i

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 replace 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] requesting, 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 for residues of

[Clodinafop-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 before 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)).]
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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 chromatography 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, 7A, 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 

Discover® 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-propargyl (CGA184927) and its significant metabolite (CGA193469). The 

original analytical methodology was modified to lower the limit of quantitiation (LOQ)

for all analytes 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 toxicity 
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endpoints in the Federal Register (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 

considerably 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 clodinafoppropargyl 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 clodinafoppropargyl is a reproductive or development toxicant. 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-FCIDTM 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 DEEMTM 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 water estimates were selected using the 

higher of the estimated drinking water concentrations (EDWCs) for surface and ground 
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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 adverse 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- 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 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 acute reference dose 

(%aRfD). At the 95th 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 above the Benchmark or below 100% of 

the aRfD, 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. 

Chronic Exposure. The clodinafop-propargyl chronic food risk assessment was 

performed for all population subgroups using a chronic reference dose of 0.00032 mg/kgbw/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 exposure (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/kgbw/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 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 dietary (food only) exposure to residues arising 

from the currently registered use on wheat. 

Cancer. Clodinafop-propargyl has been classified as having “suggestive evidence of 

carcinogenicity”, although cancer assessments have not been previously performed or 
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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 CGA302371) 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 EDWCs 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 surface water 

EDWCs exceeds the ground water EDWC, the surface water values were used for risk 

assessment purposes 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-FCIDTM 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 95th

percentile, 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/kgbw/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 

aRfD, Syngenta believes that there is a reasonable certainty that no harm will result from 

drinking water exposures 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-FCIDTM 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-population 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 cRfD, Syngenta 

believes that there is a reasonable certainty that no harm will result from drinking water 

exposures 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.]
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D. Cumulative Effects

[Section 408(b)(2)(D)(v) requires that, when considering whether to establish, 

modify, or revoke a tolerance, the Agency considers “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 determine 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 clodinafoppropargyl 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. population from acute and chronic aggregate exposures arising from the 

currently registered use on wheat.]

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.]