The metabolism of racemic fenvalerate and of its (2S, alphaS) isomer was examined in cabbage plants grown under laboratory conditions and treated (20 ug per leaf) with (14)C-chlorophenyl- and phenyl-(14)C-benzyl-labelled preparations of the two compounds. Both compounds disappeared from the treated leaves with similar half-lives of approximately 12-14 days. They underwent ester cleavage to a significant extent, together with some hydroxylation at the 2- or 4-position of the phenoxy ring and hydrolysis of the nitrile group to amide and carboxyl groups. Most of the carboxylic acids and phenols thus produced occurred as glycoside conjugates. ... The uptake and metabolism of 2-(4-chlorophenyl)isovelaric acid (CPIA) ... was examined in the laboratory using abscised leaves of kidney bean, cabbage, cotton, cucumber, and tomato plants. The acid ... was found to be readily converted, mainly into glucose or 6-O-malonylglucose esters in kidney bean, cabbage, and cucumber, into glucosylxylose, sophorose, and gentiobiose esters in cotton, and into two types of triglucose esters with differing isomerism in tomato. One of the acetyl-derived glucoside conjugates was identical with the authentic decaacetyl derivative of the (1-6)-triglucose ester ... .
Pydrin insecticide (Y-rich) is an isomerically enriched form of fenvalerate containing an excess ratio of the active diastereomers SS and RR (designated Y) over the less active diastereomers RS and SR (designated X) at a ratio of approximately 85:15. Fenvalerate contains Y:X in a ratio of 45:55. Following a single oral dose of the Y-rich insecticide (8.4 mg/kg) to male and female Sprague-Dawley rats ... there was no major difference between /chlorophenyl-(14)C- and phenoxyphenyl-(14)C-/ fenvalerate preparations in ... the metabolites distribution profile. Cleavage of the ester linkage was the primary metabolic pathway. The acid and alcohol portions of the parent molecule underwent hydroxylation, oxidation, and conjugation. These metabolic reactions were not dependent on the isomeric composition of the test material. Tissue residue data showed that (14)C residues were not retained in the various organs ... . /Pydrin insecticide (Y-rich)/
In mice, fenvalerate is metabolized in a similar way to that in rats, but the following significant species differences were found ... (a) the taurine conjugate of phenoxybenzoic acid (PBacid) was found in mice but not in rats; (b) 4'-OH-PBacid sulfate occurred to a greater extent in rats than in mice; and (c) a greater amount of thiocyanate was excreted in mice than in rats. No significant sex differences were observed in rats and mice. The metabolism of the stereoisomers of fenvalerate, ((2S, alphaRS) and (2S, alphaS)) was apparently similar to that of racemic fenvalerate.
In an in vitro study on the metabolism of the four chiral isomers of fenvalerate using homogenates from various tissues of mice, rats, dogs, and monkeys, only the (2R, alphaS) isomer yielded cholesteryl-(2R)-2-(4-chloro-phenyl)isovalerate (CPIA-cholesterol ester) as a major metabolite. Mouse tissues exhibited a higher rate of CPIA-cholesterol ester formation than those of other animals. Of the mouse tissues tested, the kidney, brain, and spleen showed the greatest ability to form this ester, the relevant enzyme activity being mainly localized in the microsomal fractions. Carboxyesterases for mouse kidney microsomes hydrolyzed the (2R, alphaS) isomer only of fenvalerate to give CPIA and yielded the corresponding cholesterol ester in the presence of artificial liposomes containing cholesterol. It appears that the CPIA-cholesterol ester resulted from the stereoselective ((2R, alphaS) only) formation of the CPIA-carboxyesterase complex, which subsequently reacted with cholesterol to yield the CPIA-cholesterol ester ... The /mouse/ kidney, spleen and brain hydrolyzed only the (2R, alphaS) isomer. Liver hydrolyzed the (2R, alphaS) and (2R, alphaR) isomers to a greater extent than the (2S, alphaR) and (2S, alphaS) isomers, while plasma hydrolysed the (2S, alphaR) and (2R, alphaR) isomers more rapidly than the (2S, alphaS) and (2R, alphaS) isomers. The stereoselectivity of hydrolysis of the four isomers by mouse liver microsomes was found to be same as that in vivo. Of the four isomers, the (2R, alphaS) isomer alone was transformed to cholesteryl-(2R)-2-(4-chlorophenyl) isovalerate (CPIA-cholesterol ester) by microsomes of the brain, kidney, spleen, or liver but not by plasma. The rate of CPIA-cholesterol ester formation was lower in the liver than in other tissues. The optimum pH (7.4-9.0) for the formation of this ester was nearly the same as that for hydrolysis of the (2R, alphaS) isomer to form CPIA in mouse kidney microsomes. /Fenvalerate isomers/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
癌症分类：E组 人类非致癌性证据
Cancer Classification: Group E Evidence of Non-carcinogenicity for Humans
来源:Hazardous Substances Data Bank (HSDB)
毒理性
暴露途径
该物质可以通过吸入其气溶胶和通过吞食被吸收进人体。
The substance can be absorbed into the body by inhalation of its aerosol and by ingestion.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
毒理性
吸入症状
咳嗽。喉咙痛。眩晕。头痛。恶心。
Cough. Sore throat. Dizziness. Headache. Nausea.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
毒理性
皮肤症状
Redness.
Redness.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
毒理性
眼睛症状
红肿。疼痛。
Redness. Pain.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
On a single oral dose or five consecutive oral doses of (14)C esfenvalerate or (14)C-fenvalerate labeled in the acid moiety to 13-day pregnant rats at rates of 2.5 and 10 mg/kg/day, respectively, the maternal blood and placenta generally showed higher (14)C levels as compared with the fetus and amniotic fluid. Both compounds and their metabolites did not transfer readily from the maternal blood to the fetus, the amount of (14)C transferred being less than 0.07% of the dose. There were no substantia differences in the fetal (14)C level and the transfer ratio ((14)C tissue level/(14)C maternal blood level) between both labeled preparations. Major (14)C-compounds in the fetus, maternal blood and placenta were the parent compounds, CPIA(2-(4-chlorophenyl)isovaleric acid) and CPIA-hydroxylated derivatives and there was no qualitative difference in metabolic fates between the two compounds, except that a trace amount of CPIA-cholesterol ester (cholesteryl (2R)-2-(4-chlorophenyl)isovalerate) was detected in the maternal blood and placenta only with fenvalerate. CPIA-cholesterol ester did not seem to transfer from the maternal blood to the fetus. Overall, esfenvalerate and fenvalerate seem to behave in the same manner as far as placental transfer was concerned.
Pydrin insecticide (Y-rich) is an isomerically enriched form of fenvalerate containing an excess ratio of the active diastereomers SS and RR (designated Y) over the less active diastereomers RS and SR (designated X) at a ratio of approximately 85:15. Fenvalerate contains Y:X in a ratio of 45:55. Following a single oral dose of the Y-rich insecticide (8.4 mg/kg) to male and female Sprague-Dawley rats, more than 90% of the administered radioactivity from the acid moiety (chlorophenyl-(14)C) and the alcohol moiety (phenoxyphenyl-(14)C) was eliminated within the first 24 hr. There was no major difference between the two different fenvalerate preparations in either the elimination rate or the metabolites distribution profile. Cleavage of the ester linkage was the primary metabolic pathway. The acid and alcohol portions of the parent molecule underwent hydroxylation, oxidation, and conjugation. These metabolic reactions were not dependent on the isomeric composition of the test material. Tissue residue data showed that (14)C residues were not retained in the various organs ... . /Pydrin insecticide (Y-rich)/
Following a single oral administration of the four chiral isomers of (14)C-chlorophenyl-fenvalerate to Sprague-Dawley rats and ddY mice (2.5 mg/kg body weight), the (2R, alphaS) isomer showed, in both rats and mice, relatively greater residues in the analyzed tissues (except fat), particularly in adrenal glands, compared with the other three isomers. Similarly, this isomer showed higher tissue concentrations than the other isomers when mice were fed a diet containing 500 mg/kg of the (2S, alphaS), (2R, alphaS), or (2R, alphaR) isomers for two weeks. The greater amount of radioactive residues from the administration of (2R, alphaS) isomer, as compared with those of other isomers, was explained by the preferential formation of a lipophilic metabolite from the (2R, alphaS) isomer found in all examined tissues, which was not easily excreted. The amounts of the lipophilic metabolite differed among tissues, being higher in adrenal, liver, and mesenteric lymph nodes. This metabolite was identified as cholesteryl (2R)-2-(4-chlorophenyl)isovalerate. The presence of the same metabolite was also indicated in rat tissues ... . /Fenvalerate isomers/
Two 3-month-old lambs were fed a diet containing 45 mg/kg fenvalerate for 10 days and then killed to determine the concentrations of fenvalerate in the kidney, liver, leg muscle, and renal fat ... . Among the analyzed tissues, fat showed the highest fenvalerate level (3.6-4.4 mg/kg dry weight) while other tissues contained less than 0.3 mg/kg. Fenvalerate gave two gas chromatographic peaks and each peak contained a pair of its enantiomers. In all cases, the ratio of the areas of these peaks (peak 1 (RS,SR)/peak 2 (SS,RR)) was 1.08 both for fenvalerate in the diet and for fenvalerate recovered from the fortified control fat. In contrast, the fenvalerate isolated from lamb fat had a peak area ratio of 0.76-0.78. Thus,one or both of the first eluting enantiomers appeared to be metabolized more rapidly than the other enantiomers. /Fenvalerate isomers/
Development of an Immunoassay for the Pyrethroid Insecticide Esfenvalerate
摘要：
A competitive enzyme-linked immunosorbent assay was developed for the detection of the pyrethroid insecticide esfenvalerate. Two haptens containing amine or propanoic acid groups on the terminal aromatic ring of the fenvalerate molecule were synthesized and coupled to carrier proteins as immunogens. Five antisera were produced and screened against eight different coating antigens. The assay that had the least interference and was the most sensitive for esfenvalerate was optimized and characterized. The I-50 for esfenvalerate was 30 +/- 6.2 mu g/L, and the lower detection limit (LDL) was 3.0 +/- 1.8 mu g/L. The assay was very selective. Other pyrethroid analogues and esfenvalerate metabolites tested did not cross-react significantly in this assay. To increase the sensitivity of the overall method, a C-18 sorbent-based. solid-phase extraction (SPE) was used for water matrix. With this SPE step, the LDL of the overall method for esfenvalerate was 0.1 mu g/L in water samples.
[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.
