Absorption, Distribution and Excretion
Eight autopsy samples from an individual who had ingested a large amt of malathion were analyzed for 4 components: intact pesticide, malaoxon, malathion monocarboxylic acid (MCA), and malathion dicarboxylic acid (DCA). Malathion was present in all samples except liver. The highest concn were found in the gastric content (8621 ppm) and adipose tissue (76.4 ppm). Malaoxon was identified in some tissues at very low levels; a significant amt was found only in fat (8.2 ppm). The MCA and DCA were detected in all tissues. The former was found in greater abundance: 221 ppm in bile, 106 ppm in kidney, and 103 ppm in the gastric content.
The fate of malaoxon was studied in a susceptible and a resistant strain of housefly following topical application. Sublethal doses were used: 160 pmol for the S-strain (0.17 times LD50) and 1570 pmol for the R-strain (0.1 times LD50). The penetration rates are dose dependent and semilog plots of the external amt versus time show that these rates are not proportional to this external amt. Internal concn of malaoxon rapidly increase following administration, reach max values between 30 min and 2 hr (depending on dose), and then slowly decrease. The rate of metabolic degradation is highest in the early stage of the intoxication process. A 3 compartment pharmacokinetic model is postulated to explain the experimental data quantitatively. The 1st compartment represents external malaoxon, the other 2 represent internal parent cmpd. Statistical analysis shows that the penetration rate is better described with a sum of 2 exponentials rather than with a single exponential decay. In the model, degradation occurs in the 1st internal compartment and is assumed to be 1st order. Malaoxon is distributed between the 2 internal compartments slowly with 1st order kinetics. Parameter estimations with curve fitting procedures for the internal processes (degradation and exchange) shows that there is not one set of parameter values that can be used for both strains simultaneously. Interstrain differences in degradation capacity studies showed that in vitro the R-strain had a 4-fold higher oxidative breakdown rate. Taking this difference into account, it is possible to explain the 2 sets of data with one kinetic model, although other alternatives cannot be excluded.
... 7% OF TOTAL METABOLITES IN FECES /FROM COW GIVEN MALATHION ORALLY/ WAS CHLOROFORM SOLUBLE, OF WHICH 855 WAS MALATHION & 12% MALAOXON. THE MILK CONTAINED A SMALL AMOUNT OF MALATHION METABOLITES (9.2% OF TOTAL DOSE AFTER 7 DAYS); OF THIS, ONLY 29% WAS EXTRACTABLE OUT OF MILK AND PARTITIONED IN FAVOR OF WATER OVER BENZENE, INDICATING THE ABSENCE OF EITHER MALATHION OR MALAOXON.
Most organophosphate compounds are ... absorbed from skin, conjunctiva, gastrointestinal tract, & lung. /Organophosphate compounds/
For more Absorption, Distribution and Excretion (Complete) data for MALAOXON (10 total), please visit the HSDB record page.

---

Metabolism / Metabolites
ALTHOUGH NO METABOLITE FOR MALAOXON WITH HYDROLYZED CARBOETHOXY GROUP HAS BEEN IDENTIFIED, CARBOXYESTERASE HYDROLYSIS OF MALAOXON UNDOUBTEDLY MUST OCCUR IN VIEW OF GREAT DIFFICULTY ENCOUNTERED IN DETECTING MALAOXON IN ANIMAL TISSUE.
IN VITRO STUDIES WITH MOUSE LIVER INDICATED THAT ONLY ABOUT HALF OF TOTAL MALAOXON DETOXIFICATION WAS ACCOUNTED FOR BY CARBOXYESTERASE HYDROLYSIS.
WITH RESISTANT & NON-RESISTANT HOUSEFLY STRAINS, IN VITRO STUDIES SHOWED THAT RESISTANT STRAINS DEGRADED MALAOXON OXIDATIVELY @ RATE 10X HIGHER THAN THAT OF SUSCEPTIBLE STRAIN. THE OXIDATION PRODUCT WAS MALAOXON BETA-MONOCARBOXYLIC ACID WHEN A SUSCEPTIBLE STRAIN WAS USED. THE RESISTANT STRAIN PRODUCED SOME BETA MONOACID BUT THE MALAOXON ALPHA-MONOACID WAS PROBABLY THE MAIN METABOLITE.
A "BINDING" TYPE OF INACTIVATION BY LIVER & OTHER TISSUES HAS BEEN DEMONSTRATED FOR ... MALAOXON. THIS APPEARS TO REPRESENT A LOSS OF THE ACTIVE CHOLINESTERASE INHIBITORS TO NONCRITICAL TISSUE BINDING SITES, THEREBY SPARING CRITICAL ACETYLCHOLINESTERASE OF NERVE TISSUE FROM INHIBITION.
For more Metabolism/Metabolites (Complete) data for MALAOXON (12 total), please visit the HSDB record page.
Maloxon is a known human metabolite of Malathion.

Interactions
TOXICITY OF MALATHION IS POTENTIATED BY O-ETHYL O-PARA-NITROPHENYL PHENYLPHOSPHOROTHIOATE, TRI-O-TOLYLPHOSPHATE, & SOME OTHER ORGANOPHOSPHORUS CMPD. IT IS POSTULATED THAT THIS POTENTIATION RESULTS FROM THE INHIBITION OF CARBOXYLESTERASE OR ALIESTERASE ENZYMES RESPONSIBLE FOR DEGRADATION OF MALATHION IN MAMMALS. PRESUMABLY, THIS MECHANISM WOULD LEAD TO INCR FORMATION OF MALAOXON, THE ACTIVATION PRODUCT, BECAUSE THE ENZYMES RESPONSIBLE FOR DEGRADATION OF MALAOXON WOULD BE INHIBITED.
Pretreatment of rats with chloramphenicol (100 mg/kg, ip) 30 min prior to a single oral LD50 dose of malathion at 340 mg/kg completely protected against malathion induced inhibition of cholinesterase. It appears that the inhibition of malathion toxicity by chloramphenicol pretreatment is attributable to inhibition by chloramphenicol of the metabolic activation of malathion to malaoxon.
Some phenothiazines may antagonize & some may potentiate the toxic anticholinesterase effects of ... /organophosphorus insecticides/. /Organophosphate cholinesterase inhibitors/
In long term therapy, adrenocorticoids antagonize the antiglaucoma effects of anticholinesterases (incr ocular pressure). ... Anticholinergics antagonize the miotic (antiglaucoma) & other muscarinic effects of anticholinesterases on the autonomic & central nervous systems. Tricyclic antidepressants (anticholinergic effects) antagonize the antiglaucoma (miotic) effects of anticholinesterases in glaucoma. ... Antihistamines with anticholinergic effects antagonize the miotic (antiglaucoma) & CNS effects of anticholinesterases. Anticholinesterases potentiate tranquilizing & behavioral changes induced by antihistamines. The actions of anticholinesterase agents on autonomic effector cells, & to some extent those on CNS, are antagonized by atropine, an antidote of choice. Barbiturates are potentiated by anticholinesterases. ... Dexpanthenol potentiates the effects of anticholinesterases. Fluorophosphate insecticides potentiate the effects of other anticholinesterases. /Anticholinesterases/
For more Interactions (Complete) data for MALAOXON (6 total), please visit the HSDB record page.

---

Non-Human Toxicity Values
LD50 Rat oral 158 mg/kg
LD50 Rat ip 17,500 ug/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 weak unpleasant odor. (NTP, 1992)
Diethyl 2-[(dimethoxyphosphoryl)thio]succinate is a diester that is diethyl succinate in which position 2 is substituted by a (dimethoxyphosphoryl)thio group. It is a diester, an ethyl ester and an organic thiophosphate.

---

Mechanism of Action
MALAOXON, ACTIVE ANTICHOLINESTERASE METABOLITE OF MALATHION ... HAS ALIESTERASES INHIBITING ACTIVITY.
MOSQUITO CULEX TARSALIS SHOWS REMARKABLE MALATHION RESISTANCE ORIGINATING FROM (FRESNO, CA,) SO SPECIFIC THAT IT EXTENDS TO NO OTHER ORGANOPHOSPHATE CMPD EXCEPT MALAOXON.
Organophosphorus derivatives act by combining with and inactivating the enzyme acetylcholinesterase (AChE). ... 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/
The characteristic pharmacological effects of the anti-ChE agents are due primarily to the prevention of hydrolysis of ACh by AChE at sites of cholinergic transmission. Transmitter thus accumulates, and the response to ACh that is liberated by cholinergic impulses or that is spontaneously released from the nerve ending is enhanced. With most of the organophosphorus agents ... virtually all the acute effects of moderate doses are attributable to this action. /Anticholinesterase agents/
For more Mechanism of Action (Complete) data for MALAOXON (12 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.)