EPA REGI STRATION DIVISION COMPANY NOTICE OF FILING FOR PESTI CI DE

PETI TI ONS PUBLISHED IN THE FEDERAL REGI STER EPA Registration Division contact: Susan Lewis; (703)305 - 7090 Inter - Regional Research Project Number 4 (IR - 4 Project) Petition 4E8328 EPA ha s received a pesticide petition ( 4E8328 ) from Interregional Research Project No. 4 (IR - 4), 500 College Road East, Suite 201 W, Princeton, NJ 08540 proposing, pursuant to section 408(d) of the Federal Food, Drug, and Cosmetic Act (FFDCA), 21 U.S.C. 346a(d), to amend 40 CFR part 180 by establishing a tolerance for residues of fluazifop - p - butyl in or on the raw agricultural commodit ies : lettuce , head and leaf at 5 .0 parts per million (ppm); strawberry at 3.0 ppm; onion, green at 1.5 ppm; grass hay at 15 ppm; grass forage at 4.0 ppm; caneberry subgroup 13 - 07A at 0.05 ppm; bushberry subgroup 13 - 07B at 0.3 ppm; tuberous and corm vegetables (except for potato) subgroup 1D at 1.5 ppm; small fruit vine climbing, except for fuzzy kiwifruit subgroup 13 - 07F, 0.03 ppm; and onion, bulb subgroup 3 - 07A at 0.5 ppm and amending a tolerance for residues of fluazifop - p - butyl in or on rhubarb, from 0.5 ppm to 0.4 ppm. Upon the approval of the aforementioned tolerances, IR - 4 requests removal of the existing tolerances for grape at 0.01 ppm; onion, bulb at 0.5 ppm; and sweet potato, roots at 0.05 ppm. EPA has determined that the petition contains data or information regarding the elements set forth in section 408 (d) ( 2) of FDDCA; however, EPA has not fully evaluated the sufficien cy

of the submitted data at this time or whether the data supports granting of the petition. Additional data may be needed before EPA rules on the petition. A. Residue Chemistry 1. Plant metabolism. The metabolism of fluazifop - p - butyl is adequatel y unde rstood for the purpose of the proposed amended tolerance . 2. Analytical method. Syngenta has developed and validated anal yt ical methodology

for enforcement purposes. This method has been submitted to the Agency and is in PAM Vol. II, Method II. An exte nsive database of method validation data using this method on various crop commodities is available. 3. Magnitude of residues. Complete residue data to support the requested amended tolerance are submitted with this petition. The requested tolerances are adequatel y supported. These studies were conducted per EPA Test Guideline s 860 Series. B. Toxicological Profile 1. Acute toxicity. Fluazifop - p - but yl t echnical and the end - use formulation have low acute toxicity

b y oral, dermal and inhalation exposure r outes. F or fluazifop - p - butyl2

technical, the oral LD50 in rats is 3680 mg/kg for males and 2451 mg/kg for females. The rabbit dermal toxicity L D50 is >2000 mg/kg and the rat inhalation LD50 is 1.7 mg/l air. F luazifop - p - butyl technical is mildly i rritatin g to the rabbit ey e and slightly i rritating to rabbit skin. Fluazifop - p - butyl technical is not a skin sensitizer. 2. Genotoxicty. Fluazifop - p - butyl has been tested for its potential to induce gene mutation and chromosomal changes in different test sy ste ms. F luazifop - p - butyl was negative in bacterial reverse gene mutation assays and in mouse ly mphoma mammalian cell mutation assay s. Fluazifop - p - butyl was negative in in vitro chromosomal aberrations assay i n human blood lymphocy tes and was negative in the in vivo mouse micronucleus test. 3. Reproductive and developmental toxicity. A number of developmental toxicity studies have been conducted. B ased on an HED review of all relevant data, the Agency concluded that the degree of concern is low. T he overa ll NOAEL for the rat studies is 2.0 mg/kg/day

and the LOAELi s 5.0 mg/kg/day . F or single dose effects, the NOAELi s 50 mg/kg/day

and the LOAE L is 200 mg/day b ased on diaphragmatic hernia malformations. 4. Subchronic toxicity . Fluazifop - p - butyl was evaluated in a number of subchronic studies. In a 90 - day

r at oral toxicity

s tudy the NOAEL was 0.5 mg/kg/day . E ffects at higher doses included decreased spleen and testicular weight and decreased hematological parameters in males. F luazifop - p - butyl was also e valuated in a 90 - day oral toxicity

s tudy w ith hamsters. T he NOAEL was 78.3 mg/kg/day , based on decreased body w eight and body

w eight gain as well as food efficiency i n males at higher doses levels. S igns of liver toxicity and centrilobular eosinophilia w ere observed in males and females. N o dermal toxicity s tudy w as conducted; however, the study w as conducted with a similar compound, fluazifop - butyl. In a 21/28 day d ermal rabbit study

c onducted with fluazifop - butyl, the NOAEL was 100 mg/kg/day . L OAEL w as 500 mg/kg/day based on the death of a male. 5. Chronic toxicity. The Agency has classified fluazifop - p - butyl as not likely to be carcinogenic in humans. In a hamster carcinogenicity study the NOAEL was 12.5 mg/kg/day

for males and 12.1 mg/kg/day for f emales. In a combined carcinogenicity

/chronic toxicity

study in Wistar rats, in males the L OAEL was 80 ppm (4.15 mg/kg/day) and the NOAEL was 10 ppm (0.51 mg/kg/day). For females the LOAEL was 250 ppm (16.0 mg/kg/day) and the NOAEL was 80 ppm (5.2 mg/kg/ day). 6. Animal metabolism. The metabolism of fluazifop - p - butyl in rats is adequately understood. 7. Metabolite toxicology . The major metabolites of fluazifop - p - but yl are fluazifop acid (free and conjugated), 5 - triflurometh yl - 2 - py ridone and 2 - (4 - hydrox y

phenoxy) propionic acid (free and conjugated). Based on their structures, these compounds are likely to be significantl y less toxic than parent.3 8. Endocrine disruption . There is no indication of endocrine disrupt ion potential from the fluazifop - p - but yl toxicology data. There is no hormonal disruption or evidence of developmental or reproductive toxicity in the absence of maternal toxicity . Furthermore, the chemical structure of fluazifop - p - butyl indicates that it is unlikely to disrupt mammalian hormone s. C. Aggregate Exposure 1. Dietary exposure. Acute (Tier I), short - term, and chronic (Tier III) aggregate exposure evaluations were performed for fluazifop - P - butyl using the Dietary Exposure Evaluation Model (DEEM - FCIDTM, version 3.16) software from Exp onent. All consumption data for these assessments were taken from the National Health and Nutrition Examination Survey /“What We Eat in America” (NHANES/WWEIA) dietary survey conducted in 2003 - 2008 . These exposure assessments included all currentl y regist ered uses of fluazifop - P - butyl as well as proposed IR - 4 uses on caneberry , lettuce, blueberry , rhubarb, grasses grown for seed, strawberry , sweet potato and green onions . The Tier I acute assessments incorporated established or proposed tolerances (40CFR1 80.411) in or on a variet y of agricultural commodities including meat, milk and eggs; percent of crop treated values were conservatively estimated to be 100% for all uses in the acute assessments. The Tier III chronic assessments incorporated field trial residue values where fluazifop - P - butyl was applied at the maximum intended use rate and samples were harvested at the minimum pre - harvest interval (PHI) to obtain the maximum expected residues. Estimated percent crop treated (%CT) values were incorporated into the Tier III chronic assessments based upon economic, pest, and competitive pressures. Anticipated residues in meat, milk and eggs were calculated by constructing theoretical nutritionally balanced diets and used in the chronic risk assessments. Empirically derived or DEEM TM (version 7.87) default processing factors were input into the DEEM - FCIDTM software. Drinking water estimates were included directly into the dietary

exposure assessment using the higher of the estimated drinking water concentrat ions (EDWCs) for surface and ground water. i. Food. Acute Exposure. The acute assessment was performed for females (13 - 49 ye ars old) subpopulation, as this subpopulation was the only one for which an acute endpoint was determined. The acute dietary risk assessment was performed with an acute reference dose (aRfD) of 0.50 mg/kg - bw/day based on a developmental toxicity study in rats with an acute no observed adverse effect level (NOAEL) of 50 mg/kg/day and an uncertainl y factor of 100X to account for intra - and interspecies variations. No additional FQPA safety

factor was applied. For the purpose of aggregate risk assessment, the exposure value was expressed in terms of margin of exposure (MOE), which was calculated b y dividing the NOAEL b y the exposure f or the females (13 - 49 y ears old) subgroup. In addition, exposure was expressed as a percent of the acute reference dose (% aRfD). Acute food exposure to the females (13 - 49 y ears old) subpopulation resulted in a MOE of 777 (12.9% of the aRfD of 0.5 mg/kg - bw/day). Since the Benchmark MOE for this assessment was 100 and since EPA generally has no concern for exposures above the benchmark or below 100% of the aRfD, S yn genta believes that there is a reasonable certaint y that no harm will result from acute die tary (food) exposure to residues arising4

from all current, pending and proposed uses of fluazifop - P - butyl. Chronic Exposure. The chronic assessment was run using DEEM - FCIDTM software, average field trial residue values and %CT values. The chronic dietary risk assessment was performed for all population subgroups with a chronic reference dose (cRfD) of 0.0074 mg/kg - bw/day

based on a two - generation reproduction study in rats with a NOAEL of 0.74 mg/kg/day and an uncertainl y factor of 100X to account for intr a - and interspecies variations. No additional FQPA safety factor was applied. For the purpose of the aggregate risk assessment, the exposure values were expressed in terms of MOE, which was calculated b y dividing the NOAEL b y the exposure for each population subgroup. In addition, exposure was expressed as a percent of the chronic reference dose (% cRfD). Chronic food exposure to the U.S. population resulted in a MOE of 1,154 (8.7% of the cRfD of 0.0074 mg/kg - bw/day). Chronic food exposure to children 1 - 2 ye ars old, the most exposed population subgroup, resulted in a MOE of 350 (28.6% of the cRfD of 0.0074 mg/kg - bw/day). Since the Benchmark MOE for this assessment was 100 and since EPA generall y has no concern for exposures above the benchmark or below 100% of the cRfD, S yn genta believes that there is a reasonable certainty that no harm will result from chronic dietary (food) exposure to residues arising from all current, pending and proposed uses of fluazifop - P - but yl . C ancer. Fluazifop - p - but yl has bee n classified as “not likely carcinogen to humans”. Therefore no dietary

cancer assessment was performed. ii. Drinking water. The Estimated Drinking Water Concentrations (EDWCs) of fluazifop - P - butyl (evaluated as fluazifop - p - acid, the acid degradate of f luazifop - P - butyl) were determined using Tier l model SCI - GROW which estimates pesticide concentration in ground water and Tier II PRZM/EXAMS which estimates pesticide concentration in surface water. EDWCs of fluazifop - p - acid from the currently registered uses as well as the proposed IR - 4 uses on caneberry , lettuce, blueberry , rhubarb, grasses grown for seed, strawberry , sweet potato and green onions were determined. For ground water, SCI GROW provided an EDWC of 0.255 ppb (acute and chronic) based on the currently registered uses on tree fruits (apricots, cherries, nectarines, peaches, plums, prunes), pecans, non - bearing crops, ornamentals, bananas, citrus, and grapes. For surface water, PRZM/EXAMS provided an acute EDWC of 44.6 ppb based on the currentl y registered use on citrus and a chronic EDWC of 6.58 ppb based on the currently registered use on grapes. No Percent Cropped Area (PCA) adjustments were made to the surface water EDWCs. T he surface water EDWCs were used for risk assessment purposes. Acute Exposure from Drinking Water . The acute surface water EDWC of 44.6 ppb was input directly

into the DEEM - FCIDTM software as “water, direct and indirect, all sources” to model the acute drinking water exposures. Exposure contributions at the 95.0% - il e of exposures were determined by taking the difference between the aggregate (food + drinking water) exposures and the food (alone) exposures. Acute drinking water exposure to the females (13 - 49 y ears old) subpopulation resulted in a MOE of 62,500 (0.2% of the aRfD of 0.50 mg/kg - bw/day). Since the Benchmark MOE for this assessment was 100 and since EPA generally has no concern for exposures below 100% of the aRfD, S yn genta believes that there is a reasonable certainty that no harm will result5

from acute drinking water exposure to residues arising from the current, pending and proposed uses for fluazifop - P - butyl. Chronic Exposure from Drinking Water: The chronic surface water EDWC of 6.58 ppb was input directl y into the DEEM - FCIDTM software as “water, dire ct and indirect, all sources” to model the chronic drinking water exposures. Chronic drinking water exposure to the U.S. population resulted in a MOE of 5,371 (1.9% of the cRfD of 0.0074 mg/kg - bw/day). Chronic drinking water exposure to the most exposed sub - population (infants, <1 ye ar old) resulted in a MOE of 2,083 (4.8% of the cRfD of 0.0074 mg/kg bw/day). Since the Benchmark MOE for this assessment was 100 and since EPA generall y has no concern for exposures below 100% of the cRfD, S yn genta believes that there is a reasonable certainty that no harm will result from chronic drinking water exposure to residues arising from the current, pending and proposed uses for fluazifop - P butyl. 2. Non - dietary exposure . Fluazifop - P - butyl is a selective herbicide used in the post - emergent control of grasses in agricultural, ornamental, residential and recreational (golf course) settings. A residential exposure and risk assessment was performed for Fluazifop - P - butyl uses on turf and ornamentals using the endpoints and uncertaint y factors established by

the EPA. The fluazifop - P - butyl end - use products are formulated as both liquid concentrates and ready - to - use (RTU) liquids. Homeowners can apply the liquid formulations using a low - pressure hand - wand (LPHW), hose - end spray er, backpack or watering can. Homeowners can apply the RTU liquids using a hose - end spray er, trigger - pump spray er, or watering can. The homeowner handler and residential post - application exposure and risks were determined based on the highest use r ates for all lawn and garden products that contain fluazifop - P - butyl. Based on the labels for the various products containing fluazifop - P - but yl , there is a potential for residential handler exposure from consumers making applications to home lawns and orn amentals. There is also a potential for post - application residential exposure to adults and children re - entering treated lawns and to adults and youths playing golf on treated turf. A short - term incidental oral NOAEL of 100 mg/kg/day , a short - term dermal NOAEL of 2 mg/kg/day and a short - term inhalation NOAEL of 2 mg/kg/day (all from a developmental toxicity study in rats) were used in these residential risk assessments. Combined short - term MOEs were 231 for adult handlers (backpack sprayer) and 128 for c hildren 1 - 6 y ears old (post - application risk); both are above the Benchmark MOE of 100 and do not exceed the EPAs level of concern (LOC) of 100. D. Cumulative Effects Cumulative Exposure to Substances with a Common Mechanism of Toxicity . Section 408(b)( 2)(D)(v) requires that, when considering whether to establish, modify , or revoke a tolerance, the Agency

consider “available information” concerning the cumulative effects of a particular pesticide’s residues and “other substances that have a common mechan ism of toxicity”. The EPA does not have, at this time, available data to determine whether fluazifop - P - butyl has a common mechanism of toxicity with other substances or how to include this pesticide in a cumulative risk assessment. For the purposes of th is tolerance6

action, the EPA has not assumed that fluazifop - P - butyl has a common mechanism of toxicity with other substances. E. Safety Determination 1. U.S. population. Using the conservative assumptions described above, and based on the completeness and reliability of the toxicity

data, current, pending and proposed uses of fluazifop - P - butyl resulted in an acute aggregate MOE of 767 (13.0% of the aRfD of 0.5 mg/kg - bw/day) for females 13 - 49 y ears old (the onl y population subgroup of concern). A short - t erm aggregate MOE of 128,370 (LOC = 100) and a chronic aggregate MOE of 950 (10.6% of the cRfD of 0.0074 mg/kg - bw/day) was determined for the U.S. population. Since the aggregate MOEs exceed the Benchmark MOEs of 100, Sy

ngenta believes that there is a rea sonable certaint y that no harm will result to the U.S. population from acute, short - term, or chronic aggregate exposures arising from all current, pending and proposed uses of fluazifop - P - but yl . 2. Infants and children . Acute aggregate exposure calculati ons were not performed for infants and children, since a relevant acute endpoint has not been identified for these subgroups. Using the conservative assumptions described above, and based on the completeness and reliability of the toxicity

data, short - ter

m aggregate MOE of 128 (LOC = 100) was determined for children 1 - 6 y ears old, and a chronic aggregate MOE of 320 (31.3% of the cRfD of 0.0074 mg/kg - bw/day) was determined for children 1 - 2 y ears old. Since the aggregate MOEs exceed the Benchmark MOE of 100 , S yn genta believes that there is a reasonable certainty that no harm will occur to infants or children from short - term and chronic aggregate exposures arising from all current, pending and proposed uses of fluazifop - P - butyl. F. International Tolerances There are currently

no Maximum Residue L imits (MRL s) set for fluazifop - P - butyl for crops b y the Codex Alimentarius Commission however international MRLs for fluazifop P - butyl have been established for various agricultural commodities.