Flufenoxuron

488.77

488.77

417-680-3

OD068OSS0N

DTXSID1041978

Colorless crystals|White crystalline solid

67.4

6.16

1.57 g/mL

171 °C (decomp)

1.574

In water, 0.0186 (pH 4); 0.00152 (pH 7); 0.00373 (pH 9) mg/L (25 deg C)

0-6°C

6.52X10-9 mPa /SRC: 4.89X10-14 mm Hg/ at 20 deg C

Odorless

Henry's Law constant = 2.64X10-12 atm-cu m/mol at 25 °C (est)

pKa = 10.1 (calc)

204.46 Ų [M+H]+ [CCS Type: TW]|204.96 Ų [M+H]+

White, crystalline solid /Technical form/

III

9

3077

20

22

CV2474500

Xn

P201, P260, P263, P264, P270, P273, P308+P313, P391, P501

H332

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.

USEPA Office of Prevention, Pesticides and Toxic Substances, Pesticide Fact Sheet for Flufenoxuron (September 2006).[Available from, as of June 1, 2011: http://www.epa.gov/opprd001/factsheets/]

|Warning|H362: May cause harm to breast-fed children [Reproductive toxicity, effects on or via lactation]|P201, P260, P263, P264, P270, P273, P308+P313, P391, and P501|H362 (99.44%): May cause harm to breast-fed children [Reproductive toxicity, effects on or via lactation]|Aggregated GHS information provided by 177 companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H332 (88.37%): Harmful if inhaled [Warning Acute toxicity, inhalation]|P261, P271, P304+P312, P304+P340, and P312|Aggregated GHS information provided by 43 companies from 5 notifications to the ECHA C&L Inventory.

LC50 Rat inhalation >5.1 mg/L/4 hr|LD50 Mouse dermal > 2 g/kg|LD50 Rat dermal >2 g/kg|LD50 Rat oral >3 g/kg|For more Non-Human Toxicity Values (Complete) data for Flufenoxuron (6 total), please visit the HSDB record page.

Flufenoxuron's production may result in its release to the environment through various waste streams; its use as an insecticide/acaracide(1) will result in its direct release to the environment(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1.3X10+4(SRC), determined from a log Kow of 6.16(2) and a regression-derived equation(3), indicates that flufenoxuron is expected to be immobile in soil(SRC). Volatilization of flufenoxuron from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.6X10-12 atm-cu m/mole(SRC), using a fragment constant estimation method(4). Flufenoxuron is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 4.89X10-14 mm Hg at 20 °C(5). Biodegradation data in soil were not available(SRC, 2011).|TERRESTRIAL FATE: Flufenoxuron was applied at a nominal concentration of 97.5 g active ingredient/ha annually for three years via tractor-driven mist blower to experimental apple orchards in Sittingbourne, Kent U.K. Monitoring over a three-year period indicated that flufenxouron does remain in the soil at low residue concentrations(1).[(1) Gilbert JM et al; in Brighton Crop Prot. Conf. - Pests Dis. 1992|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1.3X10+4(SRC), determined from a log Kow of 6.16(2) and a regression-derived equation(3), indicates that flufenoxuron 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 2.6X10-12 atm-cu m/mole(SRC), developed using a fragment constant estimation method(5). According to a classification scheme(5), an estimated BCF of 5400(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is very high, provided the compound is not metabolized by the organism(SRC). Hydrolysis half-lives of 112 days (pH 5), 104 days (pH 7), 36.7 days (pH 9), and 2.7 days (pH 12)(6) indicate that the compound does undergo hydrolysis in the environment but the rate is affected by pH(SRC). An aqueous photodegradation half-life of 11 days in ambient water was reported(6). Biodegradation data in water were not available(SRC, 2011).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), flufenoxuron, which has a vapor pressure of 4.89X10-14 mm Hg at 20 °C(2), is expected to exist solely in the particulate phase. Particulate-phase flufenoxuron may be removed from the air by wet or dry deposition(SRC). Flufenoxuron is stable to natural sunlight(4), and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC).

Reported flufenoxuron hydrolysis half-lives of 112 days (pH 5), 104 days (pH 7), 36.7 days (pH 9), and 2.7 days (pH 12) indicate that the compound does undergo hydrolysis in the environment but the rate is affected by pH(1). Flufenoxuron is stable to natural sunlight at temperatures equal to or below 190 °C(1) and therefore is not expected to be susceptible to direct photolysis by sunlight(SRC). The half-life using thin film on glass ranged from stable to >100 hours in simulated sunlight. An aqueous photodegradation half-life of 11 days in ambient water was reported(1).

An estimated BCF of 5400 was calculated in fish for flufenoxuron(SRC), using a log Kow of 6.16(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is very high(SRC), provided the compound is not metabolized by the organism(SRC).

The Koc of flufenoxuron is estimated as 1.3X10+4(SRC), using a log Kow of 6.16(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that flufenoxuron is expected to be immobile in soil.

The Henry's Law constant for flufenoxuron is estimated as 2.6X10-12 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that flufenoxuron is expected to be essentially nonvolatile from water and moist soil surfaces(2). Flufenoxuron is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 4.89X10-14 mm Hg(3).

Flufenoxuron residues were tested for but not detected in twelve tomato samples from local Greek markets; detection limit = 0.01 mg/L(1). The compound was detected in 2 of an unspecified number of Japanese agricultural samples (carrot or grapefruit) at 20.2-50.7 ng/g; detection limit = 18.8 ng/g(2).

Occupational exposure to flufenoxuron may occur through inhalation and dermal contact with this compound at workplaces where flufenoxuron is produced or used. Limited monitoring data indicate that the general US population may be exposed to flufenoxuron via ingestion of imported food. (SRC)

/In rats/ Flufenoxuron exhibited a dose-dependant absorption following a single low dose (3.5 mg/kg) or single high dose (350 mg/kg). At the high dose, saturated absorption was observed. Approximately 86% of the low dose and 1% of the high dose was absorbed in 168 hours, the majority of which occurred within 48 hours. For the difluorobenzene ring test article, urine was a major route of excretion in the low-dose group, but not in the high-dose group (<1%). Conversely, 93-102% of the high dose and 4-19% of the low dose was eliminated in feces. Elimination via expired air was insignificant. Biliary excretion using the aniline ring label showed that all the radioactivity in the feces of females and 40% of that in males are biliary excretion products. Although, the majority of both urinary and fecal excretion occurred within 48 hours, excretion by both routes was biphasic, with slower phase occurring throughout the post-exposure, resulting in accumulation in adipose tissue. This phenomenon was probably due to entero-hepatic circulation. Accumulation of radioactivity in muscle and adipose tissue 4 hours post dosing with 3.5 mg/kg benzyl label was 30% and 42%, respectively. At 168 hours post dose, these values were 6% and 19%, respectively, suggesting an accumulation in the adipose tissue. High doses of both labels resulted in negligible tissue burden (<0.3%) indicating saturation absorption.

Metabolism proceeds via hydrolysis to a benzoic acid and aryloxyphenylurea and aryoxyaniline moieties.|The metabolic fate of flufenoxuron was determined using two radiolabeled positions (aniline and difluorobenzene ring). Flufenoxuron exhibited a dose-dependant absorption following a single low dose (3.5 mg/kg) or single high dose (350 mg/kg). ... For the flufenoxuron aniline ring test article, the parent and a total of 10 urinary metabolites accounted for approximately 5% of the administered dose, and were considered non-significant. Fecal excretion of metabolites was quantitatively greater with parent compound accounting for the greatest portion of radioactivity. However, most fecal metabolites represented < 1% of the administered dose. Both [4-(2-chloro, alpha,alpah,alpha-trifluoro-p-tolyoxy)-2-fluorophenyl urea] and [4- (2-chloro, alpha,alpah,alpha-trifluoro-p-tolyoxy)-2-fluoroaniline] were detected in the feces and urine following administration of the aniline ring labeled test article. Unextractable residues accounted for 7-8% of the dose. The major urinary metabolite of [14C- 2,6-difluorobenzene]flufenoxuron was the corresponding benzoic acid which, over 48 hours, accounted for 10-12% of the administered dose. Difluorobenzamide (<1%) was also detected in the urine along with unknown components all of which individually represented <1% of the dose. The only component detected in the feces of rats given the 2,6-difluorobenzene label was the parent compound. The results of the metabolism characterization studies with both label positions suggest that metabolism of flufenoxuron proceeds via hydrolysis to a benzoic acid metabolite, a phenyl urea metabolite ( 4-[2-chloro, alpha,alpah,alpha-trifluoro-p-tolyoxy]-2-fluorophenyl urea), an aniline metabolite (4-[2-chloro, alpha,alpah,alpha-trifluoro-p-tolyoxy]-2-fluoroaniline), and subsequently several minor components.

Flufenoxuron is a benzoylurea type acaricide/insecticide which inhibits chitin biosynthesis (MOA Group 15) in nymphal mites and caterpillars.

/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/ A 72-year-old woman was brought to the emergency department by ambulance. The person accompanying her brought an empty 100 mL bottle of an insecticide (Cascade), which was found at the scene. The active ingredient of the product is flufenoxuron and the other components include surfactants and solvents. A detailed composition obtained from the manufacturer was flufenoxuron, ethoxylated nonylphenol phosphate, polyoxyethylene nonylphenol, N-methyl-2-pyrrolidone, and cyclohexanone. Upon arrival at the intensive care unit (ICU), her arterial pH was 7.093, her bicarbonate level was 7.4 mEq/L, and the anion gap was 33.8 mEq/L. Her lactic acid concentration was 16.5 mmol/L. Lactic acidosis was not considered to be a consequence of circulatory shock, because there was no clinical sign of shock other than lactic acidosis, and cardiac output was never below 4.5 L/min. Her acid-base status began to improve and returned to near normal on the next day. It can be hypothesized that the toxicity of the product includes inhibition of the oxygen utilization mechanism at the cellular level. The product is composed of a number of components, similar to many other herbicide products. It is not possible to identify which of the ingredients was specifically responsible for the toxic effects in this case.|/GENOTOXICITY/ In a mammalian cell cytogenetics assay (Chromosome aberration), human lymphocyte (whole blood) cultures were exposed to WL115110 (/flufenoxuron/ 98.1% ai) in dimethyl sulfoxide (DMSO) at concentrations of 0, 78.4, 112, or 160 ug/mL for three hours with and without metabolic activation (S-9 mix). Cells were harvested 17 hours following termination of treatment both with and without S-9 mix. Cells were also harvested 41 hours following termination of treatment in another experiment at the highest concentration with S-9 mix. An additional assay was conducted by exposing cells to test material concentrations of 0, 78.4, 112, or 160 ug/mL without S9-mix for 20 hours with immediate post-treatment harvest. Yet another assay was conducted by exposing cells to test material concentrations of 0 or 160 ug/mL without S9-mix for 44 hours with immediate posttreatment harvest. Blood was obtained from a healthy male donor. The S9-fraction was obtained from Aroclor 1254 induced male Sprague-Dawley rat liver. Flufenoxuron was tested up to concentrations limited by solubility. The maximum mitotic inhibition detected was a decrease of 42% in the mitotic index following the 20-hour treatment at the highest concentration in the absence of S-9 mix. Precipitate was seen in the culture media at all concentrations tested. There were no statistically significant increases in the percentage of cells with structural aberrations including or excluding gaps or in polyploidy over the solvent control values at any test material concentration with or without S9-mix. The solvent and positive control values were appropriate, and solvent control values were within the testing laboratory's historical control ranges in all assays. There was no evidence of chromosome aberrations induced over background.

1-(4-(2-chloro-4-(trifluromethyl)phenoxy)-2-fluorophenyl)-3-(2,6-difluorobenzoyl)urea

Flufenoxuron is formulated as 50 and 100 g/L emulsifiable concentrates (EC), dispersible concentrate (DC) or flowable concentrate (FlC) under the trade name Cascade.

The WHO Recommended Classification of Pesticides by Hazard identifies flufenoxuron (technical grade) as Class III: slightly hazardous; Main Use: insecticide.

An adequate HPLC/ultraviolet (UV) method (SAMS 432-3) and liquid chromatography (LC)/mass spectrometry (MS)/MS method (BASF Method 544/0) are available for collecting data on flufenoxuron residues in/on plant commodities. The limit of quantification (LOQ) for flufenoxuron in/on plant commodities is 0.05 ppm for the HPLC/ UV method and 0.01 ppm for the LC/ MS/MS method. Method SAMS 432-3, which is also the proposed enforcement method for plant commodities, has been radio-validated and undergone a successful independent laboratory validation (ILV) trial.|Adequate HPLC/UV methods are also available for collecting data on flufenoxuron residues in milk (Method SAMS 486-1) and livestock tissues (Method SAMS 457-2). The validated LOQ for flufenoxuron is 0.01 ppm in milk, 0.3 ppm in fat, and 0.1 ppm in other tissues.|Product by LC. Residues by HPLC.

Agrochemicals -> Insecticides|Acaricides, Insecticides