Simazine is metabolized and excreted in the rat within 72 hours of dosing. Most of the excreted simazine residues were detected in the urine (49%) and feces (41%) with minor amounts respired as CO2. Simazine is metabolized in the rat through the removal of alkyl side chains and conjugation of the triazine ring with glutathione-S-transferase. The mono- and di-dealkylated compounds, 2-chloro-4-ethylamino- 6-amino-s-triazine and diaminochlorotriazine (DACT), respectively, are the major rat degradates. Conjugated mercapturates of hydroxy simazine were also detected.
The metabolic pathway in plants is similar to that in rats. Plant metabolism occurs via several competing routes. In one major route the N-ethyl groups are cleaved leaving the bare amine attached to the ring. First one ethyl group is lost, then both are lost, ultimately leaving diaminochlorotriazine (DACT). DACT can subsequently proceed to replacement of the chlorine with a proline group, which is attached to the triazine via the proline nitrogen. In a second major route of metabolism, the chloro group on simazine is replaced by a hydroxy group to hydroxysimazine, which can proceed by loss of the ethyl groups to diaminohydroxytriazine, the hydroxy equivalent of DACT. The diaminohydroxytriazine can then under go replacement of one or both amines by hydroxy groups ultimately leading to cyanuric acid. Alternatively, the chlorine in simazine can be replaced by glutathione and through a variety of intermediate conjugates can be eventually lysed to NH2-simazine, and then presumably loss of one or both ethyl groups.
The metabolic pathway in livestock is also similar to that in plants and rats with one exception; animals do not metabolize simazine directly to hydroxy-simazine, but animals may receive hydroxy simazine through feeds. Several studies have been performed on the metabolism of simazine in livestock and poultry. In animals, in general, simazine residues tend to lose one or both ethyl groups to form the chloro-metabolites or to replace the chloro- group with a hydroxygroup and then to lose one of both ethyl groups. Feeding with hydroxy-simazine leads to formation, through loss of one or both ethyl groups of hydroxy-metabolites only. A glutathione conjugate is also formed from the hydroxy-simazine.
Ruminants. In a goat dosed for 10 days with [14C]simazine at a dose equivalent of 5 ppm [12x the maximum theoretical dietary burden (MTDB)], total radioactive residue (TRR) in milk plateaued by Day 5 at 0.10 ppm. TRR in tissue samples collected 48 hours after the final dose ranged from 0.02 ppm in fat to 0.93 ppm in liver. After residues plateaued in milk (at 2% of the administered dose), the major metabolite in milk (23.5% TRR) was identified as diaminochlorotriazine, along with minor amounts (0.25% TRR) of simazine and of desethylsimazine (1.3% TRR). Metabolites in the aqueous fraction and the hydrolysate of the casein fraction were characterized as amino acid and peptide conjugates of simazine. In another study, a goat was dosed for 7 days with [14C]simazine at a dose equivalent to 50 ppm in the diet (119x). TRR in milk ranged from 0.71-1.07 ppm during the 7-day dosing period. TRR in tissues collected within 24 hours of the final dose were 0.06-0.10 ppm in fat, 0.69-0.71 ppm in muscle, 3.03 ppm in kidneys, 2.59 ppm in brain, 0.78 ppm in heart, and 3.24 ppm in liver. Components of the TRR identified in milk and tissues are listed in the table below. Simazine accounted for 3.8-10.8% of the TRR in tissues, but was not detected in milk. DACT was the major metabolite in milk (30.3% TRR) and accounted for 4.2-5.2% TRR in liver and kidney, and 13.8% TRR in muscle. Desethylsimazine was detected in liver and kidney at 10.7-16.9% TRR, but was not detected in muscle and milk. A glutathione conjugate of desethylsimazine was also tentatively identified in kidney (18.7% TRR) and milk (14.9% TRR). Desethylhydroxy-simazine constituted up to 32.9% of the TRR in liver, but may have been an artifact of proteolysis.
Evaluation: There is inadequate evidence in humans for the carcinogenicity of simazine. There is limited evidence in experimental animals for the carcinogenicity of simazine. Overall evaluation: Simazine is not classifiable as to its carcinogenicity to humans (Group 3).
At the low dose (0.5 mg/kg) of radiolabeled simazine, the principal route of excretion was via the urine, however, at the higher dose (200 mg/kg) the principal route of excretion was via the feces. Significant radioactive residues remained in the tissues of the rat for extended periods of time. Results indicate that 94 to 99% of the elimination of radioactive material occurred within 48 to 72 hours with a half-life of 9 to 15 hours. Elimination of the remaining radioactivity exhibited 21- to 32-hour half-life values. Heart, lung, spleen, kidney, and liver appear to be principal sites of retention of radioactivity. However, erythrocytes concentrated radioactivity to higher levels than did other tissues, perhaps due to high affinity of the triazine ring for cysteine residues of hemoglobin, a phenomenon apparently unique to rodent species.
In a dermal absorption study, male Charles River Sprague-Dawley rats received either 0.1, 0.5 mg/sq cm of 14C-simazine ( two vials used: radiochemical purity: 98% for the low dose and 96%, for the high dose, specific activity: 28.0 uCi/mg and 2.4 uCi/mg). Four animals per dose were treated and then the treated area of skin and the surrounding area were covered with a protective device. Animals were then placed in metabolism cages for the duration of the exposure period. Either 2, 4, 10 or 24 hrs following exposure animals were sacrificed. Following sacrifice the exposure sites were washed with liquid Dove and water and both the treated area of skin and skin surrounding the treated area (the skin covered by the protective device) were collected. The soap and water rinses, the skin samples, urine, feces, blood, carcass, cage wash, and other relevant samples were all analyzed for radioactivity. Dermal absorption was less than 1% at both doses and all time points. However, 11-20% of the low dose and 31-41% of the high dose remained on the skin and is thus potentially absorbable.
/Simazine is/ absorbed mostly through plant roots with little or no foliar penetration. It has low adhering ability and is readily washed from foliage by rain. Following root absorption it is translocated acropetally in the xylem, accumulating in apical meristems and leaves of plants.
Simazine was readily absorbed and distributed in spruce seedlings. Degradation of simazine took place in roots and stem to the hydroxy analog... metabolites, but no simazine, were observed in needles.
1.周国泰，化学危险品安全技术全书，化学工业出版社，1997 2.国家环保局有毒化学品管理办公室、北京化工研究院合编，化学品毒性法规环境数据手册，中国环境科学出版社.1992 3.Canadian Centre for Occupational Health and Safety,CHEMINFO Database.1998 4.Canadian Centre for Occupational Health and Safety, RTECS Database, 1989
[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] 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.
