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EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER

EPA Registration Division contact: [ Kay Montague (703) 305

- 1243 ]

INSTRUCTIONS: 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. Simply re place the instructions that appear in green , i.e., “ [ insert
company name ] ,” with the information specific to your action.

TEMPLATE:

[Syngenta Crop Protection, LLC ]
[Insert petition number]

EPA has received a pesticide petition ( [insert petition number] ) from [Syngenta Crop Protection, LLC ]
, [ PO Box 18300, Greensboro NC 27419 ] request ing, 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

.

1. by establishing a tolerance fo r residues of

[ C lodinafop

- propargyl ] in or on the raw agricultural commodity [ wheat grain ] at [ 0.02 ] 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 data at this time or whether the data supports granting of the petition. Additional data may be needed befo re EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism

. [The metabolism of clodinafop

- propargyl in wheat is adequately understood for the purpose of the proposed tolerances. Metabolism involves hydrolysis of the parent to the resulting acid followed by conjugation, arylhydroxylation at the 6 position of the pyridyl ring followed by sugar conjugation, and cleavage of the pyridinyloxy

- phenoxy ether bridge which forms the breakdown products 2

- (4

- hydroxyphenoxy) propanoic acid and 2

- hydroxy

- 3

- fluoro

- 5

- chloropyridine

. ( Federal Register (April 26, 2000, (Volume 65, Number 81), page 24471

- 24477) )

. ]2

2. Analytical method. [Syngenta has developed and validated analytical methodology for tolerance enforcement purposes. This method has been submitted to the Agency and is in the Pesticide Analytical Method ( PAM ) Vol. II. The method uses both normal and reverse phase liquid ch romatography with UV detection (HPLC

- UV). ( Federal Register (June 22, 2000 (Volume 65, Number 121), page 38765

- 38774) )

. ] An analytical method to support the residue data for the requested wheat grain tolerance has been submitted with this petition.

3. Magnitude of residues. [Complete residue data to support the requested tolerance has been submitted with this petition. The study was conducted in Canada Major and Minor Crop Field Trial Regions for wheat including zones 5, 7, 7 A , and 14. A single application of the formulated product HORIZON ® 240EC at a rate of 70 g ai/ha (0.0625 lb ai/A) was made during the growing season with an application timing of the 3

- 6 leaf stage. This rate is consistent with current EPA approved directions for use on Disco ver ® Herbicide (100

- 907) and Discover ® NG Herbicide (100

- 1173). The applications were all conducted with the adjuvant SCOR E ®

. At all 20 sites grain was collected at normal harvest. All of the harvested samples were analyzed for residues of clodinafop

- pr opargyl (CGA184927) and its significant metabolite ( CGA193469). The original analytical methodology was modified to lower the limit of quantitiation ( LOQ ) for all an alytes to 1 ppb and establish a Limit of Detection (LOD) of 0.5 ppb for all analytes. The residue levels of all of the analytes in all wheat grain samples harvested 62

- 110 days after the application were below the limit of detection, ( <0.5 ppb )

. ]

B. Toxicological Profile

1. Acute toxicity. [The database for acute toxicity of clodinafop

- propargyl is considered complete. Clodinafop

- propargyl has a low order of acute toxicity. The acute toxicity profile of clodinafop

- propargyl was published previously in the Federal Register (April 26, 2000, (Volume 65, Number 81), page 24471

- 24477). The EPA has previously published the acute toxicity endpoints in the Federal Register (June 22, 2000 (Volume 65, Number 121), page 38765

- 38774).]

2. Genotoxicty. [ The genotoxicity profile of clodinafop

- propargyl was published previously in the Federal Register (April 26, 2000, (Volume 65, Number 81), page 24471

- 24477). The EPA has previously published the genotoxicity endpoints in the Federal Register (June 22, 2000 (Volume 65, Number 121), page 38765

- 38774).]

3. Reproductive and developmental toxicity. [ The reproductive and developmental toxicity profile of clodinafop

- propargyl was published previously in the Federal Register (April 26, 2000, (Volume 65, Number 81), page 24471

- 24477). The EPA has previously published the reproductive and developmental toxicity endpoints in the Federal Register (June 22, 2000 (Volume 65, Number 121), page 38765

- 38774). ]

4. Subchronic toxicity. [ The subchronic toxicity profile of clodinafop

- propargyl was published previously in the Federal Register (April 26, 2000, (Volume 65, Number 81), page 24471

- 24477). The EPA has previously published the subchronic toxicity3

endpoints in the Federal Regist er (June 22, 2000 (Volume 65, Number 121), page 38765

- 38774). ]

5. Chronic toxicity. [ The chronic toxicity profile of clodinafop

- propargyl was published previously in the Federal Register (April 26, 2000, (Volume 65, Number 81), page 24471

- 24477). The EPA has previously published the chronic toxicity endpoints in the Federal Register (June 22, 2000 (Volume 65, Number 121), page 38765

- 38774). ]

6. Animal metabolism. [ The metabolism of clodinafop

- propargyl in animals is well understood, as was published previously in the Federal Register (April 26, 2000, (Volume 65, Number 81), page 24471

- 24477) . In rats, clodinafop

- propargyl was rapidly absorbed through the gastrointestinal tract. Absorption through the skin of rats is

cons iderably slower with 15% of a dermally applied dose being absorbed within 8 hours. The EPA HIARC estimated the dermal absorption rate for clodinafop

- propargyl to be 2.5% derived by taking the ratio of the LOAEL from the 28

- day oral toxicity study in rats (5 mg/kg/day) and 28

- day dermal toxicity study in rats (200 mg/kg/day). ]

7. Metabolite toxicology

. [ The metabolite toxicity profile of clodinafop

propargyl in animals is well understood, as was published previously in the Federal Register (April 26, 2000, (Volume 65, Number 81), page 24471

- 24477) )

. ]

8. Endocrine disruption

. [ Clodinafop

- propargyl is a known peroxisome proliferator. In the rat, this class of chemicals is known to interfere with sex steroid metabolism and alter plasma sex hormone concentrations. However, specific studies designed to address pre

- and post

- natal toxicity did not find evidence that clodinafop

propargyl is a reproductive or development toxican t. Results from rat and rabbit pre

- natal development toxicity studies, two

- generation reproductive toxicity study in rats, and a development neurotoxicity study in the rat indicate that the mammalian endocrine system is not adversely affected by clodinafop

- propargyl. ]

C. Aggregate Exposure

1. Dietary exposure

. [ Tier 1 acute and chronic aggregate exposure assessments were performed for clodinafop

- propargyl and its corresponding hydrolysis product, CGA193469, using the Dietary Exposure Evaluation Model (DEEM

- FCID TM Ver. 2.16, Exponent, Inc.) to evaluate the currently registered use on wheat with a proposed revised tolerance of 0.02 ppm for wheat grain; these assessments also included the established tolerances for wheat forage and hay (0.1 ppm) and straw (0.5 ppm) and a continued restriction against fall applications . Existing or proposed tolerances were based upon field trial residue data where wheat was treated in the spring at the maximum labeled treated treatment rate and harvested at the minimum pre

- harvest interval

. An experimental processing factor of 1.43X was used for aspirated grain fractions (AGFs); all other processing factors utilized DEEM TM Ver. 7.87 defaults. Anticipated residues in meat, milk and eggs were calculated by constructing a theoretical “maximum reasonably balanced diet” (MRBD; June 2008). No adjustments were made for “percent crop treated”, i.e., 100%CT was assumed. Drinking w ater estimates were selected using the higher of the estimated drinking water concentrations ( EDWCs) for surface and ground4

water. All consumption data for these assessments were taken from the USDA ’s Continuing Survey of Food Intake by individuals (CSFII ) with the 1994

- 1996 consumption database and the Supplemental CSFII children’s survey (1998) consumption database. ]

i. Food. [ Acute Exposure : For the general population (including infants and children), the clodinafop

- propargyl acute food risk assessment was performed using an acute reference dose (aRfD) of 0.025 mg/kg

- bw/day based upon a developmental toxicity study in rabbits with a no observed ad verse effect level (NOAEL) of 25 mg/kg

- bw/day and an uncertainty factor of 100X FQPA for intra

- and inter

- species variations and an additional 10X FQPA safety factor due to database uncertainty. For females 13

- 49 years old, the clodinafop

- propargyl acute food risk assessment was performed using an acute reference dose (aRfD) 0f 0.005 mg/kg

- bw/day based upon a developmental toxicity study in rats with a no observed adverse effect level (NOAEL) of 5 mg/kg

- bw/day and an uncertainty factor of 100X for intra

- a nd interspecies variations and an additional 10X FQPA safety factor due to database uncertainty. For the purpose of aggregate risk assessment, the exposure values were expressed in terms of margin of exposure (MOE), which was calculated by dividing the NO AEL by the exposure for each population subgroup. In addition, exposure was expressed as a percent of the acute reference dose (%aRfD). At the 95 th percentile, acute food exposure to the U.S. population resulted in a MOE of 235, 670 (0.4% of the aRfD of 0.025 mg/kg

- bw/day). The most exposed subpopulation was females 13

- 49 years old with a MOE of 73,621 (1.4% of the aRfD of 0.005 mg/kg

- bw/day. Since the Benchmark MOE for this assessment was 1000 and since the EPA generally has no concern for exposures ab ove the Benchmark or below 100% of the aRfD, S y ngenta believes that there is a reasonable certainty that no harm will result from dietary (food only) exposure to residues arising from the currently registered use on wheat.

Chronic Exposure

. The clodinafop

- propargyl chronic food risk assessment was performed for all population subgroups using a chronic reference dose of 0.00032 mg/kg

bw/day based upon a chronic toxicity study in rats with a no observed adverse effect level (NOAEL) of 0.32 mg/kg

- bw /day and an uncertainty factor of 100X for intra

- and interspecies variations and an additional 10X FQPA safety factor due to database uncertainty. For the purpose of aggregate risk assessment, the exposure values were expressed in terms of margin of expo sure (MOE), which was calculated by dividing the NOAEL by the exposure for each population subgroup. In addition, exposure was expressed as a percent chronic reference dose (%cRfD). Chronic food exposure to the U.S. population resulted in a MOE of 8, 467 (11.8% of the cRfD of 0.00032 mg/kg

bw/day). The most exposed subpopulation was children 1

- 2 years old, with a MOE of 3,180 (31.4% of the cRfD of 0.00032 mg/kg

- bw/day). Since the Benchmark MOE for this assessment was 1000 and since the EPA generally has n o 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 dietary (food only) exposure to residues arising from the currently registered use on wheat.

Canc er. Clodinafop

- propargyl has been classified as having “suggestive evidence of carcinogenicity”, although cancer assessments have not been previously performed or5

required by the Agency. (Ref.: Dodd, Nancy
, “ Clodinafop

- propargyl. Acute and Chronic Aggregate Dietary (Food and Drinking Water) Exposure and Risk Assessments for the Section 3 Registration Action on Wheat”, PC Code 125203, DP 328474, Health Effects Division, US EPA, 30

- Jan

- 2007). ]

ii. Drinking water

. [ The Estimated Drinking Water Concentrations (EDWCs) were determined for total residues of clodinafop

- propargyl and its three degradates (CGA193469, CGA193468 and C GA 302371) using Tier 1 SCI

- GROW which estimates pesticide concentration in ground water and Tier 2 PRZM/EXAMS which estimates pesticide concentrations in surface water. The currently registered use on wheat was assessed for the proposed tolerance revision on wheat. Modeling results provided a ground water EDWC of 0.226 ppb (acute and chronic) and surface water EDWC s of 1.635 ppb for acute and 0.911 ppb for chronic. The surface water EDWCs were corrected for a 0.56 Percent Cropped Area (PCA) factor. Since the su rface water EDWCs exceeds the ground water EDWC, the surface water values were used for risk assessment pur poses and will be considered protective for any ground water exposure

concerns.
Acute Exposure from Drinking Water

. The acute surface water EDWC of 1.635 ppb was input directly into DEEM

- FCID TM software as “water, direct and indirect, all sources” to obtain the acute exposure from food and drinking water. Drinking water exposures were determined by taking the difference between the aggregate exposures (food + drinking water) and food exposures (food only) for each population subgroup. At the 95 th

p ercentile, acute drinking water exposure to the U.S. population resulted in a MOE of 409, 836 (0.2% of the aRfD of 0.025 mg/kg

- bw/day). The most exposed sub

- population was females 13

- 39 years old with a MOE of 87,719 (1.1% of the aRfD of 0.005 mg/kg

bw/da y). Since the Benchmark MOE for this assessment was 1000 and since the EPA generally has no concern for exposures above the Benchmark or below 100% of the

a RfD, Syngenta believes that there is a reasonable certainty that no harm will result from drinking water exposure s to residues arising from the currently registered use on wheat.

Chronic Exposure from Drinking Water

. The chronic surface water EDWC of 0.911 ppb was input directly into DEEM

- FCID TM software as “water, direct and indirect, all sources” to obtain the chronic exposure from drinking water. Chronic drinking water exposure to the U.S. population resulted in a MOE of 16, 665 (6.0% of the cRfD of 0.00032 mg/kg

- bw/day).The most exposed sub

- p opulation was all infants <1 year old, with a MOE of 5, 083 (19.7% of the cRfD of 0.00032 mg/kg

- bw/day). Since the Benchmark MOE for this assessment was 1000 and since the EPA generally has no concern for exposures above the Benchmark or below 100% of the c RfD, Syngenta believes that there is a reasonable certainty that no harm will result from drinking water
exposure s to residues arising from the currently registered use on wheat. ]

2. Non

- dietary exposure

. [ There are currently no registered residential uses for clodinafop

- propargyl and therefore no contributions to aggregate risk, so a residential exposure assessment was not performed. ]6

D. Cumulative Effects

[ Section 408(b)(2)(D)(v) requires that, when considering whether to establish, modify, or rev oke a tolerance, the Agency consider s “available information” concerning the cumulative effects of a particular pesticide’s residues and “other substances” that have a common mechanism of toxicity. EPA does not have, at this time, sufficient data to dete rmine whether clodinafop

- propargyl 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 action, therefore, EPA has not assumed that clodinafop

proparg yl 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, the acute aggregate exposure analysis for all current uses of clodinafop

- propargyl resulted in a MOE of 149, 497 for the U.S. population and a MOE of 40, 034 for females 13

- 49 years old (the most exposed subgroup). The chronic dietary exposure analysis for all current uses of clodinafop

- propargyl resulted in a MOE of 5,614 for the U.S. population. Since the worst case aggregate MOE of 5, 614 for chronic aggregate exposures exceeds the Benchmark MOE of 1000, Syngenta believes that there is a reasonable certainty that no harm will occur to the U.S. p opulation from acute and chronic aggregate exposures arising from the currently registered use on wh eat

. ]

2. Infants and children

. [ Using the conservative assumptions described above, and based on the completeness and reliability of the toxicity data, the acute aggregate exposure analysis for all current uses of clodinafop

- propargyl resulted in a MOE of 70,270 for all infants <1 year old. The chronic dietary exposure analysis for all current uses of clodinafop

- propargyl resulted in a MOE of 2, 478 for children 1

- 2 years old

.

Since the worst case aggregate MOE of for chronic exposures of 2, 478 for children 1

- 2 years old exceeds the Benchmark MOE of 1000, Syngenta believes that there is a reasonable certainty that no harm will occur to infants and children from acute and chronic aggregate exposures arising from the currently registered use on wheat

. ]

F. International Tolerances

[ There is no Codex Alimentarius Commission (CODEX) maximum residue levels (MRLs) established for residues of clodinafop

- propargyl in or on raw agricultural commodities

. ]