From livestock metabolism studies, the residues with concentrations >10% total radioactive residue were chosen as residues of concern for livestock. Therefore, besides the parent compound, M2 and M4 (free and conjugated) for ruminants and M2, M4 (free and conjugated), and M6 for poultry were determined to be residues of concern. M4 is the major metabolite in the livestock. ((14)Cphenyl)-pinoxaden and ((14)C-phenyl)-M4 were the only compounds that were fed to ruminants in two separate studies.
The metabolism of pinoxaden in rats primarily involves the initial hydrolysis of the ester moiety to form metabolite M2 (NOA 407854), which is then extensively excreted in the urine and feces. To a minor extent, metabolite M2 is also further metabolized via hydroxylation, dealkylation, ring cleavage, ring formation, and conjugation into a wide variety of minor metabolites. The proposed pathway is also supported by the appended in vitro study, which indicates that pinoxaden is rapidly hydrolyzed to M2 in rat plasma (half life = approximately 0.1 min) at concentrations up to 100 uM (approximately 40 ppm).
In a ... rabbit metabolism study, a single oral dose of (Phenyl-1-(14)C) NOA 407855 (/pinoxaden/ Batch/lot # ILA-8.1B-5 and ILA-8.1C-1B; radiochemical purity $98.9%) was administered in aqueous 0.5% carboxymethylcellulose and 0.1% Tween 80 to female Chbb-HM rabbits (3/dose) via gavage at nominal dose levels of 0.5 and 300 mg/kg. Urine, feces, and blood samples were collected up to 168 hours after dosing. Metabolites in urine and feces were quantified and identified by HPLC, TLC, and LC/MS. ... Essentially all of the metabolites excreted in the urine and feces were identified (92.8-97.7% dose), and the metabolite profile was the same regardless of dose level. For both dose groups, Metabolite M2 (NOA 407854) was identified as the major component in both urine (88.6-91.0% dose) and feces (3.6-6.2% dose). Minor amounts of Metabolites M4 (0.4-0.6% dose), K4 (0.2% dose), M12 (0.2% dose) and K3 (0.1% dose) were also identified in urine and/or feces. Unidentified metabolites accounted for less than or equal to 0.6% dose. In rabbits, the metabolism of NOA 407885 proceeds predominantly by hydrolysis of the ester linkage to form Metabolite M2 (NOA 407854), which is the major metabolite in urine and feces (92-97% dose). Minor secondary reactions include either: hydroxylation at the 4-methyl group of the phenyl moiety to yield M4 (excreted in urine and feces); or glucuronidation of M2 to form metabolite M12. The metabolic pathway in the rabbit is essentially identical to the rat.
来源:Hazardous Substances Data Bank (HSDB)
代谢
在小白鼠代谢研究中，给4组雄性和雌性C57BL/10Jf/CD-1小白鼠口服了(pyr azol-3,5-(14)C) NOA 407855(皮诺克森/纯度大于或等于97.6%;批号ILA-76.3B ILA-76.3C),具体如下:(1)G1组口服1次或每天口服1次,剂量为1.4毫克/千克体重;(2)G2组口服1次或每天口服1次,剂量为140毫克/千克体重;饮食;(3)G3组喂食10毫克/千克的饮食;(4)G4组喂食1000毫克/千克的饮食。每个组的最大给药持续时间为18天。 口服NOA 407855后,小鼠的血液、尿液和粪便中的代谢物轮廓在性别、剂量水平、给药方法(口服vs.饮食)、给药持续时间(单次vs.多次)和时间收集上都是定性和定量独立的,尽管在粪便中观察到了一些定量变化。未检测到母体化合物。代谢物M2(NO A 407854)是三个基质中鉴定出的主要组分,占约67-93%的可提取血液放射性,69-89%的尿液总放射性,和35-75%的可提取粪便放射性。在血液(2-11%的可提取血液放射性)、尿液(5-14%的总放射性)和粪便(12-41%的可提取放射性)中也检测到大量的代谢物M4。每个基质中检测到的其余组分都是少量的(<8%的样品放射性),包括血液提取物中的5个组分、尿液中的8个组分和粪便提取物中的8-11个组分。通过LC/MS和LC/NMR分析从复合样品中分离出的馏分,证实了尿液和粪便中存在代谢物M2和M4。这些分析还鉴定了尿液中代谢物M13、M21、M50和M51的少量(<3%的样品放射性)和粪便提取物中代谢物M13、M19、M20、M22、M49和M50的少量。根据在血液、尿液和粪便中确定的代谢物及其相对丰度,NOA 407855在小鼠体内的代谢主要涉及将酯部分水解形成代谢物M2,这是尿液和粪便中主要排泄的组分。在较小的程度上,代谢物M2也可能经历一些次级反应,产生多种少量的代谢物。这些次级反应包括:羟基化、氧化、水解、脱烷基、成环和切断氧化二氮杂环中的醚键。
In a ... mouse metabolism study, (pyrazol-3,5-(14)C) NOA 407855 (/pinoxaden/ greater than or equal to 97.6% radiochemical purity; Lots ILA-76.3B ILA-76.3C) was administered to 4 groups of male and female C57BL/10Jf/CD-1 mice as follows: (I) Group G1 was given either a single-dose or repeated daily dose of 1.4 mg/kg body-weight by gavage; (ii) Group G2 was administered either a single-dose or repeated daily dose of 140 mg/kg body-weight by gavage; (iii) Group G3 was fed at 10 ppm in the diet; and (iv) Group G4 was fed a 1000 ppm diet. The maximum duration of dosing in each group was for 18 days. ... Following oral administration of NOA 407855 to mice either by gavage or in the diet, the metabolite profiles in blood, urine and feces were qualitatively and quantitatively independent of sex, dose level, dosing method (gavage vs. dietary), dosing duration (single vs. multiple doses) and time of collection, although some quantitative variations were observed in feces. Parent compound was not detected in blood, urine or feces. Metabolite M2 (NOA 407854) was the major component identified in all three matrices, accounting for approximately 67-93% of the extractable blood radioactivity, 69-89% of the total radioactivity in urine, and 35-75% of the radioactivity extractable from feces. Substantial amounts of Metabolite M4 were also detected in blood (2-11% extractable blood radioactivity), urine (5-14% of total radioactivity), and feces (12-41% of the extractable radioactivity). The remaining components detected in each matrix were minor (<8% of the sample radioactivity) and included five components in blood extracts, eight components in urine, and 8-11 components in fecal extracts. The presence of Metabolites M2 and M4 in urine and feces were confirmed by LC/MS and LC/NMR analyses of fractions isolated from composited samples. These analyses also identified minor amounts (<3% sample radioactivity) of Metabolites M13, M21, M50, and M51 in urine and Metabolites M13, M19, M20, M22, M49, and M50 in fecal extracts. Based on the metabolites identified in blood, urine and feces and their relative abundance, the metabolism of NOA 407855 in mice primarily involves hydrolysis of the ester moiety to form Metabolite M2, which is the primary component excreted in urine and feces. To a minor extent, Metabolite M2 may also undergo a number of secondary reactions to produce variety of minor metabolites. These secondary reactions include: hydroxylation, oxidation, hydrolysis, dealkylation, ring formation, and cleavage of the ether bond in the oxadiazepine moiety.
In a ... study designed to correlate the levels of Metabolite M2 (NOA 407854) in the blood with the ingestion of NOA 407855 /pinoxaden/ in the diet, four groups of C57Bl/10JfCD-1 mice (24/sex/dose group) were fed diets containing NOA 407855 (97.2% ai, Lot #EZ005006) for at least 39 consecutive days. Two groups were fed diets containing NOA 407855 at 1000 or 2500 ppm for the entire period; the third group was fed at 2500 ppm for 7 days, followed by 5000 ppm for at least 32 consecutive days; and the fourth group was fed at 2500 ppm for 7 days, followed by 5000 ppm for 14 days, and then 7000 ppm for at least 18 days. A fifth group of mice (3 or 4/sex) of the same source and strain served as controls for the duration of the study. ... Concentrations of M2 in blood on Study days 40 and 41 averaged 1.7-2.3 mg/kg at 1000 mg/kg, 4.6-7.4 mg/kg at 2500 ppm, 11.8-12.7 mg/kg at 5000 ppm, and 17.0-20.8 mg/kg at 7000 ppm. Linear regression showed a direct correlation between the concentration of M2 in the blood and the concentration of the test material in the diet, with R2 = 0.96 for females and 0.98 for males. There were no apparent differences in M2 blood concentrations between sexes or time of blood sampling at any dose.
/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/
/GENOTOXICITY/ In two independent trials of a mammalian cell cytogenetics assay, lymphocyte cultures were prepared from human peripheral blood and exposed to SYN 502836 (a metabolite of Pinoxaden tech.; pinoxaden; 99% a.i., Batch # KI 6513/3M) in dimethylsulfoxide (DMSO) at concentrations of 50, 100, 200, 500, 1000, 1500, 2000, and 2750 ug/mL for either 3 hours with a 17 hour recovery period (Trial 1, +/-S9 and Trial 2, +S9) or 20 hours with no recovery period (Trial 2, -S9). SYN 502836 was tested up to a maximum concentration of 2000 ug/mL (+/-S9), which was limited by reductions in the pH of the treatment medium. Cytotoxicity (as evidenced by reduced mitotic index) was noted at greater than or equal to 1000 ug/mL in Trial 1 (+S9) and at 2000 ug/mL in Trial 2 (+/-S9). No significant increases in aberration frequencies (excluding gaps) were observed in the presence or absence of S9 in either trial. The positive controls induced the appropriate response in all assays. There was no evidence of chromosome aberrations induced over background in the presence or absence of S9-activation. /SYN 502836/
/LABORATORY ANIMALS: Acute Exposure/ 5/sex/dose Wistar rats (Age: 8 weeks, Weight: 185.9-199.4 g males, 162.6-176.8 g females) were given a single oral dose of pinoxaden technical(Propanoic acid: 97.2%; Batch #: EZ005006; beige solid) or a control dose of 0.5% w/v carboxymethylcellulose in 0.1% w/v polysorbate 80 by oral gavage. The study was performed at a limit dose of either 5,000 mg/kg or 0 mg/kg (control). Individual animal body-weights were recorded prior to dosing, and again on days 7 and 14. Clinical signs of toxicity were made several times post-dosing on the initial study day and daily thereafter for 14 days. All animals were necropsied on study day 14 or immediately after death. ... All control animals survived, gained weight and appeared healthy during the study. No gross internal findings were observed at necropsy. For those animals dosed at 5,000 mg/kg clinical signs of toxicity noted included slight soft feces and hunched posture, but animals recovered from these symptoms by day 1 of the study. One male was found dead on day 5 post-dosing. Gross necropsy of this animal revealed reddish small and large intestines and a reddish caecum. The surviving animals all gained weight during the study and had no gross internal findings at necropsy.
In a ... rabbit metabolism study, a single oral dose of (Phenyl-1-(14)C) NOA 407855 (/pinoxaden/ Batch/lot # ILA-8.1B-5 and ILA-8.1C-1B; radiochemical purity $98.9%) was administered in aqueous 0.5% carboxymethylcellulose and 0.1% Tween 80 to female Chbb-HM rabbits (3/dose) via gavage at nominal dose levels of 0.5 and 300 mg/kg. Urine, feces, and blood samples were collected up to 168 hours after dosing. Metabolites in urine and feces were quantified and identified by HPLC, TLC, and LC/MS. Animals were sacrificed after 168 hours, and tissues were collected to determine of residual radioactivity. Absorption and elimination of (14)C NOA 407855 were rapid and essentially complete regardless of dose level. Maximum concentrations (Cmax) in blood were attained within 0.5 hours at the low dose and within approximately 2 hours at the high dose. Half lives for radioactivity in the blood were 3 and 12 hours for the low and high dose groups, and radioactivity in blood was non-detectable by 48 and 96 hours for the low and high dose groups. The total recovery of the radioactive dose averaged 94.7-100.1% at 168 hours post-dose. The route of excretion was essentially independent of dose, although excretion was slightly retarded at the high dose compared to the low dose. Approximately 90% of the dose was excreted in the urine within 24 (low dose) or 48 (high dose) hours. An additional 4-7% dose was excreted in the feces within 48 hours. For both dose groups, concentrations of radioactivity remaining in the tissues were negligible by 168 hours post-dose and accounted for less than or equal to 0.1% of the dose. Quantifiable residues were detect in gall bladder and gastrointestinal (GI) tract for both the low dose group (0.0020-0.0025 ppm Eq) and high dose group (1.66-1.69 ppm Eq), and in the kidneys, liver, plasma, and blood (0.017-0.158 ppm) of the high dose group. However, radioactivity in the remaining tissues was below the limit of quantitation (LOQ). Essentially all of the metabolites excreted in the urine and feces were identified (92.8-97.7% dose), and the metabolite profile was the same regardless of dose level. For both dose groups, Metabolite M2 (NOA 407854) was identified as the major component in both urine (88.6-91.0% dose) and feces (3.6-6.2% dose). Minor amounts of Metabolites M4 (0.4-0.6% dose), K4 (0.2% dose), M12 (0.2% dose) and K3 (0.1% dose) were also identified in urine and/or feces. Unidentified metabolites accounted for less than or equal to 0.6% dose. In rabbits, the metabolism of NOA 407885 proceeds predominantly by hydrolysis of the ester linkage to form Metabolite M2 (NOA 407854), which is the major metabolite in urine and feces (92-97% dose). Minor secondary reactions include either: hydroxylation at the 4-methyl group of the phenyl moiety to yield M4 (excreted in urine and feces); or glucuronidation of M2 to form metabolite M12. The metabolic pathway in the rabbit is essentially identical to the rat.
Dermal absorption is estimated to be 40% based on the results of the in vivo/in vitro dermal penetration study in rats using the EC 100 formulation. (The emulsifiable concentrate (EC) formulation will be used in the field and is believed to be much more absorbable than technical pinoxaden without the emulsifiers.) In this study with the EC formulation, 36% of the dose applied to the skin of rats in an in vivo study was absorbed over the following day (24 hours post-exposure). Absorption of the EC formulation from excised rat skin in an in vitro study was 65.5% of the applied dose after 24 hours post-exposure. For excised human skin, absorption of radioactivity was minimal regardless of the dosing vehicle and dose level in an in vitro study. Absorption accounted 0.36-1.84% of the applied dose after a 24-hour exposure at doses from 5-400 :g/cm2. Thus, in the in vitro studies, absorption was considerably higher in rat skin than in human skin. Additionally, absorption of the test substance in the in vivo rat study was comparable to the absorption in the in vitro study with rat skin. Therefore, the data suggest that in vivo absorption in humans would be considerably lower than in the rat.
In a ... mouse metabolism study, (pyrazol-3,5-(14)C) NOA 407855 (/pinoxaden/ greater than or equal to 97.6% radiochemical purity; Lots ILA-76.3B ILA-76.3C) was administered to 4 groups of male and female C57BL/10Jf/CD-1 mice as follows: (I) Group G1 was given either a single-dose or repeated daily dose of 1.4 mg/kg body-weight by gavage; (ii) Group G2 was administered either a single-dose or repeated daily dose of 140 mg/kg body-weight by gavage; (iii) Group G3 was fed at 10 ppm in the diet; and (iv) Group G4 was fed a 1000 ppm diet. The maximum duration of dosing in each group was for 18 days. Terminal blood samples were collected to determine a time course of the concentration of radioactivity in whole blood, and urine and feces were collected over 24 hours after varying time periods of dosing. The stated objectives of this study were to: (I) investigate the duration of dosing required to reach steady-state kinetics; (ii) compare systemic exposure following gavage or dietary dosing and determine any marked sex difference; (iii) compare blood and excreta metabolite profiles after single and multiple dosing to male and female mice; and (iv) resolve which metabolite should be analyzed during dietary studies. Radioactivity levels in whole blood sampled at various post-dose intervals indicated that the gavage dose was rapidly absorbed (Tmax = 0.5 hours) and eliminated regardless of the dose level or the duration of dosing. Absorption was slower for the dietary dosing groups (Tmax = 8-12 hours), but elimination from the blood was rapid once mice were withdrawn from the treated diet. Concentrations in blood at Tmax following 1, 7, 14, and 18 days of dietary dosing indicated that a steady state in blood levels was achieved within 18 days. Although urinary excretion was typically higher than fecal excretion, there was no clear pattern in the distribution of excreted radioactivity between urine and feces based on sex, dosing group, or duration of dosing. Radioactivity in urine (including cage wash) varied from 26-83% of the excreted radioactivity and in feces from 17-74%. Following oral administration of NOA 407855 to mice either by gavage or in the diet, the metabolite profiles in blood, urine and feces were qualitatively and quantitatively independent of sex, dose level, dosing method (gavage vs. dietary), dosing duration (single vs. multiple doses) and time of collection, although some quantitative variations were observed in feces. Parent compound was not detected in blood, urine or feces. Metabolite M2 (NOA 407854) was the major component identified in all three matrices, accounting for approximately 67-93% of the extractable blood radioactivity, 69-89% of the total radioactivity in urine, and 35-75% of the radioactivity extractable from feces. Substantial amounts of Metabolite M4 were also detected in blood (2-11% extractable blood radioactivity), urine (5-14% of total radioactivity), and feces (12-41% of the extractable radioactivity). The remaining components detected in each matrix were minor (<8% of the sample radioactivity) and included five components in blood extracts, eight components in urine, and 8-11 components in fecal extracts. The presence of Metabolites M2 and M4 in urine and feces were confirmed by LC/MS and LC/NMR analyses of fractions isolated from composited samples. These analyses also identified minor amounts (<3% sample radioactivity) of Metabolites M13, M21, M50, and M51 in urine and Metabolites M13, M19, M20, M22, M49, and M50 in fecal extracts. Based on the metabolites identified in blood, urine and feces and their relative abundance, the metabolism of NOA 407855 in mice primarily involves hydrolysis of the ester moiety to form Metabolite M2, which is the primary component excreted in urine and feces. To a minor extent, Metabolite M2 may also undergo a number of secondary reactions to produce variety of minor metabolites. These secondary reactions include: hydroxylation, oxidation, hydrolysis, dealkylation, ring formation, and cleavage of the ether bond in the oxadiazepine moiety.
In an in vivo dermal penetration study, (pyrazole-3, 5-(14)C) NOA407855 (/pinoxaden/ >95% radiochemical purity, lot/batch #EZ005006) was suspended in an emulsifiable concentrate (EC) formulation and applied neat or as aqueous dilutions to approximate exposure to the undiluted commercial formulation and to the dilute aqueous spray used in the field. The formulated test substance was administered to the shaved intact skin (10 sq cm) of 4 male Alpk:APfSD (Wistar-derived) rats/time point/dose at dose levels of 5 and 25 ug/sq cm for the aqueous dilutions (1/200 and 1/40) and 400 ug/cm2 for the neat EC formulation for a 4- or 10-hour exposure period. At the end of the exposure period, the skin of each rat was washed, and 4 rats/time point/dose were sacrificed for examination of dermal-absorption. A further 4 rats/dose were exposed for 10 hours and then retained for 24 hours after the skin was washed to determine further post-exposure absorption. In addition, in vitro studies were conducted using excised rat skin and human skin mounted in a static diffusion cell apparatus to compare dermal-absorption. The dosing regimen used in the in vitro studies was the same as in the in vivo study, except that an additional dose level of 1000 ug/sq cm was employed for human skin using the neat EC formulation. Absorption from excised skin samples was examined after 10- and 24-hour exposure durations, except at the 1000 ug/sq cm dose level which used only a 10-hour exposure. For the in vivo rat study, total recovery of the applied dose ranged from 84-96% for all dose groups. For the neat EC formulation (400 ug/sq cm), 17% of the dose was absorbed after 4 hours and 30% dose after 10 hours, increasing to 36% dose over the following day (24 hours post-exposure). Regardless of exposure duration, 7% dose remained available in or on the skin for potential absorption, with 1.3-1.4% of the dose in the stratum corneum. At 24 hours post-exposure, the potentially absorbable dose declined to 5.3% dose, with 1.4% of the dose in the stratum corneum. Most of the absorbed radioactivity was excreted in the urine (including cage wash), accounting for approximately 30% of the applied dose (83% of the absorbed dose), and 3.3% dose was eliminated in the feces (9% of the absorbed dose). Excretion was virtually complete within 24 hours, with only 1.5% of the dose being recovered in the GI tract and carcass. For the 1/40 aqueous spray dilution (25 ug/sq cm), absorption was markedly lower than for the EC formulation, with only 0.7 and 1.6% of the dose being absorbed by 4 and 10 hours, respectively. After a 10-hour exposure and washing, there was an increase in absorption up to 3.8% dose by 24 hours post-dose. Potentially absorbable radioactivity in or on the skin following washing accounted for 2.6-3.1% of the dose at all sampling intervals and was primarily associated with the stratum corneum (2.0-2.3% dose). As with the high-dose group, most of the absorbed radioactivity was excreted within 24 hours in the urine (66% of absorbed dose) and feces (11% of absorbed dose). For the in vitro studies using excised rat and human skin, total recovery of the applied dose ranged from 94-104% for all dose groups at both exposure intervals. As in the in vivo study, absorption from excised rat skin was higher for the neat EC formulation (400 ug/sq cm) than for either of the 1/200 or 1/40 aqueous dilutions (5 and 25 ug/sq cm, respectively). Following a 10-hour exposure, 40.3% of the applied dose from the EC formulation was absorbed compared to 34.1 and 25.0% of the applied dose from aqueous dilutions (5 and 25 ug/sq cm). After 24 hours of exposure, absorption rose to 65.5% dose for the EC formulation and 49.0 and 44.7% dose for the aqueous dilutions. Regardless of exposure duration, potentially absorbable radioactivity remaining on the skin accounted for 8.8-11.8% dose for the neat EC formulation, 12.1-12.9% dose for the 1/40 aqueous dilution, and 18.5-20.6% dose for the 1/200 aqueous dilution. For excised human skin, absorption of radioactivity was minimal regardless of the dosing vehicle and dose level. Absorption accounted for 0.34-1.55% of the applied dose after a 10-hour exposure at doses from 5-1000 ug/sq cm and 0.36-1.84% of the applied dose after a 24-hour exposure at doses from 5-400 ug/sq cm. Potentially absorbable radioactivity remaining in or on the skin (stratum corneum and epidermis) accounted for 2.42-3.61% dose in the greater than or equal to 25 ug/sq cm dose groups and 8.49-8.80% dose in the 5 ug/sq cm dose group. Thus, in the in vitro studies, absorption was considerably higher in rat skin than in human skin. Additionally, absorption of the test substance in the in vivo rat study was comparable to the absorption in the in vitro study with rat skin. Therefore, the data may suggest that in vivo absorption in humans would be considerably lower than in the rat.
[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.
