The metabolism of ... methyl parathion has been extensively studied in a wide variety of organisms, incl microorganisms, plants, insects and mammals. ... /Its biotransformation/ depend on oxidative activation by replacement of thiono sulfur with oxygen for ... toxicity. Competing with this intoxication reaction are hydrolysis reactions that result in detoxification. The ring nitro group can also be reduced, particularly in bovine rumen fluid, to amino group; this results in amino parathion ... oxidative activation takes place primarily in liver. A number of ... /studies/ have shown that, in liver microsomal mixed function oxidase systems, presence of reduced nicotinamide adenine dinucleotide phosphate and oxygen are responsibe for this reaction. ... Degradative reactions that result in detoxification of ... methyl parathion involve either demethylation or dearylation. The resulting desmethyl compounds & dimethyl phosphoric acids are essentially nontoxic.
Methyl paraoxon may be metabolized by way of the same pathways as methyl parathion, resulting in the oxygen analogue ... /of O-methyl-O-para-nitrophenyl phosphate or dimethyl phosphoric acid, which require glutathione-dependent alkyl and aryl transferases, respectively/.
Effects of peppermint (Mentha piperita) and wild tomato (Lycopersicon hirsutum glabratum) on the toxicity, penetration and metabolism of methyl parathion were studied in larvae of the tobacco budworm, Heliothis virescens. Third-instar larvae fed wild tomato or peppermint leaves for 1 day were 3.3 and 2.7 times more tolerant to methyl parathion, respectively, as compared to insects fed an artificial diet. These tolerance levels were only 2.2 and 1.7 fold, respectively, in fifth-instar larvae when fed leaves of the same plant species for 1 day. Penetration studies did not indicate any difference in the rate of penetration of methyl parathion in larvae fed different diets. Methyl parathion injected into fifth-instar larvae was converted into 3 chloroform soluble and 5 water soluble metabolites. Five hr after injection, the extent of methyl parathion metabolism was greater in larvae fed wild tomato leaves (77.4%) or peppermint leaves (72.8%), than in those fed an artificial diet (64.55%). The major metabolite was p-nitrophenol and its formation was higher in larvae fed wild tomato leaves (49.4%) than in larvae fed peppermint leaves (44.23%), which in turn were higher than those fed an artificial diet (38.19%).
The role of human fetal liver glutathione S-transferases in the detoxification of methyl parathion was investigated. Glutathione S-transferases were partially purified by affinity chromatography utilizing reduced glutathione as the ligand coupled to epoxy-activated Sepharose 4B. This resulted in the isolation of material with an average activity (mean + or - SE ) of 58.90 + or - 4.83 mu mol 1-chloro-2,4-dinitrobenzene conjugate formed/min/mg, representing a purification of 70 fold. These partially purified fetal liver transferase catalyzed the metabolism of methyl parathion exclusively to desmethyl parathion via O-dealkylation. High-performance liquid chromatography, radiometric analysis of the enzymic reaction, and co-chromatography with reference standard on thin-layer chromatography confirmed the sole metabolite as desmethyl parathion. The range of fetal liver activity towards methyl parathion was from 30 to 122 mmol desmethyl parathion formed/min/mg. Analysis of the kinetic parameters of three partially purified fetal liver preparations with gestational ages of 14, 16 and 21 weeks resulted in Km values for methyl parathion of 0.24, 0.38, and 0.86 mM, respectively; whereas, the Km values assessed for glutathione were 0.20, to 0.10 and 0.18 mM. The ability of human fetal liver glutathione S-transferases to catalyze the metabolism of methyl parathion exclusively to desmethyl parathion via O-dealkylation represents a major qualitative biochemical difference from the rat liver isozymes.
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.
IDENTIFICATION: Methyl parathion is an organophosphorus insecticide that is relatively insoluble in water, poorly soluble in petroleum ether and mineral oils, and readily soluble in most organic solvents. Pure methyl parathion consists of white crystals; technical methyl parathion is a light tan color with a garlic-like odor. It is thermally unstable. HUMAN EXPOSURE: The production, formulation, handling, and use of methyl parathion as an insecticide are the principal potential sources of exposure of humans. Skin contact and, to a lesser degree, inhalation are the main routes of exposure to workers. The general population may be exposed to air-, water-, and food-borne residues of methyl parathion as a consequence of agricultural or forestry practices, the misuse of the agent resulting in the contamination of fields, crops, water, and air through off-target spraying. Methyl parathion is a highly toxic organophosphorus ester insecticide. Overexposure from handling during manufacture, use, and/or accidental or intentional ingestion may cause severe or fatal poisoning. Methyl parathion formulations may, or may not, be irritating to the eyes or to the skin, but are readily absorbed. Several cases of acute methyl parathion poisoning have been reported. Signs and symptoms are those characteristic of systemic poisoning by cholinesterase-inhibiting organophosphorous compounds. They include peripheral and central cholinergic nervous system manifestations appearing as rapidly as a few minutes after exposure. In case of dermal exposure, symptoms may increase in severity for more than one day and may last several days. Studies of methyl parathion suggest a decrease in blood cholinesterase activities without clinical manifestations. No cases of organophosphorous-induced, delayed peripheral neuropathy have been reported. An increase in chromosomal aberrations has been reported in cases of acute intoxications. No human data were available to evaluate the teratogenic and reproductive effects of methyl parathion. The available epidemiological studies deal with multiple exposure to pesticides and it is not possible to evaluate the effects of long-term exposure to methyl parathion. ANIMAL STUDIES: Methyl parathion poisoning causes the usual organophosphate cholinergic signs attributed to accumulation of acetylcholine at nerve endings. Methyl parathion becomes toxic when it is metabolized to methyl paraoxon. In short term toxicity studies, using various routes of administration on the rat, dog, and rabbit, inhibition of plasma, red blood cell, and brain ChE, and related cholinergic signs were observed. There is no evidence of carcinogenicity in mice and rats, following long-term exposure. In reproduction studies, at toxic dose levels (ChE inhibition), there were no consistent effects on litter size, number of litters, pup survival rates, and lactation performance. No primary teratogenic or embryotoxic effects were noted. Methyl parathion is readily absorbed via all routes of exposure (oral, dermal, inhalation) and is rapidly distributed to the tissues. The liver is the primary organ of metabolism and detoxification. The elimination of methyl parathion and metabolic products occurs primarily via the urine.
Methyl parathion 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
Classification of carcinogenicity: 1) evidence in humans: no adequate data; 2) evidence in animals: evidence suggesting lack of carcinogenicity. Overall summary evaluation of carcinogenic risk to humans is Group 3: The agent is not classifiable as to its carcinogenicity to humans. /From table/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
A4；不可分类为人类致癌物。
A4; Not classifiable as a human carcinogen.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
通过呼吸、胃肠和皮肤途径被身体吸收。
... Absorbed into body by respiratory, gastrointestinal, & cutaneous pathways.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
甲基对硫磷可以通过皮肤、粘膜和眼睛轻易被吸收，这些吸收途径存在极大的潜在危险。
Methyl parathion is readily absorbed through the skin, mucous membranes, and eyes which presents a potentially great danger from these avenues of absorption.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
只有组织积累...观察到的是与酯酶酶的不可逆结合。最高浓度在肝脏和肺。
Only tissue accumulation ... observed is irreversible binding to esterase enzymes. Highest concn are in liver & lung.
Nitrophenolic and alkyl phosphate metabolites of methyl and ethyl parathion in the urine of human subjects soon after doses of 1 to 4 mg have been ingested. Particular alkyl phosphates can serve as specific indices of absorption of the respective parathions. Paranitrophenol and diethyl thiophosphate are rapidly eliminated in the urine, while excretions of dimethyl phosphate, and particularly diethyl phosphate, are more protracted. Cumulative excretions of paranitrophenol and alkyl phosphates exhibit sufficient dose-dependence at convenient intervals following parathion ingestion to encourage use of metabolite measurements in estimating occupational absorption of the parathion insecticides.
Facile and sensitive electrochemical detection of methyl parathion based on a sensing platform constructed by the direct growth of carbon nanotubes on carbon paper
[EN] BICYCLYL-SUBSTITUTED ISOTHIAZOLINE COMPOUNDS<br/>[FR] COMPOSÉS ISOTHIAZOLINE SUBSTITUÉS PAR UN BICYCLYLE
申请人：BASF SE
公开号：WO2014206910A1
公开（公告）日：2014-12-31
The present invention relates to bicyclyl-substituted isothiazoline compounds of formula (I) wherein the variables are as defined in the claims and description. The compounds are useful for combating or controlling invertebrate pests, in particular arthropod pests and nematodes. The invention also relates to a method for controlling invertebrate pests by using these compounds and to plant propagation material and to an agricultural and a veterinary composition comprising said compounds.
The present invention relates to azoline compounds of formula (I) wherein A, B1, B2, B3, G1, G2, X1, R1, R3a, R3b, Rg1 and Rg2 are as defined in the claims and the description. The compounds are useful for combating or controlling invertebrate pests, in particular arthropod pests and nematodes. The invention also relates to a method for controlling invertebrate pests by using these compounds and to plant propagation material and to an agricultural and a veterinary composition comprising said compounds.
