1,2,4-Triazole (1,2,4-T); triazole alanine (TA); and triazole acetic acid (TAA) are common metabolites to the class of compounds known as triazoles. In plants, 1,2,4-T is rapidly conjugated with serine to form TA. The TA can then be oxidized to form TAA. The extent to which 1,2,4-T, TA, and/or TAA forms in a given plant or animal is primarily dependent on the parent triazole-derivative fungicide. Across the various parent compounds, maximum formation of 1,2 4-T in plants ranges from 0% of the total radioactive residue (TRR) to 17% TRR, with the majority of compounds yielding 1,2,4-T at around 5-10% TRR. In rats, goats, and hens, maximum 1,2,4-T formation ranges from 0 to 77% TRR. Formation of 1,2,4-T in the rat is less than 20% TRR for the majority (approximately 80%) of the triazole-derivative fungicides for which data are available. Formation of TA ranges from 0 to 89% TRR in plants. Triazole acetic acid formation in plants ranges from 0 to 76% TRR. Triazole alanine and triazole acetic acid have generally not been found to be significant metabolites in rats, lactating goats, or laying hens. The exception to this appears to be fenbuconazole. In studies with radio-labeled fenbuconazole fed to goats and hens, TA formation ranges from 0 to 35% TRR; formation of TA from fenbuconazole was not noted in the rat metabolism studies. There is evidence from toxicological studies that there can be limited reduction of TA to 1,2,4-T following oral exposure to TA. /Triazole-derivative fungicide compounds/
Metabolism of two triazole-containing antifungal azoles was studied using expressed human and rat cytochrome P450s (CYP) and liver microsomes. Substrate depletion methods were used due to the complex array of metabolites produced from myclobutanil and triadimefon. Myclobutanil was metabolized more rapidly than triadimefon, which is consistent with metabolism of the n-butyl side-chain in the former and the t-butyl group in the latter compound. Human and rat CYP2C and CYP3A enzymes were the most active. Metabolism was similar in microsomes prepared from livers of control and low-dose rats. High-dose (115 mg/kg/day of triadimefon or 150 mg/kg/day of myclobutanil) rats showed increased liver weight, induction of total CYP, and increased metabolism of the two triazoles, though the apparent Km appeared unchanged relative to the control.
Myclobutanil metabolizes into 1,2,4-triazole, which has a lower acute toxicity than the parent compound (L2093). 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)
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
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).
来源:Toxin and Toxin Target Database (T3DB)
毒理性
健康影响
Myclobutanil is listed as a developmental toxin (L2094).
Myclobutanil is listed as a developmental toxin (L2094).
Workers exposed to myclobutanil have reported symptoms such as skin rash, allergic dermatitis, itchiness, nausea, heachache, diarrhea, abdominal pain, vomiting, nosebleed, and eye irritation (L2093).
Rapidly absorbed and excreted. Completely eliminated by 96 hrs. Extensively metabolized prior to excretion. Metabolic patterns similar for both sexes. Disposition & metabolism after pulse administration is linear over dose range. ... Elimination of label from plasma biphasic and evenly distribution between urine and feces. No tissue accumulation after 96 hours. At least 7 major metabolites recovered and identified. Highest amounts of radioactivity found in liver, kidneys, large and small intestines. No tissue accumulation.
[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.
[EN] SUBSTITUTED QUINAZOLINES AS FUNGICIDES<br/>[FR] QUINAZOLINES SUBSTITUÉES, UTILISÉES EN TANT QUE FONGICIDES
申请人：SYNGENTA PARTICIPATIONS AG
公开号：WO2010136475A1
公开（公告）日：2010-12-02
The present invention relates to a compound of formula (I) wherein wherein the substituents have the definitions as defined in claim 1or a salt or a N-oxide thereof, their use and methods for the control and/or prevention of microbial infection, particularly fungal infection, in plants and to processes for the preparation of these compounds.
