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2D Structure
Also known as: Dimpylate, 333-41-5, Diazinone, Oleodiazinon, Ciazinon, Neocidol
Molecular Formula
C12H21N2O3PS
Molecular Weight
304.35  g/mol
InChI Key
FHIVAFMUCKRCQO-UHFFFAOYSA-N
FDA UNII
YUS1M1Q929

A cholinesterase inhibitor that is used as an organothiophosphorus insecticide.
1 2D Structure

2D Structure

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
diethoxy-(6-methyl-2-propan-2-ylpyrimidin-4-yl)oxy-sulfanylidene-5-phosphane
2.1.2 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
2.1.3 InChI Key
FHIVAFMUCKRCQO-UHFFFAOYSA-N
2.1.4 Canonical SMILES
CCOP(=S)(OCC)OC1=NC(=NC(=C1)C)C(C)C
2.2 Other Identifiers
2.2.1 UNII
YUS1M1Q929
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Bazudine

2. Dimpylate

3. Neocidol

4. Neotsidol

2.3.2 Depositor-Supplied Synonyms

1. Dimpylate

2. 333-41-5

3. Diazinone

4. Oleodiazinon

5. Ciazinon

6. Neocidol

7. Dassitox

8. Diazitol

9. Ektoband

10. Nedcidol

11. Spectracide

12. Antigal

13. Basudin

14. Bazuden

15. Dacutox

16. Dazzel

17. Diazide

18. Diazol

19. Exodin

20. Flytrol

21. Galesan

22. Nucidol

23. Sarolex

24. Dicid

25. Alfa-tox

26. Diazajet

27. Dimpylat

28. Garden Tox

29. Neocidol (oil)

30. Bassadinon

31. Terminator

32. Compass

33. Disonex

34. Dizinon

35. Drawizon

36. Kayazinon

37. Kayazol

38. Meodinon

39. Dyzol

40. Nipsan

41. Diazinon Ag 500

42. Knox-out

43. Delzinon

44. Dimpylatum

45. Dipofene

46. Dizictol

47. Neodinon

48. Optimizer

49. Bazudin

50. Dizinil

51. Srolex

52. Basudin 10 G

53. Geigy 24480

54. Basudin S

55. Knox Out 2fm

56. Diagran

57. Fezudin

58. Nci-c08673

59. Ag-500

60. G-24480

61. Dimpylate [inn]

62. Ent 19,507

63. Isopropylmethylpyrimidyl Diethyl Thiophosphate

64. Diziktol

65. O,o-diethyl 2-isopropyl-4-methylpyrimidyl-6-thiophosphate

66. New Z Diazinon

67. G 301

68. O,o-diethyl O-(2-isopropyl-6-methyl-4-pyrimidinyl) Phosphorothioate

69. 4-pyrimidinol, 2-isopropyl-6-methyl-, O-ester With O,o-diethyl Phosphorothioate

70. Diethyl 4-(2-isopropyl-6-methylpyrimidinyl)phosphorothionate

71. O-2-isopropyl-4-methylpyrimidyl-o,o-diethyl Phosphorothioate

72. Optimizer Insecticide

73. O,o-diethyl O-(2-isopropyl-4-methyl-6-pyrimidyl) Thionophosphate

74. Chebi:34682

75. O,o-diethyl O-6-methyl-2-isopropyl-4-pyrimidinyl Phosphorothioate

76. Nsc-8938

77. Phosphorothioate, O,o-diethyl O-6-(2-isopropyl-4-methylpyrimidyl)

78. Thiophosphate De O,o-diethyle Et De O-2-isopropyl-4-methyl-6-pyrimidyle

79. Diethyl 2-isopropyl-4-methyl-6-pyrimidyl Thionophosphate

80. Phosphorothioic Acid, O,o-diethyl O-(6-methyl-2-(1-methylethyl)-4-pyrimidinyl) Ester

81. Yus1m1q929

82. Diethyl 2-isopropyl-4-methyl-6-pyrimidinyl Phosphorothionate

83. O,o-diethyl 2-isopropyl-6-methyl-4-pyrimidinylphosphorothioate

84. Nsc8938

85. Dimpylate (inn)

86. O,o-diethyl-o-(2-isopropyl-4-methyl-pyrimidin-6-yl)-monothiofosfaat

87. Phosphorothioic Acid, O,o-diethyl O-(2-isopropyl-6-methyl-4-pyrimidinyl) Ester

88. Ncgc00091073-01

89. Bazudine

90. Neotsidol

91. Dsstox_cid_407

92. O,o-diethyl O-(2-isopropyl-4-methyl-6-pyrimidinyl) Phosphorothioate

93. O,o-diethyl O-[6-methyl-2-(1-methylethyl)pyrimidin-4-yl] Thiophosphate

94. Kleen-dok

95. Dsstox_rid_75567

96. Phosphorothioic Acid, O,o-diethylo-[6-methyl-2-(1-methylethyl)-4-pyrimidinyl] Ester

97. Dsstox_gsid_20407

98. Diazinon, Analytical Standard

99. Kfm Blowfly Dressing

100. Compass (insecticide)

101. Caswell No. 342

102. Gardentox

103. Dimpilato

104. Antlak

105. Diaterr-fos

106. Dimpylatum [inn-latin]

107. O,o-diaethyl-o-(2-isopropyl-4-methyl-pyrinidin-6-yl)-monothiophosphat

108. O,o-diethyl O-(2-isopropyl-4-methyl-6-pyrimidyl) Phosphorothioate

109. Cooper's Flystrike Powder

110. Dimpilato [inn-spanish]

111. Nsc 8938

112. Phosphorothioic Acid, O,o-diethyl O-[6-methyl-2-(1-methylethyl)-4-pyrimidinyl] Ester

113. Diazinon [ansi:bsi:iso]

114. Cas-333-41-5

115. Ccris 204

116. Hsdb 303

117. Knox Out Yellow Jacket Contorl

118. Oms 469

119. Einecs 206-373-8

120. Pt 265

121. Epa Pesticide Chemical Code 057801

122. Brn 0273790

123. Unii-yus1m1q929

124. Spertacide

125. Bazanon

126. Ai3-19507

127. Root Guard

128. Diethyl Dimpylatum

129. Diethoxy-(6-methyl-2-propan-2-ylpyrimidin-4-yl)oxy-sulfanylidene-?^{5}-phosphane

130. Dimpylate, Inn

131. Basudin 5g

132. Spectracide 25ec

133. G 24480

134. Agridin 60

135. Basudin 10g

136. Spectrum_001777

137. Dimpylate [inn:ban]

138. Diazinon [hsdb]

139. Diazinon [iarc]

140. New Z Diazinon (tn)

141. Specplus_000344

142. Diazinon [iso]

143. Diazinon [mi]

144. O,o-diethyl O-(2-isopropyl-6-methyl-4-pyrimidinyl)phosphorothioate

145. O,o-diethyl-o-(2-isopropyl-4-methyl-6-pyrimidyl)phosphorothioate

146. Spectrum2_001226

147. Spectrum3_000802

148. Spectrum4_000642

149. Spectrum5_001929

150. Thiophosphoric Acid 2-isopropyl-4-methyl-6-pyrimidyl Diethyl Ester

151. O,o-diethyl-o-(2-isopropyl-4-methyl-6-pyrimidinyl)-phosphorothioate

152. Phosphorothioic Acid, O,o-diethyl O-(isopropylmethylpyrimidinyl) Ester

153. Dimpylate [mart.]

154. O,o-diaethyl-o-(2-isopropyl-4-methyl)-6-pyrimidyl-thionophosphat [german]

155. O,o-diaethyl-o-(2-isopropyl-4-methyl-pyrimidin-6-yl)-monothiophosphat [german]

156. O,o-diethyl O-(6-methyl-2-(1-methylethyl)-4-pyrimidinyl)phosphorothioate

157. O,o-diethyl-o-(2-isopropyl-4-methyl-pyrimidin-6-yl)-monothiofosfaat [dutch]

158. O,o-dietil-o-(2-isopropil-4-metil-pirimidin-6-il)-monotiofosfato [italian]

159. Dimpylate [who-dd]

160. Optimizer Insecticide (tn)

161. Thiophosphate De O,o-diethyle Et De O-2-isopropyl-4-methyl-6-pyrimidyle [french]

162. Schembl17453

163. Bspbio_002263

164. Kbiogr_000983

165. Kbioss_002258

166. 5-23-11-00187 (beilstein Handbook Reference)

167. Mls002207243

168. Bidd:er0457

169. Divk1c_006440

170. Spbio_001072

171. Chembl388560

172. Zinc1309

173. Dtxsid9020407

174. Fhivafmuckrcqo-uhfffaoysa-

175. Kbio1_001384

176. Kbio2_002257

177. Kbio2_004825

178. Kbio2_007393

179. Kbio3_001763

180. Amy3613

181. Hms3264i04

182. Pharmakon1600-00330017

183. Hy-b1113

184. O,o-diaethyl-o-(2-isopropyl-4-methyl)-6-pyrimidyl-thionophosphat

185. O,o-diethyl O-2-isopropyl-6-methylpyrimidin-4-yl Phosphorothioate

186. Diazinon 100 Microg/ml In Acetone

187. Tox21_111077

188. Tox21_201409

189. Tox21_300730

190. Bdbm50005409

191. Ccg-39143

192. Ent 19507

193. Nsc755893

194. O,o-diaethyl-o-(2-isopropyl-4-methyl-pyrimidin-6-yl)-monothiophosphat

195. O,o-dietil-o-(2-isopropil-4-metil-pirimidin-6-il)-monotiofosfato

196. Diazinon 10 Microg/ml In Cyclohexane

197. Diazinon 1000 Microg/ml In Toluene

198. Akos025311513

199. Diazinon 1000 Microg/ml In Methanol

200. Diethoxy-(2-isopropyl-6-methyl-pyrimidin-4-yl)oxy-thioxo-$l^{5}-phosphane

201. O,o-diethyl O-(6-methyl-2-(1-methylethyl)-4-pyrimidinyl) Phosphorothioate

202. O,o-diethyl O-[6-methyl-2-(propan-2-yl)pyrimidin-4-yl] Phosphorothioate

203. Tox21_111077_1

204. Cs-4712

205. Diazinon 10 Microg/ml In Acetonitrile

206. Diazinon 100 Microg/ml In Cyclohexane

207. Nsc-755893

208. Diazinon 100 Microg/ml In Acetonitrile

209. Diethoxy-(6-methyl-2-propan-2-ylpyrimidin-4-yl)oxy-sulfanylidene-lambda5-phosphane

210. Ncgc00091073-02

211. Ncgc00091073-03

212. Ncgc00091073-04

213. Ncgc00091073-05

214. Ncgc00091073-06

215. Ncgc00091073-07

216. Ncgc00254636-01

217. Ncgc00258960-01

218. Smr000777921

219. Sbi-0052498.p002

220. Db-048387

221. Diazinon, Pestanal(r), Analytical Standard

222. Ft-0603088

223. Ft-0778116

224. D07856

225. Ab00053004_04

226. 333d415

227. Q411202

228. Sr-01000872734

229. Q-200952

230. Sr-01000872734-1

231. Brd-k60567437-001-04-5

232. Diazinon, Certified Reference Material, Tracecert(r)

233. 4-pyrimidinol, O-ester With O,o-diethyl Phosphorothioate

234. Wln: T6n Cnj By1 & 1 Dops & O2 & O2 F1

235. O, O-diethyl 2-isopropyl-4-methylpyrimidyl-6-thiophosphate

236. O,o-diethyl-o-(2-isopropyl-4-methylpyrimidyl)thiophosphate

237. O,o-dietil-o-(2-isopropil-4-metil-pirimidin-il)-monotiofosato

238. Phosphorothioate,o-diethyl O-6-(2-isopropyl-4-methylpyrimidyl)

239. O,o-diethyl O-(2-isopropyl-6-methyl-4-primidinyl)phosphorothioate

240. O,o-diethyl O-(2-isopropyl-6-methyl-4-pyrimidinyl) Thiophosphate

241. O,o-diethyl O-(2-isopropyl-6-methyl-4-pyrimidinyl) Thiophosphate #

242. O,o-diethyl O-(2-isopropyl-6-methyl-4-pyrimidinyl)thio-phosphate

243. O,o-diethyl-o-(2-isopropyl-4-methyl-6-pyrimidyl) Thiophosphate

244. Diethoxy-(6-methyl-2-propan-2-ylpyrimidin-4-yl)oxy-sulfanylidenephosphorane

245. O,o-diethyl-o-(6-methyl-2-(1-methylethyl)-4-pyrimidinyl)phosophorothioate

246. Phosphorothioic Acid, O,o-diethyl 2-isopropyl-6-methyl-4-pyrimidinyl Ester

247. Phosphorothioic Acid,o-diethyl O-(2-isopropyl-6-methyl-4-pyrimidinyl) Ester

248. Diazinon Solution, 100 Mug/ml In Acetonitrile, Pestanal(r), Analytical Standard

249. Diethoxy-(6-methyl-2-propan-2-ylpyrimidin-4-yl)oxy-sulfanylidene-$l^{5-phosphane

250. Ethyl 6-methyl-2-(propan-2-yl)pyrimidin-4-yl Ethoxy(sulfanylidene)phosphonite

251. Phosphorothioic Acid O,o-diethyl O-(6-methyl-2-(1-methylethyl)-4-pyrimidinyl) Ester

252. Phosphorothioic Acid, O,o-diethyl {o-[6-methyl-2-(1-methylethyl)-4-pyrimidinyl]} Ester

253. Phosphorothioic Acid,o-diethyl O-[6-methyl-2-(1-methylethyl)-4-pyrimidinyl] Ester

2.4 Create Date
2005-03-25
3 Chemical and Physical Properties
Molecular Weight 304.35 g/mol
Molecular Formula C12H21N2O3PS
XLogP33.8
Hydrogen Bond Donor Count0
Hydrogen Bond Acceptor Count6
Rotatable Bond Count7
Exact Mass304.10105071 g/mol
Monoisotopic Mass304.10105071 g/mol
Topological Polar Surface Area85.6 Ų
Heavy Atom Count19
Formal Charge0
Complexity307
Isotope Atom Count0
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Therapeutic Uses

VET: Used against ... flies and ticks in veterinary practice.

Worthing, C.R. and S.B. Walker (eds.). The Pesticide Manual - A World Compendium. 8th ed. Thornton Heath, UK: The British Crop Protection Council, 1987., p. 248


4.2 Minimum/Potential Fatal Human Dose

The estimated adult oral fatal dose is approximately 25 g.

Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 1071


Estimated adult oral fatal dose is approximately 25 g.

Ellenhorn, M.J. and D.G. Barceloux. Medical Toxicology - Diagnosis and Treatment of Human Poisoning. New York, NY: Elsevier Science Publishing Co., Inc. 1988., p. 1071


5 Pharmacology and Biochemistry
5.1 MeSH Pharmacological Classification

Insecticides

Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. (See all compounds classified as Insecticides.)


Cholinesterase Inhibitors

Drugs that inhibit cholinesterases. The neurotransmitter ACETYLCHOLINE is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. (See all compounds classified as Cholinesterase Inhibitors.)


5.2 Absorption, Distribution and Excretion

Four laying Leghorn hens were treated with 2-14C-diazinon (specific activity 30.3 uCi/mg) in gelatin capsules for seven consecutive days at daily doses of 1.7 mg/kg body weight, corresponding to a dietary exposure of 25 mg/kg in feed. ... Elimination of most of the administered radioactivity occurred via the excreta, with 78.6% of the total dose being excreted during the study period. Approximately 0.1% of the radioactivity was found in tissues and blood, less than 0.01% appeared in the egg yolks and 0.07% was detected in the egg whites. The residual radioactivity in the tissues amounted to 0.148 mg/kg diazinon equivalents in the kidney, 0.137 mg/kg in blood, 0.11 mg/kg in the liver and 0.01-0.025 mg/kg in the other tissues examined. The residues in the egg yolks ranged from 0.006 mg/kg diazinon equivalents to 0.065 mg/kg while those in the egg whites ranged from 0.038 mg/kg to 0.066 mg/kg. On a whole egg basis, a plateau concentration of 0.047 mg/kg was reached on day 4 of treatment.

WHO; Environ Health Criteria 198: Diazinon (333-41-5) (1998); Available from, as of August 31, 2011: https://www.inchem.org/pages/ehc.html


A lactating Hereford cow (body weight 268 kg) was orally treated with a gelatin capsule containing 20 mg/kg 32P-diazinon (specific activity 518 cpm/ug). ... Within 36 hr, approximately 74% of the administered radioactivity was excreted with the urine, 6.5% appeared in the feces and 0.08% was found in the milk. A peak concentration of 2.27 mg/kg diazinon equivalents was reached 18 hr after the administration.

WHO; Environ Health Criteria 198: Diazinon (333-41-5) (1998); Available from, as of August 31, 2011: https://www.inchem.org/pages/ehc.html


Two lactating goats were orally treated with (pyrimidine-14C)-diazinon (specific activity 9.7 uCi/mg) in gelatin capsules for four consecutive days at a dose level of 4.5 mg/kg per day, corresponding to a dietary exposure of 100 mg/kg of feed. During the observation period, an average 64.1% of the administered radioactivity was excreted with urine, 10.4% with the feces and 0.31% with the milk. A plateau of radioactivity in the milk was reached after 3 days of dosing at a mean level of 0.46 mg/kg diazinon equivalent. At sacrifice, radioactivity in the blood accounted for 0.2% and the tissues examined accumulated 0.92% of the administered dose. The highest residual radioactivity was detected in the kidney (2.0 mg/kg) and the liver (1.2 mg/kg). The other tissues examined contained 0.23-0.3 mg/kg diazinon equivalents.

WHO; Environ Health Criteria 198: Diazinon (333-41-5) (1998); Available from, as of August 31, 2011: https://www.inchem.org/pages/ehc.html


Two female Beagle dogs were intravenously dosed with 0.2 mg/kg (ethoxy-14C)-diazinon (specific activity 3.4 uCi/mg) in 0.7 mL ethanol. ... The half-life of elimination from blood for this second phase was calculated to be 363 min. Approximately 58% of the administered radioactivity was recovered in the urine within 24 hr after the administration. Another two female beagle dogs were orally dosed by capsule with 4.0 mg/kg (ethoxy-14C) diazinon in ethanol. Approximately 85% of the administered radioactivity was recovered within 24 hr after oral administration, with 53% of it occurring in urine.

WHO; Environ Health Criteria 198: Diazinon (333-41-5) (1998); Available from, as of August 31, 2011: https://www.inchem.org/pages/ehc.html


For more Absorption, Distribution and Excretion (Complete) data for DIAZINON (8 total), please visit the HSDB record page.


5.3 Metabolism/Metabolites

The main metabolic pathways of degradation of diazinon are: cleavage of the ester bond leading to the hydroxypyrimidine derivatives; transformation of P-S moiety to the P-O derivative; oxidation of isopropyl substituent leading to the corresponding tertiary and primary alcohol derivatives; oxidation of the methyl substituent leading to the corresponding alcohol; glutathione-mediated cleavage of the ester bond leading to a glutathione conjugate.

WHO; Environ Health Criteria 198: Diazinon (333-41-5) (1998); Available from, as of August 31, 2011: https://www.inchem.org/pages/ehc.html


/STUDY OF METABOLISM IN RATS OF DIAZINON FOUND THAT/ THE METABOLITES 2-ISOPROPYL-4-METHYL-6-HYDROXYPYRIMIDINE ... /& TWO UNIDENTIFIED METABOLITES/ WHICH WERE EXCRETED IN THE URINE AND FECES, ACCOUNT FOR 70% OF THE DOSE. ... METB IN RATS OF DIAZINON ... LABELLED WITH (14)C, ... 3 METABOLITES WERE LOCATED ON GENERAL METABOLIC PATHWAY BY FOLLOWING THEIR METABOLIC FATE AFTER IV INJECTION. SINCE ACUTE ORAL TOXICITIES OF ALL 3 CMPD ARE LESS THAN 1/10 OF THAT OF DIAZINON, BIOTRANSFORMATION IS ASSOC WITH DETOXICATION.

The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 2: A Review of the Literature Published Between 1970 and 1971. London: The Chemical Society, 1972., p. 286


DIAZINON ... APPEARS TO BE METABOLIZED INTO CORRESPONDING PHOSPHATE IN LACTATING COWS, AND INTO THE HYDROLYTIC PRODUCTS DIETHYL PHOSPHOROTHIOATE AND DIETHYL PHOSPHATE WITH LIBERATION OF 2-HYDROXY-6-ISOPROPYL-4-METHYLPYRIMIDINE /PLUS METABOLITE DIAZOXON/.

The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 1: A Review of the Literature Published Between 1960 and 1969. London: The Chemical Society, 1970., p. 280


AFTER ADMIN OF DIAZINON BY STOMACH TUBE TO SHEEP, HYDROXYDIAZINON WAS FOUND IN TISSUES. DIAZINON, WHEN FED TO SHEEP, WAS METABOLIZED ALSO BY HYDROXYLATION OF C-4 METHYL GROUP. RESIDUES OF THIS & C-1' ISOPROPANOL ANALOG WERE FOUND ... .

Menzie, C. M. Metabolism of Pesticides, An Update. U.S. Department of the Interior, Fish, Wild-life Service, Special Scientific Report - Wildlife No. 184, Washington, DC: U.S. Government Printing Office, l974., p. 154


For more Metabolism/Metabolites (Complete) data for DIAZINON (10 total), please visit the HSDB record page.


Diazinon has known human metabolites that include Diazoxon, Diethyl thiophosphate, and Pyrimidinol.

S73 | METXBIODB | Metabolite Reaction Database from BioTransformer | DOI:10.5281/zenodo.4056560


5.4 Biological Half-Life

ORAL DOSE OF ECTOPARASITICIDE, (14)C DIAZINON, WAS RAPIDLY ELIMINATED FROM RAT (BIOLOGICAL HALF-LIFE WAS 12 HR). 80% OF (14)C WAS EXCRETED IN URINE & 18% IN FECES. COMPARABLE EXCRETION PATTERN & LOWER BIOLOGICAL HALF-LIFE OF 9 HR WAS OBTAINED AFTER IV ADMIN OF 3 (14)C METABOLITES OF DIAZINON.

The Chemical Society. Foreign Compound Metabolism in Mammals. Volume 2: A Review of the Literature Published Between 1970 and 1971. London: The Chemical Society, 1972., p. 148


AFTER ORAL ADMIN TO RATS, EXCRETION OF RING & SIDE CHAIN LABELED DIAZINON EXCEEDED 90% AFTER 168 HR. BIOLOGICAL HALF-LIFE VARIED FROM 7 HR IN MALE RATS FOR ETHYL-(14)C-DIAZINON TO 12 HR FOR 2-(14)C-DIAZINON IN MALE & FEMALE RATS.

Menzie, C. M. Metabolism of Pesticides, An Update. U.S. Department of the Interior, Fish, Wild-life Service, Special Scientific Report - Wildlife No. 184, Washington, DC: U.S. Government Printing Office, l974., p. 154


Two female Beagle dogs were intravenously dosed with 0.2 mg/kg (ethoxy-14C)-diazinon (specific activity 3.4 uCi/mg) in 0.7 mL ethanol. ... The half-life of elimination from blood for this second phase was calculated to be 363 min. ...

WHO; Environ Health Criteria 198: Diazinon (333-41-5) (1998); Available from, as of August 31, 2011: https://www.inchem.org/pages/ehc.html


5.5 Mechanism of Action

PURE DIAZINON IS POOR ANTICHOLINESTERASE, BUT IS READILY CONVERTED TO STRONG INHIBITOR UPON STORAGE OR HEATING, PARTICULARLY IN PRESENCE OF TRACE OF MOISTURE. THERMAL DECOMPOSITION OF PURE DIAZINON ... PRODUCTS OBTAINED ARE PYROPHOSPHATES THAT PROBABLY ARE RESPONSIBLE FOR INCR IN ANTICHOLINESTERASE ACTIVITY.

White-Stevens, R. (ed.). Pesticides in the Environment: Volume 1, Part 1, Part 2. New York: Marcel Dekker, Inc., 1971., p. 170


The organothiophosphate diazinon inhibits the target site acetylcholinesterase only after activation to its metabolite diazoxon. Commonly, the toxicity of xenobiotics toward aquatic organisms is expressed as a function of the external concentration and the resulting effect on the individual level after fixed exposure times. This approach does not account for the time dependency of internal processes such as uptake, metabolism, and interaction of the toxicant with the target site. Here, ...a mechanistic toxicodynamic model for Daphnia magna and diazoxon /is developed/, which accounts for the inhibition of the internal target site acetylcholinesterase and its link to the observable effect, immobilization, and mortality. The model was parametrized by experiments performed in vitro with the active metabolite diazoxon on enzyme extracts and in vivo with the parent compound diazinon. The mechanism of acetylcholinesterase inhibition was shown to occur irreversibly in two steps via formation of a reversible enzyme-inhibitor complex. The corresponding kinetic parameters revealed a very high sensitivity of acetylcholinesterase from D. magna toward diazoxon, which corresponds well with the high toxicity of diazinon toward this species. Recovery of enzyme activity but no recovery from immobilization was observed after in vivo exposure to diazinon. The toxicodynamic model combining all in vitro and in vivo parameters was successfully applied to describe the time course of immobilization in dependence of acetylcholinesterase activity during exposure to diazinon. The threshold value for enzyme activity below which immobilization set in amounted to 40% of the control activity. Furthermore, the model enabled the prediction of the time-dependent diazoxon concentration directly present at the target site.

PMID:21539304 Kretschmann A et al; Environ Sci Technol 45 (11): 4980-7 (2011)