AChE

After three hours of culture, acephate starts to decrease basal androgen output in rat immature Leydig cells in a dose-dependent manner, commencing at 0.5 μM. At 50 μM, acephate dramatically reduces the production of testosterone induced by 8-Br-cAMP and luteinizing hormone. At 50 μM, acephate dramatically reduces progesterone-mediated androgen production [1].

Sperm motility and count reduced at doses of 14 and 28 mg/kg/day when adult male mice were administered Acephate at 0, 7, 14, and 28 mg/kg/day for 28 days [1].

Absorption, Distribution and Excretion
Within 1 hour, 130-day-old pine seedlings absorbed and distributed (14)C-catechol from the nutrient solution. Most organophosphorus compounds…are absorbed through the skin, conjunctiva, gastrointestinal tract, and lungs. /Organophosphorus compounds/
The skin absorption rate of organophosphorus pesticides may…be affected by the solvent used. /Organophosphorus pesticides/
…Compared to chlorinated pesticides, organophosphorus pesticides are metabolized and excreted rapidly and do not accumulate in large quantities in tissues. /Organophosphorus pesticides/
For more complete data on the absorption, distribution, and excretion of acephate (7 species), please visit the HSDB record page.

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Metabolism/Metabolites…White Leghorn laying hens treated with acephate were administered acephate dissolved in water at a dose of 5 ml/kg via gavage at a dose of 5 to 700 mg/kg. The hens were euthanized 23.5 to 24 hours after treatment. Methamidophos accounts for 10% to 16% of the total brain concentration of acephate and methamidophos. The lower the acephate dose, the higher the relative percentage of methamidophos. In plant tissues, catechol is partially metabolized to O,S-dimethylthiophosphoramide, the active ingredient of this insecticide. The toxicity of catechol to insects is related to the formation and degradation of the monitoring agent. O- and S-demethylation prior to deacetylation leads to resistance. In detached cotton leaves, catechol is converted into some monitoring agents as well as O-demethylated catechol. Plasma and tissue enzymes are responsible for hydrolyzing organophosphorus compounds into their corresponding phosphates and phosphonates. However, oxidases are also involved in the metabolism of some organophosphorus compounds. /Organophosphorus compounds/
These chemicals are detoxified in the liver by cytochrome P450-mediated monooxygenases, but some metabolites are more toxic than the parent compound…Metabolites are usually detected within 12 to 48 hours after exposure. /Organophosphorus compounds/
Organophosphorus metabolism mainly occurs through oxidation, esterase hydrolysis, and reactions with glutathione. Demethylation and glucuronidation may also occur. Oxidation of organophosphorus pesticides can produce moderately toxic products. Generally, thiophosphates themselves are not directly toxic and require oxidative metabolism to be converted into proximal toxins. Products produced by glutathione transferase reactions are generally less toxic. Paraoxygenase (PON1) is a key enzyme in organophosphorus metabolism. PON1 can inactivate some organophosphorus compounds through hydrolysis. PON1 hydrolyzes active metabolites in many organophosphorus pesticides and nerve agents such as soman, sarin, and VX. The presence of PON1 polymorphism leads to differences in the enzyme 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.

Toxicity Summary
Acetaminophen is a cholinesterase, or acetylcholinesterase (AChE) inhibitor. Cholinesterase inhibitors (or "anticholinesterases") inhibit the activity of acetylcholinesterase. Because acetylcholinesterase has important physiological functions, chemicals that interfere with its activity are potent neurotoxins; even low doses can cause excessive salivation and lacrimation, followed by muscle spasms, ultimately leading to death. Nerve gases and substances used in many pesticides have been shown to work by binding to serine residues at the active site of acetylcholinesterase, thus completely inhibiting the enzyme's activity. Acetylcholinesterase breaks 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 the continuous transmission of nerve impulses and the inability to stop muscle contractions. The most common acetylcholinesterase inhibitors are phosphorus-containing compounds designed to bind to the enzyme's active site. Its 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
Mouse LCLo = 2,200 mg/m³/5hInteractions
Anticholinesterase (organophosphorus) insecticides antagonize the effects of polarizing muscle relaxants. Phenothiazines/and thioxanthates/:…may enhance the toxic effects of organophosphorus insecticides. /Insecticides, Organophosphorus/
…Aluminum is a common metallic compound, and acephate is an organophosphorus insecticide; both chemicals are widely used due to their neurotoxic effects. To assess the toxic interactions between aluminum and acephate, we conducted acute toxicity studies of aluminum chloride, acephate, and mixtures thereof. Male Wistar albino rats were orally administered distilled aqueous solutions of aluminum chloride, acephate, and mixtures thereof (1 part aluminum: 1 part acephate) in ascending geometric progressions. The median lethal doses (LD50) of aluminum chloride, acephate, and their mixtures were 3630±400, 2851±269, and 4074±388 mg/kg body weight, respectively. Logarithmic dose-response curves showed a reduction in acute toxicity of the metal and pesticide mixtures, indicating an antagonistic effect. The antagonistic effect of the compound combination suggests that aluminum reduces the toxicity of the organophosphorus pesticide acephate. ...
The efficacy of a reactive skin disinfectant emulsion against organophosphorus nerve agents in vivo was investigated. The agents used included tabun, sarin, soman, and VX. The disinfectant consisted of a 1.25 mol concentration of polyethylene glycol methyl ether of potassium 2,3-butanedione monooxime and a 10% aqueous solution. This reactive skin disinfectant was highly effective against all four tested agents. In Sprague Dawley rats, the inactivation process was dose-dependent, with a 1:1 molar ratio of organophosphate to potassium 2,3-butanedione monooxime providing complete protection against toxic effects. In primary cultures of chicken embryo neurons, the inactivation process (as a function of anticholinesterase activity) was also time-, dose-, and agent-specific. Soman showed a relatively slow detoxification rate within 24 hours compared to the other three agents. Even so, after 7 days, the anticholinesterase activity of all agents was less than 0.1% of the initial activity. Therefore, this cell culture system demonstrates advantages in assessing the prevention and treatment of nerve agent poisoning.

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Non-human toxicity values
Oral LD50 in male rats: 945 mg/kg (technical grade)
Oral LD50 in female rats: 866 mg/kg (technical grade)
Acute oral LD50 in male rats (technical grade): 866 mg/kg
Acute oral LD50 in female rats (technical grade): 945 mg/kg
For more non-human toxicity values (complete data) for acephate (9 types in total), please visit the HSDB record page.

[1]. Acephate interferes with androgen synthesis in rat immature Leydig cells. Chemosphere. 2020 Apr;245:125597.

Acephate is a white solid used as a contact and systemic insecticide. Acephate is a phosphoramide compound, formed by replacing one hydrogen atom of methamidophos with an acetyl group. It functions as an acaricide, an EC 3.1.1.7 (acetylcholinesterase) inhibitor, and an agrochemical. It is a mixed diamide, phosphoramide, organothiophosphate, and organothiophosphate insecticide. Its functions are related to methamidophos compounds. Acephate is a synthetic organothiophosphate compound and a weak organophosphate acetylcholinesterase inhibitor used as an insecticide. It is a moderately persistent, highly soluble colorless to white solid that can be absorbed through inhalation, contact, or ingestion. Acephate is a moderately persistent organophosphate foliar insecticide with residual systemic activity of approximately 10-15 days at recommended application rates. It is mainly used to control aphids, including resistant aphids, in vegetables (such as potatoes, carrots, greenhouse tomatoes and lettuce) and horticultural crops (such as roses and greenhouse ornamental plants). It can also control leaf miners, caterpillars, sawflies and thrips in the above crops as well as in lawns and forestry. Direct application to ant mounds can effectively eliminate invasive fire ants.

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Mechanism of Action
Many newly introduced organophosphates (such as acephate) have a weak inhibitory effect on acetylcholinesterase in nerve tissue, and phosphorylated enzymes are more likely to spontaneously dissociate.
Organophosphate derivatives exert their effects by binding to and inactivating acetylcholinesterase. Cholinesterase inhibitor insecticides produce a wide range of effects by inactivating cholinesterase, leading to the accumulation of large amounts of acetylcholine. These effects can be divided into four categories: (1) enhanced postganglionic parasympathetic nerve activity; (2) sustained depolarization of skeletal muscle; (3) initial stimulation after central nervous system cell inhibition; (4) varying degrees of ganglion stimulation or blockade. /Cholinesterase Inhibitors/
1. The molecular composition of acetylcholinesterase (acetylcholinesterase) extracted from cockroach nerve tissue and mouse brain tissue differs. Vertebrate enzymes have a higher degree of polymerization than insect enzymes. 2. Acephate is a potent inhibitor of cockroach acetylcholinesterase, but its inhibitory effect on mouse acetylcholinesterase is weaker. Unlike acephate, methamidophos is a potent inhibitor of both cockroach and mouse acetylcholinesterase. Acephate has a higher affinity for cockroach acetylcholinesterase than for rat acetylcholinesterase, and acephate phosphorylates cockroach acetylcholinesterase several times faster than rat acetylcholinesterase. In the presence of methamidophos, the phosphorylation rates of insect and rat acetylcholinesterase are similar. Triton X-100 solubilizes acetylcholinesterase and alters the inhibitory kinetics of acephate on rat acetylcholinesterase. However, solubilization did not alter the inhibitory kinetics of methamidophos on rat acetylcholinesterase, nor did it alter the inhibitory kinetics of either methamidophos or methamidophos on cockroach acetylcholinesterase. 3. The mechanism of interaction between methamidophos and cockroach acetylcholinesterase differs from that between methamidophos and rat acetylcholinesterase. Some studies suggest that rat and cockroach acetylcholinesterases, in addition to anion-binding sites and ester-binding sites, may also contain an electron-deficient binding site, which may be selective for methamidophos and nefopam. The electron-deficient site in rat acetylcholinesterase exhibits allosteric properties, while cockroach acetylcholinesterase does not. Furthermore, some studies suggest that the electron-deficient site in cockroach acetylcholinesterase may be located inside or near the active site; therefore, methamidophos may bind to this electron-deficient site, with its phosphate group interacting with the enzyme's ester-binding site. Although nefopam can also bind to the electron-deficient site in cockroach acetylcholinesterase, it did not inhibit the enzyme's activity. This study also showed that the electron-deficient site in rat acetylcholinesterase may be located peripheral to the active site, and the binding of acephate to this site prevents phosphorylation of rat acetylcholinesterase by methamidophos. Unlike acephate, methamidophos can specifically bind to the active sites of rat and cockroach acetylcholinesterase.

C4H10NO3PS

183.17

183.011

30560-19-1

Acephate-d3;2140327-70-2

1982

White to yellow solid powder

1.3±0.1 g/cm3

2ºC

93°C

2 °C

1.475

-0.85

1

4

3

10

172

0

YASYVMFAVPKPKE-UHFFFAOYSA-N

InChI=1S/C4H10NO3PS/c1-4(6)5-9(7,8-2)10-3/h1-3H3,(H,5,6,7)

N-[methoxy(methylsulfanyl)phosphoryl]acetamide

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)

H2O: 125 mg/mL (682.43 mM)

Solubility in Formulation 1: 100 mg/mL (545.94 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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