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Proposed Registration of the First Food Uses for the Herbicide Flazasulfuron on Citrus, 

Grapes and Sugarcane, as well as uses on Christmas Trees and Industrial Vegetation 

Management Areas

Regulatory Rationale

The Agency is proposing to grant the first food uses of the registered active ingredient, 

flazasulfuron, formulated as a technical product and an end use product. This registration action 

proposes first food uses on citrus, grapes and sugarcane, as well as uses on Christmas trees and 

industrial vegetation management areas. Flazasulfuron is currently registered for use on nonresidential turf including golf courses, sod farms, athletic fields, and commercial lawns (EPA 

Registration Number 71512-12).

I. Chemical Information

Chemical Name: Flazasulfuron (N-[[(4,6-dimethoxy-2-pyrimidinyl)amino]carbonyl]-3-

(trifluoromethyl)-2-pyridinesulfonamide)

EPA PC Code: 119011

Chemical Abstracts Service (CAS) Number: 104040-78-0

Mode of Action: Flazasulfuron is a systemic sulfonylurea (SU) herbicide that is absorbed both 

by roots and foliage and is translocated in the xylem and phloem. The mode of action is through 

the inhibition of the enzyme acetohydroxyacid synthase (AHAS; sometimes also referred to as 

“acetolactate synthase (ALS)”) leading to the blocking of the synthesis of the branch-chain 

amino acids such as valine, leucine, and isoleucine that are essential in the formation of new 

cells. 

Registrant: ISK Biosciences Corporation

Proposed Products: Technical Flazasulfuron (EPA Reg. No. 71512-11) is proposed for use in 

the formulation of the following proposed end-use product: 

ISK Flazasulfuron Herbicide (EPA Reg. No. 71512-RI) is formulated as a water 

dispersible granule and contains 25.0% of the active ingredient, flazasulfuron. Soil 

directed spray application for citrus and grapes and over-the-top applications and postdirected applications for sugarcane are proposed at a maximum rate of 0.15 lb ai/A per 

year. Over-the-top and soil directed spray applications are proposed for Christmas trees 

at rates of 0.033 – 0.045 lb ai/A/application. Application rates for vegetation 

management in nonagricultural areas are proposed at 0.047 lb ai/A/application where 

these applications may not be made near residential properties or near sensitive desired 

plants. 
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II. Human Health Risk 

A summary of the human health effects and risk of flazasulfuron as assessed in the Agency 

document entitled “Flazasulfuron: Human Health Risk Assessment for Proposed Uses on Citrus, 

Grapes, Sugarcane, Christmas Trees, and Industrial Vegetation” is provided below.

A. Summary of Toxicological Effects

The existing toxicology database is deemed sufficient for characterizing the hazard of 

flazasulfuron. The database consists of an acute neurotoxicity study in the rat, 90-day oral 

studies in the rat and dog, a 21-day dermal study in the rabbit, developmental studies in the rat 

and rabbit, a multi-generation study in the rat, chronic/cancer studies in the rat and mouse, a 

battery of in vitro and in vivo mutagenicity studies, and a battery of metabolism and 

pharmacokinetics studies in the rat.

Flazasulfuron exhibits low acute toxicity via oral, dermal and inhalation routes of exposure. It is 

not irritating to the skin or eyes and is not a dermal sensitizer. Subchronic studies in animals 

indicated decreased body weight gain, slight anemia in rats, and liver abnormalities in dogs. 

Dermal or systemic toxicity was not seen in a subchronic dermal study in rabbits at dose levels 

up to the limit dose.

In the longer-term mammalian toxicity studies, the kidney and liver were the primary target 

organs of flazasulfuron toxicity. Observed effects included adverse changes in kidney function

(chronic nephropathy) and kidney physiology (enlargement, dark color of kidney), increases in 

liver weight and hepatocellular hypertrophy, increases in inflammatory cell infiltration, 

hepatocellular necrosis, hepatocellular swelling, and bile duct proliferation.

Developmental toxicity was observed in both rats and rabbits. Reduced fetal weights and delays

in ossification were seen in a developmental toxicity study with Sprague-Dawley rats; an 

increased incidence of visceral malformations (intraventricular septal defect) was seen in a 

developmental study with Wistar rats. The developmental study in rabbits showed high 

incidences of abortion at the highest dose tested. Decreases in body weight and chronic 

nephropathy were observed in offspring in a 2-generation rat reproduction toxicity study. The 

effects on offspring in these studies occurred at dose levels which were also toxic to the parents. 

A transient decrease in motor activity 5 hours post-dosing on Day 0 was observed at the middose in an acute neurotoxicity study. The effect was reversed by the next scheduled observation 

(Day 7), and neurohistopathologic evaluation of tissues from the central and peripheral nervous 

systems of high dose and control animals did not demonstrate any test material-related 

neurotoxic lesions. As such, this observation may be associated with a systemic effect and not 

with neurotoxicity.

There was no evidence of carcinogenicity in the mouse oncogenicity study or the combined 

chronic toxicity/carcinogenicity study in the rat and no evidence of genotoxic potential in in vitro 

and in vivo mutagenicity studies. Based on the results of these studies, EPA has classified 

flazasulfuron as “No evidence of carcinogenicity to humans.”
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B. FQPA Safety Factor

EPA has determined that reliable data show the safety of infants and children would be 

adequately protected if the FQPA SF for flazasulfuron were reduced to 1x. That decision is based 

on the following findings:

1. The toxicity database for flazasulfuron is complete except for an immunotoxicity study 

(OPPTS Guideline 870.7800) and a subchronic neurotoxicity study (OPPTS Guideline 

870.6200b). These studies are now requirements under 40 CFR §158.500 for pesticide 

registration. In the absence of specific immunotoxicity and subchronic neurotoxicity 

studies, EPA has evaluated the available flazasulfuron toxicity database to determine 

whether an additional database uncertainty factor is needed to account for potential 

immunotoxicity or neurotoxicity. 

With the exception of a transient decrease in motor activity at a high dose level (1000 

mg/kg/day) in the acute neurotoxicity study, which may be associated with a systemic 

effect, there is no evidence of neurotoxicity in the flazasulfuron toxicity database. There 

is no evidence of immunotoxicity in the database, as indicated by hematology, lymphoid 

organ weights and histopathology in standard studies. 

Consequently, EPA believes the existing data are sufficient for endpoint selection for 

exposure/risk assessment scenarios and for evaluation of the requirements under FQPA, 

and an additional database uncertainty factor is not needed to account for the lack of 

these studies.

2. There is no evidence of increased quantitative susceptibility of fetuses or offspring to 

flazasulfuron in any of the developmental or reproductive toxicity studies, since the 

effects on offspring occurred at dose levels which were also toxic to the parents. There is 

a potential concern for increased qualitative susceptibility of offspring based on the 

intraventricular septal defect seen in offspring at minimally toxic maternal dose levels in 

the Wistar rat developmental toxicity study; however, the concern for the increased 

susceptibility is low, and EPA did not identify any residual uncertainties after 

establishing toxicity endpoints and traditional uncertainty factors (UFs) to be used in the 

risk assessment for flazasulfuron. There was a clear “No Observed Adverse Effects 

Level” (NOAEL) and a clear “Lowest Observed Adverse Effects Level” (LOAEL) in the 

Wistar rat study, and thus the dose response for the observed effect is well defined. In 

addition, since the Agency is using points of departure (PODs) for risk assessment that 

are lower than the NOAEL in the Wistar rat study, the PODs are protective of the adverse 

developmental effect. 

3. There are no significant residual uncertainties in the exposure databases. Confirmatory 

data will be required to verify the reported storage intervals in the grape storage stability 

study, and a confined rotational crop study will be required to support an unconditional 

registration on sugarcane. Pending submission of the rotational crop data, the label will 

specify a 12-month interval between the last application of flazasulfuron to sugarcane and 

the planting of rotational crops to ensure that residues do not occur in the subsequently 

planted crops. 
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The dietary and non-dietary exposure estimates for flazasulfuron were based on several 

conservative assumptions. The dietary food exposure assessments were performed 

assuming tolerance-level residues and 100% crop treated for all commodities; and EPA 

made conservative (protective) assumptions in the ground and surface water modeling 

used to assess exposure to flazasulfuron in drinking water. These assessments will not 

underestimate the exposure and risks posed by flazasulfuron.

C. Toxicological End Points and Doses Used in the Human Health Risk Assessment

1. Acute Dietary, All Populations (including Females 13-49 years old): EPA established an 

acute reference dose (aRfD) and an Acute Population Adjusted Dose (aPAD) for flazasulfuron 

of 0.50 mg/kg body weight (wt), based on the NOAEL of 50 mg/kg body wt from the acute 

neurotoxicity study in rats and an uncertainty factor of 100. In this study, a transient decrease 

in motor activity was observed on Day 0 (5 hours post-dosing) at the LOAEL of 1000 mg/kg

body wt.

2. Chronic Dietary: EPA established a chronic reference dose (cRfD) and a Chronic Population 

Adjusted Dose (cPAD) for flazasulfuron of 0.013 mg/kg body wt/day, based on the NOAEL 

of 1.3 mg/kg body wt/day from the combined chronic toxicity/carcinogenicity study in rats 

and an uncertainty factor of 100. In this study, an adverse change in kidney function (chronic 

nephropathy) was observed at the LOAEL of 13.3 mg/kg body wt/day.

3. Short- and Intermediate-Term Incidental Oral: For short- and intermediate-term 

incidental oral exposure assessment, EPA selected the NOAEL of 2 mg/kg body wt/day from 

the subchronic (90-day) oral toxicity study in dogs, based on changes in the liver (increase in: 

deposition of brown pigments, glutamic pyruvic transaminase, creatine phosphokinase, 

inflammatory cell infiltration, and microgranulomas) observed at the LOAEL of 10 mg/kg 

body wt/day. However, since incidental exposure from the current and proposed uses of 

flazasulfuron is expected to be negligible, a quantitative exposure assessment using the 

selected endpoint and dose was not conducted.

4. Short- and Intermediate-Term Dermal: No hazard was identified at the limit dose (1,000 

mg/kg/day) following dermal exposure of rats in the 21-day dermal toxicity study, and there 

are no concerns for developmental toxicity (in the absence of maternal toxicity) or 

neurotoxicity; therefore, there is no risk potential for this exposure scenario.

5. Short- and Intermediate-Term Inhalation: For short- and intermediate-term inhalation 

exposure assessment, EPA selected the NOAEL of 2 mg/kg body wt/day from the subchronic 

(90-day) oral toxicity study in dogs, based on changes in the liver (increase in: deposition of 

brown pigments, glutamic pyruvic transaminase, creatine phosphokinase, inflammatory cell 

infiltration, and microgranulomas) observed at the LOAEL of 10 mg/kg body wt/day. An 

inhalation absorption rate of 100% was assumed in the exposure assessments. 

EPA’s Level of Concern (LOC) for short- and intermediate-term inhalation exposure is a 

Margin of Exposure (MOE; calculated as the NOAEL ÷ exposure) of 100; the LOC is based
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on the uncertainty factor of 100x (10x for extrapolation of animal data to humans 

(interspecies) and 10x to account for potential variation in sensitivity among members of the 

human population (intraspecies)). MOEs less than 100 represent a potential risk concern. 

6. Cancer

D. Aggregate Risk Assessment

: Based on a lack of evidence of carcinogenicity in the rat and mouse carcinogenicity 

studies and lack of a mutagenicity concern, flazasulfuron has been classified as “No evidence 

of carcinogenicity to humans.”

1. Dietary (Food + Drinking Water) Risk:

Acute and chronic dietary risk assessments were conducted using the Dietary Exposure 

Evaluation Model- Food Commodity Intake Database (DEEM-FCID, Version 2.03), which 

incorporates food consumption data from the USDA’s Continuing Surveys of Food Intakes by 

Individuals (CSFII) from 1994-1996 and 1998. As to residues in food, EPA assumed that 100% 

of citrus fruit, grape, and sugarcane commodities are treated with flazasulfuron and that residues 

on these commodities are present at the tolerance levels. Drinking water inputs were derived 

from screening-level water exposure models. These assumptions are considered to be highly 

conservative (i.e., protective).

Acute Dietary Risk: All acute analyses yielded risk estimates well below the threshold level of 

concern (100% of the aPAD) for each population subgroup. The acute aggregate dietary 

exposure to flazasulfuron from food and drinking water will occupy 1.1% of the aPAD for the 

general U.S. population. For the subgroup with the highest estimated exposure (infants <1 year 

old), acute aggregate dietary risk will occupy 4% of the aPAD.

Chronic Dietary Risk: Estimated chronic dietary exposure to flazasulfuron from food and 

drinking water will occupy 17% of the cPAD for the general U.S. population and 54% for infants 

less than 1 year old, the population subgroup with the highest estimated chronic exposure. 

Chronic dietary risk estimates are below the threshold level of concern (100% of the cPAD) for 

all population subgroups.

2. Residential Risk:

Flazasulfuron is currently registered for use on golf courses and other non-residential turf areas 

such as industrial parks, tank farms, sod farms, seed farms, and professionally managed sports 

fields. There is a potential for post-application short-term dermal exposure of adults and 

children entering recreation areas, including golf courses and sports fields, that have been treated 

with flazasulfuron. However, since no hazard associated with dermal exposure was identified in 

the toxicity database for flazasulfuron, flazasulfuron is not expected to pose a risk from postapplication dermal exposure. 

In accordance with current policy, EPA did not conduct a quantitative assessment of postapplication inhalation exposure to flazasulfuron; however, volatilization of pesticides may be a 

source of post-application inhalation exposure of individuals nearby pesticide applications. The 

Agency sought expert advice and input on issues related to volatilization of pesticides from its 
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Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (SAP) in 

December 2009, and received the SAP’s final report on March 2, 2010 

(http://www.epa.gov/scipoly/sap/meetings/2009/120109meeting.html). EPA is currently in the 

process of evaluating the SAP report and may, as appropriate, develop policies and procedures to 

identify the need for and, subsequently, the way to incorporate post-application inhalation 

exposure into the Agency's risk assessments. In the case of flazasulfuron, although EPA has not 

conducted a quantitative assessment of post-application inhalation exposure, the Agency’s 

concern for such exposures is low due to flazasulfuron’s low vapor pressure (< 1 x 10-7 torr) and 

low acute toxicity.

3. Aggregate Risk:

• Acute Risk: An acute aggregate risk assessment takes into account acute exposure estimates 

from dietary consumption of food and drinking water. As reported above in section D.1., 

estimated acute dietary exposure to flazasulfuron is low for all population subgroups (≤ 4% 

of the aPAD) and, therefore, not of concern.

 

• Chronic Risk: EPA has concluded that chronic exposure to flazasulfuron from food and 

water will utilize 54 % of the cPAD for infants less than 1 year old, the most highly exposed 

population subgroup. Chronic residential exposure to residues of flazasulfuron is not 

expected.

• Short-Term Risk: Short-term aggregate exposure takes into account short-term residential 

exposure plus chronic exposure from food and drinking water (considered to be a 

background exposure level). Although there is potential for short-term residential dermal 

post-application exposure to flazasulfuron, no short-term dermal hazard was identified for 

flazasulfuron; therefore, EPA relies on the chronic dietary risk assessment for evaluating 

short-term aggregate exposure to flazasulfuron.

• Intermediate-Term Risk: Intermediate-term aggregate exposure takes into account 

intermediate-term residential exposure plus chronic exposure from food and water 

(considered to be a background exposure level). Flazasulfuron is not registered for any use 

patterns that would result in intermediate-term residential exposure. Therefore, EPA relies 

on the chronic dietary risk assessment for evaluating intermediate-term aggregate exposure to 

flazasulfuron. 

• Aggregate Cancer Risk: Based on the lack of evidence of carcinogenicity in two adequate 

rodent carcinogenicity studies, flazasulfuron is not expected to pose a cancer risk to humans.

E. Cumulative Effects

Unlike other pesticides for which EPA has followed a cumulative risk approach based on a 

common mechanism of toxicity, EPA has not made a common mechanism of toxicity finding as 

to flazasulfuron and any other substances, and flazasulfuron does not appear to produce a toxic 

metabolite produced by other substances. For the purposes of this tolerance action, therefore, 

EPA has not assumed that flazasulfuron has a common mechanism of toxicity with other 
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substances. For information regarding EPA’s efforts to determine which chemicals have a 

common mechanism of toxicity and to evaluate the cumulative effects of such chemicals, see the 

policy statements released by EPA’s Office of Pesticide Programs concerning common 

mechanism determinations and procedures for cumulating effects from substances found to have 

a common mechanism on EPA’s website at http://www.epa.gov/pesticides/cumulative/.

F. Occupational Risk Assessment

1. Handler Exposure and Risk: 

EPA assessed short- and intermediate-term inhalation exposures of occupational handlers. 

Dermal exposures were not assessed, since a dermal hazard was not identified in the 

flazasulfuron database. Short- and intermediate-term MOEs for occupational handlers range 

from 1,400 (for mixer/loader/applicators using a low-pressure hand wand and making 

applications to Christmas trees or non-crop areas) to 97,000 (for mixing/loading dry flowable 

products for right-of-way applications). EPA is concerned when the MOE is less than 100. Since 

all MOEs are well above 100, short– and intermediate-term risks for handlers are not of concern. 

Short- and intermediate-term exposure and risk estimates are considered protective of potential 

intermediate-term exposure and risk.

2. Occupational Post-application Exposure and Risk: 

There is a possibility for agricultural workers to have post-application dermal exposure to 

flazasulfuron following its use on the proposed food crops. However, since a dermal hazard was 

not identified, post-application dermal exposure to flazasulfuron is not expected to pose a risk to 

workers.

A quantitative post-application inhalation exposure assessment was not performed for 

flazasulfuron. However, there are multiple potential sources of post-application inhalation 

exposure of individuals performing post-application activities in previously treated fields. These 

potential sources include volatilization of pesticides and resuspension of dusts and/or particulates 

that contain pesticides. The Agency sought expert advice and input on issues related to 

volatilization of pesticides from its Federal Insecticide, Fungicide, and Rodenticide Act 

Scientific Advisory Panel (SAP) in December 2009, and received the SAP’s final report on 

March 2, 2010 (http://www.epa.gov/scipoly/sap/meetings/2009/120109meeting.html). The 

Agency is in the process of evaluating the SAP report as well as available post-application 

inhalation exposure data generated by the Agricultural Reentry Task Force and may, as 

appropriate, develop policies and procedures to identify the need for and, subsequently, the way 

to incorporate occupational post-application inhalation exposure into the Agency's risk 

assessments. In the case of flazasulfuron, although EPA has not conducted a quantitative 

assessment of post-application inhalation exposure, the Agency’s concern for such exposures is 

low due to flazasulfuron’s low vapor pressure (< 1 x 10-7 torr) and low acute toxicity.
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III. Environmental Risk

A summary of the environmental fate and ecological effects and risks of flazasulfuron as 

assessed in the Agency document titled “Ecological Risk Assessment for First Food Uses on 

Citrus, Grapes and Sugarcane and New Outdoor Non-food Uses on Christmas Trees and 

Industrial Vegetation Management” is provided below.

A. Environmental Fate 

The most significant degradation pathway for flazasulfuron is hydrolysis with a half-life between 

15 and 18 days at environmentally relevant pHs. Parent flazasulfuron also degraded in photolysis 

and metabolism studies with similar half-lives; however, degradation in these studies was driven 

by hydrolytic processes. Major degradates of flazasulfuron, consisting primarily of bridgecontraction products including N-(4,6-dimethoxy-2-pyrimidinyl)-N-[3-(trifluoromethyl)-2-

pyridinyl]urea (DTPU) and 4,6-dimethoxy-N-[3-(trifluoromethyl)-2-pyridinyl]-2-

pyrimidinamine (DTPP), persist in hydrolysis and metabolism studies, but readily degrade via 

photolysis. The photolysis half-life for total toxic residues of flazasulfuron is 34 days. 

Degradates persist in all metabolism studies. 

Like all sulfonylurea herbicides, flazasulfuron can exhibit high mobility in soil. Flazasulfuron is 

a weak acid (pKa of 4.37) and the mobility of flazasulfuron is expected to increase with 

increasing pH. The pH of the environmental media (water column; soil/sediment) controls the 

persistence of the parent and the nature of transformation products. Flazasulfuron has low 

potential to volatilize from soil or water or to bioaccumulate. 

Flazasulfuron has the potential to leach to ground water or reach surface water by runoff. 

Therefore, exposure to flazasulfuron and transformation products would be expected in terrestrial 

and aquatic systems through ground deposition, spray drift, and runoff following ground spray 

application and spot application using backpack sprayers.

To address concerns with the potential leaching and runoff of flazasulfuron that may result from 

the mobility described above, labels are required to have language including a ground water 

advisory that describes the conditions that may promote leaching to groundwater. In addition,

spray drift management language and buffer restrictions are required. Required label language is 

described more fully under the “Regulatory Decision” section below.

B. Ecological Risk

Ecological risk characterization integrates the results of the exposure and ecotoxicity data to 

evaluate the likelihood of adverse ecological effects. The means of integrating the results of 

exposure and ecotoxicity data is called the quotient method. For this method, risk quotients 

(RQs) are calculated by dividing exposure estimates by ecotoxicity values, both acute and 

chronic (RQ = Exposure/Toxicity). RQs are then compared to EPA's levels of concern (LOCs). 

The LOCs are criteria used by the Agency to indicate potential risk to non-target organisms. The 

criteria indicate whether a pesticide, when used as directed, has the potential to cause adverse 

effects to non-target organisms. 
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A risk assessment of the proposed uses suggests, as explained below, that flazasulfuron presents 

potential risk to terrestrial and aquatic vascular plants, and thus to the organisms that depend on 

the plants for habitat and forage. Mitigation of this risk, in the form of data and labeling 

requirements, is discussed in section IV, below.

1. Risk to Birds:

Acute Risk: Available acute toxicity data for birds suggest that flazasulfuron is practically nontoxic to birds on acute oral and dietary bases. Study results indicate that the acute toxicity 

thresholds are greater than the highest concentrations tested (acute LD50 >2000 mg a.i./kg-bw 

and subacute dietary LC50 >5589 mg a.i./kg-diet). Since definitive acute toxicity thresholds were 

not established, acute avian RQs (dose- and dietary-based) were not estimated; however, since

no mortality or sub-lethal effects were observed in the studies, the potential risk to birds 

(surrogate for reptiles and terrestrial-phase amphibians) from the proposed new uses is presumed 

to be minimal. 

Chronic Risk: To evaluate the chronic risk of flazasulfuron to birds, dietary-based RQs were 

calculated using the bobwhite quail NOAEC of 484 mg/kg-diet. Based on the highest exposure 

scenarios for both application rates of 0.045 lb a.i./A and 0.047 lb a.i./A, the chronic RQs were 

all <0.1, with the highest RQ of 0.06 for 20g birds consuming short grass; therefore, chronic risk 

to birds from the proposed uses is presumed to be minimal. These RQs are below the LOC of 1.0 

and, therefore, not of concern.

2. Risk to Mammals:

Acute Risk: Flazasulfuron is practically non-toxic to mammals (LD50 = 5000 mg/kg-bw). The 

highest acute RQ was 0.01 for small mammals consuming short grass; since the RQ is below the 

LOQ of 0.5 acute risk to mammals from the proposed uses is presumed to be minimal. 

Chronic Risk: To evaluate the chronic risk to mammals, dose-based and dietary-based RQs were 

calculated using the rat NOAEL of 473 mg/kg bw/day (male) and NOAEC of 9,460 mg/kg-diet

from the 2-generation study in rats. Assuming maximum residue levels of the proposed new 

uses, the dietary-based risk quotients do not exceed the chronic LOC for mammals of 1.0. The 

highest dose-based chronic RQ was 0.03 for small mammals consuming short grass; therefore,

chronic risk to mammals from the proposed uses is presumed to be minimal. 

3. Risk to Pollinators and other Terrestrial Invertebrates:

Flazasulfuron is categorized as practically non-toxic to honeybees. The LD50 is greater than 

the maximum concentration tested (>100 μg a.i./bee). Precautionary labeling is not required for 

honeybees. Flazasulfuron poses minimal risk to earthworms since the LD50 is greater than the 

highest concentration tested (>15 mg a.i./kg soil). Based on these studies, minimal risk to honeybees and other terrestrial invertebrates is assumed from all the proposed flazasulfuron uses.
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4. Risk to Fish and Aquatic Invertebrates (Freshwater and Estuarine/Marine):

Acute Risk: Flazasulfuron is practically non-toxic to freshwater and marine fish and aquatic 

invertebrates on an acute exposure basis. The highest calculated RQ of 0.1 is less than the LOC 

of 0.5; therefore, acute risk to aquatic organisms is not expected from the proposed uses.

Chronic Risk: Following chronic exposure, a decrease in larval survival and hatching success 

was observed in freshwater fish. However, as the calculated RQ (less than 0.1) was less than the 

chronic risk LOC of 1.0 for all the proposed new uses, flazasulfuron is not expected to pose a 

risk to freshwater fish from chronic exposure. Estimated chronic effects for estuarine/marine fish 

and invertebrates are uncertain because no chronic data on saltwater species were submitted by 

the registrant. However, comparison of freshwater and saltwater species acute toxicity values 

does not suggest considerable differences in sensitivity between freshwater and saltwater 

species; therefore, chronic risk to estuarine/marine fish and invertebrates is not expected. 

5. Risk to Plants:

Terrestrial Plants: As is expected with herbicides, terrestrial plants are sensitive to flazasulfuron. 

Based on the proposed uses and the available toxicity information, the LOC was exceeded for 

non-listed and listed monocots and dicots located in adjacent areas and in semi-aquatic areas as 

the result of receiving a combination of runoff and spray drift from ground applications. In 

addition, the LOCs were exceeded for terrestrial plants receiving spray drift alone from ground 

application. 

Aquatic Plants: Aquatic vascular plants are more sensitive to flazasulfuron than aquatic 

nonvascular plants. LOCs for listed and non-listed aquatic vascular plants were exceeded for all 

proposed uses. The non-listed plant LOC is only exceeded for aquatic non-vascular plants grown 

adjacent to impervious surfaces in non-agricultural areas. The listed plant LOC is exceeded for 

aquatic non-vascular plants grown adjacent to impervious surfaces, citrus, sugarcane and 

Christmas trees sites from surface water runoff and spray drift. The LOC is not exceeded for 

aquatic non-vascular plants grown adjacent to non-impervious surfaces or grape sites. The 

green-algae (P. subcapitata) was the most sensitive non-vascular plant tested. The most 

sensitive aquatic vascular plant was duckweed (L. gibba).

To address and mitigate risks to non-target terrestrial, aquatic and semi-aquatic plants, spray drift 

language intended to keep the pesticide on the treatment area, thereby reducing the potential for 

non-target plant exposure, must be added to the labeling of flazasulfuron products, along with a 

buffer restriction. Required label language is described more fully under the “Regulatory

Decision” section below.
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IV. Proposed Regulatory Decision

The Agency is proposing to conditionally register products containing flazasulfuron to be used 

on citrus, grapes, sugarcane, Christmas trees and industrial vegetation management areas. As 

required by FIFRA, the Agency published a notice of receipt (NOR) of the registration 

application in the Federal Register of March 19, 2010 (75 FR 13,282). No comments were 

received in response to the notice of receipt. 

A. Data Requirements

The human health risk assessment concluded that the database is largely complete and adequate 

for a dietary, residential, and occupational risk assessment. The following studies are being 

required as a condition of registration, as the application for the proposed uses was submitted 

prior to the deadline of December 26, 2009 in which EPA began requiring all applications to 

include functional immunotoxicity and subchronic neurotoxity testing of all food and non-food 

use pesticides:

• 870.7800 Immunotoxicity. Although this study remains outstanding for flazasulfuron, 

there is no evidence that flazasulfuron targets the immune system, and the existing 

toxicology data for flazasulfuron are deemed adequate for endpoint selection; therefore, 

this study is not expected to alter the Agency’s risk conclusions for flazasulfuron.

• 870.6200 Neurotoxicity Battery (Subchronic Studies) The subchronic neurotoxicity 

screening battery is required to fulfill current 40 CFR Part 158 data requirements. Except 

for a transient decrease in motor activity observed at the highest dose tested in the acute 

neurotoxicity study, there is no evidence that flazasulfuron is a neurotoxic chemical, and 

EPA does not expect the subchronic neurotoxicity study to alter the Agency’s risk 

conclusions for flazasulfuron.

The environmental fate and effects review concluded that the database is adequate for a 

screening level assessment of the proposed uses. The following study is being required as a 

condition of registration:

163-1 Adsorption/Desorption: Adsorption/desorption data were submitted for flazasulfuron, 

providing sorption coefficients (Koc) for soils with a pH range of 4.9 to 7.6. However, based on 

data for other sulfonylurea chemicals, the mobility of flazasulfuron may increase in soils with 

higher pH. Adsorption/desorption data for parent flazasulfuron is not available for soils with a 

pH above 7.6 and data is unavailable for the degradates. Given this, EPA used modeling 

(EpiSuite) to estimate the Koc for each toxic residue of flazasulfuron using the lowest estimated 

Koc. The modeled Koc was in turn used in the tier II PRZM-GW model to estimate residues of 

flazasulfuron in groundwater used for drinking water. Despite the use of a modeled Koc, the 

drinking water assessment is considered protective because of the conservative characteristics of 

the PRZM-GW model and the assumptions EPA made in the assessment, including the 

following:
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• The PRZM-GW model is based on a rural drinking water well drawing from an 

unconfined high-water table aquifer in a pesticide use area. In fact, in many instances, 

drinking water is drawn from deeper wells not directly overlapping with a pesticide use 

area.

• The estimated drinking water concentration (EDWC) used to estimate exposure to 

flazasulfuron in drinking water was based on the most vulnerable crop scenario 

(Delmarva corn) and the leaching-prone meteorological data from Tallahassee, Florida 

(i.e., soil type and meteorological conditions most likely to promote leaching).

• The EDWC used in the drinking water exposure assessment included parent flazasulfuron 

and several degradates as well as unextracted (bound) residues that were assumed to be 

toxic residues. EPA used this conservative approach because toxicity data was not 

available for the degradates. In the absence of data, EPA assumed the degradates to be 

toxic and included them as residues of concern in drinking water.

The guideline requirements for an adsorption/desorption study do not specify the range of pHs to 

be tested. However, because mobility may increase at pHs above those tested in the submitted 

study, EPA will require adsorption/desorption data for flazasulfuron using batch equilibrium 

methods on additional soils representing a wider range of pHs as a condition of registration to 

confirm that the modeled Koc used in the drinking water exposure assessment is protective

The following ecological studies were initially listed as data gaps in the Ecological Risk 

Assessment dated May 4, 2011, but will only be required if the Registrant wishes to further 

refine the conservative assumptions used in the risk assessment.:

• 161-2 Photodegradation in Water: Available data on photodegradation in water provides 

sufficient modeling inputs for parent flazasulfuron. While no data are available for 

photodegradation in water of flazasulfuron degradates, which are more stable to 

hydrolysis, EPA made conservative (protective) assumptions in its modeling to ensure its 

assessment did not underestimate residues of flazasulfuron and its degradates in ground 

and surface water. If the Registrant wishes to reduce the uncertainty concerning 

estimated flazasulfuron total toxic residues in surface water and ground water, additional 

studies on the hydrolysis degradates DTPU and DTPP at the pH(s) at which they are the 

most stable to hydrolysis may be submitted.

• 162-1 Aerobic Soil Metabolism/162-4 Aerobic Aquatic Metabolism: The submitted 

aerobic soil metabolism study is currently considered supplemental because the study 

was not conducted long enough to capture the formation and decline of degradates. The 

submitted aerobic aquatic metabolism study is currently considered supplemental because

the test system was not incubated under aerobic conditions. However, in lieu of 

acceptable studies, EPA made conservative (protective) assumptions in its modeling to 

ensure that its assessment did not underestimate residues of flazasulfuron and its 

degradates in ground and surface water. If the Registrant wishes to reduce the 

uncertainty concerning estimated flazasulfuron total toxic residues in surface water and 

ground water, additional information concerning aerobic aquatic metabolism and aerobic 

soil metabolism of flazasulfuron and degradates may be submitted.
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B. Labeling Requirements

In order to mitigate risks to non-target plants, label language that is intended to keep the 

pesticide on the treatment area, thereby reducing the potential for exposure of non-target plants, 

is required. For example, spray drift management language on the occupational/agricultural use

labeling that advises users of applicator responsibilities and requires specific techniques to 

reduce the possibility of spray drift must be included. 

Language Required for Labels that include Agricultural and Noncrop Uses: 

• Buffer Language: “A 25 foot buffer for ground applications must be maintained between 

the point of direct application and the closest downwind edge of sensitive terrestrial 

habitats (including grasslands, forested areas, shelter belts, woodlots, hedgerows, riparian 

areas and shrub lands), sensitive freshwater habitats (including lakes, rivers, sloughs, 

ponds, creeks, marshes, streams, reservoirs and wetlands) and estuarine/marine habitats.”

• Ground Water Advisory: “This chemical has properties and characteristics associated 

with chemicals detected in ground water. This chemical may leach into ground water if 

used in areas where soils are permeable, particularly where the water table is shallow.”

• Do not apply aerially.

• Do not apply through any irrigation system.

• Rate Restriction: “Do not apply more than 0.15 lb ai per acre per year.

• Spray Drift Management Language:

“SPRAY DRIFT MANAGEMENT:

The applicator must be familiar with the effects of temperature inversions. 

Apply as a medium or coarser spray (ASAE Standard 572).

The interaction of many equipment and weather related factors determines the potential for 

spray drift. The applicator and the grower are responsible for considering all factors 

involved in minimizing drift potential.

Where states have more stringent regulations, they must be observed.

Avoid making applications when spray particles may be carried by air currents to areas 

where sensitive crops and plants are growing. Do not spray near sensitive plants if wind is 

gusty, below 2 mph, or in excess of 10 mph and moving in the direction of adjacent areas 

of sensitive crops or plants. Do not apply during temperature inversions. Always make 

applications when there is some air movement to determine the direction and distance of 

possible spray drift. 

Apply using a nozzle height of no more than 2 feet above the ground or crop canopy.

Information on Droplet Size
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The best drift management strategy is to apply large droplets and to limit or eliminate small 

droplets. Applying large droplets reduces drift potential, but will not prevent drift if 

applications are made improperly or under unfavorable environmental conditions (see 

sections below).

Volume: Use sufficient volume to form droplets large enough to avoid drift potential.

Controlling Droplet Size

Pressure: Pressure and nozzle type and orientation should be carefully managed to avoid 

formation of fine droplets.

Number of nozzles: Use the minimum number of nozzles that provide uniform coverage.

Nozzle type: Use a nozzle type that is designed for the intended application. With most 

nozzle types, narrower spray angles product larger droplets. Consider using low-drift 

nozzles. Properly designed solid stream nozzles should produce the lowest drift potential. 

Select nozzles which do not have a wide discharge profile.

Equipment should be calibrated regularly according to manufacturer’s specifications.

Calibration

Applications must not be made when wind exceeds 10 mph. Use caution when applying in 

wind speeds less than 2-3 mph because a temperature inversion may be present and wind 

direction may vary. Many factors, including droplet size and equipment type, determine 

drift potential at any given wind speed. Note: Local terrain can influence wind patterns. 

The applicator must be familiar with local wind patterns and must monitor wind conditions 

at the site at the time of application.

Wind

Low humidity and high temperature increase the evaporation rate of droplets and therefore 

increase spray drift potential. The applicator must compensate for temperature and 

humidity.

Temperature and Humidity

Because of high drift potential, applications must not be made when droplets may reach a 

temperature inversion layer. It is the applicator’s responsibility to identify the presence of 

a temperature inversion at the time of application. Accurate measurements of temperature, 

relative humidity, and wind speed help determine if an inversion exists. Local sources of 

weather information may help identify the presence of temperature inversions.

Temperature Inversions

The pesticide must only be applied when the potential for drift to adjacent sensitive areas 

(e.g., residential areas, bodies of water, known habitat for threatened or endangered 

species, non-target crops) is minimal (e.g., when wind is blowing away from the sensitive 

areas).”

Sensitive Areas 
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Language Required for Labels That Include Agricultural Uses:

• Minimum retreatment interval (RTI): at least 3 months for citrus and at least 2 weeks for 

grapes. 

• Preharvest Interval : For grapes- 75 days; For citrus- 1 day; For sugarcane- 180 days.

• For sugarcane, a 12-month interval between the last application and the planting of the 

rotational crop is required. 

• A restricted entry interval (REI) of 12 hours is required.

V. Conclusion

Based on these considerations, consistent with the requirements of FIFRA section 3(c)(7)(B), 

EPA concludes that (i) it has satisfactory data pertaining to the proposed uses of flazasulfuron in 

citrus, grapes, sugarcane, Christmas trees and industrial vegetation management areas; and (ii) 

approving this application as set forth above will not cause any unreasonable adverse effect on 

the environment. Accordingly, the Agency is proposing to conditionally grant the first food use 

U.S. registrations of flazasulfuron.