2 Proposed Registration of the First Food Uses for the Herbicide Flazasulfuron on Citrus, Grapes and Sugarcane, as well as uses on Christmas Trees and I ndustrial 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 non

residential turf including golf courses, sod farms, athletic fiel ds, 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 ac etohydroxyacid 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 contain s 25.0% of the active ingredient, flazasulfuron. Soil directed spray application for citrus and grapes and over

- the

- top applications and post

directed applications for sugarcane are proposed at a maximu m 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.3 II. Human Health Risk

A summary of the human health effects and risk of flazasulfuron as assessed in the Agency document enti tled “ Flazasulfuron: Human Health Risk Assessment for Proposed Uses on Citrus, Grapes, Sugarcane, Christmas Trees, and Industrial Vegetation ” is provided below.

A. S ummary of Toxicological Effects

The existing toxicology database is deemed sufficient f or characterizing the hazard of flazasulfuron. The database consist s 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 s tudy 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 toxici ty 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. Observe d effects included adv erse c hanges in kidney function ( chronic nephropathy) and kidney physiology (enlargement, dark color of kidney), increase s in liver weight an d hepatocellular hypertrophy, increase s in inflammatory cell infiltration, hepatocellular necrosis, hepatocellular swelli ng, 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 (intra ventricular septal defect) was seen in a dev elopmental study with Wistar rats . The deve lopmental study in rabbits showed high incidences of abortion at the highest dose tested. Decreases in body weight and chronic nephropathy were obs erved 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 observ ed at the mid

dose 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.

The re was no evidence of carcinogenicity in the mouse oncogenicity study or the combined chronic tox icity / carcinogenicity study in the rat and no evidence of genotoxic potential in i n vitro and in vivo mutagenicity studies. Based on the results of these studies, EPA has classified flazasulfuron as “No evidence of carcinogenicity to humans.”4 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 fla zasulfuron is complete except for an immunotoxicity s tudy (OPPTS Guideline 870.7800) and a subchronic neurotoxicity study (OPPTS Guideline 870. 6200b). These studies are now requirements under 40 CFR §158.5 00 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 data base . 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/ris k 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 off spring 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 off spring 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 stabili ty 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

.5 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% c rop treated for all commodities; and EPA made conservative (protective) assumptions in the ground and surface water modeling used to assess exposure to flazasulfuron in drinki ng 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 a n 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 10 0 0 mg/kg body wt.

2. Chronic Dietary : EPA established a chronic reference dose (cRfD) and a Chronic Population Adjusted Dose (c PAD) 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 i n 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 t he 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 Int ermediate

- 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 t he 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 bod y 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 based6 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 poten tial risk concern.

6. Cancer

D . Aggregate Ri sk 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 :

A cute and chronic dietary risk assessments were conducted using the Di etary Exposure Evaluation Model

- Food Commodity Intake Database (DEEM

- FCID, Version 2.03), which incorporates food consumption d ata 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. D rinking water inputs were derived from screening

- level water exposure models. These assumptions are considered to be highly conservative (i.e., protective).

Acute Dietary Ris k : A ll acute analys e s 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 :

F lazasulfuron 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 profe ssionally managed sports fields

. T here 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, sin ce no hazard associated with dermal exposure was identified in the toxicity database for flazasulfuron, flazasulfuron is not expected to pose a risk from post

application dermal exposure.

In accordance with current policy, EPA did not conduct a quantita tive assessment of post

application inhalation exposure to flazasulfuron; however, v olatilization 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 its7 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 th e 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

e xposure 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

- t erm 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: B ased on the lack of evidence of carcinogenicity in tw o adequate rodent carcinogenicity studies, flazas ulfuron 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 h as 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 other8 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 mech anism 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 f lowable products for right

- of

- w ay a pplications )

. EPA is concerned when the MOE is less than 100. Since all MOEs ar e well above 100, short

– and intermediate

- term risk s 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 exposu re 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

- ap plication inhalation exposure of in dividuals 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/200 9/120109meeting.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 id entify 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

.9 III. Environmental Risk

A summary of the environmental fate and ecological effects and risks of f lazasulfuron 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 env ironmentally 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 bridge

contraction 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

- pyri m idinamine (DTPP) , persist in hydrolysis and metabolism studies

, but rea dily degrade via photolysis. The photolysis half

- life for total toxic residues of flazasulfuron is 34 days. Degrada tes persist in all metabolism studies.

Like all sulfonylurea herbicides, flazasulfuron can exhibit high mobility in soil. Flazasulfuron is a weak acid (pK a of 4.37) and the mobility of flazasulfuron is expected to increase with increasing pH. The pH o f 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.

F lazasulfuron 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 Decis ion” 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 ecotoxici ty 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.10 A risk assessment of the p roposed 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 non

toxic to birds on acute oral and dietary bases. Study results indicate tha t the acute toxicity thresholds are greater than the highest concentrations tested (acute LD 50 >2000 mg a.i./kg

- bw and subacute dietary LC 50 >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 we re 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, n ot of concern.

2. Risk to Mammals:

Acute Risk: Flazasulfuron is practically non

- toxic to mammals (LD 50 = 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 LD 50 is greater than the maximum concentration tested (>100 μg a.i./bee). Precautionary labeling is not required for honeybees. Flazasulfuron poses minimal risk to earthworm s since the LD 50 is greater than the highest concentration tested (>15 mg a.i./kg soil). B ased on these studies, minimal risk to honey

bees and other terrestrial invertebrates is assumed from all the proposed flazasulfuron uses.11 4. Risk to Fish and Aquatic Invertebrates (Freshwater and Estuarine/Marine):

Acute Risk: F lazasulfuron is pra ctically 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, flazasulf uron 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, compa rison 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 l ocated 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 aquat ic 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 r unoff 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 vascula r 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 expo sure , 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.12 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) o f 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 comp lete 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 w hich EPA began requiring all applications to include functional immunotoxicity and subchronic n eurotoxity 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 flazasulfur on.

**•** 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 teste d 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 flaza sulfuron, providing sorption coefficients (K oc ) 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 fl azasulfuron 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 K oc for each toxic residue of flazasulfuron using the lowest estimated K oc . The modeled K oc 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 K oc , the drinking water assessment is considered protective because of the conservative characteristics o f the PRZM

- GW model and the assumptions EPA made in the assessment, including the following:13 **•** 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 flazasu lfuron 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 degradat es 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 K oc used in the drinking water e xposure 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 us ed 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 residu es of flazasulfuron and its degradates in ground and surface water. If the Registrant wishes to redu ce the uncertainty concerning estimated flazasulfuron total toxic residues in surface water and ground water , a dditional 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 form ation and decline of degradates. The submi tted 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 wat er , a dditional information concerning aerobic aquatic metabolism and aerobic soil metabolism of flazasulfuron and degradates may be submitted

.14 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 responsibi lities 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 lak es, 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 yea r.

**•** 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 fact ors 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 w hen 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 c rops 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 Size15 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 c arefully 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 sp ray 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. Man y factors, including droplet size and equipment type

, determine drift potential at any given wind speed. Note: L ocal terrain can influence wind patterns. The applicator must be familiar with local wind patterns and must monitor wind conditions at the si te 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 In versions

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 Areas16 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

- mont h 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 wil l 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.