diazinon

ダイアジノン

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2017/08/18 19:29:46」(JST)

wiki en

[Wiki en表示]

Diazinon

Names
IUPAC name O,O-Diethyl O-[4-methyl-6-(propan-2-yl)pyrimidin-2-yl] phosphorothioate
Other names Diethoxy-[(2-isopropyl-6-methyl-4-pyrimidinyl)oxy]-thioxophosphorane Basudin Diazide Spectracide
Identifiers
CAS Number	333-41-5 Y
3D model (JSmol)	Interactive image
ChEBI	CHEBI:34682 Y
ChemSpider	2909 Y
ECHA InfoCard	100.005.795
KEGG	D07856 Y
PubChem CID	3017
UNII	YUS1M1Q929 Y
InChI InChI=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 Y Key: FHIVAFMUCKRCQO-UHFFFAOYSA-N Y InChI=1/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 Key: FHIVAFMUCKRCQO-UHFFFAOYAQ
SMILES S=P(OCC)(OCC)Oc1nc(nc(c1)C)C(C)C
Properties
Chemical formula	C12H21N2O3PS
Molar mass	304.34 g·mol−1
Appearance	Colorless to dark brown liquid
Odor	faint, ester-like
Density	1.116-1.118 g/cm3 at 20 °C
Boiling point	decomposes
Solubility in water	40 mg/L
log P	3.81 (octanol/water)
Pharmacology
ATCvet code	QP53AF03 (WHO)
Hazards
Flash point	82 °C; 180 °F; 355 K
US health exposure limits (NIOSH):
PEL (Permissible)	none
REL (Recommended)	TWA 0.1 mg/m3 [skin]
IDLH (Immediate danger)	N.D.
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Y verify (what is YN ?)
Infobox references

Diazinon (IUPAC name: O,O-Diethyl O-[4-methyl-6-(propan-2-yl)pyrimidin-2-yl] phosphorothioate, 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 cockroaches, silverfish, ants, and fleas 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 wasps in the western U.S. Diazinon is used in flea collars for domestic pets in Australia and New Zealand. Residential uses of diazinon were outlawed in the U.S. in 2004 but it is still approved for agricultural uses. An emergency antidote is atropine.

History

Diazinon was developed in 1952 by the Swiss company Ciba-Geigy to replace the insecticide DDT. Diazinon became available for mass use in 1955, as DDT production tapered. Before 1970 diazinon had issues with contaminants in the solution. but by the 1970s, alternative purification methods were used to reduce residual materials. After this, diazinon became an all-purpose indoor and outdoor commercial pest control product. In 2004, U.S. residential use of diazinon was outlawed, except for agricultural purposes and cattle ear tags .

Structure and reactivity

The structure of diazinon contains a thiophosphoric ester. The phosphorus center is the reactive site of the chemical. However, no known mechanisms currently exist. A novel mechanism does exist, which proposes that the sulfur is protonated in acidic medium via a hydronium ion which ultimately delivers a hydroxide group to the phosphorus center and can react readily.

The form of diazinon varies widely as it can be in dusts, granules, liquids, concentrates, microencapsulations, wettable powders, and seed dressings. Its appearance varies depending on purity, ranging from a dark brown (industrial grade), to a colorless liquid (pure). Indicative of its functionality of a thiophosphoric ester, the chemical has a pronounced smell similar to that of diethyl ether.

Diazinon is relatively stable under standard ambient temperature and pressure but is susceptible to form toxic phosphine gas upon heating. Furthermore, diazinon can oxidize into toxic phosphorus oxides if in the presence of a strong oxidizing agent.

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.

Metabolism and mechanism of action

Diazinon functions as an acetylcholinesterase (AChE) inhibitor. This enzyme breaks down the neurotransmitter acetylcholine (ACh) into [choline] and an acetate group. (1) The inhibition of the AChE causes an abnormal accumulation of ACh in the synaptic cleft. When Diazinon enters the body, it is oxidatively degenerated to diaxozon, an organophosphate compound that is much more poisoning than diazinon and causes mainly the inhibition of AChE (6). The activation of diazinon (Reaction 1) is located in the liver microsomal enzyme system and requires O₂ and NADPH. Additionally it can also be degenerated via oxidation in the microsomal enzyme system (Reaction 2). Both reactions are possible, and likely are catalyzed nonspecifically by the same mixed function oxidase. Once formed diazoxon is biotransformed again as it is degenerated. Diazoxon is degenerated due to the very effective hydrolyases in the microsomal and other sub cellular factions within the liver (Reaction 3). Mammalian specie degenerate diazoxon at a much slower rate though (with a half-life of 2 to 6 weeks). Insects lack this hydrolysis step which allows for the toxic species to accumulate rapidly. The detoxification of diazoxon is processed through the mircosomal mixed function oxidase system. Although not fully known, it is believed that this is the cause for the selectivity of diazinon against insects. After the hydrolysis or oxidation diazinon is further degenerated (Reaction 4).

The mechanism, described above of the biotransformation of Diazinon

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:

• Colics
• Diarrhea and/or Vomiting
• Vertigo
• Headaches
• Miosis
• Bradycardia
• Sudden Drop in blood pressure
• Convulsion
• Apnea

Lethal Dose	Observations
LD50	214 mg•kg−1 (human, oral, TDLo) (2,3) 66 mg•kg−1 (rat, oral, LD50) (2,4) 17 mg•kg−1 (mouse, oral, LD50) (2,5)

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

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 suffering from diazinon poisoning include:

• Assisted Breathing
• Intravenous fluids (IV)
• Irrigation (washing of the skin and eyes)
• Medicinal Treatments; including the antidotes atropine and oxime.
• Gastric Lavage

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.

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 synapses and neuromuscular junctions. This results in abnormal accumulation of ACh within the nervous system. Diazinon, although a 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.

Symptoms of acute diazinon exposure develop in minutes to hours following exposure, depending of 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 as well including memory loss, confusion, and depression.

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 24–96 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.

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 poisoning victims have shown increased levels of serum amylase and glucose as well as elevated urinary diastase levels accompanied by symptoms considered to be indicative of acute pancreatitis.

External links

• Diazinon general information - National Pesticide Information Center
• Diazinon Technical Fact Sheet - National Pesticide Information Center
• Diazinon Pesticide Information Profile - Extension Toxicology Network
• EPA Documents: Diazinon
• CDC - NIOSH Pocket Guide to Chemical Hazards - Diazinon
• Chemical Fact Sheet
• Diazinon, Public Health Statement
• Diazinon Use

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 有機リン剤およびカルバメート中毒 organophosphate and carbamate poisoning
• 2. 殺鼠剤中毒の概要 overview of rodenticide poisoning
• 3. 有機食品と小児 organic foods and children
• 4. Sickle cell disease in sub-Saharan Africa
• 5. 南京虫 bedbugs

English Journal

• Physiological response of alligator gar juveniles (Atractosteus spatula) exposed to sub-lethal doses of pollutants.

• González CA1, Cruz J, Alfaro RM.
• Fish physiology and biochemistry.Fish Physiol Biochem.2015 Aug;41(4):1015-27. doi: 10.1007/s10695-015-0066-5. Epub 2015 May 7.
• Alligator gar populations have declined because of overfishing, habitat loss and pollution. Over time, the exposure to different pollutants have affected these fishes as a consequence of their high trophic level, bottom-dwelling habits and long life span. In order to evaluate the physiological effec
• PMID 25948055

• Organophosphate insecticide use and cancer incidence among spouses of pesticide applicators in the Agricultural Health Study.

• Lerro CC1, Koutros S2, Andreotti G2, Friesen MC2, Alavanja MC2, Blair A2, Hoppin JA3, Sandler DP4, Lubin JH5, Ma X6, Zhang Y6, Beane Freeman LE2.
• Occupational and environmental medicine.Occup Environ Med.2015 Jul 6. pii: oemed-2014-102798. doi: 10.1136/oemed-2014-102798. [Epub ahead of print]
• OBJECTIVES: Organophosphates (OPs) are among the most commonly used insecticides. OPs have been linked to cancer risk in some epidemiological studies, which have been largely conducted in predominantly male populations. We evaluated personal use of specific OPs and cancer incidence among female spou
• PMID 26150671

• Analysis of organophosphorus pesticides in whole blood by GC-MS-μECD with forensic purposes.

• Valente NI1, Tarelho S2, Castro AL3, Silvestre A4, Teixeira HM5.
• Journal of forensic and legal medicine.J Forensic Leg Med.2015 Jul;33:28-34. doi: 10.1016/j.jflm.2015.03.006. Epub 2015 Mar 28.
• In the present work, two multi-residue methods for the determination of ten organophosphorus pesticides (OPs), namely chlorfenvinphos, chlorpyrifos, diazinon, dimethoate, fenthion, malathion, parathion, phosalone, pirimiphos-methyl and quinalphos, in post-mortem whole blood samples are presented. Th
• PMID 26048493

Japanese Journal

• Difference between Consensus Value of Participants' Results and Isotope-Dilution Mass Spectrometric Results in Proficiency Testing for Pesticide Residues in Husked Wheat

• Analytical Sciences 32(5), 557-580, 2016
• NAID 130005150949

• 16-5 Is the content of pesticides and pesticides metabolites in the ground water still important for medical hydrology

• 日本温泉気候物理医学会雑誌 77(5), 541-542, 2014
• NAID 130004719532

• Safety prediction of topically exposed biocides using permeability coefficients and the desquamation rate at the stratum corneum

• The Journal of Toxicological Sciences 39(3), 475-485, 2014
• NAID 130004447131

Related Links

• Diazinon - Wikipedia, the free encyclopedia

Diazinon (IUPAC name: O,O-Diethyl O-[4-methyl-6-(propan-2-yl)pyrimidin-2-yl] phosphorothioate), a colorless to dark brown liquid, is a thiophosphoric acid ester developed in 1952 by Ciba-Geigy, a Swiss chemical company (later Novartis ...

Related Pictures