Isoxaflutole

359.32

359.32

604-222-4

0T9R0O0EYT

DTXSID5034723

Off-white or pale yellow solid|Granular powder

85.6

2.32

1.590 g/cu cm

140 °C

575.1±50.0 °C at 760 mmHg

>130 °C

1.534

In water, 6.2 mg/L at pH 5.5 and 20 deg C

0-6°C

7.5X10-9 mm Hg at 25 deg C

Slight acetic acid-like odor /Technical/

pH = 4.6 at 25 °C

1.85e-10 atm-m3/mole|Henry's Law constant = 1.85X10-10 atm-cu m/mol at 20 °C

Hydroxyl radical reaction rate constant = 5.9X10-12 cu cm/molecule-sec at 25 °C /Estimated/

UN30779/PG3

50/53-63

36/37-60-61

Xn,N

Stable after storage at 54 deg C for 14 days in its initial package, a laboratory stored sample found to be stable for one year under ambient conditions. /Converge 75 WDG Herbicide/ /from table/

P273-P281-P501

H361d-H410

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure 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, aquatic, and plant life; and conformance with environmental and public health regulations.

Mild oxidation with potassium permanganate, no reaction with granular zinc, compatible with water, monoammonium phosphate and mineral spirits. /Converge 75 WDG Herbicide/ /from table/

Health Canada, Pest Management Regulatory Agency; Regulatory Note- Isoxaflutole REG2000-16 (November 8, 2000). Available from: http://www.pmra-arla.gc.ca/english/pdf/reg/reg2000-16-e.pdf as of October 20, 2004.

|Warning|H361d ***: Suspected of damaging the unborn child [Warning Reproductive toxicity]|P201, P202, P273, P281, P308+P313, P391, P405, and P501|H361 (100%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]|Aggregated GHS information provided by 225 companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H361d: Suspected of damaging the unborn child [Warning Reproductive toxicity]

LD50 Rat oral >5000 mg/kg|LD50 Rabbit dermal >2000 mg/kg|LC50 Rat inhalation >5.23 mg/L 4 hr

Isoxaflutole's production may result in its release to the environment through various waste streams; it's 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 440(SRC), determined from a log Kow of 2.32(2) and a regression-derived equation(3), indicates that isoxaflutole is expected to have moderate mobility in soil(SRC). Neither isoxaflutole nor any of its metabolites were detected in the soil below 10 cm during a field dissipation study(4). Volatilization of isoxaflutole from moist soil surfaces is not expected to be an important fate process(SRC) given a Henry's Law constant of 1.85X10-10 atm-cu m/mole(2). Isoxaflutole is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 7.50X10-9 mm Hg(2). The half-life for the photolysis of isoxaflutole has been reported as 23 hours in soil(5). Half-lives of isoxaflutole in laboratory soil degradation studies range from 12 hours to 13.9 days(6,7,8). The effects of moisture and temperature on isoxaflutole degradation and the similarity of the degradation patterns between sterile and non-sterile samples indicate that chemical hydrolysis to the active product (2-cyano-3-cyclopropyl-1-(2-methylsulfonyl-4-trifluoromethylphenyl)-propane-1,3-dione) is the primary route of isoxaflutole degradation in soil(6-8). The half-lives for the conversion of isoxaflutole into its primary metabolite in the 0-10 cm surface soil layer of corn crops were between 9 and 18 days during a soil field dissipation study(4). The sum of isoxaflutole and this metabolite disappeared in the 0-10 cm layer with half-lives of 45-65 days(4).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 440(SRC), determined from a log Kow of 2.32(2) and a regression-derived equation(3), indicates that isoxaflutole may adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon a Henry's Law constant of 1.85X10-10 atm-cu m/mole(2). According to a classification scheme(4), an estimated BCF of 34(SRC), from its log Kow(2) and a regression-derived equation(5), suggests the potential for bioconcentration in aquatic organisms is moderate(SRC). The half-lives reported for the hydrolysis of isoxaflutole in aqueous mineral buffered solutions were 433, 241, 95, 43, 65, and 5 hours at pH values of 5.2, 6.0, 7.2, 8.0, 8.3, and 9.3, respectively, at 22 °C(1). The half-lives at these same pH values were 182, 87, 18, 8, 9, and 1.2 hours, respectively, at 35 °C(6). The half-life for the photolysis of isoxaflutole has been reported as 6.7 days in water(7). Half-lives of isoxaflutole in laboratory soil degradation studies range from 12 hours to 13.9 days(8-10). The effects of moisture and temperature on isoxaflutole degradation and the similarity of the degradation patterns between sterile and non-sterile samples indicate that chemical hydrolysis to the active product (2-cyano-3-cyclopropyl-1-(2-methylsulfonyl-4-trifluoromethylphenyl)-propane-1,3-dione) is the primary route of isoxaflutole degradation in soil(8-10) and may also true for water(SRC).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), isoxaflutole, which has a vapor pressure of 7.50X10-9 mm Hg at 25 °C(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase isoxaflutole may be removed from the air by wet and dry deposition(SRC).

The half-lives reported for the hydrolysis of isoxaflutole in aqueous mineral buffered solutions were 433, 241, 95, 43, 65, and 5 hours at pH values of 5.2, 6.0, 7.2, 8.0, 8.3, and 9.3, respectively, at 22 °C(1). The half-lives at these same pH values were 182, 87, 18, 8, 9, and 1.2 hours, respectively, at 35 °C(1). Isoxaflutole hydrolysis half-lives have also been reported as 11.1 hours at pH 5, 20.1 hours at pH 7, and 3.2 hours at pH 9(2). The half-life for the photolysis of isoxaflutole has been reported as 6.7 days in water and 23 hours in soil(2).

An estimated BCF of 34 was calculated for isoxaflutole(SRC), using a log Kow of 2.32(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), provided the compound is not altered physically or chemically once released into the environment.

The Koc of isoxaflutole is estimated as 440(SRC), using a log Kow of 2.32(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that isoxaflutole is expected to have moderate mobility in soil. Neither isoxaflutole nor any of its metabolites were detected in the soil below 10 cm during a soil field dissipation study(4).

The Henry's Law constant for isoxaflutole is 1.85X10-10 atm-cu m/mole(1). This Henry's Law constant indicates that isoxaflutole is expected to be essentially nonvolatile from moist soil or water surfaces(2). Isoxaflutole is not expected to volatilize from dry soil surfaces(SRC) based upon a vapor pressure of 7.50X10-9 mm Hg(1).

The goats were dosed (balling gun) at a dietary burden of 10 ppm for seven days. The administered radioactivity was mainly eliminated via the urine and feces with the remaining radioactivity found in tissues, milk and cage wash and debris. Isoxaflutole was not identified in any of the tissues and milk. RPA 202248 was identified as a major component in all tissues, including milk. RPA 207048 was identified as a minor component in tissues and milk.

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

In a metabolism study /in rats/, 14C-isoxaflutole was rapidly and extensively absorbed and metabolized. ...Elimination was rapid and dose-dependent. The mean total recovery was 99.21%. Urinary eliminaton was predominant in the two low dose groups while the major portion of radiolabel was excreted via the feces in the high dose group. The higher fecal elimination possibly resulted from the saturation of absorption resulting in elimination of unchanged parent compound. The majority of the radiolabel was eliminated in the first 24 and 48 hours for the low and the high dose groups, respectively. The elimination half-lives were similar among single low and high dose groups, with an estimated mean blood half-life of 60 hours. No sex differences were observed in the metabolism of 14C-isoxaflutole.|Following oral administration, isoxaflutole is rapidly excreted.|The absorption, distribution, metabolism and excretion of 14C-phenyl labelled isoxaflutole (14C-RPA 201772, purity >98%) was examined in Sprague-Dawley (SD) rats. For the single oral low- and high-dose groups, five animals/sex received a single dose of either 1 or 100 mg/kg bw of 14C-RPA 201772, respectively, by oral gavage. For the repeat oral low-dose, another 5 animals/sex received a nonradiolabelled low dose (1 mg/kg bw) for 14 consecutive days followed by a single dose of 1.0 mg/kg bw of 14C-RPA 201772 by oral gavage. For blood pharmacokinetic experiments another 5 animals/sex received a single dose of 1.0 or 100 mg/kg bw 14C-RPA 201772 by oral gavage. All animals were sacrificed at 168 hr post-dosing. RPA 201772 was rapidly absorbed at both 1.0 and 100 mg/kg bw. The maximal whole blood concentration was achieved within 1 hr at both dose levels. On the basis of available urinary excretion data (radioactivity detected in urine, cage washes and tissues) the mean estimated proportion of the administered dose absorbed was approximately 39, 73 and 75% for the high-, low- and repeat-dose groups, respectively. Tissue distribution of radioactivity between the sexes appeared to be similar. In the high-dose group, the highest levels in both sexes were found in the blood and plasma and to a lesser extent in the liver and kidneys of males and in the liver, kidneys, lungs and heart of females. In the single and repeat low-dose groups, higher tissue concentrations were found in the liver and kidneys. Elimination was rapid and dose dependent. The major route of elimination in the high-dose group was via the feces (approximately 55-63% of the administered dose) and in the single and repeat low-dose groups was via the urine (68-74% of the administered dose). The majority of the activity was eliminated within 24 and 48 hr post-dosing for the low- and high-dose groups, respectively. The terminal elimination phase T½ was about 60 hr in both sexes at both dose levels. Higher fecal elimination at the high dose may be due to saturation of absorption, resulting in elimination of unchanged parent compound. Mean recovery of radioactivity in the tissues at 168 hr post-dosing was low, indicating that there was most likely a good systemic clearance of the test substance with little potential for accumulation. RPA 201772 was rapidly and extensively metabolized. The major metabolite was the diketonitrile RPA 202248 (70-85% of the administered dose). Minor metabolites included RPA 203328 (0.6-3.6% of the administered dose), RPA 207048, RPA 205834 and RPA 205568. The parent compound, RPA 201772, was only detected in fecal extracts in the single high-dose group during the first 24 hr. Data suggest that only Phase I reactions occurred; there was no indication of any metabolites resulting from Phase II (conjugation) reactions. ... . The absorption, distribution, metabolism and excretion were not influenced by repeat oral administration.|The goats were dosed (balling gun) at a dietary burden of 10 ppm for seven days. The administered radioactivity was mainly eliminated via the urine and feces with the remaining radioactivity found in tissues, milk and cage wash and debris. Isoxaflutole was not identified in any of the tissues and milk. RPA 202248 was identified as a major component in all tissues, including milk. RPA 207048 was identified as a minor component in tissues and milk.|For more Absorption, Distribution and Excretion (Complete) data for ISOXAFLUTOLE (6 total), please visit the HSDB record page.

Metabolism of isoxaflutole in ruminants proceeded via hydrolysis of the isoxazole ring to form RPA 202248 and RPA 205834 (further hydrolysed to produce RPA 207048).|In a metabolism study /in rats/, ...RPA 202248, a major metabolite, a diketonitrile derivative, represented 70% or more of the radioactivity excreted in the urine and feces from the two lowest dose groups. The other minor metabolite, RPA 203328, was more polar.|Metabolism of isoxaflutole in poultry involved hydrolysis of the isoxazole ring to form RPA 202248 and RPA 205834. Metabolite RPA 205834 was further hydrolysed to produce RPA 207048 (further degrades to RPA 203328) and RPA 203328. Hens were dosed (gelatin capsule) at a dietary burden of 10 ppm for 14 consecutive days.

...Estimated mean blood half-life of 60 hours /in rats/.

/SRP:/ Basic treatment: Establish a patent airway. 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 normal saline 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 ... . /Poison 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 respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

IFT cpd

Trade names: Balance, BalancePro|Water dispersible granules|Technical is about 98% pure.|Tradenames: Merlin; Alliance; Converge; Provence. Mixtures: Acajou (+aclonifen); Atoll (+atrazine); Lagon (+aclonifen); Cadou Star (+flufenacet); Epic (+flufenacet).|Formulation type: Water dispersible granule; Guarantee: 75% /isoxaflutole/. /Converge 75 WDG Herbicide/ /from table/

Preparation: P.A. Cain et al., EP 527036 (1993 to Rhone-Poulenc)

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

Isoxaflutole has known environmental transformation products that include Benzoic acid (RPA 203328), Diketonitrile (RPA 202248), and RPA 205834.