Absorption, Distribution and Excretion
Four laying hens were administered 2-14C-diazinon (specific activity 30.3 μCi/mg) gelatin capsules for seven consecutive days at a daily dose of 1.7 mg/kg body weight, equivalent to adding 25 mg/kg of radioactive material to the feed. …Most of the radioactive material was excreted, with 78.6% of the total dose excreted during the study period. Approximately 0.1% of the radioactive material was present in tissues and blood, less than 0.01% in egg yolk, and 0.07% in egg white. The residual radioactive material content in tissues was as follows: kidney 0.148 mg/kg diazinon equivalent, blood 0.137 mg/kg, liver 0.11 mg/kg, and other tested tissues 0.01–0.025 mg/kg. The residual levels in egg yolks ranged from 0.006 mg/kg to 0.065 mg/kg diazinon equivalent, while the residual levels in 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 (weighing 268 kg) was orally administered a gelatin capsule containing 20 mg/kg 32P-diazinon (specific activity 518 cpm/ug). …Within 36 hours, approximately 74% of the administered radioactive material was excreted in urine, 6.5% in feces, and 0.08% in milk. The peak concentration of radioactive material in milk, equivalent to 2.27 mg/kg diazinon equivalent, was reached 18 hours after administration. Two lactating goats were orally administered (pyrimidine-14C) diazinon (specific activity 9.7 μCi/mg) at a dose of 4.5 mg/kg/day for four consecutive days, equivalent to an intake of 100 mg/kg of radioactive material from the feed. During the observation period, an average of 64.1% of the administered radioactive material was excreted in urine, 10.4% in feces, and 0.31% in milk. After 3 days of administration, the radioactive material concentration in milk reached a plateau, with an average level of 0.46 mg/kg diazinon equivalent. At euthanasia, the radioactive material in the blood accounted for 0.2% of the administered dose, and 0.92% of the administered dose was accumulated in the examined tissues. The highest residual radioactivity was detected in the kidneys (2.0 mg/kg) and liver (1.2 mg/kg). Other examined tissues contained 0.23–0.3 mg/kg diazinon equivalents. Two female beagle dogs were intravenously injected with 0.2 mg/kg of (ethoxy-14C)-diazinon (specific activity 3.4 μCi/mg), dissolved in 0.7 mL of ethanol. The calculated elimination half-life in the blood was 363 minutes. Within 24 hours of administration, approximately 58% of the administered radioactive material was excreted in the urine. Two other female beagle dogs were orally administered 4.0 mg/kg of (ethoxy-14C)-diazinon (dissolved in ethanol). Within 24 hours of oral administration, approximately 85% of the radioactive material was recovered, with 53% excreted in the urine. For more complete data on the absorption, distribution, and excretion of diazinons (a total of 8), please visit the HSDB record page.
Metabolism/Metabolites
The main metabolic degradation pathways of diazinon include: ester bond cleavage to form hydroxypyrimidine derivatives; partial conversion of PS to PO derivatives; oxidation of isopropyl substituents to form corresponding tertiary and primary alcohol derivatives; oxidation of methyl substituents to form corresponding alcohols; and glutathione-mediated ester bond cleavage to form glutathione conjugates.
Studies on the metabolism of diazinon in rats revealed that the metabolite 2-isopropyl-4-methyl-6-hydroxypyrimidine… and two unidentified metabolites were excreted in urine and feces, accounting for 70% of the administered dose. …Metabolites of diazinon in rats…labeled with ¹⁴C…The positions of the three metabolites in the general metabolic pathway were determined by tracing the metabolic pathway after intravenous injection. Since the acute oral toxicity of these three compounds is less than one-tenth that of diazinon, biotransformation is related to detoxification.
Diazinon…appears to be metabolized in lactating cows to the corresponding phosphate and hydrolyzed to diethyl thiophosphate and diethyl phosphate, releasing 2-hydroxy-6-isopropyl-4-methylpyrimidine (and its metabolite diazinon).
Hydroxydiazinon was detected in tissues after gavage administration of diazinon to sheep. Diazinon is also metabolized in sheep via C-4 hydroxylation. Residues of this hydroxylation product and a C-1' isopropanol analogue were found in sheep….
For more complete data on the metabolism/metabolites of diazinon (10 metabolites in total), please visit the HSDB record page.
Known human metabolites of diazinon include diethyl thiophosphate, diazinon, and pyrimidinol.
The metabolism of organophosphates mainly occurs through oxidation, esterase hydrolysis, and reaction with glutathione. Demethylation and glucuronidation may also occur. Oxidation of organophosphate pesticides can produce moderately toxic products. Generally, thiophosphates themselves are not directly toxic and require oxidative metabolism to be converted into proximal toxins. The products of glutathione transferase reactions are generally less toxic. Paraoxygenase (PON1) is a key enzyme in organophosphate metabolism. PON1 can inactivate certain organophosphates through hydrolysis. PON1 can hydrolyze active metabolites in various organophosphate insecticides and nerve agents (such as soman, sarin, and VX). The existence of PON1 polymorphism leads to differences in the enzyme activity level and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effects of organophosphate exposure.

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Biological half-life
After oral administration of the in vitro parasite killer (14)C diazinon, it is rapidly eliminated from rats (biological half-life is 12 hours).
80% of (14)C is excreted in urine and 18% in feces. Following intravenous injection of the three (14)C metabolites of diazinon, the excretion patterns were similar, but the biological half-life was shorter, at 9 hours. In rats, after oral administration, the excretion rate of ring- and side-chain labeled diazinon exceeded 90% after 168 hours. The biological half-life of ethoxy-(14)C-diazinon in male rats was 7 hours, while the biological half-life of 2-(14)C-diazinon in both male and female rats was 12 hours. Two female beagle dogs were intravenously injected with 0.2 mg/kg ethoxy-14C-diazinon (specific activity 3.4 μCi/mg), dissolved in 0.7 mL of ethanol. …The calculated elimination half-life of the drug in the blood during the second phase was 363 minutes. …

Toxicity Summary
Identification: Diazinon is a colorless, transparent liquid with a slightly ester-like odor. It is soluble in most organic solvents. It is stable in neutral media but hydrolyzes slowly in alkaline media and more rapidly in acidic media. Diazinon is a contact organophosphate insecticide with broad-spectrum insecticidal activity. It is also frequently used in combination with other insecticides. Another major use is as a veterinary drug. Human Exposure: Concentrations of diazinon in the environment are typically low. Exposure to the general population occurs via inhalation and ingestion. Water exposure is negligible. Occupational exposure is primarily through skin contact. Several cases of accidental or suicide poisoning by diazinon have been reported, some fatal. In some cases, cholinergic syndrome may be more severe than expected due to the presence of highly toxic impurities (e.g., TEPP). In some cases, acute reversible pancreatitis has been associated with severe cholinergic syndrome. Reported cases of post-exposure poisoning have all been related to the presence of impurities. Animal Studies: Acute oral, dermal, and inhalation 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 acetylcholinesterase activity. Diazinon is mildly irritating to rabbit skin but not to the eyes. Diazinon is not skin-sensitizing. Reproductive and developmental studies have not revealed embryotoxicity or teratogenicity. No effects on reproductive performance have been observed at dose levels that are non-toxic to parents. Mutagenicity studies at various in vivo and in vitro endpoints have not revealed mutagenicity. Carcinogenicity has not been found in rats or mice. Diazinon has been reported to cause acute pancreatitis in dogs and guinea pigs; this is considered a species-specific effect. Diazinon can be absorbed via the gastrointestinal tract, intact skin, and inhalation. Diazinon is oxidized by microsomal enzymes to cholinesterase inhibitor metabolites, such as diazinon, hydroxydiazinon, and hydroxydiazinon. Diazinon is a cholinesterase or acetylcholinesterase (AChE) inhibitor. Cholinesterase inhibitors (or “anticholinesterases”) inhibit the activity of acetylcholinesterase. Because acetylcholinesterase plays a vital physiological role, chemicals that interfere with its activity are potent neurotoxins. Even low doses can cause excessive salivation and lacrimation, followed by muscle spasms and ultimately death. Substances used in nerve gases and many pesticides have been shown to exert their effects by binding to serine residues at the active site of acetylcholinesterase, thus completely inhibiting the enzyme's activity. Acetylcholinesterase is responsible for breaking down the neurotransmitter acetylcholine, which is released at the neuromuscular junction, causing muscle or organ relaxation. Inhibition of acetylcholinesterase results in the accumulation and sustained action of acetylcholine, leading to continuous nerve impulse transmission and unstoppable muscle contractions. The most common acetylcholinesterase inhibitors are phosphorus-containing compounds designed to bind to the enzyme's active site. Their structural requirements include: a phosphorus atom with two lipophilic groups, a leaving group (e.g., a halide or thiocyanate), and a terminal oxygen atom.

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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)

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Interactions
This study investigated the potential combined toxicity of diazinon, propoxyurea, and bisphenol A (BPA) to the proliferation of cultured mouse RAW264.7 cells. Cytotoxicity was assessed using the MTT assay. The half-maximal inhibitory concentrations (IC50) and their 95% confidence intervals (CIs) of diazinon, propoxyurea, and bisphenol A, individually and in combination (mixed according to IC50 ratio), were determined using a weighted probability unit method. Three commonly used methods for assessing the toxic interactions of binary mixtures—the additional index method, the equivalent effect curve method, and the logistic regression method—were employed to evaluate the types of toxic interactions between diazinon and bisphenol A (BPA), and between propoxyurea and BPA. Twenty-four hours after exposure, the IC50 values and 95% confidence intervals for diazinon, propoxyurea, and BPA in RAW264.7 cells were 194.1 μg/mL (173.4 μg/mL–217.4 μg/mL), 448.4 mg/L (358.2 μg/mL–573.2 μg/mL), and 37.5 μg/mL (35.3 μg/mL–39.9 μg/mL), respectively. The IC50 values and their 95% confidence intervals for the mixtures of diazinon and bisphenol A, and the mixture of propoxyurea and bisphenol A, were 168.8 μg/mL (160.1 μg/mL–178.2 μg/mL) and 253.4 μg/mL (236.0–273.0 μg/mL), respectively. In the interaction assessment, all three methods showed an antagonistic effect between diazinon and bisphenol A, while propoxyurea showed an additive effect. ...

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Non-human toxicity values
Oral LD50 for male rats: 1340 mg/kg
Oral LD50 for female rats: 1160 mg/kg
Inhalation LC50 for rats: >5540 mg/cu m 4 hr
Inhalation LC50 for rats: >2330 mg/cu m 4 hr
For more complete (52 data points) non-human toxicity values for diazinon, please visit the HSDB record page.

Therapeutic Use
Veterinary Use: Used in veterinary practice to combat...flies and ticks.

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.

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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.

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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.

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