... Two goats were dosed with ring-labeled (14)C-asulam at 20 ppm in the diet for 7 consecutive days. The total radioactive residues were nondetectable (<0.005 ppm) in fat and muscle, 0.162 ppm in kidneys, 0.090 ppm in liver, and up to 0.021 ppm in milk. The parent compound, asulam, constituted the majority of the residues in milk (81% of total reactive reside (TRR)) and kidneys (100% of TRR) and its metabolite N4-acetylsulfanilamide constitutes the majority of residues in liver (58% of TRR). The parent was not identified in liver samples. In a previous study, sulfanilamide was found in ruminant liver and muscle, and N4-acetylasulam was found in liver, kidney, milk, muscle, and fat.
... Laying hens were dosed with ring-labeled (14)C-asulam at 22.5 ppm in the diet for 7 consecutive days. The maximum total radioactive residues were 0.027 ppm in egg yolks, 0.062 ppm in egg whites, 0.011 ppm in fat, 0.074 ppm in muscle, 0.444 ppm in kidneys, and 0.086 ppm in liver. The parent compound asulam, and its metabolite N4-acetylsulfanilamide constituted the majority of the residues in poultry, comprising 63 and 44% of the total reactive reside (TRR), respectively, in egg yolks, 21 and 52% of the TRR, respectively, in egg whites, 35 and 51% of the TRR, respectively, in muscle, and 83 and 14% of the TRR, respectively, in kidney. The parent was not identified in liver samples; N4-acetyl sulfanilamide represented 81% of the TRR in liver samples.
来源:Hazardous Substances Data Bank (HSDB)
代谢
Metabolism studies were conducted in male and female Sprague-Dawley rats. The tests used a single oral or iv dose, or repeated i.v. doses for 14 days. The pharmacokinetics of asulam were similar after all dose regimens in both sexes. Peak blood levels were attained at 0.5 hours. No unusual localization of asulam occurred in tissues and all tissue levels were low at 72 hours. Asulam was rapidly eliminated, mostly within 24 hours. 76.5% to 101.5% of the administered dose was eliminated in the urine, and 1.4% to 25.3% of the dose in feces. The major excretory product was unchanged parent compound (70% to 80%), with acetylasulam (3% to 8%) and acetylsulphanilamide (<3%) being the two major metabolites.
Metabolism studies were conducted in male and female Sprague- Dawley rats. The tests used a single oral or iv dose, or repeated i.v. doses for 14 days. The pharmacokinetics of asulam were similar after all dose regimens in both sexes. Peak blood levels were attained at 0.5 hours. No unusual localization of asulam occurred in tissues and all tissue levels were low at 72 hours. Asulam was rapidly eliminated, mostly within 24 hours. 76.5% to 101.5% of the administered dose was eliminated in the urine, and 1.4% to 25.3% of the dose in feces. The major excretory product was unchanged parent compound (70% to 80%), with acetylasulam (3% to 8%) and acetylsulphanilamide (<3%) being the two major metabolites.
The metabolism of [ring-(14)C]asulam, a systemic herbicide highly effective against bracken, has been studied in rats. Most of the radioactivity (76-100% dose) administered orally or intravenously is excreted in the urine in 24 hr as unchanged asulam (61-74% dose), N4-acetylasulam (8-14%) and N4-acetylsulphanilamide (0.1-2.6%). Small amounts of radioactivity (0.3-7.4% dose) were present in the feces, only traces (0.2-0.3%) were excreted in the bile, and no significant (14)CO2 was detected. Perfusion of rat liver with (14)C-asulam resulted in more extensive metabolism. Total amounts present in perfusate (81% total), bile (1%) plus liver (14%) were 23.1% for unchanged asulam, 25.7% for acetylasulam, less than 1% for acetylsulphanilamide, and 4.5% as conjugates of asulam and acetylasulam, together with several other unidentified metabolites. Asulam is acetylated more readily than sulphanilamide, by rat-liver homogenate, and the highest enzyme activity was associated with the mitochondrial fraction (2.4 pmol/mg protein per min). Although not hydroxylated by rats in vivo, evidence was obtained for the hydroxylation of asulam by rat-liver microsomal preparations in vitro.
来源:Hazardous Substances Data Bank (HSDB)
代谢
氨基甲酸酯通过肝脏酶促水解；降解产物通过肾脏和肝脏排出。
The carbamates are hydrolyzed enzymatically by the liver; degradation products are excreted by the kidneys and the liver. (L793)
IDENTIFICATION AND USE: Asulam is a herbicide used for weed control. Asulam is formulated into and applied as the asulam sodium salt. HUMAN STUDIES: In vitro cytogenetics assay in human lymphocytes were negative for asulam. ANIMAL STUDIES: Application of technical asulam to rabbit eyes produced mild chemosis, irritation, and redness which cleared by day seven posttreatment. Asulam was not an irritant in a primary skin irritation study in rabbits. It did not cause dermal sensitization in guinea pigs. In a six-month feeding study of asulam in beagle dogs doses of asulam at 300 mg/kg/day and 1,500 mg/kg/day were associated with reductions in food consumption, body weight gain, emesis, diarrhea, and reductions in red blood cells, hemoglobin and packed cell volume. There were also elevated thyroid and kidney weights and reduced testicular weights. In a two-year carcinogenicity study mice, asulam was administered in the diet at 0, 500, 5,000 or 50,000 ppm. There was no increase in the incidence of any tumors. A two-year combined chronic feeding/carcinogenicity study was conducted using rats. Hyperplastic changes were observed in the adrenal medulla and in thyroid follicular cells of males at the doses of 180 and 953 mg/kg/day. There was a statistically significant increase in thyroid gland c-cell carcinomas and in adenomas and carcinomas combined in both the low- and mid-dose males. There was a statistically-significant increase in benign adrenal medullary pheochromocytomas at the high dose in males. No teratogenic effects were produced by asulam in either rats or rabbits. The Ames Assay which is used to detect gene mutation with Salmonella typhimurium was negative. Mutagenicity assays which detect structural chromosome aberrations included the dominant lethal test in mice and were negative for asulam. ECOTOXICITY STUDIES: When tested in bobwhite quail (Colinus virginianus) dietary study, asulam had no effect on food consumption, body weight, or cumulative mortality, and no signs of toxicity were seen during the 28-day feeding period. Similarly, the chemical had no effect on egg production, fertility, or hatchability of fertile eggs, or on abnormalities in the F1 generation.
Asulam 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.
... Two goats were dosed with ring-labeled (14)C-asulam at 20 ppm in the diet for 7 consecutive days. The total radioactive residues were nondetectable (<0.005 ppm) in fat and muscle, 0.162 ppm in kidneys, 0.090 ppm in liver, and up to 0.021 ppm in milk. The parent compound, asulam, constituted the majority of the residues in milk (81% of total reactive reside (TRR)) and kidneys (100% of TRR) and its metabolite N4-acetylsulfanilamide constitutes the majority of residues in liver (58% of TRR). The parent was not identified in liver samples. In a previous study, sulfanilamide was found in ruminant liver and muscle, and N4-acetylasulam was found in liver, kidney, milk, muscle, and fat.
... Laying hens were dosed with ring-labeled (14)C-asulam at 22.5 ppm in the diet for 7 consecutive days. The maximum total radioactive residues were 0.027 ppm in egg yolks, 0.062 ppm in egg whites, 0.011 ppm in fat, 0.074 ppm in muscle, 0.444 ppm in kidneys, and 0.086 ppm in liver. The parent compound asulam, and its metabolite N4-acetylsulfanilamide constituted the majority of the residues in poultry, comprising 63 and 44% of the total reactive reside (TRR), respectively, in egg yolks, 21 and 52% of the TRR, respectively, in egg whites, 35 and 51% of the TRR, respectively, in muscle, and 83 and 14% of the TRR, respectively, in kidney. The parent was not identified in liver samples; N4-acetyl sulfanilamide represented 81% of the TRR in liver samples.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
Metabolism studies were conducted in male and female Sprague-Dawley rats. The tests used a single oral or iv dose, or repeated i.v. doses for 14 days. The pharmacokinetics of asulam were similar after all dose regimens in both sexes. Peak blood levels were attained at 0.5 hours. No unusual localization of asulam occurred in tissues and all tissue levels were low at 72 hours. Asulam was rapidly eliminated, mostly within 24 hours. 76.5% to 101.5% of the administered dose was eliminated in the urine, and 1.4% to 25.3% of the dose in feces. The major excretory product was unchanged parent compound (70% to 80%), with acetylasulam (3% to 8%) and acetylsulphanilamide (<3%) being the two major metabolites.
Metabolism studies were conducted in male and female Sprague- Dawley rats. The tests used a single oral or iv dose, or repeated i.v. doses for 14 days. The pharmacokinetics of asulam were similar after all dose regimens in both sexes. Peak blood levels were attained at 0.5 hours. No unusual localization of asulam occurred in tissues and all tissue levels were low at 72 hours. Asulam was rapidly eliminated, mostly within 24 hours. 76.5% to 101.5% of the administered dose was eliminated in the urine, and 1.4% to 25.3% of the dose in feces. The major excretory product was unchanged parent compound (70% to 80%), with acetylasulam (3% to 8%) and acetylsulphanilamide (<3%) being the two major metabolites.
The metabolism of [ring-(14)C]asulam, a systemic herbicide highly effective against bracken, has been studied in rats. Most of the radioactivity (76-100% dose) administered orally or intravenously is excreted in the urine in 24 hr as unchanged asulam (61-74% dose), N4-acetylasulam (8-14%) and N4-acetylsulphanilamide (0.1-2.6%). Small amounts of radioactivity (0.3-7.4% dose) were present in the feces, only traces (0.2-0.3%) were excreted in the bile, and no significant (14)CO2 was detected. Perfusion of rat liver with (14)C-asulam resulted in more extensive metabolism. Total amounts present in perfusate (81% total), bile (1%) plus liver (14%) were 23.1% for unchanged asulam, 25.7% for acetylasulam, less than 1% for acetylsulphanilamide, and 4.5% as conjugates of asulam and acetylasulam, together with several other unidentified metabolites. Asulam is acetylated more readily than sulphanilamide, by rat-liver homogenate, and the highest enzyme activity was associated with the mitochondrial fraction (2.4 pmol/mg protein per min). Although not hydroxylated by rats in vivo, evidence was obtained for the hydroxylation of asulam by rat-liver microsomal preparations in vitro.
产品信息
磺草灵（商品名称：Asilan，其他名称：Asulox、MB9057）属于氨基甲酸酯类选择性内吸传导型苗期除草剂。它是细胞生长抑制剂。于1965年由H. J. Cottrell & B. J. Heywood首次报道，并由May和Baker公司（现属拜耳）上市。主要应用于甘蔗、冷杉、草皮、观赏性作物及非作物领域，剂型为水剂。
A Convenient Method of Protection and Mild Deprotection of α-Aminoacids
摘要：
Functionalisation of beta or gamma carboxyl group of aspartic and glutamic acids with labile substituents was performed via the use of N-trichloroethoxycarbonyl-5-oxazolidinone as protective group.
[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.
[EN] 3-[(HYDRAZONO)METHYL]-N-(TETRAZOL-5-YL)-BENZAMIDE AND 3-[(HYDRAZONO)METHYL]-N-(1,3,4-OXADIAZOL-2-YL)-BENZAMIDE DERIVATIVES AS HERBICIDES<br/>[FR] DÉRIVÉS DE 3-[(HYDRAZONO))MÉTHYL]-N-(TÉTRAZOL-5-YL)-BENZAMIDE ET DE 3-[(HYDRAZONO)MÉTHYL]-N-(1,3,4-OXADIAZOL-2-YL)-BENZAMIDE UTILISÉS EN TANT QU'HERBICIDES
申请人：SYNGENTA CROP PROTECTION AG
公开号：WO2021013969A1
公开（公告）日：2021-01-28
The present invention related to compounds of Formula (I): or an agronomically acceptable salt thereof, wherein Q, R2, R3, R4, R5 and R6 are as described herein. The invention further relates to compositions comprising said compounds, to methods of controlling weeds using said compositions, and to the use of compounds of Formula (I) as a herbicide.
[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。
[EN] HERBICIDALLY ACTIVE HETEROARYL-S?BSTIT?TED CYCLIC DIONES OR DERIVATIVES THEREOF<br/>[FR] DIONES CYCLIQUES SUBSTITUÉES PAR HÉTÉROARYLE À ACTIVITÉ HERBICIDE OU DÉRIVÉS DE CELLES-CI
申请人：SYNGENTA LTD
公开号：WO2011012862A1
公开（公告）日：2011-02-03
The invention relates to a compound of formula (I), which is suitable for use as a herbicide wherein G is hydrogen or an agriculturally acceptable metal, sulfonium, ammonium or latentiating group; Q is a unsubstituted or substituted C3-C8 saturated or mono-unsaturated heterocyclyl containing at least one heteroatom selected from O, N and S, or Q is heteroaryl or substituted heteroaryl; m is 1, 2 or 3; and Het is an optionally substituted monocyclic or bicyclic heteroaromatic ring; and wherein the compound is optionally an agronomically acceptable salt thereof.
The present invention provides triazole compounds useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.
