In rats, the absorbed compound was rapidly cleared with extensive metabolism, particularly through hydrolysis of the ester group. Other significant metabolic routes were O-demethylation of the methoxyimino group and oxidation of the methyl side chain to the corresponding alcohol and carboxylic acid.
Male and female rats were dosed by gavage with either [Glyoxyl-Phenyl-(U)-14C] (radiochemical purity range: >97 to >99%) or [Trifluormethyl-Phenyl-(U)-14C]-/trifloxystrobin/ (CGA- 279202) (radiochemical purity: >99%). For all of the groups except D2, the animals were dosed with [Glyoxyl-Phenyl-(U)-14C]-/trifloxystrobin/ (CGA 279202). ...Thirty five metabolites were isolated and identified from the urine, feces and bile samples. Major metabolic pathways included 1) hydrolysis of the methyl ester to the corresponding acid, 2) O-demethylation of the methoxyimino group, and 3) oxidation of the methyl side chain to a primary alcohol, followed by further oxidation to the carboxylic acid. This last reaction was a more prominent metabolic pathway in the female rats with the resultant isolation of major sex-specific urinary metabolites. Cleavage of the glyoxyl-phenyl and trifluoromethyl-phenyl moieties accounted for 10% of the dose. For the trifluoromethyl phenyl fragment, oxidation of the hydroxyimino group led to the formation of a nitro compound and oxidation of the methyl group resulted in the formation of the carboxylic acid. In addition, hydrolysis of the imino group formed an intermediate ketone with succeeding reactions ultimately leading to trifluoromethyl benzoic acid. For the glyoxyl-phenyl moiety, oxidation resulted in the formation of a benzoic acid. O-demethylation of the methoxyimino group resulted in the hydroxyimino compound. Hydrolysis of the imino group yielded the a-keto acid followed by decarboxylation to the phthalic acid. Conjugates with glucuronide or sulfate were isolated from the bile. Four to 7% and 31 to 47% of the low and high doses, respectively, were eliminated in feces as the unmetabolized test material. The absorbed dose was predominantly isolated in the bile. Further processing returned the test material and/or metabolites to the intestinal tract and elimination in the feces or reuptake via the enterohepatic pathway.
IDENTIFICATION AND USE: Trifloxystrobin is a white powder. It is used as agricultural fungicide. HUMAN EXPOSURE AND TOXICITY: Trifloxystrobin is harmful if absorbed through skin. Prolonged or frequently repeated skin contact may cause allergic reactions in some individuals. ANIMAL STUDIES: Trifloxystrobin was considered to be of low acute toxicity by the oral route in mice and rats, by the dermal route in rabbits, and by the inhalation route in rats. Trifloxystrobin was not selectively neurotoxic following acute gavage or subchronic dietary administration in rats. There were no treatment-related effects upon the mating, fertility, or litter size in rats. It was not mutagenic in S. typhimurium strains TA98, TA100, TA102, TA1535, or TA1357, or in E. coli strain WP2 uvrA with and without metabolic activation. ECOTOXICITY STUDIES: Trifloxystrobin is toxic to nontarget aquatic organisms. Trifloxystrobin could affect the activities of antioxidant enzymes, disrupt photosynthesis in Chlorella vulgaris, and damage cellular structure. Trifloxystrobin is highly toxic to fish embryos. It is very toxic to Daphnia magna and can cause harm to D. magna at environmentally relevant concentrations. Trifloxystrobin was very highly toxic to sheepshead minnows.
来源:Hazardous Substances Data Bank (HSDB)
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
副作用
职业性肝毒素 - 第二性肝毒素：在职业环境中的毒性效应潜力是基于人类摄入或动物实验的中毒病例。
Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
毒理性
毒性数据
LC50 (大鼠) > 4,646 毫克/立方米
LC50 (rat) > 4,646 mg/m3
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
Get medical aid. Eyes: Immediately rinse with plenty of running water. Skin: Flush with plenty of soap and water; remove contaminated clothing. Inhalation: Remove victim to fresh air. Apply artificial respiration if necessary.
Male and female rats were dosed by gavage with either [Glyoxyl-Phenyl-(U)-(14)C] (spec. act. range: 54.3 to 63.5 uCi/mg, radiochemical purity range: >97 to >99%) or [Trifluormethyl-Phenyl-(U)-14C] /trifloxystrobin/ (CGA- 279202) (spec. act.: 59.2 uCi/mg, radiochemical purity: >99%). For all of the groups except D2, the animals were dosed with [Glyoxyl-Phenyl-(U)-(14)C]-/trifloxystrobin/ (CGA 279202). In Groups B1 and D1, urine and feces samples were collected up to 7 days from 5 animals/sex dosed with 0.5 or 100 mg/kg of the test material, respectively. For Group C1, 5 animals/sex were pretreated for 14 days with 0.5 mg/kg of unlabelled /trifloxystrobin/ (CGA 279202) (purity: 99.7%), followed by 0.5 mg/kg of the labelled test material. Urine and feces samples were likewise collected from these animals for up to 7 days. In Group D2, 5 animals/sex were dosed with 100 mg/kg of [Trifluormethyl-Phenyl-(U)-(14)C] /trifloxystrobin/ (CGA-279202) and urine and feces samples were collected up to 7 days. Twelve animals/sex were dosed with either 0.5 or 100 mg/kg of the test material in Groups F1 and 5 and Groups F2 and 6, respectively. Tissue residues were determined at 4 time points based upon pharmacokinetic determinations derived from the previous groups. The bile ducts of animals in Group G were cannulated. In Groups G1 and 3, 6 males and 5 females were treated with 0.5 mg/kg of the test material. Six males and 4 females were dosed with 100 mg/kg of the test material in Groups G2 and 4, respectively. At the low dose level, 56 to 65% of the dose was absorbed with 41 to 47% of the dose recovered from the bile. In the high dose group, 25 to 45% of the dose was absorbed with 19 to 35% of the dose recovered from the bile. In the low dose treatment, 18 to 19% and 79% of the dose was excreted in the urine and feces, respectively, of the males. For the females, 35 to 42% was excreted in the urine and 56 to 63% in the feces. Pretreatment with unlabelled test material did not alter the pattern of excretion. In the high dose groups, the males excreted 10 to 12% and 82 to 84% in the urine and feces, respectively. The females excreted 27% in the urine and 64 to 66% in the feces. Very minimal levels of radiolabel were recovered from the expired air of the animals in Group D2. The half lives for the depletion of radiolabel from the tissues ranged from 13 to 42 hours except for the spleen and blood of the high dose females (68 and 82 hours, respectively). The times to maximal concentration of the test material in the blood were either 12 to 24 hours after dosing. The times to maximal concentration ranged from 23 to 67 hours after dosing. Residual retention of the radiolabel in the carcass after 7 days was very minimal with 0.3 to 0.5% of the dose administered recovered.
Trifloxystrobin was moderately absorbed from the gastrointestinal tract and rapidly distributed. In the low-dose group, approximately 56% and 65% administered dose (AD) was absorbed in males and females respectively (based on the total recovery from urine, feces, bile and tissues), with 41 and 47% being in bile of males and females, respectively. In the high-dose, group, the degree of absorption was 41 and 27%, while the bile content was 35% and 19%, respectively for males and females. The blood kinetics revealed a moderate absorption rate in both sexes with two peaks (after 0.5 and 12 hours at the low dose and 12 and 24 hours at the high dose). The highest residues were found in blood, kidneys, spleen and liver and were comparable between sexes. Excretion of the radioactivity was rapid. Approximately 85-96% of the dose was excreted within 48 hours. The route of elimination was influenced by the sex of the animals, females eliminated twice the amount with the urine than males, accounting for 27-42% and 12-19% of the dose, respectively. The amounts excreted via feces were 79-82% and 56-64% of the dose in males and females, respectively. In both sexes biliary excretion was the major route of elimination. The involvement of an enterohepatic shunt mechanism in the elimination process is indicated.
Environmental Fate of Trifloxystrobin in Soils of Different Geographical Origins and Photolytic Degradation in Water
摘要：
In vitro biodegradation of trifloxystrobin (TFS) under darkness could best be explained by two-compartment first + first-order rate kinetics with half-lives ranging between 1.8 and 2.3 days. Hydrolysis was found to be the major pathway of degradation resulting in the formation of the acid metabolite, TFS-acid, with an EE conformation. The adsorption rate kinetics of both TFS and TFS-acid followed linear and Freundlich isotherms. The extent of adsorption was directly correlated with organic matter and clay contents, whereas desorption had a negative correlation. The high partition coefficients (K-D) indicate strong adsorption of TFS on all of the test soils without any appreciable risk of groundwater contamination. In case of the TFS-acid, however, the adsorption was weaker; hence, if its further degradation is slow, it may contaminate lower soil horizons under worst case conditions. TFS did not cause any adverse effect on the soil microbial population. TFS was susceptible to aquatic photolysis in summer with an environmental half-life of 0.7-1.3 days irrespective of the latitudes.
Environmental Fate of Trifloxystrobin in Soils of Different Geographical Origins and Photolytic Degradation in Water
摘要：
In vitro biodegradation of trifloxystrobin (TFS) under darkness could best be explained by two-compartment first + first-order rate kinetics with half-lives ranging between 1.8 and 2.3 days. Hydrolysis was found to be the major pathway of degradation resulting in the formation of the acid metabolite, TFS-acid, with an EE conformation. The adsorption rate kinetics of both TFS and TFS-acid followed linear and Freundlich isotherms. The extent of adsorption was directly correlated with organic matter and clay contents, whereas desorption had a negative correlation. The high partition coefficients (K-D) indicate strong adsorption of TFS on all of the test soils without any appreciable risk of groundwater contamination. In case of the TFS-acid, however, the adsorption was weaker; hence, if its further degradation is slow, it may contaminate lower soil horizons under worst case conditions. TFS did not cause any adverse effect on the soil microbial population. TFS was susceptible to aquatic photolysis in summer with an environmental half-life of 0.7-1.3 days irrespective of the latitudes.
Compounds of the formula I Formula (I) wherein the substituents are as defined in claim 1, are useful as active ingredients, which have microbiocidal activity, in particular fungicidal activity.
The present invention relates to hydroximoyl-tetrazole derivatives of formula (I), their process of preparation, their use as fungicide active agents, particularly in the form of fungicide compositions and methods for the control of phytopathogenic fungi, notably of plants, using these compounds or compositions, wherein A represents a tetrazoyi group, Het represents a pyridyl group or a thiazolyl group and X represents various substituents.
[EN] MICROBIOCIDAL PYRAZOLE DERIVATIVES<br/>[FR] DÉRIVÉS MICROBICIDES DE PYRAZOLE
申请人：SYNGENTA PARTICIPATIONS AG
公开号：WO2014075874A1
公开（公告）日：2014-05-22
The present invention relates to compounds of formula (I) wherein substituents are as defined in the claims. The invention also relates to methods of using the compounds of formula I to control or prevent infestation of plants, propagation material thereof, harvested crops or non-living materials by phytopathogenic or spoilage microorganisms or organisms potentially harmful to man.
