View source for Diazinon

{{More citations needed|date=January 2013}}
{{chembox
| Watchedfields = changed
| verifiedrevid = 443634240 
| ImageFile1=Diazinon-Structural Formula V1.svg
| ImageFile2=Diazinon-Molecule-3D-balls-by-AHRLS.png
| PIN= ''O'',''O''-Diethyl ''O''-[4-methyl-6-(propan-2-yl)pyrimidin-2-yl] phosphorothioate
| OtherNames=Diethoxy-[(2-isopropyl-6-methyl-4-pyrimidinyl)oxy]-thioxophosphorane<br />Basudin<br />Diazide<br />Spectracide
|Section1={{Chembox Identifiers
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = YUS1M1Q929
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D07856
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 388560
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C12H21N2O3PS/c1-6-15-18(19,16-7-2)17-11-8-10(5)13-12(14-11)9(3)4/h8-9H,6-7H2,1-5H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = FHIVAFMUCKRCQO-UHFFFAOYSA-N
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo=333-41-5
| PubChem=3017
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 2909
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 34682
| SMILES = S=P(OCC)(OCC)Oc1nc(nc(c1)C)C(C)C
}}
|Section2={{Chembox Properties
| C=12 | H=21 | N=2 | O=3 | P=1 | S=1
| Appearance=Colorless to dark brown liquid
| Odor = faint, [[ester]]-like
| Density=1.116-1.118 g/cm<sup>3</sup> at 20 °C<ref>{{cite book |editor1-last=Budavari |editor1-first=S. |title=The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals |location=Whitehouse Station, NJ |publisher=Merck |year=1996 |page=508}}</ref>
| MeltingPt=
| BoilingPt=
| BoilingPt_notes = decomposes<ref name=PGCH/>
| Solubility=40 mg/L<ref>{{cite journal |doi=10.1016/0043-1354(80)90158-X |title=Behaviour of 12 insecticides in soil and aqueous suspensions of soil and sediment |year=1980 |last1=Sharom |first1=M.S. |last2=Miles |first2=J.R.W. |last3=Harris |first3=C.R. |last4=McEwen |first4=F.L. |journal=Water Research |volume=14 |issue=8 |pages=1095–100|bibcode=1980WatRe..14.1095S }}</ref>
| LogP=3.81 (octanol/water)<ref>{{cite book |last1=Hansch |first1=Corwin |last2=Leo |first2=Albert |first3=David |last3=Hoekman |title=Exploring QSAR: Volume 2: Hydrophobic, Electronic, and Steric Constants |location=Washington, DC |publisher=American Chemical Society |year=1995 |page=106 |isbn=978-0-8412-2991-4}}</ref>
 }}
|Section6={{Chembox Pharmacology
| ATCvet = yes
| ATCCode_prefix = P53
| ATCCode_suffix = AF03
}}
|Section7={{Chembox Hazards
| MainHazards=
| FlashPtF=180
| FlashPt_ref=<ref name=PGCH/>
| AutoignitionPt =
| PEL = none<ref name=PGCH>{{PGCH|0181}}</ref>
| IDLH = N.D.<ref name=PGCH/>
| REL = TWA 0.1 mg/m<sup>3</sup> [skin]<ref name=PGCH/>
 }}
}}

'''Diazinon''' ([[IUPAC]] name: '''''O'',''O''-Diethyl ''O''-[4-methyl-6-(propan-2-yl)pyrimidin-2-yl] phosphorothioate''', [[International Nonproprietary Name|INN]] - '''Dimpylate'''), a colorless to dark brown liquid, is a thiophosphoric acid ester developed in 1952 by [[Ciba-Geigy]], a Swiss chemical company (later [[Novartis]] and then [[Syngenta]]). It is a nonsystemic [[organophosphate]] [[insecticide]] formerly used to control [[cockroach]]es, [[silverfish]], [[ant]]s, and [[flea]]s in residential, non-food buildings. Diazinon was heavily used during the 1970s and early 1980s for general-purpose gardening use and indoor pest control. A bait form was used to control scavenger [[wasp]]s in the western U.S. Diazinon is used in flea collars for domestic pets in Australia and New Zealand. Diazinon is a major component in the "Golden Fleece" brand [[sheep dip]]. Residential uses of diazinon were outlawed in the U.S. in 2004 because of human health risks<ref name=":0">{{Cite web|last=Cone|first=Marla|date=1 Jan 2005|title=EPA Takes Pest Killer Diazinon Off the Shelves|url=https://www.latimes.com/archives/la-xpm-2005-jan-01-na-pest1-story.html|access-date=2 Jul 2020|website=Los Angeles Times}}</ref> but it is still approved for agricultural uses. An emergency antidote is [[atropine]].<ref>{{cite journal |doi=10.1067/mem.2003.103 |title=Atropine availability as an antidote for nerve agent casualties: Validated rapid reformulation of high-concentration atropine from bulk powder |year=2003 |last1=Geller |first1=Robert J. |last2=Lopez |first2=Gaylord P. |last3=Cutler |first3=Stephen |last4=Lin |first4=Diana |last5=Bachman |first5=George F. |last6=Gorman |first6=Susan E. |journal=Annals of Emergency Medicine |volume=41 |issue=4 |pages=453–6 |pmid=12658242}}</ref> 

'''Specific Health Risks:''' Routes of contact for Diazinon include breathing it, consuming it, or contact with skin. The negative health effects when in contact with Diazinon includes eye watering, drool or runny nose, not having any appetite, throwing up, intense coughing, abdominal pain, or even stiffness in various muscles/paralysis.<ref>{{Cite web |title=Diazinon General Fact Sheet |url=http://npic.orst.edu/factsheets/Diazgen.html |access-date=2024-03-14 |website=npic.orst.edu}}</ref> Headaches can also be health risks.<ref>{{Cite journal |last=Dahlgren |first=J. G. |last2=Takhar |first2=H. S. |last3=Ruffalo |first3=C. A. |last4=Zwass |first4=M. |date=2004 |title=Health effects of diazinon on a family |url=https://pubmed.ncbi.nlm.nih.gov/15462149/ |journal=Journal of Toxicology. Clinical Toxicology |volume=42 |issue=5 |pages=579–591 |doi=10.1081/clt-200026979 |issn=0731-3810 |pmid=15462149}}</ref> Some other physiological effects include pinpoint pupils, increased heart rate, seizures, or even coma. Larger exposure to diazinon is known to yield these risks. If it is a smaller exposure, the symptoms may be reduced such as just a runny nose or some eye watering.<ref>{{Cite web |title=Diazinon {{!}} Public Health Statement {{!}} ATSDR |url=https://wwwn.cdc.gov/TSP/PHS/PHS.aspx?phsid=511&toxid=90 |access-date=2024-03-14 |website=wwwn.cdc.gov}}</ref> One thing to note is that while Diazinon has many different health risks, the EPA has not categorized it as a carcinogen.<ref>{{Cite web |title=Diazinon {{!}} Public Health Statement {{!}} ATSDR |url=https://wwwn.cdc.gov/TSP/PHS/PHS.aspx?phsid=511&toxid=90 |access-date=2024-03-14 |website=wwwn.cdc.gov}}</ref> 

==History==
Diazinon was developed in 1952 by the Swiss company [[Ciba-Geigy]] (now [[Novartis]]) to replace the formerly dominant [[insecticide]] [[DDT]]. In 1939, the chemist [[Paul Hermann Müller]] from the then-independent Geigy company had discovered that DDT was effective against [[malaria]]-bearing insects. This capability made use of DDT important enough that Müller even received the 1948 [[Nobel Prize in Medicine]].{{Citation needed|date=January 2021}}

However, as the decades following the award passed, DDT was found to be such an environmental danger that developed countries and eventually world-level organizations banned the insecticide for all purposes except for combating [[disease-vector]] insects, leading Ciba-Geigy to research alternatives.{{Citation needed|date=January 2021}}

Diazinon became available for mass use in 1955, while DDT production tapered. Before 1970, diazinon had issues with [[Impurity|contaminants]] in its [[Solution (chemistry)|solution]]; but by the 1970s, alternative [[Purification (chemistry)|purification methods]] were used to reduce the residual, unwanted materials. {{Citation needed|date=January 2021}}

After this processing improvement, diazinon became an all-purpose, indoor-and-outdoor, commercial pest control product. In 2004, the US outlawed residential use of diazinon when the EPA determined that its ability to damage the nervous system posed a risk to human health (especially the health of children).<ref name=":0" /> The chemical is still used for industrial agricultural purposes.

==Synthesis==
According to the German Patent bureau, the industrial synthesis of diazinon is as follows:

:β-isobutyrylaminocrotonic acid amine was cyclized with NaOR (R is either a hydrogen or aliphatic chain of 1 to 8 carbons) in a mixture of 0 to 100% by weight of water and an alcohol having 1 to 8 carbon atoms, above 90°C (but below the boiling point of the mixture used). Sodium pyrimidinolate was precipitated out in an inert solvent, such as benzene, with simultaneous removal of the water formed. The potassium salt is then reacted with diethylthiophosphoryl chloride by heating for several hours. When the reaction finished, the potassium chloride formed was washed with water and the solvent was removed under reduced pressure leaving diazinon.{{Citation needed|date=January 2021}}

==Metabolism and mechanism of action==

Diazinon functions as an [[Acetylcholinesterase inhibitor|acetylcholinesterase (AChE) inhibitor]]. This enzyme breaks down the neurotransmitter [[acetylcholine]] (ACh) into [[choline]] and an [[acetate]] group.<ref>{{cite web |title=Diazinon Technical Fact Sheet |url=http://npic.orst.edu/factsheets/archive/diazinontech.html |website=National Pesticide Information Center |publisher=NPIC |access-date=31 May 2019}}</ref> The inhibition of AChE causes an abnormal accumulation of ACh in the [[synaptic cleft]].{{Citation needed|date=January 2021}}

When diazinon enters the body, it is oxidatively decomposed to diazoxon, an [[organophosphate]] compound that is much more poisonous than diazinon; it mainly causes the inhibition of AChE.<ref>{{cite journal |last1=Kretschmann |first1=Andreas |display-authors=etal |title=Mechanistic Toxicodynamic Model for Receptor-Mediated Toxicity of Diazoxon, the Active Metabolite of Diazinon, in Daphnia magna |journal=Environmental Science & Technology |volume=45 |issue=11 |pages=4980–4987 |doi=10.1021/es1042386 |pmid=21539304 |year=2011 |bibcode=2011EnST...45.4980K |s2cid=31463849 }}</ref> The conversion of diazinon to diazoxon (Reaction 1) is performed by the [[Liver#Breakdown|liver]] [[Microsome|microsomal]] enzyme system and requires O<sub>2</sub> and [[NADPH]]. Diazinon can also be decomposed via oxidation in the liver (Reaction 2). Both reactions are possible, and likely are catalyzed nonspecifically by the same mixed function [[oxidase]]. Diazoxon is further broken down by [[hydrolase]]s in the microsomal and other subcellular functions within the liver (Reaction 3). Mammals metabolize diazoxon with a half-life of 2 to 6 weeks. Insects lack this hydrolysis step, which allows the toxic substance to accumulate rapidly; the detoxification of diazoxon is processed through the microsomal mixed function oxidase system. Although not fully understood, it is believed that this is the cause for the selectivity of diazinon against insects.  After the hydrolysis or oxidation diazinon is broken down further (Reaction 4).{{Citation needed|date=January 2021}}

[[File:Diazinon Biotransformation Mechanism.pdf|thumb|center|400px|alt=Mechanism for diazinon in vivo.|The mechanism, described above of the biotransformation of Diazinon]]

==Removal of diazinon==
To date, several methods such as electrochemistry, adsorption, enzymatic biodegradation, and photocatalysis have been tested for the elimination of diazinon from aqueous solutions. The removal of [[organophosphate]]s (OPE) from water by adsorption techniques is regarded as one of the competitive methods because of its simple operation and low cost. Development of new adsorbents with high adsorption capacities is very important for removal of the OPE pollutants in the environment.<ref>{{Cite journal |doi = 10.1007/s13762-017-1469-x|title = Removal of diazinon pesticide from aqueous solutions using MCM-41 type materials: Isotherms, kinetics and thermodynamics|journal = International Journal of Environmental Science and Technology|volume = 15|issue = 6|pages = 1301–1312|year = 2017|last1 = Amani|first1 = M. A|last2 = Latifi|first2 = A. M|last3 = Tahvildari|first3 = K|last4 = Karimian|first4 = R| s2cid=104194226 }}</ref>

'''Banning of Diazinon'''

During the Clinton Era, President Clinton signed a tougher pesticide law in 1996. Diazinon was banned from use as an agricultural insecticide. At the time 80% of United States could find Diazinon in their residential products. In fact it still may be in use in certain households, as it is still used and considered legal in 14 states including California. Yet with the ban starting in 2004, having had 20 years pass, states which have accepted that ban have had hardware stores and other suppliers report that they have "ran out" of products with diazinon. These states which continue to use Diazinon is their products consider their risks low, yet its greatest affect is through inhalation and skin contact. Certain environmental groups continue to protest these states which still continue its use. <ref>{{Cite web |last=Cone |first=Marla |date=2005-01-01 |title=EPA Takes Pest Killer Diazinon Off the Shelves |url=https://www.latimes.com/archives/la-xpm-2005-jan-01-na-pest1-story.html |access-date=2024-03-14 |website=Los Angeles Times |language=en-US}}</ref>

==Toxicity and effects on animals==
Diazinon is considered to be of relatively high [[toxicity]] for [[vertebrates]]. The common method of administering diazinon is absorption although inhalation is possible as well. The observed toxification symptoms conform to other [[acetylcholinesterase inhibitors]]. Symptoms are as follows:
* [[Colic]]
* [[Diarrhea]] and/or [[vomiting]] 
* [[Vertigo]]
* [[Headaches]]
* [[Miosis]]
* [[Bradycardia]]
* Sudden [[drop in blood pressure]]
* [[Convulsion]]
* [[Apnea]]

{| class="wikitable"
|-
! Lethal Dose !! Observations
|-
| LD<sub>50</sub> ||
* 214&nbsp;mg•kg−1 (human, oral, TD<sub>Lo</sub>) (2,3)
* 66&nbsp;mg•kg−1 (rat, oral, LD<sub>50</sub>) (2,4)
* 17&nbsp;mg•kg−1 (mouse, oral, LD<sub>50</sub>) (2,5)

|}

On the other hand, in regard to [[chronic toxicity]], the WHO/FAO joint committee on pesticide residues gives the admissible daily intake (ADI) to be 0.005&nbsp;mg/kg of body weight, while the Australian Pesticides and Veterinary Medicine authority gives the no-observed-adverse-effect-level (NOAEL) to be 0.02&nbsp;mg/kg of body weight for adults.

==Symptoms in humans==
Intoxication of diazinon produces the following signs and symptoms:
* Eyes, ears, nose, and throat
**Small pupils (unreactive to light)
**Tearing, increased 
* Cardiovascular
**Low or high blood pressure
**Slow or rapid heart rate
* Respiratory
**Breathing difficulty
**Chest tightness
* Nervous system
**Anxiety
**Convulsions
**Coma
**Dizziness
**Excitability
**Headache
**Weakness
**Tremor
**Twitching
* Skin
**Irritation
**Redness
**Sweating
* Gastrointestinal 
**Abdominal cramps
**Diarrhea
**Loss of appetite
**Nausea
**Vomiting{{Citation needed|date=January 2021}}

Typically treatments will vary depending on exposure and method of administration of the toxin. Critical biomarkers such as urine samples, blood content and heart rates are measured while detoxifying the patient. Common treatments for patients with diazinon poisoning include:

* Assisted Breathing
* Intravenous fluids (IV)
* Irrigation (washing of the skin and eyes)
* Medicinal Treatments; including the antidotes [[atropine]] and [[oxime]].<ref>{{cite web |last=Office of Chemical Safety  Department of Health and Ageing  Canberra |title=AUSTRALIAN PESTICIDES AND VETERINARY MEDICINES AUTHORITY |url=http://www.apvma.gov.au/products/review/docs/diazinon_hh_tox_part_2.pdf |url-status=dead |archive-url=https://web.archive.org/web/20130419083945/http://www.apvma.gov.au/products/review/docs/diazinon_hh_tox_part_2.pdf |archive-date=2013-04-19 |access-date=2024-05-14 |website=www.apvma.gov.au}}</ref>
* Gastric Lavage{{Citation needed|date=January 2021}}

Patients that continue to improve over the first 4 to 6 hours (after medical treatment) usually recover unscathed. Prolonged treatment often is needed to reverse the poisoning, including intensive care hospitalization and long-term therapy. Some toxicity may persist for weeks or months, or even longer.{{Citation needed|date=January 2021}}

==Efficacy and side effects==
Diazinon is a contact insecticide which kills insects by altering normal [[neurotransmission]] within the nervous system of the insect. As mentioned above, diazinon inhibits the enzyme acetylcholinesterase (AChE), which hydrolyzes the neurotransmitter acetylcholine (ACh) in [[cholinergic]] [[synapse]]s and [[neuromuscular junction]]s. This results in abnormal accumulation of ACh within the nervous system. Diazinon, although a [[Organophosphate|thiophosphoric ester]], shares a common mechanism of toxicity with other organophosphate insecticides such as [[chlorpyrifos]], [[malathion]] and [[parathion]], and is not very effective against the organophosphate-resistant insect populations.{{Citation needed|date=January 2021}}

Symptoms of acute diazinon exposure develop in minutes to hours following exposure, depending on the exposure pathway. The initial symptoms of humans are nausea, dizziness, salivation, headache, sweating, [[lacrimation]], and [[rhinorrhea]]. The symptoms can progress to vomiting, abdominal cramps, diarrhea, muscle twitching, weakness, tremor, a lack of coordination and [[miosis]]. Furthermore, some studies have even reported some psychiatric side effects including memory loss, confusion, and depression.{{Citation needed|date=January 2021}}

Because diazinon is fat soluble, there is potential for delayed toxicity if significant amounts of diazinon are stored in fatty tissues. Intermediate syndrome generally occurs within 24&ndash;96 hours after exposure. Intermediate syndrome in humans is characterized by difficulty breathing and muscular weakness, often in the face, neck and proximal limb muscles. Cranial nerve palsies and depressed tendon reflexes have also been reported.{{Citation needed|date=January 2021}}

Studies have suggested that exposure to some organophosphate pesticides can result in long-term neurological problems including organophosphate-induced delayed neuropathy (weakness or paralysis as well as [[paresthesia]] in the extremities); however, reports of these symptoms following diazinon exposures are rare. Human who have been poisoned show increased levels of serum [[Amylase#Hyperamylasemia|amylase]] and glucose as well as elevated urinary [[diastase]] levels accompanied by symptoms considered to be indicative of acute [[pancreatitis]].{{Citation needed|date=January 2021}}

A study found that 10% of 21 typically developing [[child]]ren show 2-isopropyl-6-methyl-4-pyrimidinol (IMPy, a metabolite of diazinon) in [[Molar (tooth)|molars]]. Molars from the two oldest subjects contained the largest concentrations of IMPy. And this concentration in molars may be a biomarker of perinatal exposure and during molar formation.<ref>{{Cite journal|last1=Camann|first1=David E.|last2=Schultz|first2=Stephen T.|last3=Yau|first3=Alice Y.|last4=Heilbrun|first4=Lynne P.|last5=Zuniga|first5=Michelle M.|last6=Palmer|first6=Raymond F.|last7=Miller|first7=Claudia S.|date=March 2013|title=Acetaminophen, pesticide, and diethylhexyl phthalate metabolites, anandamide, and fatty acids in deciduous molars: potential biomarkers of perinatal exposure|journal=Journal of Exposure Science and Environmental Epidemiology|language=en|volume=23|issue=2|pages=190–196|doi=10.1038/jes.2012.71|pmid=22805989|issn=1559-0631|doi-access=free}}</ref>

==References==
{{reflist}}

==External links==
* [http://npic.orst.edu/factsheets/Diazgen.html Diazinon general information] - [[National Pesticide Information Center]] 
* [http://npic.orst.edu/factsheets/archive/diazinontech.pdf Diazinon Technical Fact Sheet - National Pesticide Information Center]
* [http://extoxnet.orst.edu/pips/diazinon.htm Diazinon Pesticide Information Profile - Extension Toxicology Network]
* [http://www.epa.gov/pesticides/op/diazinon.htm EPA Documents: Diazinon]
* [https://www.cdc.gov/niosh/npg/npgd0181.html CDC - NIOSH Pocket Guide to Chemical Hazards - Diazinon]
* [https://web.archive.org/web/20110718120843/http://www.speclab.com/compound/c333415.htm Chemical Fact Sheet]
* [http://www.atsdr.cdc.gov/toxprofiles/tp86-c1-b.pdf Diazinon], Public Health Statement

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

[[Category:Acetylcholinesterase inhibitors]]
[[Category:Organophosphate insecticides]]
[[Category:Pyrimidines]]
[[Category:Organothiophosphate esters]]
[[Category:Isopropyl compounds]]
[[Category:Ethyl esters]]