Twelve metabolites of pirimiphos-methyl were separated by thin-layer chromatography from the urine of rats & a dog. No unchanged compound was detected & no metabolite had anticholinesterase activity. Briefly, the P-O bond is cleaved extensively & N-dealkylation &/or conjugation is a further step in the metabolism of the pyrimidine leaving group.
The mechanism by which large repeated doses of pirimiphos-methyl reduces the hemoglobin of rats is unknown. It may be caused by 2-diethylamino-4-hydroxy-6-methylpyrimidine, a metabolite formed by both mammals and plants. Although this metabolite has an acute toxicity of the same order of magnitude as the parent compound, it was (unlike the parent compound) tolerated by rats at a dosage of 400 mg/kg for 2 wk; even so, its action on the blood was indicated by an incr in reticulocytes & a decr in lymphocytes.
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.
Pirimiphos-methyl 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：尚未确定
Cancer Classification: Not Yet Determined
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌物分类
喷洒和应用非砷杀虫剂涉及到的暴露可能对人类具有致癌性（2A组）。
Spraying and application of nonarsenical insecticides entail exposures that are probably carcinogenic to humans (Group 2A). (L135)
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)
吸收、分配和排泄
皮里米磷-甲基已知可以通过完好无损的皮肤、胃肠道和吸入途径被吸收。
Pirimiphos-methyl is known to be absorbed through intact skin, from the GI tract, & by inhalation.
Oral administration of 2-(14)C-ring-labelled pirimiphos-methyl at a dose of 0.6 mg/kg bw to five male rats resulted in a mean urinary excretion of 80.7% and mean fecal excretion of 7.3% in 24 hr, indicating rapid absorption. At 96 h, 86.0% and 15.2% of the administered dose had been excreted in urine and feces, respectively. Nine (unidentified) metabolites were present in the urine.
Female rats given 2-(14)C-pirimiphos-methyl at a dose of 7.5 mg/kg bw orally were bled (cardiac puncture, three rats per time interval) at 0.5, 1, 3, 5, 7 or 24 hr after dosing. Maximum blood concentrations (at 0.5 hr) were 2-3 ug/mL, declining by 50% 1 hr after dosing. By 24 hr, concentrations of (14)C in blood were 0.2-0.3 ug/mL, and of pirimiphos-methyl, 0.01-0.02 ug/mL. Rats treated for 4 days with 2-(14)C-pirimiphos-methyl at a dose of 7.5 mg/kg bw per day and sacrificed at intervals of 24 hr did not show any increase in blood concentrations with time. Tissue concentrations of total radioactivity in the liver, kidney and fat over the 4 days were generally less than 2 mg pirimiphos-methyl equivalents/kg tissue (concentrations of unchanged pirimiphos-methyl being less than 0.15 mg/kg tissue). There was no evidence of tissue accumulation.
Adult male Wistar rats were intubated with (14)C-labelled pirimiphos-methyl at a dose of 1 mg/kg bw per day. Four groups of three animals were dosed for 3, 7, 14 or 21 days and sacrificed 24 hr after the final dose. A further five groups of three rats were given similar doses for 28 days and sacrificed 1, 3, 7, 14, or 28 days after dosing. For each of the nine groups, one rat that did not receive pirimiphos-methyl was used as a control. After sacrifice, samples of liver, kidney, muscle, fat, erythrocytes and plasma were taken for analyses. Urine and feces were collected from two rats during the 24 hr after the seventh dose. Recovery of (14)C from (14)C-labelled pirimiphos-methyl added to control tissues was 96.9 +/- 5.2%. In all tissue samples taken at all time intervals, the concentration of radioactivity was very low, close to or below detection limits. Concentrations did not increase with repeated dosing. Liver concentrations were fairly constant (0.03 ppm) and similar concentrations were detected in some kidney samples. In other tissues, the concentration of radioactivity was generally below the limits of detection (0.04-0.06 ppm). Three days after cessation of dosing, one animal had detectable concentrations of radioactivity in the kidney. At 7 days and on subsequent days, no residues were found. Excretion was between 70% and 80% of a single dose, after administration of seven consecutive doses, providing evidence for rapid metabolism and elimination rather than poor absorption.
[EN] ACC INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE L'ACC ET UTILISATIONS ASSOCIÉES
申请人：GILEAD APOLLO LLC
公开号：WO2017075056A1
公开（公告）日：2017-05-04
The present invention provides compounds I and II useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.
Compounds of the formula (I) wherein the substituents are as defined in claim 1, useful as a pesticides, especially fungicides.
式(I)的化合物，其中取代基如权利要求1所定义，作为杀虫剂特别是杀菌剂有用。
Thieno-pyrimidine compounds having fungicidal activity
申请人：Brewster Kirkland William
公开号：US20070093498A1
公开（公告）日：2007-04-26
The present invention relates to thieno[2,3-d]-pyrimidine compounds having fungicidal activity.
本发明涉及具有杀真菌活性的噻吩[2,3-d]-嘧啶化合物。
[EN] INSECTICIDAL TRIAZINONE DERIVATIVES<br/>[FR] DÉRIVÉS DE TRIAZINONE INSECTICIDES
申请人：SYNGENTA PARTICIPATIONS AG
公开号：WO2013079350A1
公开（公告）日：2013-06-06
Compounds of the formula (I) or (I'), wherein the substituents are as defined in claim 1, are useful as pesticides.
式(I)或(I')的化合物，其中取代基如权利要求1所定义的那样，可用作杀虫剂。
N-ARYLAMIDINE-SUBSTITUTED TRIFLUOROETHYL SULFIDE DERIVATIVES AS ACARICIDES AND INSECTICIDES
申请人：BAYER CROPSCIENCE AG
公开号：US20140315898A1
公开（公告）日：2014-10-23
The present invention relates to novel N-arylamide-substituted trifluoroethyl sulfide derivatives of the formula (I)
in which X
1
, X
2
, X
3
, X
4
, R
1
, R
2
, R
3
, n have the meanings given in the description—to their use as acaricides and insecticides for controlling animal pests and to processes and intermediates for their preparation
