Clodinafop-propargyl

349.74

349.74

600-662-6

QEH394TY6Y

DTXSID6032354

Colorless crystals|Crystalline solid|Cream powder

29333990

57.6

3.90 at 25 deg C

White crystal powder.

1.37 g/cm³ @ Temp: 22 °C

59.5 °C

432.7±45.0 °C(Predicted)

215.5±28.7 °C

1.559

In water, 4.0 mg/L at 25 deg C

0-6°C

2.40X10-8 mm Hg at 25 deg C

LD50 in rats (mg/kg): 1829 orally; >2000 dermally; LC50 in rats (4 hr): >2325 mg/m3 by inhalation (Amrein)

Lower 1.0%; Upper 7.0% /Discover Herbicide/

D20 +45.4° (c = 2 in acetone)

Odorless

pH = 4.1 at 25 °C

Henry's Law constant = 2.76X10-9 atm-cu m/mol at 25 °C (est)

180.36 Ų [M+H]+

Relatively stable in acidic media at 50 °C; hydrolyses half-life in alkaline media (25 °C): 64 hours (pH 7), 2.2 hours (pH 9)|Hydroxyl radical reaction rate constant = 2.66X10-11 cu cm/molec-sec at 25 °C (est)|Ozone radical reaction rate constant = 3.0X10-19 cu cm/molec-sec at 25 °C (est)

950 °F /Discover Herbicide/

Lower 1.0%; Upper 7.0% /Discover Herbicide/

III

6.1

UN 2811

3

20/22-43-50/53-48/22

36/37-60-61-46-24

Xn;N,N,Xn

Relatively stable in acidic media at 50 deg C, hydrolyses in alkaline media; DT50 (25 deg C) 4.8 days (pH 7), 0.07 days (pH 9).

P261-P273-P280-P304 + P340 + P312-P333 + P313-P391

H302 + H332-H317-H373-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.|Wastes resulting from the use of this product may be disposed of on site or at an approved waste disposal facility. /Discover Herbicide/|Do not reuse empty container. Triple rinse (or equivalent), puncture, and dispose of empty container in a sanitary landfill, or by incineration, or, if allowed by state and local authorities, by burning. If burned, stay out of smoke. /Discover Herbicide/|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.

Combustible liquid. Can release vapors that form explosive mixtures at temperatures at or above the flash point. Heavy vapors can flow along surfaces to distant ignition sources and flash back. /Discover Herbicide/

USEPA Office of Prevention, Pesticides and Toxic Substances, Pesticide Fact Sheet for Clodinafop-propargyl (June 6, 2000).[Available from, as of June 1, 2011: http://www.epa.gov/opprd001/factsheets/]

|Warning|H302: Harmful if swallowed [Warning Acute toxicity, oral]|P260, P261, P264, P270, P272, P273, P280, P301+P312, P302+P352, P314, P321, P330, P333+P313, P363, P391, and P501|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|Aggregated GHS information provided by 271 companies from 9 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Personal Protective Equipment ... Applicators and other handlers must wear: Coveralls over short-sleeved shirt and short pants; Chemical-resistant gloves, such as barrier laminate or viton; Chemical-resistant footwear plus socks; Chemical-resistant apron when cleaning equipment, mixing, or loading. /Discover Herbicide/|... Restricted-entry interval (REI) of 12 hours. PPE required for early entry to 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 over short-sleeved shirt and short pants; Chemical-resistant gloves, such as barrier laminate or viton; Chemical-resistant footwear plus socks. /Discover Herbicide/|... Chemical-resistant gloves ... Protective eyewear.

Use appropriate extinguishing media for combustibles in the area. 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. /Discover Herbicide/|Combustible liquid. Can release vapors that form explosive mixtures at temperatures at or above the flash point. Heavy vapors can flow along surfaces to distant ignition sources and flash back. /Discover Herbicide/|During a fire, irritating and possibly toxic gases may be generated by thermal decomposition or combustion. /Discover Herbicide/

Do not contaminate water when disposing of equipment wash water or rinsate. /Discover Herbicide/|Control the spill at its source. Contain the spill to prevent from spreading or contaminating soil or from entering sewage and drainage systems or any body of water. Clean up spills immediately, ... . Cover entire spill with absorbing material and place into compatible disposal container. Scrub area with hard water detergent (e.g. commercial products such as Tide, Joy, Spic and Span). Pick up wash liquid with additional absorbent and place into compatible disposal container. Once all material is cleaned up and placed in a disposal container, seal container and arrange for disposition. /Discover Herbicide/

Use this product only in accordance with its labeling and with the Worker Protection Standard, 40 CFR part 170. /Discover Herbicide/|Follow manufacturer's instructions for cleaning/maintaining PPE. If no such instructions for washables, use detergent and hot water. Keep and wash PPE separately from other laundry. /Discover Herbicide/|Do not apply directly to water, to areas where surface water is present, or to intertidal areas below the mean high water mark. /Discover Herbicide/|Do not enter or allow worker entry into treated areas during the restricted-entry interval (REI) of 12 hours. /Discover Herbicide/|For more Preventive Measures (Complete) data for CLODINAFOP-PROPARGYL (9 total), please visit the HSDB record page.

LD50 Rat percutaneous >2000 mg/kg|LC50 Rat inhalation 2.325 mg/L air/ 4 hr|LD50 Rat (male) oral 1392 mg/kg /Clodinafor-propargyl technical/|LD50 Rat (female) oral 2271 mg/kg /Clodinafop-propargyl technical/|For more Non-Human Toxicity Values (Complete) data for CLODINAFOP-PROPARGYL (8 total), please visit the HSDB record page.

/AQUATIC SPECIES/ Zebrafish (Danio rerio) ... Embryos were exposed to a range of concentrations from 0.2 uM to 5 uM starting at late cleavage stage (2 hr postfertilization, (hpf)) or late gastrulation stage (10 hpf). The results showed that the two exposure strategies had the same minimum teratogenic concentration of 0.6 uM but caused different groups of morphogenetic malformations. When exposure was initiated at 2 hpf, clodinafop-propargyl caused various embryonic phenotypes, including embryos with a fin gap in the ventral tail and embryos with coiled tail. When exposure was initiated at 10 hpf, clodinafop-propargyl resulted in failure of the tail to detach, in which the ventral tissues failed to grow out but instead adhered to the yolk extension, and the defect differed to various degrees among embryos. Similar effects were observed for embryos exposed to clodinafop, the metabolite of clodinafop-propargyl. Because these defects were mainly confined to the posterior and ventral region that derived from ventral blastoderm cells, we have evaluated the expression of the ventral mesoderm marker gene gata-1 and ventral ectoderm marker gene gata-3. No significant alteration was seen in gata-1 expression except for the expanded blood islands, whereas the expression of gata-3 was significantly reduced. Our findings showed that clodinafop-propargyl exposure disturbed embryonic patterning and fate specification of ventrally derived gastrula ectoderm cells.|/OTHER TERRESTRIAL SPECIES/ In the present study, DNA damage caused by clodinafop-propargyl was evaluated in silkworm, Bombyx mori, by the alkaline single-cell gel electrophoresis (SCGE). The second, fourth and fifth instar larvae of silkworm were exposed to clodinafop-propargyl by oral feeding with mulberry leaves treated using the different concentration of 30, 60, 120, 240, 480 mg/L, respectively. The results showed that comet percentage, the head DNA percentage, tail DNA percentage, tail length, tail moment and olive moment of the five tested groups were significantly different from the controlled group (P<0.01). A statistically significant (olive tail moment, P<0.01) dose-dependent increase in DNA damage was observed in silkworm. In addition, the significant dose-dependent reduce in percentage of cocooning and pupating was found in the second instar larvae of silkworm exposed to clodinafop-propargyl. ...

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

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 2,000(SRC), determined from a log Kow of 3.90(2) and a regression-derived equation(3), indicates that clodinafop-propargyl is expected to have slight mobility in soil(SRC). Volatilization of clodinafop-propargyl from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.8X10-9 atm-cu m/mole(SRC), derived from its vapor pressure, 2.4X10-8 mm Hg(2), and water solubility, 4 mg/L(2). Clodinafop-propargyl is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(2). A biodegradation half-life in soil of 0.5 to 1.5 days(4) suggests that biodegradation may be an important environmental fate process in soil(SRC).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 2,000(SRC), determined from a log Kow of 3.90(2) and a regression-derived equation(3), indicates that clodinafop-propargyl is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 2.8X10-9 atm-cu m/mole(SRC), derived from its vapor pressure, 2.4X10-8 mm Hg(2), and water solubility, 4.0 mg/L(2). According to a classification scheme(5), an estimated BCF of 170(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is high, provided the compound is not metabolized by the organism(SRC). The aqueous chemical hydrolysis half-life of clodinafop-propargyl is 184 days at pH 5, 2.7 days at pH 7, and 2.2 hours at pH 9(6). A biodegradation half-life in soil of 0.5 to 1.5 days(6) suggests that biodegradation may be an important environmental fate process in water(SRC).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), clodinafop-propargyl, which has a vapor pressure of 2.40X10-8 mm Hg at 25 °C(2), will exist in both the vapor and particulate phases in the ambient atmosphere. Vapor-phase clodinafop-propargyl is degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to be 5 hours(SRC), calculated from its rate constant of 2.7X10-11 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(3). Particulate-phase clodinafop-propargyl may be removed from the air by wet or dry deposition(SRC). Clodinafop-propargyl does not contain chromophores that absorb at wavelengths >290 nm(4), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of clodinafop-propargyl with photochemically-produced hydroxyl radicals has been estimated as 2.7X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 5 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for the vapor-phase reaction of clodinafop-propargyl with ozone has been estimated as 3.0X10-19 cu cm/molecule-sec at 25 °C(SRC) that was derived using a structure estimation method(1). This corresponds to an atmospheric half-life of about 380 days at an atmospheric concentration of 7X10+11 ozone molecules per cu cm(2). The aqueous chemical hydrolysis half-life of clodinafop-propargyl is 184 days at pH 5, 2.7 days at pH 7, and 2.2 hours at pH 9(3). Clodinafop-propargyl does not contain chromophores that absorb at wavelengths >290 nm(4), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC). There is no readily apparent photolysis of clodinafop-propargyl on soil surfaces(3).

An estimated BCF of 170 was calculated in fish for clodinafop-propargyl(SRC), using a log Kow of 3.90(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is high(SRC), provided the compound is not metabolized by the organism(SRC).

The Koc of clodinafop-propargyl is estimated as 2,000(SRC), using a log Kow of 3.90(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that clodinafop-propargyl is expected to have slight mobility in soil. Clodinafop-propargyl is mobile in low organic soil to immobile in high organic soil(4).

The Henry's Law constant for clodinafop-propargyl is estimated as 2.8X10-9 atm-cu m/mole(SRC) derived from its vapor pressure, 2.4X10-8 mm Hg(1), and water solubility, 4.0 mg/L(1). This Henry's Law constant indicates that clodinafop-propargyl is expected to be essentially nonvolatile from water and moist soil surfaces(2). Clodinafop-propargyl is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).

Occupational exposure to clodinafop-propargyl may occur through inhalation and dermal contact with this compound at workplaces where clodinafop-propargyl is produced or used. (SRC)

Clodinafop-propargyl is rapidly and for at least for 75% absorbed in males (based on radiolabel recovered in urine, tissues, cage wash and residual carcass) within 168 hours. Oral absorption in females is higher (> or = 92%). The excretion is also rapid, mainly in the urine. Total excretion after 168 hours is higher in females (92-96%) than in males (66-85%). It is widely distributed and the highest concentration was found in fat, muscle, liver, blood and kidneys. Residues were higher in males than in females. There was a potential for accumulation in fat. Elimination from ovaries, pancreas, thymus and thyroid was slow.

/In animals,/ hydrolyzed to the corresponding acid, which is excreted in urine and feces. ... In plants, rapidly degraded to the acid derivative as major metabolite.|In a rat metabolism study, two (14)C-labeled variants of clodinofop-propargyl (one labeled on the 2 pyridil carbon & the other uniformly labeled on the phenyl ring, purity >98%) were admin to groups of male Tif:RAI f (SPF) rats, approx 7 wk of age by gavage at concns of 25.2 mg/kg ( [2-14C]pyridil) & 24.6 mg/kg ([U-14C]phenyl). In the urine, the major metabolite was determined to be (R)-2-[4-(5-chloro-3-fluoro-2-pyridinyloxy)-phenoxy]-propionic acid, reference material CGA-193469, accounting for 36.7% to 39.1% of the admin dose (AD). Metabolite fraction U3 hydrolysed to yield fraction U7 (i.e., CGA-193469), when treated with NaOH or HCl. Unchanged clodinofop-propargyl was not identified. In the feces, the major metabolite (fraction F*7) corresponded to the urinary metabolite U7 (CGA 193469), accounting for 15.7% to 16.9% of the AD. Metabolite fraction F*8 was determined to be unchanged clodinofop-propargyl, accounting for 0.4% to 1.7% of the AD. In the fat, all metabolites were reportedly acylglycerides, the majority of which were hybrid di- & triacylglycerides, (i.e., approx 3.5% & 17.0% of the AD, respectively).|Clodinafop-propargyl is extensively metabolized (<0.3% remaining as clodinafop-propargyl). The major metabolites evident in the excreta were clodinafop (CGA 193469) and its taurine conjugate. The metabolites in fat were diacylglycerides and triacylglycerides of clodinafop.

Mechanistic studies were conducted to elucidate the mechanisms involved in the increased incidence of neoplastic lesions in liver in rats and mice and to assess the human relevance of these effects. Clodinafop-propargyl was shown to cause peroxisome proliferation in rodent studies. Peroxisome proliferation is a consequence of expression and activation of the alpha subtype of the peroxisome proliferator-activated receptor (PPAR-alpha). The activation of this receptor has been shown to be associated with several responses typical for peroxisome proliferators, such as hepatocellular hypertrophy, stimulation of peroxisomal fatty acid alpha-oxidation, induction of cytochrome P450 isoenzymes of subfamily CYP4A, and hepatocellular proliferation. Several studies were performed to confirm these effects. The mechanistic in vitro and in vivo studies in rodents confirm that clodinafop-propargyl causes a peroxisome proliferative response in rodents, ultimately leading to the formation of liver tumours, as observed in chronic toxicity studies with clodinafop-propargyl. Based on the non-genotoxic characteristics of clodinafop-propargyl and the peroxisome proliferative properties of clodinafop-propargyl, a threshold approach is applicable for the liver tumour formation in rats and mice.|Aryloxyphenoxypropionates, inhibitors of the plastid acetyl-CoA carboxylase (ACC) of grasses, also inhibit Toxoplasma gondii ACC. Clodinafop, the most effective of the herbicides tested, inhibits growth of T. gondii in human fibroblasts by 70% at 10 microM in 2 days & effectively eliminates the parasite in 2-4 days at 10-100 microM. Clodinafop is not toxic to the host cell even at much higher concns. Parasite growth inhibition by different herbicides is correlated with their ability to inhibit ACC enzyme activity, suggesting that ACC is a target for these agents. Fragments of genes encoding the biotin carboxylase domain of multidomain ACCs of T. gondii, Plasmodium falciparum, Plasmodium knowlesi, & Cryptosporidium parvum were sequenced. One T. gondii ACC (ACC1) amino acid sequence clusters with P. falciparum ACC, P. knowlesi ACC, & the putative Cyclotella cryptica chloroplast ACC. Another sequence (ACC2) clusters with that of C. parvum ACC, probably the cytosolic form.

/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/

/CASE REPORTS/ Three cases of adverse effects /to clodinafop-propargyl/ were reported: feeling of empty head and sleepiness, and stinging in the eyes.|/CASE REPORTS/ In one plant accidental exposure to clodinafop-propargyl was reported. The injury was described as chemical burn on the skin.

clodinafop-propargyl

Emulsifiable concentrate, wettable powder.|Premix Partners: Cloquintocet-mexyl; Florasulam; Propiconazole; Trifluralin.|97.5% technical product; 22.3% end use product (Discover Herbicide)|Discover Herbicide (Syngenta Crop Protection, LLC) Clodinafop-propargyl 22.3%|For more Formulations/Preparations (Complete) data for CLODINAFOP-PROPARGYL (6 total), please visit the HSDB record page.

The petitioner has proposed residue analytical methods for tolerance enforcement that use both normal and reverse phase liquid chromatography with UV detection.|Residues in soil by HPLC/UV, LC/MS or GC/MS|HPLC determination in ... plant samples.

Pharmaceuticals|Environmental transformation -> Pesticides (parent, predecessor)

Clodinafop has known environmental transformation products that include CGA 193469 and CGA 302371.