Azoxystrobin

403.38700

403.39

603-524-3

NYH7Y08IPM

DTXSID0032520

White crystalline solid|Powdery

2933599014

103.56000

4.09318

white crystalline

1.34(20ºC)

116 °C

581.3ºC at 760 mmHg

305.3ºC

1.626

In water, 6 mg/L at 20 deg C

0-6ºC

1.67E-13mmHg at 25°C

LD50 in rats (mg/kg): >5000 orally; >2000 dermally (Godwin)

Henry's Law constant = 7.3X10-14 atm-cu m/mol at 25 °C (est)

195.75 Ų [M+H]+ [CCS Type: TW]|194.59 Ų [M-H]-

Color: Beige solid /Heritage fungicide/

III

6.1

UN 2811

2

R23; R50/53

S22-S45-S60-S61

T

Chemically stable for at least 14 days at 54 deg C.

P261-P273-P311-P501

H331-H410

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal and plant life; and conformance with environmental and public health regulations.|SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.|Dispose of product containers, waste containers, and residues according to local, state, and federal health and environmental regulations.|Safe Disposal of Pesticides. The best way to dispose of small amounts of excess pesticides is to use them - apply them - according to the directions on the label. If you cannot use them, ask your neighbors whether they have a similar pest control problem and can use them. If all of the remaining pesticide cannot be properly used, check with your local solid waste management authority, environmental agency, or health department to find out whether your community has a household hazardous waste collection program or a similar program for getting rid of unwanted, leftover pesticides. These authorities can also inform you of any local requirements for pesticide waste disposal. /Residential users/|Safe Disposal of Pesticides. An empty pesticide container can be as hazardous as a full one because of residues left inside. Never reuse such a container. When empty, a pesticide container should be rinsed carefully three times and the rinsewater thoroughly drained back onto the sprayer or the container previously used to mix the pesticide. Use the rinsewater as a pesticide, following label directions. Replace the cap or closure securely. Dispose of the container according to label instructions. Do not puncture or burn a pressurized container like an aerosol - it could explode. Many communities have programs to recycle household waste such as empty bottles and cans. Do not recycle any pesticide containers, however, unless the recycling program specifically accepts pesticide containers and you follow the program's instructions for preparing the empty containers for collection. /Residential users/

Azoxystrobin Summary Document Registration Review: Initial Docket,EPA-HQ-OPP-2009-0835 (December 2009)[Available from, as of August 23, 2012: http://www.regulations.gov]

|Danger|H331: Toxic if inhaled [Danger Acute toxicity, inhalation]|P261, P271, P273, P304+P340, P311, P321, P391, P403+P233, P405, and P501|H331 (99.72%): Toxic if inhaled [Danger Acute toxicity, inhalation]|Aggregated GHS information provided by 355 companies from 7 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|P261, P271, P304+P340, P311, P321, P403+P233, P405, and P501

Personal Protective Equipment (PPE) ... Applicators and other handlers must wear: Long-sleeved shirt and long pants; Chemical resistant gloves made of any waterproof material such as polyvinyl chloride, nitrile rubber or butyl rubber; Shoes plus socks. /Abound Flowable Fungicide/|Chemical-resistant gloves. Long-sleeved shirt and long pants. Shoes plus socks.

Use dry chemical, foam or CO2 extinguishing media. Wear full protective clothing and self-contained breathing apparatus. Evacuate nonessential personnel from the area to prevent human exposure to fire, smoke, fumes or products of combustion. Prevent use of contaminated buildings, area, and equipment until decontaminated. Water runoff can cause environmental damage. If water is used to fight fire, dike and collect runoff.

In case of spill on floor or paved surfaces, mop and remove to chemical waste storage area until proper disposal can be made if product cannot be used according to the label. /Abound Flowable Fungicide/|If a spill occurs, clean it up promptly. Don't wash it away. Instead, sprinkle the spill with sawdust, vermiculite, or kitty litter. Sweep it into a plastic garbage bag, and dispose of it as directed on the pesticide product label./Residential users/|After Applying a Pesticide, Indoors or Outdoors. To remove pesticide residues, use a bucket to rinse tools or equipment three times, including any containers or utensils that you used when mixing the pesticide. Then pour the rinsewater into the pesticide sprayer and reuse the solution by applying it according to the pesticide product label directions. After applying any pesticide wash your hands and any other parts of your body that may have come in contact with the pesticide..To prevent tracking pesticides inside, remove or rinse your boots or shoes before entering your home. Wash any clothes that have been exposed to a lot of pesticide separately from your regular wash. /Residential users/

SRP: Contaminated protective clothing should be segregated in such a manner so that there is no direct personal contact by personnel who handle, dispose, or clean the clothing. The completeness of the cleaning procedures should be considered before the decontaminated protective clothing is returned for reuse by the workers. Contaminated clothing should not be taken home at the end of shift, but should remain at employee's place of work for cleaning.|Use this product only in accordance with its labeling and with the Worker Protection Standard, 40 CFR part 170. /Abound Flowable Fungicide/|Do not apply this product in a way that will contact workers or other persons, either directly or through drift. Only protected handlers may be in the area during application. /Abound Flowable Fungicide/|Do not enter or allow worker entry into treated areas during the restricted entry interval (REI) of 4 hours. /Abound Flowable Fungicide/|For more Preventive Measures (Complete) data for AZOXYSTROBIN (12 total), please visit the HSDB record page.

SOURCE DOMINATED: Average daily ambient azoxystrobin concentrations were 1.2X10-10, 2.1X10-10 and 1.5X10-10 ug/cu m over golf courses in Boston, MA, Philadelphia, PA and Rochester, NY, respectively(1). Maximum concentrations of azoxystrobin over the same golf courses were 2.3X10-9, 3.9X10-9 and 2.9X10-9 ug/cu m, respectively(1).

LD50 Rat oral >5000 mg/kg|LD50 Rat percutaneous >2000 mg/kg

/AQUATIC SPECIES/ ...The acute and chronic physiological effects of the strobilurin fungicide azoxystrobin on three clones of D. magna originating from different Danish lakes were evaluated. Significant clonal variation in the sensitivity of D. magna toward azoxystrobin was demonstrated. One clone had a 48 hr median lethal concentration (LC50) of 0.277 mg/L (95% confidence limits (CL), 0.145 and 0.427 mg/L), which is comparable to the value widely used in risk assessments (0.259 mg/L). The two remaining clones were far more sensitive, however, and had LC50s of 0.071 mg/L (95% CL, 0.034 and 0.126 mg/L) and 0.098 mg/L (95% CL, 0.066 and 0.139 mg/L), respectively. Furthermore, through respiration measurements and life-table experiments, sublethal stress was shown to exist at exposure to an ecologically relevant concentration (0.026 ug/L). Based on these results, we may expect changes in daphnid populations at azoxystrobin concentrations much lower than previously thought.|/AQUATIC SPECIES/ Atlantic salmon smolts were exposed to three doses of the fungicide azoxystrobin for 4 days, and physiological blood parameters and transcriptional effects in liver and muscle were evaluated in search for potential negative effects. Azoxystrobin exposure mediated up-regulation of catalase, MAPK1 /mitogen-activated protein kinase 1/ and IGFBP1 /insuline-like growth factor binding protein 1/ in liver tissue. Catalase, transferrin, IGFBP1 and TNFR /tumor necrosis factor receptor/ were up-regulated and CYP1A /cytochrome p450 1A/ down-regulated in muscle tissue. Blood parameters glucose, hematocrit, pCO(2), HCO(3) and pH grouped together with transcripts levels of MnSOD, MAPK1, IGFBP1, MAP3K7 /mitogen-activated protein kinase kinase kinase 7/ and GPx4 in liver of fish exposed to the highest azoxystrobin concentration (352 ug/L) using principal component analysis (PCA). In muscle, the blood parameters glucose, hematocrit, pCO(2), HCO(3) and pH grouped together with transcript levels of heme oxygenase, thioredoxin, MnSOD, TNFR and MMP9.|/AQUATIC SPECIES/ ...In this study... the joint effect of the imidazole fungicide prochloraz together with the herbicides acifluorfen, diquat and terbuthylazine, the fungicide azoxystrobin and the insecticides chlorfenvinphos, dimethoate, and pirimicarb on the bacteria Vibrio fischeri (six binary mixtures), the crustacean Daphnia magna (four binary mixtures), the algae Pseudokirchneriella subcapitata (four binary mixtures) and the floating plant Lemna minor (three binary mixtures) /was tested/. All the binary mixtures were evaluated both in relation to the model of concentration addition and independent action using isobolograms. The study showed strong synergy in relation to concentration addition between prochloraz and azoxystrobin, diquat and esfenvalerate on D. magna with sums of toxic units for the 50:50% effect mixture (summation TU(50:50)) as low as 0.25. The mixture with dimethoate was however antagonistic with summation TU(50:50) of 2.04. Four out of the six mixtures tested on V. fisheri showed synergy in relation to concentration addition, but for three of the mixtures the response could be explained by independent action. ... There was no significant synergy for any of the combinations tested on the plant and the algae species in relation to concentration addition and only for diquat in the algae-test in relation to independent action. Hence, prochloraz does synergise the effect of some pesticides in the aquatic environment, but not consistently across species. The organism most susceptible to synergy by prochloraz in this study was D. magna. Especially the combination with insecticides such as esfenvalerate, where the concentration needed to immobilize 50% of the daphnia was reduced from >3 ug/L to less than 0.5 ug/L when prochloraz was added, could be problematic as these concentrations are environmentally realistic.|/AQUATIC SPECIES/ The effects of the strobilurin fungicide azoxystrobin were studied in brackish water microcosms, with natural plankton communities and sediment. Two experiments were conducted: Experiment 1 (nominal concentration 0, 15 and 60 ug/L, 24-L outdoor microcosms for 21 days) and a second, follow-up, Experiment 2 (nominal concentrations 0, 3, 7.5, 15 ug/L, 4-L indoor microcosms for 12 days). The microcosms represent a simplified brackish water community found in shallow semi-enclosed coastal areas in agricultural districts in the Baltic Sea region. Measured water concentrations of the fungicide (Experiment 1) were, on average, 83 and 62% of nominal concentrations directly after application, and 25 and 30% after 21 days, for the low and high dose treatments, respectively, corresponding to mean DT50-values of 15.1 and 25.8 days, for low and high dose treatments, respectively. In Experiment 1, direct toxic effects on calanoid copepods at both test concentrations were observed. Similarly, in Experiment 2, the copepod abundance was significantly reduced at all tested concentrations. There were also significant secondary effects on zooplankton and phytoplankton community structure, standing stocks and primary production. ...Azoxystrobin is toxic to brackish water copepods at considerably lower concentrations than previously reported from single species tests on freshwater crustaceans...|For more Ecotoxicity Excerpts (Complete) data for AZOXYSTROBIN (6 total), please visit the HSDB record page.

Azoxystrobin's production may result in its release to the environment through various waste streams; its use as a fungicide(1) will result in its direct release to the environment(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), reported Koc values of 207 to 594(2) indicate that azoxystrobin is expected to have moderate to low mobility in soil(SRC). Volatilization of azoxystrobin from moist soil surfaces is not expected to be an important fate process(SRC) given a Henry's Law constant of 7.3X10-14 atm-cu m/mole(SRC), based upon its vapor pressure, 8.25X10-13 mm Hg(3), and water solubility, 6 mg/L(3). Azoxystrobin is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(3). Azoxystrobin was present at 22.3 and 60.9% of applied dose (100 mg/kg) to compost aged for 3 and 12 months, respectively, in 125-day tests(2), suggesting that biodegradation is not an important environmental fate process in soil(SRC).|AQUATIC FATE: Based on a classification scheme(1), reported Koc values of 207 to 594(2) indicate that azoxystrobin is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 7.3X10-14 atm-cu m/mole(SRC), derived from its vapor pressure, 8.25X10-13 mm Hg(4), and water solubility, 6 mg/L(4). According to a classification scheme(5), an estimated BCF of 21(SRC), from its log Kow of 2.50(4) and a regression-derived equation(6), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Azoxystrobin, in aqueous solution absorbs light at wavelengths of >290 nm and can be photodegraded, ten photo products have been tentatively identified(7). In the dark and under aerobic conditions, the half-life of azoxystrobin was in the range of eight to 12 weeks and the major metabolite formed upon degradation resulted from the hydrolysis of the ester moiety(7). Azoxystrobin has been experimentally shown to be stable to hydrolysis at pH 5 and 7, at pH 9 a half-life of 12.1 days is reported(8).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), azoxystrobin, which has a vapor pressure of 8.3X10-13 mm Hg at 25 °C(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase azoxystrobin may be removed from the air by wet or dry deposition(SRC).

A base-catalyzed second-order hydrolysis rate constant for azoxystrobin of 2.1X10-3 L/mole-sec(SRC) was estimated using a structure estimation method(1); this corresponds to half-lives of 110 and 11 years at pH values of 7 and 8, respectively(1). Azoxystrobin has been experimentally shown to be stable to hydrolysis at pH 5 and 7, at pH 9 a half-life of 12.1 days is reported(2). In aqueous solutions, azoxystrobin absorbs at wavelengths >290 nm and ten photo products have been tentatively identified(3). Pyrimidine-4,6-diol and 2-hydroxy-benzonitrile form immediately upon irradiation, Z-azoxystrobin isomer forms rapidly in the first 20-25 hours of irradiation(3). Other photo degradates include 2-(6-hydroxy-pyrimidin-4-yloxy)-benzonitrile, beta-methoxyacrylic acid, {2-[6-(2-cyanophenoxy)-pyrimidin-4-yloxy]-phenyl}-acetic acid methyl ester, {2-[6-(2-cyanophenoxy)-pyrimidin-4-yloxy]-phenyl}-oxo-acetic acid methyl ester and 2-[6-(2-cyanophenoxy)-pyrimidin-4-yloxy]-benzoic acid and two newly identified isomers of 2-{2-[6-(2-formyl-phenoxy)-pyrimidin-4-yloxy]-phenyl}-3-methoxy-acrylic acid methyl ester(3).

An estimated BCF of 21 was calculated in fish for azoxystrobin(SRC), using a log Kow of 2.50(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Koc of azoxystrobin has been reported to range from 207 to 594(1). According to a classification scheme(2), this Koc range suggests that azoxystrobin is expected to have moderate to low mobility in soil(SRC). Using a constructed biobed, which is an excavation lined with clay and filled with a mixture of shopped straw, sphagnum and soil with turf on top, it was observed that azoxystrobin concentration in leachate from day zero to day 563 was always <0.5 ug/L(3).

The Henry's Law constant for azoxystrobin is estimated as 7.3X10-14 atm-cu m/mole(SRC) derived from its vapor pressure, 8.25X10-13 mm Hg(1), and water solubility, 6 mg/L(1). This Henry's Law constant indicates that azoxystrobin is expected to be essentially nonvolatile from moist soil and water surfaces(2). Azoxystrobin is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 8.3X10-13 mm Hg(1). Azoxystrobin, applied to golf courses in Boston, MA, Philadelphia, PA and Rochester, NY exhibited minimal volatilization (0% of annual application) based on atmospheric sampling(3).

Azoxystrobin residue in fresh grapes was 0.63 to 1.76 mg/kg, in washed grapes was 0.11 to 0.25 mg/g, in sun dried grapes (raisins) 1.68 to 2.08 mg/kg and in alkali washed sun dried grapes 0.51 to 1.49 mg/kg(1). Of 173 agricultural products analyzed in 2006 in Japan, eight were reported to contain azoxystrobin at 5.4-77.9 ng/g(2).

Occupational exposure to azoxystrobin may occur through inhalation of dust and dermal contact with this compound at workplaces where azoxystrobin is produced or used. Monitoring data indicate that the general population may be exposed to azoxystrobin via ingestion of food containing residual and dermal contact in places azoxystrobin is used(SRC). Chronic non-carcinogenic hazard quotients from inhalation of azoxystrobin were calculated for golf courses in Boston, MA, Philadelphia, PA and Rochester, NY as 9.3X10-14 to 1.8X10-12, 1.6X10-13 to 3.1X10-12 and 1.2X10-13 to 2.3X10-12, respectively(1).

Eight male and female rats were given 14 consecutive daily oral doses of unlabelled azoxystrobin at 1 mg/kg bw followed by a single oral dose of (14)C-pyrimidinyl-labelled azoxystrobin at 1 mg/kg bw. For the repeated doses, about 89.1% and 86.5% of the administered dose was excreted in the feces of the males and females rats within 7 days, respectively, and about 12.5% and 17.0% of the administered dose was excreted in the urine of the males and females rats within 7 days, respectively. In males and females, excretion of radioactivity was rapid, with > 96% being excreted during the first 48 hr. Approximately 0.62% and 0.39% of the administered dose was found in the carcass and tissues within 7 days after dosing in male and female rats, respectively. For the repeated dose, the highest concentrations of azoxystrobin-derived radioactivity were found in the kidneys (males and females, < 0.04 ug equivalents/g). The concentrations found in the liver were 0.02 and 0.01 ug equivalents/g for males and females, respectively. At termination, the total concentration of radioactivity in blood was 0.01 ug equivalents/g for males and females.|In toxicokinetic studies, groups of male and female Alpk:APfSD rats (five to eight per group, depending on experiment) were given azoxystrobin (purity, 99%) with or without pyrimidinyl label as a single dose at 1 or 100 mg/kg bw by gavage or as 14 repeated doses of 1 mg/kg bw per day. Biliary metabolites were assessed using rats with cannulated bile ducts given a single dose at 100 mg/kg bw by gavage. The vehicle was polyethylene glycol (PEG 600) at 4 mL/kg bw. Treated rats were housed in stainless steel metabolism cages for 7 days. Urine was collected at 6 hr, and urine and feces were collected separately at 12, 24, 36, 48 h and at 24 hr intervals until 7 days after dosing. At each collection, cages were rinsed with water and cage-washing collected together with the urine. At the end of the study, cages were thoroughly rinsed with ethanol/water (1:1 v/v) and retained for radiochemical analysis. Carbon dioxide and volatiles were trapped. After 7 days, various organs and tissues were removed and analyzed for radioactivity. ... For rats receiving a single lower dose (1 mg/kg bw), total excretion of radioactivity (urine, feces, and cage wash) was 93.75% and 91.44% for males and females, respectively over the 7 days. Most (> 85%) of the urinary and fecal excretion took place during the first 36 hr after dosing. In these rats, about 83.2% and 72.6% of the administered dose was excreted in the feces of males and females within 7 days, respectively, and about 10.2% and 17.9% of the administered dose was excreted in the urine of the males and females within 7 days, respectively. Approximately 0.34% and 0.31% of the administered dose was found in the carcass and tissues within 7 days after dosing in males and females, respectively. For rats at this dose (1 mg/kg bw), the highest concentrations of radiolabel were found in the liver (mean for males and females, 0.009 ug equivalents/g) and in the kidneys (males, 0.027 ug equivalents/g; and females, 0.023 ug equivalents/g). At termination, the total concentration of radioactivity in blood was 0.004 ug equivalents/g for males and females. Less than 0.6% of the administered dose was recovered in the expired. For rats receiving the single higher dose (100 mg/kg bw), total excretion of radioactivity (urine, feces, and cage wash) was 98.29% and 97.22% for males and females, respectively, over the 7 days. Most (> 82%) of the urinary and fecal excretion took place during the first 48 hr after dosing. At this dose, about 89.37% and 84.53% of the administered dose was excreted in the feces of the males and females within 7 days, respectively, and about 8.54% and 11.54% of the administered dose was excreted in the urine of the males and females within 7 days, respectively. Approximately 0.33% and 0.33% of the administered dose was found in the carcass and tissues within 7 days after dosing in males and females rats, respectively. At this higher dose, the highest concentrations of radiolabel were found in the kidneys (males, 1.373 ug equivalents/g; and females, 1.118 ug equivalents/g) and in the liver (males, 0.812 ug equivalents/g; and females, 0.714 ug equivalents/g). At termination, the total concentration of radioactivity in blood was 0.389 ug equivalents/g for males and 0.379 ug equivalents/g for females|The excretion and tissue distribution of radioactivity was investigated for 48 h in male and female rats given a single dose of azoxystrobin at 1 mg/kg bw by gavage. Treated rats were housed in metabolism cages to facilitate the collection of urine, feces, exhaled air and volatiles. One male and one female rat receiving azoxystrobin radiolabelled in each position were killed at 24 hr and 48 hr after dosing. Each carcass was frozen and sectioned in preparation for whole-body radiography. About 89% and 86% of the administered dose of (14)C-pyrimidinyl-labelled azoxystrobin was excreted within 48 hr in the urine and feces of male and female rats, respectively. Most of the radioactivity was excreted in the feces, with < 17% in the urine. The male and female rats treated with (14)C-phenylacrylate-labelled azoxystrobin excreted about 80% and 97% of the administered dose within 48 hr, respectively. Most of the radioactivity was excreted via the feces with < 21% in the urine. At 48 hr, males and females, excreted approximately 0.01% of the administered dose as carbon dioxide trap and approximately 0.01% as volatile metabolites. The male and female rats treated with (14)C-cyanophenyl- labelled azoxystrobin excreted about 95% and 98% of the administered dose within 48 hr, respectively. Most of the radioactivity was excreted via the feces, with < 16% in the urine. At 48 hr, males and females excreted small amounts of radioactivity as carbon dioxide (< 0.3%) and as volatile metabolites (0.01%). For all radiolabels, the distribution of radioactivity was similar in males and females, as shown by whole-body autoradiography. At 24 hr, most of the radiolabel was present in the alimentary canal, moderate amounts in the kidneys and small amounts in the liver. Forty-eight hours after dosing, the whole-body autoradiography results showed a marked reduction in radioactivity. The results of these studies indicated that there were no significant differences between the rates and routes of excretion or tissue distribution of azoxystrobin labelled in one of three positions. No sex-related difference in excretion profile was evident. Minor differences in excretion were primarily due to the small numbers of rats used in the study. No significant differences in the amount of radioactivity recovered in the exhaled air and as volatiles were observed between the three radiolabels or between sexes. On the basis of the results of this study, other studies of excretion and tissue retention were conducted using only pyrimidinyl-labelled azoxystrobin.

... (14)C-Cyanophenyl-labelled azoxystrobin was given to bile duct cannulated and non-cannulated rats at a dose of 100 mg/kg bw. Samples of urine, feces and bile were collected for up to 72 hr. The purpose of this study was to reevaluate certain plant and goat metabolites that were previously not identified in rats and further elucidate the metabolic pathway of azoxystrobin in rats. Three further metabolites, previously detected in either plants or goats, were identified. Compound 13 (2-hydroxybenzonitrile), resulting from cleavage of the diphenyl ether link, was detected in the bile and urine as the glucoronide conjugate at a concentration of up to 1.8% of the administered dose. Compound 20 ((2-(6-(2-cyanophenoxy) pyrimidin-4-yloxy) phenyl)acetic acid) was also detected in the bile and urine at a concentration of up to 1.3%. Compound 35 (2-(2-(6-(2-cyanophenoxy) pyrimidin-4-yloxy) phenyl)glycolic acid) was detected in the urine, feces and bile at a concentration of up to 0.6%. Compounds 24 (Methyl 2-(2(6-(2-cyanophenoxy)pyrimidin-4-yloxy) phenyl)-glycolate) and 30 (2-(6-(2-cyanophenoxy) pyrimidin-4-yloxy) benzoic acid) were not detected.|Bile-duct cannulated rats were given azoxystrobin radiolabelled in either the pyrimidinyl, cyanophenyl or phenylacrylate rings at 100 mg/kg bw by gavage. Comparison of the rates and routes of excretion and the profile of the metabolites showed (as previously) that there were no significant differences in the metabolism of the three differently labelled forms, thus indicating that there was minimal cleavage of the ether linkages between the aromatic rings. Experiments designed to identify metabolites were therefore conducted in bile-duct cannulated rats given (14)C-pyrimidinyl labelled azoxystrobin by gavage. In the bile-duct cannulated rats, excreta, bile, and cage wash were collected at 6, 12, 24, 36, and 48 hr and stored at -20 °C. Samples of bile, feces and urine were collected between 0 hr and 48 hr and pooled. Samples for males and females were separated. Urine and feces were collected at up to 168 hr after dosing from rats given the single dose (higher or lower) and from rats receiving repeated doses for 14 days, and were used for quantification of metabolites. Some bile samples were enzymatically digested using cholylglycine hydrolase at 30 units/mL, pH 5.6 at 37 °C overnight. Metabolites were identified using various analytical techniques, such as thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), proton nuclear magnetic resonance spectroscopy (NMR) and mass spectrophotometry (MS). On the basis of biliary excretion data for rats given a single dose of either (14)C-pyrimidinyl-, (14)C-phenylacrylate-, or (14)C-cyanophenyl-labelled azoxystrobin at 100 mg/kg bw, 74.4% (males) and 80.7% (females) of the pyrimidinyl-derived radioactivity was excreted in the bile after 48 hr. For the cyanophenyl-derived radioactivity, 56.6% and 62.5% was excreted in the bile of males and females, respectively. For the phenylacrylate-derived radioactivity, 64.4% (males) and 63.6% (females) was excreted in the bile. Quantitatively, there were no significant differences in biliary excretion between males and females. Azoxystrobin was found to undergo extensive metabolism in rats. A total of 15 metabolites were detected in the excreta and subsequently identified. Seven additional metabolites were detected but not identified. None of the unidentified metabolites represented more than 4.9% of the administered dose. The quantitative data for the various metabolites in the faeces, urine and bile of rats receiving a single dose of azoxystrobin at 100 mg/kg bw ... . The mass balance for the study of metabolite identification indicated that a substantial percentage of the administered radiolabel (45.6-73.6%) was unaccounted for, although the studies of excretion showed total recovery of 91.75-103.99%, with 72.6-89.3% being in the feces. The percentage of unaccounted-for radiolabel was especially notable in the groups receiving a single lower dose and a repeated lower dose. The study authors indicated that the variable efficiency in recovery could be explained by the fact that, for metabolite identification, feces were extracted with acetonitrile which allowed partitioning of the parent compound when it was present in the faeces (i.e. rats receiving the higher dose). For the groups receiving a single lower dose or repeated lower dose (where quantities of the parent compound were minimal), most of the faecal radiolabel was associated with polar metabolites that would not be present in the acetonitrile extract. The resulting concentration of radiolabel in the extract would, therefore, be very low. For the group receiving the higher dose, greater amounts of parent compound were left unabsorbed, thereby resulting in greater amounts of parent compound available for partitioning into the acetonitrile extract. The glucuronide conjugate (metabolite V) was the most prevalent biliary metabolite in both males (29.3%) and females (27.4%). Metabolite I (parent compound) was not detected in the bile. Each of the other biliary metabolites accounted for between 0.9% and 9.0% of the administered dose. In the bile-duct cannulated rats, about 15.1% and 13.6% of the faecal radioactivity was metabolite I (parent compound) in male and female rats, respectively. No parent compound was detected in the urine of bile-duct cannulated male and female rats. The predominant metabolite in the urine of the bile-duct cannulated rats was unidentified metabolite 2, which accounted for about 1.8% and 2.0% of the administered dose in male and female rats, respectively. There was no evidence for a dose-influencing metabolism, but a sex-specific difference in biotransformation was observed, with females producing more metabolites than did males. Biotransformation was unaffected by dose. The study authors suggested that absorption was dose-dependent. The oral absorption at 1 mg/kg bw was nearly complete (100%) since no parent compound was detected. The oral absorption at the higher dose (100 mg/kg bw) was estimated to be approximately 74-81% since about 19-26% of the parent compound was detected. However, it is difficult to estimate the true oral absorption value owing to poor recoveries after extraction, especially at the lower dose. ... There were two principal metabolic pathway: hydrolysis to the methoxyacid, followed by glucuronide conjugation to give metabolite V; and glutathione conjugation of the cyanophenyl ring followed by further metabolism via a number of intermediates (VI, VII, and VIII) to the mercapturic acid metabolite IX. Azoxystrobin was also hydroxylated at the 8 and 10 positions on the cyanophenyl ring followed by glucuronide conjugation (metabolites II, III, IVa and IVb). There were several minor pathways involving the acrylate moiety, resulting in formation of the metabolite XIII and XIV. Three metabolites (X, XII, and XV) arising via the cleavage of the ether linkages were identified.|The metabolic fate of [(14)C]-methyl-(E)-2-[2-[6-(2-cyanophenoxy)pyrimidin-4-yloxy]phenyl]-3-methoxyacrylate (azoxystrobin) was determined in the male and female rat following a single oral dose of 1 and 100 mg x kg(-1) and in surgically prepared, bile duct-cannulated rats following a single oral dose of 100 mg x kg(-1). 2. Azoxystrobin was extensively metabolized with at least 15 metabolites. There was a sex difference, with females producing more metabolites than males. 3. The two principal metabolic pathways were hydrolysis of the methoxyacid followed by glucuronic acid conjugation and glutathione conjugation of the cyanophenyl ring followed by further metabolism leading to the mercapturic acid. There were also several other minor pathways.

Mode of action: fungicide with protectant, eradicant, translaminar & systemic properties. Powerfully inhibits spore germination &, in addition to its ability to inhibit mycelial growth, also shows antisporulant activity. Acts by inhibiting mitochondrial respiration by blocking electron transfer between cytochrome b & cytochrome c1. Controls pathogenic strains resistant to the 14 demethylase inhibitors, phenylamides, dicarboxamides or benzimidazoles.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/GENOTOXICITY/ In vitro chromosome aberrations in human lymphocytes assay: The test was positive for the induction of chromosomal aberrations in both the presence and absence of S9 activation at doses (5-50 ug/mL +S9) that were moderately to severely cytotoxic (ie, > or = 16-70% reductions in mitotic cells, respectively).

amistar

Wettable granule, flowable, suspension concentrate.|Premix Partners: Chlorothalonil; Cyproconazole, Difenoconazole; Fenpropimorph; Fludioxonil; Metalaxyl-M; Propiconazole; Spinosad; Thiabendazole; Thiamethoxam.|Heritage Fungicide (Syngenta Crop Protection, LLC): Azoxystrobin 50%.|Abound Flowable Fungicide (Syngenta Crop Protection, LLC): Azoxystrobin 22.9%.|For more Formulations/Preparations (Complete) data for AZOXYSTROBIN (51 total), please visit the HSDB record page.

The WHO Recommended Classification of Pesticides by Hazard identifies azoxystrobin as unlikely to present an acute hazard in normal use; Main Use: fungicide, other than for seed treatment.

Residues by gc/NPD or lc/ms/ms. Residues in water by hplc/uv. Residues in soil by hplc/uv, or by gc/ms.

Agrochemicals -> Fungicides|Fungicides|Pesticides -> Fungicides -> Antibiotic fungicides -> Strobilurin fungicides|Environmental transformation -> Pesticides (parent, predecessor)

Azoxystrobin has known environmental transformation products that include Azoxystrobin acid.|Azoxystrobin has known environmental transformation products that include Azoxystrobin TP 10, Azoxystrobin acid, R219277, R401553, R402173, and R403314.