Cyazofamid

324.79

324.79

203-625-9

QJC4S2YQ4B

DTXSID9034492

Ivory powder

87.4

3.2

1.446 at 20 deg C

152.7°

498.2±37.0 °C at 760 mmHg

4 °C

1.634

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

-20°C

1.3X10-2 mPa /9.75X10-8 mm Hg/ at 35 deg C

Odorless

pH = 4.9 at 25 °C

Henry's Law constant = 3.89X10-7 atm-cu m/mol at 25 °C (est)

No pKa evident in pH range 2-12

166.69 Ų [M+H]+ [CCS Type: TW]

UN12943/PG2

11-38-48/20-63-65-67-20/21/22-50/53-52/53

36/37-62-36-61-60-16

F,Xn,N

P261-P273-P302 + P352 + P312-P304 + P340 + P312-P391-P501

H302 + H312 + H332-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.|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.

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]

|Warning|H400: Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]|P273, P391, and P501|H400 (100%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]|Aggregated GHS information provided by 251 companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H410: Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]

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/

Do not contaminate waters when disposing of equipment wash waters or rinsate. /Ranman 400SC/

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.

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.

LD50 Rat oral >5,000 mg/kg|LD50 Rat dermal >2,000 mg/kg

Cyazofamid'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), 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#7186]|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).

Reported cyazofamid hydrolysis half-lives are 11.9, 12.9, 11.9 and 10.8 days at pH 4, 5, 7 and 9, respectively, all at 25 °C(1). Photolysis half-lives in water and soil of 30 minutes and 47 days, respectively, have been reported(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 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).

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).

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).

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.

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.

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.

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.

If swallowed call a poison control center or doctor immediately for treatment advice. Have person sip a glass of water if able to swallow. Do not induce vomiting unless told to do so by a poison control center or doctor. Do not give anything by mouth to an unconscious person. If inhaled move person to fresh air. If person is not breathing, call 911 or an ambulance, then give artificial respiration, preferably by mouth-to mouth, if possible. Call a poison control center or doctor for further treatment advice. Note to Physician: Probable mucosal damage may contraindicate the use of gastric lavage. /Ranman 400SC/|/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/

4-chloro-2-cyano-N,N-dimethyl-5-p-tolylimidazole-1-sulfonamide

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.

Cyazofamid has limited systemic activity so it is used as a protectant fungicide applied by ground or aerial spray.

An adequate analytical methodology is available to enforce the proposed tolerances. Cyazofamid and the metabolite CCIM are completely recovered (>80% recovery) using the Food and Drug Administration's (FDA) Multi-Residue Protocol D (without cleanup). In addition, High performance liquid chromatography/ultraviolet detector (HPLC/UV) method is available for use as a single analyte confirmatory method.

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

Cyazofamid has known environmental transformation products that include 4-chloro-5-p-tolylimidazole-2-carbonitrile, 4-chloro-5-p-tolylimidazole-2-carboxamide, and 4-chloro-5-p-tolylimidazole-2-carboxylic acid.|Cyazofamid has known environmental transformation products that include CCIM, CCIM-AM, and CTCA.