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Isoxaflutole

HCID 84098
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Basic information

CAS
141112-29-0
Standard SMILES
CS(=O)(=O)c1cc(C(F)(F)F)ccc1C(=O)c1cnoc1C1CC1
InChIKey
OYIKARCXOQLFHF-UHFFFAOYSA-N
Molecular formula
C15H12F3NO4S
Average molar mass
359.3 g/mol
Monoisotopic mass
359.04391352

Overview

Isoxaflutole can cause cancer according to The Environmental Protection Agency (EPA).

Names & identifiers

Preferred name
Isoxaflutole
IUPAC
(5-cyclopropyl-1,2-oxazol-4-yl)-[2-methylsulfonyl-4-(trifluoromethyl)phenyl]methanone
English name
ISOXAFLUTOLE
Molecular formula
C15H12F3NO4S
Molecular weight
359.32

Names & synonyms

Isoxaflutole141112-29-0MerlinBalanceIFT cpdDTXSID5034723EXP 31130ARPA 201772RP 2017720T9R0O0EYTRPA-201772264-EUP-99
Show more names
Hsdb 7275IsoxautoleSOXAFLUTOLEIsoxasoloneIsoxastrobone
DTXCID3014723CHEBI:1412135-cyclopropyl-1,2-oxazol-4-yl alpha,alpha,alpha-trifluoro-2-mesyl-p-tolyl ketone5-cyclopropyl-4-[2-methanesulfonyl-4-(trifluoromethyl)benzoyl]-1,2-oxazole(5-Cyclopropyl-4-isoxazolyl)(2-(methylsulfonyl)-4-(trifluoromethyl)phenyl)methanone5-CYCLOPROPYLISOXAZOL-4-YL 2-MESYL-4-TRIFLUOROMETHYLPHENYL KETONE(5-cyclopropyl-4-isoxazolyl)[2-(methylsulfonyl)-4-(trifluoromethyl)phenyl]methanone5-CYCLOPROPYL-4-(2-METHANESULFONYL-4-TRIFLUOROMETHYLBENZOYL)ISOXAZOLE

Database identifiers

CAS
141112-29-0
PubChem CID
84098
DTXSID
DTXSID5034723
ChEMBL
CHEMBL1887147
ChEBI
CHEBI:141213
UNII
0T9R0O0EYT
EC Number
604-222-4
Nikkaji
J794.343A

Properties

Computed structural propertiesFilling in

XLogP
2.4
Topological polar surface area
85.6 Ų
Hydrogen bond donors
0
Hydrogen bond acceptors
8
Rotatable bonds
4
Heavy atoms
24
Formal charge
0
Complexity
597

Experimental & physicochemical properties

DrugsPharmaceuticals -> Listed in ZINC15
pHpH = 4.6 at 25 °C
Pesticides · 6 items

Agrochemicals -> Pesticide active substances

Active substance -> EU Pesticides database: Approved

Pesticides -> Herbicides, Other

Herbicides

Environmental transformation -> Pesticides (parent, predecessor)

Pesticide (Isoxaflutole) -> USDA PDB

LogPlog Kow = 2.32
OdorSlight acetic acid-like odor /Technical/
Density1.590 g/cu cm
Color/Form · 2 items

Off-white or pale yellow solid

Granular powder

SolubilityIn water, 6.2 mg/L at pH 5.5 and 20 °C
Endocrine DisruptorsPotential endocrine disrupting compound

Safety & regulation

Safety information is for reference only and does not replace the supplier’s Safety Data Sheet (SDS), applicable regulations, or professional assessment.

GHS classification

GHS Classification · 6 items

Warning

H361d ***: Suspected of damaging the unborn child [Warning Reproductive toxicity]

P203, P273, P280, P318, P391, P405, and P501 (click each P-code to see the statement)

Warning

H361 (35.4%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]

P203, P273, P280, P318, P391, P405, and P501 (click each P-code to see the statement)

Hazard information

Regulatory Information · 4 items

Hazard Traits - Carcinogenicity

Commission Regulation No 844/2012

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

03/68/EC, Reg. (EU) 2016/950, Reg. (EU) 2017/841, Reg. (EU) 2018/917, Reg. (EU) 2019/717, Reg. (EU) No 540/2011, Reg. (EU) No 823/2012

Hazards SummaryLiver is target organ. [HSDB] May cause irritation; [MSDSonline]
Special ReportsHealth 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.
FIFRA Requirements · 2 items

Tolerances are established for combined residues of the herbicide isoxaflutole [5-cyclopropyl-4-(2-methylsulfonyl-4-trifluoromethyl benzoyl) isoxazole] and its metabolites 1-(2-methylsulfonyl-4-trifluoromethylphenyl)-2-cyano-3-cyclopropyl propan-1,3-dione (RPA 202248) and 2-methylsulphonyl-4-trifluoromethyl benzoic acid (RPA 203328), calculated as the parent compound, in or on the following raw agricultural commodities: corn, field, forage; corn, field, grain; and corn, field, stover.

Tolerances are established for combined residues of the herbicide isoxaflutole [5-cyclopropyl-4-(2-methylsulfonyl-4-trifluoromethyl benzoyl) isoxazole] and its metabolite 1-(2-methylsulfonyl-4-trifluoromethylphenyl)-2-cyano-3-cyclopropyl propan-1,3-dione (RPA 202248), calculated as the parent compound, in or on the following raw agricultural commodities: cattle, fat; cattle, liver; cattle, meat; cattle, meat byproducts, except liver; egg; goat, fat; goat, liver; goat, meat; goat, meat byproducts, except liver; hog, fat; hog, liver; hog, meat; hog, meat byproducts, except liver; horse, fat; horse, liver; horse, meat; horse, meat byproducts, except liver; milk; poultry, fat; poultry, liver; poultry, meat; sheep, fat; sheep, liver; sheep, meat; and sheep, meat byproducts, except liver.

Chemistry & industry

Pharmacology

Biological Half-Life...Estimated mean blood half-life of 60 hours /in rats/.
Metabolism/Metabolites · 3 items

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.

Absorption, Distribution and Excretion · 5 items

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.

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Compound notes

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Melting Point
138-138.5 °C
Vapor Pressure · 2 items

0.00000001 [mmHg]

7.5X10-9 mm Hg at 25 °C

Henry's Law ConstantHenry's Law constant = 1.85X10-10 atm-cu m/mol at 20 °C

Physicochemical properties

Melting point
138 · 138-138.5° (Cain); mp 140°
Boiling point
575.1 · 575.1±50.0 °C(Predicted)
Density
1.59 · 1.59
Flash point
130 °C · >130 °C
storage temp.
2 · Sealed in dry,2-8°C
solubility
Chloroform, DCM, Ethyl Acetate, Methanol
pka
-4.29 · -4.29±0.50(Predicted)
form
Solid
color
White
BRN
8344543 · 8344543
Henry's Law Constant
5.3 · 5.3×104 mol/(m3Pa) at 25℃, MacBean (2012)
Major Application
agriculturecleaning productscosmeticsenvironmentalfood and beveragespersonal care
InChI
InChI=1S/C15H12F3NO4S/c1-24(21,22)12-6-9(15(16,17)18)4-5-10(12)13(20)11-7-19-23-14(11)8-2-3-8/h4-8H,2-3H2,1H3
InChIKey
OYIKARCXOQLFHF-UHFFFAOYSA-N
SMILES
C(C1=C(C2CC2)ON=C1)(C1=CC=C(C(F)(F)F)C=C1S(C)(=O)=O)=O
LogP
2.32 · 2.320
CAS DataBase Reference
141112 · 141112-29-0
EWG's Food Scores
3 · 3
FDA UNII
0 T9R0O0EYT · 0T9R0O0EYT
Proposition 65 List
Isoxaflutole
Pesticides Freedom of Information Act (FOIA)
Isoxaflutole
EPA Substance Registry System
Isoxaflutole (141112-29-0)
UNSPSC Code
41116107 · 41116107
NACRES
24 · NA.24
Symbol(GHS)
8 · GHS08,GHS09
Signal word
Warning
Hazard statements
361 d-H410 · H361d-H410
Precautionary statements
202 · P202-P273-P280-P308+P313-P391-P405
PPE
3 · Eyeshields, Gloves, type P3 (EN 143) respirator cartridges
Hazard Codes
Xn,N
Risk Statements
50 · 50/53-63
Safety Statements
36 · 36/37-60-61
RIDADR
3077 · UN3077 9/PG 3
WGK Germany
3 · 3
Storage Class
11 · 11 - Combustible Solids
Hazard Classifications
1 Aquatic · Aquatic Acute 1Aquatic Chronic 1Repr. 2
Hazardous Substances Data
141112 · 141112-29-0(Hazardous Substances Data)
Toxicity
50 in · LD50 in rats, quails, mallard ducks (mg/kg): >5000, >2150, >2150 orally; in rabbits (mg/kg): >2000 dermally (Luscombe)
Hazard Classes and Categories · 3 items

Repr. 2 (35.4%)

Reproductive toxicity - category 2

Repr. 2

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

Safety & protection

Disposal Methods · 1 item

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.

Allowable Tolerances · 2 items

Tolerances are established for combined residues of the herbicide isoxaflutole [5-cyclopropyl-4-(2-methylsulfonyl-4-trifluoromethyl benzoyl) isoxazole] and its metabolites 1-(2-methylsulfonyl-4-trifluoromethylphenyl)-2-cyano-3-cyclopropyl propan-1,3-dione (RPA 202248) and 2-methylsulphonyl-4-trifluoromethyl benzoic acid (RPA 203328), calculated as the parent compound, in or on the following raw agricultural commodities: corn, field, forage 1.0 ppm; corn, field, grain 0.20 ppm; and corn, field, stover 0.50 ppm.

Tolerances are established for combined residues of the herbicide isoxaflutole [5-cyclopropyl-4-(2-methylsulfonyl-4-trifluoromethyl benzoyl) isoxazole] and its metabolite 1-(2-methylsulfonyl-4-trifluoromethylphenyl)-2-cyano-3-cyclopropyl propan-1,3-dione (RPA 202248), calculated as the parent compound, in or on the following raw agricultural commodities: cattle, fat 0.20 ppm; cattle, liver 0.50 ppm; cattle, meat 0.20 ppm; cattle, meat byproducts, except liver 0.10 ppm; egg 0.01 ppm; goat, fat 0.20 ppm; goat, liver 0.50 ppm; goat, meat 0.20 ppm; goat, meat byproducts, except liver 0.10 ppm; hog, fat 0.20 ppm; hog, liver 0.50 ppm; hog, meat 0.20 ppm; hog, meat byproducts, except liver 0.10 ppm; horse, fat 0.20 ppm; horse, liver 0.50 ppm; horse, meat 0.20 ppm; horse, meat byproducts, except liver 0.10 ppm; milk 0.02 ppm; poultry, fat 0.20 ppm; poultry, liver 0.30 ppm; poultry, meat 0.20 ppm; sheep, fat 0.20 ppm; sheep, liver 0.50 ppm; sheep, meat 0.20 ppm; and sheep, meat byproducts, except liver 0.10 ppm.

Toxicology

Ecotoxicity Values · 5 items

LD50 Bee contact >100 ug/bee

LC50 Anas platyrhynchos (Mallard duck, age 5 days) dietary >4255 ppm (8 days)[USEPA, Office of Pesticide Programs; Pesticide Ecotoxicity Database (2000) on (5-Cyclopropyl-4-isoxazolyl)

LD50 Anas platyrhynchos (Mallard duck, age 2 wk) oral >2150 mg/kg[USEPA, Office of Pesticide Programs; Pesticide Ecotoxicity Database (2000) on (5-Cyclopropyl-4-isoxazolyl)

LD50 Colinus virginianus (Northern bobwhite, age 26 wk) oral >2150 mg/kg[USEPA, Office of Pesticide Programs; Pesticide Ecotoxicity Database (2000) on (5-Cyclopropyl-4-isoxazolyl)

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

Environmental Fate · 3 items

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).

Adverse EffectsOccupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.
Milk Concentrations · 1 item

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.

Soil Adsorption/Mobility · 1 item

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).

Artificial Pollution SourcesIsoxaflutole'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).
Environmental Biodegradation · 3 items

AEROBIC: The half-life for the aerobic soil metabolism of isoxaflutole has been reported as 2.4 days(1). Half-lives for the terrestrial field dissipation of this compound have been reported to range from 1.4 to 3.0 days(1). Additional information regarding these values were not provided(1). The effects of temperature and moisture on isoxaflutole degradation have been studied(2-4). During a controlled laboratory soil degradation study, half-lives of 1.5 and 2.4 days were measured at moisture contents of -100 kPa (25%) and -1500 kPa (13%), respectively, while the half-life in air-dry soil (3% moisture content) was reported as 9.6 days(2). No mineralization was observed in the air-dry soil, although degradation was rapid after water was added (-100 kPa) to an air dry soil sample on day 14(2). Half-lives reported in a similar study were 67, 49, and 33 hours at moisture contents of 17, 29, and 45%, respectively(3). A third laboratory study reported half-lives of 24, 24, 22, and 19 hours in sandy loam at moisture content 5, 10, 20, and 30%, respectively, and an application rate of 100 g/ha(4). Half-lives in sandy loam at these moisture contents were 41, 36, 32, and 29 hours, respectively, for a 750 g/ha application rate using a water dispersible granule formulation(4). Half-lives in clay loam at moisture contents <2, 10, 20, and 30% were 144, 33, 20, and 12 hours, respectively, for a 250 g/ha application rate(4). Isoxaflutole degradation was inversely affected by changes in temperature. Half-lives were 13.9 days at 5 °C, 3.3 days at 15 °C, 1.3 days at 25 °C, and 0.8 days at 35 °C(2). The activation energy calculated from the rate constants at these temperatures was 67 kJ/mol(2). The authors reported that an activation energy above 60 kJ/mol and responsiveness to changes in temperature such as was observed with isoxaflutole are indicative of a chemically controlled process as opposed to an enzyme-mediated biological process(2).

AEROBIC: Half-lives observed in sterile and non-sterile soils were similar (1.8 days and 1.4 days, respectively)(1). Four percent mineralization was observed in the non-sterile soil by day 56 while no mineralization was observed in the sterile soil throughout the experiment(1). Based on the data from these tests, the authors concluded 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 the environment(1-3). Any mineralization observed was considered to be from the degradation of this active product while forming inactive metabolites through biological processes(1). An activation energy of 81.2 kJ/mol, calculated using isoxaflutole degradation rate constants measured at various temperatures in non-sterile soil, was similar to a value of 82.4, calculated from degradation rates in sterile aqueous solutions(2). 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).

Carcinogen ClassificationNot listed by IARC.
Environmental Bioconcentration · 1 item

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.

Volatilization from Water/Soil · 1 item

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).

Non-Human Toxicity Excerpts · 5 items

/LABORATORY ANIMALS: Acute Exposure/ Not a skin irritant; minimal eye irritation (rabbits). Not a skin sensitiser.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ In a 90-day dietary study, groups of 10 CD rats/sex/dose received either 0, 1.0, 3.0, 10 or 100 mg/kg bw/day isoxaflutole (purity 99.4%) via dietary administration daily for 13 weeks and three days. There were no treatment-related mortalities and no treatment-related effects on body weight, body-weight gain, food consumption or food efficiency. There were no significant treatment-related effects on hematological, clinical chemistry or urinalysis parameters examined. Treatment-related findings in males at 100 mg/kg bw/day included increased absolute and relative liver weights, with an associated increased incidence of periacinar hepatocytic hypertrophy; these were considered to be an adaptive response and not adverse. Significant treatment-related clinical, ophthalmoscopic, gross pathological and histopathological findings were observed in the eye in males at 10 mg/kg bw/day and in both sexes at 100 mg/kg bw/day. Clinical and ophthalmoscopic observations included increased incidences of bilateral and unilateral opaque eyes and focal corneal opacity, respectively. Focal corneal opacity was first apparent during week 3 and persisted throughout the study. Significant gross pathological observation included an increased incidence of corneal opacity (unilateral and bilateral) in both sexes at 100 mg/kg bw/day. The overall incidence of corneal lesions was similar in both sexes, although the severity of the lesions was more significant in the males. The most notable histopathological findings included vacuolation (males and females) and superficial exfoliation of the epithelial cells (males and females), epithelial thickening (males), necrosis and inflammation (males and females), subepithelial fibroblastic reaction (males and females) and vascularization of the stroma (males and females). The changes were considered by the study author to be reversible after a short recovery period following cessation of treatment in the previous study..., with the exception of residual evidence of tissue repair detectable only by histopathological examination. There were no treatment-related effects at 1.0 or 3.0 mg/kg bw/day; therefore, the NOEL for isoxaflutole was 3.0 mg/kg bw/day.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ In a 28-day preliminary dietary study, groups of 10 male or female CD-1 mice received isoxaflutole (99.9% purity) via dietary administration at concentrations of 0, 175, 700, 2800 or 7000 ppm daily for 28 days. The dose levels were equal to 0, 29.4, 120.7, 474.6 and 1140.1 mg/kg bw/day in males and 0, 34.7, 142.9, 534.4 and 1347.4 mg/kg bw/day in females. There were no treatment-related mortalities, clinical or ophthalmoscopic observations or treatment-related effects on body weight, body-weight gain or food consumption. The liver appeared to be the target organ. Significant treatment-related clinical chemistry findings included increased alanine aminotransferase (ALAT) (males at 2800 and 7000 ppm and females at 700, 2800 and 7000 ppm) and aspartate aminotransferase (ASAT) (males at 2800 and 7000 ppm and females at 7000 ppm) activity. Increased liver weights were observed at all dose levels in both sexes. Significant treatment-related gross pathological observations were noted in the liver and included enlarged liver (males at 700, 2800 and 7000 ppm and females at 2800 and 7000 ppm) and white striations (both sexes at 7000 ppm). Treatment-related histopathological findings in the liver included centrilobular hepatocellular hypertrophy (both sexes at 700 ppm and above) and hepatocellular necrosis (males at 2800 and 7000 ppm and females at 7000 ppm). Other histopathological findings included increased extramedullary hematopoiesis in spleen(both sexes at 7000 ppm) and X-zone cell vacuolation in the adrenal glands (females at 7000 ppm). In the absence of any other significant findings at 175 ppm, the increased liver weights were considered a minor adaptive change; therefore, the no observed adverse effect level (NOAEL) was 175 ppm, equal to 29 mg/kg bw/day in males and 35 mg/kg bw/day in females.

Evidence for CarcinogenicityCancer Classification: Likely to be Carcinogenic to Humans

Regulatory information

FIFRA Requirements · 2 items

Tolerances are established for combined residues of the herbicide isoxaflutole [5-cyclopropyl-4-(2-methylsulfonyl-4-trifluoromethyl benzoyl) isoxazole] and its metabolites 1-(2-methylsulfonyl-4-trifluoromethylphenyl)-2-cyano-3-cyclopropyl propan-1,3-dione (RPA 202248) and 2-methylsulphonyl-4-trifluoromethyl benzoic acid (RPA 203328), calculated as the parent compound, in or on the following raw agricultural commodities: corn, field, forage; corn, field, grain; and corn, field, stover.

Tolerances are established for combined residues of the herbicide isoxaflutole [5-cyclopropyl-4-(2-methylsulfonyl-4-trifluoromethyl benzoyl) isoxazole] and its metabolite 1-(2-methylsulfonyl-4-trifluoromethylphenyl)-2-cyano-3-cyclopropyl propan-1,3-dione (RPA 202248), calculated as the parent compound, in or on the following raw agricultural commodities: cattle, fat; cattle, liver; cattle, meat; cattle, meat byproducts, except liver; egg; goat, fat; goat, liver; goat, meat; goat, meat byproducts, except liver; hog, fat; hog, liver; hog, meat; hog, meat byproducts, except liver; horse, fat; horse, liver; horse, meat; horse, meat byproducts, except liver; milk; poultry, fat; poultry, liver; poultry, meat; sheep, fat; sheep, liver; sheep, meat; and sheep, meat byproducts, except liver.

Safety data

PPE
Eyeshields, Gloves, type P3 (EN 143) respirator cartridges
wgk
3
ridadr
UN3077 9/PG 3
Toxicity
LD50 in rats, quails, mallard ducks (mg/kg): >5000, >2150, >2150 orally; in rabbits (mg/kg): >2000 dermally (Luscombe)
risk_code
50/53-63
Signal word
Warning
Symbol(GHS)
GHS08,GHS09
hazard_code
Xn,N
safety_code
36/37-60-61
Storage Class
11 - Combustible Solids
Hazard statements
H361d-H410
Hazard Classifications
Aquatic Acute 1Aquatic Chronic 1Repr. 2
Precautionary statements
P202-P273-P280-P308+P313-P391-P405
Hazardous Substances Data
141112-29-0(Hazardous Substances Data)

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.

Uses & manufacturing

Uses · 5 items

Used as pre-emergence herbicide for maize; [Merck Index]

Farming (Pesticides) [Category: Industry]

For isoxaflutole (USEPA/OPP Pesticide Code: 123000) ACTIVE products with label matches. /SRP: Registered for use in the U.S. but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses./

Herbicide; for use on corn fields

This is a man-made compound that is used as a pesticide.

Methods of ManufacturingIsoxaflutole is produced by reaction of 1-(4-trifluoromethyl-2-methylsulfonylphenyl)-3-cyclopropyl-2-ethoxymethylenepropane-1,3-dione with hydroxylamine.
Formulations/Preparations · 5 items

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/

Use Classification · 2 items

Herbicides

Environmental transformation -> Pesticides (parent, predecessor)

General Manufacturing InformationPreparation: P.A. Cain et al., EP 527036 (1993 to Rhone-Poulenc)
Applications · 3 items

DescriptionIsoxaflutole is a 4-benzoyl isoxazole molecule and is used as a pre- and early post-emergence herbicide for the control of a wide range of important broadleaf and grass weeds in maize (Zea mays), both in Europe and in North America. It is also registered for use in sugarcane in Central and South America (2–4). It causes characteristic bleaching of newly developed tissues of susceptible species followed by growth cessation and necrosis. Marketed as Balance for corn (maize) in the United States, and Merlin for corn in Europe; and in sugarcane, it mixes well with metolachlor, acetochlor, dimethenamid, and atrazine to complete the weed spectrum and to reduce the application rates of the latter compounds (2). Isoxaflutole also controls triazineresistant weeds in the field (4).

UsesIsoxaflutole is an pesticide used to selectively control both grass and broad-leaved weeds in maize and sugar cane. Isoxaflutole is known to work by inhibiting the enzyme 4-Hydroxyphenylpyruvate dioxygenase (HPPD) which results in the disruption of pigment biosynthesis.

UsesHerbicide.

Upstream & downstream products

Upstream raw materials

Cyclopropyl methyl ketoneBenzonitrile, 2-(methylthio)-4-(trifluoromethyl)-2-Methylthio-4-trifluoroMethylbenzoic Acid Methyl Ester2-NITRO-4-(TRIFLUOROMETHYL)BENZONITRILE
Additional notes · 1 item

DefinitionChEBI: Isoxaflutole is a member of the class of isoxazoles that is 1,2-oxazole substituted by a 2-(methanesulfonyl)-4-(trifluoromethyl)benzoyl group and a cyclopropyl group at positions 4 and 5, respectively. It is a 4-hydroxyphenylpyruvate dioxygenase inhibitor which is used as a herbicide for weed control in maize and sugarcane. It has a role as an EC 1.13.11.27 (4-hydroxyphenylpyruvate dioxygenase) inhibitor, a proherbicide and an agrochemical. It is a member of cyclopropanes, a member of isoxazoles, an aromatic ketone, a member of (trifluoromethyl)benzenes and a sulfone.

ANAEROBIC: The half-life for the anaerobic aquatic metabolism of isoxaflutole was reported to be less than 2 hours(1).

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ In a 28-day oral subchronic toxicity study, RPA 203328 (a metabolite of isoxaflutole) was administered in the diet to male and female rats. There were no compound related adverse effects on survival, clinical signs, body weight, food consumption, clinical chemistry, hematology, and gross or microscopic pathology. The LOAEL is >1,117.79 mg/kg/day in males and 1,268.73 mg/kg/day in females. The NOEL for both sexes is 1,117.79 mg/kg/day in males and 1,268.73 mg/kg/day in females. /RPA 203328 (metabolite)/

For more Non-Human Toxicity Excerpts (Complete) data for ISOXAFLUTOLE (18 total), please visit the HSDB record page.