Absorption, Distribution and Excretion
The concentrations of profenofos in whole blood, urine, and gastric contents were 1200 ng, 350 ng, and 3.35 mg/mL, respectively. In rats, 14C-profenofos was rapidly excreted after oral administration. The main metabolic pathways involve stepwise dealkylation and hydrolysis, followed by conjugation reactions. Metabolism/Metabolites Organophosphate metabolism primarily occurs through oxidation, esterase hydrolysis, and reactions 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. Products produced by 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 a variety of organophosphate pesticides and nerve agents (such as soman, sarin, and VX). The polymorphism of PON1 leads to differences in the enzyme activity level and catalytic efficiency of this esterase, suggesting that different individuals may be more susceptible to the toxicity of organophosphates.

Toxicity Summary
Profenofos 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 and ultimately death. Substances used in nerve gases and 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 are: 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
LC50 (rat) = 3,000 mg/m³/4hInteractions
... Four hours after intraperitoneal injection into mice, five organophosphorus pesticides inhibited 50% of the brain fatty acid amide hydrolysis activity (ED50) at doses below 30 mg/kg; the inhibitory effects of chlorpyrifos, diazinon, and methamidophos occurred near acute toxic doses, while profenofos and triphenylphosphine were effective at asymptomatic doses. …An inhibition rate of ≥76% of the brain fatty acid amide hydrolysis inhibited movement in mice injected intraperitoneally with 30 mg/kg anandamide, often leading to limb paralysis. Therefore, organophosphorus pesticides and related fatty acid amide hydrolysis inhibitors can enhance the activity of anandamide in mice. …A mixture of atropine with physostigmine, pyridoxime, or the dipyridine compound SAD-128 increased the LD50 of profenofos by 7-fold and 4-fold, respectively, in chicks and mice when administered simultaneously. The poor efficacy of atropine and oxime compounds as antidotes to profenofos suggests that the acetylcholinesterase (AChE) inhibited by profenofos may be rapidly aging. The cerebral acetylcholinesterase in chicks poisoned with profenofos could not be reactivated by pyridoxime mesylate, while the cerebral acetylcholinesterase in chicks poisoned with methamidophos could be reactivated by pyridoxime mesylate. Similarly, eel acetylcholinesterase (AChE) was inhibited in vitro by bioactivated (-)-propanofos (the most toxic isomer) but not reactivated, in contrast to AChE inhibited by methamidophos, non-bioactivated (-)-propanofos, and (+)-propanofos (regardless of bioactivation).

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Non-human toxicity values
Oral LD50 in rats: 400 mg/kg
Dermal LD50 in rats: 300 mg/kg
Oral LD50 in mice: 162 mg/kg
Oral LD50 in rabbits: 700 mg/kg
For more complete non-human toxicity data on propofol (7 types), please visit the HSDB record page.

[1]. Profenofos, an Acetylcholinesterase-Inhibiting Organophosphorus Pesticide: A Short Review of Its Usage, Toxicity, and Biodegradation J Environ Qual.2016 Sep;45(5):1478-1489.

Profenofos is a pale yellow liquid with a garlic odor and is corrosive, used as an insecticide. Profenofos is an organothiophosphate insecticide, belonging to the organophosphate and organochlorine insecticide classes, and is also a monochlorobenzene compound. It is an EC 3.1.1.7 (acetylcholinesterase) inhibitor, acaricide, and agricultural chemical. Its structure is similar to 4-bromo-2-chlorophenol. Profenofos is a widely used insecticide for various crops, mainly for controlling lepidopteran insects and mites. It is a non-systemic insecticide with contact and stomach poison action, and is an acetylcholinesterase (AChE) inhibitor. It is a broad-spectrum organophosphate pesticide widely used for pest control in cotton fields. It is a pale yellow liquid with a garlic odor and is corrosive. Organophosphates readily generate highly toxic and flammable phosphine gas in the presence of strong reducing agents (such as hydrides). Partial oxidation by oxidizing agents may lead to the release of toxic phosphorus oxides.

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Mechanism of Action
Non-systemic insecticides and acaricides, with contact and stomach poison effects. Systemic action is also present. Cholinesterase inhibitor.

C11H15BRCLO3PS

373.63

371.935

41198-08-7

38779

Colorless to light yellow liquid

1.5±0.1 g/cm3

401.8±55.0 °C at 760 mmHg

196.8±31.5 °C

0.0±0.9 mmHg at 25°C

1.553

4.6

0

4

7

18

296

0

CCCSP(=O)(OCC)OC1=C(C=C(C=C1)Br)Cl

QYMMJNLHFKGANY-UHFFFAOYSA-N

InChI=1S/C11H15BrClO3PS/c1-3-7-18-17(14,15-4-2)16-11-6-5-9(12)8-10(11)13/h5-6,8H,3-4,7H2,1-2H3

4-bromo-2-chloro-1-[ethoxy(propylsulfanyl)phosphoryl]oxybenzene

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

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 (133.82 mM)

Solubility in Formulation 1: 2.5 mg/mL (6.69 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
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 (6.69 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 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 (6.69 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.)