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	{{Chembox		{{Chembox
			| Watchedfields = changed
	| verifiedrevid = 430760129
			| verifiedrevid = 443409794
	| ImageFile = Azinphos-methyl-2D-skeletal.png
			| ImageFile = Azinphos-methyl-2D-skeletal V1.svg
	| ImageFile_Ref = {{chemboximage|correct|??}}		| ImageFile_Ref = {{chemboximage|correct|??}}
	| ImageSize = 244		| ImageSize = 244
	| ImageName = Kekulé, skeletal formula of azinphos-methyl		| ImageAlt = Kekulé, skeletal formula of azinphos-methyl
			| ImageFile1 = Azinphos-methyl-3D-balls.png
	| IUPACName = ''O'',''O''-Dimethyl ''S''-dithiophosphate{{Citation needed|date = May 2011}}
			| ImageAlt1 = Ball-and-stick model of the azinphos-methyl molecule
	| OtherNames = Guthion
			| ImageFile2 = Azinphos-methyl-3D-spacefill.png
	| Section1 = {{Chembox Identifiers
			| ImageAlt2 = Space-filling model of the azinphos-methyl molecule
	| Abbreviations = AZM
			| PIN = ''O'',''O''-Dimethyl ''S''- phosphorodithioate
	| CASNo = 86-50-0
			| OtherNames = Guthion, azinphosmethyl, azinphos
	| CASNo_Ref = {{cascite|correct|CAS}}
			|Section1={{Chembox Identifiers
	| PubChem = 2268
			| Abbreviations = AZM
	| PubChem_Ref = {{Pubchemcite|correct|pubchem}}
			| CASNo = 86-50-0
	| ChemSpiderID = 2181
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}		| CASNo_Ref = {{cascite|correct|CAS}}
	| EINECS = 201-676-1		| PubChem = 2268
	| UNNumber = 2811		| ChemSpiderID = 2181
			| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
	| KEGG = C11018
			| EINECS = 201-676-1
	| KEGG_Ref = {{keggcite|correct|kegg}}
			| UNNumber = 2811
	| MeSHName = Azinphosmethyl
	| ChEBI = 2953		| KEGG = C11018
			| KEGG_Ref = {{keggcite|correct|kegg}}
	| ChEMBL = 530115
			| MeSHName = Azinphosmethyl
	| ChEMBL_Ref = {{ebicite|correct|EBI}}
			| ChEBI_Ref = {{ebicite|correct|EBI}}
	| RTECS = TE1925000
	| Beilstein = 280476		| ChEBI = 2953
	| UNII = 265842EWUV		| ChEMBL = 530115
			| ChEMBL_Ref = {{ebicite|correct|EBI}}
	| SMILES = COP(=S)(OC)SCn1nnc2ccccc2c1:o
			| RTECS = TE1925000
	| SMILES1 = COP(=S)(OC)SCN1N=NC2=CC=CC=C2C1=O
			| Beilstein = 280476
	| SMILES2 = O=C2N(CSP(OC)(OC)=S)N=NC1=CC=CC=C12
			| UNII_Ref = {{fdacite|correct|FDA}}
	| StdInChI = 1S/C10H12N3O3PS2/c1-15-17(18,16-2)19-7-13-10(14)8-5-3-4-6-9(8)11-12-13/h3-6H,7H2,1-2H3
			| UNII = 265842EWUV
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
			| SMILES = COP(=S)(OC)SCn1nnc2ccccc2c1=O
	| StdInChIKey = CJJOSEISRRTUQB-UHFFFAOYSA-N
			| SMILES1 = COP(=S)(OC)SCN1N=NC2=CC=CC=C2C1=O
	| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
			| SMILES2 = O=C2N(CSP(OC)(OC)=S)N=NC1=CC=CC=C12
			| StdInChI = 1S/C10H12N3O3PS2/c1-15-17(18,16-2)19-7-13-10(14)8-5-3-4-6-9(8)11-12-13/h3-6H,7H2,1-2H3
			| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
			| StdInChIKey = CJJOSEISRRTUQB-UHFFFAOYSA-N
			| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
	}}		}}
	| Section2 = {{Chembox Properties		|Section2={{Chembox Properties
	| Formula = {{Chem|C|10|PN|3|H|12|S|2|O|3}}		| C=10 | H=12 | N=3 | O=3 | P=1 | S=2
			| Appearance = Pale, dark orange, translucent crystals
	| MolarMass = 317.324 g mol<sup>-1</sup>
	| ExactMass = 317.005769157 g mol<sup>-1</sup>		| Density = 1.44 g cm<sup>−3</sup>
			| MeltingPtK = 346
	| Appearance = Pale, dark orange, translucent crystals
			| BoilingPt = >
	| Density = 1.44 g cm<sup>-3</sup>
	| MeltingPtK = 346		| BoilingPtC = 200
			| BoilingPt_notes = (decomposes)
	| BoilingPt = >200 °C
			| Solubility = 28 mg dm<sup>−3</sup>
	| Boiling_notes = decomposes
			| LogP = 2.466
	| Solubility = 28 mg dm<sup>-3</sup>
			| VaporPressure = 8 x 10<sup>−9</sup> mmHg<ref name=PGCH/>
	| LogP = 2.466
	}}		}}
	| Section3 = {{Chembox Hazards		|Section3={{Chembox Hazards
	| ExternalMSDS =		| ExternalSDS =
	| GHSPictograms = {{GHS skull and crossbones}} {{GHS environment}}<ref name="sigma">{{SigmaLink		| GHSPictograms = {{GHS skull and crossbones}} {{GHS environment}}<ref name="sigma">{{Sigma-Aldrich|Sial|id=45333|name=Azinphos-methyl|accessdate=2022-03-17}}</ref>
			| GHSSignalWord = Danger
	| Productgroup = Fluka
			| HPhrases = {{H-phrases|300|311|317|330|410}}<ref name="sigma"/>
	| Productcode = 45333
			| PPhrases = {{P-phrases|260|264|273|280|284|301+310}}<ref name="sigma"/>
	| Accessdate = May 22, 2011}}</ref>
			| NFPA-H = 3
	| GHSSignalWord = Danger
			| NFPA-R = 1
	| HPhrases = {{H-phrases|300|311|317|330|410}}<ref name="sigma" />
			| NFPA-F = 2
	| PPhrases = {{P-phrases|260|264|273|280|284|301+310}}<ref name="sigma" />
			| FlashPtC = 69
	| EUIndex = 015-039-00-9
			| LC50 = 69 mg/m<sup>3</sup> (rat, 1 hr)<br/>79 mg/m<sup>3</sup> (rat, 1 hr)<ref name=IDLH>{{IDLH|86500|Azinphos-methyl}}</ref>
	| EUClass = {{Hazchem T+}} {{Hazchem N}}
			| LD50 = 16 mg/kg (rat, oral)<br/> 80 mg/kg (guinea pig, oral)<br/>11 mg/kg (rat, oral)<br/>13 mg/kg (rat, oral)<br/>8.6 mg/kg (mouse, oral)<br/>7 mg/kg (rat, oral)<br/>8 mg/kg (mouse, oral)<br/>10 mg/kg (dog, oral)<ref name=IDLH/>
	| RPhrases = {{R24}}, {{R26/28}}, {{R43}}, {{R50/53}}
			| NIOSH_ref = <ref name=PGCH>{{PGCH|0681}}</ref>
	| SPhrases = {{S1/2}}, {{S28}}, {{S36/37}}, {{S45}}, {{S60}}, {{S61}}
			| PEL = TWA 0.2 mg/m<sup>3</sup>
	| NFPA-H = 3
			| REL = TWA 0.2 mg/m<sup>3</sup>
	| NFPA-R = 1
			| IDLH = 10 mg/m<sup>3</sup>
	| NFPA-F = 2
	| FlashPt = 69 °C
	}}		}}
	| Section4 = {{Chembox Related		|Section4={{Chembox Related
	| Function = ]s		| OtherFunction_label = ]s
	| OtherFunctn = ]<br />		| OtherFunction = ]<br />
	]		]
	}}		}}
	}}		}}
	'''Azinphos-methyl''' (Guthion) is a broad spectrum ] ] manufactured by ], Gowan Co., and ].<ref name="EPA">{{dead link|date=January 2011}}</ref> Like other ]s in this class, it owes its insecticidal properties (and human toxicity) to the fact that it is an ] ].		'''Azinphos-methyl''' (Guthion) (also spelled azinophos-methyl) is a broad spectrum ] ] manufactured by ], Gowan Co., and ].<ref name=Tox1>{{cite journal|title=EPA's Interrum Reregistration Eligibility Decision for Azinphos-methyl.}}</ref> Like other ]s in this class, it owes its insecticidal properties (and human toxicity) to the fact that it is an ] ] (the same mechanism is responsible for the toxic effects of the ] ] ]s). It is classified as an ] in the United States as defined in Section 302 of the U.S. ] (42 U.S.C. 11002), and is subject to strict reporting requirements by facilities which produce, store, or use it in significant quantities.<ref name="gov-right-know">{{Cite journal | publisher = ] | title = 40 C.F.R.: Appendix A to Part 355—The List of Extremely Hazardous Substances and Their Threshold Planning Quantities | url = http://edocket.access.gpo.gov/cfr_2008/julqtr/pdf/40cfr355AppA.pdf | edition = July 1, 2008 | access-date = October 29, 2011 | archive-url = https://web.archive.org/web/20120225051612/http://edocket.access.gpo.gov/cfr_2008/julqtr/pdf/40cfr355AppA.pdf | archive-date = February 25, 2012 | url-status = dead }}</ref>
	==History and uses==		== History and uses ==
	Azinphos-methyl is a ] derived from nerve agents developed during World War II. In the US, it is registered for use on select nut trees, vegetable crops, and fruit trees. It is not registered for consumer or residential use. It has been linked to health problems of farmers who apply it, and the U.S. ] (EPA) considered a denial of reregistration, citing, “concern to farm workers, pesticide applicators, and aquatic ecosystems".<ref name="EPA"/> After settling a 2004 lawsuit brought by the ] and other groups, the EPA accounced it would begin phasing out the remaining uses of the pesticide in 2007 with all uses ending in 2012. In January 2007, the suit was reopened, with the plaintiffs seeking a quicker phaseout.<ref></ref>		Azinphos-methyl is a ] derived from nerve agents developed during World War II.<ref name=Tox1/> It was first registered in the US in 1959 as an insecticide and is also used as active ingredient in organophosphate (OP) pesticides.<ref name=Tox2>{{cite book|last1=Gungordu,A |author2=Uckun, M|title=Comparative assessment of in vitro and in vivo toxicity of azinphos methyl and its commercial formulation.|date=2014|publisher=Environ Toxicol}}</ref> It is not registered for consumer or residential use. It has been linked to health problems of farmers who apply it, and the U.S. Environmental Protection Agency (EPA) considered a denial of reregistration, citing, “concern to farm workers, pesticide applicators, and aquatic ecosystems.<ref name=Tox1/> The use of AZM has been fully banned in the USA since 30 September 2013, ending a phase-out period of twelve years.<ref name=Tox3>{{cite web|url=http://www.epa.gov/pesticides/reregistration/azm/phaseout_fs.htm.|title=EPA's Azinphos-methyl Page|access-date=15 April 2015}}</ref>
			Azinphos-methyl has been banned in the ] since 2006<ref>{{cite news |url=http://www.chemweek.com/envirotech/regulatory/13435.html |title=Europe Rejects Appeal for Use of Azinphos-methyl Pesticide |last=Scott |first=Alex |date=August 4, 2008 |publisher=Chemical Week |access-date=2008-08-11}}</ref> and in Turkey since 2013.<ref name=Tox2/>
			The New Zealand ] made a decision to phase out azinphos-methyl over a five-year period starting from 2009.<ref> {{webarchive |url=https://web.archive.org/web/20100131054046/http://www.ermanz.govt.nz/news-events/archives/media-releases/2009/mr-20091106.html |date=January 31, 2010 }} - press release</ref> In 2014, it was still used in Australia and partly in New Zealand.<ref name=Tox2/>
			== Available forms ==
	Azinphos-methyl has been banned in the ] since 2006.<ref>{{cite news|url=http://www.chemweek.com/envirotech/regulatory/13435.html|title=Europe Rejects Appeal for Use of Azinphos-methyl Pesticide|last=Scott|first=Alex|date=August 4, 2008|publisher=Chemical Week|accessdate=2008-08-11}}</ref>
			AzM is often used as active ingredient in organophosphate pesticides like Guthion, Gusathion (GUS), Gusathion-M, Crysthyron, Cotnion, Cotnion-methyl, Metriltrizotion, Carfene, Bay 9027, Bay 17147, and R-1852. This is why Guthion is often used as a nickname for AzM.
			Studies have shown that pure AzM is less toxic than GUS. This increased toxicity can be explained by the interactions between the different compounds in the mixture.<ref name=Tox2/>
			== Synthesis ==
	The New Zealand ] made a decision to phase out azinphos-methyl over a five year period starting from 2009.<ref> - press release</ref>
			The synthesis (in this case, of carbon-14-labelled material) can be seen in figure 1. In the first step, ] (compound 1) is purified through dissolution in hot water-ethanol mixture in relation 2:1. is added and the result is filtrated for clarifying. The filtrate is chilled while kept in movement to generate crystals, usually at 4&nbsp;°C, but if needed it can also be cooled to -10&nbsp;°C. The crystals are then collected, washed and dried. If it is pure enough it is used for the following steps, which take place at 0 till 5&nbsp;°C.
			To produce ] (compound 2), the first component o-nitroaniline and (concentrated reagent grade) ] are put together with ice and water. ], dissolved in water, is added to this thin slurry. After the formation of a pale-yellow solution, which indicates the completion of the ] reaction, the pH should be adjusted to 6. After this, the solution is introduced to a mixture of ] and ]. At room temperature the toluene layer is removed. The aqueous layer is washed and dried and the purified product is isolated by crystallization.
			The third product is ] (compound 3). It is formed out of o-Nitrobenzonitrile-14C, which is first solved in ethanol and ]. The solvent is heated subsequently, treated in a well-ventilated hood with small periodic charges, smaller than 10&nbsp;mg, of ]. Under nitrogen atmosphere the ethanolic solution is clarified and dried.
			The next step is to form ] (compound 4). In water dissolved sodium nitrite is added to ] and hydrochloric acid in ice water. Because this is a diazotization reaction, the product is pale-yellow again. After this the pH is adjusted to 8,5. This causes the ring closure to form 1,2,3-Benzotriazin-4(3H)-one-14C. This results in a sodium salt slurry that can be treated with hydrochloric acid, what lowers the pH down to 2 till 4. The 1,2,3-Benzotriazin-4(3H)-one-14C is collected, washed and dried.
			In the following step ] has to be formed. Therefore, 1,2,3-Benzotriazin-4(3H)-one-14C and ] are added to ] and heated to 40&nbsp;°C. Then ] is added and the whole solvent is further heated to 65&nbsp;°C. After four hours of heating the solution is cooled down to room temperature. Water is added and the solution is neutralized. The ethylene dichloride layer is removed and put together with the result of the washed aqueous layer. The solvent was filtered and dried. The last step is the actual synthesis of Azinphos methyl. Ethylene dichloride is added to the compound resulting from the fifth step, 1,2,3-Benzotriazin-4-(3-chloromethyl)-one-14C. This mixture is heated to 50&nbsp;°C and ] and O,O-dimethyl phosphorodithioate sodium salt in water are added. The ethylene dichloride layer is removed, reextracted with ethylene dichloride and purified by filtration. The pure filtrate is dried. This product is once again purified by recrystallization from methanol. What is left is pure azinphos-methyl in form of white crystals.<ref name=Tox6>{{cite journal|last1=White|first1=E.R.|title=Synthesis of carbon-14-benzenoidring-labeled Guthion.|journal=Journal of Agricultural and Food Chemistry|date=1972|volume=20 | issue = 6 |pages=1184–1186|doi=10.1021/jf60184a037}}</ref>
	==See also==		== Absorption ==
			Azinphos-methyl can enter the body via inhalation, ingestion and dermal contact.<ref name=Tox7>{{cite book|author=Roney.N., C.S.|author2=Stevens. Y.W.|author3=Quinones-Rivera.A.|author4=Wohlers.D|author5= Citra.M.|title=Toxicological Profile For Guthion.|date=2008|publisher=U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES}}</ref> Ingestion of azinphos-methyl is responsible for the low-dose exposure to a large part of the population, due to their presence as residues in food and drinking water. After ingestion it can be absorbed from the digestive tract.<ref name=Tox8>{{cite journal|last1=Buratti|first1=F.M.|title=CYP-specific bioactivation of four organophosphorothioate pesticides by human liver microsomes.|date=2003|journal=Toxicol Appl Pharmacol|pages=143–154|volume=186 | issue = 3|doi=10.1016/s0041-008x(02)00027-3|pmid=12620367 }}</ref> By skin contact, AzM can also enter the body through ].<ref name=Tox7/> Absorption through the skin is responsible for the occupational exposure to relatively high doses, mainly in agriculture workers.<ref name=Tox8/>
			== Mechanism of toxicity ==
			Once azinphos-methyl is absorbed it can cause neurotoxic effects, like other organophosphate insecticides.<ref name=Tox9>{{cite journal|author1=Carrier, G. |author2=R.C. Brunet|title=A toxicokinetic model to assess the risk of azinphosmethyl exposure in humans through measures of urinary elimination of alkylphosphates.|date=1999|journal=Toxicol Sci|pages=23–32|volume=47 | issue = 1|doi=10.1093/toxsci/47.1.23|pmid=10048150 |doi-access=}}</ref> At high concentrations AzM itself can be toxic because it can function as an ] (AChE) inhibitor. But its toxicity is mainly due to the bioactivation by a ] (CYP450)-mediated desulfuration to its phosphate triester or oxon(gutoxon) (see figure 2).<ref name=Tox8/> Gutoxon can react with a ] hydroxyl group at the active site of the AChE. The active site is then blocked and AChE is inactivated. Under normal circumstances acetylcholinesterase rapidly and efficiently degrades the neurotransmitter acetylcholine (ACh) and thereby terminates the biological activity of acetylcholine. Inhibition of AChE results in an immediate accumulation of free unbound ACh at the ending of all ], which leads to overstimulation of the nervous system.<ref name=Tox9/>
			== Efficacy and side effects ==
			Cholinergic nerves play an important role in the normal function of the central nervous, endocrine, neuromuscular, immunological, and respiratory system. As all cholinergic fibers contain high concentrations of ACh and AChE at their terminals, inhibition of AChE can impair their function. So exposure to azinphosmethyl, whereas it inhibits AChEs, may disturb a lot of important systems and may have various effects.<ref name=Tox7/><ref name=Tox9/>
			In the autonomic nervous system, accumulation of acetylcholine leads to the overstimulation of muscarinic receptors of the ]. This can affect exocrine glands (increased ], ], ]), the respiratory system (excessive ] secretions, tightness of the chest, and wheezing), the gastrointestinal tract (nausea, vomiting, diarrhea), the eyes (], blurred vision) and the cardiovascular system (decrease in blood pressure, and ]). Overstimulation of the nicotinic receptors in the para- or sympathetic nervous system may also cause adverse effects on the cardiovascular system, such as pallor, tachycardia and increased blood pressure. In the somatic nervous system, accumulation of acetylcholine may cause muscle fasciculation, paralysis, cramps, and flaccid or rigid tone. Overstimulation of the nerves in the central nervous system, specifically in the brain, may result in drowsiness, mental confusion and lethargy. More severe effects on the central nervous system include a state of coma without reflexes, cyanosis and depression of the respiratory centers.<ref name=Tox10>{{cite book|author=Klaassen CD |author2=A.M., Doull J|title=Toxic effects of pesticides, in Casarett and Doull's toxicology: The basic science of poisons.|date=1995|publisher=McGraw-Hill Companies: New York.|pages=643–689}}</ref> Thus the inhibition of the enzyme AChE may have a lot of different effects.
			== Detoxification ==
			To prevent the toxic effects, AzM can be biotransformed.
			Although AzM (in figure 2 named guthion) can be bioactivated by a cytochrome P450 (CYP450)-mediated desulfuration to its phosphate triester or oxon (gutoxon), it may also be detoxified by CYP itself (reaction 2 in figure 2).<ref name=Tox8/> CYP450 is namely able to catalyze the oxidative cleavage of the P-S-C bond in AzM to yield ] and ].
			The other pathways of detoxification involves glutathione (GSH)-mediated dealkylation via cleavage of the P-O-CH3 bond, which than forms mono-demethylated AzM and GS-CH3 (reaction 3 in figure 2). This mono-demethylated AzM may be further demethylated to di-demethylated AzM and again GS-CH3 (reaction 4 in figure 2).
			AzM also may undergo glutathione-catalyzed dearylation which forms ] and glutathione-conjugated mercaptomethyl benzazimide (reaction 5 in figure 2)
			Gutoxon, the compound that mainly causes AzM to be toxic, can also be detoxified. Gutoxon can again be detoxified with the help of CYP450. CYP450 catalyzes the oxidative cleavage of gutoxon, which than yields ] and MMBA (reaction 6 in figure 2). Other detoxification pathways of gutoxon are via glutathione-mediated dealkylation, which goes via cleavage of the P-O-CH3 bond to form demethylated AzM and GS-CH3 (reaction 7 in figure 2), and via glutathione-catalyzed dearylation to yield DMTP and glutathione-conjugated mercaptomethyl benzazimide (reaction 8 in figure 2).<ref name=Tox11>{{cite journal|author1=Levine, B.S. |author2=S.D. Murphy|title=Effect of piperonyl butoxide on the metabolism of dimethyl and diethyl phosphorothionate insecticides.|date=1977|journal=Toxicol Appl Pharmacol|pages=393–406|volume=40 | issue = 3|doi=10.1016/0041-008x(77)90067-9|pmid=882978 }}</ref><ref name=Tox12>{{cite journal|author1=Sultatos, L.G. |author2=L. Woods|title=The role of glutathione in the detoxification of the insecticides methyl parathion and azinphos-methyl in the mouse.|date=1988|journal=Toxicol Appl Pharmacol|pages=168–174|volume=96 | issue = 1|doi=10.1016/0041-008x(88)90259-1|pmid=3188022 }}</ref><ref name=Tox13>{{cite book|author=Motoyama N, D.W.|title=The in vitro metabolism of azinphosmethyl by mouse liver.|date=1972|publisher=Pesticide Biochemistry and Physiology|pages=170–177}}</ref>
			== Treatment ==
			There are two different main mechanism of treatment for toxification with AzM. One possibility is to treat the patient before exposure to AzM and the other one is to treat the patient after poisoning.
			]s of AChE can be used for pre-treatment. They can reduce mortality, which is caused by exposure to AzM.<ref name=Tox14>{{cite book|author=Petroianu, G.A|title=Reversible cholinesterase inhibitors as pre-treatment for exposure to organophosphates: assessment using azinphos-methyl.|date=2014|publisher=J Appl Toxicol}}</ref> Organophosphorus AChE inhibitors can bind temporally to the catalytic site of the enzyme. Because of this binding, AzM cannot phosphorylate the enzyme anymore and the enzyme is shorter inhibited.<ref name=Tox14/>
			The mechanism for treatment after exposure is to block the muscarinic receptor activation. ] are used to control the seizures and oximes are used to reactivate the inhibited AChE.<ref name=Tox14/> Oximes remove the phosphoryl group bound to the active site of the AChE by binding to it.<ref name=Tox15>{{cite journal|author=Iyer, R. |author2=B. Iken |author3=A. Leon|title=Developments in alternative treatments for organophosphate poisoning.|date=2015|journal=Toxicol Lett|pages=200–206|volume=233 | issue = 2|doi=10.1016/j.toxlet.2015.01.007|pmid=25595305 }}</ref>
			There are a few oximes that are the most efficacious by AzM poisoning, namely oxime K-27 and physostigmine.<ref name=Tox14/>
			These two treatments are also used together, some patients are namely treated with ] (a competitive antagonist of AChE) and reactivating oximes. When patients are resistant to atropine, the patients can be treated with low doses of ], a cholinergic and alpha-1 adrenergic antagonist, to achieve a shorter recovery time.<ref name=Tox15/>
			Treatment with a combination of different alkaloids or synergistically with atropine is safer than using high ] concentrations, which can be toxic.
			Another possibility is to use ] technology. When this technology is used, no other chemical compounds need to be added.<ref name=Tox16>{{cite journal|author=Ghoshdastidar, A.J.|title=Membrane bioreactor treatment of commonly used organophosphate pesticides.|date=2012|journal=J Environ Sci Health B|pages=742–750|volume=47 | issue = 7|doi=10.1080/03601234.2012.669334|pmid=22560038 |s2cid=11572803 }}</ref>
			In general, pretreatment is much more efficient than post-treatment.<ref name=Tox14/>
			== Indications (biomarkers) ==
			The most common biomarker for exposure to AzM is the inhibition of AChE. Also other esterase enzymes as CaE and ] are inhibited by AzM. In general AzM exposure can be better detected by AChE inhibition than CaE inhibition. In amphibians and also zebrafish, AChE is a more sensitive biomarker for low AzM exposure-levels.<ref name=Tox2/>
			As already mentioned in paragraph 7 “detoxification”, AzM can be metabolized into nontoxic dimethylated alkylphosphates (AP), with the help of CYP450 and glutathione. These APs are: ] (DM), dimethylthiophosphate (DMTP) and dimethyldithiophosphate (DMDTP). These three metabolites may be excreted into the urine and can be used as reliable biomarkers of exposure to AzM. However these metabolites are not specific to AzM, because other organophosphate pesticides might also be metabolized into the three alkylphosphates.
			The amount of erythrocyte acetylcholinesterase (RBE-AChE) in the blood can also be used as a biomarker of effect for AzM. According to Zavon (1965) RBC-AChE is the best indicator of AChE activity at the nerve synapse, because this closely parallels the level of AChE in the CNS and PNS. A depression of RBC-AChE will correlate with effects due to a rapid depression of AChE enzymes found in other tissues, this is due to the fact that both enzymes can be inhibited by AzM.<ref name=Tox9/>
			== Environmental degradation ==
			AzM is very stable when dissolved in acidic, neutral or slightly alkaline water but above pH11 it is rapidly hydrolyzed to ], ], and other chemicals. In natural water-rich environments microorganisms and sunlight cause AzM to break down faster, the half-life is highly variable depending on the condition, from several days to several months. Under the normal conditions, biodegradation and evaporation are the main routes of disappearance, after evaporation AzM has more exposure to UV-light, which causes ]. With little bioactivity and no exposure to UV light, it can reach half-lives of roughly a year.<ref name=Tox17>{{cite journal|author=Wauchope, R.D|title=The SCS/ARS/CES pesticide properties database for environmental decision-making.|date=1992|journal=Rev Environ Contam Toxicol|pages=1–155|volume=123|pmid=1732992 }}</ref>
			== Effect on animals ==
			Possible effects on animals are endocrine disruption, reproductive and immune dysfunction and cancer.<ref name=Tox18>{{cite journal|author=Cortes-Eslava, J|title=The role of plant metabolism in the mutagenic and cytotoxic effects of four organophosphorus insecticides in Salmonella typhimurium and in human cell lines.|date=2013|journal=Chemosphere|pages=1117–1125|volume=92 | issue = 9|doi=10.1016/j.chemosphere.2013.01.058|pmid=23434078}}</ref>
			A remarkable phenomenon that has been demonstrated in numerous animal studies is that repeated exposure to organophosphates causes the mammals to be less susceptible to the toxic effects of the AChE inhibitors, even though cholinesterase activities are not normal. This phenomenon is caused by the excess of agonists (ACh) within the synapse, ultimately leading to a down-regulation of cholinergic receptors. Consequently, a given concentration of ACh within the synapse causes fewer receptors to be available, which then causes a lower response.<ref name=Tox9/>
			Studies have shown that the AChEs in fish brains are more prone to ] than amphibian brains. This can be explained by the affinity for AzM and rate of phosphorylation of the enzymes. Frog brain AChE has for example a lower affinity for AzM and a slower rate of ] than fish brain AChE.<ref name=Tox2/>
			The effects on amphibians are “reduced size, ] bending, abnormal pigmentation, defective gut and gills, swimming in circles, body shortening, and impaired growth”.<ref name=Tox2/>
			In ], specifically the ], AzM modifies the ] assembly at high concentrations and can alter the deposition of the skeleton of the larva at low concentrations.<ref name="Tox 19">{{cite journal|author=Buono, S.|title=Toxic effects of pentachlorophenol, azinphos-methyl and chlorpyrifos on the development of Paracentrotus lividus embryos.|date=2012|journal=Ecotoxicology|pages=688–697|volume=21 | issue = 3|doi=10.1007/s10646-011-0827-6|pmid=22101977 |s2cid=22703287 }}</ref>
			In mice, AzM causes weight loss, inhibits brain cholinesterase (ChE) and lowers the food consumption of the mice. A decrease of 45-50% of brain ChE is lethal in mice.<ref name=Tox20>{{cite journal|author1=Meyers, S.M. |author2=J.O. Wolff|title=Comparative toxicity of azinphos-methyl to house mice, laboratory mice, deer mice, and gray-tailed voles.|date=1994|journal=Archives of Environmental Contamination and Toxicology|pages=478–482|volume=26 | issue = 4|doi=10.1007/bf00214150|pmid=8198427 |s2cid=38234684 }}</ref> Also in earthworms and rats, AzM decreases AChE activity.<ref name=Tox21>{{cite journal|author=Jordaan, M. |author2=S. Reinecke |author3=A. Reinecke|title=Acute and sublethal effects of sequential exposure to the pesticide azinphos-methyl on juvenile earthworms (Eisenia andrei).|date=2012|journal=Ecotoxicology|pages=649–661|volume=21 | issue = 3|doi=10.1007/s10646-011-0821-z|pmid=22086221 |s2cid=12930098 }}</ref><ref name=Tox22>{{cite journal|author=Kimmerle, G.|title=Subchronic inhalation toxicity of azinphos-methyl in rats.|date=1976|journal=Archives of Toxicology|pages=83–89|volume=35 | issue = 2|doi=10.1007/bf00372761|pmid=947316 |s2cid=1818533 }}</ref>
			In order to prevent stretching it too long, you may take a look at the following animal studies and their references:
			* ]<ref name=Tox23>{{cite journal|author=Kluver, N.|title=Toxicogenomic response of azinphos-methyl treated zebrafish embryos and implication for the development of predictive models for chronic (fish) toxicity.|date=2009|journal=Toxicology Letters|page=94|volume=189|doi=10.1016/j.toxlet.2009.06.284}}</ref>
			* Amphipod ], the earthworm ]<ref name=Tox24>{{cite journal|author=Jordaan, M.S. |author2=S.A. Reinecke |author3=A.J. Reinecke|title=Acute and sublethal effects of sequential exposure to the pesticide azinphos-methyl on juvenile earthworms (Eisenia andrei).|date=2012|journal=Ecotoxicology|pages=649–661|volume=21 | issue = 3|doi=10.1007/s10646-011-0821-z|pmid=22086221 |s2cid=12930098 }}</ref>
			* ]<ref name=Tox25>{{cite journal|author=Jordaan, M.S. |author2=S.A. Reinecke |author3=A.J. Reinecke|title=Biomarker responses and morphological effects in juvenile tilapia Oreochromis mossambicus following sequential exposure to the organophosphate azinphos-methyl.|date=2013|journal=Aquat Toxicol|pages=133–140|volume=144–145|doi=10.1016/j.aquatox.2013.10.007|pmid=24177216 }}</ref>
			* Frog ] and salamander ]<ref name=Tox26>{{cite journal|author=Nebeker, A.V.|title=Impact of guthion on survival and growth of the frog Pseudacris regilla and the salamanders Ambystoma gracile and Ambystoma maculatum.|date=1998|journal=Arch Environ Contam Toxicol|pages=48–51|volume=35 | issue = 1|doi=10.1007/s002449900347|pmid=9601918 |s2cid=7877744 }}</ref>
			* Toad ]<ref name=Tox27>{{cite journal|author=Ferrari, A|title=Effects of azinphos methyl and carbaryl on Rhinella arenarum larvae esterases and antioxidant enzymes.|date=2011|journal=Comp Biochem Physiol C|pages=34–39|volume=153 | issue = 1|doi=10.1016/j.cbpc.2010.08.003|pmid=20709623 }}</ref>
			* Rainbow trout ]<ref name=Tox28>{{cite journal|author=Ferrari, A. |author2=A. Venturino |author3=A.M. Pechen de D'Angelo|title=Muscular and brain cholinesterase sensitivities to azinphos methyl and carbaryl in the juvenile rainbow trout Oncorhynchus mykiss.|date=2007|journal=Comp Biochem Physiol C|pages=308–313|volume=146 | issue = 3|doi=10.1016/j.cbpc.2007.04.002|pmid=17509940 }}</ref>
			* Comparison between the toad ] and the rainbow trout ]<ref name=Tox29>{{cite journal|author=Ferrari, A.|title=Different susceptibility of two aquatic vertebrates (Oncorhynchus mykiss and Bufo arenarum) to azinphos methyl and carbaryl.|date=2004|journal=Comp Biochem Physiol C|pages=239–243|volume=139 | issue = 4|doi=10.1016/j.cca.2004.11.006|pmid=15683833 }}</ref>
			* Comparison between fish ] and ]<ref name=Tox30>{{cite journal|author=Morton, M.G|title=Acute and chronic toxicity of azinphos-methyl to two estuarine species, Mysidopsis bahia and Cyprinodon variegatus.|date=1997|journal=Arch Environ Contam Toxicol|pages=436–441|volume=32 | issue = 4|doi=10.1007/s002449900210|pmid=9175513 |s2cid=33618631 }}</ref>
			== See also ==
	* ]		* ]
	* ]		* ]
	==References==		== References ==
	{{Reflist|2}}		{{Reflist|30em}}
	==External links==		== External links ==
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			{{Insecticides}}
			{{Acetylcholine metabolism and transport modulators}}
	{{insecticides}}
	{{Cholinergics}}
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