The metabolic fate of flufenoxuron was determined using two radiolabeled positions (aniline and difluorobenzene ring). Flufenoxuron exhibited a dose-dependant absorption following a single low dose (3.5 mg/kg) or single high dose (350 mg/kg). ... For the flufenoxuron aniline ring test article, the parent and a total of 10 urinary metabolites accounted for approximately 5% of the administered dose, and were considered non-significant. Fecal excretion of metabolites was quantitatively greater with parent compound accounting for the greatest portion of radioactivity. However, most fecal metabolites represented < 1% of the administered dose. Both [4-(2-chloro, alpha,alpah,alpha-trifluoro-p-tolyoxy)-2-fluorophenyl urea] and [4- (2-chloro, alpha,alpah,alpha-trifluoro-p-tolyoxy)-2-fluoroaniline] were detected in the feces and urine following administration of the aniline ring labeled test article. Unextractable residues accounted for 7-8% of the dose. The major urinary metabolite of [14C- 2,6-difluorobenzene]flufenoxuron was the corresponding benzoic acid which, over 48 hours, accounted for 10-12% of the administered dose. Difluorobenzamide (<1%) was also detected in the urine along with unknown components all of which individually represented <1% of the dose. The only component detected in the feces of rats given the 2,6-difluorobenzene label was the parent compound. The results of the metabolism characterization studies with both label positions suggest that metabolism of flufenoxuron proceeds via hydrolysis to a benzoic acid metabolite, a phenyl urea metabolite ( 4-[2-chloro, alpha,alpah,alpha-trifluoro-p-tolyoxy]-2-fluorophenyl urea), an aniline metabolite (4-[2-chloro, alpha,alpah,alpha-trifluoro-p-tolyoxy]-2-fluoroaniline), and subsequently several minor components.
/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/
/CASE REPORTS/ A 72-year-old woman was brought to the emergency department by ambulance. The person accompanying her brought an empty 100 mL bottle of an insecticide (Cascade), which was found at the scene. The active ingredient of the product is flufenoxuron and the other components include surfactants and solvents. A detailed composition obtained from the manufacturer was flufenoxuron, ethoxylated nonylphenol phosphate, polyoxyethylene nonylphenol, N-methyl-2-pyrrolidone, and cyclohexanone. Upon arrival at the intensive care unit (ICU), her arterial pH was 7.093, her bicarbonate level was 7.4 mEq/L, and the anion gap was 33.8 mEq/L. Her lactic acid concentration was 16.5 mmol/L. Lactic acidosis was not considered to be a consequence of circulatory shock, because there was no clinical sign of shock other than lactic acidosis, and cardiac output was never below 4.5 L/min. Her acid-base status began to improve and returned to near normal on the next day. It can be hypothesized that the toxicity of the product includes inhibition of the oxygen utilization mechanism at the cellular level. The product is composed of a number of components, similar to many other herbicide products. It is not possible to identify which of the ingredients was specifically responsible for the toxic effects in this case.
/GENOTOXICITY/ In a mammalian cell cytogenetics assay (Chromosome aberration), human lymphocyte (whole blood) cultures were exposed to WL115110 (/flufenoxuron/ 98.1% ai) in dimethyl sulfoxide (DMSO) at concentrations of 0, 78.4, 112, or 160 ug/mL for three hours with and without metabolic activation (S-9 mix). Cells were harvested 17 hours following termination of treatment both with and without S-9 mix. Cells were also harvested 41 hours following termination of treatment in another experiment at the highest concentration with S-9 mix. An additional assay was conducted by exposing cells to test material concentrations of 0, 78.4, 112, or 160 ug/mL without S9-mix for 20 hours with immediate post-treatment harvest. Yet another assay was conducted by exposing cells to test material concentrations of 0 or 160 ug/mL without S9-mix for 44 hours with immediate posttreatment harvest. Blood was obtained from a healthy male donor. The S9-fraction was obtained from Aroclor 1254 induced male Sprague-Dawley rat liver. Flufenoxuron was tested up to concentrations limited by solubility. The maximum mitotic inhibition detected was a decrease of 42% in the mitotic index following the 20-hour treatment at the highest concentration in the absence of S-9 mix. Precipitate was seen in the culture media at all concentrations tested. There were no statistically significant increases in the percentage of cells with structural aberrations including or excluding gaps or in polyploidy over the solvent control values at any test material concentration with or without S9-mix. The solvent and positive control values were appropriate, and solvent control values were within the testing laboratory's historical control ranges in all assays. There was no evidence of chromosome aberrations induced over background.
/In rats/ Flufenoxuron exhibited a dose-dependant absorption following a single low dose (3.5 mg/kg) or single high dose (350 mg/kg). At the high dose, saturated absorption was observed. Approximately 86% of the low dose and 1% of the high dose was absorbed in 168 hours, the majority of which occurred within 48 hours. For the difluorobenzene ring test article, urine was a major route of excretion in the low-dose group, but not in the high-dose group (<1%). Conversely, 93-102% of the high dose and 4-19% of the low dose was eliminated in feces. Elimination via expired air was insignificant. Biliary excretion using the aniline ring label showed that all the radioactivity in the feces of females and 40% of that in males are biliary excretion products. Although, the majority of both urinary and fecal excretion occurred within 48 hours, excretion by both routes was biphasic, with slower phase occurring throughout the post-exposure, resulting in accumulation in adipose tissue. This phenomenon was probably due to entero-hepatic circulation. Accumulation of radioactivity in muscle and adipose tissue 4 hours post dosing with 3.5 mg/kg benzyl label was 30% and 42%, respectively. At 168 hours post dose, these values were 6% and 19%, respectively, suggesting an accumulation in the adipose tissue. High doses of both labels resulted in negligible tissue burden (<0.3%) indicating saturation absorption.
Development of a Compound-Specific ELISA for Flufenoxuron and an Improved Class-Specific Assay for Benzoylphenylurea Insect Growth Regulators
摘要：
This study describes immunochemical approaches for the compound-specific detection of flufenoxuron and class-specific detection of benzoylphenylurea (BPU) insecticides. With the aim of developing a highly specific immunoassay for flufenoxuron, a hapten was synthesized by introducing a spacer arm at the 2,6-difluoro substituent aromatic ring of a flufenoxuron derivative. An IC50 value of 2.4 ppb was obtained for flufenoxuron, with detection of the other four BPUs being more than 4000-fold less sensitive. For the development of class-specific ELISA for five BPUs, a new approach was used for the hapten preparation in which a butanoic acid linkage was introduced into the 3,5-dichloro-substitued aniline ring of chlorfluazuron analogue. Although the resultant ELISA still exhibited slightly differing cross-reactions for these five BPUs, this method had broader specificity than the previously reported polyclonal antibody-based ELISA. Spike and recovery studies for five BPUs in soil and water indicated that both the compound- and class-specific ELISAs were able to quantitatively detect BPU residues in soil and water. This study also provided additional insights into the influence of the immunizing hapten structure on the specificities of the antibodies obtained.
[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] 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.
