Absorption, Distribution and Excretion
Pirimiphos-methyl is known to be absorbed through intact skin, from the GI tract, & by inhalation.
Oral administration of 2-(14)C-ring-labelled pirimiphos-methyl at a dose of 0.6 mg/kg bw to five male rats resulted in a mean urinary excretion of 80.7% and mean fecal excretion of 7.3% in 24 hr, indicating rapid absorption. At 96 h, 86.0% and 15.2% of the administered dose had been excreted in urine and feces, respectively. Nine (unidentified) metabolites were present in the urine.
Female rats given 2-(14)C-pirimiphos-methyl at a dose of 7.5 mg/kg bw orally were bled (cardiac puncture, three rats per time interval) at 0.5, 1, 3, 5, 7 or 24 hr after dosing. Maximum blood concentrations (at 0.5 hr) were 2-3 ug/mL, declining by 50% 1 hr after dosing. By 24 hr, concentrations of (14)C in blood were 0.2-0.3 ug/mL, and of pirimiphos-methyl, 0.01-0.02 ug/mL. Rats treated for 4 days with 2-(14)C-pirimiphos-methyl at a dose of 7.5 mg/kg bw per day and sacrificed at intervals of 24 hr did not show any increase in blood concentrations with time. Tissue concentrations of total radioactivity in the liver, kidney and fat over the 4 days were generally less than 2 mg pirimiphos-methyl equivalents/kg tissue (concentrations of unchanged pirimiphos-methyl being less than 0.15 mg/kg tissue). There was no evidence of tissue accumulation.
Adult male Wistar rats were intubated with (14)C-labelled pirimiphos-methyl at a dose of 1 mg/kg bw per day. Four groups of three animals were dosed for 3, 7, 14 or 21 days and sacrificed 24 hr after the final dose. A further five groups of three rats were given similar doses for 28 days and sacrificed 1, 3, 7, 14, or 28 days after dosing. For each of the nine groups, one rat that did not receive pirimiphos-methyl was used as a control. After sacrifice, samples of liver, kidney, muscle, fat, erythrocytes and plasma were taken for analyses. Urine and feces were collected from two rats during the 24 hr after the seventh dose. Recovery of (14)C from (14)C-labelled pirimiphos-methyl added to control tissues was 96.9 +/- 5.2%. In all tissue samples taken at all time intervals, the concentration of radioactivity was very low, close to or below detection limits. Concentrations did not increase with repeated dosing. Liver concentrations were fairly constant (0.03 ppm) and similar concentrations were detected in some kidney samples. In other tissues, the concentration of radioactivity was generally below the limits of detection (0.04-0.06 ppm). Three days after cessation of dosing, one animal had detectable concentrations of radioactivity in the kidney. At 7 days and on subsequent days, no residues were found. Excretion was between 70% and 80% of a single dose, after administration of seven consecutive doses, providing evidence for rapid metabolism and elimination rather than poor absorption.
For more Absorption, Distribution and Excretion (Complete) data for PIRIMIPHOS-METHYL (6 total), please visit the HSDB record page.

---

Metabolism / Metabolites
Twelve metabolites of pirimiphos-methyl were separated by thin-layer chromatography from the urine of rats & a dog. No unchanged compound was detected & no metabolite had anticholinesterase activity. Briefly, the P-O bond is cleaved extensively & N-dealkylation &/or conjugation is a further step in the metabolism of the pyrimidine leaving group.
The mechanism by which large repeated doses of pirimiphos-methyl reduces the hemoglobin of rats is unknown. It may be caused by 2-diethylamino-4-hydroxy-6-methylpyrimidine, a metabolite formed by both mammals and plants. Although this metabolite has an acute toxicity of the same order of magnitude as the parent compound, it was (unlike the parent compound) tolerated by rats at a dosage of 400 mg/kg for 2 wk; even so, its action on the blood was indicated by an incr in reticulocytes & a decr in lymphocytes.
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
Female rats given 2-(14)C-pirimiphos-methyl at a dose of 7.5 mg/kg bw orally were bled (cardiac puncture, three rats per time interval) at 0.5, 1, 3, 5, 7 or 24 hr after dosing. Maximum blood concentrations (at 0.5 hr) were 2-3 ug/mL, declining by 50% 1 hr after dosing.

Toxicity Summary
Pirimiphos-methyl 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
LC (rat) > 5040 mg/m3/4h

---

Interactions
The effect of L-ascorbic acid supplementation on Pirimiphos-methyl induced toxicity was studied in albino rats. Biochemical estimations were made in rats administered orally the insecticide at 100 and 200 mg/kg body weight with or without oral supplementation of L-ascorbic acid at 200 mg/kg b.w. The biochemical assessments included estimations of brain and plasma cholinesterases, levels of ascorbic acid in liver, kidney and adrenals, urinary levels of ascorbic acid and glucuronic acid. A lower degree of inhibition of the cholinesterases was evident in ascorbic acid supplemented rats. Marked elevation in urinary levels of ascorbic acid and glucuronic acid was observed in the insecticide treated rats. Results of this study suggests that L-ascorbic acid supplementation partially offsets Pirimiphos-methyl induced toxicity
Technical hexachlorocyclohexane (100 mg/kg/d) and pirimiphosmethyl EC 50 (250 mg/kg/d) given individually and in combination to female rats for 7, 15 or 30 d by skin application caused poisoning, pathomorphological changes in vital organs, and significant enzymatic changes in liver and serum. The changes produced by the 2 compounds in combination did not suggest potentiation at the tested dose levels.
The pesticides benomyl, a benzimidazole fungicide, and pirimiphos-methyl, an organophosphorus insecticide, were tested separately and in combination at a ratio of 6:1, a mixture frequently found in foodstuffs by residual analysis, to determine their possible genotoxic action. The effect was measured by the micronucleus test carried out on cultured rat hepatocytes stimulated to proliferate by epidermal growth factor (EGF). Adult rat hepatocytes were exposed in vitro for 48 hr to the substances at increasing non-cytotoxic doses, chosen on the basis of cytotoxicity tests such as LDH and Neutral red assays. Benomyl induced a significant dose-related increase in micronucleus frequency; in contrast, pirimiphos-methyl was not genotoxic at any dose tested. When the hepatocytes were exposed to the two pesticides together at increasing doses, an enhancement in micronucleus frequency similar to that of benomyl alone was found, indicating that at this ratio and non-cytotoxic doses (up to 25 micrograms/mL benomyl + 4.2 micrograms/mL pirimiphos-methyl) no interaction occurs.

---

Non-Human Toxicity Values
LD50 Rat oral 1250 mg/kg
LD50 Mouse oral 1180 mg/kg
LD50 Rabbit oral 1150 mg/kg
LD50 Guinea pig oral 1000 mg/kg
For more Non-Human Toxicity Values (Complete) data for PIRIMIPHOS-METHYL (15 total), please visit the HSDB record page.

[1]. Detection of Pirimiphos-Methyl in Wheat Using Surface-Enhanced Raman Spectroscopy and Chemometric Methods. Molecules. 2019 Apr 30;24(9):1691.

[2]. In Vitro Toxicity of Pirimiphos-Methyl in Atlantic Salmon Hepatocytes. Toxicol In Vitro. 2017 Mar;39:1-14.

[3]. Atmospheric Degradation of the Organothiophosphate Insecticide - Pirimiphos-methyl. Sci Total Environ. 2017 Feb 1;579:1-9.

Pirimiphos-methyl is a yellow liquid. Corrosive to tin and mild steel. Used as an insecticide.
Pirimiphos-methyl is an organic thiophosphate that is O,O-dimethyl O-pyrimidin-4-yl phosphorothioate substituted by a methyl group at position 6 and a diethylamino group at position 2. It has a role as an EC 3.1.1.7 (acetylcholinesterase) inhibitor, an acaricide, an agrochemical, an insecticide and an environmental contaminant. It is an organic thiophosphate and an aminopyrimidine. It is functionally related to a 2-diethylamino-6-methylpyrimidin-4(1H)-one.
Pirimiphos-methyl is an organophosphate and fumigant insecticide with pirimiphos-methyl and no longer in production. It is used to control a wide range of insects and mites in stores, animal houses, domestic and industrial premisies. It is considered to be an acetylcholinesterase (AChE) inhibitor with contact and respiratory action. This is one of several compounds used for vector control of Triatoma.

---

Mechanism of Action
Systemically, pirimiphos-methyl inhibits cholinesterase, & this is the only known mechanism of its toxic action. In spite of its rapid absorption, rats, given a dosage of 1,450 mg/kg, did not show clear signs of poisoning until 24 hr later, when their brain cholinesterase was inhibited by 46%. Recovery of cholinesterase activity began to be apparent in 72 hr; it was complete for plasma enzyme by 96 hr but was slower for the red cell enzyme.

C11H20N3O3PS

305.33

305.096

29232-93-7

Pirimiphos-methyl-d6;1793055-06-7

34526

Light yellow to yellow liquid

1.2±0.1 g/cm3

386.5±52.0 °C at 760 mmHg

15°C

187.6±30.7 °C

0.0±0.9 mmHg at 25°C

1.555

4

0

7

7

19

310

0

CCN(CC)C1=NC(=CC(=N1)OP(=S)(OC)OC)C

QHOQHJPRIBSPCY-UHFFFAOYSA-N

InChI=1S/C11H20N3O3PS/c1-6-14(7-2)11-12-9(3)8-10(13-11)17-18(19,15-4)16-5/h8H,6-7H2,1-5H3

4-dimethoxyphosphinothioyloxy-N,N-diethyl-6-methylpyrimidin-2-amine

AI3-27699 Actelic Pirimiphos-methyl

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

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

DMSO : ~50 mg/mL (~163.76 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (8.19 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 (8.19 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 (8.19 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.)