Fenvalerate undergoes hydroxylation to give 2'- or 4'- hydroxylated phenoxy esters and hydrolysis to give 3-phenoxybenzoic acid and its hydroxy derivatives (free and conjugates), 3-(4-chlorophenyl)-isovaleric acid and its hydroxy derivatives (free, lactones, and conjugates), thiocyanate, and CO2.
The fate of fenvalerate in rats and mice has been studied using fenvalerate radiolabelled in the acid moiety or benzyl or cyano groups. The administered radioactivity, except that of the cyano-labelled compounds, is readily excreted (up to 99% in 6 days). The major metabolic reactions are ester cleavage and hydroxylation at the 4' position. Various oxidative and conjugation reactions that lead to a complex mixture of products have been shown to occur. When studies were carried out with fenvalerate radiolabelled in the cyano group, elimination of the radioactive dose was less rapid (up to 81% in 6 days). The remaining radioactivity was retained mainly in the skin, hair, and stomach as thiocyanate. A minor, but very important, metabolic pathway is the formation of a lipophilic conjugate of (2R)-2-(4-chlorophenyl)isovalerate. This congugate, which is implicated in the formation of granuloma, has been detected in the adrenals, liver mesenteric lymph nodes of rats, mice, and some other species.
Despite its lack of a cyclopropane ring in the acid, fenvalerate is rapidly metabolized in rats by ester cleavage and hydroxylation, as are the more traditional pyrethroids.
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 substantial 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.
Both type I and type II pyrethroids exert their effect by prolonging the open phase of the sodium channel gates when a nerve cell is excited. They appear to bind to the membrane lipid phase in the immediate vicinity of the sodium channel, thus modifying the channel kinetics. This blocks the closing of the sodium gates in the nerves, and thus prolongs the return of the membrane potential to its resting state. The repetitive (sensory, motor) neuronal discharge and a prolonged negative afterpotential produces effects quite similar to those produced by DDT, leading to hyperactivity of the nervous system which can result in paralysis and/or death. Other mechanisms of action of pyrethroids include antagonism of gamma-aminobutyric acid (GABA)-mediated inhibition, modulation of nicotinic cholinergic transmission, enhancement of noradrenaline release, and actions on calcium ions. They also inhibit calium channels and Ca2+, Mg2+-ATPase. (T10, T18, L857)
来源:Toxin and Toxin Target Database (T3DB)
毒理性
致癌性证据
癌症分类:人类非致癌性证据E组
Cancer Classification: Group E Evidence of Non-carcinogenicity for Humans
Evaluation: No data were available from studies in humans. There is inadequate evidence for the carcinogenicity of fenvalerate in experimental animals. Overall evaluation: Fenvalerate is not classifiable as to its carcinogenicity to humans (Group 3).
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌物分类
国际癌症研究机构致癌物:芬螨酯
IARC Carcinogenic Agent:Fenvalerate
来源:International Agency for Research on Cancer (IARC)
毒理性
致癌物分类
国际癌症研究机构(IARC)致癌物分类:第3组:无法归类其对人类致癌性
IARC Carcinogenic Classes:Group 3: Not classifiable as to its carcinogenicity to humans
来源:International Agency for Research on Cancer (IARC)
Metabolism and bioaccumulation of fenvalerate and its fenvalerate its metabolites in liver, kidney and brain of rat following the oral administration of a sub-lethal dose (15 mg/kg) of the pesticide for 7, 15 and 30 day periods was investigated by high-performance liquid chromatography (HPLC) in terms of the relative mole concentrations in rat tissues. The cleavage of the ester linkage in fenvalerate yielding two metabolites was found to be primary step in the biodegradation of fenvalerate in rat organs. These metabolites were purified to homogeneity by HPLC and characterized by infra-red spectroscopy as 4-chloro-alpha-(1-methylethyl) benzeneacetic acid and 3-phenoxy benzoic acid.
The disposition kinetics of fenvalerate were studied in goats after dermal application of 100 mL of 0.25% (w/v) solution. The insecticide persisted in the blood for 72 hr. The mean (+/- SEM) Vd(area) and apparent t 1/2 (beta) were 9.92 +/- 1.44 L/kg and 17.51 +/- 2.65 hr, while the AUC and ClB values were respectively 82.15 +/- 7.40 ug hr/mL and 0.56 +/- 0.05 L/(kg hr). Four days after the dermal application, the highest concentration of fenvalerate residues was found in the adrenal gland, followed by the biceps muscle, omental fat, liver, kidney, lung and cerebrum in that order. Fenvalerate caused hyperglycaemia but had no effect on serum protein and cholesterol levels. Serum acetylcholinesterase activities were increased after 24 hr but were below the initial values from 48 to 120 hr.
Elimination from body fat is slow, with a half-life of 7-10 days; elimination from brain is less slow, with a half-life of 2 days, presumably due to the more effective perfusion of brain and the presence of esterases in brain tissue.
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] 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.