Sprague-Dawley Crl:CD/BR rats of both sexes were dosed with either 10 or 1,000 mg/kg of [(14)C] ... /bifenazate/ ( ... radiochemical purity: >98%, specific activity: 34.4 mCi/mmol, label on the aromatic ring, ... /bifenazate/ (unlabeled ... purity: 99.6%) by oral gavage. ... Analysis of the radiolabeled moieties recovered in the feces revealed a number of modifications of the parent cmpd. Hydrazine oxidation, demethylation, ring hydroxylation, separation into biphenyl and hydrazinecarboxylic acid moieties and conjugation with glucuronic acid or sulfate. For the 10 mg/kg group, identified moieties extracted from the feces constituted 39% of the administered dose (AD). The predominant compounds were ... /bifenazate/ glucuronide (6.3-8.9% of AD), ... /bifenazate/ (4.8-7.2% of AD) and ... biphenyl, 4-hydroxy (5.5-7.1% of AD). In contrast, for the 1,000 mg/kg group, the parent cmpd which was recovered in the feces constituted 48-61% of the AD. ... /Bifenazate/ glucuronide constituted 4.7-5.6% of the AD. The primary moieties recovered in the urine were conjugates of ... p, p-biphenol or sulfates of ... /p, p'-biphenol/ and ... /biohenyl, 4-hydroxy/. The total of these cmpds constituted 19-21% of the administered dose for the 10 mg/kg group and 6-7% of the administered dose for the 1,000 mg/kg group. Major metabolites identified in the bile were ... /biphenyl, 4-hydroxy/ (17-20% of AD in the 10 mg/kg group and 2.1-2.5% of the AD in the 1,000 mg/kg group), ... biphenyl, 4-hydroxy, 4-methoxy (17-19% of the AD in the 10 mg/kg and 2.8% of the AD in the 1,000 mg/kg group) and ... /bifenazate/ glucuronide (9-12% of the AD in the 10 mg/kg and 9-13% of the AD in the 1,000 mg/kg group).
IDENTIFICATION AND USE: Bifenazate is a solid. It is used as acaricide/miticide (insecticide). HUMAN EXPOSURE AND TOXICITY: There are no data available. ANIMAL STUDIES: Bifenazate causes slight eye and skin irritant to rabbits. In dogs it caused myeloid hyperplasia and a dose-related decrease in numbers of erythrocytes and increased numbers of platelets and level of serum bilirubin at concentrations of 400 and 1000 ppm. The only developmental effects noted in rats were a slightly delayed balanopreputial separation for the males treated with concentrations of 80 and 200 ppm, and vaginal perforation for the females treated with 200 ppm. It was not mutagenic in S. typhimurium strains TA98, TA100, TA1535, and TA1537 and E. coli strain WP2 uvrA. There was no treatment-related increase in the percentage of cells with chromosomal aberrations in Chinese Hamster Ovary cells. Treatment with bifenazate did not result in an increase in the number of micronuclei in mice. ECOTOXICITY STUDIES: Bifenazate is categorized as slightly toxic to avian species on an acute oral basis (LD50=1032 mg/kg) and as moderately toxic to avian species on a subacute dietary basis (LC50=656-1862 ppm). Bifenazate is categorized as practically nontoxic to small mammals on an acute oral basis (LD50>5000 mg/kg). The available data indicate that bifenazate is categorized as highly toxic to freshwater fish (LC50=0.58-76 ppm) and aquatic invertebrates (LC50/EC50=0.50 ppm) on an acute basis.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
癌症分类：不太可能对人类致癌
Cancer Classification: Not Likely to be Carcinogenic to Humans
来源:Hazardous Substances Data Bank (HSDB)
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).
来源:Toxin and Toxin Target Database (T3DB)
毒理性
副作用
职业性肝毒素 - 第二性肝毒素：在职业环境中的毒性效应潜力是基于人类摄入或动物实验的中毒案例。
Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
... The ability of well-known organophosphates and carbamates to inhibit the activation of bifenazate and thus compromise its acaricidal potential was tested. Esterase activity determined in vivo after pre-exposure of mites with organophosphates and carbamates revealed-depending on the compound-varying esterase inhibition nicely correlated with the ability of the individual compound to antagonise bifenazate action on mites. The findings illustrate that organophosphates and carbamates interfere with bifenazate efficacy, most probably by inhibiting carboxylesterases responsible for the activation of the pro-drug. As a result of the strong antagonism, mixtures of bifenazate with carbamates or organophosphates should not be used under field conditions. Moreover, there exists a real threat in repeatedly applying organophosphates and bifenazate. The present study again illustrates how important mode of action information is for the proper planning of resistance management strategies.
Sprague-Dawley Crl:CD/BR rats of both sexes were dosed with either 10 or 1,000 mg/kg of [(14)C] ... /bifenazate/ ... (radiochemical purity: >98%, specific activity: 34.4 mCi/mmol, label on the aromatic ring, /bifenazate/... (unlabeled ... purity: 99.6%) by oral gavage. In the Distribution, Metabolism and Excretion study, 5 animals/sex/group were dosed and urine and feces were collected for 7 days. In the Biliary study, 3 animals/sex/group with cannulated bile ducts were dosed and urine, feces and bile were collected for 72 hrs. The Pilot Pharmacokinetic and Pharmacokinetic studies were performed in which 3 animals/sex/group and 5 animals/sex/group, respectively, were dosed. In the pilot study, urine and feces were collected for 4 days and blood samples were collected via a jugular cannula for 72 hrs. In the main study, urine and blood were collected for 4 days from the animals in the 10 mg/kg treatment group. In the 1,000 mg/kg group, urine, feces and blood were collected for 7 days. In the Tissue Distribution study, 9 animals/sex/group were dosed. In the 10 mg/kg group, 3 animals/sex/time point were serially euthanized at 6, 24 and 48 hrs after dosing. In the 1,000 mg/kg group, 3 animals/sex/time point were euthanized at 18, 42 and 72 hrs post-dose. Urine and feces were collected at designated intervals. Tissue samples from Distribution, Metabolism and Excretion study and the Tissue Distribution study were processed for the presence of radiolabel. Radiolabeled materials were isolated from the urine and feces derived from the Distribution, Metabolism and Excretion and the Biliary studies and structurally analyzed for a metabolic profile. The predominant route of excretion for both doses was via the feces. For the 10 mg/kg group, 66% of the administered dose (AD) was recovered in the feces with 75-82% of that total excreted in the first 24 hrs. Radiolabel recovered in the urine and cage wash constituted 27-29% of the AD after 7 days. For the 1,000 mg/kg treatment group, the % of AD recovered in the feces up to 7 days post-dose was 82% with 46-57% of that total recovered in the first 24 hrs. The % of AD isolated in the urine and cage wash was 10-15%. The Biliary study demonstrated that the bile was a significant pathway for excretion by the 10 mg/kg treatment group with 69-74% of the administered dose recovered in the bile up to 72 hrs after dosing. In contrast, for the high dose group, 21-26% of the dose was isolated in the bile by 72 hrs. Recovery in the feces of the 10 mg/kg group was limited to 7-8% of the AD as compared to 56-64% of the AD for the 1,000 mg/kg group. A significant fraction of the AD for the high dose group was not being absorbed. The following pharmacokinetic parameters were derived: tmax, 5 and 6 hrs and 18- 24 hrs for males and females of the 10 mg/kg and 1,000 mg/kg groups, respectively, Cmax, 6.4 and 5.6 ug equiv./g and 119 and 71 ug equiv./g for the males and females in the 10 mg/kg and 1,000 mg/kg groups, respectively, and t1/2, 11.5 and 13.3 hrs and 12 and 15.6 hrs for males and females in the low and high dose groups, respectively. In the Tissue Distribution study, among the 10 mg/kg animals, maximal residue levels were noted at 6 hrs with none of the radiolabel being sequestered in any of the tissues. In the 1,000 mg/kg group, maximal residue levels were noted in a majority of the tissues at 18 hrs post-dose for the males and 42 hrs post-dose for the females. For some of the organs, appreciable levels of radiolabel were still evident at 7 days (e.g., spleen, red blood cell, liver, and kidney). Analysis of the radiolabeled moieties recovered in the feces revealed a number of modifications of the parent cmpd. Hydrazine oxidation, demethylation, ring hydroxylation, separation into biphenyl and hydrazinecarboxylic acid moieties and conjugation with glucuronic acid or sulfate. For the 10 mg/kg group, identified moieties extracted from the feces constituted 39% of the AD. The predominant compounds were ... /bifenazate/ glucuronide (6.3-8.9% of AD), ... /bifenazate/ (4.8-7.2% of AD) and ... biphenyl, 4-hydroxy (5.5-7.1% of AD). In contrast, for the 1,000 mg/kg group, the parent cmpd which was recovered in the feces constituted 48-61% of the AD. /Bifenazate/... glucuronide constituted 4.7-5.6% of the AD ... Overall, the test material was well absorbed at the low dose, metabolized and conjugated before being excreted in the bile. At the high dose level, a much lower % of the dose was absorbed.
[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.
