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

---

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.
/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.
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/.
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 ... .
For more Metabolism/Metabolites (Complete) data for DIAZINON (10 total), please visit the HSDB record page.
Diazinon has known human metabolites that include Diethyl thiophosphate, Diazoxon, and Pyrimidinol.
Metabolism of organophosphates occurs principally by oxidation, by hydrolysis via esterases and by reaction with glutathione. Demethylation and glucuronidation may also occur. Oxidation of organophosphorus pesticides may result in moderately toxic products. In general, phosphorothioates are not directly toxic but require oxidative metabolism to the proximal toxin. The glutathione transferase reactions produce products that are, in most cases, of low toxicity. Paraoxonase (PON1) is a key enzyme in the metabolism of organophosphates. PON1 can inactivate some organophosphates through hydrolysis. PON1 hydrolyzes the active metabolites in several organophosphates insecticides as well as, nerve agents such as soman, sarin, and VX. The presence of PON1 polymorphisms causes there to be different enzyme levels and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effect of organophosphate exposure.

---

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.
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.
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. ...

Toxicity Summary
IDENTIFICATION: Diazinon is a clear colorless liquid with a faint ester-like odor. Diazinon is soluble in most organic solvents. It is stable in neutral media, but is slowly hydrolyzed in alkaline media and more rapidly in acid media. Diazinon is a contact organophosphorus insecticide with a wide range of insecticidal activity. It is also available in mixed formulations with other insecticides. Another major use is as a drug in veterinary medicine. HUMAN EXPOSURE: Environmental levels of diazinon are generally low. The routes of exposure for the general population are inhalational and dietary. Exposure through water is negligible. Occupational exposure is primarily dermal. Several cases of accidental or suicidal poisoning by diazinon hae been reported, some of which were fatal. In some of these the cholinergic syndrome may have been more severe than expected because of the presence of highly toxic impurities such as TEPP. In certain cases, acute reversible pancreatitis was associated with a severe cholinergic syndrome. Reported cases of poisoning after occupational exposure have always been associated with the presence of impurities. ANIMAL STUDIES: The acute oral, dermal and inhalational toxicity is low. Short-term and long-term studies in mice, rats, rabbits, dogs and monkeys have shown that the only effect of concern is dose-related inhibition of acetyl cholinesterase activity. Diazinon is slightly irritant to rabbit skin but not to the eye. Diazinon is not a dermal sensitizer. Reproductive and developmental studies have revealed no evidence of embryotoxic or teratogenic potential. There was no effect on reproductive performance at dose levels that were not toxic to the parent animals. Mutagenicity studies with various end-points in vivo and in vitro gave no evidence of a mutagenic potential. There is no evidence of carinogenicity in rats or mice. In the dog and guinea-pig, diazinon has been reported to cause acute pancreatitis; this is considered to be a species-specific effect. Diazinon may be absorbed from the gastrointestinal tract, through the intact skin and following inhalation. Diazinon is oxidized by microsomal enzymes to cholinesterase inhibiting metabolites such as diazoxon, hydroxydiazoxon and hydroxydiazinon.
Diazinon is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen.

---

Toxicity Data
LD50: 66 mg/kg (Oral, Rat) (T14)
LD50: 180 mg/kg (Dermal, Rat) (T14)
LD50: 65 mg/kg (Intraperitoneal, Rat) (T14)
LD50: 58 mg/kg (Subcutaneous, Mouse) (T14)
LD50: 180 mg/kg (Intravenous, Mouse) (T14)

---

Interactions
To investigate possible joint toxic effects of diazinon, propoxur and bisphenol A (BPA) on proliferation of /mouse/ RAW264.7 cells in vitro. Cytotoxicity was assessed by MTT assay. The median inhibiting concentration values (IC50) and 95% confidence interval (CI) of diazinon, propoxur and BPA individually and in mixture (mixed according to ratio of IC50) were established by weighted probit method. The types of toxic interaction of diazinon and BPA and propoxur and BPA were assessed by three methods commonly used for binary mixtures, which were Additional Index Method, Equivalent Effect Curve Method and Logistic Regression Method. After 24-hr expoxure, the IC50 and 95% CI of diazinon, propoxur and BPA to RAW264.7 cells were 194.1 microg/mL (173.4 microg/mL-217.4 microg/mL), 448.4 mg/L (358.2 microg/mL-573.2 microg/mL), and 37.5 microg/mL (35.3 microg/mL-39.9 microg/mL), respectively. Those of mixtures of diazinon and BPA and propoxur and BPA were 168.8 microg/mL (160.1 microg/mL-178.2 microg/mL) and 253.4 microg/mL (236.0-273.0 microg/mL). In the interaction assessment, three methods all demonstrated an antagonistic action of diazinon and BPA and an addition action of propoxur and BPA. ...

---

Non-Human Toxicity Values
LD50 Rat male oral 1340 mg/kg
LD50 Rat female oral 1160 mg/kg
LC50 Rat inhalation >5540 mg/cu m 4 hr
LC50 Rat inhalation >2330 mg/cu m 4 hr
For more Non-Human Toxicity Values (Complete) data for DIAZINON (52 total), please visit the HSDB record page.

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

C12H21N2O3PS

304.34

304.101

333-41-5

3017

Light brown to brown liquid

1.2±0.1 g/cm3

353.9±44.0 °C at 760 mmHg

>120°C (dec.)

167.9±28.4 °C

0.0±0.8 mmHg at 25°C

1.524

3.81

0

6

7

19

307

0

S=P(OCC)(OCC)OC1=NC(C(C)C)=NC(C)=C1

FHIVAFMUCKRCQO-UHFFFAOYSA-N

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

diethoxy-(6-methyl-2-propan-2-ylpyrimidin-4-yl)oxy-sulfanylidene-λ5-phosphane

Dicid; Diazitol; Diazinon

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~328.57 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.21 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: 2.5 mg/mL (8.21 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (8.21 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

 (Please use freshly prepared in vivo formulations for optimal results.)