Fipronil gives effective control of early shoot borer and termites in sugarcane. The persistence and metabolism of fipronil in sugarcane leaves and juice were studied following application of fipronil (Regent 0.3 G) at 75 and 300 g a.i./ha. Samples of sugarcane leaves were collected at various time intervals. Samples of sugarcane juice were collected at harvest. Residues of fipronil and its metabolites were quantified by gas liquid chromatograph. The limit of quantification of fipronil and its metabolites was 0.01 mg/kg for sugarcane leaves and juice. Total residues of fipronil and its metabolites in sugarcane leaves after 7 days of its application at 75 and 300 g a.i./ha were 0.26 and 0.66 mg/kg, respectively. Residues could not be detected after 60 and 90 following fipronil application at either concentration. In sugarcane leaves, fipronil was found to be the main constituent, followed by its metabolites amide, desulfinyl, sulfone and sulfide. Samples of sugarcane juice did not reveal the presence of fipronil or its metabolites following its application at both the dosages at harvest.
The enantioselective bioaccumulation and elimination of fipronil in Anodonta woodiana (A. woodiana) were studied and the main metabolites fipronil desulfinyl, fipronil sulfide and fipronil sulfone were determined. The acute toxicity of the enantiomers of fipronil and the three metabolites were also investigated. In the bioaccumulation process, fipronil in A. woodiana reached equilibrium after 11 days with BCF value of 0.2, and the enantiomeric fraction (EF) values showed that the bioaccumulation was enantioselective with enantioenrichment of S-fipronil. The degradation of fipronil in A. woodiana fitted first-order kinetics model with half-lives of the enantiomers were 5.8 d for R-fipronil and 7.6 d for S-fipronil, and the EF values decreasing from 0.5 gradually indicating the R-enantiomer was preferentially degraded. The degradation of single enantiomers was also performed and the results revealed a fast conversion of R-fipronil to S-fipronil by A. woodiana. The three metabolites were all detected in A. woodiana-water system, in which fipronil sulfone and fipronil sulfide had higher concentration levels. According to the 72-hr LC50 values, S-fipronil was much more toxic than the racemate and R-fipronil. Moreover, the metabolites were more toxic than the parent fipronil. The results suggested the individual enantiomers of chiral pollutants and the metabolites should be considered in the risk assessments.
Fipronil is a phenylpyrazole insecticide commonly used in residential and agricultural applications. To understand more about the potential risks for human exposure associated with fipronil, urine and serum from dosed Long Evans adult rats (5 and 10 mg/kg bw) were analyzed to identify metabolites as potential biomarkers for use in human biomonitoring studies. Urine from treated rats was found to contain seven unique metabolites, two of which had not been previously reported-M4 and M7 which were putatively identified as a nitroso compound and an imine, respectively. Fipronil sulfone was confirmed to be the primary metabolite in rat serum. The fipronil metabolites identified in the respective matrices were then evaluated in matched human urine (n=84) and serum (n=96) samples from volunteers with no known pesticide exposures. Although no fipronil or metabolites were detected in human urine, fipronilsulfone was present in the serum of approximately 25% of the individuals at concentrations ranging from 0.1 to 4 ng/mL. These results indicate that many fipronil metabolites are produced following exposures in rats and that fipronil sulfone is a useful biomarker in human serum. Furthermore, human exposure to fipronil may occur regularly and require more extensive characterization.
... In this study, the tissue distribution, the metabolic fate, and the elimination of fipronil was investigated in rats using radiolabeled fipronil. When a single oral dose of (14)C-fipronil (10 mg/kg b.w.) was given to rats, the proportion of dose eliminated in urine and feces 72 hr after dosing was ca 4% for each route. At the end of the experiment the highest levels of radioactivity were found in adipose tissue and adrenals. The main part of the radioactivity present in investigated tissues (adipose tissue, adrenals, liver, kidney, testes) was due to fipronil-sulfone. Five additional metabolites, isolated from urine were characterized by LC-MS/MS. Most of them are formed by the loss of the trifluoromethylsulphinyl group and subsequent hydroxylation and/or conjugation to glucuronic acid or sulfate. In conclusion, the retention of the metabolite fipronil sulfone in tissues following fipronil administration raises the question of the potential toxicity of this insecticide.
Organic nitriles are converted into cyanide ions through the action of cytochrome P450 enzymes in the liver. Cyanide is rapidly absorbed and distributed throughout the body. Cyanide is mainly metabolized into thiocyanate by either rhodanese or 3-mercaptopyruvate sulfur transferase. Cyanide metabolites are excreted in the urine. (L96)
IDENTIFICATION AND USE: Fipronil is a solid. Fipronil is a pyrazole acaricide and insecticide that may be used for insect, tick, lice, and mite control on pets. HUMAN STUDIES: Most cases of exposure (89%) had mild, temporary health effects. Neurological symptoms (50%) such as headache, dizziness, and paresthesia were the most common, followed by ocular (44%), gastrointestinal (28%), respiratory (27%), and dermal (21%) symptoms. Exposures usually occurred from inadvertent spray/splash/spill of products or inadequate ventilation of the treated area before re-entry. Fipronil was tested in an in vitro cytogenetics assay using human lymphocyte cultures. No increase in chromosome aberrations was reported at any dose level. However, in an alkaline comet assay fipronil induced DNA damage in human peripheral blood lymphocytes in vitro. ANIMAL STUDIES: No skin irritation was observed in rabbits. In studies with female rats, the clinical signs of toxicity did not reach their peak until 2 days after treatment in some animals, and deaths did not occur until 4 days after treatment. Some signs of toxicity and body-weight loss were still evident when the observation period ended at day 7 after treatment. Since these findings suggested that bioaccumulation of the test material could occur, a 5-day study with cumulative treatment was performed in which groups of 4 female rats were given fipronil at 75 mg/kg bw/day orally for up to 5 days. Clinical signs of neurotoxicity were seen after administration of 2 doses, and 3 of 4 rats died after admin of 3 or 4 doses. In the only rat that survived the study, abnormal behavioral responses persisted until 6 days after administration of the final dose, at which time it had regained most of its pretreatment weight. A commercial product that contains fipronil was administered orally to pregnant Wistar rats at dosages of 0.1, 1.0, or 10.0 mg/kg/day from the 6th to the 20th day of gestation. The fipronil caused a disturbance of the maternal aggressive behavior; the aggression against a male intruder decreased at the lowest dose, but increased at the highest dose, without interfering with the general activity of the dams in the open field test at either dose. The histopathological analysis revealed no abnormalities. In pregnant rats fipronil interfered with development of neonatal female reproductive system as evidenced by delay in vaginal opening and estrus cycle alterations without apparent significant effects on fertility. The agonistic and antagonistic activities of fipronil and its metabolite, fipronil sulfone were evaluated by in vitro reporter gene assays using CHO-K1 cells. For estrogenic and antiestrogenic activities, both fipronil and fipronil sulfone showed no agonistic activities but exhibited the similarly antagonistic activities via estrogen receptor alpha (ERalpha). In the thyroid hormone receptor (TR) assay, only fipronil sulfone showed anti-thyroid hormone activity. Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, and TA1538 were exposed to a photodegradation product (desulfinyl fipronil) of fipronil with or without metabolic activation with negative result. ECOTOXICITY STUDIES: Fipronil exposure in red-legged partridge (Alectoris rufa) altered blood biochemistry and sexual hormone levels and reduced cellular immune response, antioxidant levels, and carotenoid-based coloration. Exposed pairs also had reduced egg fecundation rate and produced eggs with fewer antioxidants and offspring that had reduced cellular immune response. Fipronil is applied as an equal mixture of two enantiomers. Enantioselective toxicity was observed in larval fathead minnows (Pimephales promelas) after the 7-d subchronic exposure, with increased toxicity of the racemate and (+) enantiomer observed compared with the (-) enantiomer. Curiously, toxicities of the racemate and (+) enantiomer were not significantly different, even though the racemate contains 50% of the (+) enantiomer and 50% of the less toxic (-) enantiomer. Fipronil modulated enzyme biomarkers in the honeybee Apis mellifera.
Fipronil blocks the passage of chloride ions through the GABA-regulated chloride channel, disrupting CNS activity. (T10) Organic nitriles decompose into cyanide ions both in vivo and in vitro. Consequently the primary mechanism of toxicity for organic nitriles is their production of toxic cyanide ions or hydrogen cyanide. Cyanide is an inhibitor of cytochrome c oxidase in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells). It complexes with the ferric iron atom in this enzyme. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted and the cell can no longer aerobically produce ATP for energy. Tissues that mainly depend on aerobic respiration, such as the central nervous system and the heart, are particularly affected. Cyanide is also known produce some of its toxic effects by binding to catalase, glutathione peroxidase, methemoglobin, hydroxocobalamin, phosphatase, tyrosinase, ascorbic acid oxidase, xanthine oxidase, succinic dehydrogenase, and Cu/Zn superoxide dismutase. Cyanide binds to the ferric ion of methemoglobin to form inactive cyanmethemoglobin. (L97)
来源:Toxin and Toxin Target Database (T3DB)
毒理性
致癌物分类
对人类无致癌性（未列入国际癌症研究机构IARC清单）。
No indication of carcinogenicity to humans (not listed by IARC).
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和摄入被身体吸收。
The substance can be absorbed into the body by inhalation and by ingestion.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
毒理性
吸入症状
抽搐。颤抖。
Convulsions. Tremor.
来源:ILO-WHO International Chemical Safety Cards (ICSCs)
... In this study, the tissue distribution, the metabolic fate, and the elimination of fipronil was investigated in rats using radiolabeled fipronil. When a single oral dose of (14)C-fipronil (10 mg/kg b.w.) was given to rats, the proportion of dose eliminated in urine and feces 72 hr after dosing was ca 4% for each route. At the end of the experiment the highest levels of radioactivity were found in adipose tissue and adrenals. The main part of the radioactivity present in investigated tissues (adipose tissue, adrenals, liver, kidney, testes) was due to fipronil-sulfone. Five additional metabolites, isolated from urine were characterized by LC-MS/MS. Most of them are formed by the loss of the trifluoromethylsulphinyl group and subsequent hydroxylation and/or conjugation to glucuronic acid or sulfate. In conclusion, the retention of the metabolite fipronil sulfone in tissues following fipronil administration raises the question of the potential toxicity of this insecticide.
To investigate the localization of fipronil in dog skin, (14)C-fipronil was topically applied to a male beagle dog (spot-on administration) at the therapeutic dose of 10 mg/kg. By means of autohistoradiography, the radioactivity was precisely detected in the skin and appendages at various intervals after application. Radioactivity was predominantly observed within the stratum corneum, the viable epidermis, and in the pilo-sebaceous units (mainly in the sebaceous glands and epithelial layers). (14)C-fipronil was significantly detected in these structures up to 56 days post-treatment, in the application zone (neck) but also in the lumbar zone, thus indicating the mechanical displacement of fipronil. No radioactivity was detected in either the dermal or the hypodermal layers, confirming the low percutaneous passage of fipronil.
Absorption of (14)C-fipronil through epidermal membranes of humans, rabbits, and rats was measured in vitro in horizontal glass diffusion cells. ... The epidermal membranes were set up as a barrier between the two halves of the diffusion cells, and the absorption rates of a neat suspension of fipronil (200 g/L) as a formulation in EP60145A (a formulation base) and of two aqueous dilutions of the formulation containing 0.2 and 4 g/L of fipronil suspended in EP 60145A were determined ... . Fipronil at doses of 4 and 200 g/L penetrated rabbit and rat epidermal membranes to a greater extent than those of humans, whereas at 0.2 g/L the extent of penetration was similar through human and rat skin. The extent of penetration increased with time across species. The % of the applied dose that had penetrated the different membranes after 8 hr was 0.08% through rat epidermal membranes, 0.07% through rabbit membranes, and 0.01% through human membranes for the neat formulation; 0.14, 0.67, and 0.07% of the dose of 4.0 g/L active ingredient; and 0.9, 13.9, and 0.9% of the dose of 0.2 g/L active ingredient, respectively. At the dose of 4.0 g/L, fipronil penetrated the skin of all three species more slowly than either testosterone or hydrocortisone. These two reference permeants were selected because their intrinsic rates of dermal penetration differ by two orders of magnitude, that of testosterone being faster. On the basis of the results for these two compounds, fipronil was considered to be a slow penetrant when applied as a formulation in EP 60145A.
In a study of the absorption, distribution, metabolism, and excretion of fipronil in ruminants, [phenyl(U)-14C]-fipronil (19.2 mCi/mmol) was administered orally by capsule twice daily before feeding to three lactating goats at a dose of 0.05, 2, or 10 ppm for 7 days; assuming a daily intake of 2.0 kg dry matter, these doses are approx equivalent to nominal daily doses of 0.1, 4, and 20 mg, respectively. Milk was collected twice daily. The animals were killed about 24 hr after admin of the final dose and tissues obtained for analysis. The recovery of radiolabel in urine, milk, and tissues indicated that the min absorption of test material was about 19% at 0.05 ppm, 33% at 2 ppm, and 15% at 10 ppm. Of the administered radiolabel, 18-64% was recovered in feces, 1-5% in the milk, and 8-25% in the tissues. Total recovery was similar at the low (83%) and high doses (77%) but was somewhat lower at the intermediate dose (50%). The greatest contributor to the difference in recovery between the animals at the low and high doses and those at the intermediate dose was the amount of radiolabel excreted in the feces: 18% of the total radiolabel administered at 2 ppm, 64% at 0.05 ppm, and 61% at 10 ppm. The reason for this difference is not clear. The greatest total tissue residues were observed in omental and renal fat (about 1.9 ppm at the 10 ppm dose), followed by liver (0.86 ppm) and much lower concns in kidney, milk (0.17 ppm), and skeletal muscle.
[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.
