Flufenoxuron

Colorless crystals

White crystalline solid

In xylene 6, n-hexane 0.11, cyclohexane 95, dichloromethane 18.8, methanol 3.5, acetone 73.8 (all in g/L, 25 °C)

Solubility in g/100 mL at 20 °C: hexane 0.012; octan-1-ol 1.12; methanol 3.55; dichloromethane 18.7; cyclohexane 96.4; dimethyl sulfoxide 287; dimethyl formamide 287; acetone 73.6

In water, 3.8 ug/L (deionized water)

In water, 4.0X10-6 g/L at 25 °C

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

215.8 Ų [M-H]- [CCS Type: DT; Buffer gas: N2; Ionization: ESI-; Dataset: TOXCAST; Source Identifier: DTXSID1041978]

204.46 Ų [M+H]+ [CCS Type: TW]

218.91 Ų [M+Na]+；204.96 Ų [M+H]+

Warning

H362: May cause harm to breast-fed children [Reproductive toxicity, effects on or via lactation]；H400: Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]；H410: Very toxic to aquatic life with long lasting effects [Warning Hazardous to the aquatic environment, long-term hazard]

P203, P260, P263, P264, P270, P273, P318, P391, and P501 (click each P-code to see the statement)

Warning

Commission Regulation (EC) No 33/2008

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

2008/934, Reg. (EU) No 942/2011

Status: Active Update: 15-12-2008 https://echa.europa.eu/registration-dossier/-/registered-dossier/2851

Benzamide, N-[[[4-[2-chloro-4-(trifluoromethyl)phenoxy]-2-fluorophenyl]amino]carbonyl]-2,6-difluoro-: HSNO Approval: HSR007164 Approved with controls

Lact. (99.3%)；Aquatic Acute 1 (99.3%)；Aquatic Chronic 1 (100%)

Reproductive toxicity - effects on or via lactation；Hazardous to the aquatic environment (acute) - category 1；Hazardous to the aquatic environment (chronic) - category 1

Hazardous to the aquatic environment (Acute) - Category 1；Hazardous to the aquatic environment (Long-term) - Category 1

Lact.；Aquatic Acute 1；Aquatic Chronic 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.

EC50; Species: Selenastrum capricornutum (Green Algae); Concentration: 24.6 mg/L for 96 hr; Effect: Biomass /Conditions of bioassay not specified in source examined/

LC50; Species: Oncorhynchus mykiss (Rainbow Trout); Concentration: 4.9 ug/L for 96 hr /Conditions of bioassay not specified in source examined/

LC50; Species: Colinus virginianus (Northern Bobwhite Quail) diet >5243 mg/kg /Conditions of bioassay not specified in source examined/

LD50; Species: Colinus virginianus (Northern Bobwhite Quail) >2000 mg/kg /Conditions of bioassay not specified in source examined/

For more Ecotoxicity Values (Complete) data for Flufenoxuron (9 total), please visit the HSDB record page.

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).

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).

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.

/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.

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 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).

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ In a 90-day oral toxicity study, WL 115110 (/flufenoxuron/ 98 % ai) was administered to four beagle dogs/sex/dose in the diet at dose levels of 0, 0.05% (500 ppm), 0.5% (5000 ppm), or 5% (50,000 ppm) (0, 38, 375 or 3750 (> 3.5 times limit dose) mg/kg/day, respectively). A mistake in the dose preparation of the 0.5% group was corrected in the second week of the study, and therefore the study was extended to 15 weeks. There were no differences between the controls and the flufenoxuron treated groups in body weights, food and water consumption, ophthalmology, and electrocardiography. There was no mortality during the study. The clinical observations were confined to pallor of the gums or sclera which occurred late in the study in the mid-and high-dose groups. In all treated males, the levels of methemoglobin were increased in a dose-related manner and were significantly higher (p<0.001) in the mid-and high-dose groups than the controls. The effect was seen in males of the 50,000 ppm group by Week 2 (p<0.05). The levels of sulfhemoglobin were also increased (p<0.05 and p<0.001) in the mid-and high-dose groups. These changes were associated with the decreases in hemoglobin, hematocrit and erythrocyte counts in the mid-and high-dose groups at Week 9, with recovery by Week 15. In addition, these changes also correlated with the increase in mean cell volume of red blood cells in the mid-dose group (at Week 9) which persisted to Week 15 in the high dose group. The effect of flufenoxuron on hematology parameters at doses > or = 0.05% was first observed at Week 9, followed by some compensatory effect and recovery in the low-and mid-dose groups. The effect persisted to Week 15 in male beagle dogs that received the mid- and high doses. Similar effects of flufenoxuron were observed in the treated females but to a lesser extent than males in the mid-and high-dose groups. In females, the presence of methemoglobinemia in the mi

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ In a 90-day oral study, flufenoxuron (96.6% ai) was administered in the diet to groups of 10 male and 10 female mice in the treated groups and 20 male and 20 female mice in the control groups. An additional subgroup of ten mice/sex/dose group in the treated groups and twenty mice/sex for controls were used to provide blood for clinical chemistry. The concentrations administered were 0 (controls), 50, 500, 5,000, 10,000, or 50,000 ppm (equivalent to 0, 7.5, 75, 750, 1500 or 7500 mg/kg/day, respectively, based on a food conversion factor of 0.15). ... Five animals either died or were sacrificed prematurely during the study. These included two females in the 5,000 ppm group, two males in the 10,000 ppm group and one female in the 50,000 ppm subgroup used for clinical chemistry bleeding. The causes of death were not determined in necropsy and did not appear to be treatment-related. The only clinical sign observed in any group, treated or controls, was the presence of pale feces in the highest-dosed group in both males and females throughout the study which appeared to be unabsorbed compound. Mean body weight was decreased in the highest-dose (50,000 ppm) males compared to controls throughout the study, although these decreases were <10% of controls. Mean body weight gain was also decreased in the 50,000 ppm males starting at week three and ranged from 14-28% less than controls without a time-response. Overall, the high-dose males had a total weight gain that was 22% less than controls. Treated females had body weight and weight gain comparable to controls throughout the study. Food consumption data were marginally collected. From the limited data endpoints, males did not exhibit any treatment-related differences and no conclusions could be made on the females. A statistically significant (p < or = 0.01) decrease in some erythrocyte parameters including: red blood cell count, erythrocyte cell size variability (red c

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ In a 90-day oral toxicity study flufenoxuron (91.5-96.6% ai) was administered to groups of 10 Fischer 344 rats/sex/dose in the diet at concentrations of 50, 500, 5000, 10,000 or 50,000 ppm (equivalent to 2.5, 25, 250, 500 and 2500 mg/kg/day, respectively, based on a food conversion factor of 0.05). Twenty control rats/sex were maintained on basal diet without the test compound. There were no toxicologically significant compound-related effects based on the assessment of mortality, clinical signs, body weight, food consumption, urinalysis, ophthalmic examination, gross necropsy and histopathology. Evidence of regenerative anemia, which included statistically significant (p < or = 0.01) decreases in red blood cell count, hematocrit and hemoglobin levels and significant increases in reticulocytes (p < or = 0.01), hemoglobin variant production, and spleen weights (p < or =0.01) was seen in females only between 5000 and 50,000 ppm. Further, evidence of anemia was associated with a significant increase in methemoglobinemia in males and females at 5000 and 50,000 ppm. A significant (p < or =0.01) increase in medullary hematopoiesis and a twofold decrease in the myeloid to erythroid ratio was seen at 50,000 ppm in both males and females. The LOAEL = 5000 ppm (approximately 250 mg/kg/day) based on a two-fold increase in a hemoglobin variant production and increased RBC turnover in females and increased methemoglobinemia in males and females. The NOAEL = 500 ppm (25 mg/kg/day) in males and females.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ In a 52-week oral chronic toxicity study, WL 115110 (/flufenoxuron/ 98 % ai) was administered to four beagle dogs/sex/dose in the diet at dose levels of 0, 10, 100, 500, or 50,000 (> limit dose) ppm (0, 0.75, 7.5, 37.5 or 3750 mg/kg/day). There were no differences between the controls and the flufenoxuron treated groups in body weights, food and water consumption, ophthalmology, electrocardiography, clinical chemistry, or urinalysis. There were no treatment related mortalities and no treatment related clinical observations. One female dog in the 500 ppm group diagnosed with "autoimmune hemolytic anemia" was humanly sacrificed. Males that received 50,000 ppm flufenoxuron showed increases in absolute liver weight of 136% of the control (p<0.001). In males in the 50,000 ppm group, the levels of methemoglobin were increased from 208 to 296% of the control (p<0.05 or p<0.01) during Weeks 5 to 40. The levels of sulfhemoglobin were also increased from 214 to 680% of the control (p<0.05 and 0.001) in the same group through out the study period. In addition, in the 500 ppm group, there were increases of methemoglobin (159% of the control, p<0.05) but only in Week 27 and sulfhemoglobin (267 to 286% of the control, p<0.05) during Weeks 27 and 40. These changes were associated with a decrease in hemoglobin and erythrocyte values in the 50,000 ppm group and to a lesser extent, in the 500 ppm group. In addition, these changes also correlated with an increase in mean cell volume of red blood cells in the 50,000 ppm group in Weeks 13 to 40 and in the 500 ppm group at Week 27. The effects of flufenoxuron on hematology parameters at 50,000 ppm was first observed at Week 5 and continued. The destruction of red blood cells by flufenoxuron was compensated by the increase of red blood cell production and platelets. These effects on the blood also correlated with increases in brown pigment deposition in the liver Kupffer cells, hem

For more Non-Human Toxicity Excerpts (Complete) data for Flufenoxuron (17 total), please visit the HSDB record page.

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).

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)

Flufenoxuron's production may result in its release to the environment through various waste streams; its use as an insecticide/acaracide will result in its direct release to the environment. If released to air, a vapor pressure of 4.89X10-14 mm Hg at 20 °C indicates flufenoxuron will exist solely in the particulate phase in the atmosphere. Particulate-phase flufenoxuron will be removed from the atmosphere by wet or dry deposition. Flufenoxuron is stable to natural sunlight, and therefore is not expected to be susceptible to direct photolysis by sunlight. If released to soil, flufenoxuron is expected to have no mobility based upon an estimated Koc of 1.3X10+4. Volatilization from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 2.6X10-12 atm-cu m/mole. Flufenoxuron may not volatilize from dry soil surfaces based upon its vapor pressure. Biodegradation data were not available. If released into water, flufenoxuron is expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's estimated Henry's Law constant. An estimated BCF of 5400 suggests the potential for bioconcentration in aquatic organisms is very high, provided the compound is not metabolized by the organism. 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. An aqueous photodegradation half-life of 11 days in ambient water was reported. 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)

Commission Regulation (EC) No 33/2008

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

2008/934, Reg. (EU) No 942/2011

Status: Active Update: 15-12-2008 https://echa.europa.eu/registration-dossier/-/registered-dossier/2851

Benzamide, N-[[[4-[2-chloro-4-(trifluoromethyl)phenoxy]-2-fluorophenyl]amino]carbonyl]-2,6-difluoro-: HSNO Approval: HSR007164 Approved with controls

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.

/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.

Insecticide/acaricide

There are currently no food/feed uses or tolerances for flufenoxuron in the U.S. BASF Corporation is supporting the use of flufenoxuron on apples, grapes and oranges grown for export to the U.S. in selected European and South American countries.