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 hr, 130 day-old loblolly pine seedlings absorbed and distributed (14)C-orthene from nutrient solution.
Most organophosphate compounds are ... absorbed from skin, conjunctiva, gastrointestinal tract, & lung. /Organophosphate compounds/
The rate of dermal absorption /of organophosphorus pesticides/ may be ... influenced by the solvent used. /Organophosphorus pesticides/
... The organophosphorus insecticides are, in contrast to the chlorinated insecticides, rapidly metabolized & excreted and are not appreciably stored in body tissues. /Organophosphorus insecticides/
For more Absorption, Distribution and Excretion (Complete) data for ACEPHATE (7 total), please visit the HSDB record page.

---

Metabolism / Metabolites
... Acephate treated /White Leghorn laying hen/ received appropriate doses, 5 to 700 mg/kg, of the agent dissolved in water by gavage at 5 ml/kg. The birds were sacrificed 23.5 to 24 hr after treatment. Brain methamidophos levels were 10 to 16% of the total acephate plus methamidophos brain concentration. The lower the dose of acephate, the higher the relative percentage of methamidophos.
In plant tissue, orthene is partially metabolized to O,S-dimethyl phosphoramidothioate, the active ingredient in the insecticide monitor. /Monitor - product name/
Toxicity of orthene to insects was related to monitor production and degradation. O- and S-Demethylation, prior to deacetylation, contributed to resistance. With excised cotton leaves, orthene was converted to some monitor as well as O-demethyl orthene. /Monitor - product name/
Plasma & tissue enzymes are responsible for hydrolysis /of organophosphorus compounds/ to the corresponding phosphoric & phosphonic acids. However, oxidative enzymes are also involved in the metabolism of some organophosphorus compounds. /Organophosphorus compounds/
These chemicals are detoxified by cytochrome p450-mediated monooxygenases in the liver, but some metabolites are more toxic than parent cmpd ... Metabolites usually are detected from 12 to 48 hr postexposure. /Organophosphate cmpd/
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.

Toxicity Summary
Acephate 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
LCLo (mice) = 2,200 mg/m3/5h

---

Interactions
Anticholinesterase (organophosphorus) insecticides antagonize polarizing muscle relaxants. Phenothiazines /and thioxanthene/: ...may enhance toxic effects of organophosphorus insecticides. /Insecticides, organophosphorus/
... Aluminium, a common metal compound, and acephate, an organophosphorous pesticide, are two widely used chemicals known for their neurotoxic effects. To assess the toxic interaction of aluminium and acephate, acute toxicity study of aluminium chloride, acephate, and their combination was made. Male Wistar albino rats were dosed orally in a increasing geometric progressive doses of aluminium chloride, acephate, and their combination (1 part aluminium:1 part acephate) in distilled water. The median lethal oral dose of aluminium chloride, acephate, and their combination was found to be 3630 +/- 400, 2851 +/- 269, and 4074 +/- 388 mg/kg body weight respectively. Log dose-response curve revealed the acute toxic effects of combination of metal and pesticide to be reduced, suggesting antagonistic action. Antagonistic action of the combination of compounds shows that aluminium reduced the toxic effect of organophosphorous pesticide acephate. ...
The efficacy of a reactive skin decontaminant lotion against organophosphorus nerve agents in-vivo was examined. The agents used included tabun, sarin, soman, and VX. The decontaminant location consisted of a 1.25 modal solution of the potassium salt of 2,3-butanedione monoxime in polyethylene glycol methylether and 10% water mixture. This reactive skin decontaminant was highly effective against each of the four agents tested. In Sprague Dawley rats the inactivation process was dose dependent, with a 1:1 organophosphorus/potassium salt of 2,3-butanedione-monoxime molar ratio offering total protection against the toxic effects. The inactivation process, as a function of anticholinesterase activity in primary cultures of chick embryo neurons, was also time, dose and agent dependent. Soman was relatively slow in detoxifying over a 24 hour period when compared to the other three agents. Even so, in all cases less than 0.1% of the original organophosphate anticholinesterase activity remained after a 7 day period. It was concluded that this cell culture system is advantageous in evaluating the prophylaxis and therapy of nerve agent poisoning.

---

Non-Human Toxicity Values
LD50 Rat male oral 945 mg/kg /Technical grade/
LD50 Rat female oral 866 mg/kg /Technical grade/
LD50 Rat, male acute oral (technical) 866 mg/kg
LD50 Rat, female acute oral (technical) 945 mg/kg
For more Non-Human Toxicity Values (Complete) data for ACEPHATE (9 total), please visit the HSDB record page.

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

Acephate appears as a white solid. Used as a contact and systemic insecticide.
Acephate is a phosphoramide that is methamidophos in which one of the hydrogens is replaced by an acetyl group. It has a role as an acaricide, an EC 3.1.1.7 (acetylcholinesterase) inhibitor and an agrochemical. It is a mixed diacylamine, a phosphoramide, an organic thiophosphate and an organothiophosphate insecticide. It is functionally related to a member of methamidophos.
Acephate is a synthetic organic thiophosphate compound and weak organophosphate acetylcholinesterase inhibitor that is used as a pesticide. It is characterized as a moderately persistent and highly soluble colorless to white solid, and exposure occurs by inhalation, contact, or ingestion.
Acephate is an organophosphate foliar insecticide of moderate persistence with residual systemic activity of about 10–15 days at the recommended use rate. It is used primarily for control of aphids, including resistant species, in vegetables (e.g. potatoes, carrots, greenhouse tomatoes, and lettuce) and in horticulture (e.g. on roses and greenhouse ornamentals). It also controls leaf miners, caterpillars, sawflies and thrips in the previously stated crops as well as turf, and forestry. By direct application to mounds, it is effective in destroying imported fire ants.

---

Mechanism of Action
Many of the more recently introduced organophosphorus esters (acephate ...) are less tenacious inhibitors of nervous tissue acetylcholinesterase, the phosphorylated enzyme being more readily and spontaneously dissociated.
Organophosphorus derivatives act by combining with and inactivating the enzyme acetylcholinesterase. ... The inactivation of cholinesterase by cholinesterase inhibitor pesticides allows the accumulation of large amounts of acetylcholine, with resultant widespread effects that may be ... separated into 4 categories: (1) Potentiation of postganglionic parasympathetic activity. ... (2) Persistent depolarization of skeletal muscle ... (3) Initial stimulation following depression of cells of central nervous system ... (4) Variable ganglionic stimulation or blockade ... /Cholinesterase inhibitor pesticides/
1. The molecular composition of acetylcholinesterase (acetylcholinesterase) obtained from cockroach neural, and rat brain tissues was different. Vertebrate enzyme exhibited a higher degree of polymerization than insect enzyme. 2. Acephate was a potent inhibitor of cockroach acetylcholinesterase, but a poor inhibitor of rat acetylcholinesterase. Unlike acephate, methamidophos was a potent inhibitor of both cockroach and rat enzymes. Acephate exhibited greater affinity for the cockroach acetylcholinesterase than for the rat acetylcholinesterase, and acephate phosphorylated the cockroach acetylcholinesterase several times faster than the rat enzyme. The rate of phosphorylation of insect and rat acetylcholinesterase was similar in the presence of methamidophos. Solubilization of acetylcholinesterase by Triton X-100 altered the kinetics of inhibition of rat acetylcholinesterase by acephate. However, solubilization did not alter the kinetics of inhibition of rat acetylcholinesterase by methamidophos or the kinetics of inhibition of cockroach acetylcholinesterase by acephate or methamidophos. 3. The mechanism of acephate cockroach acetylcholinesterase interaction was different than the mechanism of acephate rat acetylcholinesterase interaction. It is proposed that both the rat and cockroach enzyme may contain, along with the anionic and esteratic sites, an "electron deficient" binding site which may exhibit selectivity for acephate and nefopam. The electron deficient site in rat acetylcholinesterase has allosteric properties, whereas the cockroach acetylcholinesterase does not. It is also proposed that the electron deficient site in cockroach acetylcholinesterase may be situated in or adjacent to the active site and, therefore, acephate may be bound to the electron deficient site such that the phosphate moiety of acephate interacts with the enzyme's "esteratic" site. Although nefopam also bound to the electron deficient site in cockroach acetylcholinesterase, it did not inhibit the enzyme. This study also indicated that the electron deficient site in rat acetylcholinesterase may be peripheral to the active site, and that the binding of acephate to this site prevented the phosphorylation by methamidophos of the rat acetylcholinesterase. Unlike acephate, methamidophos specifically bound to the active site in both the 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.

---

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