Male and female rats were treated with (14)C-bifenthrin labeled in the acid or alcohol moiety at single oral doses of 4 and 35 mg/kg. (14)C was rapidly excreted into feces and urine, and the excretion rates of the (14)C to feces and urine were 66-83% and 13-25%, respectively. ... The major fecal metabolites possessed intact ester linkage hydroxylated in the acid or alcohol moiety such as hydroxymethyl-bifenthrin, 4'-OH-bifenthrin, and 3'- or 4'-OH-hydroxymethyl bifenthrin. Ester-cleaved products derived from mono- and dihydroxylated parent compounds were also detected. On the other hand, the majority of urinary metabolites were ester-cleaved products such as 4'-OH-BPacid (4'-hydroxy-2-methyl-3-phenylbenzoic acid), BPacid (2-methyl-3-phenylbenzoic acid), 4'-OH-BPalcohol (4'-hydroxy-2-methyl-3-phenylbenzyl alcohol), dimethoxy-BPacid, 4'-methoxy BPacid, dimethoxy BPalcohol, BPalcohol, TFPacid [3-(2-chloro-3,3,3-trifluoro-1-propenyl-2,2-dimethyl-cyclopropanecarboxylic acid], cis- and trans-hydroxymethyl TFPacid. The major metabolic pathways are considered to be hydrolysis of ester linkage, oxidation at the methyl group of the acid moiety and at the 3'- and 4'-positions of the phenyl group, and O-methylation. The conjugation reactions are considered to take place; however, detailed information is not available.
Fastest breakdown is seen with primary alcohol esters of trans-substituted acids since they undergo rapid hydrolytic and oxidative attack. For all secondary alcohol esters and for primary alcohol cis-substituted cyclopropanecarboxylates, oxidative attack is predominant. /Pyrethroids/
Pyrethrins are reportedly inactivated in the GI tract following ingestion. In animals, pyrethrins are rapidly metabolized to water soluble, inactive compounds. /Pyrethrins/
Bifenthrin, a pyrethroid pesticide, is estrogenic in vivo in fishes. However, bifenthrin is documented to be anti-estrogenic in vitro, in the ER-CALUX (estrogen receptor) cell line. We investigated whether metabolite formation is the reason for this incongruity. We exposed Menidia beryllina (inland silversides) to 10 ng/L bifenthrin, 10 ng/L 4-hydroxy bifenthrin, and 10 ng/L bifenthrin with 25 ug/L piperonyl butoxide (PBO) - a P450 inhibitor. Metabolite-exposed juveniles had significantly higher estrogen-mediated protein levels (choriogenin) than bifenthrin/PBO-exposed, while bifenthrinalone was intermediate (not significantly different from either). This suggests that metabolites are the main contributors to bifenthrin's in vivo estrogenicity.
Synthetic pyrethroids are generally metabolized in mammals through ester hydrolysis, oxidation, and conjugation, and there is no tendency to accumulate in tissues. In the environment, synthetic pyrethroids are fairly rapidly degraded in soil and in plants. Ester hydrolysis and oxidation at various sites on the molecule are the major degradation processes. /Pyrethroids/
IDENTIFICATION AND USE: Bifenthrin is a light brown viscous oil. Bifenthrin is registered for use to control a variety of insects including aphids, worms, ants, gnats, moths, beetles, grasshoppers, mites, midges, spiders, ticks, yellow jackets, maggots, thrips, caterpillars, flies, fleas, and other pests in domestic, public health, agricultural, and industrial situations. HUMAN EXPOSURE AND TOXICITY: Neurological effects include symptoms such as dizziness, headache, tingling and numbness sensation, muscle spasms and tremors. Dermal effects include symptoms such as rash, hives, blisters, sores and itchiness. Respiratory effects include symptoms such as: shortness of breath, asthma, respiratory distress, respiratory irritation, coughing, difficulty in breathing, sinus problems, and chest pain. Most of the gastrointestinal symptoms were nausea, vomiting and few cases presented with abdominal pain and diarrhea. Ocular symptoms were redness, pain and swelling of eyes, itchy watery eyes and blurred vision. Few cases presented with cardiovascular symptoms such as high blood pressure, irregular heartbeat, and heart attack. Exposure to bifenthrin, even at "acceptable" limits, can increase the risk for and frequency of inflammatory responses and diseases such as asthma. ANIMAL STUDIES: Non-irritant to skin; virtually non-irritating to eyes (rabbits); no skin sensitization (guinea pigs). Bifenthrin Technical, 88.35% a.i., 98% cis, 2% trans; 200, 100, 50, 12 and 0 ppm /was given to rats in feed; 50/sex/dose for 2 years. No oncogenic effects reported. Effects included tremors, abrasions, alopecia, tail lacerations, reduced weight gain (females only), and reduced RBC 12% (males only). All effects were observed at 200 ppm. Technical (Bifenthrin), 89.7%, administered to 4 Beagles/sex/group at nominal concentrations of 0, 0.75, 1.50, 3.0, and 5.0 mg/kg/day in gelatin capsules for 52 weeks; Intermittent delayed onset of tremors occurring through week 29 at 3.0 and 5.0 mg/kg/day. Bifenthrin technical, 88.35% a.i., 98% cis, 2% trans; 100, 60, 30 and 0 ppm was given to rats in the feed for 8 weeks prior to F0 mating through F2b weaning; 25/sex/dose; no fertility or reproductive effects, other effects include tremors during lactation, ovary weight reduction in adults. Non-teratogenic in rats (> or = 2 mg/kg/day) & rabbits (8 mg/kg/day). Tremors were observed in 6 pups out of 40 examined (4 males on post-natal day (PND) 10 and 2 females on PND 28) at the highest dose (9 mg/kg/day). Bifenthrin was not mutagenic in the Ames assay, and did not produce chromosome aberrations in Chinese hamster ovary (CHO) cells. ECOTOXICITY STUDIES: Based on available data, bifenthrin has been classified as slightly toxic on an acute basis to birds. Bifenthrin showed no adverse effects to reproduction at the highest concentration tested for birds. Mammalian toxicity data suggest that this compound is moderately toxic to small mammals on an acute basis. Relative to steelhead, rainbow trout have different responses to bifenthrin acute toxicity as well as different rates of hepatic bifenthrin biotransformation. Bifenthrin is highly toxic on an acute and chronic basis to freshwater fish and aquatic-phase amphibians, and very highly toxic to freshwater aquatic invertebrates. Bifenthrin has also been classified as very highly toxic to estuarine/marine fish and invertebrates on an acute basis.
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. (T18, L857)
来源:Toxin and Toxin Target Database (T3DB)
毒理性
致癌性证据
癌症分类：C组可能的人类致癌物
Cancer Classification: Group C Possible Human Carcinogen
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).
As for every type I pyrethroid, bifenthrin effects typically include rapid onset of aggressive behavior and increased sensitivity to external stimuli, followed by fine tremor, prostration with coarse whole body tremor, elevated body temperature, coma,
and death. (L857)
Male and female rats were treated with (14)C-bifenthrin labeled in the acid or alcohol moiety at single oral doses of 4 and 35 mg/kg. (14)C was rapidly excreted into feces and urine, and the excretion rates of the (14)C to feces and urine were 66-83% and 13-25%, respectively. Highest residues were found in the fat, with values of slightly more than 1 ppm after low-dose administration and 8 and 16 ppm in males and females, respectively, after application of the high dose. Residue levels in other organs were in most cases <0.2 ppm after low-dose administration and <1 ppm after high-dose administration.
The tissue residues /of rats/ were examined after oral administration of (14)C-bifenthrin at 0.5 mg/kg/day for 70 days. The peak (14)C concentrations on an average were 9.6 ppm in fat, 1.7 ppm in skin, 0.4 ppm in liver, 0.3 ppm in kidney, 1.7 ppm in ovaries, 3.2 ppm in sciatic nerve, 0.06 ppm in whole blood, and 0.06 ppm in plasma. Analyses were extended for an additional 85 days following cessation of dosing (depuration phase). Half-lives of 51 days (fat), 50 days (skin), 19 days (liver), 28 days (kidney), and 40 days (ovaries and sciatic nerve) were estimated from (14)C-depuration. Analysis of the fat revealed that the parent chemical accounted for a majority (65-85%) of the (14)C-residues in fat.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
杀虫剂是透过完整皮肤被吸收的，当局部应用时。
Pyrethrins are absorbed through intact skin when applied topically. /Pyrethrins/
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
...在大鼠口服、吸入和静脉给药后，对双甲脒的药代动力学进行了描述。还介绍了通过口服和吸入途径的拟除虫菊酯类急性毒性。将雄性大鼠分组，通过口服灌胃给药3.1 mg/kg，用1 mL/kg的玉米油（临界、急性、口服基准剂量下限，BMDL）和等效剂量通过吸入（0.018 mg/L）4小时。在给药开始后2、4、6、8和12小时，测量血浆和大脑中双甲脒的浓度。血浆中双甲脒的最大浓度为361 ng/mL或0.853 uM（口服）和232 ng/mL或0.548 uM（吸入），在大脑中为83和73 ng/g。口服灌胃给药后，浓度-时间曲线下的面积（AUC）值为1969 h ng/mL（血浆）和763 h ng/mL（大脑），吸入后为1584 h ng/mL（血浆）和619 h ng/mL（大脑）。静脉给药导致明显的终末半衰期（t1/2）值为13.4 h（血浆）和11.1 h（大脑），血浆和大脑的AUC0-∞值为454和1566 h ng/mL。从血浆中清除的速率为37 mL/min/kg。口服给药后，血浆和大脑的峰浓度通常略高（约14%）。双甲脒的吸入给药没有因为避免肝脏的首过效应而在血浆或大脑中引起暴露增加。消除半衰期与其他拟除虫菊酯类相似，表明生物积累潜力很小。...
... The pharmacokinetics of bifenthrin in the rat after oral, inhalation and intravenous administration is described. Pyrethroid acute toxicity via oral and inhalation routes is also presented. Groups of male rats were dosed by oral gavage at 3.1 mg/kg in 1 mL/kg of corn oil (the critical, acute, oral benchmark dose lower limit, BMDL) and at an equivalent dose by inhalation (0.018 mg/L) for 4 hr. At 2, 4, 6, 8 and 12 hr after dosing initiation, blood plasma and brain bifenthrin concentrations were measured. The maximum concentrations of bifenthrin in plasma were 361 ng/mL or 0.853 uM (oral) and 232 ng/mL or 0.548 uM (inhalation), and in brain they were 83 and 73 ng/g. The area under the concentration versus time curve (AUC) values were 1969 h ng/mL (plasma) and 763 h ng/mL (brain) following oral gavage dosing, and 1584 h ng/mL (plasma) and 619 h ng/mL (brain) after inhalation. Intravenous dosing resulted in apparent terminal half-life (t1/2 ) values of 13.4 h (plasma) and 11.1 h (brain) and in AUC0-infinity values of 454 and 1566 h ng/mL for plasma and brain. Clearance from plasma was 37 mL/min/kg. Peak plasma and brain concentrations were generally a little higher after oral dosing (by ca 14%). Inhalation administration of bifenthrin did not cause increases in exposure in plasma or brain by avoiding first-pass effects in the liver. The elimination t1/2 was comparable with other pyrethroids and indicated little bioaccumulation potential. ...
... This study evaluated the oral disposition and bioavailability of bifenthrin in the adult male Long-Evans rat. In the disposition study, rats were administered bifenthrin (0.3 or 3 mg/kg) by oral gavage and serially sacrificed (0.25 hr to 21 days). Blood, liver, brain and adipose tissue were removed. In the bioavailability study, blood was collected serially from jugular vein cannulated rats (0.25 to 24 hr) following oral (0.3 or 3 mg/kg) or intravenous (0.3 mg/kg) administration of bifenthrin. Tissues were extracted and analyzed for bifenthrin by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Bifenthrin concentration in blood and liver peaked 1-2-hr post-oral administration and were approximately 90 ng/mL (or g) and 1000 ng/mL (or g) for both tissues at 0.3 and 3 mg/kg, respectively. Bifenthrin was rapidly cleared from both blood and liver. Brain concentrations peaked at 4-6 hr and were lower than in blood at both doses (12 and 143 ng/g). Bifenthrin in adipose tissue peaked at the collected time points of 8 (157 ng/g) and 24 (1145 ng/g) hr for the 0.3 and 3 mg/kg doses, respectively and was retained 21 days post-oral administration. Following intravenous administration, the blood bifenthrin concentration decreased bi-exponentially, with a distribution half-life of 0.2 hr and an elimination half-life of 8 hr. Bifenthrin bioavailability was approximately 30%. These disposition and kinetic bifenthrin data may decrease uncertainties in the risk assessment for this pyrethroid insecticide.
[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.
