Nine male volunteers were exposed to the pyrethroid insecticide cyfluthrin. ... The main urinary cyfluthrin metabolites, cis-/trans-3-(2,2-dichlorovinyl)-2,2-dimethylycyclopropane carboxylic acid (DCCA) and 4-fluoro-3-phenoxybenzoic acid (FPBA), were determined. The limit of detection (LOD) for all metabolites was 0.0025 ug in an urine sample of 5 mL (0.5 ug/L). After inhalative exposure of 40 ug cyfluthrin/cu m air for 60 min, the amount of metabolites in urine collected in the first 2 hr after exposure was less than the LOD, namely 0.14 ug for cis-DCCA, 0.15-0.28 ug for trans-DCCA and 0.12-0.23 ug for FPBA. Of the metabolites, 93% was excreted within the first 24 hr (peak excretion rates between 0.5 and 3 hr) after inhalative exposure of 160 ug/cu m. ... The amount of metabolites in urine depends on the applied dose, on the exposure time and shows interindividual differences.
Eight hours after oral administration of 14C-labelled cyfluthrin at a dose of 10 mg/kg bw to three male Sprague-Dawley rats, about 60% of the labelled cyfluthrin was eliminated in the urine in conjugated forms. Conjugates of 4'-hydroxy-3-phenoxyfluorobenzoic acid (50%) were identified; a second major metabolite was identified after hydrochloric acid hydrolysis as a conjugate of 3-phenoxy-4-fluorohippuric acid (40%). These metabolites represented 33 and 27% of the administered radiolabel, respectively. A glycine conjugate constituted 2.5% of the conjugated metabolites.
In another study ... , four groups of five male and five female rats received 14C-cyfluthrin ... . The initial step in cyfluthrin biotransformation was ester hydrolysis, giving a 3-phenoxy-4-fluorobenzyl alcohol intermediate and the permethric acid fraction. The metabolism of permethric acid has been well established in the rat in studies with chemically similar pyrethroids. After ester hydrolysis, the 3-phenoxy-4-fluorobenzyl alcohol moiety was oxidized to the free metabolite 3-phenoxy-4-fluorobenzoic acid. This metabolite can then either be conjugated with glycine to form 3-phenoxy-4-fluorohippuric acid (a minor metabolite constituting < 3% of the recovered urinary radiolabel, dependent on neither sex nor dose) or hydroxylated to give 4'-hydroxy-3-phenoxy-4-fluorobenzoic acid (conjugates of which account for 41-50% of the total urinary radiolabel recovered from rats given one or multiple doses of cyfluthrin at 0.5 mg/kg bw). Females tended to excrete more of this metabolite as the free form in the faeces than did males. Males and females at the high dose (10 mg/kg bw) excreted about 35% of the administered dose as conjugates of 4'-hydroxy-3-phenoxy-4-fluorobenzoic acid, whereas females excreted about 5% more than males as the free metabolite. After repeated oral doses of 0.5 mg/kg bw for 14 days, 12-16% of labelled metabolite was found in the faeces as cyfluthrin, whereas < 1% was found when single oral doses were administered. After a single high dose of 10 mg/kg bw, 17-19% was recovered in the faeces as parent compound. The authors concluded that the metabolism of cyfluthrin is slightly dose-dependent.
The metabolic pathways for the breakdown of the pyrethroids vary little between mammalian species but vary somewhat with structure. ... Essentially, pyrethrum and allethrin are broken down mainly by oxidation of the isobutenyl side chain of the acid moiety and of the unsaturated side chain of the alcohol moiety with ester hydrolysis playing and important part, whereas for the other pyrethroids ester hydrolysis predominates. /Pyrethrum and pyrethroids/
The initial step in cyfluthrin biotransformation is ester hydrolysis, giving a 3-phenoxy-4-fluorobenzyl alcohol intermediate and the permethric acid fraction. After ester hydrolysis, the 3-phenoxy-4-fluorobenzyl alcohol moiety is oxidized to the free metabolite 3-phenoxy-4-fluorobenzoic acid. This metabolite can then either be conjugated with glycine to form 3-phenoxy-4-fluorohippuric acid or hydroxylated to give 4'-hydroxy-3-phenoxy-4-fluorobenzoic acid. The metabolites as well as a small pert of the unmetabolized compound are excreted in the urine in the feces. (L857, A562)
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：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).
At high doses, signs of poisoning attributable to cyfluthrin include profuse salivation and pulmonary edema, clonic seizures, opisthotonos (i.e., the spine is bent forward such that a supine body rests on its head and heels), coma, and death. At lower doses, commonly observed effects include paresthesia and erythema. As for other type 2 pyrethroids, cyfluthrin produces a severe syndrome characterized by salivation and choreoathetosis. (L863)
来源:Toxin and Toxin Target Database (T3DB)
毒理性
暴露途径
这种物质可以通过吸入、皮肤接触和摄入被身体吸收。
The substance can be absorbed into the body by inhalation, through the skin and by ingestion.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
Nine male volunteers were exposed to the pyrethroid insecticide cyfluthrin. The study was performed in an exposure room, where an aerosol containing cyfluthrin was sprayed to obtain atmospheres with mean cyfluthrin concentrations of 160 and 40 ug/cu m. Four volunteers were exposed for 10, 30 and 60 min at 160 ug/cu m and another five volunteers were exposed for 60 min at 40 ug/cu m. For 160 ug/cu m exposure urine samples were collected before and immediately after exposure as well as for the periods 1-2, 2-3, 3-4, 4-5, 5-6, 6-12 and 12-24 hr after exposure. For 40 ug/cu m exposure urine samples were collected before and 2 hr after exposure. ... Of the metabolites, 93% was excreted within the first 24 hr (peak excretion rates between 0.5 and 3 hr) after inhalative exposure of 160 ug/cu m. ... The amount of metabolites in urine depends on the applied dose, on the exposure time and shows interindividual differences.
14C derived from the alcohol moiety was rapidly and completely excreted into urine and feces after single oral administration of 14C-alcohol labeled preparation to rats at 0.5 and 10 mg/kg, 55-70 and 25-35% of the dose being excreted into urine and feces, respectively. Excretion of 14C into bile was about 34%. The fat and sciatic nerve showed relatively higher 14C tissue residues.
The influence of the formulation vehicle on the rate of absorption of cyfluthrin was studied in groups of 14 fasted male Wistar rats given single doses by gavage of 10 mg/kg bw dissolved in either polyethylene glycol (PEG) 400 or a Cremophor EL:water emulsion. Two rats from each group were killed 0.5, 1, 2, 4, 6, 16, and 24 hr after treatment. The concentrations of cyfluthrin and its respective enantiomers were determined in the blood and stomach. When the compound was emulsified in the Cremophor EL:water solution, absorption was rapid; the cis isomer was that most frequently detected within 30 min after treatment. Maximum peak blood concentrations occurred within 1 hr of treatment. Cyfluthrin emulsified in PEG 400 was not detected until 4 hr after administration, and peak blood levels were observed only 6 hr after treatment. Examination of the stomach contents revealed a larger quantity of cyfluthrin in the stomachs of rats treated with the drug in a PEG 400 emulsion
Four groups of 30 male and 24 female Mura:SPRA (SPF 68 Han) rats received 14C-radiolabelled cyfluthrin as either oral doses of 0.5 or 10 mg/kg bw or iv or intraduodenal doses of 0.5 mg/kg bw. Another group received unlabelled cyfluthrin orally once a day for 14 consecutive days, followed by a single oral dose of 0.5 mg/kg bw 14C-cyfluthrin. Excreta, organs, tissues, and blood samples were collected at several intervals and assayed for radiolabel. After oral administration by any schedule, up to 80% of the labelled cyfluthrin was effectively absorbed by females and about 90% by males. ... Less than 2% of radiolabelled drug was present 48 hr after oral administration. No significant pulmonary excretion pathway exists, as < 0.001% was detected in the expired gaseous phase as 14CO21. About 98-99% of the orally administered dose was readily available for renal and fecal excretion ... . Males excreted two to three times more in the urine than in the feces, whereas the renal:fecal excretion ratio in females was 1.2-1.7:1 after oral administration. Consequently, the area under the curve (AUC) is two times larger for females than males. Forty-eight hours after the iv injection, 93-95% of the dose was excreted, with a renal:fecal excretion ratio of 2.9:1 in males and 2.3:1 in females. Therefore, excretion depends somewhat on the route of administration and on sex. ... The residues found in the organs and tissues were influenced by the route of administration, as the mean relative concentration of cyfluthrin in the bodies of males and females at sacrifice was lower after oral administration (0.013) than after intravenous injection (0.06). Female rats had higher plasma concentrations after oral administration of the single high or low dose; 48 hr after administration, lower concentrations were detected in the bone and muscle of animals of each sex and in the testes of males rats. The sciatic nerve showed a similar relative concentration value, which may explain the toxic effects observed on the peripheral nervous system. Higher concentrations were detected in the spleen, adrenal glands, liver, and plasma of both males and females and in the ovaries. The renal fatty tissue concentration was about seven times higher after either oral or intravenous administration, whereas the mean concentration in brain was significantly lower ( p = 0.0006-0.006)...
[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.
