Absorption, Distribution and Excretion
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/
Many organophosphorus insecticides are excreted in milk. /Organophosphorus insecticides/
After absorption, almost all organophosphorus compounds are excreted in urine as hydrolysis products. /Anticholinesterase agents/
For more complete data on the absorption, distribution, and excretion of phenyl sulfides (6 in total), please visit the HSDB record page.

---

Metabolism/Metabolites ELSAN is rapidly degraded in /cabbage seedlings, strawberries, and apple fruits/…and hydrolyzed into non-toxic derivatives. The main metabolites…are ELSAN carboxyl derivatives, mandelic acid, and bis(ethoxycarbonylbenzyl) disulfide.
After mice were administered a 30 mg/kg dose of thiophene, the major metabolites in their urine were O-demethyl acid (25.8%), O-demethyloxo acid (18.4%), and dimethyl phosphate dithiosulfate (16.9%). The initial products of PS cleavage…are further metabolized to the corresponding sulfides, mandelic acid, and S-methylated derivatives.
In plants, thiophene is first oxidized to thiophosphate, then hydrolyzed. Identified metabolites include phosphoric acid, dimethyl phosphate, and monomethyl phosphate.
Five metabolites were detected in the plasma and urine of a patient who ingested the organophosphate insecticide thiophene. Intact thiophene was detected only in the gastric lavage fluid. Following methylation of acidic extracts from plasma and urine, phenylsulfate, demethyl phenylsulfate, oxyphenylsulfate, S-isomer of demethyl phenylsulfate, and S-isomer of demethyl phenylsulfate were identified by gas chromatography and gas chromatography-mass spectrometry (GC-MS) in conjunction with synthesized phenylthiophosphoric acid analogs. The major metabolites were phenylsulfate and oxyphenylsulfate. Although demethylbenzoic acid oxy is an important metabolite, benzoic acid oxy, benzoic acid oxy, or demethylbenzoic acid oxy were not detected. If oxy is generated in the patient, it may be rapidly degraded to demethylbenzoic acid oxy by carboxylesterases or glutathione transferases. For more complete metabolite/metabolite data on benzoic acid (7 metabolites), please visit the HSDB record page.

Toxicity Data
LC50 (Rat) = 59 mg/m³/4h

---

In vitro metabolic studies were conducted on rats following oral administration of a 100 mg/kg non-toxic dose of benzoate (O,O-dimethyl S-(α-(ethoxycarbonyl)benzyl)dithiophosphate). The same metabolic studies were also performed after concurrent administration of 0.5% O,S,S-trimethyl dithiophosphate (OSS-Me). When administered alone, benzoate is primarily metabolized via ethoxycarbonyl ester hydrolysis and PO and CS bond cleavage, producing at least six metabolites. The main metabolite excreted in urine is benzoic acid. Concurrent administration of 0.5% OSS-Me did not alter the types of excreted metabolites. However, a reduction in carboxylesterase-catalyzed products (benzoate) was observed, indicating inhibition of the enzyme responsible for the main benzoate detoxification pathway.
The levels of total lipids, free fatty acids, cholesterol, and lipase activity in specific tissues of the snakehead (Channa punctatus Bloch) were investigated during both single and combined exposure to carbaryl and benzoate. Under all exposure conditions, total lipid levels decreased, while free fatty acid and lipase activity increased, indicating increased lipid hydrolysis for energy to cope with pesticide toxicity stress. Cholesterol levels showed an increasing trend. ...The combined treatment with carbaryl and benzoate produced a higher effect than either pesticide alone, indicating an additive effect.
Some phenothiazines may antagonize, while others may enhance... (organophosphate insecticides) toxic anticholinesterase activity. /Organophosphate cholinesterase inhibitors/
For more complete data on interactions of phenyl sulfides (7 in total), please visit the HSDB record page.

---

Non-human toxicity values
Mice oral LD50 350-400 mg/kg /Technical Product/
Rat oral LD50 300-400 mg/kg /Technical Product/
Rat oral LD50 77.7 mg/kg
Rat oral LD50 118 mg/kg
For more complete non-human toxicity data for phenyl sulfides (10 in total), please visit the HSDB record page.

[1]. Fatal Poisoning With Both Dichlorvos and Phenthoate. J Forensic Sci. 2018 Nov;63(6):1928-1931.

[2]. Elucidating the Potential Neurotoxicity of Chiral Phenthoate: Molecular Insight From Experimental and Computational Studies. Chemosphere. 2020 Sep;255:127007.

Phenthoate is an organothiophosphate ester, a compound in which the hydroxyl group of ethyl mandelate is replaced by a thiodiyl group of (dimethoxythiophosphate). It is an EC 3.1.1.7 (acetylcholinesterase) inhibitor, acaricide, and agrochemical. It is an organothiophosphate ester, organothiophosphate insecticide, and ethyl ester. Phenthoate is a synthetic organothiophosphate ester compound and an organophosphate acetylcholinesterase inhibitor used as an insecticide. It is a colorless crystalline solid with an aromatic odor and can be accessed through inhalation, ingestion, or contact. Mechanism of Action: Cholinesterase inhibitor. The cardiovascular effects of anticholinesterase drugs are complex because they reflect the intraganglionic and postganglionic effects of accumulated acetylcholine on the heart and blood vessels. The main effect of accumulated acetylcholine (ACh) on the heart through peripheral action is bradycardia, leading to a decrease in cardiac output. Higher doses typically lead to a drop in blood pressure, often a result of the effects of anticholinesterase drugs on the medullary vasomotor center of the central nervous system. /Anticholinesterase drugs/
Organophosphate derivatives exert their effects by binding to and inactivating acetylcholinesterase. …Cholinesterase inhibitors inactivate cholinesterase, leading to the accumulation of large amounts of acetylcholine, resulting in a wide range of effects, which can be categorized into four types: (1) Enhanced postganglionic parasympathetic activity. …(2) Continuous depolarization of skeletal muscle. …(3) Initial stimulation following central nervous system cell inhibition. …(4) Varying degrees of ganglion excitation or blockade. … /Cholinesterase inhibitors/
The main characteristic of the toxic mechanism of organophosphate pesticides is the inhibition of esterase activity, particularly cholinesterase, which plays an important role in physiological processes. Organophosphate pesticides can also indirectly interact with the biochemical receptors of acetylcholine. /Organophosphate pesticides/
For more complete data on the mechanisms of action of phenyl sulfides (7 in total), please visit the HSDB record page.

C12H17O4PS2

320.36

320.03

2597-03-7

17435

Colorless to light yellow liquid

1.3±0.1 g/cm3

379.5±52.0 °C at 760 mmHg

156ºC

183.3±30.7 °C

0.0±0.9 mmHg at 25°C

1.564

3.96

0

6

8

19

324

0

CCOC(=O)C(C1=CC=CC=C1)SP(=S)(OC)OC

XAMUDJHXFNRLCY-UHFFFAOYSA-N

InChI=1S/C12H17O4PS2/c1-4-16-12(13)11(10-8-6-5-7-9-10)19-17(18,14-2)15-3/h5-9,11H,4H2,1-3H3

ethyl 2-dimethoxyphosphinothioylsulfanyl-2-phenylacetate

Dimephenthioate; Phenthoate; Phenthoate

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 : ~250 mg/mL (~780.37 mM)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

---

Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

View More

Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

---

Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

View More

Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

---

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

---

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