EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE 

PETITIONS PUBLISHED IN THE FEDERAL REGISTER 

EPA Registration Division contact: Susan Lewis; (703)305-7090

Inter-Regional Research Project Number 4 (IR-4 Project)

Petition 4E8328

EPA has 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 commodities: 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 sufficiency 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 adequately 

understood for the purpose of the proposed amended tolerance.

2. Analytical method. Syngenta has developed and validated analytical 

methodology for enforcement purposes. This method has been submitted to the Agency

and is in PAM Vol. II, Method II. An extensive 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 

adequately supported. These studies were conducted per EPA Test Guidelines 860 

Series.

B. Toxicological Profile

1. Acute toxicity. Fluazifop-p-butyl technical and the end-use formulation have 

low acute toxicity by oral, dermal and inhalation exposure routes. For fluazifop-p-butyl 
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technical, the oral LD50 in rats is 3680 mg/kg for males and 2451 mg/kg for females. 

The rabbit dermal toxicity LD50 is >2000 mg/kg and the rat inhalation LD50 is 1.7 mg/l 

air. Fluazifop-p-butyl technical is mildly irritating to the rabbit eye and slightly irritating 

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 systems. Fluazifop-p-butyl was 

negative in bacterial reverse gene mutation assays and in mouse lymphoma mammalian 

cell mutation assays. Fluazifop-p-butyl was negative in in vitro chromosomal aberrations 

assay in human blood lymphocytes and was negative in the in vivo mouse micronucleus 

test.

3. Reproductive and developmental toxicity. A number of developmental toxicity

studies have been conducted. Based on an HED review of all relevant data, the Agency 

concluded that the degree of concern is low. The overall NOAEL for the rat studies is 

2.0 mg/kg/day and the LOAEL is 5.0 mg/kg/day. For single dose effects, the NOAEL is 

50 mg/kg/day and the LOAEL is 200 mg/day based on diaphragmatic hernia 

malformations.

4. Subchronic toxicity. Fluazifop-p-butyl was evaluated in a number of subchronic 

studies. In a 90-day rat oral toxicity study the NOAEL was 0.5 mg/kg/day. Effects at 

higher doses included decreased spleen and testicular weight and decreased 

hematological parameters in males. Fluazifop-p-butyl was also evaluated in a 90-day

oral toxicity study with hamsters. The NOAEL was 78.3 mg/kg/day, based on decreased 

body weight and body weight gain as well as food efficiency in males at higher doses 

levels. Signs of liver toxicity and centrilobular eosinophilia were observed in males and 

females. No dermal toxicity study was conducted; however, the study was conducted 

with a similar compound, fluazifop-butyl. In a 21/28 day dermal rabbit study conducted 

with fluazifop-butyl, the NOAEL was 100 mg/kg/day. LOAEL was 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 females. In a combined 

carcinogenicity/chronic toxicity study in Wistar rats, in males the LOAEL 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-butyl are fluazifop 

acid (free and conjugated), 5-trifluromethyl-2-pyridone and 2-(4-hydroxyphenoxy) 

propionic acid (free and conjugated). Based on their structures, these compounds are 

likely to be significantly less toxic than parent.
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8. Endocrine disruption. There is no indication of endocrine disruption potential 

from the fluazifop-p-butyl 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 hormones.

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 Exponent. 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 currently 

registered 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 

(40CFR180.411) in or on a variety 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 DEEMTM (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 concentrations (EDWCs) for surface and ground water.

i. Food. Acute Exposure. The acute assessment was performed for females (13-49 

years 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 

uncertainly 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 by dividing the NOAEL by the exposure for the females (13-49 years old) 

subgroup. In addition, exposure was expressed as a percent of the acute reference dose 

(% aRfD). Acute food exposure to the females (13-49 years 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, Syngenta believes that there is a reasonable 

certainty that no harm will result from acute dietary (food) exposure to residues arising 
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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 uncertainly factor of 100X to account for intra- 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 by dividing the NOAEL by 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 

years 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 generally has no concern for exposures above the benchmark or below

100% of the cRfD, Syngenta 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-butyl.

Cancer. Fluazifop-p-butyl has been 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 fluazifop-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, SCIGROW 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 currently 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. The 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%-ile 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 years 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, Syngenta believes that there is a reasonable certainty that no harm will result 
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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 directly into the DEEM-FCIDTM software as “water, direct 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 year old) resulted in a MOE of 2,083 (4.8% of the cRfD of 0.0074 mg/kgbw/day). Since the Benchmark MOE for this assessment was 100 and since EPA 

generally has no concern for exposures below 100% of the cRfD, Syngenta 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-Pbutyl.

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 uncertainty 

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 sprayer, 

backpack or watering can. Homeowners can apply the RTU liquids using a hose-end 

sprayer, trigger-pump sprayer, or watering can. The homeowner handler and residential 

post-application exposure and risks were determined based on the highest use rates for all 

lawn and garden products that contain fluazifop-P-butyl. Based on the labels for the 

various products containing fluazifop-P-butyl, there is a potential for residential handler 

exposure from consumers making applications to home lawns and ornamentals. 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 children 1-6 years 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 mechanism 

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 this tolerance 
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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 years old (the only population 

subgroup of concern). A short-term 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, Syngenta believes that there is a reasonable certainty 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-butyl.

2. Infants and children. Acute aggregate exposure calculations 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-term aggregate MOE of 128 

(LOC = 100) was determined for children 1-6 years 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 years 

old. Since the aggregate MOEs exceed the Benchmark MOE of 100, Syngenta 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 Limits (MRLs) set for fluazifop-P-butyl for 

crops by the Codex Alimentarius Commission however international MRLs for fluazifopP-butyl have been established for various agricultural commodities.