Absorption, Distribution and Excretion
Eight autopsy samples from an individual who ingested a large amount of malathion were analyzed, detecting four components: intact pesticide, malathion, malathion monocarboxylic acid (MCA), and malathion dicarboxylic acid (DCA). Malathion was detected in all samples except the liver. The highest concentrations were found in the stomach contents (8621 ppm) and adipose tissue (76.4 ppm). Malathion was present in very low amounts in some tissues; a significant amount was detected only in adipose tissue (8.2 ppm). MCA and DCA were detected in all tissues. MCA levels were higher: 221 ppm in bile, 106 ppm in the kidneys, and 103 ppm in the stomach contents. The metabolism of malathion after topical application in susceptible and resistant houseflies was investigated. The doses used were sublethal: 160 pmol for strain S (0.17 times the LD50) and 1570 pmol for strain R (0.1 times the LD50). Permeability was dose-dependent, and a semi-logarithmic plot of external drug concentration over time showed that permeability was not directly proportional to external drug concentration. Following administration, the in vivo concentration of malathion rapidly increased, peaking between 30 minutes and 2 hours (dose-dependent), and then slowly decreased. The metabolic degradation rate was highest in the early stages of poisoning. A three-compartment pharmacokinetic model was assumed to quantitatively interpret the experimental data. The first compartment represents the external malathion, and the other two compartments represent the internal parent compound. Statistical analysis showed that permeability was better described by the sum of two exponential functions than by a single exponential decay function. In this model, degradation occurred in the first inner compartment and was assumed to be a first-order reaction. The distribution of malathion between the two inner compartments was slow, conforming to first-order kinetics. Parameter estimation of the internal processes (degradation and exchange) using curve fitting procedures showed that no single set of parameter values could be used simultaneously for both strains. Studies on the differences in degradation capacity among strains showed that, in in vitro experiments, strain R exhibited a 4-fold higher oxidative degradation rate. Considering this difference, while other possibilities cannot be ruled out, a kinetic model can explain these two sets of data. ... In cow feces after oral administration of malathion, 7% of the total metabolites were soluble in chloroform, of which 85% were malathion and 12% were malathion. Milk contained small amounts of malathion metabolites (9.2% of the total dose after 7 days); of these, only 29% could be extracted from milk, and primarily partitioned into water rather than benzene, indicating the absence of malathion or malathion. Most organophosphate compounds... can be absorbed through the skin, conjunctiva, gastrointestinal tract, and lungs. /Organophosphates/ For more complete data on the absorption, distribution, and excretion of malathion (10 in total), please visit the HSDB records page.

---

Metabolism/Metabolites
Although the hydrolytic carboxyethoxylated metabolites of malathione have not yet been identified, given the extreme difficulty in detecting malathione in animal tissues, carboxylesterase hydrolysis of malathione is undoubtedly necessary.
In vitro studies in mouse livers show that only about half of the total detoxification of malathione is accomplished by carboxylesterase hydrolysis.
In vitro studies of resistant strains show that non-resistant housefly strains oxidatively degrade malathione at a rate 10 times higher than sensitive strains. When sensitive strains are used, the oxidation product is malathione β-monocarboxylic acid. Resistant strains also produce some β-monocarboxylic acid, but malathione α-monocarboxylic acid is likely the major metabolite.
Malathione has been shown to undergo “binding” inactivation in the liver and other tissues. This appears to indicate that active cholinesterase inhibitors are released from non-critical tissue binding sites, thereby protecting key acetylcholinesterases in nerve tissue from inhibition. For more complete data on the metabolism/metabolites of malathion (12 metabolites in total), please visit the HSDB record page. Malathion is a known human metabolite of malathion.

Interactions
The toxicity of malathion can be enhanced by O-ethyl-O-p-nitrophenylphenyl thiophosphate, tri-O-tolyl phosphate, and several other organophosphate compounds. This enhancement is presumably due to the inhibition of carboxylesterases or esterases responsible for the degradation of malathion in mammals. This mechanism is thought to lead to increased production of the activated product malathion, as the enzyme responsible for its degradation is inhibited. Pretreatment in rats with intraperitoneal injection of chloramphenicol (100 mg/kg) 30 minutes before a single oral LD50 dose (340 mg/kg) of malathion completely protected them from malathion-induced cholinesterase inhibition. The inhibitory effect of chloramphenicol pretreatment on malathion toxicity appears to be due to chloramphenicol inhibiting the metabolic activation of malathion to malathion. Some phenothiazines may antagonize, while others may enhance the anticholinesterase activity of organophosphate insecticides. /Organophosphate cholinesterase inhibitors/
During long-term treatment, corticosteroids antagonize the anti-glaucoma effect (increased intraocular pressure) of anticholinesterase. …Anticholinergic drugs antagonize the miotic (anti-glaucoma) effects of anticholinesterase on the autonomic and central nervous systems, as well as other muscarinic effects. Tricyclic antidepressants (with anticholinergic activity) antagonize the anti-glaucoma (miotic) effect of anticholinesterase in glaucoma. …Antihistamines with anticholinergic activity antagonize the miotic (anti-glaucoma) and central nervous system effects of anticholinesterase. Anticholinesterase enhances the sedation and behavioral changes induced by antihistamines. The effects of anticholinesterase drugs on autonomic effector cells, and to some extent on the central nervous system, can be antagonized by atropine, the first-line antidote. Barbiturates can be enhanced by anticholinesterase. …Dexpansionol can enhance the effects of anticholinesterase. Fluorophosphate insecticides can enhance the activity of other anticholinesterases. /Anticholinesterase/
For more complete data on interactions of MALAOXON (6 in total), please visit the HSDB record page.

---

Non-human toxicity values
Oral LD50 in rats: 158 mg/kg
Intraperitoneal LD50 in rats: 17,500 μg/kg

: Angelini DJ, Moyer RA, Cole S, Willis KL, Oyler J, Dorsey RM, Salem H. The Pesticide Metabolites Paraoxon and Malaoxon Induce Cellular Death by Different Mechanisms in Cultured Human Pulmonary Cells. Int J Toxicol. 2015 Sep-Oct;34(5):433-41. doi: 10.1177/1091581815593933. Epub 2015 Jul 14. PubMed PMID: 26173615.

Malaoxon is a colorless, viscous, oily liquid with a slightly unpleasant odor. (NTP, 1992)
2-[(dimethoxyphosphoryl)thio]succinate diethyl ester is a diester with the structure diethyl succinate, wherein the 2-position is replaced by a (dimethoxyphosphoryl)thio group. It is a diester, ethyl ester, and organothiophosphate.
Mechanism of Action

Maloxyphosphene is the active anticholinesterase metabolite of malathion…possessing inhibitory activity against acetylcholinesterase.
Culex tarsalis, a mosquito species from Fresno, California, exhibits remarkable resistance to malathion, a resistance that is highly specific, showing no resistance to any other organophosphate compound besides maloxyphosphene.
Organophosphate derivatives exert their effects by binding to and inactivating acetylcholinesterase (AChE). Cholinesterase inhibitors produce a wide range of effects by inhibiting cholinesterase activity, leading to the accumulation of large amounts of acetylcholine. These effects can be categorized into four types: (1) enhanced postganglionic parasympathetic nerve activity; (2) sustained depolarization of skeletal muscle; (3) initial stimulation following central nervous system cell inhibition; and (4) varying degrees of ganglion stimulation or blockade. /Cholinesterase Inhibitors/
The characteristic pharmacological effects of anticholinesterase (ChE) pesticides are primarily attributed to their inhibition of the hydrolysis of acetylcholine (ACh) by acetylcholinesterase (AChE) at the cholinergic transmission site. Consequently, neurotransmitter accumulation and enhanced responses to acetylcholine released by cholinergic impulses or spontaneously released acetylcholine from nerve endings occur. The acute effects of most organophosphate pesticides at moderate doses are almost entirely attributed to this effect. /Anticholinesterase Agents/
For more complete data on the mechanisms of action of MALAOXON (12 in total), please visit the HSDB record page.

C10H19O7PS

314.29246

314.058

1634-78-2

1634-78-2

15415

Colorless to light yellow liquid（Density：1.248±0.06 g/cm3）

1.2±0.1 g/cm3

376.0±52.0 °C at 760 mmHg

<20℃

181.2±30.7 °C

0.0±0.9 mmHg at 25°C

1.470

2.07

0

8

11

19

339

0

CCOC(=O)CC(C(=O)OCC)SP(=O)(OC)OC

WSORODGWGUUOBO-UHFFFAOYSA-N

InChI=1S/C10H19O7PS/c1-5-16-9(11)7-8(10(12)17-6-2)19-18(13,14-3)15-4/h8H,5-7H2,1-4H3

diethyl 2-dimethoxyphosphorylsulfanylbutanedioate

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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.)