Flufenoxuron

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)