EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR

PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER

EPA Registration Division contact: Joanne I. Miller 703

- 305

- 6224

INSTRUCTIO NS: Please utilize this outline in preparing the pesticide petition. In cases where the outline element does not apply, please insert “NA

- Remove” and maintain the outline. Please do not change the margins, font, or format in your pesticide petition. Simp ly replace the instructions that appear in green , i.e., “ [ insert
company name ] ,” with the information specific to your action.

TEMPLATE:

Syngenta Crop Protection, Inc.

[Insert petition number]

EPA has received a pesticide petition ( [insert pet ition number] ) from Syngenta Crop Protection, Inc. , PO Box 18300, Greensboro, NC 27419

- 8300 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.

( Options (pick one)

b y establishing a t oleranc e for residues of fluazifop

- p - butyl in or on the raw agricultural commodit i es banana at 0.01 parts per million (ppm), plantains at 0.01 parts per million (ppm), citrus (whole fruit) at 0.05 parts per million (p pm), citrus (dried pu lp) at 0.40 parts per million (ppm), citrus (oil) at 0.05 parts per million (ppm), citrus (juice) at 0.05 parts per million (ppm) , grapes at 0.01 parts per million (ppm), sugarbeet (root) at 0.25 parts per milli on (ppm), sugarbeet (top) at 1.5 parts per mi llion (ppm), sugarbeet (dried pulp) at 1.0 parts per million (ppm), and sugarbeet (molasses) at 3.5 parts per million (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 d a ta 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 tolerances.]

2. Analytical method

. [ Syngenta has developed and validated analytical2

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 tolerances are sub mitted with this petition . The requested tolerances are adequately supported. These studies were conducted per EPA Test Guideline s 860.1000, 860.1500 , and 860.1520. ]

B. Toxicological Profile

1. Acute toxicity. [ Fluazifop

- p - butyl technical and th e end

- use formulation have low acute toxicity by oral, dermal and inhalation exposure routes. For fluazifop

- p - butyl 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 th e 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 test ed 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 ba sed 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

e fficiency 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, the3

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 huma ns. In a hamster carcinogenicity studythe 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 (0.5 1 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 metabolite s 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. ]

8. Endocrine disruption

. [ There is no indication of endocrine disrupt ion 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. Fu rthermore, the chemical structure of fluazifop

- p - butyl indicates that it is unlikely to disrupt mammalian hormones. ]

C. Aggregate Exposure

1. Dietary exposure. Acute (Tier III) and chronic (Tier III) dietary exposure evaluations were made for fluaz ifop

- p - butyl using the Dietary Exposure Evaluation Model software with the Food Commodity Intake Database (DEEM

- FCIDTM, version 2.16) from Exponent. All consumption data for these assessments was taken from the USDA’s Continuing Survey of Food Intake by individuals (CSFII) with the 1994

- 96 consumption dat abase and the Supplemental CSFII children’s survey (1998) consumption database. These exposure assessments included all currently registered uses of fluazifop

- p - butyl plus uses on bananas, citrus fruits, grapes and sugar beets. Residue data was taken fro m field trials 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 maximum residue values. Calculated and projected percent crop treated (%CT) values were inco rporated in these assessments. Anticipated residues in meat and milk were calculated by constructing theoretical nutritionally balanced diets. Drinking water estimates were included directly into the dietary exposure assessment using the higher of the es timated drinking water concentrations (EDWCs) for surface and ground water.4

i. Food. Acute Exposure. The acute assessment was only performed for the females (13

- 49 years old) subpopulation as this subpopulation was the only one for which an acute end point was determined. The acute dietary risk assessment was performed with an acute reference dose of 0.5 mg/kg

- bw/day based on an acute no observed adverse effect level (NOAEL) of 50 mg/kg/day developmental toxicity study in rats and an uncertainly facto r of 100X. The 1 00X safety factor includes intra

- and interspecies variations. No additional FQPA safety factor was applied. The acute assessment was run using DEEM

- FCIDTM software using field trail residues and %CT values. For the purpose of the aggregate risk assessme nt, 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 20,935 (0.5 % of the acute RfD of 0.5 mg/kg

- bw/day). Since the Benchmark MOE for this assessment was 100 and since the EPA generally has no concern for expo sures below 100% of the RfD, Syngenta believes that there is a reasonable certainty that no harm will result from acute dietary (food) exposure to residues arising from the current and proposed uses for fluazifop

- p - butyl

.

Chronic Exposure. The chronic as sessment was run using DEEM

- FCIDTM software using average field trial residue values and %CT values. The chronic dietary risk assessment was performed for all population subgroups with a chronic reference dose of 0.0074 mg/kg

- bw/day based on a two

- generation repro duction study in rats with a NOAEL of 0.74 mg/kg/day and an uncertainly factor of 100X. The 100

- fold safety factor includes intra

- and interspecies variations. No additional FQPA safety factor was applied. For the purpose of the aggregate risk assessmen t, the exposure values were expressed in terms of margin of exposure (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 9,035 (1.1% of the cRfD of 0.0074 mg/kg

- bw/day). Chronic food exposure to the most exposed sub

population (children, 1

- 2 years old) resulted in a MOE of 3,801 (2.6% 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 below 100% of the RfD, Syngenta believes that there is a reasonable certainty that no harm will result from chronic dietary (food) exposu re to residues arising from the current and proposed uses for 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 Estima ted Drinking Water Concentrations (EDWCs) of fluazifop

- p - butyl (evaluated as fluazifop

- p - acid) were determined using Tier l SCI

- GROW which estimates pesticide concentration in ground water and Tier II5

PRZM/EXAMS which estimates pesticide concentration in s urface water. EDWCs of fluazifop

- p - acid from the currently registered uses plus the proposed uses on bananas, citrus, grapes, and sugar beets were determined. Based on the SCI

GROW modeling, the groundwater EDWC for fluazifop

- p - acid is 0.255 ppb (acute and chronic) based on the currently registered uses on tree fruits (apricots, cherries, nectarines, peaches, plums, prunes) and pecans and proposed uses on bananas, citrus, and grapes. Based on Tier II PRZM/EXAMS modeling for surface water, the proposed citrus use provided an acute EDWC of 38.807 ppb and a chronic EDWC of 5.566 ppb (adjusted for 0.87 Percent Cropped Area, PCA). Since the surface water EDWCs exceed the ground water EDWC, the surface water values were used for risk assessment purposes and will be considered protective for any ground water concentration concerns.

Acute Exposure from Drinking Water

. The acute surface water EDWC of 38.807 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 99.9%

- ile of exposures were determined by taking the difference between the aggregate (food + dr inking water) exposures and the food (alone) exposures for each population subgroup. Acute drinking water exposure to the females (13

- 49 years old) subpopulation resulted in a MOE of 15,718 (0.6% of the acute RfD 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 below 100% of the acute RfD, Syngenta believes that there is a reasonable certainty that no harm will result from acute drinking water exposure to residues arising from t he current and proposed uses for fluazifop

- p - butyl

.
Chronic Exposure from Drinking Water: The chronic surface water EDWC of 5.566 ppb was input directly into the DEEM

- FCIDTM software as “water, direct and indirect, all sources” to model the chronic drinkin g water exposures. Chronic drinking water exposure to the U.S. population resulted in a MOE of 6,308 (1.6% 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 1,924 (5.2% 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 below 100% of the cRfD, Syngenta believes that there is a reasonable certainty that no harm will res ult from chronic drinking water exposure to residues arising from the current 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, or namental, 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 pressure6

handwand (LPHW) or a hose end sprayer with either a dial type spray attachment (DTS) or a sprinkler attachment. Homeowners can apply the RTU liquids using a hose end sprayer with a sprinkler attachment or a trigger

- pump sprayer 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 or namentals. 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. The following endpoints were used in these residential risk assessments : NOAEL = 100 mg/kg/day (short

- term incidental oral endpoint from a developmental toxicity study in rats) and NOAEL = 2 mg/kg/day (short

- term dermal endpoint from a developmental toxicity study in rats), and NOAEL = 2 mg/kg/day (short

- term inhalation endp oint from a developmental toxicity study in rats). The resultant combined short

- term MOEs were 238 (adult handler risk for hose

- end

- dial type sprayer) and 240 (combined total post

- application risk for children 1

- 6 years old). Both children (1

- 6 years old ) and adults (20

- 49 years old) MOEs are above the benchmark MOE of 100 and thus do not exceed the EPA’s level of concern.

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 acti on, 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 reliabilit y of the toxicity data, the acute aggregate exposure calculation for current and proposed uses of fluazifop

- p - butyl provided a MOE of 8,978 (1.1% of the aRfD of 0.5 mg/kg

- bw/day) for the females (13

- 49 years old) subpopulation. The acute assessment was o nly performed for the females (13

- 49 years old) subpopulation as this subpopulation was the only one for which an acute endpoint was determined. The chronic aggregate exposure calculation for current and proposed uses of fluazifop

- p - butyl provided a MOE of 3,719 (2.7% of the cRfD of 0.0074 mg/kg

- bw/day) for the U.S. population. Since the aggregate MOEs exceed the Benchmark MOE of 100, Syngenta believes that there is a7

reasonable certainty that no harm will occur to the U.S. Population and the females (13

- 49 years old) subpopulation from acute or chronic aggregate exposures arising from the current and proposed uses for fluazifop

- p - butyl

.

2. Infants and children

. No acute aggregate exposure calculation was performed for the infants and children subgroups for the acute assessment, since no acute endpoint was determined for these subgroups. Using the conservative assumptions described in the exposure section above, and based on the completeness and reliability of the toxicity data, the c hronic aggregate exposure calculation for current and proposed uses of fluazifop

- p - butyl provided a MOE of 1,648 (6.1% of the cRfD of 0.0074 mg/kg

- bw/day) for the infants < 1 year old (the most sensitive population subgroup for the chronic assessment). Si nce the aggregate MOEs exceed the Benchmark MOE of 100, Syngenta believes that there is a reasonable certainty that no harm will occur to infants and children from the chronic aggregate exposures arising from the current and proposed uses for fluazifop

- p - b utyl

.

F. International Tolerances

There are currently no Maximum Residue Limits (MRLs) set for fluazifop

- p butyl for crops by the Codex Alimentarius Commission. International MRLs for the herbicide fluazifop

- p - butyl have been established for vario us agricultural commodities in a number of countries including Czech Republic, Denmark, Luxembourg, Netherlands, and Sweden.