10265-92-6

Hazards Identification

Pictogram(s):

Signal:

Danger

GHS Hazard Statements:

H300: Fatal if swallowed [Danger Acute toxicity, oral]
H311: Toxic in contact with skin [Danger Acute toxicity, dermal]
H330: Fatal if inhaled [Danger Acute toxicity, inhalation]
H400: Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]

Precautionary Statement Codes:

P260, P264, P270, P271, P273, P280, P284, P301+P316, P302+P352, P304+P340, P316, P320, P321, P330, P361+P364, P391, P403+P233, P405, and P501

Hazard Classes and Categories:

Acute Tox. 2 *
Acute Tox. 3 *
Aquatic Acute 1
Acute toxicity (inhalation) - category 2
Acute toxicity (ingestion) - category 2
Acute toxicity (dermal) - category 3
Hazardous to the aquatic environment (acute) - category 1
Acute toxicity (Oral) - Category 2
Acute toxicity (Dermal) - Category 2
Acute toxicity (Inhalation: Dusts and mists) - Category 2
Serious eye damage/eye irritation - Category 2B
Specific target organ toxicity - Single exposure - Category 2 (nervous system)
Specific target organ toxicity - Repeated exposure - Category 2 (nervous system)
Hazardous to the aquatic environment (Acute) - Category 1
Hazardous to the aquatic environment (Long-term) - Category 1

Hazards Summary:

Classified as highly toxic, it may be used only by certified applicators. [EXTOXNET] A small number of the organophosphates (OPs) can Induce Delayed Neuropathy (OPIDN). OPIDN usually occurs after ingestion and is usually nonoccupational. [Levy, p. 431] An eye irritant; Can be absorbed through skin; A cholinesterase inhibitor that may cause CNS effects (convulsions and respiratory failure) on short-term exposure; Extended or repeated exposure may cause delayed neuropathy; [ICSC] Reports of delayed neuropathy form occupational exposures; [HSDB] Also a metabolite of the OP pesticide acephate; A cholinesterase inhibitor that is one of the most acutely toxic of the OP pesticides; A moderate eye (corneal opacity persisting up to ten days in 2/6 rabbits) and mild skin irritant; Not sensitizing to guinea pig skin; Neuropathology observed in hens but not in rats; [Reference #2] Ranked second in the US for percentage of cases with life-threatening symptoms among occupational Poison Control Center cases; Reproductive studies have shown effects to several parameters at relatively low exposure levels; No evidence of mutagenicity or carcinogenicity; [UNEP DGDs] The average of two baseline respective cholinesterase activity determinations three days apart, with no exposures to enzyme inhibiting pesticides for at least 30 days, is recommended for each worker prior to exposure to cholinesterase inhibitors because of large inter-individual differences in published baseline values. To be established at least once a year. Removal from workplace exposures is recommended until the cholinesterase activity returns to within 20% of baseline. [TLVs and BEIs]

Usage

Uses

Used in Agricultural Industry:
Methamidophos is used as an insecticide, acaricide, and avicide for controlling a wide range of insects and mites in various crops. It is effective against chewing and sucking insects such as aphids, flea beetles, worms, whiteflies, thrips, cabbage loopers, Colorado potato beetles, potato tubeworms, armyworms, mites, and leafhoppers. Crop uses include broccoli, Brussels sprouts, cauliflower, grapes, celery, sugar beets, cotton, tobacco, and potatoes. It is also used on many vegetables, hops, corn, peaches, and other crops.
Used in Rice Fields:
Methamidophos is an organophosphate insecticide used in great quantities in rice fields in rice-producing countries.
Used as a Breakdown Product:
Methamidophos is also a breakdown product of another organophosphate, namely, acephate.
Note: Methamidophos is a highly toxic compound and is classified as a Restricted Use Pesticide (RUP) by the US EPA. It is not approved for use in EU countries. Proper safety measures, including wearing protective clothing and using a respirator, chemical goggles, rubber gloves, and impervious protective clothing, should be taken when handling this chemical substance.

Reactivity Profile

Organophosphates, such as Methamidophos, are susceptible to formation of highly toxic and flammable phosphine gas in the presence of strong reducing agents such as hydrides. Partial oxidation by oxidizing agents may result in the release of toxic phosphorus oxides. Avoid strong acids or alkalis. [EPA, 1998].

Health Hazard

Methamidophos is harmful or fatal if swallowed, inhaled, or absorbed through the skin.

Health Hazard

Methamidophos is highly toxic to mammals. Inhalation of methamidophos causing weakness, tightness in the chest, wheezing, headache, blurred vision, pinpoint pupils, tearing,and runny nose are common early symptoms. On accidental ingestion and with severe poisoning, methamidiophos causes nausea, vomiting, diarrhea, and cramps, sweating and twitching, weakness, shakiness, blurred vision, pinpoint pupils, dyspnea (shortness of breath), tightness in the chest, sweating, confusion, changes in heart rate, convulsions, coma, respiratory failure, and death. People with health disorders, such as high blood pressure, problems of the gastrointestinal, heart, liver, lung, or nervous system, have been reported to be more sensitive to methamidophos-induced toxicity. Reports have indicated that occupational workers exposed to methamidophos who developed poisoning with symptoms such as pain (needle type) in the feet, legs, and hands, high blood pressure, gastrointestinal disorders, heart, liver, lung, or nervous system problems, may be more sensitive to methamidophos.

Fire Hazard

(Non-Specific -- Organophosphorus Pesticide, n.o.s.) Container may explode in heat of fire. Fire and runoff from fire control water may produce irritating or poisonous gases. (Non-Specific -- Phosphoramidothioic Acid, O-Ethyl S-Methyl Ester) Emits very toxic fumes of nitrogen oxides, phosphorus oxides, and sulfur oxides when heated to decomposition. Stable at neutral pH. Avoid strong acids or alkalis.

Trade name

ACEPHATE-MET?; BAY 71625?; BAYER 71628?; CHEVRON 9006?; CHEVRON ORTHO 9006?; FILITOX?; GS-13005?; HAMIDOP?; METAFOS?; MONITOR?; MTD?; NITOFOL?; NURATRON?; ORTHO 9006?; PATROLE?; PILLARON?; SRA 5172?; SUPRACIDE?; SWIPE?; TAHMABON?; TAMARON?; VITARON?

Safety Profile

Poison by ingestion, inhalation, sh contact, subcutaneous, and intraperitoneal routes. Human systemic effects by ingestion: fasciculations, pupdlary constriction, and sweating. A cholinesterase inhbitor type of insecticide. When heated to decomposition it emits very toxic fumes of NOx, POx, and SOx. See also PARATHION.

Potential Exposure

A potential danger to those involved in the manufacture, formulation, and application of this insecticide on vegetables and cotton

Environmental Fate

Chemical/Physical. Emits toxic fumes of phosphorus, nitrogen and sulfur oxides when heated to decomposition (Sax and Lewis, 1987).

Metabolic pathway

Methamidophos is a contact insecticide which is particularly effective against caterpillars and aphids. It also has some systemic action although much less than acephate. There is some uncertainty concerning the nature of the leaving group when the compound inhibits acetylcholinesterase although most evidence suggests that it is methanethiolate. There are claims that it requires metabolic activation to a more active inhibitor (Eto et al., 1977) and yet other evidence that it does not (Khasawinah et al., 1978). Most studies which have examined the biotransformation of acephate have identified methamidophos as one of its metabolites and the latter is considered to be the active metabolite. The main route of biotransformation in soil is through deamination. In mammals, metabolism involves de-O-methylation, de-S-methylation and deamination, with de- O-methylation in the liver probably being the most important route. There is no evidence as to whether demethylation is hydrolytic or oxidative. Methamidophos and its metabolites are highly polar and no conjugates have been identified. There is some evidence that the compound can lead to delayed neurological degeneration in mammals through inhibition of 'neuropathy target esterase'.

Metabolism

Acute oral LD50 for rats is about 20 mg/kg. Inhalation LC50 (4 h) for rats is 0.2 mg/L air. NOEL (2 yr) for rats is 2 mg/kg diet (0.1 mg/kg/d). ADI is 4 μg/kg b.w. Methamidophos itself shows only a poor anti-AChE activity, oxidative activation being suggested. It appears to cause delayed neuropathy. The major part of administered methamidophos in animals is rapidly eliminated from the body through urine and respiration. The major metabolic routes are O-demethylation, S-demethylation, and deamination. In plants, deaminated methamidophos is a major metabolite. Methamidophos is degraded rapidly in soil by deamination and demethylation, to eventually form carbon dioxide and phosphoric acid.

Degradation

Methamidophos is stable at pH 3-8 but it is hydrolysed in acids and alkalis. Photodegradation is of minor importance (PM). The physicochemical, electronic and molecular-orbital properties of methamidophos have recently been described and the compound is apparently nonionised at physiological pH (Singh et al., 1998). The alkaline hydrolysis of methamidophos and its two N-methylated derivatives was examined by Fahmy et al. (1972). In aqueous KOH the main product was S-methyl phosphoramidothioate (2), whereas in less polar media such as aqueous MeOH or acetone the route was via de-Smethylation to give methyl phosphoramidate (3). It was concluded that the two competing mechanisms for methamidophos hydrolysis were (i) addition-elirnination on phosphorus leading to P-O bond cleavage, loss of methoxide and formation of product 2, (ii) an elimination reaction involving the amido proton to give P-S bond cleavage, loss of methanethiolate and formation of product 3. Proposed routes for the hydrolysis of methamidophos are shown in Scheme 1.

Incompatibilities

Incompatible with strong acids or alkali. Attacks mild steel and copper-containing alloys (technical grade)

InChI:InChI=1/C2H8NO2PS/c1-5-6(3,4)7-2/h1-2H3,(H2,3,4)

Upstream product

• 40334-42-7 thiophosphoramidic acid O-methyl ester O'-phenyl ester 
• 77-78-1 dimethyl sulfate 
• 17321-47-0 O,O-dimethyl phosphoramidothioate 
• 67-56-1 methanol 
• 73447-20-8 O,S-dimethyl (2,2,2-trichloro-1-hydroxyethyl)phosphoramidothioate 
• 74-88-4 methyl iodide 

Downstream Products

• 152-20-5 O,O,S-trimethyl phosphorothioate 
• 75-75-2 methanesulfonic acid 
• 31754-07-1 phosphoramidic acid ethyl ester methyl ester 
• 2949-92-0 methanethiosulfonic acid S-methyl ester 
• 13882-12-7 S-methyl methanethiosulfinate 
• 82452-51-5 P,P'-dimethyl diamidodiphosphate 
• 54473-41-5 O,S-dimethyl-N-chlorobutyrylphosphoroamidothioate 
• 30560-19-1 Acephate 
• 1068-21-9 Diethyl phosphoramidate 
• 56122-47-5 O,S-dimethyl-N-(1:benzoylprop-1-en-2-yl)phosphoroamidothioate 
• 548757-66-0 tert-butyl 6-(O,S-dimethylthiophosphoramido)-3-oxopropanoate 

Relevant academic research and scientific papers

Synthesis and characterization of O,S-dimethylphosphoramidothioate and N-acetyl O,S-dimethylphosphoramidothioate

O,S-Dimethylphosphoramidothioate (methamidophos) and N-acetyl O,S-dimethylphos- phoramidothioate (acephate) were synthesized by new methods to investigate the structure-activity study of acetyl cholinesterase (AChE) inhibition through the parameters of logP,δ 31P, and IC 50. After their characterization by NMR (31P, 31P{1H}, 13C, and 1H), IR, and mass spectroscopy, logP and δ31P (31P chemical shift in NMR) were used to evaluate lipophilicity and electronical properties. The logP values for methamidophos and acephate were experimentally determined by the GC-shake-flask method, and the ability of the compounds to inhibit human AChE was evaluated by a modified Ellman's assay. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.

PROCESS FOR PREPARATION OF THIOPHOSPHORYL CHLORIDE AND ACEPHATE

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.

Synthetic method for improving yield of methamidophos intermediate

The invention discloses a synthetic method for improving the yield of a methamidophos intermediate, and belongs to the technical field of fine chemical production. The method comprises the following steps: reacting O,O-dimethyl phosphoramidothioate with a catalyst and dimethyl sulfate at 25-60 DEG C to obtain methamidophos; wherein a solvent is halogenated alkane, and the catalyst comprises one ofmethyl iodide, methyl methanesulfonate, methyl trifluoromethanesulfonate, trimethylsilyl trifluoromethanesulfonate or isopropyl titanate. The method has the advantages that the process is simple, thereaction time is short, the obtained reaction yield is 90% or above, and the target product purity is high.

Synthesis, spectroscopic characterization and structure-activity relationship of some phosphoramidothioate pesticides

In this work, some phosphoramidothioates (PATs) with the general formula of (CH3O)2P(S)X and (CH3O)(CH3S)P(O)X, where, X = NH2 (1 & 6), NH(CH3) (2 & 7), N(CH3)2 (3 & 8), N(Et)2 (4 & 9), (CH3CH2O)2P(S)NH(CH3) (5) and (CH3CH2O)(CH3CH2S)P(O)NH(CH 3) (10), were synthesized and characterized by 31P, 31P{1H}, 13C and 1H NMR spectroscopy. The ability of the compounds to inhibit AChE was predicted by PASS software (version 1.193). They were also experimentally evaluated by a modified Ellman's assay. The structure-activity relationship (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 1-10 was 1 (3.38 mM) > 2 (3.97 mM) > 3 (4.75 mM) > 4 (6.00 mM) > 5 (5.51 mM) > 6 (0.07 mM) > 7 (0.23 mM) > 8 (0.39 mM) > and 9 (0.55 mM) > 10 (0.51 mM), respectively. IC50 and logP parameters of the P=O moiety were more than the P=S moiety in PAT analogues.

Mechanisms of composition change and toxic potentiation of chloramidophos emulsifiable concentrate during storage

Storage instability is one of the serious problems that greatly restrict pesticide use. Routine checks on the composition and toxicity of 30% emulsifiable concentrates (EC) of chloramidophos (CP) during storage indicated that 78.6% of the active ingredien

Concentrates of organophosphorous insecticides

A low volatile organic compound co-solvent system is disclosed for preparing emulsion concentrates of low melting organophosphorous insecticides wherein the bioefficacy of the insecticide active is significantly enhanced. The co-solvent system comprises a water-soluble ethoxylated fatty acid/rosin acid-nonionic surfactant composition.

Nitro- and cyanoguanidines as selective preemergence herbicides and plant defoliants

There are provided novel nitroguanidine and cyanoguanidine compounds. A method of dessicating and defoliating plants by applying to the foliage thereof certain nitroguanidine or cyanoguanidine compounds and a method for the selective preemergence control of undesirable broadleaf weeds and grasses in the presence of graminaceous crops are disclosed.

Condensation products

Formamidine compounds of the formula EQU1 or WHEREIN R1 represents a substituted or unsubstituted phenyl radical, R2 represents hydroogen, alkyl, alkenyl or alkinyl and R3 represents acyl their manufacture and their use in pest control.