CALIFORNIA DEPARTMENT OF PESTICIDE REGULATION

PUBLIC REPORT 2003-6

Flumioxazin

Tracking ID Number 191861 N

DESCRIPTION OF ACTION

Valent U.S.A. Corporation submitted an application seeking California registration of

Chateau™ Herbicide SW to control certain grassy and broad-leaf weeds in various

agricultural crops. This product contains the new active ingredient flumioxazin.

The Department of Pesticide Regulation (DPR) evaluated the product label and scientific

data supporting registration of the product and found them to be acceptable to support a

conditional registration. The acute health risks from exposure to flumioxazin are

minimal due in part to its low mammalian toxicity. The precautionary and first aid

statements on the product label in conjunction with the required personal protective

equipment (PPE) adequately mitigate potential health risks to persons who may come in

contact with the pesticide. DPR does not expect significant adverse environmental

impacts to result from registration of this product.

DPR accepted Valent’s application for registration of Chateau™ Herbicide SW

concurrently with Valent’s submission of an application to the United States

Environmental Protection Agency (U.S. EPA) for federal registration. U.S. EPA

conditionally registered Chateau™ Herbicide SW on April 12, 2001. The Agency

required the following studies be submitted within two years or the registration will be

subject to cancellation: a more specific confirmatory analytical method for plant

commodities, two aqueous photolysis studies, two anaerobic soil/aqueous metabolism,

and two field dissipation studies. These studies have since been completed and reviewed

by DPR.

BACKGROUND

Registrant:

Valent U.S.A. Corporation

Common name:

Flumioxazin

Chemical name:

2-[7-fluro-3,4-dihydro-3-oxo-4-(2-propynyl)-2H-1,4-benzoxazin-

6-yl]-4,5,6,7-tetrahydro-1H-isoindole-1,3(2H)-dione

Brand names:

Chateau™ Herbicide SW

Uses:

Weed control in peanuts and soybeans and sites to be planted to

cotton, field corn, rice, sorghum, sugarcane, sunflowers, tobacco

or wheat.

Pests controlled:

Certain grassy and broad-leaf weeds, such as crabgrass, Russian

thistle, and velvetleaf.

Type of registration: Conditional for two years

Chateau™ Herbicide SW is formulated as a water dispersible granule with 51%

flumioxazin. Flumioxazin is a light-dependent peroxidizing herbicide that blocks

chlorophyll biosynthesis resulting in the accumulation of photo-toxic porphyrins in the

plant tissues. Flumioxazin is active on a broad spectrum of broad-leaf weeds and some

grassy weeds. Chateau™ Herbicide SW can be applied in peanuts and soybeans prior to

crop emergence to control existing weeds. Rainfall, a light irrigation or cultivation are

needed to activate flumioxazin. Chateau™ Herbicide SW can also be applied as a

“burndown” treatment on sites that will later be planted with the crops listed on the

product label. In California, the predominant use will probably be to “burndown” weeds

before planting cotton, field corn, rice, sorghum, sunflowers, or wheat. The label

recommends applying 2 to 3 ounces of product per acre (0.064-0.096 lb. active

ingredient) with one application per year. Applications can be made with ground and

aerial application equipment. However, application of the product through any type of

irrigation system is prohibited. For aerial applications, the product label requires a 40

foot buffer zone between the target crop and non-labeled crops and plants to mitigate the

potential for crop damage from drift.

SCIENTIFIC REVIEW

A. Chemistry

1. Product Chemistry: DPR evaluated the submitted chemistry studies for

flumioxazin and summarized the results in the following table.

Table I. Physical and Chemical Properties of Chateau™ Herbicide SW

Properties

Values

Physical state

Light tan solid

Odor

Odorless

Density*

1.51 g/cm3 at 20o C

Bulk density

0.37 g/ml (22.8 lb. ft3)

Partition Coefficient*

3.54 x 102 at 20o C

Solubility (water)*

1.79 mg/L at 25o C

pH in water

6 at 22o C

Vapor pressure*

2.41 x 10-6 mm Hg at 22o C

Stability

Stable one year in commercial pkg.

* These properties were derived using technical flumioxazin as the test substance.

DPR found the product chemistry data satisfactory to meet the regulatory data

requirements to support the registration of this product.

2. Residues in Food and Animal Feed: The submitted residue studies support the

harvest and use limitations listed on the Chateau™ Herbicide SW label for peanuts

and soybeans. The residue levels are well within the tolerances established by the

U.S. EPA for peanuts and soybeans. The established tolerances are listed in the

following table.

Table II. Tolerances for Residues of Flumioxazin

Commodity

Parts Per Million

Peanuts

0.02

Soybean seed

0.02

Valent U.S.A. Corporation submitted rotational crop studies to support the

“burndown” uses for the listed crop sites and the rotational crop statements for non-

listed crops. DPR determined the data to be adequate.

3. Environmental Fate: The environmental fate data reviewed included studies on

hydrolysis, photolysis (aqueous and soil), aerobic soil metabolism, anaerobic soil

metabolism (aquatic) and terrestrial field dissipation. Flumioxazin is unstable in the

environment with a half-life ranging from 0.01-5 days depending upon pH. The data

indicates hydrolysis is probably the primary pathway for degradation. Flumioxazin is

unstable in the presence of light with a one day half-life in water and 3-8 day half-life

on soil. The aerobic soil metabolism studies observed a moderate rate of metabolism

with a half-life of 5-19 days depending on the soil type. The anaerobic soil

metabolism study with a saturated soil observed a half-life of less than one day.

Terrestrial field dissipation of flumioxazin in loam and sandy soils ranged from 10-42

days. The high value was thought to be due to a lack of rainfall or irrigation during

the sampling period. The degradation of flumioxazin on soil was too rapid to

determine an adsorption/desorption coefficient. Two soil column leaching studies

were conducted using various types of agricultural soils. The majority of the residues

remained incorporated with the organic matter in the soil indicating flumioxazin

resists leaching.

The submitted studies were found to be satisfactory to support a conditional

registration of Chateau™ Herbicide SW. This product may be registered, provided

the registrant conducts and submits the results of a flumioxazin metabolite study in

lactating goats and a terrestrial field dissipation study (now in progress). Chateau™

Herbicide SW is expected to have minimal impact on the environment. When used in

accordance with label directions, there is little potential for flumioxazin to accumulate

or move into ground water.

B. Toxicology

DPR reviewed the toxicology studies submitted by Valent U.S.A. Corp. and found

them adequate to conduct a complete toxicological evaluation for Chateau™

Herbicide SW. DPR evaluated the data to ascertain the potential for acute adverse

health effects from exposure. The acute toxicity parameters are summarized in Table

III.

Page   4

Table III. Acute Toxicity of Chateau™ Herbicide SW

Type of Study

Acute Toxicity Values Acute Toxicity Category

Acute oral (rats)

>5000 mg/kg (M/F)

IV

Acute dermal (rabbits)

>2000 mg/kg (M/F)

III

Acute inhalation (rats)

>0.969 mg/l

III

Primary eye irritation (rabbits)

N/A

IV

Primary dermal irritation (rabbits)

N/A

IV

Dermal sensitization (guinea pigs)

N/A

Not a sensitizer

Signal word

N/A

CAUTION

N/A-Not applicable.

DPR’s evaluation indicates that Chateau™ Herbicide SW is low in mammalian

toxicity. The precautionary language on the product label adequately identifies the

acute toxicity hazards noted in the studies.

DPR found the submitted toxicology studies sufficient to satisfy the data

requirements of the Birth Defects Prevention Act (Food and Agricultural Code

section 13121 et.al.). Possible adverse health effects were observed in four of the

toxicity studies. A combined chronic toxicity and oncogenicity study in rats indicated

hypochronic and microcytic anemia. The subchronic dietary rat study noted adverse

effects of anemia and hepatic necrosis. The two-generation rat reproduction study

observed lower pup viability. The rat teratology studies observed malformations in

cardiac and skeletal development. A neurotoxicity study was not submitted. The

Code of Federal Regulations (CFR 40 section 158.340) does not require this study if

the compound is not an organophosphate compound, or does not cause cholinesterase

depression.

DPR has not yet prioritized flumioxazin for risk assessment. DPR prioritizes

pesticide active ingredients for risk assessment based on the nature of the potential

adverse health effects, number of potential adverse effects, number of species

affected, no effect levels (NOELs), potential for human exposure, use patterns and

similar factors. Based on these criteria, pesticides with the greatest potential for

health problems are placed in high priority, with other chemicals being in moderate or

low priority. The purpose of the risk assessment would be to appraise the potential

for flumioxazin to cause adverse health effects in humans if exposed to the pesticide

as the result of a legal use. The potential for exposure from eating food crops treated

with flumioxazin will also be evaluated during the risk assessment. Further toxicity

information is available in DPR’s Summary of Toxicology Data for flumioxazin,

available on DPR public website at:

http://www.cdpr.ca.gov/docs/toxsums/pdfs/5802.pdf.

C. Health & Safety

An evaluation of the medical management information on the Chateau™ Herbicide

SW label and the acute toxicity study results indicate the product label bears all of

the required statements and warnings regarding safety for handlers and other persons

who may be exposed to the pesticide. The product label bears an adequate First Aid

Statement. In addition, the product label requires persons handling and applying

Chateau™ Herbicide SW to wear long-sleeved shirt and long pants, waterproof

gloves, and shoes plus socks. Workers wearing only work clothing are not allowed

to enter a treated field until 12 hours after an application. The product label requires

that persons entering a treated area before the 12 hour restricted-entry interval (REI)

has elapsed, must wear coveralls, waterproof gloves, and shoes plus socks if they are

going to contact treated plants, soil or water.

D. Fish & Wildlife

The registrant submitted fish and wildlife toxicity studies, including studies on

northern bobwhite, mallard duck, rainbow trout, bluegill sunfish and daphnia magna.

The submitted data are adequate to characterize the toxicity to wildlife and aquatic

animals from an environmental exposure. Table IV summarizes the results of these

studies.

Table IV. Summary of Toxicity Studies for Wildlife

Test Animal

Type of Study

Acute Toxicity Valuea

Relative Toxicity

Rat (male, female)

Single acute oral dose

>5000 mg/kg(LD50)

Relatively non-toxic

Bluegill sunfish

Water exposure (96 hrs.) >21 mg a.i./l (LC50)

Slightly toxic

Sheepshead minnow Water exposure (96 hrs.) 4.7 mg a.i./l (LC50)

Moderately toxic

Rainbow trout

Water exposure (96 hrs.) >2.3 mg a.i./l (LC50)

Moderately toxic

Daphnia magna

Water exposure (48 hrs.) 17 mg a.i./l (LC50)

Slightly toxic

Mysid shrimp

Water exposure (96 hrs.) 0.23 mg a.i./l (LC50)

Highly toxic

Oyster shell

Water exposure (96 hrs.) 2.8 mg a.i./l (EC50)

Moderately toxic

Bobwhite quail

Single oral acute dose

>2250 mg/kg (LD50)

Relatively non-toxic

Bobwhite quail

Feeding study (8 days)

>5620 mg/kg (LC50)

Relatively non-toxic

Mallard duck

Feeding study (8 days)

>5620 mg/kg (LC50)

Relatively non-toxic

Honeybee

Single dermal dose

105 µg/bee (LD50)

Relatively non-toxic

Values expressed as: 1. LD50= lethal dose that will kill 50% of test population; and 2. LC50= lethal

environmental concentration that will kill 50% of test population. The test substance used for the

studies was technical flumioxazin.

The data indicate flumioxazin is relatively non-toxic to vertebrate animals, birds and

honey bees, and moderately toxic to fish. The data indicate that flumioxazin is highly

toxic to some salt water invertebrates. The label bears adequate precautionary

statements regarding the toxicity of the product to aquatic invertebrates. The

environmental fate data indicates flumioxazin is unstable in the environment and

degrades rapidly. The water solubility is low with a very low vapor pressure

indicating movement off-site should be minimal. The use of Chateau™ Herbicide

SW in production agricultural sites is not expected to pose a threat to wildlife when

used in accordance with label directions.

E. Efficacy

The submitted field studies were adequate to demonstrate the efficacy of Chateau™

Herbicide SW to control the weeds listed on the label. The field data also indicate

that unacceptable levels of phytotoxicity do not occur when recommended rotational

intervals are followed on crops grown in midwestern or southern soil types.

However, no data were submitted to demonstrate that Chateau™ Herbicide SW can

be safely used on crops grown under California climatic conditions and soils.

The submitted data are adequate to support a two-year conditional registration in

California. Additional phytotoxicity data are needed to demonstrate the labeled

preplant intervals are adequate for crops grown in California. An aerial spray drift

study is also needed to support the adequacy of the required buffer zones for sensitive

crops growing adjacent to treatment sites..

ALTERNATIVES

Chateau™ Herbicide SW is a contact herbicide which is active on a wide range of broad-

leaf weeds and some grassy weeds. It can also be used in combination with other

herbicides to broaden the spectrum of weeds controlled with a “burndown” application.

With a maximum use rate of 1.5 oz of A.I. per acre, Chateau™ Herbicide SW can

provide weed control at much lower use rates than most conventional contact herbicides.

Its use can help to reduce the amount of herbicide needed for weed control in the labeled

crops. Flumioxazin is low in mammalian toxicity and is safer for pesticide handlers to

work with compared to many other contact herbicides.

CONCLUSION

DPR evaluated the product label and scientific data submitted to Chateau™ Herbicide

SW and found them acceptable to support a two year conditional registration. The acute

health risks to humans from exposure to flumioxazin are minimal due in part to its low

mammalian toxicity. The precautionary and first aid statements on the product label, as

well as the required PPE mitigate potential health risks to persons who may be exposed to

the pesticide. If, after a risk assessment, DPR determines that exposure to flumioxazin

may result in unacceptable margins of exposure, further restrictions will be placed on the

use of flumioxazin at that time. The submitted data also indicate significant adverse

environmental impacts are not expected to occur from the use of Chateau™ Herbicide

SW. When used in accordance with label directions, this product should be effective for

the intended use.

DPR is proposing a two-year conditional registration of Chateau™ Herbicide SW. The

registrant is required to conduct and/or submit the results of the following studies: a

terrestrial field dissipation study conducted in California, a metabolism study in lactating

goats, field data to support the aerial application buffer zones for sensitive crops, and

phytotoxicity data that demonstrates the preplant intervals for crops grown under

California climatic and soil conditions are adequate.