... The aim of these studies was to determine the transdermal metabolism of three related compounds [the herbicide, fluroxypyr methylheptyl ester (FPMH), fluroxypyr methyl ester (FPM), and fluroxypyr (FP)] during penetration through human and /F344 male/ rat skin in vitro ... Both FPM and FPMH were completely metabolized during their passage through human and rat skin in vitro. The only metabolite produced was that of the hydrolysis product, FP, with no parent ester penetrating through the skin. The extent of FP formation within the skin was directly correlated to the degree of stratum corneum reservoir formation. The larger the stratum corneum reservoir, the lower the levels of FP recovered from within the skin. This suggests that as the ester partitioned out of the SC it was immediately hydrolyzed to FP, which could then pass freely through the remainder of the epidermis and dermis. Similar metabolic profiles were observed for the transdermal metabolism of FPM and FPMH in previously frozen rat skin, indicating the robust nature of the esterase enzymes involved. In conclusion, systemic exposure after skin contact with FPM or FPMH is likely to be to the acid metabolite, FP, only and not to the parent ester. In addition, the rate and extent of percutaneous absorption will be a major determinant of cutaneous metabolism. /Fluroxypyr-1-methylheptyl ester/
... With fluroxypyr acid, most of the administered dose is excreted as the fluroxypyr, without the formation of significant metabolites. The pattern with fluroxypyr-MHE is quite different: there is extensive metabolism resulting in the formation of about 20-22 metabolites, with a substantial proportion of the administered dose excreted in expired air - indicating complete mineralization - and most of the remaining dose excreted as urinary metabolites. /Fluroxypyr-1-methylheptyl ester/
Eight male Fischer 344 rats/group were treated orally by gavage with either 17.7 mg/kg of 1-methylheptanol-1-(14)C (B930-93, radiochemical purity: 97.5%, specific activity: 24.2 mCi/mmol) or 50.0 mg/kg of Fluroxypyr 1-methylheptyl-1-(14)C ester (B930-96, radiochemical purity: 99%, specific activity: 25.3 mCi/mmol). Five animals/group were included in a pharmacokinetic study in which plasma samples were drawn from an indwelling catheter at 10, 20 , 30, 45 min and 1, 1.5, 2, 3, 5, 7, 10, 12, 24, 48 hr post-dose. The 3 remaining animals/group were included in an excretion balance study in which urine, cage wash and CO2 samples were collected at 12, 24, 36, and 48 hr post-dose and fecal samples were collected at 24 and 48 hr. The pharmacokinetic parameters and excretion profiles for both test materials are very similar. The study results indicate that the metabolic profile of the methylheptanol moiety of fluroxypyr methylheptyl ester is quite similar to that of methylheptanol itself. /Fluroxypyr-1-methylheptyl ester/
Five substudies were performed in which CD rats were dosed orally by gavage with 50 mg/kg in single or multiple daily doses of (14)C-Dowco 433 MHE (lot no. 6-HD-0113-39a, specific activity: 61.8 uCi/mg, radiochemical purity: 99%) mixed with non-radiolabeled Dowco 433 MHE (lot no. EMJ 211178) with a final specific activity of 0.937 uCi/mg and a radiochemical purity of 98%. The dosing material was mixed in olive oil and administered at a volume of 2.5 mL/kg. The radiolabel was located on the pyridinyl ring. In Study A (excretion study), 3 animals/sex were dosed for 7 days, followed by 5 days of sample collection. In Study B (plasma analysis), one group of 3 animals/sex received a single dose, followed by 5 days of sample collection. A second group of 3 animals/sex were dosed daily for 7 days, followed by 5 days of sample collection. In Study C (tissue distribution), 5 animals/sex were dosed daily for 7 days, followed by serial sacrifices of 1 animal/sex/time at 1, 7, 24, 72, and 168 hr after the last dose. In Study D (whole body autoradiography), 6 males were dosed daily for 7 days, followed by serial sacrifices of 1 animal/sex/time at 1, 7, 24, 72, and 168 hr after the last dose. In Study E (biliary excretion), two animals/sex received a single dose, followed by 2 days of sample collection. In the excretion study, approximately 92% of the administered dose was ultimately excreted in the urine with no difference between the sexes. Between 90 and 96% of the first administered dose was excreted within 24 hr. In the bile duct cannulated rats, only 60 to 64% of the administered dose was recovered in the urine within the 48 hr post-dose with 26 to 29% of the dose recovered in the feces. Only 0.7% of the dose was recovered in the bile. /It was concluded/ that the absence of bile in the gastrointestinal tract resulted in reduced absorption of the test material and thereby reduced the excretion observed in the urine. Peak plasma concentration levels of radiolabeling were observed within the 1st hr post-dose after a single dose and within the first two hr post-dose after multiple doses. The radiolabel within the tissues was largely localized within the kidneys, gastrointestinal tract, and blood with a progressive diminution of the concentrations in these sites over the 7 day sample collection period. The clarity of the autoradiographic pictures was too poor to make any more than a very general characterization of the distribution. More than 93% of the excreted radiolabel was identified as Dowco 433. Metabolic transformation of the test material was largely by ester hydrolysis. /Fluroxypyr-1-methylheptyl ester/
Three fasted male Wistar rats/group were dosed orally by gavage with 20 or 200 mg/kg or intravenously through an implanted jugular cannula with 20 mg/kg of (14)C-Dowco 433 (ref. no. GHD-1030-44a, radiochemical purity: >99%, specific activity: 22.7 mCi/mmol). The radiolabel was sited at the 2 and 6 positions of the pyridinyl ring. The dosing preparation was prepared by diluting this radiolabeled material with unlabeled Dowco 433 (ref. no. 230-75-42/43, purity: 99.5%) such that each animal received 5 uCi/dose. The dose was administered in an aqueous NaOH vehicle (pH adjusted to 6.5). Samples of heparinized blood were collected at specified time intervals (up to 48 hr for the oral treatments and up to 24 hr post-dose for the iv treatment). Urine was collected at 6, 12, 24, and 48 (except for iv treatment) hr post-dose. Feces were recovered at 24 hr intervals after dosing. Urinary excretion was the major route of elimination, accounting for 88 to 94% of the administered radioactivity. Residual radioactivity in the tissues was quite minimal at 24 or 48 hr post-dose. The absorption half- life was determined to be 1.3 hr. Plasma concentration-time demonstrated a biphasic profile with a fast elimination half-life of 4.2 min and a terminal elimination half-life of 6.4 hr. The AUC (ug hr/g) values were 22.26, 864.43, and 58.72 for the oral 20 mg/kg, the oral 200 mg/kg, and the iv 20 mg/kg treatments, respectively. This disproportionate increase in the AUC value for the 200 mg/kg treatment in comparison to that of the 20 mg/kg treatment (38.8 times greater) was attributed to a saturation of the excretion pathway at the higher dosing level. The test material was largely recovered in the urine unmetabolized.
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
对人类不具有致癌性(未被国际癌症研究机构IARC列名)。
No indication of carcinogenicity to humans (not listed by IARC).
来源:Toxin and Toxin Target Database (T3DB)
毒理性
毒性数据
大鼠 LC50 > 6,200 毫克/立方米
LC50 (rat) > 6,200 mg/m3
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
/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)
吸收、分配和排泄
氟草烟被迅速吸收,主要通过肾脏以尿液形式排出。
Fluroxypyr is absorbed rapidly and excreted primarily in the urine via the kidney.
Fluroxypyr (14)C-methylheptyl ester (95.8 % a.i. unlabeled; radiochemical purity 99%; labeled on the methylheptanol portion of the molecule) or (14)C-methylheptanol (98.9% unlabeled; radiochemical purity 97.5%) showed the principal route of excretion being expired (14)CO2, which contained 61% and 63% of the radioactivity for the fluroxypyr methylheptyl ester and methylheptanol balance groups, respectively. The urine contained 30% and 27% and the feces contained 5% and 7% of the administered dose for the fluroxypyr methylheptyl ester and methylheptanol groups, respectively. Each was extensively absorbed and rapidly eliminated. Approximately 52% and 54% of the administered fluroxypyr methylheptyl ester and methylheptanol, respectively, was absorbed and expired as (14)CO2 within 12 hr post dose, and an additional 18% of the administered dose was excreted in the urine within 12 hr post dose. Based on the percentage of the dose in the expired (14)CO2, urine, and tissues, 90% of the dose was absorbed by the rats in each case. Once absorbed, both were extensively metabolized and rapidly expired as (14)CO2 and eliminated in the urine with a half-life of 6 hours. Half-lives for the elimination phase were 18.2 and 17.4 hr for fluroxypyr methylheptyl ester and Methylheptanol, respectively. Data indicate that the fluroxypyr methylheptyl ester bond is readily hydrolyzed and that the methylheptyl ester portion of fluroxypyr is bioequivalent to Methylheptanol. /Fluroxypyr-1-methylheptyl ester/
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
在大鼠中,口服给药后,氟氧苯丙酸不发生代谢,而是以原型迅速排出,主要经尿液排泄。
In rats, following oral administration, fluroxypyr is not metabolized, but is rapidly excreted unchanged, principally in the urine.
[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.