Parent and 5 metabolites were identified in the excreta of male and female /rats/ following /IV or orally/ administered [14Cpy]-bispyribac-sodium and parent and 3 metabolites identified with [14C-Bn]-bispyribac-sodium administration. The parent compound, bispyribac-sodium, was the major component identified in the feces (37-69% of the dose) and urine (5-41%of the dose), in both sexes. Metabolites identified in the excreta constituted 8.3-14.6% and unknown metabolites constituted 0.7-5.2% of the dose.
One Fischer 344 rat/sex/group was dosed by either oral gavage or intravenous injection with 100 mg/kg of (14)C Bispyribac (KIH-2023, specific activity: 1.50 GBq/mmol, radiochemical purity: 98.2%) (label on the 2nd carbon of the pyrimidine ring). Technical grade Bispyribac (KIH-2023, purity: 95.2%) was used to supplement the dosing preparations. ... Demethylation of the parent compound was the predominant metabolic process identified.
Groups of Fischer 344 rats were dosed orally by gavage or by intravenous injection with bis-(pyrimidine-2-(14)C) Bispyribac (KIH-2023, radiochemical purity: 98.3%, specific activity: 87.0 :Ci/mg) ((14)C (Py) Bispyribac) or U-(benzene-(14)C) Bispyribac (radiochemical purity: >99%, specific activity: 50 :Ci/mg) (14)C (Bn) Bispyribac). In Groups 1A, B, C and D, 5 animals/sex/group were dosed orally with 30 mg/kg of either (14)C (Py) Bispyribac (A and C) or (14)C (Bn) Bispyribac (B and D). For Groups 2 A and B, 5 animals/sex/group were dosed daily by oral gavage with 30 mg/kg of Bispyribac, technical grade (purity: 97.2%) for 14 days, followed a dose of 30 mg/kg of either (14)C (Py) Bispyribac (A) or (14)C (Bn) Bispyribac (B). For Groups 3A, B, C and D, 5 animals/sex/group were dosed orally by gavage with 600 mg/kg of either (14)C (Py) Bispyribac (A and C) or (14C) (Bn) Bispyribac (B and D). For Groups 4A, B, C and D, five animals/sex/group received intravenous injections of 30 mg/kg of either (14)C (Py) Bispyribac (A and C) or (14)C (Bn) Bispyribac (B and D). ... The test material was metabolized by cleavage of the ether linkage between the benzene and pyrimidine rings and removal of the methyl groups from the pyrimidine moieties. The position of the radiolabel did not alter the metabolic profile. ...
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
解毒与急救
/SRP:/ 高级治疗：对于无意识、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。考虑使用药物治疗肺水肿……。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇……。监测心率和必要时治疗心律失常……。开始静脉输注D5W /SRP: "保持开放"，最低流量/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸林格氏液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象……。使用地西泮或劳拉西泮治疗癫痫……。使用丙美卡因氢氯化物协助眼部冲洗……。 /Poisons A and B/
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Bispyribac (KIH-2023 technical, purity = 98.6%) was moistened with deionized water, poured onto a gauze pad, and applied to the clipped skin of 5 Sprague-Dawley Crl:CD BR rats/sex/dose at dose levels of 0 (deionized water), 10, 100, or 1000 mg/kg for 6 hrs daily for 21 consecutive days. No animals died. No treatment-related clinical signs or signs of dermal irritation were observed. Body weight determinations, hematology, serum chemistry, organ weight determinations, gross pathology, and histopathology revealed no treatment-related effects. NOEL (M/F, systemic and skin) = 1000 mg/kg/day (based on no effects at highest dose tested).
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Bispyribac (KIH-2023 technical, purity = 94.5%) was administered orally, via gelatin capsules, once daily to 4 beagle dogs per sex per dose at dose levels of 0 (empty capsule), 30, 100, or 600 mg/kg for 13 weeks. No animals died. Treatment-related vomiting, loose stool, and salivation were observed in both sexes at 600 mg/kg/day. Body weight, hematology, serum chemistry, urinalysis, ophthalmology, organ weight, and gross pathology investigations revealed no treatment-related effects. Microscopic examination revealed treatment-related proliferation of the bile ducts in the liver of males at 600 mg/kg/day. NOEL (M/F) = 100 mg/kg/day (based on clinical signs /SRP: and bile duct changes/).
A series of rat metabolism studies with [14CPy]-bispyribac-sodium and [14C-Bn]-bispyribac-sodium indicated that pretreatment, dose level, sex and position of the radiolabel made little effect on the absorption, distribution, elimination and metabolism. It was readily absorbed by male and female rats following intravenous or oral dosing. The total recovery of the administered radioactivity was 95.8-101.6% for all treatment groups. Most of the dose (>43%) of the administered dose was excreted in feces within 48 hours and essentially complete within 5 days. Less than 2% of the administered dose remained in the carcass and tissues and <0.1% of the dose was recovered in air.
Five Fischer 344 rats/sex/group were dosed orally with either 10 or 100 mg/kg of (14)C (Py) KIH-2023 (specific activity: 1.46 GBq/mmol, radiochemical purity: 97.7%, lot no. CP-1221) following overnight fasting. Bispyribac (KIH-2023, purity: 95.2%, lot no. G35-04) was used in the preparation of the dosing solutions. Bile was collected hourly through the first 6 hrs post-dose and at the 6-12 and 12-24 hr intervals. Urine and feces were collected at 0-6, 6-12 and 12-24 hr intervals post-dose. The percentage of the administered dose recovered in the bile over the first 24 hrs after dosing was approximately 36 to 37% for the males and 24 to 27% for the females at the two dose levels. In that first 24 hrs, 2.4% or less of the dose was recovered in the feces. However, at 24 hrs, 22.5 to 30.0% of the radiolabel at the low dose and 40 to 44% at the high dose was still associated with the tissues of the gastrointestinal tract and may not have been absorbed. Only two of the five major radiolabeled moieties in the bile were identified, demethylated Bispyribac and Bispyribac. These two moieties constituted 52.0 to 60.1% of the recovered radiolabel in the bile. Overall, the data indicate that the hepato-biliary pathway is a significant route for the uptake and excretion of the test material.
One Fischer 344 rat/sex/group was dosed by either oral gavage or intravenous injection with 100 mg/kg of (14)C Bispyribac (KIH-2023, specific activity: 1.50 GBq/mmol, radiochemical purity: 98.2%) (label on the 2nd carbon of the pyrimidine ring). Technical grade Bispyribac (KIH-2023, purity: 95.2%) was used to supplement the dosing preparations. Carbon dioxide was collected up to 24 hrs post-dose. Urine and feces were collected at the 0-12, 12-24, 24-48 and 48-72 hr intervals. In phase B, two rats/sex were dosed by oral gavage with 100 mg/kg of the test material. At 15 and 30 minutes and 1, 2, 4, 8, 24, and 48 hrs post-dose, blood was collected by retroorbital bleeding from one male and one female. In phase C, two rats/sex were dosed by oral gavage with 100 mg/kg of the test material. One animal/sex was euthanized by exsanguination at 2 and 72 hrs post-dose. Blood was collected along with specified tissues. In phase E, one male was treated by oral gavage with 100 mg/kg of the test material. Urine and feces were collected over 0-24 and 24-48 hr intervals post-dose for metabolite analysis. When the test material was dosed orally, a greater percentage of the dose was recovered in the feces. Intravenous injection resulted in a lower percentage of radiolabel recovered in the feces with a corresponding increase in recovery from the urine. The presence of the radiolabel in the feces after intravenous dosing indicated that biliary excretion had occurred. Recovery of radiolabeled carbon dioxide was negligible. Peak blood levels were evident at 2 hrs post-dose. The highest levels of radiolabel recovered in the 2 hr samples were in the contents of the gastrointestinal tract. Otherwise, the level of radiolabeling in the tissues had largely dissipated by 72 hrs. The predominant radioalabeled moiety in both the urine and feces was the parent compound. It constituted 86% of the recovered label. ...
Groups of Fischer 344 rats were dosed orally by gavage or by intravenous injection with bis-(pyrimidine-2-(14)C) Bispyribac (KIH-2023, radiochemical purity: 98.3%, specific activity: 87.0 :Ci/mg) ((14)C (Py) Bispyribac) or U-(benzene-(14)C) Bispyribac (radiochemical purity: >99%, specific activity: 50 :Ci/mg) (14)C (Bn) Bispyribac). In Groups 1A, B, C and D, 5 animals/sex/group were dosed orally with 30 mg/kg of either (14)C (Py) Bispyribac (A and C) or (14)C (Bn) Bispyribac (B and D). For Groups 2 A and B, 5 animals/sex/group were dosed daily by oral gavage with 30 mg/kg of Bispyribac, technical grade (purity: 97.2%) for 14 days, followed a dose of 30 mg/kg of either (14)C (Py) Bispyribac (A) or (14)C (Bn) Bispyribac (B). For Groups 3A, B, C and D, 5 animals/sex/group were dosed orally by gavage with 600 mg/kg of either (14)C (Py) Bispyribac (A and C) or (14C) (Bn) Bispyribac (B and D). For Groups 4A, B, C and D, five animals/sex/group received intravenous injections of 30 mg/kg of either (14)C (Py) Bispyribac (A and C) or (14)C (Bn) Bispyribac (B and D). For all groups designated A or B, urine and feces samples were collected at 0-12 hr, 12-24 hr, 24-48 hr, 48-72 hr, 72-96 hr and 96-120 hours post-dose. At that time the animals were euthanized, a blood sample collected and the animals dissected for specified tissues. For all groups designated C or D, blood was collected from the tail vein at 0.25, 0.5, 1, 2, 4, 8, 24, 48, 72 and 96 hours post-dose. At 120 hrs, the animals were euthanized and a blood sample collected. The feces were the primary route of excretion for both of the radiolabeled compounds. At the lower dose, the males excreted from 11 to 13% and 80 to 85% of the administered dose in the urine and feces, respectively. At the higher dose, excretion in the urine ranged from 25 to 28% of the administered dose. In the feces, 70% of the dose was excreted. For the females, the percentage of administered dose excreted by either route did not vary at both dose levels. The percent of administered dose excreted in the urine ranged from 28 to 37%. For the feces, the range was from 48 to 60% (note: two of the radiolabel recovery values from the feces, for Groups 1A and 2A, were close to or in excess of 100% of the administered dose and appeared to be at variance from all of the other data collected). At the lower dosing level via the oral route, peak plasma levels were achieved within 30 minutes of dosing for both radiolabeled compounds. At 600 mg/kg, the plasma levels remained at a peak concentration for up to 4 hrs post-dose. ... The liver, intestinal tract and plasma were the primary sites of recovery of radiolabel at 120 hrs post-dose. Analysis of the radiolabeled material revealed the unmetabolized test compound was the primary moiety excreted. This moiety constituted 68.5 to 82.9% of the administered dose recovered from both the feces and urine (note: the value for the 3B females of 99.8% was well in excess of all of the other recoveries). The quantity of administered dose, sex of the treated animal or the route of treatment did not greatly alter the percent of unmetabolized test material recovered. ...
Absorption, distribution and metabolism of Bispyribac-sodium (sodium 2,6-bis(4,6-dimethoxypyrimidin-2-yloxy)benzoate) or (KIH-2023) in rats orally dosed with 14C-KIH-2023 were investigated. More than 90% of the dosed radioactivity was detected in the excreta within 96 hr after dosing. Level of the radioactivity in the blood of male and female rats reached maxima at 2 and 1 hr after dosing, respectively, and then decreased rapidly to about a half level of maxima (C1/2). The radioactivity of tissues was lower at 96 hr after dosing than that at C1/2-time. Most of the radioactivity in the urine, feces, liver and plasma was detected as unchanged KIH-2023. The major radioactive compounds excreted into the bile were KIH-2023 and its glucuronide. Repeated oral administration of KIH-2023 for 15 days gave similar results from the single oral one in the excretion, tissue distribution and metabolism of 14C-KIH-2023.
[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.
Molecules having pesticidal utility, and intermediates, compositions, and processes, related thereto
申请人：Dow AgroSciences LLC
公开号：US20180279612A1
公开（公告）日：2018-10-04
This disclosure relates to the field of molecules having pesticidal utility against pests in Phyla Arthropoda, Mollusca, and Nematoda, processes to produce such molecules, intermediates used in such processes, pesticidal compositions containing such molecules, and processes of using such pesticidal compositions against such pests. These pesticidal compositions may be used, for example, as acaricides, insecticides, miticides, molluscicides, and nematicides. This document discloses molecules having the following formula (“Formula One”).
