MCPP-p-DMAS (14)C-MCPP-p DMAS was incubated in vitro with rat plasma, stomach content, gastro-intestinal tract (GIT) or postmitochondrial liver fraction (S9) for 30 minutes. All incubated extracts were subjected to HPLC analysis. Results indicated that all of the administered (14)C-MCPP-p DMAS in plasma, stomach contents, gastro-intestinal tract and liver (S9) was present as the ionized form of (14)C-MCPP-p.
Male and female Wistar rats with dosed orally with (14)C-Mecoprop-P (radiochemical purity: 99.5%, purity: 98.6%; spec. act.: 138.8 uCi/mg). Five rats/sex were dosed with 5 (Groups A, B, D) or 100 mg/kg (Groups C and E). The rats in Group B received 14 doses of unlabeled Mecoprop-P (purity: 99.8%) at 5 mg/kg/day prior to being dosed with the radiolabeled material. In addition,12 rats/sex were dosed with 5 mg/kg (Group F). ... The only metabolite identified in the study was hydroxymethyl-Mecoprop-P. A greater percentage of this metabolite was recovered in the urine of the males. Overall, unaltered test material and the hydroxylated metabolite constituted 92.29 to 95.34% of the recovered radiolabel in the urine in the first 48 hours after dosing. For the males, the parent material was 52.17 to 67.08% and the metabolite was 28.26 to 41.39% of the administered dose. For the females these values ranged from 84.31 to 90.03% for the parent compound and 5.16 to 10.25% for the metabolite. /Mecoprop-p/
The dissociation of Mecoprop-p-DMA salt into Mecoprop-P acid and dimethyl amine was examined in various in vitro biological test systems. (14)C-Mecoprop-p-DMA was formed by mixing (14)C-Mecoprop-p acid (radiochemical purity: 99.5%, chemical purity: 98.6%, specific activity: 138.92 uCi/mg) with a dimethylamine solution. The test material was incubated with plasma (I), stomach contents (II), the gastrointestinal tract (III) and liver S9 fraction (IV) derived from male Wistar rats. The concentrations of the test material in the incubations were 0.1 (I), 5 (II), 0.35 (III) and 0.1 (IV) mg/mL. The samples were incubated for 30 minutes at 37o C. Study results indicated that the test material had largely dissociated into Mecoprop-P acid and DMA. It was not apparent from these results whether the dissociation may have been wholly or partially mediated enzymatically.
来源:Hazardous Substances Data Bank (HSDB)
代谢
在...植物中，侧链降解为2-甲基-4-氯苯酚，环羟基化以及环开裂。
In ...plants, degradation of the side-chain to 2-methyl-4-chlorophenol, ring hydroxylation and ring opening.
CDDs are absorbed through oral, inhalation, and dermal routes of exposure. CDDs are carried in the plasma by serum lipids and lipoproteins, distributing mainly to the liver and adipose tissue. CDDs are very slowly metabolized by the microsomal monooxygenase system to polar metabolites that can undergo conjugation with glucuronic acid and glutathione. They may increase the rate of their own metabolism by inducing CDDs induce both phase I and phase II enzymes. The major routes of excretion of CDDs are the bile and the feces, though smaller amounts are excreted in the urine and via lactation. (L177)
IDENTIFICATION AND USE: Mecoprop (MCPP) is a solid. It is used as an herbicide. HUMAN STUDIES: In two cases of serious intoxication with MCPP, both patients had central nervous system involvement, became unconscious and had an inadequate respiration. Muscle cramps and rhabdomyolysis with renal failure were noted in both. Shortly after admission both patients developed a serious decrease in arterial blood pressure (160/80 mmHg to 80/45 mmHg). In one patient this was demonstrated to be caused by a reduction in peripheral vascular resistance. In another case, a patient who had ingested 500 mL of a mecoprop product died of hypotension and respiratory failure 36 hours after hospital admission. Two additional cases of MCPP ingestion followed a similar clinical course with rapid loss of consciousness, muscle cramps, and hypotension. Laboratory abnormalities included decreased platelets and hemoglobin and elevated creatine phosphokinase and myoglobin levels. One patient also developed acute renal failure secondary to rhabdomyolysis and required hemodialysis. In surviving patients, no long-term effects were reported. In male human blood lymphocytes, chromosomal aberrations were increased in the presence of activation at a cytotoxic dosing level of 2500 ug/mL. ANIMAL STUDIES: In rats, MCPP caused structural changes in spleen and thymus and changes of the number of blood lymphocytes and granulocytes. In a carcinogenicity study in mice, MCPP was administered in the diet at doses of 4, 40, and 592 mg/kg/day for males and 4, 46, and 732 mg/kg/day for females. In females, an increase in the incidence of chronic nephropathy and increased absolute and relative kidney weight were reported. There was no treatment related increase in tumor incidence compared to controls in this study. MCPP was given orally to mice at days 6-15 of pregnancy. It was embryotoxic at doses greater than or equal to 300 mg/kg and caused malformations of the skeleton at doses greater than or equal to 400 mg/kg. Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 were exposed in the presence and absence of activation to MCPP at concentrations of 0, 50, 150, 500, 1500, and 5000 ug/plate with incubation for 3 days with a repeat assay. An increase in the reversion frequency was not indicated. ECOTOXICITY STUDIES: MCPP injured shell formation with an increase of shell abnormalities following herbicide concentrations in two larval stages of marine mollusk Crassostrea gigas. However, the toxic concentrations were several orders of magnitude higher than environmental concentrations. MCPP was nontoxic to bees.
CDDs cause their toxic effects by binding to the aryl hydrocarbon receptor and subsequently altering the trascription of certain genes. The affinity for the Ah receptor depends on the structure of the specific CDD. The change in gene expression may result from the direct interaction of the Ah receptor and its heterodimer-forming partner, the aryl hydrocarbon receptor nuclear translocator, with gene regulatory elements or the initiation of a phosphorylation/dephosphorylation cascade that subsequently activates other transcription factors. The affected genes include several oncogenes, growth factors, receptors, hormones, and drug-metabolizing enzymes. The change in transcription/translation of these genes is believed to be the cause of most of the toxic effects of CDDs. This includes 2,3,7,8-tetrachlorodibenzo-p-dioxin's carcinogenicity is thought to be the result of its ability to alter the capacity of both exogenous and endogenous substances to damage the DNA by inducing CYP1A1- and CYP1A2-dependent drug-metabolizing enzymes. (L177)
There is limited evidence of the carcinogenicity of chlorophenoxy herbicides (including mecoprop) to humans. There is no data for evaluation of the carcinogenicity of chlorophenoxy herbicides to animals. Overall evaluation: Group 2B: The agent is possibly carcinogenic to humans. /Chlorophenoxy herbicides/
Exposure to large amounts of CDDs causes chloracne, a severe skin disease with acne-like lesions that occur mainly on the face and upper body. CDDs may also cause liver damage and induce long-term alterations in glucose metabolism and subtle changes in hormonal levels. In addition, studies have shown that CDDs may disrupt the endocrine system and weaken the immune system, as well as cause reproductive damage and birth defects, central and peripheral nervous system pathology, thyroid disorders, endometriosis, and diabetes. 2,3,7,8-Tetrachlorodibenzo-p-dioxin is also a known human carcinogen. (L177, L178)
Male and female Wistar rats with dosed orally with (14)C-Mecoprop-P (radiochemical purity: 99.5%, purity: 98.6%; spec. act.: 138.8 uCi/mg). Five rats/sex were dosed with 5 (Groups A, B, D) or 100 mg/kg (Groups C and E). The rats in Group B received 14 doses of unlabeled Mecoprop-P (purity: 99.8%) at 5 mg/kg/day prior to being dosed with the radiolabeled material. In addition,12 rats/sex were dosed with 5 mg/kg (Group F). In Groups A, B and C, urine and feces were collected for 7 days. Expired air was collected from two males in Group C. In Groups D and E, blood samples were collected for 7 days. In Group F, four animals/sex/timepoint were euthanized at 0.5, 3 and 6 hours after dosing. Absorption of the administered dose ranged from 82.92 to 100.47% with the absorption minimally reduced in the repeated dosing regimen and at the higher dosing level (males: A. 100.47%, B. 94.58%, C. 92.34%; females: A. 94.62%, B. 92.07%, C. 82.92%). Excretion was predominantly via the urine with the percentage of the total dose recovered in the urine and cage wash ranging from 79.74 to 100.06%. In Group A, 95.29 and 92.29% of the administered dose was collected in the urine and the cage wash within the first 24 hours for males and females, respectively. Repeated dosing reduced the amount collected in the urine and the cage wash during the first 24 hours to 88.97 and 86.46% for males and females, respectively. Likewise, at the 100 mg/kg dosing level, the percentage collected in the urine and the cage wash during the first 24 hours was reduced to 61.18 and 56.78% for males and females, respectively. The total radiolabel recovered in the feces ranged from 3.56 to 12.52% of the administered dose. No radiolabeled material was recovered in the expired air due to the positioning of the label on the phenyl ring. Radiolabel in the tissues and organs 7 days after dosing was predominantly in the fat followed by the skin, adrenals, kidneys and liver. Maximal levels of radioactivity were recovered from the various tissues and organs assayed within 3 hours of dosing (Group F). In the plasma pharmacokinetic analysis, Tmax values were 1.8 and 2.7 hours for males and females, respectively in Group D and 4.2 hours in Group E. /The half-life/ for elimination was 6.35 and 4.23 hours in Group D and 7.89 and 7.79 hours in Group E for males and females, respectively. ... /Mecoprop-p/
Groups of 5 male Wistar rats were dosed orally with 5 mg/kg of either (14)C-Mecoprop-P-EHE (radiochemical purity: 99.6%, spec. act.: 145.37 uCi/mg) (Groups A and C) or (14)C-Mecoprop-P-DMA /(dimethylamine salt)/ (radiochemical purity (based on the acid): 99.8%, spec. act.: 114.79 uCi/mg) (Groups B and D). In Groups A and B (plasma pharmacokinetic study), blood samples were collected for 7 days. In Groups C and D, urine and feces were collected for 7 days. Expired air was collected for 48 hours. In the plasma pharmacokinetic analysis, Tmax values were 3.6 and 2 hr for Groups A and B, respectively. The half-life for elimination was 8.36 and 6.61 hours for Groups A and B, respectively. Absorption of the administered dose was at least 83.26 and 97.11% for Groups C and D, respectively (the total residual radiolabel in the tissues was not determined). Excretion was predominantly via the urine with the percentage of the total dose recovered in the urine 83.26 and 97.11%. In Groups C and D, respectively, 79.73 and 93.52% of the administered dose (calculated by the reviewer) was collected in the urine and the cage wash within the first 24 hours. The total radiolabel recovered in the feces was 3.29 and 4.68% of the administered dose for Groups C and D, respectively. No radiolabeled material was recovered in the expired air due to the positioning of the label on the phenyl ring. Radiolabel in the tissues and organs 7 days after dosing was largely limited to the skin and fat. The only metabolite identified in the study was hydroxymethyl-Mecoprop-P. Overall, unaltered test material and the hydroxylated metabolite constituted 96% of the recovered radiolabel in the first 48 hours after dosing. The parent material constituted 72.91 and 70.68% and the metabolite was 23.13 and 25.26% of the administered dose for Groups C and D, respectively.
[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.
