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.
来源:Hazardous Substances Data Bank (HSDB)
代谢
离体研究中，使用小鼠肝脏表明，总马拉氧磷解毒中只有大约一半是由羧酸酯酶水解来解释的。
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.
Malaoxon 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.
来源:Toxin and Toxin Target Database (T3DB)
毒理性
致癌物分类
对人类不具有致癌性（未被国际癌症研究机构IARC列名）。
No indication of carcinogenicity to humans (not listed by IARC).
Acute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides.
Symptoms of low dose exposure include excessive salivation and eye-watering. Acute dose symptoms include severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Hypertension, hypoglycemia, anxiety, headache, tremor and ataxia may also result.
来源:Toxin and Toxin Target Database (T3DB)
毒理性
副作用
其他毒物 - 有机磷
Other Poison - Organophosphate
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
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.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
大多数有机磷化合物可以通过皮肤、结膜、胃肠系统和肺部被吸收。/有机磷化合物/
Most organophosphate compounds are ... absorbed from skin, conjunctiva, gastrointestinal tract, & lung. /Organophosphate compounds/
SUPPORTED MOLYBDENUM PEROXO COMPLEXES FOR TRANSFORMING ORGANO PHOSPHATE NEUROTOXINS TO A VALUE-ADDED, COMMODITY PHOSPHORUS CHEMICAL
申请人：Lewis & Clark College
公开号：US20180282354A1
公开（公告）日：2018-10-04
The invention relates to degradation of organophosphate neurotoxins with molybdenum complexes. In particular, the degradation of phosphate ester neurotoxins can be performed with molybdenum peroxo complexes resulting in recoverable phosphorus-containing compounds.
Process for Preparing Malathion for Pharmaceutical Use
申请人：Gutman Daniella
公开号：US20070010496A1
公开（公告）日：2007-01-11
The present invention provides a process for preparing a highly pure form of malathion having a reduced level of toxic impurities. In addition, the malathion prepared by the process of this invention is storage stable. The level of toxic impurities in the malathion, e.g., isomalathion, O,O,S-trimethyl phosphorodithioate (MeOOSPS), O,O,S-trimethyl phosphorothioate (MeOOSPO), O,S,S-trimethyl phosphorodithioate (MeOSSPO), malaoxon, isomalathion, diethyl fumarate, methyl malathion, dimethyl malathion, O,O-methyl,ethyl-S-(1,2-dicarboethoxy)ethyl-phosphorodithioate are lower than that of any other commercial preparation of malathion that may be used for pharmaceutical purposes.
Enantiomeric separation of malathion and malaoxon and the chiral residue analysis in food and environmental matrix
作者：Yifan Hua、Qian Zhou、Peng Wang、Zhiqiang Zhou、Donghui Liu
DOI：10.1002/chir.23229
日期：2020.8
used chiral phosphorus insecticide, which has a more toxic chiral metabolite malaoxon. In this work, the enantiomers of malathion and malaoxon were separated by high‐performance liquid chromatography‐mass/mass (HPLC‐MS/MS) with chiral columns using acetonitrile/water or methanol/water as mobile phase, and the chromatographic conditions were optimized. Based on the chiral separation, the chiral residue
METHOD AND DEVICE FOR THE DETECTION OF SULPHUR CONTAINING SPECIES
申请人：Fallis Ian
公开号：US20130224873A1
公开（公告）日：2013-08-29
A method is provided for detecting sulphur-containing species (such as thiophosphorous esters, in particular phosphorylating agents), in which a suspected sulphur-containing species is brought into contact with a tetrazolium compound in the presence of base, typically at a pH of at least 8. A device, kit and tetrazolium compounds for use in such a method are also disclosed.
PROCESS FOR PREPARING MALATHION FOR PHARMACEUTICAL USE
申请人：Gutman Daniella
公开号：US20090124823A1
公开（公告）日：2009-05-14
The present invention provides a process for preparing a highly pure form of malathion having a reduced level of toxic impurities. In addition, the malathion prepared by the process of this invention is storage stable. The level of toxic impurities in the malathion, e.g., isomalathion, O,O,S-trimethyl phosphorodithioate (MeOOSPS), O,O,S-trimethyl phosphorothioate (MeOOSPO), O,S,S-trimethyl phosphorodithioate (MeOSSPO), malaoxon, isomalathion, diethyl fumarate, methyl malathion, dimethyl malathion, O,O-methyl,ethyl-S-(1,2-dicarboethoxy)ethyl-phosphorodithioate are lower than that of any other commercial preparation of malathion that may be used for pharmaceutical purposes.
