In a metabolism study, /in which/ female Sprague Dawley rats received single oral doses of 0.16-0.19 mg (0.43-0.51 uC, respectively) of radiolabeled Monitor technical (S-methyl- 14C Methamidophos, 99.5%)...identified metabolites in the urine /were/ O,S-dimethyl- phosphorothioate, methyl dihydrogen phosphate and phosphoric acid... . ...There was no difference in the rate of metabolism, excretion or nature of the metabolites between males and females.
Metabolism of organophosphates occurs principally by oxidation, by hydrolysis via esterases and by reaction with glutathione. Demethylation and glucuronidation may also occur. Oxidation of organophosphorus pesticides may result in moderately toxic products. In general, phosphorothioates are not directly toxic but require oxidative metabolism to the proximal toxin. The glutathione transferase reactions produce products that are, in most cases, of low toxicity. Paraoxonase (PON1) is a key enzyme in the metabolism of organophosphates. PON1 can inactivate some organophosphates through hydrolysis. PON1 hydrolyzes the active metabolites in several organophosphates insecticides as well as, nerve agents such as soman, sarin, and VX. The presence of PON1 polymorphisms causes there to be different enzyme levels and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effect of organophosphate exposure.
(±)-Methamidophos 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
致癌性证据
癌症分类：不太可能对人类致癌
Cancer Classification: Not Likely to be Carcinogenic to Humans
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌物分类
对人类无致癌性（未列入国际癌症研究机构IARC清单）。
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.
来源:Toxin and Toxin Target Database (T3DB)
毒理性
暴露途径
这种物质可以通过吸入、皮肤接触和摄入被身体吸收。
The substance can be absorbed into the body by inhalation, through the skin and by ingestion.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
In rats and farm animals, radiolabelled methamidophos was absorbed rapidly and distributed uniformly among all organs and tissues. More than half of the radioactivity was rapidly eliminated from the body, mainly via urine and respiratory air. Radioactivity remaining in the animal was incorporated into endogenous compounds (carbon-1 pool) and eliminated with the natural turnover of these compounds.
In a metabolism study, female Sprague Dawley rats received single oral doses of 0.16-0.19 mg (0.43-0.51 uC, respectively) of radiolabeled Monitor technical (S-methyl- 14C Methamidophos, 99.5%) and were sacrificed 5-9 days after treatment. Urine, feces and CO2 were collected twice daily and brain, kidney, liver, heart, spleen, femur bone, blood and fat were analyzed for radioactivity. For studies with the 32P-labeled test substance, groups of two male and two female Sprague Dawley rats were preconditioned for 2 weeks with 0.5 mg/kg nonradioactive Monitor technical followed by daily dosing with 0.21 mg (2.72 uC) of radiolabeled Monitor technical (32P Methamidophos, 99.5%) for 1, 3, 7, 14, 21 or 28 days. Urine and feces were collected and the distribution of radioactivity was assessed in kidney, liver, heart, muscle (from the carcass) and carcass fat. Monitor technical was rapidly degraded and/or eliminated within the first 24 hr post dosing. In the 14C studies, 60% of the radioactivity was detected in CO2 and 11% in urine. Fecal excretion of radiolabel was low. In the 32P studies, 70% of the radioactivity was detected in the urine. Fecal excretion of the 32P radiolabel was initially low (2-3%) but increased 3-21 days post dosing (8-21%). The identified metabolites in the urine (O,S-dimethyl- phosphorothioate, methyl dihydrogen phosphate and phosphoric acid) are not considered to be ChE inhibitors. The content of Monitor technical in tissue 14 days post-treatment was <0.004 ppm. There was no difference in the rate of metabolism, excretion or nature of the metabolites between males and females.
Synthesis, spectroscopic characterization and structure-activity relationship of some phosphoramidothioate pesticides
作者：S. Ghadimi、K. Asad-Samani、A. A. Ebrahimi-Valmoozi
DOI：10.1007/bf03245903
日期：2011.9
software (version 1.193). They were also experimentally evaluated by a modified Ellman’s assay. The structure-activityrelationship (SAR) between IC50 and some physico-chemical properties such as lipophilicity (logP), electronic and steric effects of the compounds was studied. The logP values were experimentally determined by the shake-flask (gas chromatography) method. Inhibitory potency for the compounds
[EN] PROCESS FOR PREPARATION OF THIOPHOSPHORYL CHLORIDE AND ACEPHATE<br/>[FR] PROCÉDÉ DE PRÉPARATION DE CHLORURE DE THIOPHOSPHORYLE ET D'ACÉPHATE
申请人：UPL LTD
公开号：WO2021074775A1
公开（公告）日：2021-04-22
The present invention discloses an improved process for preparation of acephate and intermediates thereof. More particularly, the present invention relates to a process for preparation of thiophosphoryl chloride useful for commercial production of pesticides and pharmaceutically active compounds.
A reappraisal of the role of the E1cB mechanism of hydrolysis of phosphoramidic derivatives
作者：Neil K. Hamer、Robert D. Tack
DOI：10.1039/p29740001184
日期：——
lead to the conclusion that, despite considerable differences in rate with varying degree of N-substitution, there is no important contribution from an E1cB process such as operates for related phosphoramidic halides and acyl carbamates. On the basis of the results of studies on the relative rates and direction of cleavage in the basic solvolysis of some OS-dimethyl phosphoramidothioates and phosphoramidodithioates
(Alkoxycarbonyl)(alkyl)aminosulfenyl derivatives of phosphoramidothioate
申请人：The Regents of the University of California
公开号：US04279897A1
公开（公告）日：1981-07-21
A novel class of chemical compounds useful as pesticides consists of O,S-dimethyl N-(N'-alkoxycarbonyl-N'-alkylaminosulfenyl)phosphoramidothioates. The preparation of these compounds and their formulation to control insects are exemplified.
