Page 1 of 17 UNITED STATES ENVIRONMENTA L PROTECTION AGENCY

WASHINGTON, D.C. 20460 OFFICE OF CHEMICAL SA FETY A ND POLLUTION PREVENTION

MEMORANDUM DATE : July 26 , 2 010 S UBJECT : Isoxaben: Occupational and Residential Exposure Assessment for the First Food

Use on Tree Nuts and Grapes and Non - bearing Fruit and Nut Trees and Vines. PC Code: 125851 DP Barcode Nos. D374750 (62719 - LI

N) D 368834 (62719 -ARE) Decision N o s .: 3 79577 (62719 - LI

N) 417487 (62719 -ARE) Registration Nos. EPA File Symbol: 62719 - LIN ( FN - 3133 Specialty Herbicide ) EPA File Symbol: 62719 -ARE ( AmoreTM DF Herbicide ) Petition No.: 7F7222 Reg. Action: Section 3 Assessment T ype: O ccupational and Residential Case No.: 7219 TXR No.: NA CAS No.: 82558 - 50 - 7 MRID No.: NA 40 CFR § : 180.xxx (to be determined) FROM: Suku Oonnithan, Biologist

Risk Assessment Branch II Health Effects Division (7509P) THROUGH: Richard A. Loranger, Ph.D., Senior Scientist

Risk Assessment Branch II Health Effects Division (7509P) T O : Kathry

n Montague Herbicide Branch Registration Division (7505P) I. ACTION REQUESTED Perform an occupational and residential exposure (ORE) assessment for the first food use of i soxaben herbicide in bearing tree nuts and grape s and non - bearing fr uit and nut trees and grape vines .Page 2 of 17

TABLE OF CONTENTS I. ACTION REQUESTED ................................ ................................ ................................ ............. 1 II. EXECUTIVE SUMMARY ................................ ................................ ................................ ....... 3 III. BACKGROUND ................................ ................................ ................................ ..................... 6 IV . USE PATTERN OF ISOXABEN ................................ ................................ ........................... 6 V. HAZARD CHARACTERIZATION ................................ ................................ ......................... 7 VI . RESIDENTIAL AND NON - OCCUPATIONALEXPOSURES ................................ ............ 9 1. Residential Handler Exposure and Risk ................................ ................................ ............... 10 2. Residential Postapplication Exposures and Risks ................................ ............................... 11 1 VII. OCCUPATIONAL EXPOSURE ................................ ................................ ....................... 13 3 1. Exposure Scenarios, Inputs And Assumptions ................................ ................................ ... 13 3 2. Occupational Exposures and Risks ................................ ................................ .................... 14 4 VIII. OCCUPATIONAL POSTAPPLICATION EXPOSURE ................................ ................. 15 5 IX . SPRAY DRIFT ................................ ................................ ................................ ...................... 16 X. REVIEW OF HUMAN RESEARCH ................................ ................................ ................... 16 6 XI . CONCLUSIONS ................................ ................................ ................................ ................. 16 6 XII. REFERENCES ................................ ................................ ................................ ..................... 17Page 3 of 17

I I. EXECUTIVE SUMMARY INTRODUCTION : Dow AgroSciences has submitted applications to regist er two new end - use product (EP) formulations of isoxaben , FN - 3133 Specialty Herbicide (EPA File Sy mbol: 62719 - LIN) for use on bearing and non - bearing nut trees and grapes and Amor eTM DF Herbicide (EPA File Sy mbol: 62719 - ARE) for use on non - bearing tree nuts and grape vines. For isoxaben, this is the first food use registration. PROPOSED USE PATTERN : The FN - 3133 Specialty Herbicide is being proposed for broadleaf weed control i n bearing tree nuts and grapes and non - bearing fruit and nut tree s and grapes . The AmoreTM DF Herbicide label is proposed for broadleaf weed control in non - bearing tree nuts and non - bearing vineyards. Both formulations have application rate s of 0.5 - 1.0 lb ai/A using low pressure ground equipment as 1 - 2 broadcast spray s per crop ye ar in a minimum spray volume of 10 gal/A . The maximum single and ye arl y application rates are 1.0 lb ai/A. The preharvest intervals (PHI s ) are 60 and 1 65 day s for tree nuts and grapes, respectivel y. HAZARD CHARACTERIZAT ION : Technical i soxaben has low acute oral, dermal, and inhalation toxicities (Toxicity

Categories III - IV). It is not a skin irritant (Category IV), but, causes minor irritation to the eye (Category I II). Isoxab en is not a skin sensitizer. No treatment related effects were reported in a 21 - day repeated dose dermal toxicity study in the rabbit. This is consistent with the relativel y low dermal absorption (≤11% of administered dose) observed in a dermal penetrati on study in the monkey , and the low toxicity observed in subchronic oral studies in the rat, mouse and dog. Due to the absence of relevant toxic effects, n o appropriate endpoints were identified for short - term incidental oral and dermal risk assessment s . An intermediate - term dermal endpoint also was not selected. F or inter mediate term incidental oral and inhalation exposures, a no observed adverse effect level (NOAEL) of 200 mg/kg/day was selected from a reproductive toxicity study in rat based on decrea sed body weight gain in F1 female animals at the lowest observed effect level (LOAEL) of 625 or 1000 mg/kg/day

(from co - critical studies) . There was no evidence of neurotoxicity or immunotoxicity . There are low concerns for increased susceptibility of of fspring and effects on offspring viability in the reproductive study, and there was no evidence of susceptibility in developmental toxicity

studies in two species. Therefore, the 10x FQPA S afety F actor was reduced to 1 x . The combined uncertainty factor ( UF ) of 100 is based on 10X factors for both interspecies extrapolation and intraspecies variability, serving as the basis for the l evel of c oncern (LOC) , which is a margin of exposure ( MOE ) of 100 for residential and occupational risk s . Is oxaben was class ified as having “suggestive evidence of carcinogenic potential" based on increased hepatocellular adenoma incidence in male and female mice. Because there were no treatment - related increases in tumors in the rat and low concerns for genotoxicity, quantifi cation of cancer risk using a cancer potency factor i s not required. RESIDENTIAL AND NON - OCCUPATIONAL EXPOSURES : No new residential uses for isoxaben were included with the proposed new product applications. However, several EPs have been registered fo r weed control on residential lawns and recreational turf areas. For assessing residential handler exposures , two representative products, an emulsifiable concentrate (EC) and a granule , were selected based on maximum single application rates on residenti al lawns and turfPage 4 of 17

areas . Both the EC and granular products could be applied by homeowners twice a year with the maximum rate per application being 0.49 and 1.0 lb ai/A, respectively. The intervals between treatments are 56 - 60 days resulting in residential applicators being subjected to short - term exposures . The short - term dermal risks to homeowners were not estimated due to the lack of an endpoint. The short - term inhalation MOEs ranged from 2.9E+06 to 2.8E+07 with an LOC of 100, indicating the risk s are not of concern f o r residential handlers when using the EC and/or granule formulations of isoxaben on home lawns. RESIDENTIAL POSTAPPL ICATION EXPOSURES : There is a potential for postapplication dermal, inhalation and oral (children only) exposures of is oxaben to adults and children when they work and/or play on treated lawn areas. The short - term dermal and incidental oral (children) exposures were not estimated due to the lack of respective endpoints. The short - term inhalation exposure is expected to b e negligible because of soil directed applications of EC and granules and because of the label recommendation for incorporation by irrigation or rain soon a fter application. However, there is a potential for intermediate - term oral exposure to children through soil ingestion due to the second application of isoxaben granules at 56 day s after the first treatment , and because of the potential for higher persistence of isoxaben in soil. Usually HED do es not assess such intermediate - term postapplication expo sures under residential conditions, except on a case - by- case basis. Due to the persistence of i soxaben in the soil , HED decided to assess children's ’ exposure from ingesting soil when turf is treated with isoxaben at the maximum ye arl y rate . The resident ial - use product selected for this assessment was Isoxaben 75 DF where maximum single and ye arly application rate s are 1.0 and 3.0 lb ai/A. HED assume d that incidental ingestion of soil represents the worst case for oral postapplication exposure, since no other oral scenarios would be expected to have an equivalent duration of exposure to residues as high as those possible in soil. The MOE associated with soil ingestion is 1 , 3 00 ,000 with an LOC of 100 , and therefore is not of concern. This scenario is expected to be protective of all other postapplication risks for children in residential settings. OCCUPATIONAL EXPOSURE : The proposed use of FN - 3133 Specialty Herbicide and AmoreTM DF in orchards of bearing tree nuts, grapes and non - bearing fruit and nut trees is expected to result in short - and intermediate - term occupational exposures to mixers, loaders, and applicators. There are no chemical - specific data available fo r estimating occupational handler expos ure . Therefore, Health Effects Division ( HED ) used surrogate unit exposures from the Pesticide Handlers Exposure Database (PHED) to estimate occupational exposure s . S hort - and intermediate - term dermal risks were not estimated d ue to the absence of respective endpoints . Short - and intermediate - term inhalation MOEs for applicators were ≥ 2 , 7 00 with an LOC of 100 and are not of concern . OCCUPATIONAL POSTAPP LICATION EXPOSURE : Only one application of isoxaben is allowed per season at the maximum rate per application (two at lower rates) on tree nuts , grape s and non - bearing fruit and nut trees. P ostapplication workers who enter treated fields after the restricted entry

interval (REI) of 12 hours are subjected to onl y short - term dermal and inhalation exposure s and such risk s to workers are not of concern because of the soil - directed a pplication method proposed for applying isoxaben formulations , thereb y minimizing inhalation exposure,Page 5 of 17

and due to the lack of a dermal endpoint. The labels also recommend incorporation of the spray by rainfall or irrigation for maximum efficacy as a preem ergence herbicide , thereb y further minimizing postapplication exposure . CONCLUSIONS : The potential risks to occupational workers who apply FN - 3133 Specialty Herbicide and AmoreTM DF Herbicide formulations o f isoxaben to bearing tree nuts and grapes and no nbearing fruit and nut tress and grape vines are below HED's level of concern . Potential risks to homeowners from applying isoxaben formulations registered for residential use on home lawns and to adults and children from postapplication exposures are als o not of concern. Therefore , pending the results of an aggregate human health risk assessment, HED has no objection to registering the proposed new formulations of isoxaben for the proposed uses , which includ e the first food use f or isoxaben .Page 6 of 17

I I I . BACKGROUND Dow AgroSciences has appli ed to register a new end - use product FN - 3133 Specialty Herbicide (EPA File Sy

mbol . 62719 - LIN) containing isoxaben (75%) for use on bearing tree nuts and grapes and non - bearing fruit and nut trees and grape vines. For isox aben, this is the first food use registration. Another new product, AmoreTM DF Herbicide ( EPA File Sy mbol: 62719 - ARE) containing isoxaben (75%) and penoxsulam (3.12%) is proposed for use on non - bearing tree nuts and non - bearing vines. This assessment addresses only isoxaben and its occupational and residential exposures. F or p enoxsulam , tolerances have been establis h ed ( 40 CFR §180.605) for residues in almond, grape, pistachio and rice and the occupational and residential exposures were reviewed in conjunction with the aggregate risk assessment for penoxsulam. Isoxaben i s a benzami de herbicide with broad spectrum preemergen ce activity against broadleaf weeds . It is currentl y registered for use on ornamentals, home l awns, turf, and Christmas tree and conifer plantations. The registered formulations include dry flowable ( DF ) , ready- to - use ( RTU) , emulsifiable concentrate ( EC ) and granule mixed with fertilizer s . Both FN - 3133 Specialty Herbicide and AmoreTM DF are dry flowable formulations . IV . USE PATTERN OF ISOXABEN Both products are being registered f o r control of cert ain broadleaf weeds i n bearing and/or non bearing fruit and nut tree orchards and grapes . The proposed u se pattern for isoxaben is provided in the following table (Table 1). Table 1 . Proposed Use Pattern s of FN - 3133 (File Symbol : 62719 - LIN) and Am oreTM D F (File Symbol : 62719 - ARE) Formulations of Isoxaben. EPA File Symbol & Active Ingredients Use site s Application

equipment Application

rates No. appls./

season & interval 1 Comment s 62719 - LIN (FN - 3133) Isoxaben 75% (DF Formulation) Bearing tree nuts, grapes and non bearing fruit and nut trees and non bearing grape vine s Lo w pressure

ground sprayers, spray volume ≥ 10 gal/A Single = 0.66 - 1.33

lb product/A Max. single rate = 1.0 lb ai/A) Max. s easonal rate = 1.0 lb ai/A 1 - 2 per

crop year, (harvest to harvest) PHI = 60 days

for tree nuts and 165 days for grapes 62719 - ARE ( AmoreTM DF) Isoxaben = 7 5.0% plus Penoxsulam = 3.12% (DF formulation) Non -bearing tree nuts and non bearing grape vine s Single = 1 .0 - 1.33 lbs product

/A Max. single rate

= 1.0 lb ai/A) Max. s easonal rate = 1.0 lb ai/A 1 per

s eason NA Abbreviations used: DF = dry flowable, NA = not applicable and PHI = preharvest interval. 1 . No spray interval w as given in the submitted draft label . The FN - 3133 Specialty Herbicide is proposed for preemergence control of broadleaf weeds in tree nuts, grapes, and non - bearing fruit and nut trees and non - bearing grape vines. The n on bearing trees are those that will not bear fruit for at least one year after treatment .Page 7 of 17

L abels of both products recommend use of ground application equipment includi ng ground boom and low pressure handwand t o spray the base of trees and vines to avoid crop injury . A ctivation of the applied spray by

rain or irrigation for optimum weed control is recommended . Tank mixes with both formulations are allowed ; however, c hemigation or application by any type of irrigation sy stem is prohibited . The submitted draft label s of both products have CAUTION as Signal Word . The personal protective equipment (PPE) statement on FN - 3133 Specialty H erbicide include s long sleeved shirt , long pants , shoes plus socks and chemical resistant gloves ; for AmoreTM DF , the PPE statement include s only

long sleeved shirt, long pants and shoes plus socks. Both product labels h ave 12 hour restricted entry interval s (REI s ) per the worker protection standard (WPS). V. HAZARD CHARACTERIZATION Technical i soxaben has low to moderate acute toxicities by oral, dermal, and inhalation routes (Toxicity Categories III - IV). It is not a skin irritant (Category IV) or a dermal sensitizer and causes onl y mino r transient irritation to the eye (Category III). The acute toxicity

profile of isoxaben is summarized in Table 2 . Table 2. Acute Toxicity Profile – Isoxaben Guideline No. Study Type Results Toxicity Category 870.1100 Ac ute oral

– rat LD 50 > 10,000 mg/kg (both sexes) IV 870.1200 Ac ute dermal - rabbit LD 50 > 2000 mg/kg (both sexes) III 870.1300 Ac ute inhalation - rat LC 50 > 1.99 mg/L (both sexes) III 870.2400 Ac ute eye irritation - rabbit Irritation to the cornea and iris cleared within 24 hrs III 8 70.2500 Ac ute dermal irritation - rabbit Non - irritating IV 870.2600 Skin sensitization - guinea pig Not a sensitizer (Buehler method) N/A The primary

target organs for the toxicity of isoxaben are the liver and kidney . No treatment related effects wer e reported in a 21 - day repeated dose dermal toxicity study in the rabbit. This is consistent with relatively low dermal absorption (≤11% of administered dose) observed in a dermal penetration study

in the monkey

and the low toxicity

observed in sub - chroni c oral studies in the rat, mouse and dog. N o a ppropriate point s of departure (PODs) or endpoints were selected for short - term incidental oral and short - and intermediate - term dermal exposure routes d ue to the absence of adverse effects. For the intermediate - term incidental oral and short - and intermediate - term inhalation exposures, a NOAEL of 200 mg/kg/day was selected from the rat reproductive toxicity study based on decreased body weight gain in F1 females observed at the LOAEL of 625 or 1000 mg/kg/day ( co - critical studies) . There was no evidence of neurotoxicity or immunotoxicity . There are low concerns for increased quantitative susceptibility of offspring and effects on offspring viability in the reproductive toxicity study , and there was no evidence of susceptibility

in developmental toxicity studies in two species. Therefore, the 10x FQPA S afety F actor was reduced to 1 x . A combined UF of 100 is based on 10X factors for both interspeciesPage 8 of 17

extrapolation and intraspecies variability , serving as the ba sis for the level of concern (LOC), which is a margin of exposure ( MOE ) of 100 for residential and occupational risk s . HED notes that a 60 kg body weight was assumed for residential and occupational handlers in order to be protective of the offspring eff ects seen in the reproduction toxicity study . Isoxaben was classified as having “suggestive evidence of carcinogenic potential" based on increased hepatocellular adenoma incidence in male and female mice. Because there were no treatment - related increases in tumors in the rat and low concerns for genotoxicity, quantification of cancer risk with a cancer potency factor i s not required. Based on the available toxicity data and HED’s current practices, the short - and intermediate term inhalation risks for iso xaben w ere assessed using an oral toxicity study . However, HED is in the process of re - examining policies and procedures for conducting inhalation risk assessments, including route to route extrapolation of toxicity data. If any new policies or procedure s are developed, HED may revisit the need for an inhalation toxicity study for isoxaben. Endpoints and doses selected for the occupational and residential risk assessment of isoxaben are summarized in Table 3 . A detailed discussion of isoxaben's hazard a ssessment is available in the latest risk assessment (D. McNeilly, D376428 , 2010 ). Table 3 . Toxicological Doses and Endpoints of Isoxaben Selected for Occupational and Residential Risk Assessment s . Exposure Scenario 1 Point of

Departure Uncertai nty

& FQPA Safety Factors Level of

Concern Study and Toxicological Effects Ac ute dietary, General population, including children An appropriate endpoint to assess exposure for this route and duration was not identified. Incidental o ral , Short - term An appro priate endpoint to assess exposure for this route and duration was not identified. Incidental o ral , Interm. - term NOAEL=200

mg/kg/day UF A =10x

UF H =10x FQPA SF = 1x

Residential LOC for MOE = 100 Reproductive toxicity in the rat (oral).

Offspring LOAEL = 1 , 000 mg/kg/day, based on decreased body weight gain in F1 females on Day 70. One year dietary study in the rat (co critical supporting study). LOAEL = 625 mg/kg/day based on decreased body weight gain in females during the first six months with a NOAEL of 62.5 mg/kg/day. Dermal , Short and Interm. - t erm An appropriate endpoint to assess exposure for this route and duration was not identified. Inhalation, Short - term NOAEL=200

mg/kg/day Inhalation abs orp tion rate = 1 00 % UF A =10x

UF H =10x FQPA SF = 1x

Residential/ Occupational LOC for MOE = 100 Reproductive toxicity in the rat (oral).

Offspring LO AE L = 1 , 000 mg/kg/day, based on decreased F2 pup we ight s, gestation survival and live pups/litter and increased incidence of malformations.Page 9 of 17

Table 3 . Toxicological Doses and Endpoints of Isoxaben Selected for Occupational and Residential Risk Assessment s . Exposure Scenario 1 Point of

Departure Uncertai nty

& FQPA Safety Factors Level of

Concern Study and Toxicological Effects Inhalation, Interm. - term NOAEL=200

mg/kg/day Inhalation abs orp tion rate = 1 00 % UF A =10x

UF H =10x FQPA SF = 1x

Residential LOC for MOE = 100 Occupational LOC for MOE = 100 Reproductive toxicity in the rat (oral).

Offspring LOAEL = 1 , 000 mg/kg/day, based on decreased F2 pup we ight s, gestation survival and live pups/litter and increased incidence of malformations. One year dietary study in the rat (co critical supporting study). LOAEL = 625 mg/kg/day based on decreased body weight gain in females during the first six months with a NOAEL of 62.5 mg/kg/day. Cancer (oral, dermal, inhalation) Classified as having “suggestive evidence of carcinogenic potential” b ased on increased

incidence of hepatocellular adenomas in male and female mice. A quanti tative cancer risk assessment with a cancer po tency factor is not required b ecause there were no treatment related increases in tumors in the rat and low concerns for genotoxicity . Abbreviations used: FQPA SF = Food Quality Protection Act Safety Factor , LOAEL = lowest observed adverse effect level, N OAEL = no observed adverse effect level, LOC = level of concern, MOE = margin of exposure, UF A = extrapolation from animal to human, and UF H = potential variation in sensitivity among human population. 1. Short - term

is 1 - 30 day s and intermediate - term is 1 - 6 months duration. VI. RESIDENTIAL AND NON - OCCUPATIONAL EXPOSURES There are several registered liquid and solid end - use product formulations available for weed control on home lawns, recreational turf areas and ornamental plantings . Some products ar e labeled for use b y homeowner s and others are for use by professional applicators. No new residential uses for isoxaben are being requested with this application. Even though isoxaben is already registered for weed control in residential areas, quanti tative homeowner (handler) and postapplication exposure assessments were not previously conducted due to the lack of short - term incidental oral, dermal and inhalation endpoints needed to estimate the se risks . Based on the current hazard characterization and in order to complete an aggregate risk assessment in conjunction with the proposed first food use of isoxaben, residential exposures were estimated , taking into consideration all end - use products registered for residential uses. For assessing residential handler exposure, two representative product formulations having the highest single application rates were selected. They are an EC (L awn 3iP Herbicide Conc entrate, Reg. No. 72155 - 87) and a granule (T &O Fertilizer- Contains Gallery plus Team , EPA Reg. No. 62719 - 280 ) . The liquid and granule have maximum single application rate s of 0.49 and 1.0 lb ai/A , respectively . The granule product i s packaged and marketed individually as homeowner and commercial products and b oth labels have almost identical use p atterns (Table 4 ) .Page 10 of 17

Table 4 . Use Pattern of Isoxaben End - use Products Selected for Residential Handler and Postapplication Exposure Assessments. EPA Reg. No. 1 Application Equip me nt Appl. rates No. appls. / season & interval 2 Comments Lawn 3iP Herbicide Conc ., Reg. No. 72155 - 87 (EC, Isoxaben = 2.63%) Hom eowner/Commercial Label

After mixing with water

- pum p style hand held sprayer

- concentrate plus water hose - end sprayer Without mixing with water

- d ial - style hose - end sprayer

- single - rate or dual - rate hose - end sprayer Rate/appl.= 1.6 - 3.2 fl. oz. /500 sq. ft Max/appl.= 0.49 lb ai/A Max/year = 0.98 lb ai/A 2/year

60 days NA

T&O Fertilizer , EPA Reg. No. 62719 - 280 (Granule) Isoxaben = 0.38%) Hom eowner/Commercial Label

- drop or rotary- type granule spreader Rate/appl.= 174 - 2 6 5 lbs/A Max/appl.= 1.0 lb ai/A Max/year = 2.0 lb ai/A 2 - 7/year

56 days Sprinkler

irrigation or rainfall within a few hours is recommended Isoxaben 75DF Specialty Herb icide EPA Reg. No. 34704 - 917, DF Isoxaben=75% Commercial Label

- herbicide sprayer

- spray volume ≥10 gal/A Rate/appl.= 0.66 - 1.33 lbs/A Max/appl.= 1.0 lb ai/A Max/year = 4 lbs/A ( 3 .0 lb ai/A) 3 or more

60 days Sprinkler

irrigation or rainfall after application is recommended Abbreviations used: DF = dry flowable, EC = emulsifiable concentrate, NA = not applicable 1. Lawn 3iP Herbicide Conc entrate/Ready - to - Spray ( Reg. No. 72155 - 87 ) is an EC containing isoxaben (2.63%), 2,4 - D dimethylamine salt (4.73%), dicamba (0.52%) and mecoprop -p potassium salt (1.1%). T&O Fertilizer Contains Gallery plus Te am ( EPA Reg. No. 62719 - 280 ) is a granule + fertilizer containing isoxaben (0.38%), trifluralin (0.39%) and benefin (0.76%). 2. Repeat appl ications may represent rates that are lower than the max imum single rate/A . 1. Res idential Handler Exposure and Risk The use patterns used for a quantitative assessment of homeowner exposures are from EC and granul e product s (Table 4) . Potential Exposure Scenarios : The following scenarios were assessed: 1 . mixing/loading/appl yi ng EC using a hose - end sprayer 2 . mi x ing/loading/appl yi ng EC using a hand - held pump sprayer 3 . loading/appl yi ng granules using a granular push - ty pe spreader Application Rate and Exposure Durations : For residential handler exposure assessment, HED uses maximum single application rate s and frequency of treatments for determining sho rt - and intermediate - term exposures . The EC product label recommends two application s per year for weed control on home lawns at a single maximum rate of 0.49 lb ai/A . The minimum interval between treatments is 60 day s. Therefore, homeowner s are exposed to only short - term dermal and inhalation risks . The granule product label recommends repeat applications at an interval of 56 day s on cool season grass and 70 day s on warm season grass at a single maximum single ratePage 11 of 17

of 0.99 lb ai/A , resulting in short - term exposures . There are some distributor products sold in Florida (both homeowner and commercial labels) that recommend up to 7 applications per year on Bermuda grass with a maximum rate of 2 lb ai/A/year. Thes e repeated applications are assumed to be made at an average rate of 0.3 lb ai/A/application taking into account an annual limit of 2.0 lb ai/A. Despite the potential for repeated applications, HED continues to consider residential handler exposures to be short - term in duration based on the minimum 56 day retreatment interval . Exposure and Risk to Residential Handlers : No chemical specific exposure data have been submitted by

the registrant to estimate the inhalation unit exposures for residential handlers. Therefore, surrogate unit exposures from the Outdoor Residential E xposure T ask F orce database ( ORETF) were selected . S hort - term dermal risks were not estimated due to the lack of a dermal endpoint. The short - term inhalation MOEs range d from 2.9 E+0 6 to 2. 8 E+0 7 ( LOC = 100) and are not of concern (Table 5 ) . Table 5 . Exposure s and Risks for Residential Handlers Applying Liquid and Granule Formulations of Isoxaben on Residential Lawns. 1 Exposure Scenario s Max. Single

Appl. rate, lb ai/A cre 2 Area

treated A cres /day 3 Inhal. UE

mg/lb ai (ORETF) Inhal. dose

mg/kg/day 4 Sh ort - term Inhal.

MOE 5 M/L/A, liquid, hose - end sprayer 0.49 0.5 0.017 6.9 4 E - 05 2.9E+06 M/L/A, liquid, hand - held sprayer 0.49 0.5 0.0038 1. 55 E - 0 5 1. 3 E+0 7 L/A, granules, push - type spreader 0.99 0.5 0.00088 7.2 E - 0 6 2.8 E +0 7 Abbreviations used: A= applicator, L= loader, ORETF = Outdoor Residential E xposure T ask F orce, and UE= unit exposure . 1. Short - term

dermal exposures were not estimated due to the absence of a dermal endpoint. 2. The maximum single application rate is from Table 5. 3. The area treated is assumed to be 0.5 A for hose - end and hand - held sprayers (based on a standard rate of 10 gal of spray/A) and 0. 5 acres for granules. 4. Inha lation dose (mg/kg/day) = (application rate * area treated/day * inhalation unit exposure * inhalation absorption rate) / body wt. (60 kg). 5. Inhalation MOE = Short - term Inhalation NOAEL (200 mg/kg/day) / inhalation dose. 2. Res idential Postapplication E xposures and Risks For evaluating the residential postapplication exposure of isoxaben, EC, granule and solid formulations were considered (Table 4). Since the I soxaben 75 DF Specialty Herbicide, EPA Reg. No. 34704 - 917, had the highest application rate/year, it was assumed that the estimated risks would be protective of those associated with other formulations and application rates. Th is solid formulation is labeled for use b y professional applicators on established turf, landscape, container and field grown ornamentals, non - cropland, non - bearing fruit and nut trees and non bearing vineyards. It has a maximum single application rate of 1.0 lb ai/A (similar to EC and granule), with a ye arl y rate of 3.0 lb ai/A.Page 12 of 17

Dermal E xposures to C hildren , Y outh and A dults : D ermal endpoint s w ere not selected for isoxaben , for any duration of exposure, due to the lack of toxic effects via the dermal route; therefore, there is no risk of concern associated with dermal postapplication exposure . Short - Term Incidental Oral Exposures to Children from Hand - to - Mouth and Object - to - Mouth Events : Itis likel y that children playing in treated turf areas would ingest residues of isoxaben from h and - to - m outh and o bjects - to - m outh events. However, there is no endpoint applicable to short - term oral exposure, and therefore , there are no risks of concern associated with hand - to mouth and object - to - mouth exposure. Episodic Oral Exposures to Children from Ingestion of Granules : Ingestion of isoxaben granules f ollowing application of T &O Fertilizer- Contains Gallery plus Team to turf is considered to be an episodic event for children playing on treated lawns. The granules are not likely to be present on treated turf for up to 30 day s (i.e., short - term durations) due to the label recommendation for irrigation/watering within hours of application. Further, in the absence of an acute dietary endpoint attributable to a single exposure , episodic ingestion of granules was not assessed . By stander Inhalation Exposure : Based on the Agency's current practices, residential postapplication inhalation risk to children is not assessed; however, bystander exposure could occur for children playing in areas adjacent to pesticide applications . For adult by standers, postapplication inhalation exposure i s expected to be negligible because (i) technical isoxaben has low inhalation toxicity (Category

III) ; (ii) label recommend ed incorporation by rainfall or irrigation after application ; (iii) isoxaben has low volatility (vapor pressure 1.3E - 8 Pa at 2 5  ̊ C , M cNeilly 2010) ; and (iv) products are not applied using airblast or aerial equipment that would result in significant inhalation exposure . However, volatilization of pesticides may be a potential source of postapplication inhalation exposure to individuals nearb y to pesticide applications. 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. The Agency recei ved 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 and may , as appropriate, develop policies and procedures to identify the need for and , subsequently , the way to incorporate postapplication inhalation exposure into the Agency's risk assessments. If new policies or procedures are put into place, the Agency may revisit the need for a quantitative postapplication inhalation exposure assessm ent for isoxaben. Intermediate - term Incidental Oral Exposure to Children resulting from Soil Ingestion : HED does not ty

picall y consider soil ingestion to occur over intermediate - term durations, i.e., from 1 - 6 months, largel y due to use pattern and the f act that residues are removed by precipitation or through microbial degradation in soil. In the case of isoxaben, HED estimated incidental oral exposure from ingestion of soil because the use pattern calls for repeat applications, and because the environm ental fate data indicated that i soxaben is persistent in the soil , with a half life of ≥150 day s ( C. Peck., D341497, 3/18/2010) . Because of the likel y persistence of isoxaben in soil , HED conducted a conservative assessment of potential intermediate - term oral risk from soil ingestion by

using an ye arly application rate of 3.0 lb ai/A from Isoxaben 75 DF instead of the maximum single rate of 1.0 lb ai/A.Page 13 of 17

To address the persistence of isoxaben in the soil , HED assume d that exposure resulting f rom incident al oral ingestion of soil ( intermediate - term) at an exaggerated rate of 3.0 lb ai/A/year would be a conservative estimate that would address the likely p otential build up of isoxaben in the soil. The exposure and risk from incidental oral ingestion of soi l was calculated using the following formula : ADD = ( SR * IgR2 * CF4 ) / BW where, SR = AR * F3 * CF1 * CF2 * CF 3 MOE = NOAEL / ADD S R = 3.0 lb ai/A * 100%/cm * 4.5 4 E+08 μg/lb * 2.47E - 08 A/cm2 * 0.67 cm3 /g soil = 22 . 54 μg ai/g ADD = [ 22 . 54 μg ai/g * 100 mg/day * 0. 000001 g/ μg ] / 15 kg = 1.5 0 E - 04 mg/kg/day MOE = 200 mg/kg/day / 1.5 0 E - 04 mg kg/day = 1.3 0 E+06 where, ADD = Average daily dose (mg/kg/day) AR = Application rate ( 3.0 lb ai/A/year) BW = Body weight of child ( 15 kg) CF1 = Conversion fa ctor for μ/lb (4.5 4 E+08) CF2 = Conversion factor for A/cm2 (2.47E - 08) CF3 = conversion factor for volume to weight (0.67 cm3 /g soil) CF 4 = conversion factor for g/μg (0. 000 001) F3 = Percent of ai available in uppermost cm of soil (100% assumed) IgR2 = Ingestion rate of soil (100 mg/day) MOE = NOAEL (intermediate - term , mg/kg/day) / ADD (mg/kg/day) NOAEL (intermediate. - term) = 200 mg/kg/day SR = Soil residue at intermediate - term ( μ g ai/g soil ) t = postapplication day on which exposure is assessed ( interm ediate - term) It is emphasized here that the application rate of 3.0 lb ai/A/year used for estimating the intermediate - term exposure is an exaggerated rate when compared with the single application rate of 1.0 lb ai/A of granule and DF formulations. At the intermediate - term exposure duration , the risk was found to be not of concern to children who may ingest soil treated with isoxaben (MOE = 1 . 30 E+06 , L OC =100) . VI I . OCCUPATIONAL EXPOSURE 1. Exposure Scenarios , Inputs and Assumptions B oth isoxaben products ( FN - 3133 Specialty Herbicide and AmoreTM DF ) are DF formulations and have identical application rates and methods. Therefore, both products have similar exposure scenarios as shown below : 1. m ixing and loading of DF formulation for ground boom spray 2. a pp l yi ng the diluted spray

using tractor mounted ground boom spray equipment 3. mixing, loading and applying DF formulation using a tractor mounted low - pressure handwand sprayer to treat areas not covered b y boom sprayer . The inputs and assumptions used for estimating the exposure s to handlers are the following:Page 14 of 17

1. Application rate : The maximum single application rate for isoxaben is 1 .0 lb ai/A for bearing or non - bearing trees and grape vines. 2 . Unit exposures : No chemical specific exposure data are available to estimate inhalation unit exposures for handlers. Therefore, surrogate unit exposures were selected from PHED , based on the formulation ty

pe , application equipment and PPE. InPHED, there are no inhalation unit exposures for a M/L/A scenario for a solid DF formulation using a low - pressure handwand sprayer. Therefore, unit exposures for the wettable powder (WP) formulation w ere used. Since the WP is dustier than the DF, the resulting exposure estimates are expected to be conservative for assessing exposure from the DF formulation . 3 . Area treated/ 8 - hr day : ExpoSAC Policy No. 9 estimates that 40 - 200 acres can be treated/day with a tractor mounted ground boom sprayer depending upon the crop treated . F or this assessment, 80 A/day

was selected for the orchard setting based on treatment of orchard trees planted in rows. Areas not covered with a ground - boom sprayer (corners and edges of orchards) or spot treatments may

be made using a tractor mounted low - pressure handwand sprayer. It i s assumed that a handler (M/L/A) can mix, load and apply 40 gal/day ( ExpoSAC Policy

No. 9 ) ; at the label recommended spray volume of 10 gal/A , HED estimates 4 acres/day could be treated for the tractor mounted low - pressure handwand scenario . 4. P ersonal P rotective E quipment (PPE) : B aseline PPE ( long sleeved shirt, long pants and shoes with socks) was used as a starting point to calculate handler exposure s . For the present assessment additional protection (e.g. , respirator s ; engineerin g controls (enclos ed cab and cockpit, closed s ys tems) ) was not needed to obtain an MOE that is higher than the LOC. 5 . Duration of exposure : The label allow s onl y 1 application of FN - 3133 at the maximum single rate of 1.0 lb ai/A (harvest to harvest) o n tree nut s , grap e , and non - bearing fruit tree and grapevine orchards , resulting in short - term exposure to occupational handlers . However, it is possible that contract applicators may use FN - 3133 Herbicide on several fields , with sequential applications lasting longer than a month d uring the weed growing season , r esulting in intermediate - term exposure to handlers . 6 . Body weight of handlers and postapplication worker s : A body weight of 6 0 kg was used for handlers b ecause the toxicity endpoints selected for assessing inhalation risks are based on offspring effects in the reproductive toxicity study . 2. Occupational Exposures and Risks Table 6 summarizes the exposures and risks associated with the use of FN - 3133 Specialty Herbicide and AmoreTM DF Herbicide in orchards of bearing and non - bearing fruit and nut trees and grape vines .Page 15 of 17

Table 6 . Short - and Intermediate - term Exposure s Resulting from t h e Use of FN - 3133 Specialty Herbicide and Am oreTM DF Herbicide i n Orchards of Bearing and Non - bearing Fruit and Nut Trees and Grape Vines 1 . Exposure Scenario Appl . rate Area treated (A/day) PPE &

Eng . Control 2 Inhal. u nit

exposure (m g/lb ai) 3 Inhalation, Short– and

Interm ediate - term Exp osure mg/kg/day 4 MOE 5 1. Mixing/loading DF for ground boom spray (open mixing) 1.0 lb al/A 80 Baseline 0.00077 0.00103 190 ,000 2. Applying spray using ground boom Baseline & open cab. 0.00074 0.00099 200 ,000 3. Mixing, loading, and app lying using a tractor powered low pressure hand wand 4 Baseline 1.1 0.07333 2 , 7 00 1. MOE = Margin of exposure and PPE = Personal protective equipment. The inputs used for calculations are explained under Exposure Scenarios, Inputs and Assumptions. 2 . Baseline PPE includes long sleeved shirt, long pants and shoes with socks. Engineering controls include open cab (tractor) for applicator s . 3 . Lacking unit exposures in PHED for a DF formulation, unit exposures for mi xing, loading and applying a wettable powder formulation with a low -pressure handwand we re used as surrogate . 4 . I nhalation exposure = [Inhal ation unit exposure ( mg/lb ai) * appl. rate (lb ai/A) * area treated/day (acres) * inhal ation absorption 100 %] / body wt ( 6 0 kg). 5 . MOE = Short - and intermedi ate - term NOAEL ( 200 mg/kg/day) /inhalation exposure (mg/kg/day) D ermal exposure was not assessed due to the lack of dermal endpoints. The short - and intermediate - term inhalation MOEs for handlers rang ed from 2,700 to 200 ,000 which are not of concern . VI I I . OCCUPATIONAL POSTAPPLICATION EXPOSURE Workers entering treated areas to do crop related cultural practices such as irrigation, scouting, pruning, etc., may

be exposed to isoxaben residues via dermal and inhalation route s for short term durations . However, postapplication dermal risk for workers is not of concern because of the absence of a short - term dermal endpoint . Based on the Agency's current practices, a quantitative occupational postapplication inhalation exposure assessment wa s not performed for isoxaben at this time. However, there are multiple potential sources of postapplication inhalation exposure to individuals performing postapplication activities in previously treated fields. These potential sources include volatilizati on of pesticides and resuspension of dusts and/or particulates that contain pesticides. The Ag ency

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. The Agency received the SAP’s final report on March 2, 201 0 (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 postapplication inhalation exposure data generated b y the Agricultural Reentry Task Force and may , as appro priate, develop policies and procedures, to identify the need for and, subsequently , the way to incorporate occupational postapplication inhalation exposure into the Agency's risk assessments. If new policies orPage 16 of 17

procedures are put into place, the Agency m ay revisit the need for a quantitative occupational postapplication inhalation exposure assessment for isoxaben. Restricted Entry Interval (REI) : A 12 - hour REI was set for isoxaben based on the acute toxicity properties of the technical material which is classified as Categories III (acute dermal , inhalation and eye irritation) and IV ( acute oral and skin irritation). Is oxaben is not a dermal sensitizer. Th e 12 - hour REIis appropriate for isoxaben based on the WPS for a gricultural p esticides . IX . SPRAY DRIFT Spray drift is alway s a potential source of exposure to residents near to pesticide spraying operations. This is particularly the case with aerial application s , but, to a lesser extent, could also be a potential source of exposure from the ground application method s employed for isoxaben . The Agency

has been working with the Spray Drift Task Force, EPA Regional Offices and State Lead Agencies for pesticide regulation and other parties to develop the best spray drift management practices. On a ch emical by chemical basis, the Agency is now requiring for aerial applications , interim mitigation measures that must be placed on product labels. The Agency has completed its evaluation of the new database submitted by the Spray

Drift Task Force, a member ship of U.S. pesticide registrants, and is developing a policy on how to appropriatel y apply the data and the AgDrift computer model to its risk assessments for pesticides applied by air, orchard air blast and ground hydraulic methods. After the policy is in place, the Agency

may impose further refinements in spray drift management practices to reduce off - target drift with specific products with significant risks associated with drift. X. REVIEW OF HUMAN RESEARCH This risk assessment rel ies in part on d ata from studies in which adult human subjects were intentionally

exposed to determine their dermal and inhalation exposures. Many such studies , involving exposure to many different pesticides, comprise generic pesticide exposure databases, such as Pestic ide Handlers Exposure Database (PHED), the Outdoor Residential Exposure Task F orce (ORETF) d atabase and the Agricultural Reentry Task Force (ARTF) d atabase. EPA has reviewed all the studies in these multi - pesticide generic exposure databases, and on the b asis of available evidence has found them to have been neither fundamentally unethical nor significantly deficient relative to standards of ethical research conduct prevailing when they were conducted. There is no regulatory barrier to continued reliance on these studies, and all applicable requirements of EPA's Rule for the Protection of Human Subjects for Research (40 CFR part 26) have been satisfied. XI . CONCLUSIONS 1. The potential risks to occupational handlers who apply DF formulation s of isoxa ben (FN - 3133 Specialty Herbicide and AmoreTM DF Herbicide) to bearing tree nuts and grapes and non - bearing fruit and nut trees and grapes are below HED's LOC .Page 17 of 17

2. The registrant did not propose new residential uses for isoxaben with these submissions. Howe ver, there are existing uses for isoxaben in residential settings resulting in exposure to homeown er s. Residential handler exposure was estimated for a granule formulation of isoxaben applied at 1.0 lb ai/A or an EC formulation applied at 0.5 lb ai/A on residential turf grasses . Both these scenarios result ed in risks for residential handlers which are not of concern . 3. The short - term postapplication risk s to adults and children from dermal and incidental oral exposures of isoxaben were not assessed du e to the lack of respective endpoints. There is a potential for intermediate - term oral postapplication exposure to children through ingestion of soil while playing on treated lawns. HED conservatively estimated the risk from soil ingestion due to the pot ential for isoxaben to persist in soil following application to turf. A conservative estimate of children’s exposure and risk from soil ingestion demonstrated that the risk is not of concern, with an MOE of 1 . 3 0E+06 . 4. Pending the results of an aggregat e human health risk assessment , HED has no objection to registering the proposed new uses , including the first food use for isoxaben. The submitted worker protection statements on both draft labels are adequate to protect occupational handlers and postapp lication workers. XI I . REFERENCES McNeilly , D. D376428, 2010. Is oxaben . Human Health Risk Assessment for the First Food Uses of the Herbicide on Grapes, Tree Nuts and Pistachios. Peck, C. D341497, 3/18/2010) . Tier I Drinking Water Asses sment for the Isoxaben Proposed New Use on Bearing Nut Trees and Vineyards .