Cyazofamid

Agrochemicals -> Pesticide active substances

Active substance -> EU Pesticides database: Approved

Pesticides -> Fungicides

Environmental transformation -> Pesticides (parent, predecessor)

Fungicides

Pesticide (Cyazofamid) -> USDA PDB

Solvent solubility (all in g/100 mL, 21.2 °C): hexane, 0.003; methanol, 0.174, acetonitrile, 3.095, dichloroethane, 10.212; toluene, 0.600, ethyl acetate, 1.649; acetone, 4.564, octanol, 0.004

In water, 0.107 at pH 7; 0.121 at pH 5; 0.109 at pH 9 (all in mg/L at 20 °C)

Warning

H400: Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]

P273, P391, and P501 (click each P-code to see the statement)

Warning

H400 (100%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]

P273, P391, and P501 (click each P-code to see the statement)

Commission Regulation No 844/2012

Cyazofamid is listed in the dataset of EPA Human Health Benchmarks for Pesticides under the Safe Drinking Water Act (40 eCFR 141)

03/23/EC, Reg. (EU) 2016/950, Reg. (EU) 2017/841, Reg. (EU) 2018/917, Reg. (EU) 2019/707, Reg. (EU) 2020/869, Reg. (EU) 2021/843, Reg. (EU) No 540/2011, Reg. (EU) No 823/2012

A skin irritant and weak sensitizer; Minimal to moderate acute toxicity; Not likely to be carcinogenic to humans; [Reference #1] A skin sensitizer; [PubChem] In high-dose animal studies, causes kidney damage; [RTECS] May cause irritation; [MSDSonline]

USEPA Office of Prevention, Pesticides and Toxic Substances, Pesticide Fact Sheet for Cyazofamid, Reason for Issuance: New Chemical (September 2004)[Available from, as of October 11, 2012: http://iaspub.epa.gov/apex/pesticides/f?p=CHEMICALSEARCH:1]

Tolerances are established for residues of the fungicide cyazofamid, including its metabolites and degradates, in or on the commodities in the following table. Compliance with the tolerance levels specified in the following table is to be determined by measuring only the sum of 4-chloro-2-cyano-N,N-dimethyl-5-(4-methylphenyl)-1H-imidazole-1-sulfonamide and its metabolite, 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile, calculated as the stoichiometric equivalent of cyazofamid, in or on the following commodities:[Table#7176]

Time-limited tolerances are established for residues of the fungicide cyazofamid, including its metabolites and degradates, in or on the commodities in the following table. Compliance with the tolerance levels specified in the following table is to be determined by measuring only the sum of cyazofamid, 4-chloro-2-cyano-N,N-dimethyl-5-(4-methylphenyl)-1H-imidazole-1-sulfonamide and its metabolite CCIM, 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile, calculated as the stoichiometric equivalent of cyazofamid, resulting from use of the pesticide under FIFRA section 18 emergency exemptions. The tolerances expire and are revoked on the date specified in the table.[Table#7177]

Tolerances with regional registrations are established for residues of the fungicide cyazofamid, including its metabolites and degradates, in or on the commodities in the following table. Compliance with the tolerance levels specified in the following table is to be determined by measuring only the sum of 4-chloro-2-cyano-N,N-dimethyl-5-(4-methylphenyl)-1H-imidazole-1-sulfonamide and its metabolite, 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile, calculated as the stoichiometric equivalent of cyazofamid, in or on the following commodities:[Table#7178]

Aquatic Acute 1 (100%)

Hazardous to the aquatic environment (acute) - category 1

Aquatic Acute 1

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.

Container Disposal: Nonrefillable container. Do not reuse or refill this container. Triple rinse container (or equivalent) promptly after emptying. Triple rinse as follows: Empty the remaining contents into application equipment or a mix tank and drain for 10 seconds after the flow begins to drip. Fill the container 1/4 full with water and recap. Shake for 10 seconds. Pour rinsate into application equipment or a mix tank or store rinsate for later use or disposal. Drain for 10 seconds after the flow begins to drip. Repeat this procedure two more times. Then offer for recycling if available, or puncture and dispose of in a sanitary landfill, or by incineration or, if allowed by state and local authorities, by burning. If burned, stay out of smoke. /Ranman 400SC/

Improper disposal of excess pesticide, pesticide spray or rinsate is a violation of Federal law. If these wastes cannot be disposed of by use according to label instructions, contact your State Pesticide or Environmental Control Agency or the Hazardous Waste representative at the nearest EPA Regional Office for guidance. /Ranman 400SC/

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.

Use this product only in accordance with its labeling and with the Worker Protection Standard, 40 CFR Part 170. /Ranman 400SC/

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. /Ranman 400SC/

Do not apply directly to water, to areas where surface water is present or to intertidal areas below the mean high water mark. /Ranman 400SC/

Do not enter or allow worker entry into treated areas during the restricted entry interval (REI) of twelve (12) hours. /Ranman 400SC/

For more Preventive Measures (Complete) data for CYAZOFAMID (8 total), please visit the HSDB record page.

Tolerances are established for residues of the fungicide cyazofamid, including its metabolites and degradates, in or on the commodities in the following table. Compliance with the tolerance levels specified in the following table is to be determined by measuring only the sum of 4-chloro-2-cyano-N,N-dimethyl-5-(4-methylphenyl)-1H-imidazole-1-sulfonamide and its metabolite, 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile, calculated as the stoichiometric equivalent of cyazofamid, in or on the following commodities:[Table#7172]

Time-limited tolerances are established for residues of the fungicide cyazofamid, including its metabolites and degradates, in or on the commodities in the following table. Compliance with the tolerance levels specified in the following table is to be determined by measuring only the sum of cyazofamid, 4-chloro-2-cyano-N,N-dimethyl-5-(4-methylphenyl)-1H-imidazole-1-sulfonamide and its metabolite CCIM, 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile, calculated as the stoichiometric equivalent of cyazofamid, resulting from use of the pesticide under FIFRA section 18 emergency exemptions. The tolerances expire and are revoked on the date specified in the table.[Table#7173]

Tolerances with regional registrations are established for residues of the fungicide cyazofamid, including its metabolites and degradates, in or on the commodities in the following table. Compliance with the tolerance levels specified in the following table is to be determined by measuring only the sum of 4-chloro-2-cyano-N,N-dimethyl-5-(4-methylphenyl)-1H-imidazole-1-sulfonamide and its metabolite, 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile, calculated as the stoichiometric equivalent of cyazofamid, in or on the following commodities:[Table#7174]

Applicators and other handlers must wear long-sleeved shirt and long pants, socks, shoes, and chemical resistant gloves made of any waterproof material. /Ranman 400SC/

/Restricted entry interval (REI) of twelve (12) hours/ PPE required for early entry to the treated areas that is permitted under the Worker Protection Standard and that involves contact with anything that has been treated, such as plants, soil, or water, is: coveralls, chemical resistant gloves made of any waterproof material, shoes plus socks and protective eyewear. /Ranman 400SC/

TERRESTRIAL FATE: Based on a classification scheme(1), Koc values of 736-2172(2), indicate that cyazofamid is expected to have low to slight mobility in soil(SRC). Volatilization of cyazofamid from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.9X10-7 atm-cu m/mole(SRC), based upon its vapor pressure, 9.75X10-8 mm Hg(2), and water solubility, 0.107 mg/L(2). Cyazofamid is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(2). Biodegradation studies show aerobic half-lives for cyazofamid in soil to be 3.7 to 6.4 days(3). Photodegradation half-life of cyazofamid was 47 days in moist soil(3).

TERRESTRIAL FATE: Half-lives for cyazofamid using field studies conducted in the US(1).[Table#7175]

AQUATIC FATE: Based on a classification scheme(1), Koc values of 736-2172(2), indicate that cyazofamid 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 3.9X10-7 atm-cu m/mole(SRC), derived from its vapor pressure, 9.75X10-8 mm Hg(2), and water solubility, 0.107 mg/L(2). According to a classification scheme(4), an estimated BCF of 60(SRC), from a log Kow of 3.2(2) and a regression-derived equation(5), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). Photodegradation of cyazofamid in aqueous systems has a reported half-life of 30 minutes(6). Hydrolysis half-lives of cyazofamid in aqueous environments averaged 11.9 days over a pH range of 4 to 9(6). Biodegradation half-lives of cyazofamid in aerobic aquatic environments were 14.7 to 18.0 days, aqueous anaerobic half-lives were 5.6 to 6.2 days (6).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), cyazofamid, which has a vapor pressure of 9.75X10-8 mm Hg at 35 °C(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase cyazofamid may be removed from the air by wet or dry deposition(SRC).

TOXICOLOGICAL SUMMARY. Acute Toxicity: Technical grade cyazofamid has minimal to moderate acute toxicity in acute oral, dermal and inhalation tests, it is minimally irritating to the eyes and skin, and is a weak dermal sensitizer. Subchronic Toxicity: Following repeated administration in more than one species, cyazofamid seems to have mild or low toxicity. The kidney seemed to be a target organ following 13 weeks of dietary feeding in male rats .... which had increased microscopic kidney lesions characterized as increased number of basophilic tubules, graded as slight in addition to mild increases in urinary output, protein, and pH. Female rats of the same study were less sensitive; with the only change being a marginal increase in urine volume and pH ... Chronic Toxicity: Skin lesions, which may be due to systemic allergy, were observed in the males of the 18 month carcinogenicity study. At the high dose, approaching 1,000 mg/kg/day, male mice suffered hair loss due to scratching which was confirmed at necropsy by increased incidence of body sores (head, neck, trunk, limb, and/or tail), and was correlated histologically with increased incidence of acanthosis (hyperplasia), chronic active dermatitis, ulceration, and premature death. ... Cyazofamid's overall toxicity ... in dogs seems to be limited. In both the 13 week and one year dog studies, there were no major toxicity findings up to a dose of 1,000 mg/kg/day. The only possible effect was increased cysts in parathyroids of both sexes and pituitary in females observed in the high dose groups of the one year study. ... Carcinogenicity: There is no evidence that cyazofamid may be carcinogenic, as indicated in both the rat and the mouse carcinogenicity studies. It is classified as not likely to be carcinogenic to humans based on the lack of evidence of carcinogenicity in both the rat and the mouse. Developmental and Reproductive Toxicity: The pre- and post-natal toxicology database for cyazofamid includes rat and rabbit developmental toxicity studies and two-generation reproduction toxicity study in rats. There was some evidence of increased susceptibility following in utero exposure to rats in the prenatal developmental toxicity study; the increased incidence of bent ribs in the high dose fetuses was considered adverse ... . In the prenatal developmental toxicity study in rabbits, there were no maternal or developmental effects at any dose up to the limit dose of 1,000 mg/kg/day. In the two-generation reproduction study, the highest dose tested (>1,000 mg/kg/day) did not cause maternal systemic toxicity nor did it elicit reproductive or offspring toxicity. Neurotoxicity: In the acute neurotoxicity study, there were no indications of treatment-related adverse neurotoxicity findings including clinical signs, qualitative or quantitative neurobehavioral effects, brain weight, or gross/microscopic pathology. The Agency concluded that the slight increase in motor activity at day 14 among the mid- and high-dose males is marginal and should not be considered an adverse finding. Mutagenicity: Cyazofamid does not appear to have mutagenicity potential, based on several negative in vivo and in vitro studies.

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)

The Koc of cyazofamid has been reported to range from 736-2172(1). Koc values for various soils (adsorption/desorption in L/kg) are as follows: Loamy sand (Ohio), Koc = 1524/1062, Kd = 9.99/6.96; Sandy loam (UK), Koc = 1,444/2,900, Kd = 43.31/87.00; Sandy loam (UK), Koc = 1165/1124, Kd = 14.11/13.49; Sand (Germany), Koc = 815/657, Kd = 5.14/4.14(2). According to a classification scheme(3), these Koc values suggest that cyazofamid is expected to have low to slight mobility in soil. Adsorption studies found that >98% of applied radioactivity remained in the top 10 cm of soil with very limited leaching; leachate constituted <0.3% of the applied radioactivity(2).

AEROBIC: Cyazofamid's fate in soil as well as its limited mobility in soil environments appears to be controlled by biotic degradation as well as its strong affinity for adsorption to soil(1). Degradation products were reported as 4-chloro-5-p-tolylimidazole-2-carbonitrile (CCIM), 4-chloro-5-p-tolylimidazole-2-carboxamide (CCIM-AM) and 4-chloro-5-p-tolylimidazole-2-carboxylic acid(CTCA)(1). Aerobic biodegradation half-life values in soil were reported as follows: 6.1-6.4 days in a loamy sand soil from Ohio (pH 6.5 %OC 0.66); 3.7-4.0 days in a loamy sand soil from England (pH 7.6, %OC 1.2); 4.3-4.4 days in a loamy sand soil from England (pH 6.9, %OC 3.0); 4.9-6.0 days in a sand soil from Germany (pH 5.9, % OC 0.63)(1). Aerobic aqueous biodegradation half-lives ranging from 14.7 to 18.0 days were reported using a river water/sandy loam (3:1) ecosystem and half-lives ranging from 9.5 to 10.9 days using a Creek water/sandy loam eco system were observed(1).

ANAEROBIC: Under anaerobic conditions, half-lives ranging from 5.6 to 6.2 days were reported for cyazofamid using a Milli-Q/sandy loam (2:1) ecosystem(1).

An estimated BCF of 60 was calculated in fish for cyazofamid(SRC), using a log Kow of 3.2(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is moderate(SRC).

The Henry's Law constant for cyazofamid is estimated as 3.9X10-7 atm-cu m/mole(SRC) derived from its vapor pressure, 9.75X10-8 mm Hg(1), and water solubility, 0.107 mg/L(1). This Henry's Law constant indicates that cyazofamid is expected to be essentially nonvolatile from water and moist soil surfaces(2). Cyazofamid is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).

/LABORATORY ANIMALS: Acute Exposure/ Technical grade cyazofamid has minimal to moderate acute toxicity in acute oral, dermal and inhalation tests, it is minimally irritating to the eyes and skin, and is a weak dermal sensitizer. ... Primary Eye Irritation in Rabbit: Grade 2 conjunctival redness and discharge that resolved by 24 hours. Primary Skin Irritation in Rabbit: Very slight to well defined erythema that cleared by 7 days. Dermal Sensitization (Guinea Pig Maximization Test): Positive (weak sensitizer) /From table/

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ /Cyazofamid/ (Technical grade IKF-916, purity = 96.2%) was administered orally by capsule(s) daily to 4 beagle dogs per sex per dose at dose levels of 0 (empty capsules), 40, 200, or 1000 mg/kg/day for 13 consecutive weeks. No mortalities occurred. No treatment-related clinical signs were observed. No effects on body weight were observed. Hematology and clinical chemistry investigations revealed no biologically significant effects. Urinalysis revealed no treatment-related effects. Organ weight data revealed no biologically significant effects. Necropsy revealed no treatment-related abnormalities. Microscopic examination revealed no histopathological findings. NOEL (M/F) = 1000 mg/kg/day based on no effects at the highest dose tested.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ /Cyazofamid/ (Technical IKF- 916, purity = 95.5%) was moistened with deionized water and applied to the clipped dorsal skin of 5 Sprague Dawley [Crl:CD (SD)BR] rats per sex per dose at dose levels of 0 (deionized water), 250, 500, or 1000 mg/kg/day for 6 hours per day for 28 consecutive days. No mortalities occurred. No treatment-related clinical signs and no skin effects at the test site were observed. No effects on body weight were observed. Hematological and clinical chemistry investigations revealed no treatment-related effects. No treatment-related changes in organ weights were observed. Necropsies and microscopic examinations revealed no treatment-related effects. No adverse effects. NOEL (M/F, systemic and skin) = 1000 mg/kg/day (based on no effects at the highest dose tested).

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ /Cyazofamid/ (IKF-916, purity = 95.5%) was admixed to the basal diet and fed to 12 Fischer (F344/DuCrj) rats per sex per dose at dose levels of 0, 10 (males only), 50, 500, 5000, or 20000 (females only) ppm (0, 0.597, 2.906, 29.51, and 294.5 mg/kg/day, respectively, for males and 0, 3.303, 33.32, 337.6, and 1359 mg/kg/day, respectively, for females) for 13 weeks. No mortalities occurred. No treatment-related clinical signs were observed. No biologically-significant effects on body weight were observed. A treatment-related increase in serum mean chloride level and treatment-related decreases in total cholesterol and triglyceride levels were observed in males at 5000 ppm. Urinalysis revealed a treatment-related increase in mean urine volume and a treatment-related increase in protein in males at 5000 ppm. Treatment-related increases in mean relative kidney weight in females at 5000 and 20000 ppm and in mean relative liver weight in females at 20000 ppm were observed. Microscopic examination revealed a treatment-related increase in the number of basophilic tubules in the kidneys in males at 5000 ppm. No adverse effects. NOEL (M) = 29.51 mg/kg/day (500 ppm) based on an increase in the number of basophilic tubules in the kidneys, NOEL (F) = 33.32 mg/kg/day (500 ppm) based on an increase in mean relative kidney weight.

For more Non-Human Toxicity Excerpts (Complete) data for CYAZOFAMID (24 total), please visit the HSDB record page.

Occupational exposure to cyazofamid may occur through inhalation and dermal contact with this compound at workplaces where cyazofamid is produced or used(SRC). Use data indicate that the general population may be exposed to cyazofamid via inhalation of ambient air from spray drift in the vicinity of application operations(1).

Tolerances are established for residues of the fungicide cyazofamid, including its metabolites and degradates, in or on the commodities in the following table. Compliance with the tolerance levels specified in the following table is to be determined by measuring only the sum of 4-chloro-2-cyano-N,N-dimethyl-5-(4-methylphenyl)-1H-imidazole-1-sulfonamide and its metabolite, 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile, calculated as the stoichiometric equivalent of cyazofamid, in or on the following commodities:[Table#7176]

Time-limited tolerances are established for residues of the fungicide cyazofamid, including its metabolites and degradates, in or on the commodities in the following table. Compliance with the tolerance levels specified in the following table is to be determined by measuring only the sum of cyazofamid, 4-chloro-2-cyano-N,N-dimethyl-5-(4-methylphenyl)-1H-imidazole-1-sulfonamide and its metabolite CCIM, 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile, calculated as the stoichiometric equivalent of cyazofamid, resulting from use of the pesticide under FIFRA section 18 emergency exemptions. The tolerances expire and are revoked on the date specified in the table.[Table#7177]

Tolerances with regional registrations are established for residues of the fungicide cyazofamid, including its metabolites and degradates, in or on the commodities in the following table. Compliance with the tolerance levels specified in the following table is to be determined by measuring only the sum of 4-chloro-2-cyano-N,N-dimethyl-5-(4-methylphenyl)-1H-imidazole-1-sulfonamide and its metabolite, 4-chloro-5-(4-methylphenyl)-1H-imidazole-2-carbonitrile, calculated as the stoichiometric equivalent of cyazofamid, in or on the following commodities:[Table#7178]

To elucidate the background of the highly selective fungicidal activity of cyazofamid ... the biochemical mode of action of this fungicide in /a target species/ Pythium spinosum was investigated. Cyazofamid inhibited mycelial growth of P. spinosum on the order of 1 uM on agar medium containing gelatin, on water agar, and on potato dextrose agar. The mycelial growth inhibition was markedly potentiated in the presence of salicylhydroxamic acid (SHAM), an inhibitor of mitochondrial alternative oxidase. Oxygen consumption of P. spinosum mycelia treated with 4 uM cyazofamid was reduced by about 60%. At 60 min after the treatment, the oxygen consumption was recovered, but the respiration was resistant to potassium cyanide and sensitive to SHAM. From the effect of cyazofamid on electron transport activity of P. spinosum mitochondria, it was revealed that this fungicide specifically interferes with cytochrome bc1 complex (complex III) activity (I50: 0.04 uM). Cyazofamid, however, exhibited no inhibition of complex III activities in mitochondria isolated from other biological sources such as Botrytis cinerea, Saccharomyces cerevisiae, rat liver, and potato tuber. Thus, the highly selective activity of cyazofamid appeared to be due to a difference in the inhibitor susceptibility at the target enzyme. To identify the binding site of cyazofamid in complex III, reduction kinetics of cytochrome b hemes was investigated with P. spinosum mitochondria. The addition of cyazofamid immediately reduced cytochrome b hemes and the extent of reduction was higher than that without cyazofamid. Reduction of b hemes was markedly inhibited by the combined use of cyazofamid and azoxystrobin (Qo center inhibitor). These results suggest that cyazofamid binds to the Qi center of complex III.

Cyazofamid is reported to inhibit complex 3 but at the Qi site (antimycin site) which differs from that of other recent fungicidal inhibitors of complex 3 which act at the Qo site. It is claimed to be specific in its inhibitory action to mitochondria from oomycete fungi.

Pharmacokinetics and metabolism studies in rats following administration of a single low (0.5 mg/kg) or high (1,000 mg/kg) dose, showed relatively rapid absorption (irrespective of dose tcmax = 0.25-0.5 hrs) and elimination (t1/2 4.4-5.8 hrs) at the low dose and saturated absorption with prolonged elimination (t1/2 of 7.6-11.6 hrs) at the high-dose.

Both the urine and feces were major routes of excretion /in rats/ at the low dose /0.5 mg/kg/ with most of the urinary radioactivity being a metabolite named CCBA (4-(4-chloro-2-cyanoimidazol-5-yl)benzoic acid). ... Irrespective of the dosing regimen, most of the recovered fecal radioactivity was unchanged parent compound; the major fecal metabolites were CCBA and 4-chloro-5-p-tolylimidazole-2-carbonitrile (CCIM) each of which being less than 5% of the administered dose.

Major metabolites in urine and feces were identified. There were no significant products of cleavage between phenyl and imidazole substituents. Most of administered label was absorbed following low dose treatment, although 16 to 20% of administered label was found as unchanged a.i. in feces. Males given low dose treatment excreted more label in urine than in feces (about 2:1), whereas in females the ratio was about 1:1. This difference probably reflects a greater excretion of absorbed material in females via the bile compared to males. High dose level was very poorly absorbed, evidenced by 86-87% of administered label being found in feces as unchanged a.i. All identified metabolites displayed hydrolytic cleavage of the N,Ndimethylsulfonamide group away from the imidazole ring. Of remaining substituents, the methyl group on the phenyl ring was either oxidized to a carboxylic acid (the major urinary metabolite), or conjugated by GSH and further modified to form a series of metabolites. The major two of these metabolites were alpha-(methylsulfinyl)-p-tolyl and alpha-(methylsulfonyl)-p-tolyl derivatives, both of which were primarily limited to urine of low dose females. Label clearance from blood and other tissues was rapid. In low dose rats there were typically about 10-fold reductions from peak concentrations at 0.5 hr after dosing to the next sampling at 5.5 hr after dosing.

Three biliary-cannulated rats/sex/group were dosed once by gavage with either low or high dose level of cyazofamid (0.5 or 1000 mg/kg): either phenyl-labeled ((14)C-Bz)-IKF-916), or imidazole-labeled ((14)C-Im)-IKF-916). The only strong peak found in urine (50% of administered dose in M and 38% in F) was CCBA. Virtually all label in the feces of low-dose cannulated rats was the parent cyazofamid. Bile accounted for 12-22% of administered dose (M) or 29-39% of administered dose (F). Bile HPLC profiles were rather complex, displaying mostly rather polar components. Investigators justifiably concluded in the footnotes to these pages that structures were "predominantly catabolic products of the glutathione conjugate of CCIM" (CCIM is 4-chloro-5-ptolylimidazole- 2-carbonitrile). The benzoic acid metabolite, CCBA, was also a significant component of bile (about 4% of administered dose in M and F). Complex HPLC profiles of bile extracts were progressively simplified to a few major peaks upon treatment with glucuronidase and acidification. A low-dose male bile profile after such treatment yielded 19% of label in bile as CHCN, and a slight increase over the pre-processing levels of CCBA. CHCN is CCIM with the methyl group on the phenyl ring oxidized to a hydroxymethyl. Together CHCN and CCIM comprised 46% of the bile extracts thus treated, and nearly all of the balance of radiolabel was found in two peaks of relatively polar material ... Thus it appears that conjugation of bile products to glucuronides is a quantitatively important process, in addition to conjugation by glutathione. It was noted in the core metabolism study that CH3SO2-CCIM and CH3SO-CCIM (two products of glutathione addition and subsequent modification) were abundant in urine of non-cannulated females; however cannulated rats of either gender in this study yielded no common urinary metabolites other than CCBA. This suggests that these two metabolites were biliary glutathione derivatives.

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)

Pharmacokinetics and metabolism studies in rats following administration of a single low (0.5 mg/kg) or high (1,000 mg/kg) dose, showed relatively rapid absorption (irrespective of dose tcmax = 0.25-0.5 hrs) and elimination (t1/2 4.4-5.8 hrs) at the low dose and saturated absorption with prolonged elimination (t1/2 of 7.6-11.6 hrs) at the high-dose. The extent of absorption (expressed as percent of administered dose) was highly dose-dependent, being nearly 75% at the low dose and only about 5% at the high dose. Both the urine and feces were major routes of excretion at the low dose with most of the urinary radioactivity being a metabolite named CCBA (4-(4-chloro-2-cyanoimidazol-5-yl)benzoic acid). Results of biliary excretion experiments showed biliary elimination of radiolabel to be highly variable at the low dose (about 12-39% of the administered low dose) and negligible (<2%) in the high-dose groups. Urinary or biliary excretion in rats of the high-dose groups was low (each about 2%) with most of the radioactivity being CCBA. Irrespective of the dosing regimen, most of the recovered fecal radioactivity was unchanged parent compound; the major fecal metabolites were CCBA and 4-chloro-5-p-tolylimidazole-2-carbonitrile (CCIM) each of which being less than 5% of the administered dose. Tissue burdens at t1/2, tmax, and at 168 hours post dose were indicative of rapid clearance and low tissue burdens suggesting little or no bioaccumulation or sequestration.

Used as agricultural fungicide; [Merck Index] Used to control blight on tomatoes and potatoes and downy mildew on cucurbit vegetables; [Reference #1]

Farming (Pesticides) [Category: Industry]

For cyazofamid (USEPA/OPP Pesticide Code: 085651) ACTIVE products with label matches. /SRP: Registered for use in the U.S. but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./

Fungicide

For control of diseases caused by oomycete fungi. ... controls early and late blight on tomatoes and potatoes and downy mildew on cucurbit vegetables (crop group 9).

For control of Oomycete and Plasmodiophora diseases, such as potato and tomato late blight (Phytophthora infestans) and downy mildews (e.g. Pseudoperonospora cubensis of cucumber).

Soluble concentrate

Suspension concentrate

Trade Name: Docious, Mildust.

Technical Cyazofamid Fungicide (ISK Biosciences Corporation), Cyazofamid 95.3%.

For more Formulations/Preparations (Complete) data for CYAZOFAMID (7 total), please visit the HSDB record page.

Environmental transformation -> Pesticides (parent, predecessor)

Fungicides