = extoxnet>{{cite web | work = Extension Toxicology Network | title = Pesticide Information Profiles - Parathion | publisher = [[Oregon State University]] |date=September 1993 | url = http://extoxnet.orst.edu/pips/parathio.htm}}</ref>

It is classified by the [[United Nations Environment Programme]] as a [[persistent organic pollutant]]{{cn|date=February 2018}} and by the [[World Health Organization]] as [[toxicity class|Toxicity Class Ia]] (extremely hazardous).{{cn|date=February 2018}}

Parathion is toxic to [[bees]], [[fish]], [[bird]]s, and other forms of wildlife.<ref name = extoxnet/>

===Protection against poisoning===
To provide the end user with a minimum standard of protection, suitable protective gloves, clothing, and a respirator with organic-vapour cartridges is normally worn. [[Industrial safety]] during the production process requires special ventilation and continuous measurement of air contamination in order not to exceed PEL levels, as well as careful attention to personal hygiene. Frequent analysis of workers' serum acetylcholinesterase activity is also helpful with regards to occupational safety, because the action of parathion is cumulative. Also, atropine has been used as a specific antidote.{{fact|date=January 2024}}

=== Use in suicides ===
A chemist {{who?|date=March 2024}} swallowed {{convert|.00424|oz|g}} of parathion {{when?|date=March 2024}} to find the most lethal means of exposure to humans, intending to take an antidote afterwards, but was paralyzed and so died before he could reach it.<ref name=":0">{{Cite book |last=Carson |first=Rachel |url=http://worldcat.org/oclc/1346358856 |title=Silent Spring |publisher= HarperCollins|year=1962 |isbn=978-0-547-52762-8 |oclc=1346358856}}</ref>

Parathion was commonly used for suicides in the 1950s and 1960s.<ref name=":0" />

==See also==
* [[Pesticide toxicity to bees]]
* [[Parathion methyl]]

==References==
{{reflist}}

==External links==
* {{PPDB|506}}
* [http://www.atsdr.cdc.gov/risk/methyl_parathion/ ATSDR - Methyl Parathion Expert Panel Report] U.S. [[Department of Health and Human Services]] (public domain)
* [https://www.cdc.gov/niosh/npg/npgd0479.html CDC - NIOSH Pocket Guide to Chemical Hazards] U.S. [[Department of Health and Human Services]] (public domain)
* Ethyl parathion: {{ICSC|0006}}
* Methyl parathion: {{ICSC|0626}}

{{Insecticides}}
{{Acetylcholine metabolism and transport modulators}}
{{Authority control}}

[[Category:Obsolete pesticides]]
[[Category:Organophosphate insecticides]]
[[Category:Acetylcholinesterase inhibitors]]
[[Category:Organothiophosphate esters]]
[[Category:4-Nitrophenyl compounds]]
[[Category:IARC Group 2B carcinogens]]
[[Category:Phenol esters]]
[[Category:Ethyl esters]]