EPA REGISTRATION DIVISION COMPANY NOTICE OF FILING FOR
PESTICIDE PETITIONS PUBLISHED IN THE FEDERAL REGISTER ( 2/19/ 20 10 )

EPA Registration Division contact: [Shaja Joyner (PM

- 20) 703

- 308

- 3194]

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 and brackets, i.e., “ [ insert company name ] ,” with the information specific to your action.

TEMPLATE:

[Syngenta Crop Protection]

[Insert petition number]

EPA has received a pestici de petition ( [insert petition number] ) from [Syngenta Crop Protection]
, [P. O. Box 18300, Greensboro, NC 27409] 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 .532

.

(Options (pick one)

1. by establishing an import tolerance for residues of

[cyprodinil: 2

- Pyrimidinamine, 4

- cyclopropyl

- 6

- methyl

- N

- phenyl

- ] in or on the raw agricultural commodity [] at []

Fruit, Pome
, Group 11, at 1.7 part 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 granti ng of the petition. Additional data may be needed before EPA rules on the petition.

A. Residue Chemistry

1. Plant metabolism. The metabolism of cyprodinil is adequately understood for the purpose of the proposed tolerances. The metabolism of cyprod inil has been characterized in plants and animals. No toxicologically significant metabolites have2

been identified. The metabolism profile supports the use of an analytical enforcement method that accounts for only parent cyprodinil.

2. Analytical metho d. Syngenta Crop Protection has developed and validated analytical methodology for enforcement purposes. This method (Syngenta Crop
Protection Method AG

- 631B) has passed an Agency petition method validation for several commodities and is currently the enfo rcement method for cyprodinil. 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 have been submitted. The requested tolerances are adequately supported.

In support of the requested toleran ce, eighteen residue trials were completed to determine the magnitude of the residues of cyprodinil after five broadcast foliar applications of Vangard WG. Mature fruit were collected 0 day s after the last application. These studies were conducted to supp ort a change in the use pattern (shorter PHI) for the use of cyprodinil on Fruit, Pome
, Group 11. Site Selection and
number of trials were determined to satisfy the requirements listed in OPPTS 860.1500, Crop Field Trials

– Required Number of Field Trials for Crop Groups
and

– Suggested Distribution of Field Trials by Region for Crops. Apple trials were conducted accordingly

- 3 trials located in Region 1, 1 trial in Region 2, 2 trials in Region 5, 1 trial in Region 9, 1 trial in Region 10 , and 4 trials in Region 11. The required number of pear trials were also conducted accordingly

– 1 trial in Region 1, 2 trials in Region 10, and 3 trials in Region 11. At all sites, Vangard WG was applied 5 times at 0.25 lb a.i./A with a 7 day retreatment interval an d a pre

- harvest interval of 0 days for a maximum of 1.25 lb a.i./A. Trial parameters included concentrate and dilute cover sprays, simulation of aerial application, the use of an adjuvant, and residue decline. Apple and pear samples were collected 0 day s after application. Processing samples were previously reported in ABR

- 95049 (MRID 43908445) and there were no detectable residues (<0.01ppm) in the apple juice samples at the exaggerated 3X and 5X application rates. The maximum residues found in processe d apple commodities at the 1X treatment was 0.057 ppm and 0.020 ppm in wet pomace and composited, unwashed apples, respectively.

B. Toxicological Profile

An assessment of toxic effects caused by cyprodinil is discussed in Unit III.A. and Unit III.B. of the Federal Register dated June 22, 2001 (66 FR 33478) (FRL

- 6778

- 7).

The techni cal cyprodinil product is classified in toxicity categories III & IV [CAUTION] based on acute oral, dermal, inhalation toxicity and eye/skin irritation
studies. The formulated end use products are also classified in toxicity categories III & IV [CAUTION] b ased on similar studies.3

1. Acute toxicity. The acute toxicity data of cyprodinil show that this chemical is not acutely toxic by the oral, inha lation and dermal routes of exposure. Technical cyprodinil, however, is a dermal sensitizer.

2. Genotoxicty. Cyprodinil was shown to be negative in studies for point mutation, for chromosome aberration, and for DNA repair. These results indicate that

c yprodinil is unlikely to initiate cancer or cause inheritable genetic defects.

3. Reproductive and developmental toxicity

. Reproductive Toxicity: In a two

generation reproduction study in rats, the NOEL for maternal systemic toxicity is 1000 ppm and t he NOEL for reproductive toxicity is 1000 ppm. Developmental Toxicity: Cyprodinil is not teratogenic. In the rabbit developmental toxicity study, no developmental toxicity was noted even at the highest dose tested (HDT) of 400 mg/k. In the r at developmen tal toxicity study , the developmental and maternal NOELs were both 200 mg/kg based on reduced ossification and body weight in pups and decreased food consumption/weight gain in dams at 1000 mg/kg (HDT).

4. Subchronic toxicity. Subchronic Oral Toxicity: In subchronic studies, the lowest NOEL is 50 ppm based on a rat study. Subchronic Dermal Toxicity: For female rats receiving dermal applications of cyprodinil; NOEL was 5 mg/kg/.day; the
NOEL for the male rats in this study is 125 mg/kg/day.

5. Chroni c toxicity. Chronic Oral Toxicity: Two chronic studies found NOELs of 75 ppm in a 24

- month rat study and 2500 ppm in a one

- year Beagle study. Neither study found evidence of carcinogenicity for cyprodinil.

6. Animal metabolism. The metabolism of cyprod inil in rats is adequately

understood.

7. Metabolite toxicology

. The residue of concern for tolerance setting purposes is the parent compound. The EPA has reviewed the hazard profile of the pryimidine

metab olites (CGA

- 249287, NOA

- 422054) of cyprodinil. EPA has concluded that the toxicity of the CGA

- 249287 and NOA

- 422054 metabolites is no greater than that of the parent.

8. Endocrine disruption

. Cyprodinil does not belong to a class of chemicals known or

s uspected of having adverse effects on the endocrine system. Developmental toxicity studies in rats and rabbits and a reproduction study in rats gave no indication that cyprodinil might have any effects on endocrine function related to development and

repro duction. The chronic studies also showed no evidence of a long

- term effect related to the endocrine system.

C. Aggregate Exposure

1. Dietary exposure. Tier III acute and chronic dietary exposure evaluations were

p erformed for cyprodinil using the Dietary Exposure Evaluation Model (DEEM

FCID TM , version 2.16) from Exponent. These cyprodinil exposure assessments4

included all current uses and data supporting a reduced 0

- day pre

- harvest interval (PHI) for pome fruit. These assessments utilized residue data from field trials where cypro dinil was ap plied at the maximum intended use rate and samples were harvested at the minimum pre

- harvest interval (PHI) to obtain maximum residues. Empirically derived processing factors for apple juice (0.39X), apple pomace (5.22X), grape juice (0.29X), dried prune (2.05X), tomato puree (0.52X), and tomato paste (2.3X) were used in these assessments. The apple juice processing factor was used as a surrogate for pear juice. All other pr ocessing factors used the DEEM TM
defaults. 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 database and the Supplemental CSFII children’s survey (199 8) consumption database. Percent of crop treated values were estimated based upon economic, pest and competitive pressures. Secondary residues in animal commodities were estimated based on “maximum reasonably balanced diets” diets
and transfer informatio n from feeding studies.

i. Food. Acute exposure

. The acute dietary (food only) risk assessment for females

13

- 49 years old (the only population subgroup for which an acute toxicological endpoint has been established) was performed using an acute refer ence dose (aRfD) of 1.5 mg/kg

- bw/day, based upon a rabbit study with a no observable adverse effect level (NOAEL) of 150 mg/kg

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

- and inter

- species variations; no additional FQPA safety factor was appli ed. For the purpose of the 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 each population subgroup. In addition, exposure was expressed as a percent of the acute reference dose (%aRfD). Acute exposure to the
females 13

- 49 years subpopulation resulted in a MOE of 7, 315 (1. 4% of the acute RfD of 1.5 mg/kg

- bw/day). Since the Benchmark MOE for this assessment was 100 and since the EPA generally has no concern for exposures below 100% of the
reference dose , 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 cyprodinil.

Chronic exposure. The chronic reference do se (RfD) for cyprodinil is 0.03 mg/kg

- bw/day, based on a chronic rat study with a NOAEL of 2.7 mg/kg

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

- and inter

- species variations; no additional FQPA safety factor was applied. For the purpose of the agg regate 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
chronic refer ence dose (% c RfD). Chronic food exposures to the U.S. population resulted in a MOE of 2,293 (3.9% of the cRfD of 0.03 mg/kg

- bw/day). Chronic food

exposure s to the most sensitive subpopulation (children 1

- 2 years old) resulted in a
MOE of 531 ( 16.9 % of the cRfD of 0.03 mg/kg

- bw/day). Since the Benchmark MOE for this assessment was 100 and since the EPA generally has no concern for exposures below 100% of the reference dose , Syngenta believes that there is a5

reasonable certainty that no harm will result from chronic dietary (food) exposure to residues arising from the current and proposed uses for cyprodinil.

ii. Drinking water. The Estimated Drinking Water Concentrations (EDWCs) of cyprodinil and CGA294287 were determined using Tier l SCI

- GROW (versio n 2.3), which estimates pesticide concentrations in ground water and Tier II
PRZM/EXA M S (PE version 5.0) which estimates pesticide concentrations in surface

water. This drinking water assessment was conducted to assess the new use rate pattern on pome fru it (0.25 lb ai/A x 5 applications at 7 day intervals) which supports a reduced pre

- harvest interval (PHI) from 72 days to 0 day. EDWCs from this new use rate pattern do not exceed the EDWCs from the current crop driver (based on grapes). The EDWCs for gra pes were updated in this assessment based on model inputs from a recent EPA drinking water assessment ( DP Barcode D342973,
2

- May

- 2008 ) and an updated Vangard ® WG label. For ground water, the currently registered uses on almond and grapes at a rate of 3 x 0.469 lb a.i./A (1.4 lbs a.i./A/year) provided the highest EDWC (acute and chronic) of 0.0401 ppb for cyprodinil and 0.0675 ppb for CGA249287. The combined ground water EDWC is 0.1076 ppb (acute and chronic). For surface water, the NY grapes standard PRZ M scenario using three aerial applications (as a worst

- case assumption for 2 aerial + 1 ground) at 0.469 lb a.i./A (1.4 lbs a.i./A/year) with a 7

- day interval between treatments provided acute EDWCs of 36.409 ppb for cyprodinil and 3.008 ppb for CGA249287, for a combined total residue of 39.417 ppb. The chronic EDWCs were 22.159 ppb for cyprodinil and 0.532 ppb for CGA249287 resulting in a combined total residue of 22.691 ppb. The surface water EDWCs have been corrected for a
0.87 PCA factor. These surfa ce water EDWCs exceed the EPA’s surface water EDWCs (34.56 ppb for acute and 20.05 ppb for chronic) published in a 2008 Final Rule (FR 73, No. 167, 27

- Aug

- 2008) and will therefore be used for this Notice of Filing (NOF). Since surface water EDWCs exceed t he ground water EDWC, the Syngenta surface water values will be used for risk assessment purposes and considered protective for any ground water concentration concerns.

Acute Exposure from Drinking Water : The acute EDWC of 39.417 ppb (0.039417 ppm) was i ncorporated with food residues as “water, direct and indirect, all sources” directly into the DEEM

- FCID TM software to model the aggregate (food and water) exposures. The acute drinking water exposure contributions at the 99.9 th percentile of exposures were determined by taking the difference between the aggregate (food + drinking water) exposures and the fo od (only) exposures for each population subgroup. Acute drinking water exposure at the 99.9 th percentile for females (13

- 49 years), the only population subgroup for which an acute toxicological endpoint has been established, resulted in a MOE of 286,807 ( <0.1% of the aRfD of 1.5 mg/kg

- bw/day). Since the Benchmark MOE for this assessment was 100, and since the EPA generally has no concern for exposures below 100% of the reference dose, Syngenta believes that there is a reasonable certainty that no harm wil l result from acute drinking water exposure to residues arising from all current and proposed uses of cyprodinil.

Chronic Exposure from Drinking Water : The chronic EDWC of 22.691 ppb (0.0226916

ppm) was incorporated with food residues as “water, direct an d indirect, all sources” directly into the DEEM

- FCIDTM software to obtain chronic dietary (drinking water) exposures. Chronic drinking water exposure to the U.S. population resulted in a MOE of 5,645 (1.6% of the RfD of 0.03 mg/kg

- bw/day).
The most sensit ive subpopulation was all infants (<1 year old), with a MOE of 1,722 (5.2% of the RfD of 0.03 mg/kg

- bw/day). Since the Benchmark MOE for this assessment was 100 and since the EPA generally has no concern for exposures below 100% of the reference dose, Syn genta believes that there is a reasonable certainty that no harm will result from chronic drinking water exposure to residues arising from all current and proposed uses of cyprodinil.

2. Non

- dietary exposure

. Cyprodinil is not currently registered for any uses that would result in residential handler (mixer/loader/applicator) exposure. A new product label for Palladium®, containing cyprodinil and fludioxonil, allows professional applications to ornamental plants in residential settings. No post

applic ation residential exposure assessment is required because post

- application exposure to adults and children from ornamental applications is negligible.

D. Cumulative Effects

Cumulative Exposure to Substances With a Common Mechanism of Toxicity . Secti on 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 com mon mechanism of toxicity”. The EPA does not have, at this time, available data to determine whether cyprodinil 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, the EPA has not assumed that cyprodinil has a common mechanism of toxicity with other substances.

E. Safety Determination

1. U.S. population. An acute toxicological endpoint has not been established for the U.S. population, so an acute exposure assessment was not performed for the U.S. population. The chronic aggregate exposure analysis showed that exposure from all current and proposed cyprodinil uses resulted in a MOE of 1,631 ( 5

. 5 % of the c RfD of 0.03 mg/kg

- bw/day) for the U.S. population, which exceeds the Benchmark MOE of 100. A cancer exposure analysis was not performed, since there is no evidence of human carcinogenic potential for cyprodinil. Based on the completeness and reliability of the toxicity data supporting th ese petitions, Syngenta believes that there is a reasonable certainty that no harm will result from aggregate exposure from all current and proposed uses of cyprodinil.

2. Infants and children

. A n acute toxicological endpoint has not been established fo r infants and children, so an acute exposure assessment was not performed for infants and children. The chronic aggregate exposure analysis showed that exposure from7

all established and proposed cyprodinil uses resulted in a MOE of 466 (1 9

. 3 % of the

c RfD of 0.03 mg/kg

- bw/day) for children 1

- 2 years old, which exceeds the Benchmark MOE of 100. A cancer exposure analysis was not performed, since there is no evidence of human carcinogenic potential for cyprodinil. Based on the completeness and reliability o f the toxicity data supporting these petitions, Syngenta believes that there is a reasonable certainty that no harm will result from aggregate exposure from all current and proposed uses of cyprodinil.

3. Females 13

- 49 years of age

. The acute aggregate e xposure analysis showed that exposure to all current and proposed cyprodinil uses would result in a MOE of 7,1 33 (1. 4 % of the aRfD of 1.5 mg/kg

- bw/day) for females 13

- 49 years old, which exceeds the Benchmark MOE of 100. The chronic aggregate exposure ana lysis showed that exposure to all current and proposed cyprodinil uses would result in a MOE of 2, 139 ( 4.2 % of the c RfD of 0.03 mg/kg

- bw/day) for females 13

- 49 years old, which exceeds the Benchmark MOE of 100. A cancer exposure analysis was not performed , since there is no evidence of human carcinogenic potential for cyprodinil. Based on the completeness an d reliability of the toxicity data supporting these petitions, Syngenta believes that there is a reasonable certainty that no harm will result from aggregate exposure from all current and proposed uses of cyprodinil.

F. International Tolerances

Codex maximum residue levels have been established for residues of cyprodinil in or on almonds, apples, barley, beans (except broad bean and soya bean), cucumbers, dried grapes (currants, raisins and sultanas), eggplant, eggs, grapes, lettuce (head & leaf), mea t & meat

- by

- products, milk, onions (bulb), pears, peppers (sweet), poultry, prunes, raspberries, squash (summer), stone fruits, straw and fodder of cereal grains, strawberries, tomatoes, wheat, and wheat bran.